JPDS Nov 2022 A

CASE REPORT JPDS
Journal of the Philippine
Dermatological Society

crusted erythematous patches with annular configuration on Figure 2. Histopathology shows eosinophilic infiltrates filling the subepidermal blister cavity.
the arms and back (Figure 1). Superficial erosions were noted (hematoxylin and eosin stain, 10x).
on the lower lip mucosa and ventral aspect of tongue. There was
no ocular nor genital involvement. Nikolsky and Asboe-Hansen
signs were negative. Review of other systems was unremarkable
except for grade 1 bipedal pitting edema. Initial impression was
childhood BP versus linear IgA bullous dermatosis (LAD).

Skin tissue biopsy taken from the forearm showed eosino-
philic infiltrates filling the subepidermal blister cavity (Figure
2). Direct immunofluorescence (DIF) of the perilesional skin
showed linear deposits of IgG (+1) (Figure 3A), C3 (+2) (Figure
3B), and IgM (+3) on the basement membrane. Enzyme-linked
immunosorbent assay (ELISA) to BP180 antigen was elevated at
135 IU (normal <9 IU). Complete blood count revealed increased
white blood cell count with neutrophilia. Gram stain of vesicu-
lar fluid revealed eosinophils without organisms. Clinicopath-
ologic findings led to a final diagnosis of BP in childhood. Chest
X-ray done prior to giving systemic corticosteroid revealed pul-
monary tuberculosis on the left upper lung.

The patient was managed by a multidisciplinary team
composed of an immunodermatologist, a pediatrician, an oto-

Figure 1. Generalized tense vesicles and bullae filled with clear-yellowish fluid on normal and Figure 3. Direct immunofluorescence (IF) of the perilesional skin showed linear deposits of (A)
erythematous skin. There were erythematous patches topped with yellowish crusts, some IgG (+1), (B) C3 (+2) on the basement membrane zone.
grouped into annular configuration.
rhinolaryngologist, and an ophthalmologist. She was started
on quadruple anti-Koch’s regimen (pyrazinamide, rifampicin,
ethambutol, isoniazid) three tablets per day, prednisone 0.75
mg/kg/day, chlorphenamine maleate 4 mg tablet thrice a day,
and clobetasol propionate cream twice a day. Improvement was
noted on the 4th week with 10-12 new vesicles appearing every
3-4 days subsequently crusting in 2-3 days and resolving to hy-
popigmented and hyperpigmented macules and patches. Pred-
nisone was tapered to 0.5 mg/kg/day. Doxycycline 100 mg/cap
two capsules once a day was started for its immunomodulating
properties.2 Other medications were maintained. One of the
first-line treatments for BP,7 methotrexate, a folic acid analog,
with anti-inflammatory and cytotoxic properties,2 was not given
since our patient had active pulmonary tuberculosis which is an
absolute contraindication.7

On the 7th week of prednisone, only 3-4 vesicles appeared
every 2-3 days. Generalized hypopigmented and hyperpigment-

46 J Phil Dermatol Soc · November 2022 · ISSN 2094-201X

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Dermatological Society

Figure 4. Follow-up photos of patient (A) on the 12th week of prednisone with diminished cases from 1970 to 2015.6 Of these, nine were in early adoles-
generalized hypopigmented and hyperpigmented macules and patches (Image alteration cence (10-13 years) and five in middle adolescence (14-17 years).6
through cropping of sensitive area (buttocks) of patient using macOS Preview version 11.0 All cases satisfied the Nemeth et al. criteria.6,8 Limited data were
(999.4) Copyright 2002-2019 Apple Inc.) (B) on the 39th week with further diminution of obtained for late adolescence (18-21 years) which are recorded
hypopigmented and hyperpigmented macules and patches. in adult registries.6

