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Small fiber pathology with concomitant chronic neuropathic pain is a common complication of sarcoidosis. The gold standard of diagnosis of small fiber neuropathy (SFN) is the quantification of small nerve fibers in skin biopsies in combination with patient history and psychophysical tests; a new technique is the quantification of small nerve fibers in the cornea using cornea confocal microscopy (CCM). Here, we studied small fiber morphology in sarcoidosis patients with neuropathic pain using skin biopsies, CCM, and quantitative sensory testing (QST). Our aim was to construct specific phenotypes of neuropathic pain in sarcoidosis. Fifty-eight patients with a confirmed diagnosis of sarcoidosis and with moderate-to-severe neuropathic pain were tested. Decreased intraepidermal nerve fiber density (IENFD) from skin biopsies was found in 28% of patients, and CCM abnormalities were observed in 45% of patients. There was no correlation between CCM and IENFD abnormalities. Eighty-three percent of patients had abnormal thermal detection thresholds, a sign of small fiber dysfunction. Based on the presence or absence of abnormalities in IENFD and CCM, four distinct phenotypes were identified with a distinct homogeneous pattern of somatosensory symptoms. We argue that these distinct phenotypes have a similar mechanistic construct with specific phenotype-specific treatment options. Additionally, our data suggest the presence of patients with length- and nonlength-dependent SFN within this population of sarcoidosis patients.

Quantification of small fiber pathology in patients with sarcoidosis and chronic pain using cornea confocal microscopy and skin biopsies