Insights and innovations in sarcoidosis associated small fiber neuropathy

Abstract

This thesis explores small fiber neuropathy (SFN) associated with sarcoidosis, focusing on its pathophysiology, diagnosis, symptomatology, and treatment options. Given the absence of a diagnostic gold standard and the complexity of proposed criteria, this research aims to improve diagnostic accuracy and therapeutic strategies for SFN and cardiac autonomic dysfunction in sarcoidosis patients. Key findings include: Symptomatology (Chapter 3): Patients with sarcoidosis-associated SFN exhibit a higher prevalence of fatigue, restless legs syndrome (RLS), pain, and cognitive impairment compared to those without SFN. These symptoms strongly correlate, suggesting a significant disease burden. Pain Phenotyping (Chapter 4): The newly developed SFN phenotyping questionnaire (SFNPQ) identified a high prevalence of cutaneous foot pain (67%) and muscular leg pain (77%) in sarcoidosis-associated SFN, offering a refined approach for clinical and research applications. Thermal Threshold Testing (Chapter 5): Thermal threshold testing (TTT) was evaluated for diagnostic accuracy, with findings supporting the use of multiple measuring sites and parameter selection. A novel parameter, TTT number of abnormalities (TTT NOAs), was introduced to improve diagnostic precision. Corneal Confocal Microscopy (Chapter 6): No significant reduction in corneal nerve fiber length (CNFL) or corneal nerve fiber area (CNFA) was detected in sarcoidosis-associated SFN, limiting the utility of corneal confocal microscopy (CCM) for diagnosis. However, automatic image analysis methods showed good agreement, facilitating future research. Phenotypic Variability (Chapter 7): SFN symptom patterns (length-dependent vs. non-length-dependent, intermittent vs. continuous) were analyzed, revealing that length-dependent continuous pain correlated with TTT NOAs at the feet. Other diagnostic modalities showed no significant associations, highlighting the need for improved diagnostic methods. Inflammatory Treatment Effects (Chapter 8): Infliximab significantly reduced sarcoidosis-related inflammation but did not alleviate SFN symptoms, suggesting a complex and possibly independent pathophysiological mechanism underlying SFN in sarcoidosis. Cardiac Autonomic Dysfunction (Chapter 9): [123I]-MIBG scintigraphy identified abnormalities in 44% of sarcoidosis patients, supporting its potential role in assessing unexplained cardiac symptoms and therapy-resistant cases. Overall, this research advances the understanding of sarcoidosis-associated SFN by refining diagnostic tools, characterizing symptomatology, and evaluating treatment efficacy. Future studies should focus on novel diagnostic methods and targeted therapies for SFN and autonomic dysfunction in sarcoidosis.