A Case of Serum Sickness-Like Reaction and Anaphylaxis - Induced Simultaneously by Rifampin
A 25-year-old male was diagnosed with tuberculous meningitis at Chonnam National University Hospital, and was started on a treatment regime of 300 mg isoniazid (Yuhanizid®, Yu Han Pharm., Seoul, Korea), 800 mg ethambutol (Tambutol®, Chong Kun Dang Pharm., Seoul, Korea), 600 mg rifampin (Rifodex®, Chong Kun Dang Pharm.) and 1,500 mg pyrazinamide (Yu Han Pharm.) daily. He became nauseous, vomited, and had generalized abdominal discomfort 2 weeks later. He stopped taking the anti-tuberculosis drugs for 2 days, and the symptoms disappeared. He restarted taking the anti-tuberculosis drugs 2 days later but complained of pain and numbness in his extremities 30 minutes later. He was found to have conjunctival hemorrhage in both eyes, a maculopapular rash on the neck and anterior chest, and erythematous papules and vesicles on both hands.\nHe was admitted to the Department of Neurology. Laboratory tests revealed C-reactive protein, 10.9 mg/dL; erythrocyte sedimentation rate, 22 mm/h; white blood cells, 7,800/µL; eosinophils, 100/µL; hemoglobin, 15.8 g/dL; platelets, 230,000/µL; aspartate aminotransferase, 645 U/L; and alanine aminotransferase, 172 U/L. Levels of both C3 (62.9 mg/dL) and C4 (7.9 mg/dL) were low. Anti-nuclear antibody and anti-neutrophil cytoplasmic antibody were negative.\nThe anti-tuberculosis drugs were administered again. However, he developed a high fever of 39.1℃ 24 hours later, and his blood pressure decreased to 80/50 mm Hg. Pulse and respiratory rates increased to 120/min and 24/min, respectively. A maculopapular rash appeared on the neck and anterior chest and numbness and pain occurred in his extremities. A nerve conduction velocity test and electromyography showed bilateral, diffuse, axonal-type, and sensorimotor polyneuropathy. The first-line drugs were changed to second-line drugs, including 250 mg cycloserine (Closerin®, Dong-A Pharm., Seoul, Korea), 500 mg levofloxacin (Levofexin®, Il Dong-A Pharm.), and 1 g streptomycin (Chong Kun Dang Pharm.). Daily 50 mg prednisolone (Solondo®, Yuhan Pharm.) was added, and the symptoms and signs disappeared.\nBecause the first-line drugs were effective for treating the tuberculous meningitis, they were administered one at a time. Oral prednisolone was given continuously and then tapered off. Oral administration of 600 mg rifampin produced dyspnea, chest discomfort, and mild fever of 37.6℃ after 30 minutes. Blood pressure was 110/80 mm Hg, pulse rate was 132/min, respiration rate was 22/min, and oxygen saturation was 95%. The dyspnea and chest discomfort disappeared after 3 hours. Administration of 300 mg isoniazid or 800 mg ethambutol produced no symptoms. Administration of 1,500 mg pyrazinamide induced a fever of 38.3℃ after 8 hours. It was unclear whether the fever was due to the pyrazinamide or other causes related to the discontinuation of the oral steroid, because prednisolone was tapered off 1 day before administration of pyrazinamide. The drug responsible was not determined, and the patient was referred to the Department of Allergies for further evaluation.\nDrug provocation tests with pyrazinamide and rifampin were repeated. Pyrazinamide was given orally at 1 hour intervals at doses of 5, 15, 25, 100, and 355 mg, but no reactions were observed. Thereafter, rifampin was given at doses of 6, 30, 90, and 270 mg. Gastrointestinal symptoms, such as diarrhea and epigastric discomfort, developed 30 minutes after the administration of 270 mg rifampin and lasted for 24 hours. A fever of 37.5℃ occurred 3 hours after the administration and was maintained for 3 hours. Blood pressure decreased to 90/60 mm Hg 5 hours after the administration and to 70/40 mmHg 3 hours later, but returned to the normal range 15 hours later. These results confirmed that rifampin was responsible for the adverse symptoms (). The levels of both C3 (76.0 mg/dL) and C4 (9.5 mg/dL) were below the normal range 5 days after the rifampin challenge. Unfortunately, the complement levels were not measured again after the symptoms disappeared.\nRifampin skin tests were performed. Rifampin (600 mg) was dissolved in saline. The skin prick test was negative to 3 mg/mL, but the intradermal test showed an immediate positive wheal (8.0×7.6 mm) and flare reaction (22.2×22.0 mm) to 0.3 mg/mL. Saline and 1 mg/mL histamine were used as negative and positive controls, respectively. Intradermal tests to identify a non-irritating concentration (NIC) of rifampin were performed in nine normal controls. NIC was determined using the method described by Broz et al., with some modifications. NIC was considered if the ratio of rifampin-induced mean wheal diameter to histamine-induced mean wheal diameter was less than 0.4. All test subjects were male, aged 22±1.58 (mean±SD) years. NIC was 0.3 mg/mL ().\nIsoniazid, levofloxacin, ethambutol, and streptomycin were prescribed, but rifampin was not. No adverse drug reactions were observed. The tuberculous meningitis was finally cured without sequelae.