JPDS_NOV2021_NO ADS_FINAL

JPDS
Journal of the Philippine Dermatological Society
Volume 30 Issue 2 • November 2021 • ISSN 2094-201X

Immunoflourescence staining shows decreased collagen VII (C7) in a dystrophic epidermolysis bullosa
patient compared to normal collagen XVII (C7) expression

Whole-exome Herpes zoster after Determination of minimal
sequencing in the COVID-19 vaccination: erythema dose of Filipino
adults to standardize the
clinical setting: A case series initial dose of narrowband
Establishing a foothold ultraviolet B phototherapy
for precision medicine in
in a tertiary hospital
genodermatoses
and other diseases

Editorial Board 2021-2022

Journal of the Philippine Dermatological Society • Volume 30 Issue 2 • November 2021

EDITOR-IN-CHIEF

Bryan Edgar K. Guevara, MD, FPDS

DEPUTY EDITOR MANAGING EDITOR

Hester Gail Lim Bueser, MD, FPDS Mara P. Evangelista-Huber, MD, FPDS

ASSOCIATE EDITORS

Czarina Chavez, MD, FPDS Elisa Rae Coo, MD, FPDS

Lian Jamisola, MD, FPDS Maria Jasmin J. Jamora, MD, FPDS

Hanna Lucero Orillaza, MD, FPDS Melanie Joy Doria-Ruiz, MD, FPDS

Ana Aurelia M. Santos, MD, FPDS Jennifer Aileen A. Tangtatco, MD, FPDS

Patricia Tinio, MD, FPDS Angeli Eloise E. Torres, MD, DPDS

Emmerson Gale S. Vista, MD, FPDS

SECTION EDITORS

Gisella Adasa, MD, FPDS Joyce C. Castillo, MD, FPDS

Tanya Perez-Chua, MD, FPDS Lily Lyralin Laconico Tumalad, MD, FPDS

Stephen Lacson, MD, FPDS Sharon Lim, MD, FPDS

Eugenio R. Pipo III, MD, FPDS Cybill Dianne C. Uy, MD, FPDS

Mia Angela C. Verzosa, MD, FPDS

SOCIAL MEDIA EDITORS

Francesca Sumilang Sy-Alvarado, MD, FPDS Erin Jane L. Tababa-Santos, MD, DPDS

EDITORIAL ADVISER

Camille B. Angeles, MD, FPDS

COPYEDITOR LAYOUT ARTIST

Rodel C. Roño Clarence Xlasi D. Ladrero

EDITORIAL OFFICE

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endorsement by the Philippine Dermatological Society and Editors.

J Phil Dermatol Soc · November 2021 · ISSN 2094-201X i

Philippine Dermatological Society

OFFICERS AND BOARD DIRECTORS 2021-2022

Journal of the Philippine Dermatological Society • Volume 30 Issue 2 • November 2021

PRESIDENT

Francisco D. Rivera IV, MD, FPDS

VICE PRESIDENT

Noemie Salta Ramos, MD, FPDS

SECRETARY

Roberto Antonio D. Pascual, MD, FPDS

TREASURER

Mary Charmaine G. Castillo, MD, FPDS

IMMEDIATE PAST PRESIDENT

Ma. Purita Paz-Lao, MD, FPDS

DIRECTORS

Christene Pearl F. Arandia, MD, FPDS
Blossom Tian Chan, MD, FPDS

Krisinda Clare Dim-Jamora, MD, FPDS
Lonabel A. Encarnacion, MD, FPDS
Nancy Garcia-Tan, MD, FPDS
Cecilia Roxas Rosete, MD, FPDS
Arnold C. Yu, MD, FPDS

ii J Phil Dermatol Soc · November 2021 · ISSN 2094-201X

Table of Contents

Journal of the Philippine Dermatological Society • Volume 30 Issue 2 • November 2021

LET’S HEAR FROM A COLLEAGUE 40
1
Determination of minimal erythema dose of Filipino
The role of skin punch grafting with platelet rich adults to standardize the initial dose of narrowband
plasma injection on stable segmental vitiligo ultraviolet B phototherapy in a tertiary hospital
Krisinda Clare C. Dim-Jamora Michelle Isabel L. Astorga, Maria Victoria C. Dizon, Patricia
Anne T. Tinio
4
46
Whole-exome sequencing in the clinical setting:
Establishing a foothold for precision medicine in Translation and validation of a scale on the health
genodermatoses and other diseases care providers’ Attitudes Towards Persons Living
Yu-Chen Lin, Wilson Jr. F. Aala, Bryan Edgar K. Guevara, With Leprosy (AT-PLWL)
Rosa Beatriz S. Diaz, Chao-Kai Hsu Maicka Keirsten O. Agon, Abelaine Venida-Tablizo

9 CASE REPORTS
56
Functional and integrative approach to
dermatology: Useful tips for your practice HIV and leprosy in a 27-year-old Filipino male: A
Maria Tricia B. Manlongat-Malahito, Maria Jasmin J. case report
Jamora, Zharlah Gulmatico-Flores, Elvira L. Henares- Kristen Therese A. Whaley, Ma. Teresita G. Gabriel,
Esguerra, Jennifer Aileen Ang-Tangtatco, Beverly Ong- Emmanuel Jacinth C. Atienza
Amoranto, Bryan Edgar K. Guevara, Patricia V. Tin, Vermén
M. Verallo-Rowell, Lovell Cristina S. Magat 61

ORIGINAL ARTICLES Large basal cell carcinoma in a 101-year-old Filipino
15 female: A case report
Jianella Catrisse D. Diaz, Daisy King-Ismael, Ma. Luisa
A randomized, comparative study on the efficacy and Abad-Venida, Zharlah Gulmatico-Flores
safety of mangosteen 1% extract gel versus benzoyl
peroxide 5% gel in the treatment of mild to moderate 65
acne vulgaris
Janice Natasha C. Ng, Maria Vinna N. Crisostomo, Severe papulopustular rosacea with demodicosis in a
Margaret Stephanie L. Jimenez, Mary Jo Kristine S. 47-year-old Filipino female: A case report
Aira Monica R. Abella, Johannes F. Dayrit
Bunagan
69
24
AIDS-associated Kaposi sarcoma: A case series in the
Prevalence of Vitamin D insufficiency and deficiency Philippine setting
among seborrheic dermatitis patients: a cross- Ricky H. Hipolito, Ma Teresita G. Gabriel, Johannes F.
sectional study at Makati Medical Center Dayrit, Ma Carmela P. Bucoy
Reagan Grey T. Reyes, Ma. Lourdes Aragon-De Veyra
74
29
Acral lentiginous melanoma and tuberculosis
Prevalence of mucosal and cutaneous disorders verrucosa cutis in a 78-year-old Filipino: A case
among HIV/AIDS adult Filipino patients 18-60 years report
old seen in a tertiary hospital in Makati City Danielle Marlo R. Senador, Leilani R. Senador, Johannes F.
Rahina H. Galvez, Ma. Jasmin J. Jamora, Janice C. Caoili Dayrit, Gisella U. Adasa

35 79

A translation and validation study of the Filipino Herpes zoster after COVID-19 vaccination: A case
version of the Psoriasis Epidemiology Screening Tool series
(PEST) among Filipino patients with psoriasis seen Christine E. de Guia, Ivy S. Cagulada, Jonella Jean F.
at the Rizal Medical Center Nicolas, Cecilia R. Rosete, Czarina P. Chavez
Camille Clarisse S. Mundin, Rogelio B. Balagat, Jamie P. Nunez

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Journal of the Philippine
Dermatological Society

The role of skin punch grafting with platelet-rich
plasma injection on stable segmental vitiligo

Krisinda Clare C. Dim-Jamora, MD, FPDS1

ABSTRACT

Vitiligo is a non-communicable, chronic skin condition that has psychosocial effects for the patient. The case of an otherwise
healthy skin phototype IV Filipino male with a two-year history of stable vitiligo is presented here. Three sessions of skin punch
grafting and platelet-rich plasma injection under local anesthetic were done on the patient three months apart, resulting in
excellent cosmetic results and patient satisfaction.

KEYWORDS plasma-rich plasma, vitiligo, skin punch grafting

1Department of Dermatology, INTRODUCTION treatment result from these two methods plateaued.
Makati Medical Center, Legazpi Grafting skin from non-affected areas al-
Village, Makati Vitiligo is an acquired pigmentary disorder re-
sulting in depigmentation in different areas of low melanocytes to be transferred onto the vit-
Corresponding author the skin. A variety of causes contribute to its iliginous areas. These melanocytes must be kept
Krisinda Clare C. Dim-Jamora, etiology. This includes an inherent genetic pre- viable by suspending in 0.9% sodium chloride
MD, FPDS disposition, environmental factors, and oxida- solution isotonic with human plasma. Melano-
tive stress. There are various genetic protein cyte differentiation is enhanced by the injection
Conflict of interest malfunctions that cause abnormal melanocyte of platelet-rich plasma on the affected area.
None metabolism resulting in depigmentation. The
various proteins involved are tyrosinase, TRP1 Platelet-rich plasma is an increased con-
Source of funding (tryptophan1), XBP1 (Xbox Binding Protein1), centration of autologous platelets suspended in
None CCR6 (CCMotif Chemokine Receptor 6), NLRP1 a small amount of plasma. The production of
(NLR Family Pyrin Domain Containing 1), IL- platelet-rich plasma starts with harvesting 30-50
2RA(Interleukin 2RA), PTPN22 (Protein Tyrosine mL of venous blood on the same day as the pro-
Phosphatases Family) N22 and FOXP3 (Forkhead cedure. Then, alpha granules are stabilized to
Box Protein 3).1 prevent premature secretion by adding antico-
agulants before centrifugation.4,5 At the Cellular
Research shows that vitiligo has psychosocial Therapeutics Laboratory, pure platelet-rich plas-
effects, especially on the skin of color. In a study ma, a leucocyte-poor platelet-rich plasma with
from India, the daily life quality index score showed a low-density fibrin network after activation, is
that 47% of affected vitiligo patients experience obtained and brought to the procedure site using
a moderate to significant impact of the disease on a cold chain. For the face, 3 milliliters of pure
their lives.2 While in Thailand, where patients have platelet-rich plasma is used per procedure.
skin color close to that of Filipinos, a study showed
that patients with new lesions are 4.12 times likely With the secretion of platelet’s alpha gran-
to be depressed compared to those without lesions.3 ules, platelet-rich plasma increases the release of
Thus, it is essential to offer methods that can hasten growth factors, adhesion molecules, and chemo-
the treatment of this condition. kines, which promote cell growth and differen-
tiation of melanocytes in the local environment
THE PROCEDURE of the vitiliginous skin. The major growth fac-
tors secreted by the alpha granules are plate-
SKIN PUNCH GRAFTING AND PLATELET-RICH let-derived growth factor (PDGF), transforming
PLASMA INJECTION growth factor (TGF), vascular endothelial growth
Narrow-band ultraviolet B and excimer laser are factor (VEGF), epidermal growth factor (EGF), fi-
well-established treatment options for vitiligo. In broblast growth factor (FGF), connective tissue
the case of our patient, he underwent more than growth factor (CTGF) and insulin-like growth
50 sessions of excimer laser and thrice-weekly nar- factor-1 (IGF-1). In addition, platelets may release
row-band ultraviolet B treatment for 2 years. The numerous anti-inflammatory cytokines, such as

1 J Phil Dermatol Soc · November 2021 · ISSN 2094-201X

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A
B

Figure 1. A. Chin before skin punch grafting and platelet rich plasma injection. B. Chin after two sessions of skin punch grafting and platelet rich plasma injection.

IL-1 receptor antagonist (IL-1ra), soluble tumor necrosis factor AB
(TNF) receptor (sTNF-R), and interferon γ.5
Figure 2. A. Neck two weeks after first session of skin punch grafting and platelet rich
During the consultation, it is essential to establish trust plasma injection. B. Neck three months after third session of skin punch grafting and platelet
and rapport. Valuable insights obtained are medical history, in- rich plasma.
cluding allergies, and intake of blood thinners. Once consent is
secured, give preoperative instructions and prescribe sodium gauge 30 needle.
ascorbate 500 mg tablet daily, an oral antibiotic, and tranexam- 10. Dress the donor and recipient sites using non-adhesive
ic acid 500 mg tablet on the morning before the procedure. In
addition, during the COVID-19 pandemic, a COVID-19 RT-PCR sterile dressing and 2% mupirocin ointment.
test is required of the patient 48 hours prior to the procedure. Post-operative medication includes paracetamol 500 mg
tablet thrice-daily for five days, tranexamic acid 500 mg tab-
The following are the steps in skin punch grafting with let twice a day for three to five days, and an oral antibiotic of
platelet-rich plasma injection. choice to reduce bacterial colonization on both the recipient
and donor sites. Initial follow-up was done two days after the
1. Harvest the blood and secure platelet-rich plasma in procedure for a change of dressing. Sutures were removed after
cold storage at 4 degrees Celsius.7 seven days. The patient was instructed on daily wound care with

2. Mark the recipient sites.
3. Sterilize the area with 7.5% iodine scrub solution

thrice and 10% iodine antiseptic solution 10% thrice.
4. Anesthetize the donor area using a local anesthetic

composed of 1% lidocaine with epinephrine buffered
with sodium bicarbonate.
5. Harvest the normal skin from the donor area on the
abdomen using a 4-mm punch and soak the grafts in
0.9% sodium chloride solution.6
6. Remove the vitiliginous skin from the recipient site.
7. Insert the donor skin graft into the recipient site
8. Suture the grafts onto the recipient sites using a nylon
6-0 suture with P3 Needle. One may also use cyanoac-
rylate skin glue if it is available.
9. Inject the three vials of platelet-rich plasma using a

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zinc oxide cream. Two weeks after each procedure, the patient CONCLUSION
was instructed to do narrow-band UVB treatment twice a week.
Follow-up of the patient after three procedures done at three- Skin punch grafting and platelet-rich plasma injection, combined
month intervals show almost complete repigmentation (Figures with narrow-band-ultraviolet B phototherapy, shows good results in
1 and 2). providing a viable treatment option with stable vitiligo in the outpa-
tient dermatology clinic setting with minimal downtime.

REFERENCES

1. Richmond JM, Harris JE. 2017. Vitiligo In: Gaspari A., Tyring S., Kaplan D. (eds) Clinical and Basic Immunodermatology. Springer, Cham. DOI:
10.1007/978-3-319-29785-9_28.

2. Lee AH, Iwakoshi NN, Glimcher LH. XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein
response. Mol Cell Biol. 2003 Nov;23(21):7448-59. DOI 10.1128/MCB.23.21.7448-7459.2003.

3. Mishra N, Rastogi MK, Gahalaut P, Agrawal S. Dermatology Specific Quality of Life in Vitiligo Patients and Its Relation with Various Variables: A
Hospital Based Cross-sectional Study. J Clin Diagn Res. 2014 Jun;8(6):YC01-3. DOI: 10.7860/JCDR/2014/8248.4508.

4. Silpa-archa N, Pruksaeakanan C, Angkoolpakdeekul N, Chaiyabutr C, Kulthanan K, Ratta-apha W, et al. Relationship Between Depression and
Quality of Life Among Vitiligo Patients: A Self-assessment Questionnaire-based Study. Clin Cosmet Investig Dermatol. 2020;13:511-520. DOI:
10.2147/CCID.S265349.

5. Mercuri SR, Vollono L, Paolino G. The Usefulness of Platelet-Rich Plasma (PRP) for the Treatment of Vitiligo: State of the Art and Review. Drug
Des Devel Ther. 2020 May 7;14:1749-1755. doi: 10.2147/DDDT.S239912.

6. Cetin C, Köse AA, Aral E, Erçel C, Tandogdu O, Karabağli Y, Ozyilmaz M. The effects of saline and plasma on skin graft keratinocyte viability. Br J
Plast Surg. 2000 Jul;53(5):418-9. DOI: 10.1054/bjps.2000.3324.

7. Kim, JI, Bae, HC, Park, HJ, Lee, MC, Han, HS. Effect of Storage Conditions and Activation on Growth Factor Concentration in Platelet-Rich
Plasma. J Orthop Res 2020 Apr;38(4):777-784. DOI: 10.1002/jor.24520.

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Whole-exome sequencing in the clinical setting:
Establishing a foothold for precision medicine in

genodermatoses and other diseases

Yu-Chen Lin,1,2 Wilson Jr. F. Aala,3 Bryan Edgar K. Guevara,2,4
Rosa Beatriz S. Diaz,4 Chao-Kai Hsu1,2,3

ABSTRACT

The concept of “precision medicine” has been a mainstay in discourses about the future of medicine, although it was not until
the completion of the Human Genome Project that genetic associations to Mendelian diseases have risen dramatically. Since
genetic variations in most (85%) monogenic or oligogenic diseases reside in exons, whole-exome sequencing (WES) serves
as a pivotal tool in the identification of causative variants in genodermatoses and other diseases, leading to efficient and
timely diagnosis. Here, we share our current diagnosis protocol for genodermatoses using WES as a first-tier solution. Two
cases are presented to demonstrate the process of identifying germline variants and one case for a somatic variant. In the
first case, a germline missense mutation in COL7A1 (exon73:c.G6127A) was identified for a patient that presented with clinical
symptoms of dystrophic epidermolysis bullosa (DEB). Immunofluorescence study revealed decreased collagen VII expression in
the dermal-epidermal junction. In case 2, we detected a germline missense mutation in KRT16 (exon1:c.374A>G) in a patient with
palmoplantar keratoderma (PPK) and congenital pachyonychia. Sanger sequencing and segregation analysis confirmed the
variant detected in WES. For case 3, a patient with linear nevus comedonicus was found to have a somatic missense mutation
in NEK9 (exon4:c.500T>C), which was only detected in the lesional DNA sample. Thus, WES shows great potential as a diagnostic
tool for monogenic or oligogenic genodermatoses. Since omics is a technology-driven tool, we expect that reaching precision
medicine is ever closer.

KEYWORDS Whole-exome sequencing, genodermatoses, precision medicine

1Department of Dermatology, THE ROLE OF WHOLE-EXOME SE- Compared to whole-genome sequencing
National Cheng Kung University QUENCING (WES) IN PRECISION (WGS), which analyzes the entire 3.2 billion nu-
Hospital, College of Medicine, MEDICINE cleotides of human DNA, WES analyzes only the
National Cheng Kung University, exonic regions representing ~1.5% of the human
Tainan, Taiwan Precision medicine is an approach for disease genome.3,5 Since roughly 85% of reported patho-
2International Center for Wound treatment and prevention by taking into account genic mutations in monogenic and oligogenic dis-
Repair and Regeneration individual variability, and unique genetic back- eases resides at protein-coding (exonic) regions,
(iWRR), National Cheng Kung ground. Precise medical treatment entails ob- WES presents as a practical and efficient tool in
University, Tainan, Taiwan taining unbiased diagnosis supported by genetic the molecular diagnosis of mono- and oligogenic
3Institute of Clinical Medicine, and clinical information. Though the concept of diseases.6 Currently, WES accounts for roughly
College of Medicine, National precision medicine itself is not new, the associa- 90% of all novel genetic discoveries in genoder-
Cheng Kung University, Tainan, tion of genetic mutations to Mendelian diseases matoses conducted by NGS technology.3
Taiwan did not accelerate until the completion of Human
4Department of Dermatology, Genome Project during the 1990s and early 2000s, Identification of pathogenic/likely patho-
Southern Philippines Medical as shown in the increasing trend of disease-gene genic variants which agree with the disease clin-
Center, Davao, Philippines associations reported in the Online Mendelian ical presentation ascribes a high degree of con-
Inheritance in Man (OMIM) database.1–3 The fidence and precision to diagnosis workflows. A
Corresponding author inclusion of next-generation sequencing (NGS) correct and precise diagnosis not only allows for
Chao-Kai Hsu, M.D., Ph.D. technologies, such as whole-exome sequencing patients to benefit from early prevention proce-
(WES), in clinical workflows have further in- dures to be undertaken by genetic counseling,
Conflict of interest creased the reports of novel gene discoveries. but clinicians could also adapt therapeutic strat-
None Since the first documented use of NGS technology egies for the patients based on the diagnosis and
in a clinical setting in 2009, the pace of novel gen- relevant pathophysiologic focus.7–10 In this re-
Source of funding otype-phenotype discoveries has gained steadily view, we demonstrate the ability of our current
None at roughly 263 per year.4 clinical and molecular diagnostic protocol for

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Figure 1. Schematic description of the diagnostic protocol for genodermatoses. gDNA, genomic DNA; WES, whole exome sequencing; H&E, hematoxylin and eosin; EM, electron microscopy;
IF, immunofluorescence; cDNA, complementary DNA.

genodermatoses, using WES as either the first-tier solution or in also be extracted from skin biopsy specimen for RNA sequenc-
conjunction with other clinical data. ing analysis (Figure 1).

