Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease.1 The majority of BP cases are idiopathic and occur in patients older than 60 years. The disease is characterized by the development of circulating IgG autoantibodies reacting with the BP180 antigen of the basement membrane zone.1 Psoriasis vulgaris (PV) is a common, chronic, immune-mediated disease affecting approximately 2% of the world’s population including children and adults.2 Both entities may coexist with internal disorders such as hypertension, diabetes mellitus, coronary heart disease, congestive heart failure, hyperlipidemia, and cerebrovascular accident. It has been postulated that BP more often coexists with neurological disorders, such as stroke and Parkinson disease,3 whereas PV usually is associated with cardiovascular disorders and diabetes mellitus.2 We report the case of a 35-year-old man with chronic PV and metabolic syndrome who developed BP that was successfully treated with methotrexate (MTX).
Case Report
A 35-year-old man with a 15-year history of PV, class 3 obesity (body mass index, 69.2), and thrombosis of the left leg was referred to the dermatology department due to a sudden extensive erythematous and bullous eruption located on the trunk, arms, and legs with involvement of the oral mucosa that had started 4 weeks prior. The skin lesions were accompanied by severe pruritus. On admission to the hospital, the patient presented with stable psoriatic plaques located on the trunk, arms, and proximal part of the lower legs with a psoriasis area severity index score of 11.8 (Figure 1A). He also had disseminated tense blisters and erosions partially arranged in an annular pattern located on the border of the psoriatic plaques as well as on an erythematous base or within unaffected skin (Figure 1B). Additionally, a few small erosions were present on the oral mucosa.
Figure 1. Disseminated psoriatic plaques on the trunk and arms (A) and numerous tense blisters and erosions on the border of the psoriatic plaques as well as on an erythematous base or within unaffected skin, some of them showing annular arrangement located on the forearm (B).
The patient’s father had a history of PV, but there was no family history of obesity or autoimmune blistering disorders. On physical examination, central obesity was noted with a waist circumference of 180 cm and a body mass index of 69.2; his blood pressure was 220/150 mm Hg. Laboratory tests revealed leukocytosis (20.06×109/L [reference range, 4.5–11.0×109/L]) with neutrophilia (16.2×109/L [reference range, 1.6–7.6×109/L]; 80.9% [reference range, 40.0%–70.0%]), eosinophilia (1.01×109/L [reference range, 0–0.5×109/L]), elevated C-reactive protein levels (49.4 mg/L [reference range, 0.0–9.0 mg/L]), elevated erythrocyte sedimentation rate (35 mm/h [reference range, 0–12 mm/h]), elevated γ-glutamyltransferase (66 U/L [reference range, 0–55 U/L]), decreased high-density lipoprotein levels (38 mg/dL [reference range, ≥40 mg/dL]), elevated fasting plasma glucose (116 mg/dL or 6.4 mmol/L [reference range, 70–99 mg/dL or 3.9–5.5 mmol/L]), elevated total IgE (1540 µg/L [reference range, 0–1000 µg/L]), elevated D-dimer (3.21 µg/mL [reference range, <0.5 µg/mL]), and low free triiodothyronine levels (130 pg/dL [reference range, 171–371 pg/dL]). The total protein level was 6.5 g/dL (reference range, 6.0–8.0 g/dL) and albumin level was 3.2 g/dL (reference range, 4.02–4.76 g/dL). A chest radiograph showed no abnormalities.
Based on the physical examination and laboratory testing, it was determined that the patient fulfilled 4 of 5 criteria for metabolic syndrome described by the International Diabetes Federation in 2006 (Table).4 Direct immunofluorescence performed on normal-appearing perilesional skin demonstrated linear IgG and C3 deposits along the basement membrane zone. Indirect immunofluorescence detected circulating IgG autoantibodies at a titer of 1:80. Serum studies using biochip mosaics5 revealed the reactivity of circulating IgG antibodies to the epidermal side of salt-split skin and with antigen dots of tetrameric BP180-NC16a, which prompted the diagnosis of BP (Figure 2).
Figure 2. Biochip mosaics revealed a positive reaction of circulating IgG autoantibodies with the roof of salt-split skin (A) and antigen dots of tetrameric BP180-NC16a, bullous pemphigoid antigen (B).
Oral treatment with MTX 12.5 mg once weekly with clobetasol propionate cream applied to affected skin was initiated for 4 weeks. The PV resolved completely and blister formation stopped. A few weeks later BP reappeared, even though the patient was still taking MTX. The treatment failure may have been related to the patient’s class 3 obesity; therefore, the dose was increased to 20 mg once weekly for 8 weeks, which led to rapid healing of BP erosions. The patient was monitored for 2 months with no symptoms of recurrence.