Partial epilepsy as an initial manifestation in bullous systemic lupus erythematosus

Sir, Bullous systemic lupus erythematosus (BSLE) is a rare, distinctive subepidermal blistering disorder that is autoantibody mediated, occurring in fewer than 5% of patients with SLE. We report a case of a woman with BSLE, who initially presented with severe headaches and partial epilepsy. A 20-year-old Chinese woman with no significant past medical history presented with severe, sharp and constant frontal headaches. Her headaches occurred several times a day, with each episode lasting approximately 5–30min, preceded by pallor and nausea. Her neurologic examination was normal. However, an electroencephalogram (EEG) demonstrated epileptiform discharges with sharp waves and multiple spike-and-slow-wave complexes (Figure 1). Her brain magnetic resonance imaging (MRI) was within normal limits. Based on the clinical presentation, EEG and normal radiologic findings, the patient was diagnosed with partial epilepsy associated with headaches. She was prescribed oral Valproic acid (Depakin) 0.5mg per night for 1 week. The symptoms did not improve, and she stopped medication. After a further 1 week, she developed erythematous lesions on the predominantly sun-exposed areas of her skin, such as her face, neck and chest (Figure 2). Soon after, vesicles and bullae with clear fluid appeared over the erythematous lesions, some coalescing to form elongated or irregularly shaped configurations. The lesions were associated with mild pruritus. Nikolsky’s sign was negative. The patient denied systemic symptoms including fever, chills, arthralgias or Raynaud’s phenomenon. As the lesions involved the lips and perioral skin, she was initially diagnosed with generalized herpes simplex and empirically treated with oral acyclovir. After 1 week, however, there was no significant improvement in her skin lesions. A skin biopsy from a representative lesion showed subepidermal vesicles with liquefactive degeneration and extensive neutrophilic infiltration in the papillary dermis. A second biopsy was taken from an area of unaffected skin for direct immunofluorescence study, which revealed IgG and IgM linear deposition along the basement membrane. A salt split study was performed by incubating peri-lesional skin in a solution containing sodium chloride at 1.0mol/l. IgG and IgM deposits were found on the dermal side of the split, indicating that the autoantigen was localized in the papillary dermis (Figure 3). An indirect immunofluorescence study using the patient’s serum and mouse esophagus as substrate was negative. Based on the histopathological findings, our differential diagnosis was narrowed down to BSLE vs. epidermolysis bullosa acquisita (EBA). Extensive serological studies were performed, which revealed a positive antinuclear antibody titer of 1:640 with a homogeneous pattern. The anti-Smith antibody titer was also positive. The patient’s anti-dsDNA antibody level was 1163 IU/dl (reference range: less than 100 IU/dl). She tested negative for various other antibodies, including Ro/SSA, La/SSB, nuclear RNP, and antiphospholipid antibodies (aPL). Other laboratory investigations revealed an elevated erythrocyte sedimentation rate (ESR) of 58mm/h, a reduced white blood cell count (3.2 10/l), and mild anemia with hemoglobin of 9.8 g/dl. The patient had no proteinuria and her renal function was normal. A diagnosis of BSLE was made based on the clinical presentation and histopathological findings, as well as the presence of anti-dsDNA and anti-sm antibodies. The possibility of drug-related SLE was also considered, as the patient had taken valproic acid after she was diagnosed with partial epilepsy. Valproic acid is known to occasionally induce lupus. However, drug-related SLE is characterized by the presence of antihistone antibody, not antidsDNA and anti-sm antibodies as was seen in our patient. Furthermore, the majority of patients with drug-induced lupus have a history of prolonged use of the triggering medication before symptoms manifest. Also, after cessation of the medication in question, the accompanying clinical, immunologic Received 12 May 2010; accepted 4 January 2011 Correspondence to: Jie Zheng, Department of Dermatology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Email: jie-zheng2001@126.com