The main purpose of this review is to demonstrate the ILLUSTRATIVE CASES FOR THE CAPABILITY OF
practical implementation of WES as the focal point for molec- WES
ular diagnosis in clinical practice. To this end, we would share
our experience of two cases with germline mutations and one CASE 1: GERMLINE COL7A1 MISSENSE MUTATION IN EPIDER-
case with a somatic mutation as examples. Readers interested MOLYSIS BULLOSA
in a summary of historical WES applications in genodermatoses For germline mutations detected via WES, we outline the diag-
are directed elsewhere.3,11,12 nostic process in a patient with dystrophic epidermolysis bullo-
sa (DEB). The proband, a 30-year-old Taiwanese female, had
PROCESS OF WES-BASED GENETIC DIAGNOSIS erythematous papules and plaques with bullae over bilateral
WORKFLOW pretibial and elbow region (Figure 2A). Dystrophic changes on
teeth and all 20 nails were also noted. Her mother also exhibited
Patients harboring the clinical phenotypes with pedigrees sug- similar clinical features, which initially suggested an autosomal
gestive of genodermatoses would be advised to undergo genetic dominant inheritance (Figure 2B). The patient was clinically di-
investigations (Figure 1). DNA would be extracted from blood or agnosed with DEB and underwent further genetic evaluation.
biopsy skin tissue depending on the clinical presentation sug-
gesting a germline or somatic mutation, respectively. Library Both autosomal dominant and recessive forms of DEB are
preparation and WES of the extracted DNA would be done. For caused by mutations in COL7A1, which encodes collagen VII –
verifying the candidate variants identified via WES, PCR-based a major component of anchoring fibrils.13,14 Through WES, the
Sanger sequencing would also be done. proband was found to harbor a previously reported missense
mutation in COL7A1 (NM_000094:exon73:c.G6127A:p.G2043R),
Skin biopsy specimens of the patients may be sent for leading to a glycine to arginine substitution (Figure 2C).15 Segre-
further histopathological evaluation. Hematoxylin and eosin gation analysis via PCR and Sanger sequencing revealed that the
(H&E), immunofluorescence (IF), or electron-microscopy (EM) mother of the proband also harbored the same mutation (Fig-
would be performed. For transcriptome analysis, RNA could

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Figure 2. Genetic diagnosis and further IF evaluation of a patient with DEB. A. PPK and pachyonychia congenita.17
Erythematous papules and plaques on bilateral pretibial and elbow area of the patient (Left).
Dystrophic changes in teeth and all 20 nails (Right). B. Pedigree summarizing the result of CASE 3: SOMATIC NEK9 MISSENSE MUTATION IN LINEAR
segregation analysis. C. Segregation analysis revealing COL7A1 (NM_000094:exon73:c. NEVUS COMEDONICUS
G6127A:p.G2043R) mutation in both the proband and her mother. D. IF staining shows WES is also equally capable of detecting somatic mutations. Ne-
decreased collagen VII (C7) and normal collagen XVII (C17) expression in the skin specimen vus comedonicus (NC) is a severe, localized form of acne with
of the patient. linear configuration along the Blaschko lines. This suggests
that NC is a mosaic disorder resulting from a somatic mutation
during embryonic development.18,19 We show the capacity of
WES to detect low-frequency somatic mutations in a 14-year-old
Filipino diagnosed with unilateral NC (Figure 4A). Identification
of the mosaic mutational pattern was carried out by obtaining
DNA from the patient’s peripheral blood and lesional skin. WES
of the DNA extracted from the skin biopsy revealed a frequency
of 14% for the candidate variant NEK9:exon4:c.500T>C:p.I167T
(Figure 4B).19 We then targeted this region by PCR and Sanger
sequencing. Visualization of the sequencing chromatograms re-
vealed that the NEK9:exon4:c.500T>C mutation can only be de-
tected in the lesional skin DNA, confirming the candidate NEK9
variant as a somatic mutation (Figure 4C). This mutation has
been previously shown as a gain-of-function mutation resulting
in increased phosphorylation at Thr210, which is necessary for
NEK9 activation.19

STRENGTH OF WES IN GENETIC DIAGNOSIS

Since the introduction of WES into clinical practice in 2009, WES
has played a primary role in identifying monogenic and oligo-
genic genodermatoses. In the diagnostic protocol described, pa-

ure 2C). Immunofluorescence (IF) revealed decreased collagen Figure 3. Genetic diagnosis of a patient with focal PPK and pachyonychia congenita. A. The
VII expression relative to the healthy control, although collagen proband shows compact hyperkeratotic keratin plaques on bilateral soles and hypertrophic
XVII expression was unperturbed (Figure 2D). dystrophy of the toenails. B. Pedigree and summary of segregation analysis. C. Results
of Sanger sequencing reveal heterozygous KRT16:exon1:c.374A>G mutation in both the
CASE 2: GERMLINE KRT16 MISSENSE MUTATION IN PALMO- proband and her mother.
PLANTAR KERATODERMA
Another example of germline mutation detection via WES is
presented in a patient with palmoplantar keratoderma (PPK).
Thick, hyperkeratotic, compact keratin plaques on the bilateral
soles have been reported by the patient since childhood (5 years
old) (Figure 3A). The patient also showed hypertrophic dystro-
phy of the toenails. Minimal fingernail changes were noted. The
patient’s family history showed that the mother of the proband
also had a similar phenotype (Figure 3B).

PPK has been previously reported to follow an autosomal
dominant inheritance pattern. Mutated genes related to focal
PPK include KRT16, KRT6c, DSG1, and TRPV3.16 Results of genet-
ic diagnosis using WES revealed a heterozygous KRT16 mutation
(NM_005557:exon1:c.374A>G:p.N125S) in both the proband and
the proband’s mother (Figure 3B, 3C). The same mutation was
reported previously for a patient with focal non-epidermolytic

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Figure 4. WES using lesional DNA reveals somatic NEK9 mutation in a unilateral nevus comedonicus patient. A. Linear nevus comedonicus on the right neck and right cheek of the patient. B.
IGV visualization of the WES-detected NEK9:exon4:c.500T>C:p.I167T mutation. C. Sanger sequencing of DNA from the affected lesion specimen (upper) and peripheral blood (lower) reveals a
somatic mutation.

tients with phenotype(s) suggestive of genodermatoses would be sis, there are still limitations. Since WES can only target pro-
asked for consent to be enrolled in the genetic diagnosis work- tein-coding exonic regions, detection of non-coding variants is
flow using WES. Genetic diagnosis could then be confirmed by usually unsatisfactory. For compensation, WGS could be used to
histopathological evaluation, PCR/qRT-PCR, immunofluores- target the entire genome although costs for such assays is high-
cence, and immunohistochemistry. In cases where unique in- er than WES.21 Copy number variations (CNV), structural vari-
flammatory signatures or pathways are involved, RNA sequenc- ants, and homologous regions of the genome, which are highly
ing is employed to identify dysregulated genes and pathways repetitive elements, remains challenging for NGS platforms due
which can thus be used to identify possible treatments. to its reliance to the shotgun short-read approach. Instead, long-
read sequencing, also known as third-generation sequencing,
To date, WES represents an efficient technique that could which generates read lengths of over 10,000 bp could be used to
be practically implemented into clinical practice. Furthermore, improve CNV detection and structural analysis.22
WES has become a powerful tool in diagnosing complex geno-
dermatoses involving more than one gene. This is evidenced in CONCLUSION
a previous reported case showing histologic characteristics of
both epidermolysis bullosa (EB) simplex and junctional EB.20 In summary, WES has shown to be a reliable method in the mo-
WES study revealed homozygous mutations in EXPH5 and CO- lecular diagnosis of monogenic and oligogenic genodermatoses.
L17A1 – two different, unlinked EB-associated genes. Future development and universalization of various sequencing
technologies would allow for increased robustness and accura-
LIMITATIONS OF WES cy of variant detection, which brings us closer to achieving per-
sonalized precision medicine.9
Despite the capability and efficiency of WES in genetic diagno-

REFERENCES

1. Bamshad MJ, Nickerson DA, Chong JX. Mendelian Gene Discovery: Fast and Furious with No End in Sight. Am J Hum Genet. 2019;105(3):448-455. DOI:10.1016/j.
ajhg.2019.07.011

2. Collins FS, Morgan M, Patrinos A. The Human Genome Project: lessons from large-scale biology. Science. 2003;300(5617):286-290. DOI:10.1126/
science.1084564

3. Chiu FP ‐C., Doolan BJ, McGrath JA, Onoufriadis A. A decade of next‐generation sequencing in genodermatoses: the impact on gene discovery and
clinical diagnostics. Br J Dermatol. Published online February 2021:bjd.19384. DOI:10.1111/bjd.19384

4. Posey JE, O’Donnell-Luria AH, Chong JX, Harel T, Jhangiani SN, Coban Akdemir ZH, et al. Insights into genetics, human biology and disease gleaned from
family based genomic studies. Genet Med. 2019 Apr;21(4):798-812. doi: 10.1038/s41436-018-0408-7. Epub 2019 Jan 18. PMID: 30655598; PMCID: PMC6691975.

5. Takeichi T, Nanda A, Liu L, Salam A, Campbell P, Fong K, et al. Impact of next generation sequencing on diagnostics in a genetic skin disease clinic. Exp
Dermatol. 2013 Dec;22(12):825-31. doi: 10.1111/exd.12276. PMID: 24279917.

6. Sawyer SL, Hartley T, Dyment DA, Beaulieu CL, Schwartzentruber J, Smith A, et al. Utility of whole-exome sequencing for those near the end of the

7 J Phil Dermatol Soc · November 2021 · ISSN 2094-201X

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A COLLEAGUE Journal of the Philippine
Dermatological Society

diagnostic odyssey: time to address gaps in care. Clin Genet. 2016 Mar;89(3):275-84. doi: 10.1111/cge.12654. Epub 2015 Sep 22. PMID: 26283276; PMCID:
PMC5053223.
7. Manolio TA, Rowley R, Williams MS, Roden D, Ginsburg GS, Bult C, Chisholm RL, et al. Opportunities, resources, and techniques for implementing
genomics in clinical care. Lancet. 2019 Aug 10;394(10197):511-520. doi: 10.1016/S0140-6736(19)31140-7. Epub 2019 Aug 5. PMID: 31395439; PMCID: PMC6699751.
8. Dong X, Liu B, Yang L, Wang H, Wu B, Liu R, Chen H, et al. Clinical exome sequencing as the first-tier test for diagnosing developmental disorders covering
both CNV and SNV: a Chinese cohort. J Med Genet. 2020 Aug;57(8):558-566. doi: 10.1136/jmedgenet-2019-106377. Epub 2020 Jan 31. PMID: 32005694; PMCID:
PMC7418612.
9. Claussnitzer M, Cho JH, Collins R, Cox NJ, Dermitzakis ET, Hurles ME, et al. A brief history of human disease genetics. Nature. 2020 Jan;577(7789):179-189.
doi: 10.1038/s41586-019-1879-7. Epub 2020 Jan 8. PMID: 31915397; PMCID: PMC7405896.
10. Posey JE, Rosenfeld JA, James RA, et al. Molecular diagnostic experience of whole-exome sequencing in adult patients. Genet Med. 2016;18(7):678-
685. DOI:10.1038/gim.2015.142
11. McGrath JA. The Molecular Revolution in Cutaneous Biology: Era of Molecular Diagnostics for Inherited Skin Diseases. J Invest Dermatol.
2017;137(5):e83-e86. DOI:10.1016/j.jid.2016.02.819
12. Cho RJ, Simpson MA, McGrath JA. Next-generation diagnostics for genodermatoses. J Invest Dermatol. 2012;132(E1):E27-28. DOI:10.1038/skinbio.2012.8
13. Bruckner-Tuderman L. Hereditary skin diseases of anchoring fibrils. J Dermatol Sci. 1999;20(2):122-133. DOI:10.1016/S0923-1811(99)00018-3
14. Christiano AM, Anhalt G, Gibbons S, Bauer EA, Uitto J. Premature termination codons in the type VII collagen gene (COL7A1) underlie severe, mutilating
recessive dystrophic epidermolysis bullosa. Genomics. 1994;21(1):160-168. DOI:10.1006/geno.1994.1238
15. Murata T, Masunaga T, Shimizu H, Takizawa Y, Ishiko A, Hatta N, Nishikawa T. Glycine substitution mutations by different amino acids in the same codon
of COL7A1 lead to heterogeneous clinical phenotypes of dominant dystrophic epidermolysis bullosa. Arch Dermatol Res. 2000 Oct;292(10):477-81. doi:
10.1007/s004030000162. PMID: 11142768.
16. Sakiyama T, Kubo A. Hereditary palmoplantar keratoderma “clinical and genetic differential diagnosis.” J Dermatol. 2016;43(3):264-274. DOI:10.1111/1346-
8138.13219
17. Liao H, Sayers JM, Wilson NJ, Irvine AD, Mellerio JE, Baselga E, et al. A spectrum of mutations in keratins K6a, K16 and K17 causing pachyonychia
congenita. J Dermatol Sci. 2007 Dec;48(3):199-205. doi: 10.1016/j.jdermsci.2007.07.003. Epub 2007 Aug 24. PMID: 17719747.
18. Tchernev G, Ananiev J, Semkova K, Dourmishev LA, Schönlebe J, Wollina U. Nevus Comedonicus: An Updated Review. Dermatol Ther. 2013;3(1):33-40.
DOI:10.1007/s13555-013-0027-9
19. Levinsohn JL, Sugarman JL, McNiff JM, Antaya RJ, Choate KA. Somatic Mutations in NEK9 Cause Nevus Comedonicus. Am J Hum Genet. 2016;98(5):1030-
1037. DOI:10.1016/j.ajhg.2016.03.019
20. Vahidnezhad H, Youssefian L, Saeidian AH, Touati A, Sotoudeh S, Jazayeri A, et al. Next generation sequencing identifies double homozygous mutations
in two distinct genes (EXPH5 and COL17A1) in a patient with concomitant simplex and junctional epidermolysis bullosa. Hum Mutat. 2018 Oct;39(10):1349-
1354. doi: 10.1002/humu.23592. Epub 2018 Aug 3. PMID: 30016581.
21. Belkadi A, Bolze A, Itan Y, Cobat A, Vincent QB, Antipenko A, et al. Whole-genome sequencing is more powerful than whole-exome sequencing for
detecting exome variants. Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):5473-8. doi: 10.1073/pnas.1418631112. Epub 2015 Mar 31. PMID: 25827230; PMCID:
PMC4418901.
22. Lee H, Gurtowski J, Yoo S, et al. Third-Generation Sequencing and the Future of Genomics.; 2016:048603. DOI:10.1101/048603

J Phil Dermatol Soc · November 2021 · ISSN 2094-201X 8

JPDS LET’S HEAR FROM A COLLEAGUE
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Dermatological Society

Functional and integrative approach to dermatology:
Useful tips for your practice

Maria Tricia B. Manlongat-Malahito, MD, FPDS,1,2,3 Maria Jasmin J. Jamora, MD, FPDS,1,4,5
Zharlah Gulmatico-Flores, MD, FPDS,6,7 Elvira L. Henares-Esguerra, MD, FPDS, FABM, RPh,8

Jennifer Aileen Ang-Tangtatco, MD, FPDS, CWSP,9 Beverly Ong-Amoranto, MD, DPDS,4,10
Patricia V. Tin, MD, DPDS,8 Vermén M. Verallo-Rowell, MD, FPDS, FAAD, FASDP, FADA,4,8,11

Lovell Cristina S. Magat, MD, MHA, FPDS, CMA,12 Bryan Edgar K. Guevara, MD, FPDS9

1PDS Functional and Integrative INTRODUCTION ing nutrition, exercise and sleep, to mental and
Dermatology Interest Group emotional stressors related to social, work, and
2East Avenue Medical Center, The functional and integrative approach to der- community life. This enables physicians to prac-
Diliman, Quezon City matology is of great interest to both patients and tice proactive, predictive, personalized medicine
3Dr. Jose N. Rodriguez Memorial clinicians, especially since many dermatologic and empowers patients to take an active role in
Hospital, Tala, Caloocan, Metro conditions are reflections of systemic inflam- their own health. Hence, through this approach,
Manila mation. It is important for the dermatologist to dermatologic conditions can be addressed holis-
4Skin and Cancer Foundation understand the intertwined relationships be- tically in close partnership with the patient.
Inc., Medical Plaza Ortigas, tween the gut and skin microbiome and how it
San Miguel Avenue, Ortigas, impacts skin health—the gut-skin-immune and SKIN-GUT-BRAIN AXIS AND ACNE
Pasig City endocrine system axis—and the importance of
5Quirino Memorial Medical modifying lifestyle factors to prevent and treat Western type diets play a significant role in dys-
Center, JP Rial, Project 4, inflammation as we seek to manage our patients function of the gut microbiome by causing the
Quezon City in a more holistic manner. Likewise, patients are release of several neurotransmitters that may
6Jose R. Reyes Memorial Medical becoming more discerning and seek approaches play a role in skin inflammation.
Center, Rizal Avenue, Sta. Cruz, other than traditional Western medical options.
Manila Our group is pleased to share our best practices New and established data suggested that gut
7Fatima Medical Center, and tips substantiated by evidence found in the microbiome dysbiosis may trigger or aggravate
MacArthur Highway, Valenzuela, literature. acne vulgaris.2 Alteration and impairment of the
Metro Manila gut microbiome has been speculated to cause sig-
8Makati Medical Center, WHAT IS FUNCTIONAL MEDICINE? nificant changes such as an increase in Bacteri-
Amorsolo Street, Legazpi, odes species. High levels of Cutibacterium acnes
Makati City Functional medicine (FM) is a systems biology– (C. acnes) and Cutibacterium granulosum (C. gran-
9Southern Philippines Medical based approach that focuses on identifying and ulosum) are found abundantly in pustules and
Center, JP Laurel Avenue, addressing the root cause of disease. It incorpo- comedones of acne patients,3,4 as well as Malas-
Bajada, Davao City rates the latest in genetic science, systems biol- sezia species, which are hypothesized to promote
10Asian Hospital and Medical ogy, and understanding of how environmental inflammation due to its chemoattraction to neu-
Center, Alabang, Muntinlupa, and lifestyle factors influence the emergence trophils, which then release cytokines and other
Metro Manila and progression of disease. FM practitioners pro-inflammatory mediators.4,5 Consumption of
11University of the Philippines - spend time listening to patients and gathering a Western diet comprised of refined carbohy-
NIH - Institute of Herbal Medicine, their medical history. Information gathered is drates, saturated fat, dairy products, and choc-
Pedro Gil St, Ermita, Manila intended to identify the root causes of the ill- olates has been shown to cause gut imbalance
12J.P. Sioson General Hospital ness, including triggers such as poor nutrition, by impairing the normal intestinal microflora,
and Colleges, Bukidnon, Bago stress, toxins, allergens, genetics and microbi- Bifidobacterium species, and Lactobacillus spe-
Bantay, Quezon City ome. Upon identification of the triggers and per- cies.6 This gut dysbiosis leads to the production
forming a nutrient oriented physical examina- of acetylcholine, norepinephrine, and serotonin,
Corresponding author tion wherein all areas of the skin are inspected, a which raises levels of insulin-like growth factor-1
Maria Tricia B. Manlongat-Malahito, PERSONALIZED HEALTH CARE PLAN is given to (IGF-1)7 resulting in systemic inflammation in-
MD, FPDS the patient.1 The plan will address many aspects
of the patient’s life, from physical needs, includ-
Conflict of interest
None

Source of funding
None

9 J Phil Dermatol Soc · November 2021 · ISSN 2094-201X

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Dermatological Society

volving the skin.8 follow-up visit (p < .01). At the 8- and 12-week follow-up visits,
group C had a significant decrease in total lesion count versus
DAIRY ELIMINATION AND SKIN CONDITIONS groups A (p < .001) and B (p < .01). The probiotic given had a com-
AMONG PREGNANT AND BREASTFEEDING bination of Lactobacillus acidophilus (5B CFU), Lactobacillus del-
MOTHERS brueckii (5B CFU) and Bifidobacterium bifidum (20B CFU).14

Consider eliminating cow’s milk and other dairy products PREBIOTICS AND PROBIOTICS IN ATOPIC DER-
from the diet of pregnant and breastfeeding mothers with a MATITIS
history of acne and eczema.
Atopic dermatitis (AD) is characterized by immune dysregu-
Currently, mothers are advised by health professionals to drink lation and altered skin and gut microbiome. Improving nutri-
cow’s milk as a source of calcium during pregnancy and breast- tional status, nutrient digestion and dietary habits promote
feeding. However, a large body of evidence now exists that demon- beneficial effects in the gut and the skin and regulate immune
strates how certain foods and food substances such as cow’s milk response. Prebiotics support the growth of “good bacteria” on
may adversely influence hormones and cytokines that then cause the skin and in the gut, while probiotics supplement the gut
acne and eczema.3,10 Milk and other dairy products have been iden- with “good bacteria”. These common immune regulators of
tified by US law and the US Food and Drug Administration as a ma- the gut microbiota help reduce AD clinical symptoms.
jor food allergen.9,11 For pregnant and breastfeeding patients, it is
recommended to eliminate cow’s milk and other dairy products Changes of microbial composition and function, termed dysbi-
from their diet, and instead provide them with a list of calcium-rich osis, in the gut and the skin have been linked to alteration of
foods that are abundant in the country and readily-available like immune responses and development of AD. The leaky gut or the
malunggay, saluyot and beans. Patients may also be referred to a damage of gut epidermal integrity permits the penetration of
board-certified nutritionist. various foreign particles, such toxins, microbes and food parti-
cles into the systemic circulation, which may contribute to skin
PROBIOTICS, ANTIBIOTICS AND ACNE inflammation.15

Gut and skin microbiota are shifted in acne patients. Probi- Prebiotics are non-digestible components, mainly fiber
otics work synergistically with tetracycline antibiotics by and carbohydrates, that positively create an intestinal environ-
improving the acne and increasing short chain fatty acids, ment in which the good bacteria may thrive.16 Prebiotics were
which are anti- inflammatory and may diminish lipid se- found to improve immune function and Th1/Th2 ratio in AD.17
cretion. When considering systemic antibiotics for an acne Prebiotics also augment the production of short-chain fatty ac-
patient, the addition of a probiotic may provide better results ids (mainly acetate, butyrate, and propionate), which have an
and to decrease potential side effects of chronic antibiotic use. anti-inflammatory effect.18 On the other hand, probiotics are liv-
ing microorganisms that are either the same as or similar to the
Patients with acne have been found to have altered skin microbio- microorganisms naturally found in a healthy human. They are
ta compared to healthy controls and show increased numbers of C. deemed beneficial to the host when they are given on acceptable
acnes, C. granulosum, Staphylococcus epidermidis, Proteobacteria and amount.19 Probiotics reduce the severity of AD through its im-
firmicutes, Streptococcus, and fungal Malassezia.12 At the gut level, munomodulatory effects. They lessen inflammation by reduc-
acne patients are found to have decreased Actinobacteria and in- ing proinflammatory cytokines, IL-4, IL-6 and tumor necrosis
creased Proteobacteria, with low levels of Bifidobacterium, Butyr- factor-α (TNF-α).20
icicoccus, Coprobacillus, Lactobacillus, and Allobaculum.13 Tetra-
cycline class antibiotics are a standard of care for acne and work Although mechanisms between gut microbiota and skin
by inhibiting bacterial protein synthesis and are bacteriostatic but need to be further explored, improving nutritional status by
may cause gastrointestinal disturbances. supporting gut health can reduce immune activation and lead
to overall improved health beyond reducing the clinical mani-
A small randomized controlled trial (RCT) by Jung et al in festations in AD.
2013 compared 3 groups of acne patients: Group A with probiot-
ics alone, group B with minocycline alone, and Group C received OMEGA-3 FATTY ACIDS AND ITS USE IN DERMA-
both probiotics and minocycline.14 Clinical and subjective as- TOLOGY
sessments showed a significant improvement in all groups in
total lesion counts at 4 weeks after treatment initiation (p < Nutraceuticals or oral supplements may be useful adjuvants
.001), with continued improvement seen with each subsequent to skin health. Of this, Omega-3 fatty acid supplements may
significantly improve cutaneous inflammatory diseases by ex-

J Phil Dermatol Soc · November 2021 · ISSN 2094-201X 10

JPDS LET’S HEAR FROM
Journal of the Philippine A COLLEAGUE
Dermatological Society

erting strong anti-inflammatory actions against immune and tors, such as biologics. This is good for both physicians and
epithelial cells. When managing patients with inflammatory patients in managing this chronic condition. Dermatologists
skin conditions such as acne vulgaris, atopic dermatitis and should use knowledge regarding the stimulatory or regulato-
even psoriasis, consider giving Omega-3 fatty acid supple- ry effects of nutrition on psoriasis. Therefore, personalized
mentation as adjuvant treatment to decrease inflammation nutrition should be added in how psoriasis (and other chronic
and help improve disease outcome. skin conditions) is managed.

