A 36-year-old Hispanic male, with a history of ulcerative colitis (UC) presented to the inflammatory bowel disease (IBD) clinic for initial evaluation. Over the past six years, the patient had been treated for his UC with various therapies including prednisone, multiple mesalamine formulations, and budesonide but always discontinued therapy due to what he perceived were adverse drug reactions. He described onset of pruritic blisters, affecting his chest, abdomen, back, and arms.

He complained of multiple bloody bowel movements each day, associated with rectal burning, pain with defecation and an unintentional 12-pound weight loss over the past 2 months. After his most recent colonoscopy revealed pancolitis with biopsies significant for chronic inflammation throughout the colon without dysplasia with skin tags and anal fissure with rectal sparing, his diagnosis was revised to Crohn’s ileo-colitis.  Although symptomatic, he was very hesitant to start medical therapy given his previous experience. He has never been in clinical remission.

The patient was referred to a dermatologist for further evaluation of his skin lesions, as it was unclear whether the etiology of the dermatitis was a true adverse drug reaction. On physical exam, small rare intact bullae were noted on the posterior neck, along with eroded papules at the upper back (Figure 1A).  Hyperpigmented macules coalescing into hyperpigmented patches were noted on his chest and back and some appeared to have a slightly depressed appearance (Figure 1B/C). Skin biopsies were taken, for hematoxylin and eosin (H&E) and direct immunofluorescence.  H&E sectioning revealed subepidermal bulla with brisk neutrophilic inflammation (Figure 2) and linear deposition of IgA on direct immunofluorescence (Figure 3). These findings were consistent with linear IgA disease.

Given the neutrophilic nature of this bullous disease, he was prescribed dapsone 100 mg daily every other day which resulted in resolution of the rash. The patient was reassured that these skin reactions were extra- intestinal manifestations of his underlying inflammatory bowel disease and not a drug reaction to the medications he had previously taken for ulcerative colitis. He was subsequently treated with infliximab and achieved a deep remission with control of skin rash with dapsone. He did have a brief interruption of therapy with dapsone which resulted in recurrence of the rash.  This subsequently resolved with reintroduction of therapy.  Workup of a persistently elevated alkaline phosphatase with an MRI revealed intrahepatic duct dilation. Liver biopsy confirmed comorbid PSC.

Linear IgA bullous dermatosis (LABD) is suspected to be a rare extraintestinal manifestation of IBD. This autoimmune subepidermal disease presents with bullae, erosions and vesicles. LABD is characterized by the immunopathologic finding of linear IgA deposits in the basement membrane along the dermo-epidermal junction. This skin disorder was first identified by direct immunofluorescence by Chorzelski et al. [2]. Theories about pathogenesis include abnormalities in mucosal B cells and mucosal IgA production as well as abnormal mucosal permeability leading to atypical IgA production. [3,4]. The exact etiology of this rare disease is still unknown, but both drug induced and spontaneous forms of LABD have been observed. There are rare reports of an association between LABD and Crohn’s disease [5,6].

While the presence of vesicles makes LABD clinically similar to bullous pemphigoid and dermatitis herpetiformis, the presence of linear IgA deposits in the basement membrane defines Linear IgA bullous dermatosis as a distinct disease. LABD can be defined by three distinct criteria: presence of vesicles or bullae on skin, presence of subepidermal vesicles with a neutrophil predominance seen on histological examination and most definitively, the linear pattern of IgA basement membrane zone-specific deposits in the absence of other immunoglobulins [7]. The bullae associated with LABD often appear on the abdomen and limbs but bullae may also present on the hand, feet and perineum of affected patients. The form of LABD which presents in childhood (childhood onset LABD: chronic bullous disease of childhood (CBDC) has a peak age of incidence at 4-5 years of age. Adult onset LABD has a peak age of incidence at 60-65 years old. The clinical presentation of CBDC is distinct from LABD in that CBDC localizes to the lower abdomen and perineum [7].

Drug induced LABD has been associated with treatment with vancomycin, amiodarone and other antibiotics, such as penicillin and ceftriaxone; it is not associated with any of the medications this patient was on. The drug induced form of LABD has also been associated with non-steroidal anti-inflammatory drugs (NSAIDs) such as piroxicam, naproxen [8,9], as well as amiodarone. The time of onset for drug induced LABD ranges from 2 days to up to 4 weeks. The gold standard therapy for LABD is oral dapsone.

This case adds to the literature supporting the idea that LABD may be a dermatologic manifestation of IBD. In addition, this case uniquely illustrates that Linear IgA dermopathy does not track IBD disease activity as the patient continues to require dapsone to manage his skin manifestations despite achieving deep remission on infliximab therapy.  This is one of few cases confirming the association between Linear IgA bullous disease and Crohn’s disease in a patient with comorbid PSC.