An 18-year-old male with a history of epilepsy on levetiracetam, chronic constipation and abdominal pain since infancy, and chronic nocturnal enuresis since infancy started on imipramine one week prior and presented with a painful, itchy, diffuse skin eruption that worsened over 24 hours. The patient initially had tense vesicles on his neck, ears, and upper chest the previous day when evaluated by outpatient Allergy and Immunology. He was advised to discontinue imipramine due to concern for drug allergies and was prescribed empiric valacyclovir for herpes simplex virus and trimethoprim-sulfamethoxazole for bullous impetigo. However, the eruption then quickly spread to include his lower lip, abdomen, arms, and legs. The patient noted that the vesicles were tense and painful, especially after bursting. Additionally, the patient noted fatigue, generalized weakness, chronic constipation, abdominal pain in the bilateral lower quadrants with bowel movements, and occasional bright, blood-coated stools. The patient denied fever, chills, intraoral or esophageal lesions, odynophagia, dysphagia, arthralgia, myalgia, melena, nausea, vomiting, headache, and new exposures prior to the rash eruption, including poison ivy, new hygiene products, or new detergents.
Initial physical examination revealed the patient was afebrile, hemodynamically stable, with vesicles noted in the external auditory canals, moist mucous membranes without mucosal lesions, and a diffuse eruption with vesicles and bullae noted on the outer aspect of the lower lip, posterior neck, upper back, chest, arms sparing the palms, and legs sparing the soles. Some of the lesions appeared to be tense bullae, while others were less tense and umbilicated primarily on the dorsal hands and feet. Some of the lesions had burst, but most notably, there was a negative Nikolsky sign. Over the next few days, bullous lesions clustered in the classical pattern of a "string of pearls," as demonstrated in Figures 1-6.
Initial work-up included negative swabs via PCR for herpes simplex virus 1, herpes simplex virus 2, and varicella zoster, as well as a superficial wound culture of the posterior neck with rare Staphylococcus aureus. Laboratory findings included leukocytosis with eosinophilia, neutrophilia, mild monocytosis, microcytic anemia with iron deficiency, reticulocytosis, thrombocytosis, elevated inflammatory markers, elevated haptoglobin, and low ferritin (Table 1). The complete metabolic panel and lactate dehydrogenase levels were within normal limits (Table 1). The autoimmune workup was negative for the anti-nuclear antibody screening test, anti-double-stranded DNA antibodies, anti-Smith antibodies, anti-nuclear ribonucleoprotein antibodies, anti-Jo-1 antibodies (histidyl-tRNA synthetase), anti-Sjogren's-syndrome-related antigen A autoantibodies (anti-SSA/ro antibodies), anti-Sjogren's-syndrome-related antigen B (anti-SSB) autoantibodies, and scleroderma (Scl-70) antibodies. Complement component 3 (C3) and complement component 4 (C4) were within normal limits (Table 1). Immunoglobulin serum levels revealed elevated IgG1 subclasses (Table 1). Further work-up revealed negative results for the direct Coombs test, cold agglutinins, serum porphyrins, urine porphyrins, urine porphobilinogen, and 6-methylmercaptopurine. The glucose-6-phosphate dehydrogenase level was within normal limits (Table 1). A peripheral smear conducted during the hospitalization revealed mild neutrophilia attributed to the treatment plan, microcytic anemia secondary to iron deficiency and blood loss, reticulocytosis for bone marrow compensation, and reactive thrombocytosis attributed to anemia. Flow cytometry of peripheral blood had no abnormal findings. The infectious work-up was negative for HIV, hepatitis B, hepatitis C, and tuberculosis via QuantiFERON. A gastroenterological work-up revealed a positive fecal occult blood test (FOBT), significantly elevated fecal calprotectin, and negative transglutaminase IgA antibodies (Table 1). The patient had mild zinc insufficiency and an elevated vitamin B12 level, but levels for vitamin E, chromium, niacin, vitamin B6, folate, and copper were within normal limits (Table 1). Two skin-punch biopsies of the right posterior shoulder revealed a subepidermal cleft or blister with neutrophils at the tips of the dermal papillae. Direct immunofluorescence testing of the skin biopsies revealed continuous, strong linear basement membrane deposition of IgA, consistent with linear IgA bullous dermatosis.
The patient underwent esophagogastroduodenoscopy (EGD) and colonoscopy; EGD revealed a non-bleeding duodenal erosion, and duodenal biopsies were taken (Figure 7). Duodenal biopsies revealed duodenal bulb mucosa with gastric foveolar metaplasia consistent with mild peptic injury and notably negative for signs of celiac disease, malignancy, viral inclusions, and granuloma. Colonoscopy revealed moderately active (Mayo Score 2), left-sided ulcerative colitis with random colonic biopsies taken (Figures 8, 9). Random biopsies of the left colon demonstrated chronic, moderately active colitis, while random right colon biopsies revealed focal, chronic, but inactive colitis.
Imipramine was discontinued before hospitalization and not resumed due to the suggestion of drug-induced dermatosis. The patient was started on oral prednisone 10 mg when eruption failed to improve with supportive care after receiving one dose. The corticosteroid regimen was up-titrated the following day for worsening pain to methylprednisolone 125 mg intravenously twice daily, for which the patient received four days of treatment. As the eruption had improved, the patient was weaned to oral prednisone 40 mg daily, receiving two days of therapy before the eruption worsened again. Oral prednisone was increased to 60 mg with the addition of oral azathioprine 50 mg twice daily. Despite this, the eruption worsened, which necessitated further up-titration of corticosteroids to methylprednisolone 500 mg intravenously daily for three days while continuing azathioprine at the current dose. Treatment with oral dapsone was initiated, partly as a steroid-sparing medication for LABD and partly for Pneumocystis jirovecii prophylaxis. After completion of the intravenous methylprednisolone three-day course, the patient was transitioned to oral methylprednisolone 64 mg daily, at which point azathioprine was also stopped. Treatment with infliximab was initiated after discharge due to findings of ulcerative colitis on a colonoscopy. The patient was ultimately discharged on oral methylprednisolone, dapsone, and infliximab infusion as an outpatient. On follow-up four weeks and three months later, the patient had complete resolution of skin lesions, with moderate pigmentation at the site of some previous skin lesions but no scars and no abdominal pain.