Current evidence shows the increasing therapeutic benefits of Psoriasis has a strong association with genetic, environmental
nutraceuticals in the form of diet and supplements in maintain- and immunological drivers. The new “-omics” technologies have
ing healthy skin. Among these, Omega-3 fatty acid supplemen- made it possible to unravel different biomarkers that are usher-
tation has been associated with significantly improving various ing us into an era of personalized medicine.27 Having sufficient
dermatologic conditions by decreasing inflammation.21 Ome- information about the underlying immunopathogenesis of pso-
ga-3 fatty acid and its metabolites (resolvin E1, resolvin D1-5, riasis would make management more holistic. Patients living
and maresin 1) have demonstrated strong anti-inflammatory with psoriasis often show unbalanced habits, including higher
action thru phagocytosis and downregulation of inflammatory intake of fat and simple carbohydrates, and lower intake of fish
cytokines, hence its therapeutic potential in inflammatory cu- and dietary fibers.28 This nutritional difference was shown to
taneous diseases.22 In a study by Koch et al., docosahexaenoic be clearly associated with increased severity of psoriasis and
acid (DHA) supplementation significantly improved atopic der- cardiometabolic risk. Saturated fatty acids, red meat, simple
matitis disease severity, dryness, and pruritus scores compared sugars and alcohol have been shown to activate the following
to saturated fatty acid control at 8 weeks (p<.02.).23 For untreat- pro-inflammatory pathways: nucleotide-binding domain, leu-
ed mild-to-moderate acne, a 10-week supplementation of 2000 cine-rich repeats containing family, pyrin domain-containing-3
mg/d EPA + DHA and gamma-linoleic acid, significantly reduced (NLRP3) inflammasome cascade, TNF-alpha/IL-23/IL-17 axis,
inflammatory and non-inflammatory acne lesions compared to generation of reactive oxygen species (ROS), gut dysbiosis, and
the control group (p<.05).24 suppression of regulatory T cells (Tregs).29 Dermatologists can
evaluate the diet of patients with psoriasis and monitor their
Omega-3 fatty acid supplementation in the form of dietary nutritional status, suggesting dietary changes that complement
modification with the incorporation of omega-3 fatty acid-rich the current standard therapies for psoriasis and address other
foods was also proven to be beneficial. In an open-label study by associated comorbidities (e.g. cardiometabolic disease). There-
Guida et al., 44 obese patients with mild-to-severe plaque psori- fore, exploring and modifying the patient’s nutrition provide a
asis on various immunosuppressive drugs, a greater than 50% personalized framework for managing psoriasis.
reduction in Psoriasis and Severity Index (PASI)scores and 74%
improvement in Dermatology Life Quality Index (DLQI) was CIRCADIAN RHYTHM, LIFESTYLE, AND SKIN
seen versus control (p<0.02) after 6 months of being on a low-cal- HEALTH
orie diet (20kcal/kg/ideal body weight/day) supplemented with
omega-3 fatty-rich foods.25 However, in a double-blind study by Many patients need lifestyle interventions to address mood,
Soyland et al., 145 patients with moderate-to-severe plaque type stress, and metabolic health which all greatly impact the skin.
psoriasis, no statistically significant reduction in PASI was not- Dermatologists can support their patients by starting a con-
ed despite 4 months of supplementation of Omega-3 fat eicos- versation on sleep-wake cycle, how it affects hormone secre-
apentaenoic acid + decosahexaconic acid 5000mg/d.26 tion, and how aligning daily activities of feeding and physical
activity with the body clock can downregulate inflammation
Although its therapeutic benefits need further conclusive at the cellular level to improve chronic skin diseases as well
evidence, Omega-3 fatty acid supplementation may be an option as slow down aging.
to improve or maintain skin health in particular as a possible
adjuvant treatment for inflammatory skin diseases such as atop- The skin as an organ contains and produces hormones that are
ic dermatitis, acne and psoriasis. important in maintaining homeostasis locally and systemically,
as it is involved in complex neuroendocrine pathways that are
PERSONALIZED AND PRECISION MEDICINE: directed by circadian rhythmicity. Melatonin, a highly circadi-
PSORIASIS & NUTRITION an clock-dependent hormone, may be a key agent in the skin’s
ability to neutralize both endogenous and exogenous oxidative
In managing psoriasis, always explore multivariate treat- stress-generating molecules30 and to maintain mitochondrial
ment approaches. These include lifestyle and nutrition. The function in ultraviolet (UV)-exposed keratinocytes.31 If syn-
immunopathogenesis through -omics technology has expand- chronized, the circadian clock allows for a faster and more
ed our understanding of psoriasis. We have different treat-
ment options that specifically targets inflammatory media-

11 J Phil Dermatol Soc · November 2021 · ISSN 2094-201X

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A COLLEAGUE Journal of the Philippine
Dermatological Society
efficient defensive response of transcription factor nuclear
factor-erythroid factor 2 (Nrf2) against environmental insults found VCO was the best humectant and occlusive oil.42 Half-way
and cellular damage from chronic inflammation.32 Aside from analysis in a mild to moderate COVID-19 infection, found signif-
environmental light as the primary synchronizer of the master icant outcome ratings in the VCO adjunctive care group.43 More
clock in suprachiasmatic nucleus, the timing of our feeding and randomized controlled trials for asymptomatic to mild, another
exercise are potent synchronizers as well. For example, it is bet- for severe and critical COVID-19 cases, and a blended learning
ter to perform high-intensity workout earlier in the day, as do- workshop on why and how to use VCO in adjunctive care in three
ing it at night can delay the onset of melatonin secretion which tertiary hospitals are close to Philippine Council for Health Re-
can lead to sleep dysregulation.33 Acute sleep deprivation and search and Development to approval. Since VCO use in these
chronic circadian misalignment can affect cortisol level and the studies continue to show significant results, it is recommended
balance of pro- and anti-inflammatory markers.34 Although the to use topical VCO for barrier repair, antimicrobial and anti-in-
impact of the sleep-wake cycle on specific skin diseases needs flammatory effects, as it is functional and evidence-based.
further studies, improving the overall health of patients is al-
ways a good place to start. PRURITUS AND ACUPUNCTURE

BARRIER REPAIR AND BROAD-SPECTRUM ANTI- Pruritus is a common complaint of dermatology patients.
MICROBIAL EFFECTS OF VIRGIN COCONUT OIL Acupuncture may serve as an adjunct treatment to standard
IN COVID-19 STUDIES therapy.

Use Virgin Coconut Oil (VCO) as a skin disease adjunctive top- Pruritus is commonly associated with dermatologic diseases
ical treatment for barrier repair, antimicrobial and anti-in- such as atopic dermatitis, psoriasis, eczema, and urticaria. Acu-
flammatory effect. puncture, through stimulation of Aγ and C fibers and release of
vasoactive mediators from inflammatory cells, can reduce pru-
Antimicrobial lipid studies in the 1880s halted when the antibi- ritus.44 Additionally, a recent study, showed that the parasympa-
otics era was started by penicillin.35 Released in 1941, resistant thetic activity and functional connectivity of the putamen and
Staphylococcus aureus strains were already reported in 1942. An- posterior part of the midcingulate cortex could be associated
timicrobial resistance (AMR) has become a global problem for with antipruritic response to acupuncture.45 Furthermore, a lo-
many bacteria, viruses, fungi and parasites.36 The rise of more cal study in 2021 showed acupuncture as a promising adjunct
superbugs implicates the high usage now of disinfectants at treatment in atopic dermatitis, significantly reducing pruritus,
medical, other facilities, homes, and for personal use against disease severity and implement of quality of life.46
COVID-19.37,38 Continuing antimicrobial lipid studies rank the
top Fatty acids (FAs) and their Monoglycerides at #(1) Lauric CONCLUSION
(C12-0); #(2) Capric (C10:0); #(3) both Caprylic (C8:0) and Myris-
tic (C14:0). All are saturated medium chains, found highest in This paper summarizes new information on the interplay of
virgin coconut oil (VCO).39 Their mechanism of action includes skin diseases and the interplay with the immune system, en-
destruction of microbial lipid cell membranes and biofilms, in- vironment, and the gastrointestinal system. This concludes
nate immunity and anti-inflammatory effects. This differs from that the health of an individual not only focuses on a single or-
the mechanism of action of antibiotics which target proteins of gan, but different organs can also cause an imbalance in other
microbes, that microbes in turn can readily mutate.40 A com- systems of the body that can lead to alteration of bodily func-
parison review of skin barrier repair, antibacterial, antifungal, tions. The approach of functional and integrative medicine to
wound healing, and skin ageing on 19 plant oils found in VCO overall health is treating all aspects of the body, which also
had a therapeutic benefit and met all functions, except skin can- includes the microbiome. Finally, by better understanding the
cer prevention.41 Another review on plant oils to treat psoriasis root cause of the condition, a personalized treatment can be
formulated that can help control disease and prevent it from
progressing.

ACKNOWLEDGMENTS

We would like to acknowledge the help of Dr. Rea Dapiton for improving the organization of the text, and correcting grammar and syntax errors.

REFERENCES

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J Phil Dermatol Soc · November 2021 · ISSN 2094-201X 12

JPDS LET’S HEAR FROM
Journal of the Philippine A COLLEAGUE
Dermatological Society

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14. Jung GW, Tse JE, Guiha I et al. Prospective, Randomized, Open-Label Trial Comparing the Safety, Efficacy, and Tolerability of an Acne
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15. Seite S, Bieber T. Barrier function and microbiotic dysbiosis in atopic dermatitis. Clin Cosmet Investig Dermatol, 8 (2015), pp. 479-483.
16. O’Hara AM, Shanahan F. The Gut Flora as a Forgotten Organ. EMBO Rep (2006) 7(7):688–93. doi: 10.1038/sj.embor.7400731.
17. Schley PD and Field CJ: The immune-enhancing effects of dietary fibres and prebiotics. Br J Nutr 87 (Suppl 2): S221-S230, 2002.
18. Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, Schilter HC, Rolph MS, Mackay F, Artis D, et al: Regulation of inflammatory responses by
gut microbiota and chemoattractant receptor GPR43. Nature 461: 1282-1286, 2009.
19. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, et al: The International Scientific Association
for Probiotics and Prebiotics statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 11: 506-514,
2014.
20. Zheng J, Feng Q, Zheng S and Xiao X: The effects of probiotics supplementation on metabolic health in pregnant women: An evidence based
meta-analysis. PLoS One 13: e0197771, 2018.
21. Thomsen B, Chow E, Sapijaszko M. The Potential Uses of Omega-3 Fatty Acids in Dermatology: A review. J Cutan Med Surg.2020;00(0)1-14.
doi:10.1177/1203475420929925.
22. Sawada Y,Saito-Sasaki N, Nakamura M. Omega 3 Fatty Acid and Skin Diseases. Front.Immunol. 5 Feb 2021. 11:623052.doi:10.3389/fimmu.2020.623052.
23. Koch C., Dölle S, Metzger M, et al. Docosahexaenoic acid (DHA) supplementation in atopic eczema: a randomized, double-blind,controlled
trial. Br J Dermatol. 2008;158(4):786-792.
24. Jung JY, Kwon HH, Hong JS et al. Effect of Dietary Supplementation with Omega-3 fatty acid and gamma- linoleum acid on acne vulgaris: a
randomized, double-blind,controlled trial. Acts Derm Venereol.2014;94(5):521-525.doi:10.2340/00015555-1802.
25. Guida B, Napoleone A, Trio R et al. Energy-restricted, Omega-3 polunsaturated fatty acids-rich diet improves the clinical response to
immune-modulating drugs in obese patients with plaque type psoriasis: a randomized control clinical trial. Clin Nutr.2014;33(3):399-405.
doi:10.1016/j.clnu.2013.09.010.
26. Soyland E, Funk J,Rajka G, et al. Effect of dietary supplementationwith very long chain n-3 fatty acids in patients with psoriasis. N Engl J
Med.1993;328(25):1812-1816.doi:10.1056/NEJM199306243282504.
27. Aydin B, Arga KY, Karadag AS. Omics-Driven Biomarkers of Psoriasis: Recent Insights, Current Challenges, and Future Prospects. Clin Cosmet
Investig Dermatol. 2020;13:611-625. Published 2020 Aug 25. doi:10.2147/CCID.S227896.
28. Barrea L, Macchia PE, Tarantino G, Di Somma C, Pane E, Balato N, Napolitano M, Colao A, Savastano S. Nutrition: a key environmental dietary
factor in clinical severity and cardio-metabolic risk in psoriatic male patients evaluated by 7-day food-frequency questionnaire. J Transl
Med. 2015 Sep 16;13:303. doi: 10.1186/s12967-015-0658-y. PMID: 26376719; PMCID: PMC4571062.
29. Kanda N, Hoashi T, Saeki H. Nutrition and Psoriasis. Int J Mol Sci. 2020;21(15):5405. Published 2020 Jul 29. doi:10.3390/ijms21155405.
30. Ndiaye MA, Nihal M, Wood GS, Ahmad N. Skin, reactive oxygen species, and circadian clocks. Antioxid Redox Signal. 2014 Jun 20;20(18):2982-96.
doi: 10.1089/ars.2013.5645. Epub 2013 Nov 21. PMID: 24111846; PMCID: PMC4038996.
31. Bocheva G, Slominski RM, Slominski AT. Neuroendocrine Aspects of Skin Aging. Int J Mol Sci. 2019 Jun 7;20(11):2798. doi: 10.3390/ijms20112798.
PMID: 31181682; PMCID: PMC6600459.
32. Frigato E, Benedusi M, Guiotto A, Bertolucci C, Valacchi G. Circadian Clock and OxInflammation: Functional Crosstalk in Cutaneous Homeostasis.
Oxid Med Cell Longev. 2020 Apr 23;2020:2309437. doi: 10.1155/2020/2309437. PMID: 32377292; PMCID: PMC7195654.
33. Oster H, Challet E, Ott V, Arvat E, de Kloet ER, Dijk DJ, Lightman S, Vgontzas A, Van Cauter E. The Functional and Clinical Significance of the
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34. Wright KP Jr, Drake AL, Frey DJ, Fleshner M, Desouza CA, Gronfier C, Czeisler CA. Influence of sleep deprivation and circadian misalignment
on cortisol, inflammatory markers, and cytokine balance. Brain Behav Immun. 2015 Jul;47:24-34. doi: 10.1016/j.bbi.2015.01.004. Epub 2015 Jan 29.
PMID: 25640603; PMCID: PMC5401766.

35. Burtenshaw, JML. (1942). The Mechanism of Self-Disinfection of the Human Skin and Its Appendages. The Journal of Hygiene,1942; 42(2), 184–
210. http://www.jstor.org/stable/3860357.

36. World Health Organization Global Action Plan (GAP) on Antimicrobial resistance-WHO. https://www.who.int/news-room/fact-sheets/detail/
antimicrobial-resistance.

37. Rezasoltani S, Yadegar A, Hatami B, Aghdaei HA, Zali MR. Antimicrobial Resistance as a Hidden Menace Lurking Behind the COVID-19 Outbreak:
The Global Impacts of Too Much Hygiene on AMR. Mini Review Front. Microbiol, 2020 https://doi.org/10.3389/fmicb.2020.590683.

38. Bandyopadhyay S, Samanta I. Antimicrobial Resistance in Agri-Food chain and companion animals as a re-emerging menace in post-COVID
epoci: Low-and middle-income countries Perspective and mitigation strategies Review article Front. Vet. Sci., 2020. | https://doi.org/10.3389/
fvets.2020.00620.

39. Fischer CL. Antimicrobial Activity of Host-Derived Lipids. Antibiotics (Basel). 2020 Feb 11;9(2):75. doi: 10.3390/antibiotics9020075.
40. Casillas-Vargas G , Ocasios-Malave O, Medina S, Morales-Guzman C, del Valle RG, Carballeira NM et al. Review: Antibacterial FAs: An update

of possible Mechanisms of Action and Implications in the development of the next generation of Antibacterial Agents. Progress in Lipid
Research 2021. (820) 101-109.
41. Lin TK, Zhong L, Santiago JL. REVIEW : Anti-Inflammatory and Skin Barrier Repair Effects of Topical Application of Some Plant Oils. Int J Mol Sci.
2017;19(1):70.
42. Verallo-Rowell VM, Katalbas S S, Evangelista MTP, Dayrit JF Review update on Topical Therapy for Psoriasis. Current Dermatology Reports
(2018)7:24-36 DOI 10,1007/s13671-018-0029-x.
43. Verallo-Rowell VM, Calisin CM, Jamora MJ, Santiaguel JR. The efficacy and safety of topical and oral Virgin Coconut Oil on mild to moderate
COVID-19 adult patients; a randomized, open-label controlled trial. Unpublished study. 2021.
44. Lee, Kachiu C. and Lio, Peter A.Traditional Chinese Medicine and Acupuncture in Dermatology. In Norman, Robert A., Shenefelt Philip D and
Rupani Reena N. eds. Integrative Dermatology. New York, Oxford University PRess; 2014: 110-122.
45. Min S, Kim KW, Jung WM, Lee MJ, Kim YK, Chae Y, Lee H and Park HJ. Acupuncture for histamine-induced itch: association with increased
parasympathetic tone and connectivity of putamen-midcingulate cortex. Frontiers in Neurocience, 2019, 13:215.
46. Abad-Constantino, RM, Caro-Chang, LM, Gatmaitan-Dumlao, JKG, Abalos-Bubaran, S, Tan-Gatue, PN and Dofitas BL. Acupuncture as an
adjunct to standard therapy for pruritus in patients with atopic dermatitis: a patient- and assessor-blinded, randomized control trial. ACTA
Medica Philippina. 2021, 55(5): 501-515.

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JPDS ORIGINAL ARTICLE
Journal of the Philippine
Dermatological Society

A randomized, comparative study on the efficacy and
safety of mangosteen 1% extract gel versus benzoyl
peroxide 5% gel in the treatment of mild to moderate

acne vulgaris

Janice Natasha C. Ng, MD, FPDS,1 Maria Vinna N. Crisostomo, MD, DPDS,1 Margaret
Stephanie L. Jimenez, MD, DPDS,1 Mary Jo Kristine S. Bunagan, MD, FPDS1

ABSTRACT

INTRODUCTION Acne vulgaris is a common dermatologic disorder caused by follicular epidermal hyperproliferation, excess se-
bum production, inflammation, and Cutibacterium acnes (C. acnes). The mangosteen fruit rind contains large amount of xantho-
nes, which has high antimicrobial activity against C. acnes.

OBJECTIVES To compare the efficacy and safety of mangosteen 1% extract gel versus benzoyl peroxide (BPO) 5% gel in the treat-
ment of mild to moderate acne vulgaris.

METHODS A total of 60 participants with mild to moderate acne or a rating of 2 or 3 in the Investigator’s Global Assessment (IGA)
for acne were randomized to receive either mangosteen 1% extract gel or BPO 5% gel applied on the face twice daily over an
8-week period. Primary outcomes measured in the study were clinical remission graded as “clear” or “almost clear” (rating of 0 or
1) based on the IGA and any adverse reaction.

RESULTS At week 8, 73% (23/30) in the BPO group and 53% (16/30) in the mangosteen group achieved clinical remission, although
the difference between the two groups were not statistically significant (P = 0.108). In the BPO group, 4% (1/27) had a weak reac-
tion during the 2nd follow up, while in the mangosteen group all participants did not have any reactions; however, this was not
statistically significant (P = 0.627).

CONCLUSION Mangosteen 1% extract gel is a safe and effective alternative treatment for mild to moderate acne vulgaris.

KEYWORDS acne vulgaris, mangosteen extract, benzoyl peroxide

1Department of Dermatology, INTRODUCTION ranked acne as the most commonly diagnosed
Southern Philippines Medical skin disease in 2016.4
Center, Davao City Acne vulgaris is a common dermatologic disor-
der caused by follicular epidermal hyperprolif- The treatment includes benzoyl peroxide
Corresponding author eration, excess sebum production, inflamma- (BPO), tretinoin, and doxycycline.5 However,
Janice Natasha C. Ng, MD, FPDS tion, and the activity of Cutibacterium acnes (C. these can produce a number of side effects and
acnes).1,2 The C. acnes is a gram-positive, anaero- has a high cost of treatment.6 BPO is a broad-spec-
Conflict of interest bic and microaerobic bacterium found within the trum bactericidal agent known to have powerful
None sebaceous follicle.2 oxidizing activity with very mild comedolytic
properties.3 The main adverse effect is irritant
Source of funding Acne can cause emotional distress, reduced contact dermatitis (ICD); and it can also bleach
None self-esteem and impaired psychosocial develop- fabric, hair, clothes, and other colored materi-
ment due to perceived disfigurement.3 The peak als.7
incidence is in the middle-to-late teenage peri-
od, affecting more than 85% of adolescents be- Mangosteen (Garcinia mangostana) is called
tween ages 12 and 24.3 It was reported in 8% of “the queen of fruits” due to its pleasant taste and
adults aged 25 to 34 years and 3% of adults aged aroma.5,8 It is one of the most economical tropi-
35 to 44 years.3 The Philippine Dermatological cal fruits found among the Southeast Asian coun-
Society-Health Information System (PDS-HIS) tries.8,9 Most common mangosteen-producing

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areas in the Philippines are found in Mindanao, which includes (P16052601). Informed consent from all participants was ob-
Davao City.10 tained prior to treatment. Minor participants had to sign an as-
sent form together with the parent consent form.
The mangosteen fruit rind is described as firm, spongy,
and thick that is composed of a yellow, resinous juice.11 Exper- This study included male and female participants, aged
imental studies demonstrated that the mangosteen extract has 12 years old and above, diagnosed with mild to moderate acne
antifungal, antibacterial, antiviral, anti-inflammatory, and an- vulgaris, characterized clinically by non-inflammatory lesions
tioxidant properties.5,11 The fruit rind contains large amounts of (open and closed comedones) and inflammatory lesions (pap-
xanthones, such as α-mangostin, that have high antimicrobial ules to pustules) with a rating of 2 or 3 based on the IGA for acne.
activity against C. acnes.5,8,9,12,13 Participants should have no anti-acne procedures (acne surgery,
intralesional glucocorticoids, phototherapy, or lasers) done for
The concentration of mangosteen fruit rind crude extract the past 2 weeks. Excluded from this study were participants
used in the development of an anti-acne gel was 1%, based on the who are allergic to the active ingredients and who exhibited oth-
study by Jansook et al.14 The mangosteen acne gel was evaluated er facial dermatological conditions that could hinder or obstruct
for its consumer acceptance and had a mean overall preference clinical assessments. Those who needed to use another non-ac-
of 71.7%.15 However, it was not mentioned in the study on how ne topical medication that could interfere with study treatment
the gel decreased the acne lesions, and there was no compari- were also excluded. Participants with any serious and/or uncon-
son done with a standard anti-acne drug.15 A recent study done trolled cutaneous problems, systemic disease, or comorbidities
in Thailand reported that 0.5% topical mangosteen extract gel such as hypertension, diabetes, acquired immunodeficiency
was comparable to 1% clindamycin gel in the treatment of mild syndrome (AIDS), pulmonary, renal, or heart disease, cancer,
to moderate acne vulgaris, in terms of improvement in comedo- or mental illness were likewise excluded.
nes, inflammatory lesion count, clinical evaluation, porphyrin,
and post-acne erythema after 12 weeks of treatment.16 MATERIALS
The study intervention is the application of either mangosteen
The safety of using of mangosteen extract on human sub- 1% extract gel or BPO 5% gel. The mature mangosteen rind was
jects has been well discussed in several studies. A clinical study grinded into a powder by Hale and Hearty Herbaceuticals and
done in the Philippines showed that mangosteen 40% extract it was extracted by an industrial pharmacist using 95% ethanol
ointment used in the treatment of plaque-type psoriasis had for 3 days, done 3 times at room temperature. The filtrates were
no adverse reactions.17 Another study used 400 mg mangosteen pooled and concentrated by a rotary evaporator at 40°C. The ex-
rind extract taken orally thrice a day and was compared with a tract was sent to Jaskin Cosmeceutical Products, at Biñan La-
placebo. The mangosteen group showed a cure rate of 73%, but guna, for compounding of the mangosteen 1% extract gel. The
it was not statistically significant. There were no known adverse formulation of the gel was composed of carbopol 0.2%, trietha-
reactions in the treatment group.13 nolamine 0.15%, glycerine 1%, preservatives (phenoxyethanol
and ethylhexylglycerin) 0.2%, alcohol 20%, water 74.45%, and
Mangosteen rind extract was used as a periodontal gel that mangosteen crude extract 1%.
was applied topically at the subgingival area. After 3 months
of treatment, the subgingival microbial composition improved In a previous study, they formulated the mangosteen crude
with no adverse reactions.18 extract as a gel with 0.5% concentration that had a high efficacy
in inhibiting the growth of acne.15 We increased the concentra-
OBJECTIVES tion of the extract to 1% gel based on the mangosteen anti-acne
formulation done by Jansook et al.14
Our study aimed to compare the efficacy and safety of mango-
steen 1% extract gel versus BPO 5% gel in producing clinical re- Another study showed that the mangosteen crude ex-
mission in patients with mild to moderate acne vulgaris. Specif- tract (95% ethanol) had a minimum bactericidal concentration
ically, the following outcomes were determined in both groups: (MBC) against P.acnes of 15.63 ug/ml, which was equivalent to
Investigator’s Global Assessment (IGA) for acne score, the total 0.0001563%. Hence the 1% concentration of the gel was used in
number of lesions, number of weeks to achieve clinical remis- this study.5 The control intervention was BPO 5% gel obtained
sion, quality of life of the participants using dermatology life from a dermatological pharmaceutical company.
quality index (DLQI), and the incidence of adverse reactions.
RANDOMIZATION, TREATMENT ALLOCATION, AND BLINDING
METHODS Investigator B, who was not involved in the assessment of out-
come, measures randomized the participants using a comput-
TRIAL DESIGN AND PARTICIPANTS er-based randomization list. This was a double-blind study, both
This was a prospective, randomized, double-blind trial con- the participants and investigator A did not know the treatment
ducted at the dermatology out-patient department of a tertia-
ry hospital from January to April 2016. The research protocol
was approved by the Hospital Research and Ethics Committee

