Mrs. A, age 54 years, came to the clinic for further evaluation of a cough that had started five years ago and was progressively worsening. The cough was minimally productive of white sputum, had a prominent nocturnal component, and was occasionally disabling. The patient reported no associated paroxysmal wheezing, dyspnea, chest pain, hemoptysis, weight loss, or symptoms of gastroesophageal reflux disease (GERD). She was initially treated with allergy medications (although subsequent evaluations found no proof of allergies). Bronchodilators provided minimal relief. The patient did not complain of fever or night sweats. She reported no recent travel or contact with anyone who was ill, and she did not live with a pet. A lifelong nonsmoker, Mrs. A reported no environmental irritants at her job as a kindergarten teacher. Her surgical history was negative. Her medical history included hypertension and osteopenia. The only medications she was taking were hydrochlorothiazide, calcium with vitamin D, and a multivitamin. She was up to date with her mammography, colonoscopy, and Pap smear.

1. Examination findings

Mrs. A was hemodynamically stable, with 100% oxygen saturation on ambient air. She looked younger than her stated age and was in no apparent respiratory distress. No skin lesions were noted. Examination of her head and neck was unremarkable; there was no palpable lymphadenopathy. Chest and cardiac examinations were within normal limits, and she had no clubbing of her fingers or toes. 

2. Diagnostic workup

Laboratory studies, including a complete blood count, blood chemistry, and coagulation and liver panels, were within normal limits. A series of chest x-rays (CXRs) taken over the past five years had been normal. However, a CXR obtained during a recent exacerbation of Mrs. A’s cough showed a right middle-lobe infiltrate (Figure 1), and she was presumptively treated for community-acquired pneumonia. A CXR obtained at this visit for persistent cough revealed the continued presence of the right middle-lobe infiltrate.

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Given these findings, additional investigations were obtained, including pulmonary function testing (PFT) and a chest CT. Mild airway obstruction was noted on PFT. The subsequent chest CT showed multiple pulmonary nodules. Since the suspicion for lung carcinoma was quite high at this time, positron emission tomography (PET) was ordered to look for other areas that might be involved. The PET scan showed extensive bilateral hilar and mediastinal lymphadenopathy with multiple pulmonary nodules, raising the possibility of sarcoidosis. Angiotensin-converting enzyme and calcium levels were normal.

3. Diagnosis

When bronchoscopy proved not to be diagnostic, a thoracoscopic lung biopsy was performed. Findings were consistent with sarcoidosis. Mrs. A was started on low-dose prednisone, with complete resolution of her cough.

4. Discussion

Sarcoidosis can be a cause of chronic cough, but its atypical presentation makes it hard to diagnose. Mrs. A’s case illustrates the challenge presented by chronic cough, as she was presumptively treated for the more usual causes (i.e., postnasal drip, GERD, asthma, and allergic rhinitis), with no resolution of her symptoms. This prompted more invasive studies for an appropriate diagnosis. 

Sarcoidosis is a chronic, granulomatous, multisystem disease that can affect any organ. Its clinical features are dependent on age, gender, ethnicity, duration, and activity of the illness, as well as on site and extent of organ involvement. The etiology of sarcoidosis remains unknown. Approximately 5% of cases are asymptomatic and are incidentally detected by CXR. Systemic complaints, fever, anorexia, and arthralgias occur in 45% of cases. Sarcoidosis most commonly involves granuloma formation in the lungs. Pulmonary symptoms occur in about 50% of cases and may include dyspnea on exertion, cough, chest pain, and hemoptysis. Radiographic findings are positive in almost 90% of sarcoidosis patients.

Chest radiography is used in staging sarcoidosis. Patients with stage I disease have bilateral hilar lymphadenopathy (BHL). Stage II disease is characterized by BHL plus pulmonary infiltrates (as seen in Mrs. A). In stage III disease, pulmonary infiltrates are seen without BHL. Stage IV disease features pulmonary fibrosis.

Sarcoidosis can be self-limited or chronic with episodic recrudescence and remissions. Markers for a poor prognosis include advanced disease on CXR, extrapulmonary disease (predominantly affecting cardiac and nervous systems), and evidence of pulmonary hypertension. In most cases, the diagnosis of sarcoidosis requires biopsy. Although transbronchial biopsy is often performed, an endobronchial biopsy during bronchoscopy increases the yield of that procedure. However, the presence of noncaseating granulomas on biopsy should not be construed as diagnostic until a thorough investigation has excluded other known causes of granulomatous inflammation. Clinicians should be aware that most patients do not require therapy, and their condition usually will improve spontaneously. The need for medical therapy varies based on the symptoms and the organ systems involved.

Dr. Respicio is a clinical rheumatology fellow in the Department of Medicine, University of California, San Francisco.