a 34-year-old woman presented to the out-patient department of dermatology with a history of fever associated with chills, rigors, itchy red raised lesions all over the body, swelling of the face, headache, dizziness and tinnitus for the last four days. The rashes appeared on the face and progressed to involve trunk, upper limb and lower limb within a day.
Medication history revealed that she was on isoniazid (H) (5mg/kg), rifampicin (R) (10mg/kg), pyrazinamide (Z) (25mg/kg), ethambutol (E) (15mg/kg) and streptomycin (S) (15mg/kg) for the last 35 days for pulmonary tuberculosis (Fig. 1). She also revealed a past history of pulmonary tuberculosis 19 years back, which was successfully treated with HRZE for 2 months and HR for 4 months.
On clinical examination, the patient was febrile (101oF) and submandibular, axillary and inguinal lymph nodes were enlarged. Multiple maculopapular erythematous lesions were present over the face, trunk, upper and lower extremities. She had facial edema, dry lips and aphthous ulcers.
Hematological investigations revealed that the total leukocyte count (TLC) was raised (15000/mul), differential leukocyte count [neutrophils (46%), eosinophils (30%), lymphocytes (18%) and monocytes (6%)] was suggestive of eosinophilia [absolute eosinophil counts (AEC), 4500/mul]. Peripheral smear showed mild anisocytosis of red blood cells. Liver function test showed raised aspartate aminotransferase (AST) (112 IU/L, normal range<31 IU/L), low total serum proteins (6g/dl, normal range=6.4-8.3g/dl) and decreased serum albumin (3.2g/dl, normal range=3.5-5.2g/dl). Serology for dengue and malaria was negative. Blood and urine culture was sterile. Fasting and postprandial blood sugar levels, lipid profile, kidney function tests and serum electrolytes were within normal range. Skin biopsy showed mild focal spongiosis with mild perivascular lymphocytes and neutrophils infiltration. Chest radiography showed hyper-inflated lung fields with bilateral hilar lymphadenopathy. Non-contrast computed tomography (CT) head was normal. A diagnosis of DRESS was made.
Pulmonary medicine consultant advised the withdrawal of anti-tubercular therapy immediately and recommen-ded a follow up after the resolution of skin lesions. The dermat-ologist advised the administration of hydrocortisone 100mg intravenously 8 hourly for one day, tablet prednisolone 40mg once daily per orally for three days followed by tapering of the dose, tablet paracetamol 500mg per orally one as needed, tablet cetirizine 10mg per orally one daily, cream fusidic acid 2% for topical application, cream fluticasone 0.05% for topical application and calamine lotion for local application on the skin lesion. The patient became afebrile (98.6oF) immediately whereas skin lesions and facial edema started resolving after two days of treatment. After ten days, ethambutol (800mg) was re-introduced as it is least known to implicate DRESS. But within 12 hours, her periorbital edema and pruritus worsened. Her TLC (16900/mul) and AEC (4800/mul) raised further. Ethambutol was stopped immediately and tablet isoniazid (50mg) was started (day 1). The dose of isoniazid was increased to 300mg on the next day (day 2). On day 3, capsule rifampicin 150mg was added with a gradual increase in dose to 300mg and 450 mg on day 4 and 5 respectively. On day 6, tablet pyrazinamide 500mg once daily was introduced with a subsequent increase to twice a day. She tolerated H, R and Z well for the next ten days and her skin lesions and facial edema improved. The lower dose of ethambutol (100mg) was introduced again. Within a day, skin lesions worsened with the appearance of new urticarial lesions. Immediately ethambutol was replaced with a second line anti-tubercular drug, levofloxacin (750mg per orally once daily). Patient's symptoms improved and cutaneous lesions recovered completely after a week.