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ARTICLE Journal of the Philippine
Dermatological Society

allocation. or Mann-Whitney U test. The significant association between
INTERVENTIONS categorical variables and the treatment groups was analyzed us-
ing Chi-Square test or Fisher’s exact test. Survival analysis was
Both interventions were placed in identical 10-gram plastic used to compare time (in weeks) to clinical remission in both
containers that were pre-coded by investigator B. The mango- groups.
steen gel had a yellow color with a mild mangosteen smell, while
the BPO gel was colorless and had no smell. The primary analysis was carried out using the inten-
tion-to-treat (ITT) principle. A separate analysis excluding pa-
The participants were also provided with a transparent tients lost to follow-up (LTFU) was done in the per-protocol (PP)
and odorless soap, obtained from a dermatological pharmaceu- analysis. Sensitivity analysis with three scenarios was also per-
tical company. After cleansing, the participants were instruct- formed to test the robustness of the primary analysis.
ed to wait 10 minutes to allow the skin to dry completely before
applying the intervention. The intervention was applied twice RESULTS
daily for 8 weeks avoiding the areas around the eyes and lips.
They were advised to apply the intervention using the 1 fingertip STUDY POPULATION
unit (FTU) per application. A total of 60 participants were recruited and randomized to
treatment (mangosteen gel, n=30) and control (BPO gel, n=30)
OUTCOME MEASURES groups. Of these, 9 participants were LTFU as shown in Figure 1.
The participants were evaluated by investigator A at baseline, 2-, The demographic and clinical profile of the participants showed
4-, 6- and 8-week follow-up. The primary outcome of the study no significant difference between the two treatment groups at
was the clinical remission defined as “clear” or "almost clear" baseline (Table 1).
(IGA score 0 or 1). Treatment failure was defined as IGA score
same as baseline (IGA 2 or 3) or an increase in the baseline. Sec- All drop-outs were not included in the PP analysis, as pre-
ondary outcomes include the mean percentage reduction of the sented in Table 2. In the BPO group, 81% had “almost clear” score
total lesion count per treatment group at week 8 and the number at week 8 (P = 0.035). In the mangosteen group, 4% had “clear”
of participants in either group who had adverse reactions. score and 63% had “almost clear” score at week 8 (P = 0.017).

The IGA acne score, lesion count, and adverse reactions CLINICAL REMISSION (PP ANALYSIS AT WEEK 8)
such as erythema, stinging/burning, pruritus, and eczema Using the PP analysis, all LTFU were not included. At week 8, the
was evaluated by Investigator A. The adverse reaction grading BPO group had 81% clinical remission compared to mangosteen
was based from the International Contact Dermatitis Research group with 67%.
Group and was categorized as negative (0), weak (1+), strong (2+),
and extremely strong reaction (3+).19 Participants with a score of CLINICAL REMISSION (ITT ANALYSIS AT WEEK 8)
3 + were advised to discontinue the treatment. Participants with Using the ITT analysis, all LTFU were included. At week 8, the
a score of 1 + or 2 + were advised to continue with every other day BPO group had 73% clinical remission compared to mangosteen
application of the intervention. If there was an improvement in group with clinical remission of 53%.
the reaction, they will be advised to return to daily application.
On the final follow-up (8th week), participants were asked to an- SENSITIVITY ANALYSIS
swer the Dermatology Life Quality Index (DLQI) and those con- Sensitivity analysis was done to test for the robustness of the
sidered as treatment failure, were given the standard treatment. primary analysis. Three case scenarios were used:

SAMPLE SIZE COMPUTATION In the 1st scenario, we assumed that all LTFU from both
The sample size computation was based on the following as- groups achieved clinical remission with an IGA score of 0-1
sumptions: population 1 is BPO 5% with a proportion of 1.00 (clear/almost clear). At week 8, the BPO group had a clinical re-
based from the study of Busa et al. and population 2 is mango- mission rate of 83% compared to 73% in the mangosteen group
steen 1% extract gel with a proportion of 0.67 based on the study (P = 0.347).
of Delima et al.20,21 The confidence level was set at 0.95, with the
power of 0.8 and a ratio of 1:1 using a two-tailed test. A total In the 2nd scenario, it was assumed that all LTFU from the
number of at least 60 participants, 30 in each group, was the BPO group have achieved clinical remission with an IGA score of
sample size for this study. 0-1 (clear/almost clear) and all LTFU of from mangosteen group
were considered as treatment failure having an IGA score of 2-3
STATISTICAL METHODS (mild/moderate). At week 8, the BPO group had a clinical remis-
The data gathered were encoded into Microsoft Excel. Descrip- sion rate of 83% compared to 53% in the mangosteen group (P
tive analysis was used for the demographic data. The significant =0.012).
difference was analyzed using either the t-test for two samples
In the 3rd scenario, it was assumed that all LTFU from BPO
group had treatment failure having an IGA score of 2-3 (mild/
moderate) and all LTFU from mangosteen group have achieved

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Table 1. Baseline demographic and clinical data of the participants.

Characteristics BPO 5% gel (n=30) Mangosteen 1% extract gel Total p-value
(n=30) (n=60) 0.518*
Gender 12 , 57% 0.780¥
Male 18 , 46% 9 , 43% 21 , 35% 0.844*
Female 21.73 ± 5.42 21 , 54% 39 , 65% 0.617*
11 , 46% 21.37 ± 4.69 21.55 ± 5.055
Age, Mean ± SD 17 , 50% 13 , 54% 24 , 40% 0.508*
10 - 20 years old 2 , 100% 17 , 50% 34 , 57% 0.576¥
21 to 30 years old 0.481¥
31 to 40 years old 15 , 48% 0 , 0% 2 , 3% 0.677¥
13 , 52% 0.519¥
Occupation 2 , 50% 16 , 52% 31 , 52% 0.317*
Student 12 , 48% 25 , 42% 0.319*
Employed 16 , 55% 2 , 50%
Unemployed 14 , 45% 4 , 7% 0.321*
63.57 ± 23.24 13 , 45% 0.254*
Clinical severity based on IGA (baseline) 14.27 ± 7.44 17 , 55% 29 , 48%
Mild 49.3 ± 19.86 67.3 ± 28.05 31 , 52% 0.687*
Moderate 4.42 ± 3.42 15.77 ± 8.9 65.44 ± 25.65 0.642*
51.53 ± 21.49 15.02 ± 8.17
Number of lesions, mean ± SD 20 , 50% 5.1 ± 4.61 50.42 ± 20.68 18
Inflammatory 10 , 50% 4.76 ± 4.02
Non-Inflammatory 20 , 50%
22 , 51% 10 , 50% 40 , 67%
Duration, mean ± SD 8 , 47% 20 , 33%
Family history (acne) 8 , 47% 21 , 49%
1 , 33% 9 , 53% 43 , 72%
Yes 0 , 0% 9 , 53% 17 , 28 %
No 0 , 0% 2 , 67% 17 , 28 %
Acne procedures 2 , 40% 0 , 0%
No 0 , 0% 3 , 5%
Yes 4 , 50% 3 , 60% 0 , 0%
Acne surgery 26 , 49% 0 , 0%
10 , 38% 4 , 50% 5 , 8%
Intralesional glucocorticoid injection 11 , 48% 27 , 51%
Phototherapy 13 , 41% 16 , 62% 8 , 13%
Lasers 21 , 54% 12 , 52% 53 , 88%
Others (chemical peel) 1 , 25% 19 , 59% 26 , 43%
Previous treatment 3 , 60% 18 , 46% 23 , 38%
Total oral 2 , 67% 3 , 75% 32 , 53%
Total topical 2 , 40% 39 , 65%
Medicated cleansers 0 , 0% 1 , 33%
Topical retinoids 1 , 100% 4 , 7%
Topical antimicrobials 0 , 0% 5 , 8%
Astringents 3 , 38% 0 , 0% 3 , 5%
Other topical 2 , 50% 5 , 63% 1 , 2%
Oral antibiotics 2 , 50% 2 , 50%
Oral contraceptives 1 , 33% 2 , 50% 0 , 0%
Oral glucocorticoids 2 , 67% 8 , 13%
Current Treatment 4 , 7%
Total oral 4 , 7%
Total topical 3 , 5%
Topical retinoids
Topical antimicrobials
Astringents
* - Chi-square test; ¥ - t-test; IGA - Investigator’s Global Assessment.

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Dermatological Society

Figure 1. Flow chart of participants. J Phil Dermatol Soc · November 2021 · ISSN 2094-201X

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AB
Table 2. Comparison of IGA score before and after the treatment in each study arm (per-
protocol analysis). Figure 3. A. Representative clinical photo of a patient treated with BPO 5% gel at baseline.
B. At 8 weeks follow-up.
Treatment Baseline Week 8 p-value
BPO 5% gel (n=27) 0.035*
Clear 0 , 0% 0 , 0%
Almost Clear 0 , 0% 22 , 81% 0.017*
Mild 16 , 53% 5 , 19%
Moderate 14 , 47%
Mangosteen 1% extract gel 0 , 0%
(n=24) 0 , 0%
Clear 1 , 4%

Almost Clear 0 , 0% 15 , 63%
Mild 13 , 43% 8 , 33%
Moderate 17 , 57% 0 , 0%
Note: Chi-square test

AB

Figure 2. Comparison of the number of lesions after 8 weeks of treatment between both Figure 4. A. Representative clinical photo of a patient treated with mangosteen 1% gel at
groups. baseline. B. After 8 weeks.

clinical remission with an IGA score of 0-1 (clear/almost clear). Survival analysis was done using the Kaplan-Meier curve
At week 8, the BPO group had a clinical remission rate of 73% and the log rank test, to determine the number of weeks to
compared to 73% of mangosteen group (P =0.991). achieve clinical remission. At weeks 4 and 6, BPO group showed
a lower cumulative survival than mangosteen group. It took 6
COMPARISON OF THE NUMBER OF LESIONS AFTER TREAT- weeks for the BPO group compared to 6.3 weeks for the mango-
MENT BETWEEN BOTH GROUPS steen group to achieve clinical remission (P > 0.05).
In the BPO group, the percent decrease in the total number of
lesions at week 8 was (76.06%), inflammatory lesions (71.69%), ADVERSE REACTION RATE
and non-inflammatory lesions (77.3%) as presented in Figure 2. In the BPO group, 4% (1/27) presented with a weak reaction
In the mangosteen group, a decrease was noted in the total num-
ber of lesions (72.32%), inflammatory (73.81%), and non-inflam- on the 2nd follow-up. The medication was tapered to every other
matory lesions (71.86%). The decrease in the number of lesions day application. On the succeeding follow-up, the patient did not
in both groups had a P-value < 0.05. have any reaction so the treatment was continued to twice a day
application. In the mangosteen group, all participants did not

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ARTICLE Journal of the Philippine
Dermatological Society

have any adverse reactions. LTFU of EVCO group had treatment failure. This was assigned
as the worst-case scenario because the best possible outcome
QUALITY OF LIFE was assigned to all the LTFU of BPO group and the worst out-
The quality of life of the participants on both groups were com- come were assigned to all LTFU on the mangosteen group. In
pared at baseline and at week 8 follow-up. The improvement this worst-case scenario, the difference between 2 groups was
was graded as none, 1 scale, 2 scale, and 3 scale. Majority of the statistically significant (P = 0.012). The 3rd case was the best-
participants in the BPO group reported no improvement and 1 case scenario, we assumed that after 8 weeks, all LTFU of the
scale improvement (44%, 44% respectively). In the mangosteen BPO group were treatment failure and all LTFU from the man-
group, most (42%) had 1 scale improvement. Below are the rep- gosteen group achieved clearance rate after 8 weeks. The dif-
resentative photos of the participants treated with BPO 5% gel ference between two groups was not statistically significant (P
and mangosteen 1% extract gel (Figures 3 and 4). =0.991). Therefore, we can assume that the possible dropouts in
mangosteen group can significantly alter our conclusion.
DISCUSSION
In terms of observed adverse reactions, BPO group had
Using the ITT analysis, all LTFU in either group were considered more reactions compared to mangosteen group, although the
as treatment failure. The clinical remission rate after 8 weeks in difference was not statistically significant. According to pub-
BPO group was slightly higher (73%) compared to mangosteen lished literature, BPO can cause irritant contact dermatitis
group (53%) however, the difference was not statistically signif- manifesting as erythema, pruritus, stinging/burning, and ec-
icant (P=0.108). zema.1-3,7 In addition, the adverse effects of BPO were also re-
corded in the several local studies.20,21 In our study, tapering of
PP analysis was also done, which did not include LTFUs in the medication was done in the BPO group because there was 1
both groups. The BPO group had a higher clinical remission rate participant who had a weak reaction (1+). The medication was
(81%) compared to (67%). The difference between the two groups tapered to every other day. On week 4, there was improvement
was not statistically significant (P =0.634). in the reaction and was advised to return to daily application of
the medication. In the mangosteen group, several studies estab-
In both ITT analysis and PP analysis of the clinical remission lished a good safety profile of the drug.16-18 Mangosteen could be
rate, statistical results showed no significant difference between an alternative natural treatment for patients with acne vulgaris
the two treatment groups (P = 0.108, 0.634 respectively). These who experienced irritation towards BPO.
would indicate that the treatment group (mangosteen) is compara-
ble with the control group (BPO) in achieving clearance. In terms of achieving clinical remission, the standard
drug for acne- BPO group achieved clinical response at 6 weeks.
Mangosteen extract is effective in reducing acne lesions be- Based on the number of weeks, BPO group had a slightly faster
cause it can target the two main pathogenesis of acne: inflamma- effect in terms of clinical remission when compared to mango-
tion and P.acnes. Its major component α-mangostin has a potent steen group. Thus, clinically this would translate that mango-
anti-inflammatory activity and also a high antimicrobial activity steen group needs to be applied longer compared to BPO, but it
towards C. acnes.22,23 A study was done to determine the antimicro- is still effective in achieving clinical response.
bial activity of 19 medicinal plant extracts from Thailand against C.
acnes. Among these, mangosteen extract had the greatest antimi- In our study, we also assessed the lesion reduction from
crobial effect. On broth dilution method, the minimum inhibitory baseline until 8 weeks. The inflammatory lesion reduction
concentration (MIC) and (MBC) values against C. acnes were both on BPO group was 71.69% compared to 73.81% of mangosteen
0.039 mg/ml.23 Bioautography assay showed that mangosteen ex- group. This finding was consistent with the mentioned proper-
tract produced strong inhibition zones ( ≥ 15 mm) against C. acnes.23 ties of mangosteen. The non-inflammatory lesions (open and
The mature mangosteen rind contained more α-mangostin and had closed comedones) reduction on BPO group was 77.3%, while in
better bactericidal activity against C. acnes at 15.63 μg/ml as com- the mangosteen group it was 71.86%. The results for BPO was al-
pared to 31.25 μg/ml of the young rind.8 ready expected since it is known to have mild comedolytic prop-
erties.1,2,7 For the mangosteen group, the findings of our study
Mangosteen extract is also known to have anti-oxidant ac- could suggest that it has comedolytic effects. The reduction in
tivity that can inhibit reactive oxygen species (ROS) and pros- non-inflammatory lesions could be explained by its antibacte-
taglandin E2 (PGE2).9,24 These molecules can attract more in- rial activity against C. acnes, since C. acnes is also involved in
flammatory cells, thereby leading to the development of more the process of comedogenesis.16 A previous study used a combi-
inflammatory acne lesions.25 nation of herbal extracts that included mangosteen and it was
found to be effective in the treatment of acne, possibly due to the
Sensitivity analysis was done using a worst case-best case synergistic effect of each component.25
scenario. In the 1st case, we assumed that all the LTFU on both
groups achieved clearance rate after 8 weeks, the difference During the initial recruitment and completion of the study
between two groups was not statistically significant (P =0.347). (8 weeks), the participants were asked to fill up a DLQI question-
The 2nd case was the worst case scenario, we assumed that af-
ter 8 weeks, all LTFU of BPO group achieved clearance while all

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Dermatological Society

naire. In the BPO group, 7% had 2 scale improvement compared We recommend further studies with a longer duration to
to 33% of mangosteen group. Both groups showed almost simi- further evaluate its efficacy and safety and to accurately assess
lar percentage in the 1 scale improvement. However, the differ- the length of time needed to achieve clinical remission. We also
ence in the quality of life of both groups was not statistically sig- recommend to compare the anti-acne effect of the test drug us-
nificant. These would indicate that the participants from both ing different bases to determine the most appropriate formula-
treatment group had comparable quality of life. tion and to conduct a study on different skin types. The test drug
can also be combined with other anti-acne medications such as
One limitation of this study was the short duration of fol- BPO, to evaluate its possible synergistic effect that might lead to
low-up because some topical acne treatment may need a longer faster clinical remission.
duration to achieve complete remission as seen in other stud-
ies.26,27 The study participants were all Southeast Asians and CONCLUSION
different skin types among races have different skin charac-
teristics that might lead to a different effect of the drug. This Mangosteen 1% extract gel had comparable clearance rate with BPO
study was also limited by the use of monotherapy and cannot 5% gel in the treatment of mild to moderate acne vulgaris. The raw
predict the possible interactions with other anti-acne medica- materials of the test drug are indigenous to our locality and readily
tions which is important in clinical practice since the current accessible even in remote areas. Hence, mangosteen extract 1% gel
treatment approach to acne vulgaris is combination therapy. is an efficacious and safe alternative treatment for acne vulgaris.

REFERENCES

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2. Zaenglein A, Graber E, Thiboutot D. Acne Vulgaris and Acneiform Eruptions. In: Goldsmith L, Katz S, eds. Fitzpatrick's dermatology in general

medicine. 8th ed. New York: McGraw-Hill; 2012:897-917.
3. Leyden J. A review of the use of combination therapies for the treatment of acne vulgaris. J Am Acad Dermatol. 2003 Sep 30;49(3). DOI: 10.1067/

s0190-9622(03)01154-x.
4. Philippine Dermatological Society Health Information Systems. Philippine Dermatological Society; 2011. [email protected]. Accessed

October 3, 2016.
5. P othitirat W, Chomnawang MT, Gritsanapan W. Anti-acne-inducing bacterial activity of mangosteen fruit rind extracts. Med Princ Pract.

2010;19(4):281-286. DOI: 10.1159/000312714.
6. A zimi H, Fallah-Tafti M, Khakshur AA, Abdollahi M. A review of phytotherapy of acne vulgaris: perspective of new pharmacological treatments.

Fitoterapia. 2012;83(8):1306-1317. DOI: 10.1016/j.fitote.2012.03.026.
7. M otaparthi K, Hsu S. Topical Antibacterial Agents. In: Wolverton S, ed. Comprehensive Dermatologic Drug Therapy. 3rd ed. Edinburg: Elsevier;

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8. K humsupan P, Gritsanapan W. Anti-acne activity of Garcinia mangostana L.: A review. Plant Science Today. 2014 Aug 14;1(3):147-150. DOI: 10.14719/

pst.2014.1.3.39.
9. Pedraza-Chaverri J, Cárdenas-Rodríguez N, Orozco-Ibarra M, Pérez-Rojas JM. Medicinal properties of mangosteen (Garcinia mangostana).

Food Chem Toxicol. 2008;46(10):3227-3239. DOI: 10.1016/j.fct.2008.07.024.
10. Osman M, Milan A. Mangosteen Garcinia mangostana L. In: Williams JT, Smith RW, Haq N, Dunsiger Z, eds. Chichester, England, UK: Southampton

Centre for Underutilised Crops; 2006.
11. Dweck A. A review of Mangosteen (Garcinia mangostana) Linn. 2003:8. Accessed 2016 Sept 27.
12. Priya V, Jainu M, Mohan S, Saraswathi P, Gopan S. Antimicrobial activity of pericarp extract of Garcinia mangostana Linn. Int J Pharm Sci Res.

