E case #12 March 19-23, 2001

David True, M.D.

A 48 yo African American male comes into clinic complaining of fatigue & weight loss over the last 2 months. He notes significant night sweats and dyspnea on exertion as well as a dry cough. He denies sputum or hemoptysisor having been around individuals at risk for TB. He works as an engineer, has not traveled, and denies risk factors for HIV. He has no pets and has not been exposed to other animals. His past history is notable for"borderline diabetes", but his home blood sugar record has shown more normal blood sugars even as his weight has declined from 190lbs to 140lb in this5ft 8in male. He is a pack per day smoker, but has not had chronic pulmonary problems. Physical exam is remarkable for sinus congestion and bilateral inspiratory crackles on chest auscultation. No oral or skin lesions, adenopathy or abnormal breath sounds are noted. A chest XRAY is obtained which shows bilateral upper lobe infiltrates with an enlarged mediastinum.  CBC and chemistries are normal.

• What possible causes of this patient's problems would you like to rule out first, and which tests would you obtain?

• If infectious causes have been ruled out, what would be your differential diagnosis?

• How would complete the work-up?

• A tissue sample provides a definitive diagnosis. What histopathology would be most relevant in this case?

• What treatment would you recommend? How long would you continue it,and how would you monitor efficacy?

Discussion, case #12

Diagnostic workup:Three separate sputums and a PPD are obtained to rule out active TB or abacterial pneumonia. HIV testing is performed and is negative. CT scan of the chest shows a diffuse bilat upper lobe parenchymal inflitrate and significant mediastinal and hilar adenopathy. Other diseases in the differential diagnosis would include lymphoma,metastatic carcinoma, leukemia, sarcoidosis, coccidiomycosis,histoplasmosis, berylliosis. Pulmonary consultation is requested for bronchoscopy, and transbronchial needle biopsy produces tissue showing for noncaseating granulomas.

Sarcoidosis

Sarcoidosis is a granulomatous disease that may affect several differentorgan systems. Pulmonary involvement is the most common (90%), followed by hepatic (60-90%), large joints (up to 50%), bone marrow and spleen (up to40%), eye (25%), skin (25%), peripheral and CNS (5%), cardiac (5%), renal(2%), and endocrine systems. The etiology is unknown, but epidemiology shows a racial preference for African-Americans vs. white (10:1). An acute form of the disease develops within a few weeks associated with fever, fatigue,malaise, anorexia, weight loss and may or may not have associated respiratory complaints of cough, dyspnea, and retrosternal pain. Lofgrens syndrome is the combination of erythema nodosum with hilar adenopathy,fever, and arthralgias. A more chronic or insidious form of the disease develops over many months and primarily involves respiratory symptoms of dry cough, dyspnea on exertion, chest pain, and wheezing.

CXR findings may include hilar adenopathy and pulmonary infiltrates .Pulmonary function studies may show restrictive or obstructive patterns in more advanced cases involving pulmonary fibrosis. Laboratory abnormalities can include transaminase and alkaline phospatase elevations, hypercalcemia and hypercalciuria (with renal involvement), anemia/thrombocytopenia (with bone marrow involved), and hyponatremia if anterior pituitary dysfunction occurs. Cardiac arrythmias, heart block, CHF, and pericarditis can result from myocardial sarcoidosis. Serum ACE levels are elevated in 60% of patients and can be very useful in monitoring disease activity and response to treatment.

Corticosteroids are the mainstay of treatment, and are particularly effective for non-fibrotic pulmonary disease, hypercalcemia, and skin lesions. Bone marrow and cardiac lesions are less responsive. The usual starting dose is 40 mg of prednisone per day and the dose is tapered every 2weeks down to approximately 15mg/day. A response to steroid therapy should be evident within 8 weeks. If a response is seen, a dose of 10-15mg/day should be continued for up to 8 months and then tapered to the lowest effective dose. Immunosuppressive treatment with methotrexate or cytoxan maybe helpful in refractory cases.

References

Saboor & Johnson; Sarcoidosis, review, Br J Hosp Med, 1992Vol 48 #6 pg 293-302

Vouerlekis, et al, Sarcoidosis: developments in etiology,immunology, and therapeutics;  Adv Intern Med 2000; 45:209-57