Linear IgA Bullous Dermatosis and Agranulocytosis in a Patient With Crohn's Disease

Background:
A variety of dermatological lesions can be associated with inflammatory bowel diseases (IBD). Linear IgA bullous dermatosis (LABD) is a rare autoimmune condition that may be drug-induced, idiopathic, related to connective tissue diseases, malignancies or IBD, particularly ulcerative colitis (UC). To date, only 7 cases associated with Crohn’s disease (CD) have been reported.
Methods:
Case report describing a patient with CD who failed 2 immunobiological treatments and developed linear IgA bullous dermatosis in a disease flare, with severe hematological complications, requiring aggressive management.
Results:
A 62-year-old female, with penetrating CD, who previously failed Infliximab, currently on adalimumab (ADA), presented to IBD department in 2022, showing severe disease symptoms. Despite ruling out associated infections and optimizing ADA treatment, there was no clinical, laboratory, or endoscopic improvement and Ustekinumab was then requested. She has a history of recurrent genital herpes. Eleven months later, the patient presented with multiple bullous lesions on the upper thighs, vulva, and perineum, with local erythema, purulent discharge and macerated areas. Laboratory tests showed anemia, elevated C-reactive protein and fecal calprotectin. She was then admitted and started on acyclovir and empirical antibiotics. After a few days lesions got worse, showing multiple tense blisters and crusts also on the arms, axillae, feet, hands, and trunk. After Dermatology evaluation, possible differential diagnosis included anti-TNF induced bullous lupus, bullous pemphigoid and LABD. Direct immunofluorescence confirmed linear IgA deposition along the basement membrane (BM) and established the diagnosis. Treatment with dapsone and prednisone led to significant improvement of skin lesions. In January 2024, the patient presented to the emergency room with fever and chills. Initial tests showed hemoglobin 8.1 g/dL, leukocytes 640/mm³ and segmented neutrophils 45/mm³. Febrile neutropenia protocol was initiated, and dapsone was discontinued, with clinical and laboratory improvement within a week. Dermatology reevaluation led to the prescription of colchicine and tacrolimus ointment. Two months later, skin lesions had resolved, but IBD activity remained. Ustekinumab was finally approved and induction was started.
Conclusions:
LABD, an uncommon autoimmune disease associated with linear IgA deposition along the BM, can be associated with IBD, especially UC, and only 7 cases related to CD have been documented to date. Pathogenesis is not completely understood but it is hypothesized that colonic inflammation may disrupt mucosal barrier integrity, leading to abnormal antigen processing and production of cross-reactive IgA1 autoantibodies. This theory also explains the temporal association between IBD and LABD, where intestinal inflammation usually precedes dermatosis. Diagnosis is challenging and the gold standard test is direct immunofluorescence. Dapsone is the first choice treatment. IBD remission can also improve the dermatologic condition. There are reports of improvement of dermatological lesions after total colectomy in patients with UC. Severe treatment side effects, such as dapsone-induced agranulocytosis, require prompt management. Further studies are needed to clarify this association and consider this condition in the differential diagnosis of bullous lesions in IBD patients.