2 Case presentation
A 67-year-old man had a one-month history of erythema and multiple bullae with itching and pain over the whole body (Figure 1A). Two years ago, the patient was diagnosed with advanced hepatocellular carcinoma and underwent chemoembolization and systemic treatment, including half-year treatment of sorafenib (0.8 g/d) and one-year treatment of lenvatinib (0.8 mg/d). However, he developed intermittent diarrhea after the systemic treatment. One month prior, the patient began taking apatinib mesylate (850 mg/d). After ten days, the patient presented with patchy erythema, blisters, bullae, and erosion accompanying the oral mucosa, which was affected by itching and pain. He was admitted to local hospital and an initial diagnosis of pemphigus was considered, while discontinuation of apatinib mesylate and symptomatic treatments were ineffective. Then the patient was admitted to our department. Physical examination revealed a few vesicles on the trunk, blood blisters on the hands, and multiple erosions on the trunk, limbs, and scalp, while some were covered with crust. Skin biopsy and immunofluorescence (IF) were obtained from the right waist. The skin biopsy demonstrated subepidermal blisters, individual dyskeratinized cells in the spinous layer, vacuolized focal basal cells, and sparse lymphocyte infiltration around the small vessels in the superficial dermis (Figure 2). Direct IF displayed a basement membrane with linear deposition of IgA, IgG, and C3, with negative indirect IF (Figure 3). His blood pressure was 120-150mmHg/60-90mmHg while fasting blood glucose fluctuates between 8 and 15mmol/L and postprandial blood glucose fluctuates between 5 and 23mmol/L. Furthermore, laboratory investigations depicted mild anemia, hypoproteinemia, abnormal liver function, coagulopathy, fecal occult blood, and urinary tract infection with negative serum autoantibodies including anti-BP180, anti-Dsg1, anti-Dsg3, and anti-nuclear antibody. Staphylococcus squirrels and Corynebacterium striatum were cultured from buttock secretions. Chest CT indicated chronic bronchitis, pneumonectasis, and mild pulmonary infection.
Based on these findings, the patient was diagnosed with apatinib-induced bullous dermatosis (BP). The body weight of the patient was 45 kg. Methylprednisolone (80 mg daily at the initial dose), antibiotics, symptomatic treatments including albumin, niferex, furosemide, fresh frozen plasma, insulun and skin care were initiated. Owing to his multiple underlying diseases, he and his family were discharged after two weeks of treatment (Figure 1A). Methylprednisolone was replaced with oral prednisone 30 mg daily, and recombinant human epidermal growth factor gel was added to promote wound healing. Then the patient took prednisone 30 mg/d for 2 months by himself, the cutaneous and oral erosions mostly healed, with a few epithelial islands growing. At the 3-month-follow up visit, the skin lesions of the patient completely resolved (Figure 1B).