ed macules and patches with decreased crusting were noted. With seeming rarity in this group, we report a mid-adoles-
Prednisone was tapered to 0.41 mg/kg/day. Doxycycline was cent 16-year-old female with a 3-month history of pruritic, gen-
discontinued due to gastrointestinal complaints and shifted to eralized tense vesicles and bullae with annular configuration on
erythromycin, an anti-inflammatory antibacterial at 250 mg/ the arms and back, with mucosal involvement. Given this clini-
capsule four times a day for two weeks.2 cal picture, LAD versus childhood BP were considered,1 the for-
mer being the most common acquired autoimmune blistering
On the 9th week, while maintained on prednisone 0.41 mg/ disease in children.3 Distribution of tense blister formation in
kg/day and clobetasol propionate cream, disease was controlled childhood BP can be acral, or flexural involving the extremities,
with cessation of vesicle formation and resolution of pruritus.7 lower abdomen and groin, or anogenital involving the vulva.1
Prednisone was tapered to 0.36 mg/kg/day. It can be generalized and oral mucosal erosions are common,1
as observed in our patient. Ocular mucous membrane involve-
On the 12th week, hypopigmentation and hyperpigmenta- ment is common to both childhood BP and LAD1 but was absent
tion diminished (Figure 4A). Clobetasol propionate cream was in our patient. Both are non-scarring and heal with post-inflam-
discontinued and prednisone was continually tapered to 0.28 matory hypo- or hyperpigmentation.1
then 0.23 mg/kg/day every 2 weeks.
Our patient satisfied the criteria for childhood BP proposed by
On the 22nd week, occasional pruritic papules appeared on Nemeth et al.,8 specifically, (a) Age 18 years or less with tense blister
both arms which resolved within the day. Prednisone was fur- formation, and subepidermal bullae with eosinophils on histopa-
ther tapered to 0.17 mg/kg/day. Erythromycin 250mg/capsule thology, and (b) Linear IgG or C3 deposition at the basement mem-
four times a day was resumed for two weeks. Monitoring of ELI- brane on DIF or reactive IgG antibodies to the basement membrane
SA to BP180 antigen was not done due to financial constraints. on IIF, and therefore our final diagnosis was childhood BP.
Patient subsequently followed up 17 weeks after. During the in-
terim period, she remained lesion-free with further diminution Given its rarity, there are no randomized controlled trials
of hypopigmentation and hyperpigmentation (Figure 4B). Com- on childhood BP.2 Hence, treatment recommendations are the
plete remission was achieved by our patient at 10 months and is same as adult BP but are administered with caution, taking into
sustained at the time of writing. consideration their safety profile.2 Since childhood BP generally
has good prognosis, less toxic medications are recommended.2,7
During the disease course, the patient’s quality of life was
unfavorably affected. Pruritic lesions prevented her from doing For the management of widespread disease in children, first
her daily tasks, post-inflammatory dyspigmentation limited her line is prednisone or prednisolone at 0.5-2 mg/kg/day, depending
choice of clothes and she was unable to go to school. on disease severity.2 Dose is gradually tapered according to clini-
cal course.7 Anti-inflammatory antibacterial medications, which
DISCUSSION suppress blister formation are often added to topical or oral corti-
costeroids,2 are another option for mild to moderate disease.7 Dox-
Bullous pemphigoid in childhood is rare especially in adoles- ycycline which inhibits chemotaxis of eosinophils and neutrophils2
cence.6 Literature search by Patsatsi A. et al., identified only 14 has a better safety profile compared to systemic corticosteroids but
are contraindicated in <12 years old since it interferes with tooth
and bone development.2 Therapeutic benefit can be attained at one
to four weeks2 and our patient noted decrease in new vesicle for-
mation after three weeks. Erythromycin is recommended in pedi-
atric cases for its low adverse effects.7 It has shown to be effective in
childhood BP,9 with its anti-inflammatory effect obtained in one to
four weeks,2 our patient showed cessation of new lesions in 2 weeks.
In two cases of childhood BP, resolution of lesions was noted when
erythromycin was given in combination with niacinamide and dap-
sone, and in another with an addition of topical steroid.9

An immunosuppressant, methotrexate, is a treatment op-
tion for mild to severe disease.7 Adverse effects are myelosup-
pression and hepatotoxicity, hence, adequate patient screening

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CASE REPORT JPDS
Journal of the Philippine
Dermatological Society

for any contraindications, proper instruction to weekly dosing was achieved by our patient at 10 months. Relapses are uncom-
and ctompliance to regular monitoring should be emphasized.7 mon as was seen in our patient.9
In childhood BP, methotrexate 15 mg/week combined with
prednisolone was shown to elicit a favorable response after Long term monitoring is recommended until complete remis-
three months, undetectable BP180 antibodies after six months, sion is achieved and all treatment is discontinued to ensure symp-
and sustained remission after one year of disease onset.10 tom control without overtreatment and adverse effects managed.12

For disease unresponsive to treatment or relapse with very Due to the disease burden of BP, quality of life assessment
high doses of corticosteroids, other immunosuppressants such should be included in future cases for comprehensive manage-
as azathioprine or chemotherapeutic agents such as dapsone ment inclusive of psychosocial care.13
can be used alone or added to existing treatment.2 An anti-IgE
monoclonal antibody, omalizumab, has been shown to be an- CONCLUSION
other effective treatment with a steroid-sparing effect in a case
of recalcitrant infantile BP.11 BP in childhood is rare especially in adolescents. To establish
a definitive diagnosis and appropriate management, clinical,
Control of disease defined as cessation of new lesions and histopathologic, and immunologic analysis and correlation is
healing of existing ones6 is achieved from two to ten weeks,4 necessary. Prognosis of childhood BP is good. Relapses rare-
and was attained by our patient within nine weeks. Complete ly occur and treatment response is rapid from weeks to a few
remission or absence of lesions off treatment for two months6 is months. Treatment of choice is systemic corticosteroids. Long
attained at an average of 12 months or can reach five years,4 and term monitoring and quality of life assessment is recommended
to ensure treatment evaluation and psychosocial care.

