Cough, shortness of breath, and eosinophilia in a 68-year-old man

HISTORY OF THE PRESENT ILLNESS The patient is a 68-year-old Caucasian man, a former smoker with a history of paroxysmal atrial fibrillation and hypercholesterolemia, referred for evaluation of steroid-dependent asthma. The patient reports mild exertional cough and shortness of breath for 10 years. Fourteen months prior to our evaluation, he presented with ten days of severe nonproductive cough, shortness of breath, fevers to 39 °C, malaise, and axillary and cervical lymphadenopathy. He had no wheezing at that time. Total eosinophil counts in the 3000/ mm3 range were noted. A CT scan of the chest revealed slightly enlarged mediastinal, right hilar and bilateral axillary lymph nodes. Biopsies of cervical and paratracheal lymph nodes revealed follicular hyperplasia, reactive histiocytosis, and diffuse infiltration by plasma cells and eosinophils, but no Reed-Sternberg cells. Despite this, Hodgkin’s disease remained the leading diagnosis. Bone marrow biopsy revealed mild hypercellularity and moderate eosinophilia, with no evidence of lymphoma. Pulmonary function tests revealed FVC 5.64 L (119% predicted), FEV1 3.69 L (101% predicted), with a diffusion capacity of 34.17 mL/ min/mmHg (107% predicted). Spirometry values did not change significantly after inhalation of a bronchodilator. While awaiting a second review of the lymph node pathology and in anticipation of chemotherapy, the patient was begun on allopurinol. Within days, the patient developed nausea, vomiting, and elevated liver function tests. Serum revealed a positive antinuclear antibody titer of 1:320 and a positive anti-Ro antigen. Allopurinol was discontinued with resolution of his gastrointestinal upset. Review of the lymph node tissue at the National Cancer Institute confirmed no evidence of malignancy, and the patient was treated with antibiotics alone for presumed bronchitis. The patient’s cough persisted for the next several months. It was predominantly dry in quality, although at times productive of scant, clear sputum. The cough was associated with shortness of breath and the gradual development of wheezing. No diurnal variation or obvious precipitants could be discerned. In addition, he began to complain of persistent nasal congestion and postnasal drip. Eosinophil counts remained between 2800 to 3200/mm3. A CT scan of the sinuses revealed pansinusitis despite treatment with cephalosporin antibiotics. The patient was seen by a pulmonologist 6 months into his disease course. A chest radiogram revealed hyperinflation but no infiltrates. Pulmonary function testing at that time revealed an FEV1 of 2.00 L (56% predicted) with an FVC of 3.57 L (77% predicted) with a normal diffusion capacity (110% predicted). Both FEV1 and FVC improved 17% after bronchodilator. He was treated with erythromycin and prednisone 40 mg/ day tapered over 2 weeks with rapid improvement in symptoms and pulmonary function (FEV1 113% predicted). Unfortunately, his symptoms recurred within 1 week after termination of steroids (FEV1 71% predicted), requiring the reinstitution of prednisone. Laboratory studies while on 40 mg/day of prednisone were significant for an IgE of 2897 U/mL (by RIA, age dependent mean 13 U/mL, 1 SD upper limit 41 U/mL), an eosinophil count of 299/mm3 and a negative serum precipitins to Aspergillus. Immunoelectrophoresis revealed normal levels of IgG and IgM with slightly elevated IgA of 513 mg/dL (100 to 490). Serum protein electrophoresis was consistent with a chronic inflammatory response pattern; no monoclonal spike was seen. The patient was maintained on high dose inhaled steroids (up to 2400 g/day of triamcinolone) with fair control of symptoms and an FEV1 of approximately 80% predicted. An evaluation 7 months after initial presentation for persistent nasal congestion revealed bilateral nasal polyps emanating from the middle meatus with purulent nasal secretions. Endoscopic sinus surgery was performed for persistent nasal symptoms. Pathology revealed inflammatory nasal polyps with eosinophilic infiltration, but no evidence of vasculitis, granulomatous disease, or malignancy. Eleven months after his initial presentation, the patient had gradual worsening of his shortness of breath * From the Division of Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Supported by NIH Grant T32 AI07056, NIAID, Bethesda, MD. Received for publication October 9, 1995. Accepted for publication in revised form January 31, 1996.