Linear immunoglobulin A bullous dermatosis with severe ocular sequela

Abstract

Linear immunoglobulin A bullous dermatosis is a rare autoimmune disease with a good response to dapsone. We present the case of a female patient who was diagnosed with bullous pemphigoid and initially treated with systemic steroids; however, a poor response to the medication led to treatment discontinuation and loss to follow-up. The patient had lost vision in the left eye 2 years before this study and recently experienced decreased vision in the right eye.

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48
Abstract
Case Report
introduCtion
Linear immunoglobulin A bullous dermatosis (LABD) is a
rare autoimmune subepidermal bullous disease. Children with
blistering eruptions were rst described in 1901, and LABD
was recognized as a distinct entity in 1979.[1] Because LABD’s
clinical presentation is variable,[2] diagnosing the condition
exclusively based on clinical observation is dicult. Mucosal
involvement can occur, with severe adverse consequences.[3,4]
Herein is presented a comprehensive case report of a woman
who presented with LABD complicated with bilateral vision
impairment.
CAsE rEport
A 58-year-old female presented with itchy erythematous
papules, plaques, and vesicles that started from the back and
progressed to the four extremities 10 years ago. Skin rashes
did not worsen with sun exposure. According to the patient,
she underwent a skin biopsy and was diagnosed with bullous
pemphigoid. She was treated with steroids, but her response
was poor, prompting treatment discontinuation and loss to
follow-up. Approximately 3 years ago, the patient began to
experience blurred vision in the left eye. Therefore, thrice
she underwent ophthalmological debridement interventions;
however, eventually, she completely lost vision in the left eye.
A similar problem recently occurred in the right eye. Because
she feared losing vision in the right eye and she visited our
Ophthalmology Department. Ophthalmologic examination
Linear immunoglobulin A bullous dermatosis is a rare autoimmune disease with a good response to dapsone. We present the case of a female
patient who was diagnosed with bullous pemphigoid and initially treated with systemic steroids; however, a poor response to the medication led
to treatment discontinuation and loss to follow-up. The patient had lost vision in the left eye 2 years before this study and recently experienced
decreased vision in the right eye.
Keywords: Blindness, eye, linear immunoglobulin A bullous dermatosis
Address for correspondence: Dr. Wen‑Hung Chung,
Department of Dermatology, Chang Gung Memorial Hospital,
No. 199, Tung‑Hwa North Road, Taipei 105, Taiwan.
E‑mail: wenhungchung@yahoo.com
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Linear immunoglobulin A bullous dermatosis with severe ocular
sequela
Meng‑Han Shen1,2, Wen‑Hung Chung2,3*, Tseng‑Tong Kuo3
1Department of Dermatology, Chang Gung Memorial Hospital, Keelung, Taiwan,
2College of Medicine, Chang Gung University, Taoyuan, Taiwan,
3Department of Dermatology, Chang Gung Memorial Hospital, Taipei, Taiwan
Contents lists available at ScienceDirect
Dermatologica Sinica
journal homepage: www.dermsinica.org
Received: 05-Dec-2018 Revised: 25-Jun-2019 Accepted: 27-Jun-2019 Available Online: 27-Feb-2020
How to cite this article: Shen MH, Chung WH, Kuo TT. Linear
immunoglobulin A bullous dermatosis with severe ocular sequela. Dermatol
Sin 2020;38:48-50.
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Shen, et al.: Immunoglobulin A Bullous Dermatosis
49
Dermatologica Sinica ¦ Volume 38 ¦ Issue 1 ¦ January-March 2020
revealed trichiasis, cicatricial conjunctivitis, pannus ingrowth,
notable fornix shortening, and a symblepharon in the left
eye [Figure 1d]. Schirmer’s test results were negative. The
ophthalmologist suspected an autoimmune disease and
transferred the patient to the Department of Dermatology.
She had generalized excoriated papules, plaques, and several
urticaria-like wheals on the bilateral legs [Figure 1a]. Few
vesicles were observed on the back [Figure 1c]. Skin biopsy
revealed a subepidermal vesicle with neutrophils and eosinophils
[Figure 2a and b]. Direct immunouorescence (DIF) study
showed linear immunoglobulin A (IgA) staining and weak
granular C3 deposits in the basement membrane, with no
immunoglobulin G deposits [Figure 2c and d]. Furthermore,
indirect immunouorescence (IIF), including anti-intercellular
substance antibodies and anti-basement membrane zone
antibodies, was negative. In addition, anti-Ro and anti-La
antibodies were negative, and primary Sjögren’s syndrome
was ruled out. Information retrieved from the patient’s clinical
manifestations, histopathology, DIF, and IIF prompted LABD
diagnosis. The patient was treated with dapsone, and skin
lesions remarkably reduced within 2 weeks [Figure 1b].
Although conjunctival biopsy was necessary to conrm IgA
deposition at the ocular tissue, which might have provided
a more direct causality for the patient’s blindness, the
patient was unwilling to perform the procedure. Dapsone
treatment did not improve the patient’s vision, as evidenced
by chronic and irreversible scarring of the right eye. As
per the ophthalmologist’s suggestion, amniotic membrane
transplantation in the right eye was performed, with improved
visual acuity.
disCussion
LABD is a rare autoimmune disorder with low incidence
and characterized by subepidermal vesicles with linear
IgA deposition in the basement membrane.[5] Adult-onset
LABD frequently begins relatively late in life, occurring
approximately between the age of 40 and 60 years.[5-7]