REFERENCES

1. Tidman MJ, Mellerio JE, Pope E. Vesicullobullous disease. In: Schachner LA, Hansen RC, editors. Pediatric Dermatology. Elsevier; p. 974–7.
2. Kirtschig G, Khumalo NP. Management of bullous pemphigoid: Recommendations for immunomodulatory treatments. Am J Clin Dermatol

[Internet]. 2004;5(5):319–26. Available from: http://dx.doi.org/10.2165/00128071-200405050-00005
3. Kong YL, Lim YL, Chandran NS. Retrospective study on autoimmune blistering disease in paediatric patients. Pediatr Dermatol [Internet].

2015;32(6):845–52. Available from: http://dx.doi.org/10.1111/pde.12684
4. Gajic-Veljic M, Nikolic M, Medenica L. Juvenile bullous pemphigoid: the presentation and follow-up of six cases: Juvenile pemphigoid. J Eur

Acad Dermatol Venereol [Internet]. 2010;24(1):69–72. Available from: http://dx.doi.org/10.1111/j.1468-3083.2009.03264.x
5. Philippine Dermatological Society Health Information Systems. Philippine Dermatological Society. c2011 [updated (July 7, 2022); cited (July 20,

2022)]. Available by request from: [email protected].
6. Patsatsi A, Kyriakou A, Werth VP. Bullous pemphigoid in adolescence. Pediatr Dermatol [Internet]. 2019;36(2):184–8. Available from: http://

dx.doi.org/10.1111/pde.13717
7. Fuertes de Vega I, Iranzo-Fernández P, Mascaró-Galy JM. Penfigoide ampolloso: guía de manejo práctico. Actas Dermosifiliogr [Internet].

2014;105(4):328–46. Available from: http://dx.doi.org/10.1016/j.ad.2012.10.022
8. Nemeth AJ, Klein AD, Gould EW, Schachner LA. Childhood bullous pemphigoid. Clinical and immunologic features, treatment, and prognosis.

Arch Dermatol [Internet]. 1991;127(3):378–86. Available from: http://dx.doi.org/10.1001/archderm.127.3.378
9. Oranje AP, Vuzevski VD, Joost T, Kate F, Naafs B. Bullous pemphigoid in children: Report of three cases with special emphasis on therapy. Int J

Dermatol [Internet]. 1991;30(5):339–42. Available from: http://dx.doi.org/10.1111/j.1365-4362.1991.tb03871.x
10. Pankakoski A, Panelius J, Salava A, Kluger N. Bullous pemphigoid in three paediatric patients in Finland. Acta Derm Venereol [Internet].

2020;100(6):adv00086-2. Available from: http://dx.doi.org/10.2340/00015555-3445
11. Dufour C, Souillet AL, Chaneliere C, Jouen F, Bodemer C, Jullien D, et al. Successful management of severe infant bullous pemphigoid with

omalizumab: Correspondence. Br J Dermatol [Internet]. 2012;166(5):1140–2. Available from: http://dx.doi.org/10.1111/j.1365-2133.2011.10748.x
12. Venning VA, Taghipour K, Mohd Mustapa MF, Highet AS, Kirtschig G, Hughes JR, et al. British Association of Dermatologists’ guidelines for the

management of bullous pemphigoid 2012. Br J Dermatol [Internet]. 2012;167(6):1200–14. Available from: http://dx.doi.org/10.1111/bjd.12072
13. Kouris A, Platsidaki E, Christodoulou C, Armyra K, Korkoliakou P, Stefanaki C, et al. Quality of life, depression, anxiety and loneliness in patients

with bullous pemphigoid. A case control study. An Bras Dermatol [Internet]. 2016;91(5):601–3. Available from: http://dx.doi.org/10.1590/abd1806-
4841.20164935

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Dermatological Society

An unusual presentation of painless penile erosions of
pemphigus vulgaris: A case report

Ma. Bianca Therese Relova-Haresco, MD,1 Gisella U. Adasa, MD, FPDS,1 Sarah E. Nain, MD, MPH1

ABSTRACT

INTRODUCTION Pemphigus vulgaris is a life-threatening, autoimmune bullous disease caused by desmogleins (Dsg) 1 and 3 au-
toantibodies. It is a rare disease with an incidence rate of 0.5 to 3.2 per 100,000 per year. It typically presents as painful, flaccid
blisters and erosions on both the skin and mucous membranes.

CASE REPORT We present a 43-year-old male with painless penile erosions of 1-month duration. He was evaluated for sexually
transmitted infections, but laboratory tests yielded negative results. Subsequently, vesicles and bullae on the back and hyper-
keratotic lesions on the malar area appeared, leading to the differential diagnoses of bullous diseases. Skin biopsy was done
revealing intraepidermal suprabasal blisters with acantholytic cells. Direct Immunofluorescence demonstrated positive inter-
cellular deposits of IgG and C3. ELISA Dsg 1 and Dsg 3 were positive (ratio of 1.857 and 4.580, respectively). A final diagnosis of pem-
phigus vulgaris (PV) was made. The patient has remained in remission after a 3-month course of prednisone and azathioprine.

