Background/Purpose: Sarcoidosis is a multi-organ disease in which pulmonary manifestations predominate. The skin, eyes, heart, gastrointestinal tract (GI), reticuloendothelial, renal and nervous systems are also commonly involved. Prior studies have shown a gender association with organ-specific manifestations. Male gender is associated with more severe radiographic abnormalities and female gender with more frequent extra-pulmonary manifestations (EPM).  We conducted a survey of gender-based differences in organ-specific manifestations of sarcoidosis.

Methods: A retrospective chart review on patients seen in clinics from a single institution from 2006-2012 with biopsy-proven sarcoidosis and a diagnosis >1 year were included. Data were collected on sex, smoking status, EPM (cutaneous, ocular, cardiac, neurologic, GI, and renal), chest radiographs and pulmonary function testing (PFT).

Gender differences between EPMs and pulmonary sarcoidosis (defined as chest radiographic findings consistent with hilar adenopathy and pulmonary fibrosis) were calculated.  Differences in forced vital capacity (FVC), total lung capacity (TLC), and diffusion capacity of lung for carbon monoxide (DLCO) were calculated using a t-test for the mean. PFTs were stratified by time of diagnosis in five year intervals.  PFT results were averaged if more than one test was done in a five year period.

Results: Of 511 charts reviewed, 156 patients (50 Male, 106 Female) met inclusion criteria. Ocular sarcoidosis (OS) was more frequent in males (M=28.0%, F=10.4%, p=0.005) with an odds ratio of 3.35(95% CI 1.40 to 8.08).  Gender was not a significant risk factor for other EPMs, nor for all EPMs combined.

The presence of pulmonary sarcoidosis was not associated with gender. PFTs showed significant gender difference (Table 1).  Males demonstrated worse FVC (M=69.0 ± 0.71% predicted, F=82.2 ± 20.35% predicted, p=0.03) and TLC (M=63.0 ± 0.71% predicted, F=78.86 ± 16.37% predicted, p=0.003) at 5-10 years post diagnosis. DLCO was significantly lower in females compared to males at 10-15 years post diagnosis (M=72.0 ± 4.24% predicted, F=55.33 ± 15.17% predicted, p= 0.02). There was no significant difference in smoking status between male and female groups with pulmonary sarcoid (p=0.11).

Conclusion: Male gender is an independent risk factor for OS.  Though gender was not associated with radiographic sarcoidosis, when controlled for smoking, a difference in increased severity of restrictive lung disease was suggested in a very small group of males at 5-10 year post diagnosis. Interestingly, females demonstrated a lower diffusion capacity at 10-15 years after diagnosis; the implications for underlying pulmonary vascular disease with disease duration are unclear.

Table 1:  Percent Predicted FVC, TLC, and DLCO at 5 year intervals from time of diagnosis