2010;1:278-281.
13. S utono T. Efficacy of Garcinia mangostana L. (mangosteen rind extract) to reduce acne severity. Med J Indones. 2013 Aug 1;22(3):167-172. DOI:

10.13181/mji.v22i3.586.
14. Jansook P, Sompukdee A, Rattranakosekit M, Kokiatinun A, Pothitirat W. Development and evaluation of anti-acne microemulsion gel

containing extracts of mangosteen fruit rind. Thai J Pharm Sci. 2010;36:158-161.
15. Sukatta U, Rugthaworn P, Pitpiangchan P, Dilokkunanant U. Development of mangosteen anti-acne gel. Kasetsart J (Nat Sci). 2008;42(5):163-

168.
16. Lueangarun S, Sriviriyakul K, Tempark T, Managit C, Sithisarn P. Clinical efficacy of 0.5% topical mangosteen extract in nanoparticle loaded

gel in treatment of mild-to-moderate acne vulgaris: A 12-week, split-face, double-blinded, randomized, controlled trial. J Cosmet Dermatol.
2019. DOI: 10.1111/jocd.12856.
17. Gallega G, Bunagan M, Visitacion L. A pilot study on the efficacy of mangosteen 40% extract ointment compared to clobetasol propionate
0.05% ointment in the treatment of plaque type psoriasis vulgaris. In: Philippines; 2009.
18. Rassameemasmaung S, Sirikulsathean A, Amornchat C, Maungmingsook P, Rojanapanthu P, Gritsanaphan W. Topical application of Garcinia
mangostana L. pericarp gel as an adjunct to periodontal treatment. Complement Ther Med. 2008;16(5):262-267. DOI: 10.1016/j.ctim.2007.12.004.
19. F onacier L, Bernstein DI, Pacheco K, et al. Contact dermatitis: a practice parameter-update 2015. J Allergy Clin Immunol Pract. 2015;3(3

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Suppl):S1-39. DOI: 10.1016/j.jaip.2015.02.009.
20. D elima C, Belisario M, Bunagan M. A randomized investigator-blinded clinical trial evaluating the efficacy and safety of Ocimum basilicum

(Sweet Basil) 2% cream vs benzoyl peroxide 5% cream in the treatment of mild to moderate acne vulgaris. In: Philippines; 2010.
21. B usa M, Ng J, Lacuesta-Gutierrez M. A prospective, randomized, double-blind, comparative study on the efficacy and safety of 2% enzymatic

virgin coconut oil monoglyceride cream versus 5% benzoyl peroxide cream in the treatment of mild to moderate acne vulgaris. J Phil Dermatol
Soc. 2018;27(2):18-30.
22. Chomnawang MT, Surassmo S, Nukoolkarn VS, Gritsanapan W. Effect of Garcinia mangostana on inflammation caused by Propionibacterium
acnes. Fitoterapia. 2007;78(6):401-408. DOI: 10.1016/j.fitote.2007.02.019.
23. C homnawang MT, Surassmo S, Nukoolkarn VS, Gritsanapan W. Antimicrobial effects of Thai medicinal plants against acne-inducing bacteria.
J Ethnopharmacol. 2005;101(1-3):330-333. DOI: 10.1016/j.jep.2005.04.038.
24. N akatani K, Atsumi M, Arakawa T, et al. Inhibitions of histamine release and prostaglandin E2 synthesis by mangosteen, a Thai medicinal plant.
Biol Pharm Bull. 2002;25(9):1137-1141. DOI: 10.1248/bpb.25.1137.
25. Yang JH, Hwang EJ, Moon J, et al. Clinical efficacy of herbal extracts in treatment of mild to moderate acne vulgaris: an 8-week, double-
blinded, randomized, controlled trial. J Dermatolog Treat. 2021;32(3):297-301. DOI: 10.1080/09546634.2019.1657792.
26. S chmidt N, Gans EH. Clindamycin 1.2% Tretinoin 0.025% Gel versus Clindamycin Gel Treatment in Acne Patients: A Focus on Fitzpatrick Skin
Types. J Clin Aesthet Dermatol. 2011;4(6):31-40. PMCID: PMC3140902.
27. G old LS, Tan J, Cruz-Santana A, Papp K, Poulin Y, Schlessinger J, Gidner J, Liu Y, Graeber M; Adapalene-BPO Study Group. A North American study
of adapalene-benzoyl peroxide combination gel in the treatment of acne. Cutis. 2009 Aug;84(2):110-6. PMID: 19746769.

23 J Phil Dermatol Soc · November 2021 · ISSN 2094-201X

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Journal of the Philippine
Dermatological Society

Prevalence of Vitamin D insufficiency and deficiency
among seborrheic dermatitis patients: a cross-
sectional study at Makati Medical Center

Reagan Grey T. Reyes, MD, DPDS,1 Ma. Lourdes Aragon - De Veyra, MD, FPDS1

ABSTRACT

INTRODUCTION Seborrheic dermatitis is a chronic and recurrent inflammatory dermatosis affecting different age groups with a
prevalence rate of 1–5% among Asian adults. Due to its immune-modulatory and anti-inflammatory properties, vitamin D has been
correlated with inflammatory dermatoses such as seborrheic dermatitis.

OBJECTIVES To determine the prevalence of vitamin D insufficiency, deficiency and severe deficiency among Filipino adult pa-
tients with moderate to severe seborrheic dermatitis.

METHODS A single-center, analytical, cross-sectional study at Makati Medical Center, which included Filipino patients aged 18–
60 years, diagnosed with moderate-to-severe seborrheic dermatitis based on Investigator's Static Global Assessment (ISGA)
with serum vitamin D levels classified as normal, insufficient, deficient and severely deficient.

RESULTS We included 61 patients, 5 patients (8%) of whom presented with normal Vitamin D levels. Twenty-one patients (34%) pre-
sented with vitamin D insufficiency, 32 patients (52%) presented with vitamin D deficiency, while 3 patients (5%) presented with se-
vere deficiency. Vitamin D insufficiency and deficiency were more prevalent among patients in the younger age group (p = 0.001),
with predominant scalp lesions (p = 0.006), and those who are single (p = 0.015). There was no statistically significant difference in
the prevalence of vitamin D insufficiency and/or deficiency based on seborrheic dermatitis severity as per ISGA scale (p = 0.126).

CONCLUSION Seborrheic dermatitis in Filipinos has been associated with vitamin D insufficiency, deficiency and severe defi-
ciency. The prevalence of vitamin D deficiency is seen in almost half of patients while vitamin D insufficiency is seen in almost
one-third of patients with seborrheic dermatitis. While topical and oral medications have been the treatment of choice for seb-
orrheic dermatitis, the role of oral vitamin D supplementation as adjunct treatment may be studied.

KEYWORDS seborrheic dermatitis, vitamin D deficiency, vitamin D insufficiency

1Department of Dermatology, INTRODUCTION climates and during periods of increased stress.2
Makati Medical Center, Legaspi Adult seborrheic dermatitis present most
Village, Makati City, Philippines Seborrheic dermatitis is one of the most com-
mon dermatoses affecting infants, adolescents, often on the face and/or scalp as ill-defined ery-
Corresponding author and adults. It is a chronic inflammatory derma- thematous patches associated with fine scaling,
Reagan Grey T. Reyes, MD, DPDS tologic condition that usually appears on areas involving one or more sites of predilection. Al-
of the body with a large density of sebaceous though the etiology of adult seborrheic dermati-
Conflict of interest glands, such as the scalp, face, chest, back, ax- tis is not definitely known, there are three prin-
None illa, and groin. Cheong et al. in 2015 estimated cipal factors that appear to play a role: sebaceous
seborrheic dermatitis prevalence rate in Asian gland secretion, alteration in colonization and
Source of funding adults to be 1-5%.1 Although it can be associated metabolism of cutaneous microflora (Malassezia
None with nutritional deficiency, a weakened immune species), and individual susceptibility and host
system (e.g., human immunodeficiency virus response.3
infection), and neurologic disease (e.g., cardio-
vascular event, Parkinson’s disease), seborrheic Studies have shown that vitamin D has ef-
dermatitis typically occurs in healthy persons. fects on the sebaceous gland. It has been report-
It has a bimodal distribution, with peaks at two ed that incubation of the human sebaceous gland
to twelve months of age and in adolescence and cell line with 1,25-dihydroxyvitamin D results in
early adulthood. It is more severe in cold and dry a dose-dependent suppression of cell prolifera-
tion.4 This led to the conclusion that local synthe-

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sis or metabolism of vitamin D metabolites may be of impor- with inflammatory skin conditions, there is a lack of published
tance for growth regulation and various other cellular functions articles showing a correlation between vitamin D levels and
in sebaceous glands and that sebaceous glands represent prom- seborrheic dermatitis among Filipinos.11,12
ising targets for therapy with vitamin D analogs.4
The primary objective of this study is to determine the
Vitamin D is a fat-soluble nutrient that humans obtain prevalence of vitamin D insufficiency, defined as laboratory
through the diet and by synthesis in the skin upon exposure to values between 20–30 nmol/L, vitamin D deficiency, defined as
ultraviolet B. It is then converted by the liver to 25-hydroxyvi- laboratory values < 20 nmol/L, and severe vitamin D deficiency,
tamin D, which is the easily measurable and major circulating defined as laboratory values < 10nmol/L, among seborrheic der-
form, hence the best indicator of vitamin D nutritional status. matitis patients in Makati Medical Center, Makati, Philippines.
Under the influence of parathyroid hormone, the kidney then
converts 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, the Furthermore, this study aims to identify the prevalence
biologically active, hormonal form of importance in the metab- of vitamin D insufficiency, deficiency, and severe deficiency
olism of calcium and phosphorus. Outside of the skeletal sys- among patients with moderate and severe seborrheic dermati-
tem, many cell types, including various cells in the skin, also tis as classified according to the Investigator’s Static Global As-
express the vitamin D receptor.5 sessment (ISGA) scale, as well as its correlation to age, sex, civil
status, duration of illness, previous treatment for seborrheic
According to a study by Dimitrova in Bulgaria, the pre- dermatitis, past illnesses, allergies, and physical examination
ferred level of serum 25-hydroxyvitamin D for adults is 30–70 findings.
ng/mL. The value of 21–29 ng/mL is interpreted as insufficien-
cy and a level less than 20 ng/mL as deficiency. Serum 25-hy- MATERIALS AND METHODS
droxyvitamin D levels under 10 ng/mL is evaluated as a severe
deficiency based on the electrochemiluminescence immunoas- This is a single-center, analytical cross-sectional study conduct-
say (ECLIA) method analyzer.6 ed at the outpatient dermatology clinics and inpatient facilities
of Makati Medical Center, Makati City, Philippines, from 2016
In the Philippines, Tanchee-Ngo et al. studied vitamin D to 2018.
levels among admitted Filipino elderly patients and noted that
serum 25-hydroxyvitamin D levels were as follows: > 30 nmo- We included the following patients: Filipino aged 18 to 60
l/L (adequate), 20–30 nmol/L (inadequate/insufficient), and < 20 years with Fitzpatrick skin phototype III and IV; clinically diag-
nmol/L (deficient).7 nosed with moderate to severe scalp, facial, and scalp with fa-
cial seborrheic dermatitis with a baseline seborrheic dermatitis
According to a review by Mostafa et al., vitamin D defi- severity score of three (moderate: coarse scale with moderate
ciency appears to be a marker of ill health regardless of being red coloration/moderate plaque thickness) or four (severe: thick
an actual cause or an association. His review highlighted the tenacious scale with deep coloration/severe plaque thickness) as
most commonly studied dermatological diseases that were as- determined by an Investigator’s Static Global Assessment (ISGA)
sociated with vitamin D, namely: skin cancer, psoriasis, vitiligo, specific for seborrheic dermatitis (Table 1); and with signed in-
scleroderma, systemic lupus erythematosus, atopic dermatitis, formed consent.
acne vulgaris and alopecia.8
We excluded patients with: other active eczemas or pso-
Palmer et al. indicated in their study a link between vita- riasis on the same location of the seborrheic dermatitis (face
min D and eczema outcomes and showed that lower serum vita- and/or scalp); active, localized, or systemic infection diagnosed
min D levels is associated with increased incidence and sever- before determination of vitamin D levels; untreated cutaneous
ity of eczema symptoms.9 The study concluded, however, that
current available evidence does not allow firm conclusions to Table 1. Seborrheic Dermatitis-specific Investigator's Static Global Assessment (ISGA
be made on whether vitamin D status affects the development of scale).
atopic eczema.9 In a recent study, noted spontaneous remission
of seborrheic dermatitis in summer, and the therapeutic effects Score Interpretation Description
of vitamin D on other papulosquamous dermatosis such as pso-
riasis.6 0 Clear Clear, except for minor residual discoloration

Of late, studies have demonstrated that keratinocytes pos- 1 Faint Occasional fine scale, faint erythema/barely perceptible plaque
sess vitamin D receptors that inhibit the proliferation and stim-
ulate the differentiation of the epidermal cells. Furthermore, thickness
vitamin D receptor ligands diminish the expression of proin-
flammatory cytokines, exerting therapeutic effect in many au- 2 Mild Fine scale with light coloration/mild plaque elevation
toimmune and skin diseases.6
3 Moderate Coarse scale with moderate red coloration/moderate plaque
Despite several studies showing a correlation of vitamin D thickness

4 Severe Thick tenacious scale with deep coloration/severe plaque
thickness

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malignancies on the face; and compromised immune system. of the study.
The sample size was computed based on a previous study
RESULTS
of Dimitrova J,6 which showed that the estimated proportion of
vitamin D insufficiency in patients with seborrheic dermatitis is A total of 61 patients were enrolled to this study (Table 2). The
90%. With a margin of error of 8% and a 95% confidence inter- mean age was 46.5 years (SD 13.7). Forty-three percent (26) of
val, the computed sample size was 55. To account for the possi- the participants were males while 57% (35) were females; 59%
bility of 10% attrition rate and/or missing data, the final sample (36) were single while 41% (25) were married. For the duration
size was amplified to 62. of illness, 21% (13) of the participants had lesions for less than a
month, 54% (33) had lesions for less than a year, while 25% (15)
For all patients included in the study, after baseline history had lesions for more than a year. Fifty-four percent (33) of all
and physical examination, clinical photography, and determi- study patients had previous treatment for seborrheic dermati-
nation of overall skin condition severity through the ISGA scale, tis. A total of 46% (28) had illnesses such as hypertension and
vitamin D assay determination using the Abbott Architect Che- diabetes mellitus while 5% (3) had known allergies. For ISGA
miluminescent Microparticle Immunoassay (CMIA) analyzer scale, 95% (58) were classified as moderate, while 5% (3) were
method was done at Makati Medical Center Laboratory Depart- classified as severe. A total of 16% (10) were seen as inpatients
ment by a registered medical technologist who underwent prop- that were referred to Dermatology Service for the management
er training given by the tertiary hospital. of seborrheic dermatitis, while 84% (51) were seen as outpa-
tients. Majority (52%, 32) presented with lesions on the scalp,
Blood extraction was done on an accessible vein on the 36% (22) had lesions on the face, while 11% (7) had lesions on
forearm (antecubital vein). Proper calibration of the machine both the face and scalp.
was ensured and done multiple times in a year coinciding with
the change and/or refill of the reagent. The prevalence of vita- Only five patients (8%) presented with normal vitamin D
min D insufficiency, defined as values between 20–30 nmol/L, levels (median 47.8 nmol/L, IQR 34.6 to 53.2). Twenty-one pa-
vitamin D deficiency, defined as values < 20 nmol/L, as well as tients (34%) had insufficient vitamin D levels (median 23.1 nmo-
severe vitamin D deficiency, defined as values < 10nmol/L, were l/L, IQR 21.6 to 24.3), 32 (52%) had deficient vitamin D levels
determined. The clinical profile of the patients was determined (median 17.8 nmol/L, IQR 12.0 to 17.7), while 3 (5%) had severely
based on age, sex, body mass index, duration of lesions, as well deficient vitamin D levels (median 8.5 nmol/L, IQR 6.0 to 8.7)
as past illnesses. (Table 2).

A descriptive summary of the demographic and clinical A test of significance showed a statistically significant dif-
characteristics of the patients was done using frequency and ference in the mean age between the groups (p = 0.001), with pa-
proportion for categorical variables, median and interquartile tients with insufficient and deficient vitamin D levels belonging
range (IQR) for non-normally distributed continuous variables, to the younger age group.
and mean and standard deviation for normally distributed con-
tinuous variables. Shapiro-Wilk was used to test the normal- All subjects with normal vitamin D levels were married
ity of the continuous variables. One-way analysis of variance (Table 2). For participants with normal vitamin D levels, 60% (3)
(ANOVA) and Fisher’s exact test was used to determine the dif- presented with lesions on the face while 40% (2) presented with
ference of mean and frequency, respectively. Missing values lesions on both the face and scalp (Table 2). For participants
were neither replaced nor estimated. Null hypotheses were with insufficient vitamin D levels, 71% (15) had lesions on the
rejected at less than 0.05 α-level of significance. STATA version scalp and 29% (6) had lesions on the face. For participants with
13.1 was used for data analysis. The study commenced upon the deficient vitamin D levels, 53% (17) had lesions on the scalp, 34%
approval of the Institutional Review Board. (11) had lesions on the face, and 13% (4) had lesions on both the
face and scalp. Results showed that those with lesions on the
Upon knowledge of patients’ vitamin D levels, those with el- scalp primarily have lower vitamin D levels (p = 0.006). There
evated levels were referred to the appropriate Internal Medicine is no sufficient evidence to conclude that the distribution of pa-
specialist for further evaluation and management, while those tients according to vitamin D status is significantly different as
with deficient and insufficient levels were treated with daily oral to sex (p = 0.77), duration of illness (p = 0.60), previous treatment
vitamin D3 (cholecalciferol) supplementation at a dose of 6,000 for seborrheic dermatitis (p = 0.23), history of past illnesses (p
IU per day for eight weeks. All patients were given appropriate = 0.32) and allergies (p = 0.17), ISGA scale (p = 0.13) and whether
management for their seborrheic dermatitis, in the form of top- the patient is an in-patient or out-patient (p = 0.06) (Table 2).
ical corticosteroids and/or calcineurin inhibitors, topical anti-
fungal agents, moisturizers, oral antihistamine drugs, and/or DISCUSSION
oral anti-fungal agents, independent of their vitamin D levels.
This study showed that majority of patients with seborrheic
No adverse events related to blood extraction were noted dermatitis have vitamin D insufficiency or deficiency, consis-
upon follow up of the patients with their attending dermatolo- tent with the study of Dimitrova in 2013.6 The majority of the
gist after 1–2 weeks. No subject withdrew during the duration patients with vitamin D insufficiency or deficiency had lesions

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Table 2. Demographic and clinical characteristics of patients with seborrheic dermatitis (N = 61).

Variable Total Normal Vitamin D Status Deficient P-value
N (%) Insufficient N (%) 0.0045*
Age (yrs.), Median (IQR) 55 (55, 60) N (%) 0.532 †
27 (26, 33) 32 (25, 52)
Gender 2 (40.0) 0.014 ‡
3 (60.0) 11 (52.4) 22 (62.9)
Female 35 (57.4) 10 (47.6) 13 (37.1) 0.646 ‡
5 (100.0)
Male 26 (42.6) 0 (0.0) 6 (28.6) 14 (40.0) 0.535 ‡
15 (71.4) 21 (60.0) 0.011 ‡
Status 1 (20.0)
2 (40.0) 6 (28.6) 7 (20.0)
Married 25 (41.0) 2 (40.0) 12 (57.1) 18 (51.4)
4 (80.0) 3 (14.3) 10 (28.6)
Single 36 (59.0) 11 (52.4) 18 (51.4)
3 (60.0)
Duration of illness 2 (40.0) 6 (28.6) 13 (37.1)
0 (0.0) 0 (0.0) 5 (14.3)
1 month or less 14 (22.9) 15 (71.4) 17 (48.6)

1 year or less 32 (52.5)

More than a year 15 (24.6)

Previous treatment for sebor- 33 (54.1)
rheic dermatitis

Physical exam

Face 22 (36.1)

Face and scalp 7 (11.5)

Scalp 32 (52.5)

*Kruskal Wallis test; †Chi-square test; ‡ Fischer’s exact test

Table 3. ISGA scale and vitamin D status (N = 61)

ISGA scale Total Normal Vitamin D Status Deficient P-value
N (%) N (%) 0.532€
Moderate 58 (95.1) Insufficient
Severe 3 (4.9) 5 (100.0) N (%) 35 (100.0)

0 (0.0) 18 (85.7) 0 (0.0)

3 (14.3)

located predominantly on the scalp, consistent with the study of dermatitis may be related to isoenzyme alteration involved in
Rahimi et al. in 2021, which noted that scalp disease severity was vitamin D metabolism as stated by Rahimi et al.12 As such, top-
associated with lower serum vitamin D level citing a possible ical vitamin D analogues such as calcipotriol has already been
role of vitamin D in the pathogenesis of seborrheic dermatitis, used for years to treat inflammatory skin diseases such as psori-
as the scalp region presents with increased number and activity asis vulgaris. However, data are still conflicting with regards to
of sebaceous glands where vitamin D has been identified to have its effects on seborrheic dermatitis. Oral vitamin D supplemen-
effects.4,12 Furthermore, our study have shown that majority of tation, like topical vitamin D analogues, may have therapeutic
the patients with vitamin D insufficiency or deficiency were in effects on seborrheic dermatitis, which is under the spectrum of
their 30s, and according to a study by Byung et al. in 2005, seba- inflammatory skin diseases.
ceous gland activity increases through teenage years, as well as
the second and third decades of life, before it starts to decline.13 This study only included data of seborrheic dermatitis pa-
tients in a private institution setting in the Philippines, which
The correlation of vitamin D deficiency and insufficiency is a tropical country. We included only adults aged 18–60 years
and civil status were not identified by the previous studies of with Fitzpatrick skin types III and IV. The investigators recom-
Dimitrova, Rahimi and Byung. Factors like stress levels, diet mend a multicenter study with a bigger sample size, which may
and lifestyle may have a factor and these may be further eluci- include the pediatric age group, and comparison with healthy
dated by more studies. control subjects with and without other dermatologic diseases
and of different Fitzpatrick skin types. Mild seborrheic der-
Inadequate vitamin D levels in patients with seborrheic

27 J Phil Dermatol Soc · November 2021 · ISSN 2094-201X

JPDS ORIGINAL
Journal of the Philippine ARTICLE
Dermatological Society

matitis, defined as fine scales with light coloration and/or mild up for most patients. To the best of our knowledge, this is the
plaque elevation by the (iSGA) scale, were excluded from the first study in the Philippines to assess the vitamin D status of
study to be able to focus on patients presenting with exacerbat- patients with seborrheic dermatitis.
ed seborrheic dermatitis such as those with moderate and se-
vere seborrheic dermatitis based on the (iSGA) scale. CONCLUSION

One of the limitations of this study is the absence of par- Vitamin D insufficiency and deficiency have been associated
ticipant measures such as diet, lifestyle and UV history, which with numerous medical conditions, and its association with
could have been possible sources of bias and imprecision. These skin diseases, particularly inflammatory skin diseases like seb-
were not taken into account and were not added in the inclusion orrheic dermatitis, is still to be further elucidated. Seborrheic
criteria, as those who are on certain diet with vitamin D supple- dermatitis, being identified as one of the most common, recur-
mentation, as well as those with active lifestyles with sufficient rent, and infrequently debilitating skin disease when severe,
sun exposure, may be a confounding factor on the vitamin D has been treated with topical and oral medications (anti-in-
levels of the participants. flammatories, antifungals, and antihistamines) to address its
etiology. The role of oral vitamin D supplementation as an ad-
With the current global pandemic, vitamin D has been junct treatment in helping improve disease severity and recur-
widely studied by researchers not only for its role in calcium rence may be studied in the future. The investigators believe
metabolism, but also for its immune-modulatory, anti-prolif- that the results of this study will serve as a pivot and inspiration
erative and pro-differentiative properties.6 Physicians are be- for further studies between seborrheic dermatitis and vitamin
coming more aware of the promising effects of vitamin D, hence D in the Philippines.
vitamin D level determination has been an integral part of work-

REFERENCES

1. Cheong W, Yeung C, Torsekar R, Suh D, Ungpakorn R, Widaty S, et al. Treatment of seborrheic dermatitis in Asia: a consensus guide. Skin
Appendage Disord. 2015;1:187-96. DOI: 10.1159/000444682.