CONCLUSION This is a unique case of PV presenting with an unusual manifestation of painless penile erosions. There have been
limited reports of PV with penile skin involvement and all cases presented with painful lesions. Because painless penile lesions as
presenting feature is rare, the diagnosis may be easily missed. This case demonstrates that thorough dermatologic examination
and early diagnosis despite atypical findings are crucial to provide timely and appropriate treatment as this determines the clinical
outcome of the disease.

KEYWORDS pemphigus vulgaris, desmoglein, azathioprine

1Department of Dermatology, INTRODUCTION ple sexual partners. On dermatological examina-
Research Institute for Tropical tion, there were multiple erythematous painless
Medicine, Research Drive, Alabang, Pemphigus vulgaris (PV) is a potentially life-threat- erosions on the glans penis and upper part of the
Muntinlupa City ening, chronic autoimmune bullous disease penile shaft (Figure 1).
affecting the mucosa and the skin. It is charac-
Corresponding author terized by the production of autoantibodies tar- An initial working impression of herpes
Ma. Bianca Therese Relova-Haresco, geting desmogleins (Dsg) 1 and 3, leading to acan- simplex virus-2 (HSV-2) vs Primary Syphilis was
MD tholysis and epidermal bullae formation. In most made. The initial laboratory work-up included
patients, PV affects the oral mucosa, although HSV polymerase chain reaction (PCR), human
Conflict of interest involvement of other mucosae may also occur. immunodeficiency virus (HIV) immunoassay
None Mucosal involvement is commonly described as test, rapid plasma reagin (RPR), and treponema
painful erosions. There are only few reports of pallidum particle agglutination assay (TPPA).
Source of funding involvement of the penile skin and none of which Results were all negative. Upon follow-up, there
None are described as painless penile erosions. We were no oral mucosal lesions noted, however,
present a unique case of PV in a 43-year-old male the patient reported appearance of brownish-red
with an initial presentation of painless penile hyperkeratotic crusted plaques on the malar
erosions. Presence of this confers a poor prog- area accompanied with multiple well-defined
nosis, hence, aggressive intervention should be erythematous plaques and erosions, some with
implemented to achieve early remission and im- hemorrhagic crusting on the neck and upper
provement of quality of life.1 chest (Figure 2-A). Subsequently, there were new
eruptions of few flaccid and tense vesicles and
CASE REPORT bullae on the central back (Figure 2-B). During
this time, a diagnosis of bullous disease was en-
A 43-year-old male, Filipino, presented with pain- tertained specifically, Bullous Lupus Erythema-
less penile erosions of 1-month duration. The pa- tosus, Bullous Pemphigoid, and Pemphigus Vul-
tient has no known comorbidities. Sexual history garis. Antinuclear antibody (ANA), skin punch
revealed engaging in unprotected sex with multi-

