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Sarcoidosis is a systemic disease characterized by noncasefied granulomas in various organs. Incidence of splenic disease is variable and is reported to occur in 6.7 to 77 percent of the patients. Firm data establishing the clinical features and the association of splenic involvement with prognosis in sarcoidosis is scant. The aim of our study was to investigate the clinical features and the consequence of splenic involvement on the prognostic outcome of sarcoidosis patients. We evaluated the clinical and laboratory findings in 82 sarcoidosis patients. Forty-two patients with splenic involvement were compared to 48 sarcoidosis patients without splenic disease in regard to laboratory findings, endobronchial disease, extrapulmonary organ involvement, and prognosis. Lung biopsy sample was considered positive if it demonstrated noncaseating granulomas with negative fungal and mycobacterial cultures. Splenic sarcoidosis was identified by ultrasound or computed tomography and was designated as limited, diffuse or without splenic involvement. Extrapulmonary organ sarcoidosis was classified as extensive and limited. Endobronchial disease was categorized as limited or diffuse involvement. The most commonly comprised organ was lung in 95% of the cases followed by lymph nodes, skin, eye, spleen and liver in the order of frequency. Splenic disease was diffuse in 22 patients. Of these patients, 14 had extensive extrapulmonary organ involvement while 16 had diffuse endobronchial disease. There was no significant difference between the three groups for FEV1, FVC, TLC, DLCO/VA, serum and 24h urinary calcium levels. Serum ACE was higher in patients with diffuse splenic involvement (p<0.001). Incidence of persistent chronic disease was significantly higher (p<0.001) in patients with diffuse splenic sarcoidosis. Extensive extrapulmonary organ involvement and diffuse endobronchial disease were more common (p<0.001) in this group. Extensive extrapulmonary organ involvement and diffuse endobronchial disease were more frequent in patients with diffuse splenic sarcoidosis. Patients with diffuse splenic granulomas had a worse prognosis than the patients without splenic involvement or patients with limited splenic disease. Diffuse splenic involvement emerges to be a significant risk factor for persistent chronic sarcoidosis. Extensive granuloma burden in an organ may be the decisive clinical marker for the prognostic outcome of sarcoidosis patients.