2. Clark G, Pope S, Jaboori K. Diagnosis and treatment of seborrheic dermatitis. American Academy of Family Physicians. 2015;91(3):185-90.
3. Valia RG. Etiopathogenesis of seborrheic dermatitis. Indian J Dermatol Venereol Leprol. July-August 2006;72(4):253-5. DOI: 10.4103/0378-

6323.26711.
4. Wat H, Dytoc M. Off-label uses of topical Vitamin D in dermatology: a systematic review. J Cutan Med Surg. March-April 2014;18(2):91-108. DOI:

10.2310/7750.2013.13109.
5. Shahriari M, Kerr P, Slade K, Grant-Kels J. Vitamin D and the skin. Elsevier Clinics in Dermatology. November-December 2010;28(6):663-8. DOI:

10.1016/j.clindermatol.2010.03.030.
6. Dimitrova J. Study of the level of 25-hydroxyvitamin D in patients with seborrheic dermatitis. Varna Medical University Press Journals. March

2013. DOI: 10.14748/sum.v45i1.345.
7. Tanchee-Ngo MJ, Mercado-Asis LB. Serum 25 hydroxy vitamin D [25(OH) D] levels among admitted Filipino elderly patients. Philipp J Intern

Med. July 2013.
8. Mostafa W, Hegazy R. Vitamin D and the skin: focus on a complex relationship: a review. J Adv Res. Nov 2015:6(6):793-804. DOI: 10.1016/j.

jare.2014.01.011.
9. Palmer D. Vitamin D and the development of atopic eczema. J Clin Med. May 2015:4(5):1036-50. DOI: 10.3390/jcm4051036.
10. Woo Y, Jung K, Koo D, Lee J. Vitamin D as a marker for disease severity in chronic urticaria and it’s possible role in pathogenesis. Ann

Dermatology. 2015; 27(4):423-30. DOI: 10.5021/ad.2015.27.4.423.
11. Borzutzky A, Camargo C. Role of vitamin D in the pathogenesis and treatment of atopic dermatitis. Expert Rev Clin Immunology. Aug 2013:

0(8):751-60. DOI: 10.1586/1744666X.2013.816493.
12. Rahimi S, Nemati N, Shafaei-Tonekaboni S. Serum levels of 25-hydroxyvitamin D in patients with seborrheic dermatitis: a case-control study.

Hi Dani Dermatology Research and Practice. February 2021: 6623271. DOI: https://doi.org/10.1155/2021/6623271.
13. Byung I, Dawson T. The role of sebaceous gland activity and scalp microfloral metabolism in the etiology of seborrheic dermatitis and

dandruff. J Investig Dermatol Symp Proc. 2005;10:194-6. DOI: 10.1111/j.1087-0024.2005.10104.x.

J Phil Dermatol Soc · November 2021 · ISSN 2094-201X 28

JPDS ORIGINAL ARTICLE
Journal of the Philippine
Dermatological Society

Prevalence of mucosal and cutaneous disorders
among HIV/AIDS adult Filipino patients 18-60 years old

seen in a tertiary hospital in Makati City

Rahina H. Galvez, MD, DPDS,1 Ma. Jasmin J. Jamora, MD, FPDS,2 Janice C. Caoili, MD3

ABSTRACT

BACKGROUND With the recent rise in number of HIV/AIDS patients in the Philippines, knowledge of the most common mucosal and
cutaneous findings among HIV/AIDS patients can be a valuable tool of assessment.

OBJECTIVES To determine the different mucosal and cutaneous disease findings of HIV/AIDS patients; evaluate their frequency
and association with the latest CD4 cell counts, and to determine patients’ demographic and medical profiles.

METHODS This is a cross-sectional study done at a tertiary hospital in Makati city from January 2017 to September 2018. Walk-in
patients or those referred by Infectious Disease specialists were evaluated using a standardized history and physical examina-
tion form. Latest CD4 counts were also obtained.

RESULTS A total of 93 patients were enrolled. Majority were males (98%), with a mean age of 32 +/- 7.08, employed (64%), and on
HAART (87%). A large part of the group (45%) has severe immunosuppression (CD4 counts <200/mm3). The most common manifes-
tations were the following: non-infective, fungal, and drug-related dermatoses, with the most common dermatoses being seb-
orrheic dermatitis, xerosis, pruritic papular eruptions (PPE), superficial fungal infections, drug hypersensitivity reactions, and
syphilis. PPE was noted to be significantly associated with low CD4 counts.

CONCLUSION Due to small population size, significant associations between the other dermatoses with their CD4 counts were
not seen except for PPE, which was significantly associated with CD4 counts <200/mm3. Nevertheless, a strong suspicion for any
underlying HIV//AIDS infection is still warranted in the presence of these dermatoses.

KEYWORDS HIV, AIDS, CD4 cell count

1Maxicare Primary Care Center INTRODUCTION With increasing number of HIV/AIDS cas-
2Department of Dermatology, es in the Philippines, it is just appropriate that
Makati Medical Center, Legazpi Mucosal and cutaneous lesions are frequent oc- a study be made exploring the relationship be-
Village, Makati City currences among Human Immunodeficiency tween the clinical spectrum of the disease partic-
3Department of Medicine, Makati Virus (HIV)/Acquired Immunodeficiency Syn- ularly the mucosal and cutaneous manifestations
Medical Center, Legazpi Village, drome (AIDS) patients. Skin is the usual initial with their CD4 counts as they can help assess dis-
Makati City site of involvement, and it has been documented ease severity and prognosis.
that these changes occur at around 90% among
Corresponding author people living with HIV.1-4 They are also valuable Hence, this study was done to determine
Rahina H. Galvez, MD, DPDS tools of assessment that can serve as clinical in- the different mucosal, and cutaneous diseases
dicators of HIV/AIDS when correlated with their findings of HIV/AIDS patients and evaluate their
Conflict of interest CD4 counts.3-5 frequency and association with the latest CD4
None cell counts. In addition, the study also aimed to
For the month of January 2021, the Depart- determine the demographic and medical profile
Source of funding ment of Health (DOH) HIV/AIDS and Antiretrovi- of these patients.
None ral Treatment (ART) Registry of the Philippines
reported 890 newly diagnosed HIV cases. This METHODS
comprises 1% of the total 83,755 total cases since
January 1984, with National Capital Region (NCR) SETTING AND PARTICIPANTS
(41%), Calabarzon (20%), and Central Luzon (13%) This is a cross sectional study conducted at a ter-
being the regions with the highest number of re- tiary hospital in Makati city from January 2017 to
ported cases.6 September 2018. The following were the exclu-

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sion and inclusion criteria: STATISTICAL ANALYSIS
Descriptive statistics were used to summarize the demographic
INCLUSION CRITERIA and clinical characteristics of the patients. Frequency and pro-
1. Patients aged 18 to 60 years, of either sex, diagnosed with portion were used for categorical variables, and mean and SD
for normally distributed continuous variables. One-way ANOVA
Human Immunodeficiency Virus through initial screening and Fisher’s Exact test were used to determine the difference
via rapid test and confirmed by Western blot. of mean and frequency, respectively, within three CD4 count
2. Patients who were seen at the tertiary hospital as walk-in groups. Missing variables were neither replaced nor estimated.
patients or those who were referred by Infectious Disease Null hypotheses were rejected at 0.05α-level of significance, and
specialists. STATA 13.1 was used for data analysis.
3. Patients who were or were not treated with highly active an-
ti-retroviral therapy (HAART). ETHICAL CONSIDERATIONS
The study protocol adhered to the ethical considerations and
EXCLUSION CRITERIA principles set out by the Declaration of Helsinki, WHO guide-
1. Patients with no available or incomplete clinical and inves- lines, International Conference on Harmonization-Good Clin-
ical Practice, and National Ethics Guidelines for Health Re-
tigative information such as CD4 counts. search. The study also commenced upon the approval of the
Institutional Review Board. Participants signed an informed
SAMPLE SIZE consent and all data including photos were recorded and han-
A minimum of 93 subjects was required for this study. The sam- dled by the principal investigator which were kept in a secure
ple size was calculated based on the estimated proportion of office. All measures to ensure confidentiality and privacy were
41.1% seen among HIV patients with oral/esophageal/vaginal taken.
candidiasis, as noted from the study of Oninla et al.1 The width
of the 95% confidence interval was to be 20% of the proportion RESULTS
estimate (or an accuracy of ± 10%).
DEMOGRAPHIC PROFILE OF PATIENTS
DESCRIPTION OF STUDY PROCEDURE A total of 95 subjects were screened and 93 subjects were found to be
Purposive and referral sampling methods were used for the eligible and recruited for the study. Majority were males (98%), sin-
study. Flyers and posters were sent out and posted in the HIV gle (98%) and with a mean age of 32 ± 7.08. Most were also employed
treatment hub and Out-patient Department (OPD) of the hospi- (65%) and obtained a bachelor’s degree (72%). Students make up 9%
tal. Letters to ID specialists were also sent out to inform them of the study patients.
regarding the ongoing study. Patients who opted to join the
study were first assessed for eligibility, and interviews were MEDICAL PROFILE OF PATIENTS
conducted in the HIV treatment hub, OPD, or in a private clinic For the review of systems, weight loss (11%) was the most common
which was scheduled by appointment to ensure privacy. Eligible symptom, seen especially in patients with CD4 counts <200/mm3
patients were requested to provide consent to participate in the followed by fever (8%), cough (5%) and headache (4%). Previous
study. history of herpes zoster infection (15%), presence of concomitant
pneumonia (10%) and tuberculosis (9%) were among the top 3 med-
Each session comprised of a history taking followed by a ical conditions.
complete physical and dermatologic examination of recruited
patients. Assessment of the skin lesions was done by the Prin- A large number of the patients were already receiving highly
cipal Investigator using a standardized history and physical active anti-retroviral therapy (HAART) (87%). For sexual history,
examination form. The latest CD4 counts (within the last 6 28% had previous history of treated sexually transmitted infections
months) were obtained from the history or medical records, and and that majority (48%) had 5-10 sexual partners with sexual con-
documentation of lesions were done when consent was provid- tact among male to male as the most common mode of transmis-
ed. Diagnostic procedures were also done if deemed necessary. sion in 85%.
Diagnosis was based on clinical criteria in most of the cases,
and treatment was provided for positive skin findings. OUTCOMES
A total of 126 dermatoses were seen among the 93 study patients
ASSESSMENT OF OUTCOMES where 73% presented with only one dermatosis, followed by 23%
Primary outcomes include the demographic and medical profile of who presented with two dermatoses and 4% who had three or
the patients as well as the frequency of the different mucosal and more dermatoses. A large part of the group also has severe im-
cutaneous manifestations and CD4 count levels. The secondary out- munosuppression as 45% had CD4 counts of <200/mm3 (Table 1).
come includes the presence of 1, 2 or 3 or more dermatoses.

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Non-infective dermatoses (52%) were the most commonly matoses seen at 22%, similar with the studies done by Lowe et
observed manifestations followed by fungal infections (22%) al. and Blanes et al. where seborrheic dermatitis was also one of
and drug related dermatoses (13%). Top non-infective derma- the most common dermatoses seen among the severely immu-
toses include the following: seborrheic dermatitis (22%), xero- nocompromised.4,12 As mentioned earlier, the chronicity of this
sis (10%) and pruritic papular eruptions (PPE) (9%) where PPE lesion as well as its appearance in any stages of HIV infection,
was noted to be significantly associated with low CD4 counts may have contributed to its high number of cases.
(P=0.045). Oral candidiasis (6%) and superficial fungal infec-
tions (10%) were the most common types of fungal dermatoses Pruritus secondary to xerosis is also a common symptom
while drug hypersensitivity reactions secondary to HAART and among HIV/AIDS patients. In our study, there is also a high per-
non HAART (8%) were the most common drug related dermato- centage of patients who presented with xerosis (10%), similar to
ses. Syphilis also accounted for 9% of the cases. a study done by Kaushik et al.13 and Mirnezami et al.14 where
xerosis is the most prevalent dermatosis among HIV patients.
DISCUSSION Studies by Lee et al. also noted that low levels of CD4 counts
were seen to be associated with xerosis.15 As most of our study
Demographic profile of the study patients revealed that major- patients had CD4 counts <200/mm3, there was also an increased
ity were males, belonged to 25-39 age group with a history of frequency of xerosis. This higher incidence of xerosis among
sexual contact among males having sex with males. This find- HIV patients can be attributed to their decreased epidermal lip-
ing is consistent with the latest registry from DOH HIV/AIDS ids and excessive levels of epidermal carotenoids such as lyco-
and ART and a cross-sectional study done by Pan et al. in China pene, causing premature skin aging.16
where the majority of study patients were also between 20 and
40 years of age with sexual contact among male to male as the Pruritic papular eruption (PPE) is a chronic condition char-
most common mode of transmission.6,7 It was also seen that 65% acterized by the presence of pruritic papules and pustules com-
were employed and belonged to the productive age group hence monly seen on the extensor surfaces of the extremities, trunk,
may have more access to treatment (HAART) and health care and face sparing the palms and soles. The etiology of PPE re-
facilities. mains unclear, however some suggested its association with ar-
thropod bite reactions since the disease commonly occurs in the
Weight loss (11%) was the most common clinical complaint tropics, mostly involving extremities.17
similar with other studies done by Joshi et al. in Nepal and Kaur
et al. in India.8,9 Likewise, AIDS-defining illnesses such as tu- In our study, PPE is also among the top dermatoses (9%)
berculosis was also noted to be among the top 3 medical condi- seen to be significantly associated with low CD4 counts <200/
tions among the patients, similar to other epidemiologic studies mm3 (P=0.045) similar with the studies done by Lowe et al.4
done in South Africa by Kaprowicz et al. where TB/HIV coinfec- and Nnoruka et al.5 where PPE was among the frequently seen
tion epidemic is severe.10 dermatoses. This higher prevalence of the disease could be at-
tributed to its chronic nature as well as the limited success of
Several studies worldwide have been conducted to explore the available therapeutic options.
the relationship between mucocutaneous manifestations and
the CD4 lymphocyte counts. In our study, though a large part For the past few years, fungal infections accounted for
of the group was severely immunocompromised (45%), there majority of the dermatoses seen among HIV/AIDS patients who
is only a small percentage of patients (4%) who presented with were not on HAART. This was evidenced by a study done by
3 or more dermatoses. These less severe presentations may be Oninla in Nigeria, where fungal infections accounted for most
due to the fact that majority were already on HAART (87%) and of the cases (50%).1 In our study, a high number of fungal der-
may have access to health care. In contrast, Lowe et al.4 found matoses (22%) such as superficial fungal infections were also
in their study that there is a higher percentage of patients who seen but came only second to the non-infective dermatoses. It is
presented with 3 or more or dermatoses among those who were possible that because majority of our study patients (87%) were
severely immunocompromised. This may have been due to the already on HAART, the number of opportunistic fungal infec-
fact that only 32% of their study patients were on antiretroviral tions may have been greatly reduced.
treatments who were mostly hospitalized as well.
Though the incidence of opportunistic skin lesions among
The most common dermatoses in our study were the fol- patients with HIV has been greatly reduced due to HAART, there
lowing: seborrheic dermatitis, xerosis, pruritic papular erup- was also an increase in number of drug eruptions both from
tions, superficial fungal infections, drug hypersensitivity reac- HAART and non-HAART. In our study, common HAART drugs
tions and syphilis. such as lamivudine, tenofovir, efavirenz, nevirapine, and non
HAART drug such as co-trimoxazole were the common causes
It is said that 85% of HIV patients will have seborrheic der- of drug reactions accounting for 13% of the cases. This higher
matitis at some point of their illness. They can occur at any stage incidence of drug reactions has been associated with polyclonal
of infection and may flare and subside over time.11 In our study, B-cell or T-cell activation secondary to a decline in CD4 counts.17
seborrheic dermatitis accounted for the highest number of der- Other reasons for increased adverse drug reactions as cited by

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CD4 count
Table 1.
Total <200/mm3 200-500/mm3 >500/mm3 p-value
Characteristics (n=42) (n=29) (n=22)
68 (73.12) 0.128
Number of dermatoses 21 (22.58) 26 (61.90) 25 (86.21) 17 (77.27)
1 12 (28.57) 4 (13.79) 5 (22.73) 0.745
2 4 (4.30) 0.045
3 or more 48 (51.61) 4 (9.52) 0 0 0.054
21 (50) 14 (49.28) 13 (59.09) 0.237
Non-infective dermatoses 8 (8.60) 7 (16.67) 0.616
Pruritic papular eruptions 2 (2.15) 1 (3.45) 0 0.257
Dyshidrotic eczema 1 (1.08) 0 0 2 (9.09) 0.298
Contact dermatitis 20 (21.51) 0 0 1 (4.55) 0.194
Seborrheic dermatitis 9 (9.68) 10 (23.81) 3 (13.64) 0.013
Xerosis 2 (2.15) 4 (9.52) 7 (24.14) 4 (18.18) 0.812
Acute urticaria 6 (6.45) 0 1 (3.45) 1 (4.55) 1.000
Eosinophilic folliculitis 5 (5.38) 5 (11.90) 1 (3.45) 0.199
Post-inflammatory hyperpigmentation 4 (4.3) 1 (2.38) 1 (3.45) 0 0.548
Acne vulgaris 2 (2.15) 1 (2.38) 4 (18.18) 0.237
Xerotic eczema 1 (1.08) 1 (2.38) 0 1 (4.55) 0.548
Atopic dermatitis 1 (1.08) 1 (2.38) 2 (6.90) 1.000
Lichen simplex chronicus 1 (1.08) 0 1 (3.45) 0 0.237
Cherry angioma 1 (1.08) 0 3 (10.34) 0 0.616
Acrochordon 1 (1.08) 0 1 (3.45) 0 0.194
Keratosis pilaris 1 (1.08) 1 (2.38) 1 (4.55) 0.289
Vasculitis 20 (21.51) 0 0 0 0.237
6 (6.45) 10 (23.81) 1 (3.45) 0 0.298
Fungal 9 (9.68) 5 (11.90) 1 (4.55) 0.794
Oral candidiasis 1 (1.08) 3 (7.14) 0 3 (13.64) 1.000
Superficial fungal infections 2 (2.15) 0 0 0 0.499
Onychomycosis 3 (3.23) 0 7 (24.14) 1 (4.55)
Pityriasis versicolor 1 (1.08) 2 (4.76) 1 (3.45) 1 (4.55) --
Pityrosporum folliculitis 12 (12.90) 1 (2.38) 5 (17.24) 1 (4.55) 0.886
Cutaneous cryptococcosis 2 (2.15) 7 (16.67) 0 0 0.548
7 (7.53) 2 (4.76) 1 (3.45) 0 0.715
Drug-related 1 (1.08) 4 (9.52) 1 (3.45) 2 (9.09) 0.393
Toxic epidemal necrolysis 2 (2.15) 0 0 0 0.548
Drug hypersensitivity reaction 9 (9.68) 1 (2.38) 3 (10.34) 1 (4.55) 0.715
Fixed drug eruption 1 (1.08) 6 (14.29) 0 0 0.237
Acneiform eruption 2 (2.15) 0 2 (6.90) 1 (4.55) 1.000
1 (1.08) 1 (2.38) 1 (3.45) 2 (9.09) 0.146
Hair and nail changes 1 (1.08) 0 0 0 0.357
Alopecia areata 4 (4.30) 1 (2.38) 1 (3.45) 1 (4.55) 0.357
Melanonychia 8 (8.60) 4 (9.52) 1 (3.45) 1 (4.55)
Androgenetic alopecia 8 (8.60) 2 (4.76) 0 0
Paronychia 2 (4.76) 0 0
Telogen effluvium 0 2 (9.09)
0 2 (9.09)
Bacterial 4 (13.79)
Syphilis (Secondary) 4 (13.79)

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Viral 6 (6.45) 3 (7.14) 2 (6.90) 1 (4.55) 1.000
Herpes zoster 1 (1.08) 1 (2.38) 0 0 1.000
Condyloma acuminate 2 (2.15) 1 (2.38) 0 1.000
Herpes simplex 2 (2.15) 1 (2.38) 1 (3.45) 0 1.000
Herpes stomatitis 1 (1.08) 1 (3.45) 0.237
Cytomegalovirus retinitis 1 (1.08) 0 1 (4.55) 1.000
1 (2.38) 0 0
Malignancies 1 (1.08) 0 1.000
Kaposi sarcoma 1 (2.38) 0
1 (1.08) 0 1.000
Parasitic/arthropod borne dermatoses 1 (2.38) 0
Arthropod bite 1 (1.08) 0 1.000
1 (2.38) 0
Mucosal membrane lesions 0
Aphthous ulcers

Prabhakaran et al. include the following: Epstein-Barr virus also affected by different factors such as disease duration, time
and cytomegalovirus reactivation, glutathione depletion, im- since initiation of ART, and viral load levels, clinical presenta-
mune dysregulation and polypharmacy.18 tions may vary depending on these factors when the patients
were examined. In addition, due to financial constraints, addi-
In the past, the worldwide incidences of curable STDs tional work ups were also limited. The study reflected an epi-
such as syphilis has significantly declined after the discovery demiologic data obtained in a private institution with a small
of penicillin, however recently has been on the rise again. As sample size, hence the investigators recommend multicentric
mentioned earlier, syphilis was also among the top dermato- studies for a larger, and more accurate statistical data.
ses in our study, similar to the study done by Mutagoma et al.
where HIV/Syphilis co-infection was seen to be high among fe- CONCLUSION
male sex workers19 as well as with the study done by Dai et al. in
China who noted a high prevalence of HIV/Syphilis co-infection In our study, the most common manifestations were the fol-
among men who have sex with men.20 All of the patients seen in lowing: non infective dermatoses, fungal and drug-related der-
our study were on the secondary stage of syphilis who presented matoses with the most common dermatoses being seborrheic
with maculopapular lesions on the trunk and extremities inclu- dermatitis, xerosis, pruritic papular eruptions, superficial fun-
sive of palms and soles. Once confirmed using nontreponemal gal infections, drug hypersensitivity reactions, and syphilis.
and treponemal serologic tests, patients were referred to infec- Majority of our study patients were males, employed, severely
tious disease specialists for further management. immunocompromised, and on HAART. Due to a small popula-
tion size, significant associations between the other dermatoses
The presence of other benign epithelial tumors such as with their CD4 counts were not seen except for PPE which was
acrochordon and cherry angioma was also noted. As they are significantly associated with low CD4 counts <200/mm3. Hence,
not usually a common feature among HIV patients and may also larger studies are recommended. Nevertheless, due to increas-
be seen among normal healthy individuals, they may be regard- ing incidences in the Philippines, the presence of these distinct
ed as incidental findings. dermatoses should still warrant a strong suspicion for any un-
derlying HIV/AIDS infection, playing a vital role in the screen-
One of the limitations of this study is that due to the evolv- ing and overall disease management of the patients.
ing nature of some dermatologic lesions, diagnosis was only
limited during the time of consult. Since CD4 count levels are

REFERENCES

1. Oninla O. Mucocutaneous Manifestations of HIV and the correlation with WHO clinical staging in a tertiary hospital in Nigeria.Department of
Dermatology and Venereology, Faculty of Clinical Sciences, College of Health Sciences. AIDS Research and Treatment. 2014.