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Dermatological Society

biopsy, direct immunofluorescence (DIF), and enzyme-linked Figure 2. Skin lesions prior to treatment. (A) Multiple well-defined brownish-red hyperkeratotic
immunosorbent assay (ELISA) Dsg 1 and 3 were done. ANA crusted plaques on both malar areas; erythematous papules, plaques, and erosions with
showed negative results (<1:1 ratio). hemorrhagic crusting on the neck and upper chest; (B) Few flaccid and tense vesicles and bullae
on the central back.
Histology of the skin taken from the upper back revealed
intraepidermal, suprabasal blister with acantholytic cells, and Figure 3. Photographs of biopsy specimen. (A) Skin biopsy from edge of the bullae of the lower
red blood cells within the lumen. DIF demonstrated positive (++) back showing an intraepidermal, suprabasal blister with acantholytic cells and red blood cells
intercellular deposits of IgG and positive (+) intercellular depos- within the lumen and row of tombstone appearance (H&E, 10x magnification). Positive DIF
its of C3, consistent with pemphigus. ELISA Dsg 1 (ratio of 1.857) showing intercellular deposits of (B) IgG and (C) C3.
and ELISA Dsg 3 (ratio 4.580) were both positive (Figure 3). A
final diagnosis of Pemphigus Vulgaris was made. ty. Clinical improvement was noted as skin and penile mucosal
lesions have resolved leaving only post-inflammatory hyperpig-
Assessment of disease activity was done using Pemphi- mentation (Figure 4).
gus Disease Area Index (PDAI) where the patient scored 9.88%
(26/263, moderate disease activity). Prior to treatment, quality At six (6) months of therapy, the disease activity score was
of life (QoL) was measured using Autoimmune Bullous Disease even lower (PDAI score of 2/263 from 5/263) and quality of life
Quality of Life (ABQoL) and Treatment of Autoimmune Bullous was markedly improved with significant clinical improvement.
Disease Quality of Life (TABQoL) where he scored 27.45% (14/51, However, repeat ELISA Dsg 3 remained positive (ratio of 3.50)
moderate QoL) and 17.65% (9/51, moderate QoL), respectively. making our patient serologically active warranting continuous
monitoring and treatment with azathioprine.
Prednisone was initiated at 1 mg/kg body weight/day for
two (2) weeks which provided control of disease activity (i.e., es- DISCUSSION
tablished lesions begin to heal and new lesions cease to form).
After achieving control of disease activity, azathioprine 50mg/ Pemphigus vulgaris is an autoimmune bullous disease affecting
day and slow-tapering prednisone regimen (i.e., dose was de- the skin and mucous membranes, with an incidence of 0.5 to 3.2
creased by increments of 10mg every two (2) weeks followed by per 100,000 per year. In Asian countries, PV is the most preva-
decrease in increments of 5 mg every two (2) weeks after 20mg/ lent type, with a sex ratio of 1:1 to 1:2, affecting patients 40 to 60
day dose was reached) were given. At three (3) months of ther- years old.2
apy, a repeat ELISA test revealed negative Dsg 1 (ratio of 0.269)
and decreased Dsg 3 (ratio of 4.184). At this time, repeat ABQoL Nearly all patients with PV have mucosal involvement. Cu-
score decreased to 17.65% (9/51, moderate QoL) while TABQoL taneous lesions may precede other symptoms by months or may
remained at 17.65% (9/51, moderate QoL). PDAI score decreased be the only feature. In a retrospective study, Chams-Davatchi et
from 9.88% (26/263, moderate disease activity) to 1.9% (5/263, al. reported involvement of the oral cavity, conjunctiva, nasal,
mild disease activity) indicating good control of disease activi- vaginal, laryngeal/esophageal and perineal mucosae in 81%,
16%, 11%, 9%, 8% and 2% of cases, respectively.3 Common to
Figure 1. Penile lesions prior to treatment. Few erythematous painless erosions on the glans penis
and upper part of the penile shaft.

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Figure 4. Lesions after three months of treatment with prednisone and azathioprine. (A) Marked treatment, both ABQoL and TABQoL further improved.
improvement of lesions leaving only hyperpigmented macules and patches on the face, neck, PDAI was assessed to measure clinical disease activity.
and upper chest; (B) Resolution of penile lesions.
The optimal points of pemphigus disease severity score in
these mucosal involvement is the presence of painful erosions PDAI were: mild (0-15), moderate (15-45) and severe (≥45).8 In
that often result in significant discomfort and limitation to an this patient, baseline PDAI score was 9.88% (26/263, moderate
individual’s activities of daily living. disease activity). At three (3) months of treatment, clinical
improvement was noted as lesions have resolved leaving only
Genital involvement in males is rare. Sami et al. reported post-inflammatory hyperpigmentation, associated with a de-
penile skin involvement of 12 male patients diagnosed with PV. crease in PDAI score to 1.9% (5/263, mild disease activity) with
Of these, 10 patients had concomitant cutaneous lesions.4 Stieg- a further decrease to 0.76% (2/263, mild disease activity) after
er et al. reported two (2) cases of penile erosions as the initial six (6) months.
presenting sign of PV.1 All cases presented with painful penile
erosions, and all responded to 1mg/kg/body weight of predni- ELISA detects IgG autoantibodies to serologically diagnose
sone and azathioprine. This was the similar treatment given to and monitor the disease activity in PV. In this patient, ELISA
our patient. Dsg 1 and 3 titers decreased from 1.857 and 4.580 to 0.269 and
4.184, respectively. At six (6) months of therapy, ELISA Dsg 3 was
Painless penile erosions are most frequently related to in- still positive at ratio 3.50. A cut-off of 1.0 is used to detect a pos-
fectious etiologies such as HSV and Syphilis.5 Our patient pre- itive or negative result. Patients with high titers of ELISA Dsg 1
sented with painless penile erosions but had a negative result in and 3 indicate serological non-remission which would require
HSV PCR, RPR, and TPPA tests. The presence of genital lesions continuation of immunotherapy.9 Continuous treatment is war-
in PV is indicative of resistance to treatment and patients may ranted despite clinical improvement and increase in QoL. This
require high doses of systemic steroids and immunosuppressive validates the role of ELISA as an important tool in determining
regimen should be started early in the course of disease.6 treatment response and duration.

