The new england journal of medicine Case Records of the Massachusetts General Hospital Founded by Richard C. Cabot Eric S. Rosenberg, M.D., Editor Virginia M. Pierce, M.D., David M. Dudzinski, M.D., Meridale V. Baggett, M.D., Dennis C. Sgroi, M.D., Jo-Anne O. Shepard, M.D., Associate Editors Alyssa Y. Castillo, M.D., Case Records Editorial Fellow Emily K. McDonald, Sally H. Ebeling, Production Editors Case 16-2019: A 53-Year-Old Man with Cough and Eosinophilia Rachel P. Simmons, M.D., David M. Dudzinski, M.D., Jo-Anne O. Shepard, M.D., Rocio M. Hurtado, M.D., and K.C. Coffey, M.D.​​ Presentation of Case From the Department of Medicine, Bos- Dr. David M. Dudzinski: A 53-year-old man was evaluated in an urgent care clinic of ton Medical Center (R.P.S.), the Depart- this hospital for 3 months of cough. ment of Medicine, Boston University School of Medicine (R.P.S.), the Depart- Five years before the current evaluation, the patient began to have exertional ments of Medicine (D.M.D., R.M.H.), dyspnea and received a diagnosis of hypertrophic obstructive cardiomyopathy, with Radiology (J.-A.O.S.), and Pathology a resting left ventricular outflow gradient of 110 mm Hg on echocardiography. (K.C.C.), Massachusetts General Hos- pital, and the Departments of Medicine Although he received medical therapy, symptoms persisted, and percutaneous (D.M.D., R.M.H.), Radiology (J.-A.O.S.), alcohol septal ablation was performed 1 year before the current evaluation, with and Pathology (K.C.C.), Harvard Medical resolution of the exertional dyspnea. School — all in Boston. Nine months later, the patient began to have cough that was intermittently N Engl J Med 2019;380:2052-9. productive of yellow sputum. The cough developed shortly after he had returned DOI: 10.1056/NEJMcpc1900595 Copyright © 2019 Massachusetts Medical Society. from travel to Southeast Asia and the Middle East. Antitussive medications did not provide symptom relief. Three years before this cough developed, three discrete episodes of upper respiratory tract infection and sinusitis had occurred, for which courses of amoxicillin–clavulanic acid, trimethoprim–sulfamethoxazole, and azithro- mycin had been prescribed. During the current episode, the cough waxed and waned in intensity, with no clear relation to other symptoms or the time of day. Ten days before the current evaluation, the patient traveled to the Middle East; the weather was colder than he had expected and he felt chills. During the trip, the cough worsened — with more frequent and copious production of yellow- green sputum and associated coryza, pharyngitis, frontal sinus “heaviness,” malaise, and fatigue — such that he had to miss work after he returned home. He called his cardiologist and was advised to present to an urgent care clinic of this hospital for evaluation. A review of systems was negative for fever, anorexia, unintentional weight loss, night sweats, dyspnea, hemoptysis, chest pressure or discomfort, pleuritic pain, wheezing, light-headedness, palpitations, syncope, nausea, vomiting, diarrhea, myalgia, arthralgia, lymphadenopathy, and pruritus. The patient had had multiple contacts with nonspecific illnesses while he had been traveling both 3 months and 10 days before the current evaluation. The most recent tuberculin skin test had 2052 n engl j med 380;21 nejm.org May 23, 2019 The New England Journal of Medicine Downloaded from nejm.org by GIUSEPPE GIOCOLI on June 2, 2019. For personal use only. No other uses without permission. Copyright © 2019 Massachusetts Medical Society. All rights reserved. Case Records of the Massachusetts General Hospital been performed 10 years earlier and had been On examination, the patient appeared to be negative. He had not undergone seasonal influ- comfortable. The temperature was 37.2°C, the enza vaccination. pulse 66 beats per minute, the blood pressure The patient’s medical history was also notable 122/89 mm Hg, the respiratory rate 14 breaths for placement of an implantable cardioverter– per minute, and the oxygen saturation 98% while defibrillator (ICD) for ventricular tachycardia that he was breathing ambient air. During the evalu- had been induced during an electrophysiological ation, the patient coughed twice, and the second study. He had allergic rhinitis, obstructive sleep cough produced light-green sputum with a bloody apnea, gonococcal urethritis, and dyslipidemia. streak. The oropharynx had no erythema or exu- Medications included metoprolol succinate and dates, but there was a slight yellow discoloration atorvastatin. He had had no known adverse reac- on the tongue. There was no tenderness on per- tions to medications, except prolongation of the cussion of the sinuses or conjunctival hyperemia. corrected QT interval with disopyramide. There was no cervical, submandibular, supracla- The patient was born in South Asia, raised in vicular, or axillary lymphadenopathy. Ausculta- the Middle East, and educated in the United tion revealed a clear chest, without