2. Chawhan SM, Bhat DM, Solanke SM. Dermatological manifestations in human immunodeficiency virus infected patients: Morphological spectrum with
CD4 correlation. Indian J Sex Transm Dis AIDS. 2013;34(2):89-94.

3. Raju PV, Rao GR, Ramani TV, Vandana S. Skin disease: clinical indicator of immune status in human immunodeficiency virus (HIV) infection. Int J
Dermatol. 2005 Aug;44(8):646-9. doi: 10.1111/j.1365-4632.2004.02067.x. PMID: 16101864.

4. Lowe S, Ferrand RA, Morris-Jones R, Salisbury J, Mangeya N, Dimairo M, Miller RF, Corbett EL. Skin disease among human immunodeficiency virus-infected
adolescents in Zimbabwe: a strong indicator of underlying HIV infection. Pediatr Infect Dis J. 2010 Apr;29(4):346-51. doi: 10.1097/INF.0b013e3181c15da4.
PMID: 19940800; PMCID: PMC3428906.

33 J Phil Dermatol Soc · November 2021 · ISSN 2094-201X

JPDS ORIGINAL
Journal of the Philippine ARTICLE
Dermatological Society

5. Nnoruka EN, Chukwuka JC, Anisuiba B. Correlation of mucocutaneous manifestations of HIV/AIDS infection with CD4 counts and disease progression.
International Journal of Dermatology, vol. 46, pp. 14–18, 2007.

6. Department of Health HIV/AIDS and ART Registry of the Philippines. January 2021.
7. Pan X, Wu M, Ma Q, Wang H, Ma W, Zeng S, et al. High prevalence of HIV among men who have sex with men in Zhejiang, China: a respondent-driven

sampling survey. BMJ Open. 2015 Dec 11;5(12):e008466. doi: 10.1136/bmjopen-2015-008466. PMID: 26656982; PMCID: PMC4679937.
8. Joshi HS, Das R, Agnihotri AK. Clinico-epidemiological profile of HIV/AIDS patients in western Nepal a study from teaching hospital. Indian Journal of

Preventive and Social Medicine. 2004;35(1-2):69–76.
9. Kaur R, Dhakad MS, Goyal R, Bhalla P, Dewan R. Spectrum of Opportunistic Fungal Infections in HIV/AIDS Patients in Tertiary Care Hospital in India.

Canadian Journal of Infectious Diseases and Medical Microbiology, vol. 2016, Article ID 2373424, 7 pages, 2016.
10. Kaprowicz V, Achkar J, Wilson D. The Tuberculosis and HIV Epidemic in South Africa and KwaZulu-Natal Research institute for Tuberculosis and HIV.

Journal of infectious Diseases, Vol. 204, November 15, 2011.
11. Forrestel AK, Kovarik CL, Mosam A, Gupta D, Maurer TA, Micheletti RG, et al. Diffuse HIV-associated seborrheic dermatitis – A case series. Int J STD AIDS.

2016;27:1342–5
12. Blanes M, Belinchón I, Merino E, Portilla J, Sánchez-Payá J, Betlloch I. Prevalencia y características de las dermatosis relacionadas con la infección

por VIH en la actualidad [Current prevalence and characteristics of dermatoses associated with human immunodeficiency virus infection]. Actas
Dermosifiliogr. 2010 Oct;101(8):702-9. Spanish. PMID: 20965013.
13. Kaushik SB, Cerci FB, Miracle J, Pokharel A, Chen SC, Chan YH, et al. Chronic pruritus in HIV-positive patients in the southeastern United States: its
prevalence and effect on quality of life. J Am Acad Dermatol. 2014 Apr;70(4):659-664. doi: 10.1016/j.jaad.2013.12.015. Epub 2014 Feb 4. PMID: 24503217.
14. Mirnezami M, Zarinfar N, Sofian M, Botlani Yadegar B, Rahimi H. Mucocutaneous Manifestations in HIV-Infected Patients and Their Relationship to CD4
Lymphocyte Counts. Scientifica (Cairo). 2020 Aug 11;2020:7503756. doi: 10.1155/2020/7503756. PMID: 32850174; PMCID: PMC7439183.
15. Lee D, Benson CA, Lewis CE, Grunfeld C, Scherzer R. Prevalence and factors associated with dry skin in HIV infection: the FRAM study. AIDS. 2007;21(15):2051-
2057.
16. Mischo M, von Kobyletzki LB, Bründermann E, Schmidt DA, Potthoff A, Brockmeyer NH, et al. Similar appearance, different mechanisms: xerosis in HIV,
atopic dermatitis and ageing. Exp Dermatol. 2014 Jun;23(6):446-8. doi: 10.1111/exd.12425. PMID: 24758518.
17. Eisman S. Pruritic papular eruptions of HIV-1. Dermatology Clinic 2006;24:449-57.
18. Prabhakaran N, Jaisankar TJ, Hamide A, Malathi M, Kumari R, Thappa DM. Effect of antiretroviral therapy on mucocutaneous manifestations among
Human Immunodeficiency Virus-infected patients in a tertiary care centre in South India. Indian J Sex Transm Dis AIDS. 2015;36(2):166-173.
19. Mutagoma M, Nyirazinyoye L, Sebuhoro D, Riedel DJ, Ntaganira J. Syphilis and HIV prevalence and associated factors to their co-infection, hepatitis
B and hepatitis C viruses prevalence among female sex workers in Rwanda. BMC Infect Dis. 2017 Jul 28;17(1):525. doi: 10.1186/s12879-017-2625-0. PMID:
28754104; PMCID: PMC5534065.
20. Dai W, Luo Z, Xu R, Zhao G, Tu D, Yang L, et al. Prevalence of HIV and syphilis co-infection and associated factors among non-commercial men who have
sex with men attending a sexually transmitted disease clinic in Shenzhen, China. BMC Infect Dis. 2017 Jan 18;17(1):86. doi: 10.1186/s12879-017-2187-1.
PMID: 28100187; PMCID: PMC5241916.

J Phil Dermatol Soc · November 2021 · ISSN 2094-201X 34

JPDS ORIGINAL ARTICLE
Journal of the Philippine
Dermatological Society

A translation and validation study of the Filipino
version of the Psoriasis Epidemiology Screening Tool
(PEST) among Filipino patients with psoriasis seen at

the Rizal Medical Center

Camille Clarisse S. Mundin, MD,1 Rogelio B. Balagat MD, FPCP, FPDS, FPRA,1
Jamie P. Nuñez MD, FPDS1

ABSTRACT

INTRODUCTION Psoriasis is a chronic autoimmune disease that affects the skin, nails, and musculoskeletal system. Musculoskel-
etal involvement, called psoriatic arthritis occurs in 10-25% of patients with psoriasis and can lead to disability if left untreated.
Early detection and intervention of psoriatic arthritis has been shown to decrease morbidity.

The Psoriasis Epidemiology Screening Tool (PEST) may detect the presence of psoriatic arthritis and has been validated in differ-
ent countries. Currently, there is no Filipino version.

OBJECTIVES To translate, adapt, and validate PEST in Filipino language.

METHODS In the first part of the study, PEST was translated and culturally adapted into Filipino. It was pretested in 30 participants.

Three experts then assessed its content and face validity. After the content and face validity were met, 115 participants an-
swered the Filipino version of the PEST questionnaire.

RESULTS The Filipino version of the PEST questionnaire was comprehensible, clear and appropriate. All questions were relevant.
Some words were edited per expert recommendation. One hundred fifteen adult patients were asked to answer the question-
naire. It showed good reliability at 94%.

CONCLUSION The Filipino Version of the PEST was found to be reliable and valid. Larger samples to determine the tool’s applica-
bility is recommended.

KEYWORDS PEST, Filipino translation, psoriasis, psoriatic arthritis screening

1Department of Dermatology, INTRODUCTION mation refers to dactylitis and enthesitis.3,4,5
Rizal Medical Center, Pasig Clinical features of psoriatic arthritis include
Boulevard, Pasig City Psoriasis is a chronic autoimmune disease that
affects the skin, the nails, and the musculoskel- dactylitis, enthesitis, tenosynovitis, spondyloar-
Corresponding author etal system. Most present as plaques. Other sub- thritis, distal interphalangeal arthritis, and arthri-
Camille Clarisse S. Mundin, MD types are guttate, pustular, and erythrodermic. tis mutilans. Dactylitis is the inflammation of the
It has a global prevalence of 0.1% to 3%.1,2 entire finger or toe and is the marker for severity
Conflict of interest in psoriasis. Enthesitis is the inflammation of the
None Psoriasis can also affect the nails and the entheses, which is the site of the attachment of the
musculoskeletal system. Musculoskeletal in- ligaments and tendons to the bone. Tenosynovitis is
Source of funding volvement is known as psoriatic arthritis. It is the inflammation of the tendon sheath; while spon-
None present in 10% to 25% of patients with psoriasis. dyloarthritis involves the spine. Arthritis mutilans
It is estimated that 0.3 to 1% of the population has on the other hand, is the most severe form, which
psoriatic arthritis. Psoriatic arthritis has both leads to shortening and destruction of the fingers
articular and non-articular features. Articular and toes.3
or joint findings refer to peripheral and axial ar-
thritis while non-articular or soft tissue inflam- The Classification Criteria for Psoriatic Ar-

35 J Phil Dermatol Soc · November 2021 · ISSN 2094-201X

JPDS ORIGINAL
Journal of the Philippine ARTICLE
Dermatological Society

thritis (CASPAR) is used to diagnose psoriatic arthritis in a per- PART 1: TRANSLATION AND CULTURAL ADAPTATION
son with psoriasis who has a swollen digit, or pain in a joint or In the forward translation, a total of two translators with expe-
a heel. It has three parts: clinical, radiologic, and rheumatoid rience in translation and cultural adaptation measures translat-
factor test. The clinical part has three components: psoriasis, ed the questionnaire separately. Forward translation refers to
nail dystrophy, and dactylitis. Psoriasis may be current, past the translation of the questionnaire from the original language
history, or family history. Radiographs show ossification, and (English) to Filipino. Discrepancies between the two transla-
rheumatoid factor is negative. Both the clinical and the diagnos- tions were discussed and resolved through an online meeting.12
tic tests comprise the five domains. Three or more points are
required to diagnose psoriatic arthritis.4,5 During back translation, two other translators translated
the Filipino version back into English.12
A meta-analysis has shown that between 10.1% to 15.5% of
patients with psoriasis have undetected psoriatic arthritis.6 Oth- An online meeting composed of the forward, back trans-
er observational studies have found even higher percentages of lators, and the authors reviewed the translation. Thirty partici-
undiagnosed psoriatic arthritis.7,8 pants answered the pre-final version of the questionnaire.

It is recommended to screen annually for psoriatic arthri- PART 2: VALIDATION AND RELIABILITY TESTING
tis. Among the screening tools are PEST, Psoriasis and Arthritis A panel of experts who are familiar with the construct that the
Questionnaire (PAQ), Psoriatic Arthritis Screening and Evalu- questionnaire is designed to measure was formed to assess the
ation (PASE), and Psoriasis and Arthritis Screening Question- content and face validity of the questionnaire. It is composed
naire (PASQ).4,5 of one rheumatologist and two dermatologists who specialize in
psoriasis.
The PEST is highly sensitive (0.94) and specific (0.78). It is
composed of a five-item yes or no questionnaire that will be an- Content validity ensures that the questionnaire includes an
swered by patients who have a diagnosis of psoriasis, and a score adequate set of items that tap the concept of the tool, while face
of three out of five will warrant referral to a rheumatologist for validity refers to the degree to which a test appears to measure
further evaluation and management. This screening tool has what it claims to measure.13
been established as superior compared to the other screening
tools for psoriatic arthritis.4,5 Content validity was measured and analyzed using the
item level-content validity score (i-CVI). Each one rated the
SIGNIFICANCE OF THE STUDY items as 1-not relevant, 2-somewhat relevant, 3-quite relevant,
and 4-highly relevant. Face validity was also evaluated by the
A large percentage of patients with psoriasis are managed by panel of experts and their comments and suggestions were doc-
primary care physicians and dermatologists.9 Most of the pa- umented. Revisions were made according to suggestions and
tients in our country are native Filipino speakers. Currently, consensus of the experts.
there is no available Filipino version of a psoriatic arthritis
screening tool such as the PEST. That is why the translation and After content and face validity were met, 115 participants
validation of this tool would be beneficial to both physicians and answered the Filipino version of the PEST questionnaire. Reli-
patients for screening of psoriatic arthritis. It will help in the ability was assessed through test-retest.
detection of psoriatic arthritis, early intervention, and disabil-
ity prevention.10,11 STUDY DESIGN, SETTING, AND DURATION
The study was conducted in adult patients with psoriasis
OBJECTIVES
at the Rizal Medical Center outpatient clinic and online service
The general objective of this study was to translate, adapt, and from November 2020 to April 2021.
validate the Filipino version of the PEST. This study specifical-
ly aims to: 1. describe the demographic characteristics of the STUDY PARTICIPANTS
study participants, 2. translate PEST to the Filipino language, Inclusion criteria
and 3. adapt and validate the Filipino version. 1. Male or female patients diagnosed with psoriasis (of any

METHODS duration)
2. Legal age (19 and above) to sign an informed consent
This two-part study consisted of the translation and cultural ad- 3. Able to understand and speak Filipino
aptation of the PEST, and the validity and reliability testing of
the Filipino version. The process flow of the methods used in the Exclusion criteria
study is shown in Appendix 1. 1. Patients diagnosed with psoriatic arthritis or any rheumat-

Permission was obtained from the primary author of PEST ic disease
for the Filipino translation prior to conducting the study. 2. Patients who cannot understand and speak Filipino
3. Patients who did not consent to be part of the study

J Phil Dermatol Soc · November 2021 · ISSN 2094-201X 36

ORIGINAL JPDS
ARTICLE Journal of the Philippine
Dermatological Society

SAMPLE SIZE DETERMINATION AND SAMPLING ages. Means or medians of numerical data were compared using
The initial translation was pilot tested on 30 respondents. This Mann-Whitney U-test. All tests were performed using SPSS soft-
number was based on the power of 80% and the prevalence (p) ware version 26 at 5% level of significance.
of power of 5%.11, 14-15
ETHICAL CONSIDERATION
A sample size of 115 was determined for the study. This We sought permission from the original developers of PEST to
number was adequate to estimate a proportion equal to 50% translate the questionnaire. The Rizal Medical Center Institutional
with a 7.5% margin of error and a 95% level of confidence using Review Board approved the protocol. Informed consent from par-
the formula below: ticipants were obtained. Data gathered were kept confidential.

Zα/2 is the critical value of the Normal distribution at α/2 RESULTS
(e.g., for a confidence level of 95%, α is 0.05 and the critical value
is 1.96), E is the margin of error, p is the sample proportion, and PART 1: TRANSLATION OF PEST
N is the population size. Assuming N = 350, p = 50%, level of con- All of the respondents who answered the pre-final version of the
fidence or 1- α = 95% and E = 7.5%, the recommended minimum questionnaire concluded that the Filipino version was clear and
sample size is 115.11, 14-15 easy to understand. The pretested Filipino translation was used
in the second part of the study.
DATA COLLECTION
Data were collected using a self-administered paper or online PART 2: VALIDATION AND RELIABILITY TESTING OF PEST
questionnaire (Google® form). The questionnaire consisted of 5 Content validity was done and all of the items showed 100% rele-
close-ended questions answerable by yes or no. vance based on the item level content validity index score (i-CVI)
(Table 1). During face validity evaluation, one expert suggested to
DATA MANAGEMENT AND ANALYSIS change “arthritis” to “arthritis/rayuma” in item number 2. Another
A reliability test was performed through a test-retest method, expert suggested to add “buong daliri” in item number 5 (Table 2).
which measures the reliability of the tool over time. The agree- Appendix 2 shows the revised and final Filipino version.
ment or correlation was measured using the Spearman coeffi-
cient. In general, a test-retest correlation of 0.80 or greater indi- One hundred fifteen participants were included in the
cates good reliability. study. The participants had a mean age of 37 and were mostly
female. A majority had chronic plaque type psoriasis. (Table 3).
Demographic characteristics and responses were encoded
in MS Excel and summarized using descriptive statistics. Nu- Most of the participants had a PEST score of 0 (25.21%) to
merical data were shown as mean (median) ± standard devia- 1 (23.47%) in the initial test and re-test (0-24.34% and 1-25.21%).
tion. Nominal data were presented as frequencies and percent- Test-retest reliability showed a high and significant correlation
(0.94) (Tables 4 & 5).

DISCUSSION

The participants invited to join this study had a mean age of 37,
were mostly female, and had chronic plaque psoriasis. Most

Table 1. Test on the content validity of the forward translation.

Questions Frequency (%) i-CVI Decision
100% Accepted
Q1 Nakaranas ka na ba ng pamamaga ng Not relevant Somewhat relevant Quite relevant Highly relevant 100% Accepted
(mga) kasukasuan? 0 3 (100%) 100% Accepted
0 00 3 (100%) 100% Accepted
Q2 Sinabi ba ng doktor sa iyo na ikaw ay may 0 2 (66.6%) 100% Accepted
arthritis? 0 00 2 (66.6%)
0 3 (100%) 100% Accepted
Q3 Mayroon bang butas o uka sa iyong mga 0 1 (33.3%)
kuko sa kamay o paa? 0 13 (86.66%)
0 1 (33.3%)
Q4 Nagkaroon ba ng pananakit sa iyong
sakong? 00

Q5 Nakaranas ka na ba ng pamamaga at 0 2 (13.33%)
pananakit sa iyong mga daliri sa kamay o paa
nang walang dahilan?

Overall

37 J Phil Dermatol Soc · November 2021 · ISSN 2094-201X

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Dermatological Society

Table 2. Test on the face validity of the forward translation. Table 4. Actual responses of participants.

Questions Major comments from the expert panel Score distribution Initial test (n=115) Re-test (n=115)
28 (24.34%)
Q1 Nakaranas ka na ba ng pamamaga ng No modification required 0 29 (25.21%) 29 (25.21%)
(mga) kasukasuan? 14 (12.17%)
1 27 (23.47%) 17 (14.78%)
10 (8.69%)
Q2 Sinabi ba ng doktor sa iyo na ikaw ay may One expert suggested to change “arthritis” to 2 15 (13.04%) 17 (14.78%)
3 17 (14.78%)
arthritis? “arthritis/rayuma”

Q3 Mayroon bang butas o uka sa iyong mga No modification required 4 12 (10.43%)
kuko sa kamay o paa? No modification required
5 15 (13.04%)
Q4 Nagkaroon ba ng pananakit sa iyong
sakong?

Q5 Nakaranas ka na ba ng pamamaga at One expert suggested to add “buong daliri”.
pananakit sa iyong mga daliri sa kamay o paa
nang walang dahilan? Table 5. Test-retest reliability.
Test-Retest Reliability
Spearman correlation = 0.94 (0.92 to 0.96)
p-value<0.0001

Table 3. Demographic data of participants. Values and were mostly female. It had a sensitivity of 58% and a spec-
(n=115) ificity of 96.4%. The Persian version of the PEST questionnaire
Characteristics 37.7 ± 11.7 has showed acceptable performance in the Iranian psoriatic
population without a previously established diagnosis of psori-
Mean age ± SD, years 45 (39.13%) atic arthritis.19
Sex, frequency (%) 70 (60.86%)
A Thai version has found that psoriatic arthritis was asso-
Male 101 (87.82%) ciated with more than 10% body surface involvement. It had a
Female 6 (5.22%) sensitivity of 50% and a specificity of 82%.20
Psoriasis type, frequency (%) 8 (6.96%)
Chronic plaque psoriasis Finally, our Filipino version yielded a high-reliability index
Scalp of 0.94 and a validity index of 100%. The results were consistent
Others with other translations. The Filipino version of PEST can be a
good screening tool for early detection of psoriatic arthritis.
of them had a PEST score of 0-1 on the initial test and retest. With early detection, patients can be given therapeutic inter-
Test-retest reliability was high at 94%. The original version of vention early in order to prevent further disease progression
PEST has a sensitivity of 0.94 and a specificity of 0.78.16 which leads to irreversible and life-long deformities.

The Chinese version of PEST shows that individuals with Despite the presented results, this study has certain lim-
psoriatic arthritis were older with a mean age of 42, mostly itations. The study was only limited to patients in Rizal Medical
male, and had psoriasis longer. It had a 77.5% sensitivity and a Center. It was not able to correlate the results with other pa-
78.9% specificity. The results of the study showed that the Chi- rameters such as body surface area, daily quality of life index,
nese version of PEST was sensitive and specific, which is consis- duration of psoriasis and co-morbidities. For future researchers
tent with previous studies in the European and American pop- who aspire to further explore this topic, we recommend larger
ulations. The authors of the study concluded that the PEST is a samples in different hospitals for wider applicability.
useful tool in detecting psoriatic arthritis in Chinese psoriasis
patients.17 CONCLUSION

Furthermore, a Brazilian version has demonstrated that The Filipino Version of the Psoriasis Epidemiology Screening
males and low quality of life scores were associated with high- Tool or PEST was found to be reliable and valid. Larger samples
er PEST scores. It had a sensitivity of 84.6% and a specificity of in different hospitals to determine wider applicability are rec-
63.3%.18 While the Persian version of PEST showed that individ- ommended.
uals with psoriatic arthritis were older with a mean age of 46

ACKNOWLEDGMENTS

The authors would like to acknowledge Dr. Lenore Lugue-Lizardo, Dr. Alma Gay Concepcion-Amado, and Dr. Lily Lyralin Laconico-Tumalad for being the
panel of experts in the validation of this questionnaire.

J Phil Dermatol Soc · November 2021 · ISSN 2094-201X 38

ORIGINAL JPDS
ARTICLE Journal of the Philippine
Dermatological Society

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413. DOI:10.33192/smj.2019.61

39 J Phil Dermatol Soc · November 2021 · ISSN 2094-201X

JPDS ORIGINAL ARTICLE
Journal of the Philippine
Dermatological Society

Determination of minimal erythema dose of Filipino
adults to standardize the initial dose of narrowband

ultraviolet B phototherapy in a tertiary hospital

Michelle Isabel L. Astorga, MD, DPDS,1 Maria Victoria C. Dizon, MD, FPDS,1
Patricia Anne T. Tinio, MD, FPDS1

ABSTRACT

INTRODUCTION Narrowband ultraviolet B (NBUVB) phototherapy is a well-established treatment option for a variety of dermato-
logic conditions. The initial dosage is obtained either by determining the patients’ minimal erythema dose (MED) or their Fitzpat-
rick skin phototype (SPT). MED determination is a better way to establish the proper initial dose as it is more objective. However,
in practice, SPT is more commonly used as it is more convenient, and MED data in Filipinos are scarce.

OBJECTIVES To establish data determining the MED values of Filipino adults that can serve as a basis to standardize the initial
dose of NBUVB phototherapy in a tertiary hospital.