Pemphigus vulgaris can severely affect the patient’s qual- At the third and sixth months of treatment, our patient
ity of life. The chronicity of the disease poses a significant bur- was in clinical remission. Remission is defined as the absence
den to the physical, emotional, economic, and social well-being of new or established lesions for at least two (2) months while
of the patient. Scoring systems to assess the quality of life and on minimal therapy.10 However, follow-up visits are still recom-
the clinical disease severity should be used at baseline and at mended every four (4) to eight (8) weeks until oral steroids have
intervals during treatment. To measure health-related quality been discontinued and until serum anti-Dsg antibodies have
of life (HRQoL) before and after treatment, ABQoL and TABQoL normalized.8
were used.7 Both are 17-item questionnaires that are reliable
and valid in measuring HRQoL in Autoimmune Bullous Disease In conclusion, we present a 43-year-old male with histo-
(AIBD). QoL during treatment is important to evaluate to estab- pathologically proven diagnosis of PV presenting initially with
lish risk-benefit balance of therapy.7 A score above 20 points is painless penile erosions with subsequent eruption of bullae on
considered a high score and indicates poor QoL and below 7 points the posterior trunk and hyperkeratotic plaques on the malar
is considered low. In our patient, baseline ABQoL and TABQoL area. In this case, a diagnostic delay of more than one (1) month
were moderate. Assessment on the 3rd month showed a decrease may occur from the first manifestation of mucosal lesion. Since
in ABQoL while TABQoL remained unchanged. At six (6) months of mucosal lesions are common in PV and may even be the sole
manifestation, a thorough dermatological examination of all
mucosal sites is warranted and must include the genital area.
This may be of value at present, where online consultation may
make examination of certain body areas a challenge. Further-
more, a presentation of painless erosions on the penile organ
should not rule out a diagnosis of PV. Genital involvement in PV
is associated with treatment resistance and is regarded as a poor
prognostic factor and marker of disease severity. Therefore, im-
mediate treatment using a combination of oral steroid and aza-
thioprine is recommended. Finally, this study highlights the
importance of incorporating to the standard of care the scoring
systems such as the PDAI, ABQoL, and TABQoL. These tools
together with ELISA play an important role in providing treat-
ment success.

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3. Chams-Davatchi C, Valikhani M, Daneshpazhooh M, Esmaili N, Balighi K, Hallaji Z, et al. Pemphigus: analysis of 1209 cases. Int J Dermatol
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4. Sami N, Ahmed AR. Penile Pemphigus. Arch Dermatol. 2001;137(6):756–758. doi:10-1001/pubs.Arch Dermatol.-ISSN-0003-987x-137-6-dob00047
5. Kalasapura RR, Yadav DK, Jain SK. Multiple primary penile chancre: A re-emphasize. Indian J Sex Transm Dis AIDS [Internet]. 2014;35(1):71–3.

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9. Russo I, De Siena FP, Saponeri A, Alaibac M. Evaluation of anti-desmoglein-1 and anti-desmoglein-3 autoantibody titers in pemphigus patients
at the time of the initial diagnosis and after clinical remission. Medicine (Baltimore) [Internet]. 2017;96(46):e8801. Available from: http://dx.doi.
org/10.1097/MD.0000000000008801
10. Gregoriou S, Efthymiou O, Stefanaki C, Rigopoulos D. Management of pemphigus vulgaris: challenges and solutions. Clin Cosmet Investig
Dermatol [Internet]. 2015;8:521–7. Available from: http://dx.doi.org/10.2147/CCID.S75908

52 J Phil Dermatol Soc · November 2022 · ISSN 2094-201X

JPDS CASE REPORT
Journal of the Philippine
Dermatological Society

Treatment response as a diagnostic feature in zinc
deficiency-associated dermatitis in a three-month-old

Filipino male: A case report

Sher Claranza O. Liquido, MD, DPDS,1 Jamaine Melisse L. Cruz-Regalado, MD, FPDS1

ABSTRACT

INTRODUCTION Zinc deficiency is of high magnitude in developing countries such as the Philippines. Zinc deficiency dermatitis
is recognized through characteristic cutaneous presentation supported by diagnostic workups which may not be feasible or
practical in low-resource settings.

CASE REPORT A three-month-old Filipino male was brought in for erosions of three (3) weeks duration that were unrespon-
sive to topical and systemic antimicrobial treatment. On examination, he had multiple erythematous erosions with yellowish
to brownish, crusted borders with predilection on the face, inguinal and gluteal areas, flexures of the extremities, and digits.
Workup revealed normal zinc levels, decreased alkaline phosphatase, and bacterial growth in cultures. Histopathology revealed
intraepidermal vesiculobullous dermatitis. Given the clinicopathologic presentation, a diagnosis of zinc deficiency-associated
dermatitis was made. Along with antimicrobials and topical care, oral zinc sulfate with elemental zinc at 3 mg/kg/day was started,
with remarkable improvement within three (3) days and near-resolution after eight (8) days of zinc therapy. Zinc supplementation
was administered for three (3) months with gradual tapering. The skin remained clear despite the withdrawal of zinc supplemen-
tation. Response to treatment supported the impression of zinc deficiency, while sustained skin clearance upon withdrawal
verified an acquired etiology.

CONCLUSION Zinc deficiency-associated dermatitis is more common in areas where costly diagnostic modalities are not readily
available. In clinically suspected zinc deficiency, response to treatment can serve as a retrospective diagnostic feature, and sus-
tained clearance upon withdrawal may aid in identifying etiology. Trial of therapy may then be considered in optimizing the cost-ef-
fective management of zinc deficiency-associated dermatitis.

