New phenotyping questionnaire for diagnosing sarcoidosis-associated small fiber neuropathy

The etiology of small fiber neuropathy (SFN) remains unknown and a gold standard for diagnosis is lacking. This study identifies new phenotypes of sarcoidosis associated SFN (SSNF). The main objective was to identify the prevalence of length-dependent, non-length-dependent, intermittent and continuous pain. The secondary objective was to identify the association between the phenotypes and different diagnostic modalities. This was a prospective, cross-sectional and observational study. A new SFN phenotyping questionnaire was developed and compared with thermal threshold testing (TTT), intraepidermal nerve fiber density, corneal confocal microscopy, Sudoscan, and water immersion skin wrinkling. Prevalence of non-length-dependent, length-dependent, intermittent or continuous pain in patients with SSFN was established. Additionally, the association between the phenotypes and diagnostic modalities was investigated. 97 sarcoidosis patients were included, of whom 48 had probable SSFN based on symptoms and clinical signs of SFN. Of the 48 patients with probable SSFN, 17 (35%) showed a length-dependent phenotype and 21 (44%) a non-length-dependent phenotype. Intermittent pain was present in 13 (27%) patients with probable SSFN, continuous pain in 11 (23%) and mixed pain in 14 (29%). Continuous length-dependent pain was the only phenotype that correlated with TTT number of abnormalities (R=0.3; p=0.02). SSFN presents dominantly as a non-length-dependent phenotype. TTT appears to be specifically sensitive to establish continuous length-dependent pain. If this is confirmed in other cohorts, it will have implications for all underlying diseases in which SFN-related intermittent pain may be present.