METHODS We enrolled 86 volunteers in a cross-sectional analytical study to determine their MED and assess if there is any asso-
ciation between their MED and the participants’ age, sex, skin prototype, ancestry, and daily duration of sun exposure.

RESULTS The median MED of the participants is 800 mJ/cm2 (IQR 600-800 mJ/cm2). A majority of 38 participants (44.19%) have a MED
of 800mJ/cm2 followed by 600mJ/cm2 for 23 (26.74%) participants. There was also a significant association between study partici-
pants’ MED with respect to their Fitzpatrick skin type (p=<0.001) and ancestry (p=0.03), but with no association with regards to age
(p=0.291), sex (p=0.245), and daily duration of sun exposure (p=0.237).

CONCLUSION Majority of the participants have a median MED value of 800 mJ/cm2. Based on this MED value, the initial dosage of
NBUVB at 50-70% of the MED would translate to an initial dose of 400-560 mJ/cm2.

KEYWORDS erythema, phototherapy, minimal erythemus dose

1Department of Dermatology, INTRODUCTION dose that results in uniform erythema over an
Makati Medical Center, Legazpi entire square is considered the MED; thereaf-
Village, Makati CIty Phototherapy is the use of ultraviolet (UV) or ter phototherapy is initiated at 50-70% of that
visible light for therapeutic purposes. One of the amount. Alternatively, the initial dose of photo-
Corresponding author most widely used modalities of phototherapy is therapy may also be established based empiri-
Michelle Isabel L. Astorga, MD, narrowband UVB (NBUVB). Its beneficial effect cally on Fitzpatrick skin phototype (SPT).1,2
DPDS is now well established for a variety of dermato-
logic conditions, as its appeal is based on its rel- In clinical practice, most dermatologists
Conflict of interest ative safety coupled with an ongoing interest in in the Philippines utilize SPT for determining
None its molecular and biological effects.1 the initial starting dose of NBUVB phototherapy
for its practicality and convenience. However,
Source of funding The dosage of UV light is prescribed accord- the SPT has limitations as SPT has been shown
None ing to the individual’s skin sensitivity.2 There are in studies not to correspond well to constitutive
two ways to determine the initial starting dose skin color and to correlate poorly with MED val-
of NBUVB. First, the minimal erythema dose ues. Interestingly, the physician-assigned skin
(MED) is determined by exposing six square ar- phototype has been shown to correlate moder-
eas of sun-protected skin, each measuring 1 cm2, ately with race,3,4 and race assignment does not
to gradually increasing amounts of UV radiation correlate well with objective measures of pig-
from the same device that will be used for pho- mentation or self-reported skin phototype, sug-
totherapy. After twenty-four hours, the UV-ex- gesting that assignment of SPT is often based
posed squares are examined and the lowest UV

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ARTICLE Journal of the Philippine
Dermatological Society

on perceived race rather than either objective skin color or re- AB C
sponse to UV light.4 Hence, administering NBUVB phototherapy
solely on the basis of skin type can lead to undertreatment or Figure 1. A. Attaching the MED test patch on a sun-protected area (lower back), B.
overdosing of patients particularly in the Filipino population, Conducting UV exposure, C. Marking of MED test area.
in whom previous studies regarding MED testing are scarce.
Thus, MED determination is a better way to establish the proper Figure 2. MED reading of a participant showed well defined erythema at square number 4
initial dose to administer to a patient, thereby enhancing thera- corresponding to 600mJ/cm2.
peutic efficacy resulting to fewer treatment sessions and less ex-
penses for the patient. The objective of this study is to have data MED TESTING
determining the MED values of Filipino adults that can serve as Preparing for UV exposure
a basis to standardize the initial dose of NBUVB phototherapy in The investigator explained to the participants how MED testing
a tertiary hospital. is done, and that the participant has to come back to the center

METHODS

STUDY DESIGN
This is a prospective cross-sectional analytical study conducted
in the phototherapy center of a tertiary hospital. This study was
approved by the Institutional Review Board prior to commence-
ment.

PATIENT SELECTION AND RECRUITMENT
Subject participants are Filipino citizens, aged 18-60 years old,
of both sexes, with no active skin condition that might interfere
with the performance of the test or reading of the results, and
with no skin lesions in the areas to be tested (hips, lower back,
or buttocks) for the MED. Participants with known history of
photosensitivity and those who have ingested or applied the
following medications within their corresponding time frame:
photosensitizing agent within 2 months; corticosteroids within
15 days; and H1-receptor antihistamine within 7 days, from the
MED testing were excluded in the study. Eligible participants
were informed of the study process and have voluntarily signed
the informed consent.

DATA COLLECTION
On the first visit, demographic profile, and the following data:
ancestry, Fitzpatrick skin type, and daily duration of sun expo-
sure were taken, and recorded by the primary investigator.

STUDY MATERIALS
Narrowband ultraviolet B (NBUVB) phototherapy device
The medical phototherapy machine (National Biological Cor-
poration) was used for the NBUVB phototherapy sessions. It is
a combination phototherapy unit with 24 NBUVB and 24 UVA
lamps, measuring 46 x 49 x 87 inches that can treat the whole
body in one session.

Minimal erythema dose (MED) test patch
The investigators used the MED (Daavlin®) test patch. It is a dis-
posable hypoallergenic individual test patch comes with six ex-
posure windows for the corresponding doses.

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Table 1. Visual Erythema Scale. No erythema Table 2. Demographic Profile of the Study participants. Values
E0 Ill-defined erythema (faint pink) (n=86)
E1 Characteristics 31.98 + 8.15
E2 Well defined erythema (pink)
E3 Marked erythema (red) Mean age ± SD, years 30 (34.88)
E4 Fiery red with edema Sex, frequency (%) 56 (65.12)
E5
Fiery red with edema and blistering Male 71 (82.56)
Female 5 (5.81)
for 2 consecutive days for the MED testing and the MED reading. Comorbidity, frequency (%) 7 (8.14)
The Daavlin® MED test patch was attached to a sun-protected None 1 (1.16)
region of the body, which will either be the hip, lower back or Hypertension 1 (1.16)
buttocks. All other skin areas were covered using a towel and Asthma 1 (1.16)
protective clothing, with eye protection using phototherapy Allergic rhinitis 9 (10.47)
goggles worn during the entire procedure. Endometriosis
Hyperthryoidism 30 (34.88)
Conducting UV exposure Allergies, frequency (%) 3 (3.48)
The six squares of the MED test patch were exposed to NBUVB at Occupation, frequency (%)
increasing intervals of 200 mJ/cm2. At the start of the exposure, Healthcare professional 11 (12.79)
only one square of the MED test patch was open, after which an Office employee 40 (46.52)
additional square was opened and exposed for every increase Security personnel
in dose exposure.6 The timer is part of the phototherapy device, Service personnel 2 (2.33)
which automatically turns the NBUVB lamps off after the de- Others
sired dose has been reached. Smoking history, frequency (%) 12 (13.95)
Smoker 73 (84.88)
Upon completion of the UV exposure, adequate skin mark- Non smoker
ings using a permanent marker were made prior to the removal Previous smoker 1 (1.16)
of the MED test patch, in order to more easily identify the ex- Alcohol intake, frequency (%)
posed areas after 24 hours (Figure 1). Participants were remind- Occasional 55 (63.95)
ed to not wash off the markings until after the skin had been None 31 (36.05)
examined for the MED reading. Ancestry, frequency (%)
Pure Filipino 74 (86.05)
ASSESSING THE MED Mixed ancestry
The participants had only one follow-up with the principal in- 8 (9.30)
vestigator, which was after 24 hours of the MED testing to deter- East Asian 4 (4.65)
mine their MED. Mediterranean 1 (1.16)
North European
After 24 hours, the investigator examined the exposed ar- Fitzpatrick skin type, frequency (%) 0
eas of skin. Red or pink skin indicated erythema. Well-defined Type I 1 (1.16)
erythematous skin exposed to the shortest duration of NBUVB Type II 20 (23.26)
was defined as the MED (Square number 4 in Figure 2), which Type III 57 (66.28)
will also classify as E2 on the Visual Erythema Scale (Table 1). Type IV 8 (9.30)
Type V
ASSESSMENT OF OUTCOME Type VI 0
The primary outcome of interest was the smallest UV dose that Daily duration of sun exposure, frequency (%)
resulted in uniform well-defined erythema over the entire ex- Minimal (less than 10 minutes) 53 (61.63)
posed area after 24 hours of exposure to the NBUVB light source Moderate (more than 10minutes, but less than 1 hour) 31 (36.05)
using a visual erythema scale. The MED was defined as E2 or Severe (more than 1 hour)
well-defined erythema (pink) skin in the visual erythema scale. 2 (2.33)
Secondary outcome measures were the participant’s subjective
assessment of the exposure in terms of pruritus, pain or ten-
derness using a visual analog scale; and adverse events. These

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Table 3. Minimal erythema dose, and Subjective assessment of study participants to MED testing. Frequency (%); Median (IQR)
Characteristics
800 (600,800)
Minimal erythema dose (MED) value (mJ/cm2)
200 0
400
600 6 (6.98)
800
1,000 23 (26.74)
1,200
38 (44.19)
Subjective assessment of study participants to MED testing (Visual Analog Scale 0-10)
Pruritus 13 (15.12)
0
1 6 (6.98)
2
3 Immediately after MED testing 24 hours after MED testing
Pain or tenderness
0 86 (100) 82 (95.35)
1 0 0
2 0
0 2 (2.33)
Adverse Effects (Grades 1-3) 2 (2.33)
Burning sensation
0: None 86 (100) 84 (97.67)
1: Awareness of symptoms but easily tolerated 0 0
2: Enough discomfort to cause interference with daily activities 0
3: Incapacitating with inability to do work 2 (2.33)

84 (97.67)
2 (2.33)
0
0

were recorded, and attended to immediately after the MED test- visual presentation of its values. Missing variables were neither
ing, and after 24 hours of exposure to the UV light source. replaced nor estimated. STATA 13.1 was used for data analysis.

STATISTICAL CONSIDERATION AND DATA ANALYSIS RESULTS
For sample size computation, a minimum of 85 subjects
A total of 87 subjects were recruited to participate in the study.
was required for this study, based on a level of significance of All were examined for eligibility. However, one volunteer was
5%, a development of erythema at 745mJ/cm2 prevalence of excluded as she had an underlying malignancy and was under-
33.3% with a desired half-width of confidence interval of 10%, as going chemotherapy. The remaining 86 subjects were included
noted from the reference study by Pai GS, 2002.5 To compensate and were able to complete the entire study duration and analy-
for the respondents that may be lost to follow-up, an additional sis.
10% was added. However, no subjects were lost to follow-up. The
total number of subjects who completed the study is 86. DEMOGRAPHIC PROFILE OF THE STUDY PARTICIPANTS
The demographic profile of the study participants (Table 2)
Descriptive statistics were used to summarize the demo- showed that majority were female (65.12%), and with a mean age
graphic and clinical characteristics of the patients. Frequency of 31.98 + 8.15. Out of the 86 study participants, majority (82.56%)
and proportion were used for categorical variables, median and had no comorbidities. All were employed, with most working as
IQR for non-normally distributed continuous variables, and service personnel (46.52%), health care professionals (34.88%),
mean and SD for normally distributed continuous variables. and security personnel (12.79%).
Chi-square test of association was used to determine the associa-
tion of MED value of the patients and their Fitzpatrick skin type, Most of the participants were pure Filipino (86.05%), with
ancestry, daily duration of sun exposure and sex. Spearman rho a smaller percentage having mixed ancestry as follows: East
correlation analysis was used to determine the association of Asian (9.30%), Mediterranean (4.65%), and North European
MED value to patient’s age, then a scatter plot was generated for (1.16%). One participant ticked both East Asian, and Mediterra-

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Table 4. Association of MED values to Sex, Fitzpatrick skin type, Ancestry and Sun exposure.

Characteristics n 400 600 MED Values (mj/cm2) 1,000 1,200 p-value
800 0.245
Sex, frequency (%) 30 3 (10) 6 (20) 6 (20) 4 (13.33) <0.001*
Male 56 3 (5.36) 17 (30.36) 11(36.67) 7 (12.5) 2 (3.57)
Female 27 (48.21) 0.031*
1 1 (100) 0 0 0
Fitzpatrick skin type, frequency (%) 20 2(10) 11 (55) 0 1 (5) 1 (5) 0.237
Type II 57 3(5.36) 12 (21.05) 5 (25) 9 (15.79) 2 (3.51)
Type III 8 31 (54.39) 3 (37.5) 3 (37.5)
Type IV 0 0 2 (25)
Type V 74 13 (17.57) 6 (8.11)
7 3 (4.05) 17 (22.97) 35 (47.30) 0 0
Ancestry, frequency (%) 4 2 (28.57) 3 (42.86) 2 (28.57) 0 0
Pure Filipino 1 0 0
East Asian 0 3 (75) 1(25)
Mediterranean 53 1 (100) 0 0 5 (9.43) 3 (5.66)
North European 31 7 (22.58) 3 (9.68)
2 6 (11.32) 15 (28.30) 24 (45.28)
Daily duration of sun exposure, frequency (%) 0 8 (25.81) 13 (41.94) 1 (50) 0
Minimal 0
Moderate 0 1 (50)
Severe

nean as part of her mixed ancestry and was counted for both nificant association between MED values and age (p=0.291), sex
categories. Majority have Fitzpatrick skin types IV (66.28%) fol- (p=0.245), and daily sun exposure (p=0.237).
lowed by type III (23.26%). For the daily duration of sun expo-
sure, most (61.63%) had only minimal exposure, defined as less DISCUSSION
than 10 minutes of cumulative duration of daily sun exposure.
A common method for determining the initial NBUVB dose is to
PRIMARY AND SECONDARY OUTCOME MEASURES estimate it based on the patient’s Fitzpatrick SPT.7,8 This method is
Most of the participants (44.19%) had an MED of 800mJ/cm2, frequently used in clinical practice as it is more convenient, but our
followed by a smaller percentage (26.74%) who had an MED of basis for this method which is patterned after Caucasian skin, may
600mJ/cm2 (Table 3). For the subjective assessment to the MED result to suboptimal initial treatment delivery, especially for Filipi-
testing, four participants experienced pruritus (with a score of nos who have a diverse racial ancestry (predominantly SPT III and
2-3/10 using a visual analog scale (VAS), and two reported pain IV), and are more pigmented than Caucasian skin.
or tenderness (score of 2/10 on VAS) on the MED testing sites.
The same two study participants reported an adverse effect of The results of this study showed that Filipino adult patients
burning sensation with a grade of 1 on the MED testing areas, seen in a tertiary hospital, wherein majority are pure Filipinos,
defined as awareness of symptoms but easily tolerated. and some with mixed ancestry of East Asian, Mediterranean
and North European have a median MED value of 800 mJ/cm2,
ASSOCIATION OF MED VALUE TO AGE, SEX, FITZPATRICK IQR (600-800 mJ/cm2). Based on this MED value, the initial dos-
SKIN TYPE, ANCESTRY AND SUN EXPOSURE age of NBUVB at 50-70% of the MED would translate to an initial
There is a significant association between study participants’ dose of 400-560 mJ/cm2. This finding can serve as a basis for a
MED for NB-UVB with respect to their Fitzpatrick skin type higher initial dosage compared to the more conservative meth-
(p=<0.001) as more than half of participants with skin type IV od the tertiary hospital is currently using. It also supports the
(54.39%) had MED of 800 mJ/cm2, and more than half of partic- most recent guidelines for NBUVB phototherapy for psoriatic
ipants with skin type III (55%) had MED of 600mJ/cm2 (Table 4). patients that recommends an initial dosage of 500mJ/cm2 for
There is also a significant association between MED values and patients with SPT III and IV9, and the study of Lee et al. that rec-
ancestry (p=0.031) as nearly half of pure Filipino participants ommended a higher starting dose in Asian patients with vitiligo
(47.30%) had MED of 800mJ/cm2. In contrast, there was no sig- who are also predominantly SPT III and IV.10

The study also noted a significant association between the
patient’s MED values and their variables which are ancestry,

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Dermatological Society

and examiner-assigned SPT. Majority of the pure Filipino partici- initial dosage of NB-UVB for their patients.
pants had an MED range of 600-800mJ/cm2; while those with East
Asian ancestry had a range of 400-800mJ/cm2. This suggests that CONCLUSION
determining the patient’s ancestry and their SPT during their ini-
tial visit can also be a good basis on determining the patient's initial Majority of the participants have a median MED value of 800 mJ/
NBUVB dosage, as it has always been done using the latter variable. cm2. Based on this MED value, the initial dosage of NBUVB at
50-70% of the MED would translate to an initial dose of 400-560
The participants who joined the study also had only very mJ/cm2. As there is no current definite guideline for the start-
minimal reports of pruritus, pain and burning sensation to the ing dose of NBUVB for Filipino skin, we can consider a higher
MED testing suggesting that in an ideal setting, determining the starting dose for Filipino patients compared to the conservative
patient’s MED should always be considered. approach most clinicians use. This can lead to a faster onset
of efficacy, improvement, and eventually decreased number of
The limitation of this study is that it was conducted in a selected treatment sessions that translates to less expense, improved
population in a tertiary hospital, which makes the results not rep- quality of life, and patient satisfaction. Having said this, the
resentative of the entire Filipino population. Also, given the range authors of the study recommend future studies to determine
of MED values on pure Filipinos, a standardized initial dose cannot if a higher initial NBUVB dosage can lead to faster clearance
be obtained. But considering the lack of study on MED values using of skin lesions in Filipino patients with photo-responsive der-
NBUVB on Filipino skin, the results are still worthy of recognition matoses.
in its attempt to serve as a guide for clinicians in determining the

REFERENCES

1. Cafardi J, Pollack B, Elmets C. Phototherapy. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K. Fitzpatrick’s Dermatology in
General Medicine. 8th ed. New York, NY: McGraw-Hill Companies Inc; 2012: p. 2841-2850.

2. Heckman CJ, Chandler R, Kloss JD, Benson A, Rooney D, Munshi T, et al. Minimal erythema dose (MED) testing. J Vis Exp 2013; 75: 50175. DOI:
10.3791/50175

3. Verallo-Rowell VM., Meneses M., Nunez J., Laureta R. Phototyping and multi-heritage skin of Asian-Filipinos in the Philippines. Skin in the
Tropics: Sunscreens and Hyperpigmentations. Anvil Publishing Inc. 2001 pp.143-155

4. Reddy K, Lenzy M, Brown K, Gilchrest B. Racial considerations: Skin of color. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K.
Fitzpatrick’s Dermatology in General Medicine. 8th ed. New York, NY: McGraw-Hill Companies Inc; 2012: p. 91-103.

5. Pai GS. MED estimation for narrow band UV-B on type IV and type V skin in India. Indian J Dermatol Venereol Leprol 2001;67: 251-2. PMID: 17664763.
6. HOUVA4® User Manual, National Biologics Corporation, Ohio. 2012.
7. Fitzpatrick TB. The validity and practicality of sun-reactive skin types I through VI. Arch Dermatol 1988; 124: 869-71. DOI: 10.1001/archderm.124.6.869.
8. Zanolli M, Feldman SR. Phototherapy Treatment Protocols. 3rd ed. Boca Raton, FL: Taylor & Francis; 2016.
9. Elmets CA, Lim HW, Stoff B, Connor C, Cordoro KM, Lebwohl M, et al. Joint American Academy of Dermatology-National Psoriasis Foundation

guidelines of care for the management and treatment of psoriasis with phototherapy. J Am Acad Dermatol. 2019 Sep;81(3):775-804. doi:
10.1016/j.jaad.2019.04.042. Epub 2019 Jul 25. Erratum in: J Am Acad Dermatol. 2020 Mar;82(3):780. PMID: 31351884.
10. Lee H, Chu H, Oh SH. Investigation of suitable starting doses of narrowband UVB in Asian vitiligo patients: a pilot study. J Eur Acad Dermatol
Venereol. 2017 May;31(5):894-897. doi: 10.1111/jdv.13933. Epub 2016 Sep 12. PMID: 27549434.

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Dermatological Society

Translation and validation of a scale on the health
care providers’ Attitudes Towards Persons Living With

Leprosy (AT-PLWL)

Maicka Keirsten O. Agon, MD,1 Abelaine Venida-Tablizo, MD, FPDS1

ABSTRACT

INTRODUCTION Leprosy is a chronic, progressive, and complex disease. One of the factors contributing to the quality of case
detection and treatment compliance is the attitudes of health care providers towards leprosy patients. Assessment of the
attitudes of HCP towards leprosy patients is crucial because this is where leprosy patients base their care-seeking behaviors;
hence, the creation of this scale.

OBJECTIVES To create and validate a functionally equivalent Filipino translation of the HCP AT-PLWL scale.

METHODS A validity study was conducted into two phases. In Phase I, the AT-PLWL scale was translated (forward-back method)
into Filipino, which underwent a cognitive debriefing (face validity) and pre-testing to 30 health care providers. In Phase 2, the
reconciled forward translation underwent face and content validity and was pilot-tested to 100 health care providers. Reliability,
both internal consistency and test-retest, were assessed via calculating Cronbach’s α and intra-class correlation coefficient,
respectively.

RESULTS Content and face validity showed that all items in the scale were relevant. Cronbach’s α showed an adequate internal
consistency of greater than 0.7 while the intra-class correlation coefficient of responses was greater than 0.80, indicating good
correlation.

CONCLUSION Overall, the final translated Filipino version of AT-PLWL scale is valid and reliable; hence, could serve as a tool to
evaluate HCP’s attitudes.

KEYWORDS Leprosy scale, health care providers, attitude scale

1Department of Dermatology, INTRODUCTION attitude, along with knowledge and practices,
Rizal Medical Center, Pasig are necessary to know among HCPs with regard
Boulevard, Pasig City Leprosy (also known as Hansen’s disease) is a to leprosy so that required knowledge and skills
chronic, progressive, and debilitating disease can be imparted.5
Corresponding author caused by Mycobacterium leprae. The disease
Maicka Keirsten O. Agon, MD mainly affects the skin, the peripheral nerves, Health care providers play an important
eyes, and the mucosa of the upper respiratory role in the management of cases because they di-
Conflict of interest tract.1,2 Although there had been an advent of rectly handle and counsel leprosy patients. Aside
None multidrug therapy (MDT) during the 1980s, with from their job, their role is very crucial as the
the World Health Organization (WHO) providing quality of case detection and treatment compli-
Source of funding free MDT globally, still leprosy continues to be a ance relies on their kind of attitude towards lep-
None significant problem and stigma is still rampant.2-4 rosy. A positive health environment is beneficial
for patients because this is where they base their
In the literature, few studies were found as- health-seeking behaviors and compliance. This
sessing the knowledge, attitude, and practices of is where assessment of HCPs’ attitudes comes in.
health care providers (HCPs) towards persons af-
fected by leprosy.5-11 Based on the reviews done by The first half of the methodology of the orig-
Srinivas, et al. (2018), majority of the scales were inal tool/instrument by Srinivas et al. (2018) is
more representative of knowledge and practice via a scale development process which consists
rather than attitude; hence, this gave rise for a of qualitative semi-structured interviews and
need to create a scale on HCP attitudes.12 More- focus group discussion for item generation pur-
over, Ahmad et al. (2010) stated that the levels of poses and scaling exercise.12 The second part of

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