KEYWORDS zinc deficiency, nutrition, pediatric dermatology

1Department of Dermatology, St. INTRODUCTION CASE REPORT
Luke’s Medical Center, Quezon
City, Philippines Zinc deficiency is estimated to be at 20% of the A three-month-old Filipino male presented with
world population and is more common in devel- erosions of three weeks duration. The lesions
Corresponding author oping countries.1 In the Philippines, the national started as erythematous patches on the testicu-
Sher Claranza O. Liquido, MD, DPDS estimate is high at 30% of the country’s popula- lar and gluteal area which eroded and enlarged.
tion.2 Benzalkonium chloride with cetrimide cream
Conflict of interest was applied without improvement. Brownish
None Skin is the third most zinc-abundant tissue. plaques then developed on the cheeks, spread-
Deficiency can manifest through characteris- ing to the neck, ears, and occipital area. Several
Source of funding tic cutaneous involvement.3 Diagnostic tests are flaccid bullae also formed on the medial thighs.
None only supportive to the clinical picture and there Upon consultation, unrecalled dosage of cefalex-
is no consensus as to which modality is most in oral drops and fluticasone propionate cream
appropriate in establishing deficiency.4 More- were prescribed for a week. However, as febrile
over, zinc deficiency-associated dermatitis is episodes developed and lesions continued to
commonly encountered wherein cost-effective progress, medications were revised to oral clin-
management is needed and diagnostic modali- damycin (9 mg/kg/day), cefixime (8 mg/kg/day),
ties may not be feasible. In this case report, we oral fluconazole (12 mg/kg/day), and topical mi-
describe zinc deficiency-associated dermatitis conazole cream. The fever lysed, but minimal
in a pre-term infant whose therapeutic response improvement prompted admission.
aided in the diagnosis.

J Phil Dermatol Soc · November 2022 · ISSN 2094-201X 53

CASE REPORT JPDS
Journal of the Philippine
Dermatological Society

The patient was born preterm to a primigravid at 33 weeks Figure 2. Hematoxylin and eosin (x100) Intraepidermal vesiculobullous dermatitis with pallor
via normal spontaneous delivery, with a low birth weight of and ballooning degeneration on the upper epidermis (A); CD1a (x100) – relative paucity of
1,790g. He had been exclusively breastfed without latching Langerhans cells in the epidermis (B).
problems. The mother had unrestricted and adequate food in-
take. The family history was unremarkable. hours), and oral metronidazole (26 mg/kg/day), with fungal cov-
erage from fluconazole (12 mg/kg/day). Topical care consisted of
Upon examination, the patient was irritable with low- mupirocin ointment over the erosions twice daily after normal
grade fever at 37.9oC, wasted (z-score below -2), and severely saline solution compress.
underweight (z-score below -3) at 3.42kg and 54cm in length.
There were erythematous erosions with yellowish to brownish There was remarkable improvement after three (3) days of
peripheral crusts on the face extending to the ears and neck. zinc supplementation with drying of the erosions. On the eighth
The lips were dry, but other parts of the oral mucosa were unre- day of zinc therapy, minimal crusts remained, and re-epitheli-
markable. There were dusky red papules coalescing to plaques alization was complete with dusky red erythema over affected
with crusted erosions on the trunk, inguinal, gluteal area, flex- areas (Figure 1c and 1d). Upon discharge, medications were con-
ures of extremities, and digits (Figure 1a and 1b). There were no tinued as oral zinc sulfate (3 mg/kg/day elemental zinc), copper
lymphadenopathies palpated. (2.5 mg/day), folic acid (2.5 mg/day), and multivitamins. Com-
plete resolution was reported after two weeks of supplementa-
Pertinent workup revealed decreased alkaline phosphatase tion. After a month, repeat alkaline phosphatase was elevated
at 127 U/L (Reference Interval (RI): 134-518 U/L), and serum zinc at 667 U/L (RI: 134-518 U/L). To identify the cause of deficiency,
level within range at 10.1 µmol/L (RI: 8.6-19.1 µmol/L). Blood breastmilk zinc level was determined, found to be 11.2 µmol/L
culture revealed Staphylococcus epidermidis. Wound culture and at four months post-partum.
sensitivity had growth of Pseudomonas aeruginosa and Klebsiella
pneumonia. Tissue bacterial culture revealed Staphylococcus hae- Zinc was administered for three (3) months with gradu-
molyticus, while fungal culture was negative for growth. Skin al tapering. After three months of discontinuation, zinc level
biopsy from a bulla on the thigh revealed psoriasiform spongi- determination was repeated and found low at 7.95 µmol/L (RI:
osis with intraepidermal vesiculobullous dermatitis. There was 8.6-19.1 µmol/L). However, as the skin remained clear even
pallor and ballooning degeneration on the upper epidermis. Im- upon the introduction of mixed feeding, with the weight and
munohistochemical staining CD1a revealed a relative paucity of length of the patient normalized, no further supplementa-
Langerhans cells in the epidermis (Figure 2). Given the clinico- tion was pursued.
pathologic features, the diagnosis of zinc deficiency-associated
dermatitis with concomitant bacterial infection was made. DISCUSSION

