Isoniazid-induced flu-like syndrome: A rare side effect
A 10-year-old girl presented to a local physician with fever, productive cough, and weight loss for 3 months. Sputum smear for acid fast bacilli (AFB) was positive and chest radiograph had cavitary lesion right upper zone. She was put on daily therapy with HREZ. From the sixth day, she developed high fever with chill and rigor, rhinorrhoea, dry cough, mild breathlessness, and generalized body ache. She was referred to our hospital after 40 days of chemotherapy. On admission she had body weight of 22 kg, axillary temperature of 38°C, and pallor. Examination of respiratory system revealed coarse crepitation in the right infraclavicular region. Other systems were normal.\nBlood examination revealed hemoglobin 12 g/dL, normal total and differential leucocyte count with normal blood biochemistry. Sputum smear was positive for AFB. Chest radiography revealed right upper zone thin-walled empty cavity.\nHIV serology I and II were nonreactive. No organism grew on aerobic and anaerobic culture of blood and urine after 72 h. Viral culture facility was not done due to lack of facility. Real-time PCR for influenza virus was negative.\nShe was put on WHO category I ATD regimen (2H3R3E3Z3/4H3R3). After 1 h of taking the drugs, she developed fever (39°C) with chill, cough with blocked nose, mild breathlessness, body ache, and nausea. 100 mg intravenous hydrocortisone, 25 mg intramuscular promethazine, and 250 mg oral paracetamol were given immediately, but no improvement was noted in next 1 h. Except chill, all other symptoms persisted for next 14 h, after which they subsided spontaneously.\nATD was stopped for next 3 days and she remained asymptomatic. There was no change in the total leucocyte count, hepatic enzymes, or any increase in the serum immunoglobulin E (Ig E) level.\nOn the fifth day, 400 mg ethambutol was reintroduced orally which she tolerated well.\nOn the sixth day, 100 mg isoniazid was reintroduced orally. After 1 h she developed high fever (38.8°C) with chill, blocked nose, cough, body ache, and nausea. Symptomatic management was given. Fever with chill subsided after 4 h, other symptoms subsided gradually in next 12 h. Isoniazid was withheld.\nSubsequently, oral rifampicin (250 mg) and pyrazinamide (500 mg) were reintroduced successfully without any adverse reaction in next 2 days.\nSuspecting the drug isoniazid as culprit, it was reintroduced orally on the ninth day. Similar symptoms developed within an hour and recovered as before.\nOn the tenth day, isoniazid was given in a very small dose (10 mg) orally and the same symptoms developed after 1 hour but with less severity. There was fever, nasal blockage, and body ache, but no chill or breathlessness.\nOn the eleventh day, a similarly looking placebo tablet was given in empty stomach. There was no adverse reaction noted. Considering isoniazid as the culprit drug, it was withdrawn from the regimen and oral levofloxacin (LFx) (200 mg) was introduced, which she tolerated well. Anti-isoniazid antibody in serum was not done due to lack of facility.\nFinally, she was put on a modified regimen comprising REZLFx daily. Patient tolerated the regimen very well without any evidence of chondropathy. Her sputum smear for AFB was negative on 2nd, 4th, and 6th month of therapy. There was significant improvement in the chest X-ray also. She was declared cured at the end of chemotherapy.