Lesson of the Week: Minocycline and pulmonary eosinophilia

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Case reports CASE 1 One week after starting Minocin MR (Lederle Laboratories, UK) 100 mg once a day for facial acne, a 36 year old woman presented with fevers, cough, shortness of breath on exertion, and weight loss. A chest radiograph showed bilateral infiltration, and her blood eosinophil count was 1.3 x 109/l (14%). IgE in the blood measured 807 IU/l, with specific IgE against house dust mite only. Tests for antinuclear factor, antineutrophil cytoplasmic antibody, and aspergillus precipitins had negative results. The sputum contained large clumps of eosinophils with numerous Charcot-Leyden crystals. The patient was treated with 30 mg prednisolone once a day for 10 days, and minocycline was discontinued. After three weeks the patient was asymptomatic with a normal chest radiograph and eosinophil count. Rechallenge (with informed consent) resulted in a prompt recurrence of symptoms, chest radiograph changes, and blood eosinophilia (1.9 x 109/l; 24%) after three doses of Minocin MR 100 mg. Again these resolved after discontinuation of the drug. CASE 2 A 29 year old woman with facial acne who had been taking Minocin MR 100 mg once a day for six weeks reported a four week history of effort dyspnoea. A chest radiograph showed opacities peripherally in the right upper and lower zones (fig). The blood eosinophil count was 0.8x109/l (12%). Aspergillus precipitins were positive (single line). Transbronchial biopsy showed chronic inflammation in the presence of eosinophils. During the investigations the patient's minocycline had been discontinued and her symptoms and radiological results had improved, but when the drug was restarted (minocycline had not been identified as the aetiological agent at this stage), the symptoms recurred, to resolve again after discontinuation. CASE 3 A 25 year old woman became unwell within three days of starting Minocin MR 100 mg once a day for facial acne; she had nocturnal fever, non-productive cough, lethargy, and anorexia. Examination revealed a temperature of 37.6°C and acne vulgaris but was otherwise unremarkable. A chest radiograph showed patchy infiltrates peripherally in the middle and upper zones bilaterally. Her eosinophil count was 1.12x109/l (10.7%); erythrocyte sedimentation rate was 96 mm/h; antinuclear factor was weakly positive with a nucleolar fluorescence pattern; total IgE was raised (260 IU/l). Tests for aspergillus precipitins and antineutrophil cytoplasmic antibody had negative results. Minocycline was discontinued and oral amoxycillin and erythromycin were prescribed; abnormalities resolved within seven days. Eight years previously this patient had been extensively investigated for a similar illness characterised by high fevers, dry cough, raised erythrocyte sedimentation rate (120 mm/h), eosinophilia (1.4x109/l), and fleeting peripheral shadowing on chest radiography. At that time she had been treated for acne with minocycline for three months. She was treated with high dose oral corticosteroids for presumed polyarteritis nodosa and recovered completely within one month. There had been no subsequent exposure to tetracyclines. View larger version: In this window In a new window Chest radiograph shows opacifications in upper and lower zones of the right lung CASE 4 A 26 year old beauty consultant treated without adverse effect on several occasions in previous years for facial acne with Minocin R 50 mg once a day was given Minocin MR 100 mg once a day. After one week she developed a non-productive cough, night sweats, and dyspnoea. The chest radiograph showed inflammatory changes in both upper zones. The blood eosinophil count was 1.7x109/l (26%). Pulmonary function testing showed both obstructive and restrictive lung defects with reduced gas transfer. Minocycline was discontinued, and chest radiograph abnormalities and blood eosinophilia resolved within three weeks. Lung volumes returned to normal, but the gas transfer factor remained low at 60% of the predicted value two months after discontinuation of the drug.