Side effects of long-term therapy with mefenamic acid include autoimmune hemolytic anaemia [1], nephropathy [2], celiac disease-like enteropathy [3], and bullous pemphigoid [4].

We describe a 62-year-old woman with widespread, intensely itching, nonblistering papules and nodules that evolved after 2 years of treatment with mefenamic acid (0.5 to 1.0 g daily). Histologic findings were consistent with dermatitis herpetiformis, whereas marked linear subepidermal deposits of IgA shown by direct immunofluorescence suggested atypical bullous pemphigoid or linear IgA disease. Results of indirect immunofluorescence were negative. The skin cleared within 3 weeks after dapsone treatment was initiated. Because gonarthrosis worsened, the patient doubled her intake of mefenamic acid. Three weeks later, the patient was hospitalized with severe dizziness, fatigue, diarrhea, and steatorrhea. Mefenamic acid therapy was stopped, and dapsone treatment was continued.

Examination revealed normochromic, normocytic anemia (hemogloblin level, 97 g/L) without signs of hemolysis or gastrointestinal bleeding; an eosinophil count of 18%; antinuclear antibody titers up to 1:320; and moderate amounts of anti-doublestranded DNA, antihistone, and IgA antigliadin antibodies. Isotyping of the antinuclear antibodies revealed only IgA. The result of a lymphocyte stimulation test with mefenamic acid was clearly positive (dose-dependent increase of the stimulation index up to 3.6 with 100 µg of mefenamic acid per mL). All clinical symptoms resolved in 10 days, without further therapy. Dapsone therapy was tapered and discontinued after 8 weeks. The patient was negative for antinuclear, anti-double-stranded DNA and antihistone antibodies 18 months later; although no clinical symptoms were present, direct immunofluorescence and the lymphocyte stimulation test still had strongly positive results.

The induction of IgA autoantibodies against several target organs in the same patient is unusual. The patient's skin, intestinal, and hematologic symptoms made it difficult to determine the cause. Positive findings on the lymphocyte stimulation test point to an immunologic pathomechanism that resulted in uncontrolled IgA autoantibody production. Thorough monitoring for drug exposure and associated further autoimmune pathology are warranted in all cases of suspected autoimmune skin disease.