A 62-year-old Thai man presented to our facility with a generalized erythematous maculopapular rash on his trunk and extremities. Our patient had been diagnosed as having pulmonary tuberculosis two weeks earlier. He had long-standing hypertension and diabetes mellitus; his treatment for this included daily amlodipine 5mg, metformin 500mg and glipizide 5mg daily. When tuberculosis was diagnosed, anti-tuberculosis therapy of isoniazid 300mg, rifampicin 450mg and ethambutol 800mg daily was administered. After two weeks of anti-tuberculosis medication, a generalized exanthematous rash appeared on his trunk and extremities (Figure 1). All anti-tuberculosis drugs were stopped after his admission due to a clinical suspicion of drug-induced adverse cutaneous reactions. The exanthematous rash resolved within three days of admission, leaving post-inflammatory hyperpigmentation. One day later, multiple well-defined, non-blanchable, erythematous-to-purplish macules and papules, some of which showed an annular arrangement, were noticed (Figure 2). He had no history of drug allergy and a review of systems was unremarkable.
Laboratory study findings were as follows: leukocytes, 12.8x103 cells/mm3 (neutrophils 86 percent, lymphocytes 9 percent, monocytes 2 percent, eosinophils 2 percent, basophils 1 percent); hemoglobin, 7.9g/dL; platelet count, 215x103 cells/mm3; creatinine, 1.2mg/dL; aspartate aminotransferase, 31U/L; alanine aminotransferase, 34U/L; alkaline phosphatase, 582U/L; gamma-glutamyl transferase, 393U/L; total bilirubin, 9.6mg/dL; direct bilirubin, 8.4mg/dL; hepatitis B surface antigen, anti-hepatitis C virus and anti-human immunodeficiency virus (HIV) test results were all negative. Anti-nuclear antibody and anti-neutrophil cytoplasmic antibody test results were also negative. Urine analysis results showed no evidence of proteinuria or hematuria. The findings from an abdominal ultrasound were unremarkable. A skin biopsy from a purpuric annular lesion on his leg showed peri-vascular and interstitial infiltration of neutrophils with extravasation of erythrocytes and fibrin deposition (Figure 3), characteristic of LCV. A direct immunofluorescence (DIF) study was positive for IgA, IgM and C3 along superficial dermal blood vessels, consistent with cutaneous small vessel vasculitis (Figure 4). These findings were diagnostic for annular LCV associated with anti-tuberculosis drugs and drug-induced cholestasis. Our patient was treated with an oral antihistamine and topical corticosteroids. The skin eruption cleared within one week without hyperpigmentation and liver function test results returned to normal limits three weeks after the anti-tuberculosis drugs were withdrawn. Streptomycin (750mg per day), ethambutol (800mg per day) and ofloxacin (400mg per day) were subsequently administered as second-line anti-tuberculosis therapy during the hospitalization. No adverse reactions were observed. Therefore, he was subsequently treated with ethambutol, ofloxacin and streptomycin without recurrence of the skin rash.