Bullous pemphigoid (BP) is the most common autoimmune blistering disease. The classic presentation of BP is a generalized, pruritic, bullous eruption in elderly patients, which is occasionally preceded by an urticarial prodrome. Immunopathologically, BP is characterized by IgG and sometimes IgE autoantibodies that target basement membrane zone proteins BP180 and BP230 of the epidermis.1
The diagnosis of BP should be suspected when an elderly patient presents with tense blisters and can be confirmed via diagnostic testing, including tissue histology and direct immunofluorescence (DIF) as the gold standard, as well as indirect immunofluorescence (IIF), enzyme-linked immunosorbent assay (ELISA), and most recently biochip technology as supportive tests.2 Since its advent, ELISA has gained popularity as a trustworthy diagnostic test for BP. The specificity of ELISA for BP diagnosis is reported to be 98% to 100%, which leads clinicians to believe that a positive ELISA equals certain diagnosis of BP; however, misdiagnosis of BP based on a positive ELISA result can occur.3-13 The treatment of BP often involves lifelong immunosuppressive therapy. Complications of immunosuppressive therapy contribute to morbidity and mortality in these patients, thus an accurate diagnosis is paramount before introducing therapy.14
We present the case of a 74-year-old man with a history of a pruritic nonbullous eruption who was diagnosed with BP and treated for 3 years based on positive ELISA results in the absence of confirmatory histology or DIF.
Case Report
A 74-year-old man with diabetes mellitus, hypertension, hyperlipidemia, benign prostatic hypertrophy, and obstructive sleep apnea presented for further evaluation and confirmation of a prior diagnosis of BP by an outside dermatologist. He reported a pruritic rash on the trunk, back, and extremities of 3 years’ duration. He denied occurrence of blisters at any time.
On presentation to an outside dermatologist 3 years ago, a biopsy was performed along with serologic studies due to the patient’s age and the possibility of an urticarial prodrome in BP. The biopsy revealed epidermal acanthosis, subepidermal separation, and a perivascular and interstitial infiltrate of lymphocytes and eosinophils in the papillary dermis. Direct immunofluorescence was nondiagnostic with a weak discontinuous pattern of IgG and IgA linearly along the basement membrane zone as well as few scattered and clumped cytoid bodies of IgM and IgA. Indirect immunofluoresence revealed a positive IgG titer of 1:40 on monkey esophagus substrate and a positive epidermal pattern on human split-skin substrate with a titer of 1:80. An ELISA for IgG autoantibodies against BP180 and BP230 yielded 15 U and 6 U, respectively (cut off value, 9 U). Based on the positive ELISA for IgG against BP180, a diagnosis of BP was made.
Over the following 3 years, the treatment included prednisone, tetracycline, nicotinamide, doxycycline, and dapsone. Therapy was suboptimal due to the patient’s comorbidities and socioeconomic status. Poorly controlled diabetes mellitus precluded consistent use of prednisone as recommended for BP. Tetracycline and nicotinamide were transiently effective in controlling the patient’s symptoms but were discontinued due to changes in his health insurance. Doxycycline and dapsone were ineffective. Throughout this 3-year period, the patient remained blister free, but the pruritic eruption was persistent.
The patient presented to our clinic due to his frustration with the lack of improvement and doubts about the BP diagnosis given the persistent absence of bullous lesions. Physical examination revealed numerous eroded, scaly, crusted papules on erythematous edematous plaques on all extremities, trunk, and back (Figure 1). The head, neck, face, and oral mucosa were spared. His history and clinical findings were atypical for BP and skin biopsies were performed. Histology revealed epidermal erosion with parakeratosis, spongiosis, and superficial perivascular lymphocytic inflammation with rare eosinophils without subepidermal split (Figure 2). Direct immunofluorescence was negative for IgG, IgA, IgM, C3, and C1q. Additionally, further review of the initial histology by another dermatopathologist revealed that the subepidermal separation reported was more likely artifactual clefts. These findings were not consistent with BP.
Figure 1. Multiple ill-defined scaly papules and plaques with focal erosions admixed with hyperpigmented papules and plaques on the back and arms (A) as well as the right posterior arm and back (B).
Figure 2. Epidermal erosion with adjacent parakeratosis, spongiosis, and superficial perivascular lymphocytic inflammation with rare eosinophils without subepidermal split (H&E, original magnification ×100).
Given the patient’s clinical history, lack of bullae, and twice-negative DIF, the diagnosis was determined to be more consistent with eczematous spongiotic dermatitis. He refused a referral for phototherapy due to scheduling inconvenience. The patient was started on cyclosporine 0.5 mg/kg twice daily. After 10 days of treatment, he returned for follow-up and reported notable improvement in the pruritus. On physical examination, his dermatitis was improved with decreased erythema and inflammation.
The patient is being continued on extensive dry skin care with thick moisturizers and additional topical corticosteroid application on an as-needed basis.