Small Fiber Neuropathy in Pulmonary Sarcoidosis and Tuberculosis: Clinical and Histological Correlates

Abstract Sarcoidosis (SC) is the granulomatous disease of an unknown origin, where the differential diagnosis with tuberculosis (TB) is challenging and vital for patients’ prognosis. The common neurological complication in SC is a small fiber neuropathy (SFN), that is considered to be the result of the chronic inflammation, and remains significantly understudied. There is no reliable data, whether such complication is observed in TB patients, where the systemic inflammation is also described. Aim: To identify the clinical and histological correlates of the small fiber neuropathy in sarcoidosis and tuberculosis patients.Materials and methods. A study was performed in 2018 – 2019 years and included 71 patients with pulmonary sarcoidosis (n=25), pulmonary tuberculosis (n=21), and healthy subjects (n=25). For the clinical verification of the SFN, the “Small fiber neuropathy screening list” (SFN-SL) was used. A punch biopsy of the skin was performed followed by the enzyme immunoassay analysis with PGP 9.5 antibodies.Results of the study: Up to 60% of sarcoidosis patients and 19% tuberculosis patients report the presence of at least one complaint, which may be associated with SFN. The most frequent complaints included dysfunctions of the cardiovascular, musculoskeletal system and gastrointestinal tract. A negative, statistically significant correlation between the intraepidermal nerve fiber density (IEND) and SFN-SL score was revealed in both groups (Spearman coefficient, r = -0.3508, p = 0.0102, and r = -0.7382, p = 0.0064, respectively). Wherein, the density of small nerve fibers in the patients with pulmonary sarcoidosis was lower, compared to the patients with tuberculosis (Mann-Whitney test, p = 0.0047). Conclusion: In patients with pulmonary sarcoidosis, small fiber neuropathy may develop as a result of systemic immune-mediated inflammation. The most common symptoms of this complication were dysautonomia and mild sensory dysfunction. Wherein, in tuberculosis patients clinical and histological symptoms of the small fiber neuropathy were subsequently less prominent, which may represent the difference between the autoimmune and bacterial inflammation. The validated questionnaires and histologic verification of the diagnosis help to establish the severity of neuropathy of small fibers, to determine the prognosis, to plan the treatment strategн, and also may allude the possibility for the additional criteria of differential diagnosis between two diseases.