rales, wheez- States, where he had lived for the past 25 years. ing, or egophony. The jugular venous pulse was He was an executive and traveled frequently for 6 cm of water. There was a crescendo–decrescendo work, generally to urban areas and only rarely to systolic murmur (grade 3/6) along the left ster- rural areas, although he had walked barefoot nal border that increased during a Valsalva ma- near beaches in various locations in Southeast neuver. There was no edema or calf tenderness. Asia. He was divorced and had a child. He smoked The remainder of the examination was normal. cigars occasionally and drank 1 to 2 glasses of Dr. Jo-Anne O. Shepard: A posteroanterior chest wine nightly but did not use illicit substances. radiograph (Fig. 1) showed clear lungs and a He had been sexually active while traveling but slightly enlarged heart, findings that had not had used condoms. Several first-degree relatives changed from a study obtained 1 year earlier. had hypertrophic cardiomyopathy. His mother had There was a dual-lead ICD that terminated in the died 3 years earlier from pulmonary tuberculosis, right atrium and right ventricle. but he had not been in contact with her during Dr. Dudzinski: An electrocardiogram (Fig. 2) her illness. was notable for sinus rhythm, left ventricular A B Figure 1. Chest Radiograph. Posteroanterior and lateral images (Panels A and B, respectively) show clear lungs and a slightly enlarged heart, as well as implantable cardioverter–defibrillator leads in the right atrium and right ventricle. n engl j med 380;21 nejm.org May 23, 2019 2053 The New England Journal of Medicine Downloaded from nejm.org by GIUSEPPE GIOCOLI on June 2, 2019. For personal use only. No other uses without permission. Copyright © 2019 Massachusetts Medical Society. All rights reserved. The new england journal of medicine I V1 V4 aVR II V2 V5 aVL III aVF V3 V6 V1 Figure 2. Electrocardiogram. An electrocardiogram shows sinus rhythm, left ventricular hypertrophy, and T-wave inversions in leads I, aVL, V4, V5, and V6; these findings had not changed from three tracings obtained in the previous year. hypertrophy, and T-wave inversions in leads I, tests for galactomannan, 1,3-β-D-glucan, and aVL, V4, V5, and V6, findings that had not antibodies to human immunodeficiency virus changed from previous tracings. A 5-day course types 1 and 2. Testing for antibodies to para- of azithromycin was prescribed, along with acet- gonimus was negative, but testing for antibodies aminophen, oxymetazoline nasal spray, and a to strongyloides was positive. phenol-based topical throat spray. A tuberculin Additional diagnostic tests were performed. skin test was negative for induration. Results of liver-function tests were normal; other labora- Differential Diagnosis tory test results are shown in Table 1. A trans- thoracic echocardiogram was notable for a left Dr. Rachel P. Simmons: This 53-year-old man with a ventricular ejection fraction of 60%, a maximum history of hypertrophic obstructive cardiomyop- left ventricular wall thickness of 16 mm, systolic athy and allergic rhinitis presented to this hos- anterior motion of the mitral-valve chordae with pital with a chronic illness of 3 months’ dura- trace mitral regurgitation, and a resting left ven- tion that was characterized by intermittently tricular outflow gradient of 16 mm Hg; these productive cough, marked peripheral eosinophilia findings had not changed from a study obtained (with an absolute eosinophil count of 3800 to 9 months earlier. 4550 per cubic millimeter), an elevated IgE level, Azithromycin therapy resulted in decreased and normal results on pulmonary examination fatigue and malaise and reduced the frequency and chest radiography. His history is also nota- of the cough but did not eliminate it. A few epi- ble for extensive travel and habitation in Asia sodes of hemoptysis with scant blood occurred, and the Middle East. and bloody streaks were present in nasal mucus. Although several features of this patient’s pre- After the patient completed the course of azithro- sentation could point us toward the diagnosis, mycin, additional laboratory tests were performed I will focus my differential diagnosis on the (Table 1). Cultures of the stool and sputum were development of marked peripheral eosinophilia negative, as was examination of the stool and and symptoms that were localized to the respi- sputum for ova and parasites. A hypersensitivity ratory system. His travel history warrants a pneumonitis panel (including a test for antibod- thorough workup for tissue-invasive parasites, ies to aspergillus) was also negative, as were particularly helminths; however, a multitude of 2054 n engl j med 380;21 nejm.org May 23, 2019 The New England Journal of Medicine Downloaded from nejm.org by GIUSEPPE GIOCOLI on June 2, 2019. For personal use only. No other uses without permission. Copyright © 2019 Massachusetts Medical Society. All rights reserved. Case Records of the Massachusetts General Hospital Table 1.