Linear immunoglobulin A (IgA) bullous dermatosis (LABD) is a rare autoimmune disorder characterized by vesiculobullous mucocutaneous eruptions. Defined diagnostic criteria for LABD are subepidermal bullae and a continuous band of homogeneous IgA deposited along the basement membrane.1 Idiopathic LABD and drug-induced LABD are clinically indistinguishable because of a morphologically heterogeneous presentation consisting of tense vesicles arranged in a herpetiform, rosettelike, or arciform pattern with erythematous papules or urticarial plaques resembling bullous pemphigoid, dermatitis herpetiformis, or bullous erythema multiforme. A thorough history of drug intake to differentiate idiopathic LABD from drug-induced LABD and direct immunofluorescence (DIF) in any bullous eruption is advisable to prevent misdiagnosis and unwarranted treatment.2
Case Report
A 54-year-old man with a 3-week history of a nonspecific illness consisting of fever, malaise, myalgia, and minor respiratory symptoms was seen as an outpatient and prescribed a 7-day course of rimantadine and a 5-day course of zanamivir for presumed influenza. The patient noted no significant improvement and returned to his primary care physician after he completed the course of treatment. A persistent fever was present with no signs of skin eruption or pruritus. Azithromycin was prescribed. After 3 days, the patient developed a generalized papulovesicular eruption. He was instructed to discontinue the medication and was given methylprednisolone intramuscularly and fexofenadine hydrochloride. The following day, the patient awoke unable to swallow, secondary to oral swelling and odynophagia. Vesicles and bullae in a generalized distribution were present on the skin. The patient was transferred to our institution and admitted to the burn unit. Physical examination revealed generalized erythema and a widespread bullous eruption on the trunk, extremities, and scrotum, and several erosions in the intertriginous areas (Figure 1). The eyelids were edematous and erythematous and the palpebral conjunctivae injected. The oral and genital mucosae were eroded. Intubation was necessary because of respiratory compromise caused by mucosal involvement. Nikolsky sign was negative. The suspected diagnosis at the time of presentation was Stevens-Johnson syndrome versus toxic epidermal necrolysis. Biopsy specimens were taken for frozen section and hematoxylin and eosin staining. Biopsy specimens of perilesional skin were tested with DIF studies.
Histopathologic and DIF Findings—Results of the frozen section biopsies revealed subepidermal bullae with a fairly dense neutrophilic infiltrate and few eosinophils. Neutrophils also were visualized, distributed in the dermoepidermal junction and papillary dermis (Figure 2). Necrotic keratinocytes were not visualized. DIF of the skin revealed a homogeneous linear pattern of IgA deposition at the basement membrane zone (BMZ)(Figure 3).
The patient was treated with prednisone 80 mg daily. An initial attempt to taper the steroids on day 6 of treatment resulted in the development of new vesiculobullous lesions. At that time, pentoxifylline 400 mg 3 times daily was added and the eruption stabilized. On the 16th day of the patient's hospital course, he showed no evidence of active disease, mucous membranes were uninvolved, and his oral discomfort had resolved. The acute bullous eruption that resolved after the discontinuation of all new medications and steroid therapy led to the diagnosis of drug-induced LABD mimicking Stevens-Johnson syndrome.
Comment
Drug-Induced LABD—Vancomycin is the drug most frequently associated with drug-induced LABD.3 Other drugs that have been reported include amiodarone hydrochloride,4 ampicillin/sulbactam,5 benazepril hydrochloride,6 candesartan cilexetil and eprosartan,7 captopril,4,8,9 carbamazepine,10 diclofenac,11 furosemide,12 gemcitabine hydrochloride,13 interleukin 2,14 lithium carbonate,15 naproxen,16 penicillin,17 phenytoin,8,18 piroxicam olamine,19,20 somatostatin analogue,8 sulfamethoxazole-trimethoprim,21 tea tree oil,22 and vigabatrin.21 The Table outlines autoimmune blistering diseases and the triggering drugs.
The mechanism by which the offending drug induces the production of autoantibodies toward BMZ components, including the anchoring filament protein ladinin, is unknown.21 It is thought that after the drug is bound to the BMZ, a change in its 3-dimensional structure takes place that causes antigenicity. Target antigens are known to be heterogeneous; immune electron microscopy has shown localization of the IgA1 subclass in the lamina lucida, lamina densa, and sublamina densa.21 The eruption of LABD usually favors the trunk, proximal extremities, and acral regions, with mucous membrane involvement in 40% of reported cases.2 Our patient presented with an acute severe generalized blistering disease involving the mucous membranes, which showed linear IgA deposition along the BMZ on DIF. The eruption occurred in relation to the ingestion of rimantadine, zanamivir, and azithromycin. Ultimately, treatment with prednisone and pentoxifylline resulted in resolution of his symptoms and the diagnosis of drug-induced LABD mimicking Stevens-Johnson syndrome.