The patient was started on elemental zinc at 3 mg/kg/day Zinc is involved in metabolism as a cofactor of enzymatic re-
as oral zinc sulfate. Antimicrobials consisted of intravenous actions and transcription processes.3 The etiology of the defi-
vancomycin (60 mg/kg/day), cefepime (50 mg/kg/dose every 12 ciency is classified as either inborn or acquired.1 Our case was
considered acquired because the patient was a three-month-old
Figure 1. Baseline photos - erosions with yellowish to brownish crusted borders (A, B); After purely breastfed preterm who had unremarkable family histo-
eight days of zinc supplementation (C, D). ry. Inborn autosomal recessive acrodermatitis enteropathica
would have presented upon weaning or in infants who are fed
formula wherein zinc has a lower bioavailability as compared to
breastmilk.1 As a preterm infant, he is susceptible to deficiency
as relevant intrauterine zinc transfer occurs during the last 10
weeks of gestation.5 They are born with lower baseline zinc lev-
els which are challenged over the first few years of life. When

54 J Phil Dermatol Soc · November 2022 · ISSN 2094-201X

JPDS CASE REPORT
Journal of the Philippine
Dermatological Society

preterm infants undergo growth spurts, there is increased zinc as was observed in our case.8 Histopathology was also support-
demand with concomitant losses from an immature gut.5,6 Zinc ive of the diagnosis showing pallor of the upper epidermis and
in breastmilk also rapidly declines during the postpartum pe- intracellular edema, albeit nonspecific in presentation.9 With
riod.4 Cutaneous infection may increase zinc demand as well.4 the clinical presentation supported by workup findings, the
These baseline deficits of zinc in a preterm infant and increased case was still deemed dermatitis from zinc deficiency even with
demand compounded with a cutaneous infection may have led initial serum zinc level within range. Supplementation for mild
to an overt zinc deficiency-associated dermatitis. to moderate acquired zinc deficiency ranges from 0.5-1.0 mg/
kg/day elemental zinc, but this may vary depending on the dis-
The patient had characteristic cutaneous presentation of ease.8 Our patient was started at 3 mg/kg/day given the extent
symmetric eczematous plaques that progressed to vesiculobul- of cutaneous affectation. Response to treatment has been pro-
lous lesions and erosions with peripheral crusted borders on the posed as a useful diagnostic feature in a case report by Dev and
mouth, perineal, and acral areas.1 This distribution supported Sethuraman (2017), wherein total resolution was observed after
the proposal that zinc deficiency-associated dermatitis is a con- a week.10 In the case presented, near-resolution was observed
tact dermatitis involving areas exposed to irritants. This is due after eight (8) days of zinc supplementation (Figure 1). The pa-
to the decrease in the Langerhans cells in the epidermis tasked tient was able to catch up in anthropometric measurements and
to rectify the irritant dermatitis.7 As in the patient, there was improvement was sustained upon discontinuation of zinc sup-
relative paucity of Langerhans cells in the CD1a staining. plementation. Aside from being the primary form of treatment,
zinc supplementation aided in establishing the diagnosis of the
Currently, there is no consensus on the specific workup to patient wherein the dramatic response served as a retrospective
establish zinc deficiency. Zinc level determination is prone to diagnostic modality for deficiency. Sustained clearance of the
inaccuracies as it can be affected by acute inflammation, hemo- skin upon withdrawal of the supplement also supported an ac-
lyzed samples, or when blood is drawn after meals.4 With this, quired etiology, as inborn forms would have recurred, needing
zinc levels were of minimal value in the case of analyzing defi- lifelong treatment.10
ciency. For the breastmilk zinc level, there is no definite nor-
mal range interval, though supportive to the diagnosis if below As such, in patients suspected of zinc deficiency-associated
10.7 µmol/L[8]. In this case, the breastmilk zinc level at four (4) dermatitis clinically, a trial of zinc therapy to observe response
months postpartum was at 11.2 µmol/L, which was also noncon- may be considered as means of confirming deficiency and sup-
tributory to establishing etiology. Nonetheless, alkaline phos- porting considered etiology. This may be of value in maximizing
phatase, which is a zinc-dependent enzyme, was useful in estab- cost-effective management, especially in resource-limited set-
lishing the diagnosis. Alkaline phosphatase level is low in zinc tings wherein prevalence of zinc deficiency is high.
deficiency with a corresponding increase with supplementation

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http://dx.doi.org/10.1136/bcr-2017-220928

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Appendix 1

Journal of the Philippine Dermatological Society • Volume 31 Issue 2 • November 2022