A Case of Linear IgA Bullous Dermatosis Successfully Treated with Omalizumab.

Sir,

Linear IgA bullous dermatosis (LABD) is a rare autoimmune bullous disease also known as linear IgA disease, linear IgA pemphigoid, or linear dermatitis herpetiformis first described by Bowen in 1901.[1] It is clinically characterized by urticated plaques and papules with blisters arising either from normal skin or urticated lesions. LABD has two clinical variants; in children, the disease is known as chronic bullous disease of childhood (CBDC) with average presentation occurring at around 4–5 years, and in adults, bi-modal age distribution is seen: teenage years and sixties.[2] Drug of choice in LABD is currently oral dapsone therapy. We report a case of LABD successfully treated with omalizumab. Omalizumab is a monoclonal antiimmunoglobulin E (IgE) antibody. At present, it has been approved for chronic idiopathic urticaria and asthma.

A 40-year-old male presented to department of dermatology with multiple tense, hemorrhagic, non-tender bullae all over the body associated with itching since 1 month without any systemic complain or oral lesion [Figure 1]. Before presenting to our institute, he had been diagnosed via a skin biopsy as bullous pemphigoid and managed with oral steroids (prednisolone 30 mg/day), oral cyclophosphamide 50 mg/day, and topical fixed combination of clobetasol propionate with fusidic acid cream with partial improvement. However, on presentation to our institute, he had aggravated skin lesions since 2 days. Other than routine hematological, biochemical, and serological investigations [Table 1], repeat skin biopsy from fresh intact bullae and tissue for direct immunofluorescence (DIF) from perilesional skin were obtained. Examination of skin biopsy revealed subepidermal blister with eosinophil-rich infiltrate [Figure 2]. DIF examination of perilesional tissue showed a linear pattern of IgA deposition along the basement membrane zone. Based on histopathology and DIF examination findings, the diagnosis of LABD was made.

Figure 1

Pretreatment clinical presentation showing tense, hemorrhagic bullae with post-inflammatory hyperpigmentation of old healed bullae

Table 1

Summary of laboratory and radiological investigations

	Test	Result/normal laboratory range
Laboratory investigations	Complete blood count	Within normal limit
	Renal function test
	Routine and microscopic urine examination
	Serology for HIV, hepatitis B and hepatitis C viruses	Nonreactive
	Liver function test	SGPT-164 IU/L (Normal: up to 42 IU/L)
		SGOT-64IU/L (Normal: up to 37 IU/L)
	Fasting blood sugar	98 mg/dL (Normal range: 70-110 mg/dL)
	Postprandial blood sugar	190 mg/dL (Normal range 80-140 mg/dL)
	HbA1c	6.7 (normal range 4-5.6)
	Total serum IgE	2123 ng/mL (0-240 ng/mL)
	Absolute eosinophil count	330/Cumm
Radiological investigations	Ultrasonography of abdomen	No abnormality detected
	Chest X-ray	No abnormality detected

Figure 2

(a) Histopathology shows subepidermal bulla (H and E, ×40); (b) Plenty of eosinophils in the infiltrate (H and E, ×400); (c) direct immunofluorescence shows linear deposition of IgA at dermoepidermal junction (×100)

In view of altered liver function test and steroid induced hyperglycemia, cyclophosphamide was immediately stopped; dose of steroid was tapered to 20 mg per day. Other immunomodulators like dapsone, azathioprine, and methotrexate were not considered because of their potential for aggravating liver dysfunction. In view of the presence of eosinophil in skin biopsy and elevated serum IgE level, patient was given option of off-label use of omalizumab based on reported cases and our personal experience of its efficacy in bullous pemphigoid (having similar eosinophil-rich infiltrate). After obtaining informed written consent, injection omalizumab 300 mg was administered subcutaneously. Thereafter, dose of oral steroid was tapered over a period of 6 weeks and ultimately stopped. Injection omalizumab 300 mg subcutaneously was given at monthly intervals for another two doses. No new skin lesions appeared after the first dose of omalizumab and patient's skin was completely healed within 6 weeks of last dose of omalizumab. Itching subsided completely 1 week post- first dose of omalizumab requiring no antihistaminic therapy henceforth. Patient was on regular follow-up till reporting and he was off steroids since 9 months with no new skin lesion [Figure 3].

Figure 3

Post-omalizumab at 6 weeks complete resolution of skin lesions and marked improvement in post-inflammatory hyperpigmentation

In our case, cutaneous biopsy from intact bulla had subepidermal blister with predominant eosinophils. The gold standard for establishing a diagnosis of LABD is DIF examination. DIF examination characteristically showed linear deposits of IgA with or without IgG and C3 along the basement membrane zone.[3] Oral dapsone therapy is considered as first-line therapy for LABD, the dose ranging from 0.5 mg to 2 mg/kg/day, as in dermatitis herpetiformis. Its side effects include hemolytic anemia, leucopenia, and altered liver enzymes. Monotherapy with dapsone is sufficient in many cases but supplementation with corticosteroids and immunosuppressants, such as azathioprine and cyclophosphamide, may be necessary, especially due to increased adverse reactions at higher daily doses. In view of altered liver enzymes and hyperglycemia, above mentioned therapies were not the most appropriate choices for the management of our patient.

Omalizumab is a recombinant DNA-derived humanized IgG1κ monoclonal antibody that selectively binds to human IgE that is typically administered subcutaneously. It has successfully been used to treat bullous pemphigoid where the histopathological picture is one of subepidermal blister with eosinophilic infiltrate.[4] Only published report of use of omalizumab in LABD we could find was reported by Maalouf et al. where they initiated omalizumab for recalcitrant urticaria in 55-year-old female having concomitant LABD and eventually found good improvement in both.[5] Mechanism of action of omalizumab in bullous pemphigoid or LABD is not well-elucidated but the possible mechanism could be immune modulation through suppression of IgE receptors.

We present this case as omalizumab can provide safe and effective alternative to other existing therapies for LABD, particularly subset of cases having eosinophilic infiltrate in biopsy or elevated serum IgE although larger case series or controlled trials are required before any final conclusion can be reached.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.