LABD skin manifestations are variable. Diagnosis should be
considered when a patient presents tense blisters on healthy
skin or within inammatory plaques. Pruritus is a common
symptom, with other cutaneous manifestations potentially
mimicking dermatitis herpetiformis, bullous pemphigoid,
pemphigus vulgaris, varicella, or vasculitis.[5] Diagnosing the
condition exclusively based on the observations of clinical
manifestations is dicult. Skin biopsy and DIF study are
essential to distinguish LABD from other subepidermal
blistering diseases and conrm LABD diagnosis.
Although LABD pathogenesis is not well understood,
humoral and cellular immunity may contribute to the disease.
Several eliciting factors have been reported. A case report
documented LABD induction by drug exposure, especially
vancomycin.[8] Reported genetic factors include the human
leukocyte antigen (HLA) B8, HLA Cw7, HLA DR3, HLA
Figure 1: (a) Initially, skin manifestations were generalized excoriated
papules and plaques, several urticarial‑like wheals on the bilateral legs,
and generalized xerosis. (b) After dapsone treatment, the skin lesions
were markedly reduced. (c) A few vesicles across the back were noted.
(d) Fornix shortening and a symblepharon of the left eye
d
c
b
a
Figure 2: (a) Subepidermal vesicle. (b) High magnification revealed
neutrophils and eosinophils. (c) Direct immunofluorescence study showed
weak granular C3 deposits in the basement membrane zone. (d) Direct
immunofluorescence study showed linear immunoglobulin A staining in
the basement membrane zone
d
c
b
a
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Shen, et al.: Immunoglobulin A Bullous Dermatosis
50 Dermatologica Sinica ¦ Volume 38 ¦ Issue 1 ¦ January-March 2020
DQ2, and tumor necrosis factor-2 allele.[7-9] In addition to
skin involvement, the mucosa can also be aected; however,
the incidence of mucosal involvement is variable. In Western
countries, up to 80% of adult patients present mucosal
lesions, contrarily to Taiwan, where the incidence of mucosal
involvement is low (18%).[5,6] Oral and orbital mucosa are the
most commonly aected mucosas. Blister formation, painful
oral erosions, ulceration, gingivitis, and cheilitis may occur as
oral LABD manifestations,[4,10] whereas ocular manifestations
include intermittent itchiness, burning, redness of both eyes,
increased ocular discharge, or foreign-body sensation.[6] Oral
or ocular manifestations, although rare, may be the only
LABD manifestations or may precede cutaneous symptoms.
A case of predominant oral lesions for 5 years before the
development of skin lesion has been reported.[10] The patient
in the present case had oral manifestations for 6 months before
skin eruptions developed. At such an early stage, diagnosis
is dicult. Biopsy and DIF study can facilitate diagnosis.
After 8 years of oral and cutaneous lesions, the patient lost
vision in the left eye. She underwent thrice ophthalmological
debridement interventions in the left eye, with an initial slight
vision recovery after the rst operation, but complete vision
loss afterward.
One case report described a patient with mild xerostomia
and eye grittiness for 1 year and pruritic blisters on the trunk
and extremities for 2 months. Antinuclear, anti-Ro/SSA, and
anti-La/SSB antibodies were positive, but anti-DNA and serum
complement levels were normal. Skin biopsy and DIF revealed
linear IgA dermatosis. The report concluded that linear IgA
dermatosis was a rare cutaneous manifestation of primary
Sjögren’s syndrome. The patient in the present case had similar
symptoms and clinical course. However, antinuclear, anti-Ro/
SSA, and anti-La/SSB antibodies were within the normal
ranges, ruling out Sjögren’s syndrome diagnosis.[11]
The rst-line treatment for LABD is currently dapsone, starting
at a low dose (<0.5 mg/kg/day in children and 25 or 50 mg/day
in adults) and subsequently titrating upward over several
weeks according to the patient’s response. LABD exhibits a
good response to dapsone.[12] However, complications with
dapsone treatment include hemolysis, methemoglobinemia,
agranulocytosis, and dapsone hypersensitivity syndrome,
which should be carefully considered. Hemolysis and
methemoglobinemia specifically occur in patients with
glucose-6-phosphate dehydrogenase deciency. Moreover,
dapsone hypersensitivity syndrome especially occurs in
patients with HLA-B*13:01.[13] Therefore, complete blood
count, liver enzymes, and glucose-6-phosphate dehydrogenase
levels at baseline should be checked to prevent severe side
eects.
After the patient was treated with dapsone, skin lesions
remarkably reduced within 2 weeks. Due to stable chronic
and irreversible scarring of the right eye, the patient’s
vision did not improve with dapsone treatment. According
to the ophthalmologist’s suggestion, amniotic membrane
transplantation in the right eye was performed, with visual
acuity improvement.
Thus, this report describes the case of a patient suering from
linear IgA dermatosis with ocular involvement and blindness.
We aim to provide insightful dierential diagnosis and disease
manifestations to illustrate the importance of an accurate
diagnosis and treatment.
Acknowledgment
The authors would like to thank Enago (www.enago.tw) for
the English language review.
Ethical statement
Ethical approval for this study (IRB No. 201901530B0) was
provided by the Institutional Review Board of Chang Gung
Medical Foundation on 14 October 2019. The IRB agreed to
waive the informed consent.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conicts of interest.
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