14 Aims and outline of the thesis The aim of this thesis is to gain more insight into the diagnosis, symptoms, measurement of patientreported outcomes, and treatment of SFN and cardiac autonomic dysfunction in patients with sarcoidosis. Chapter 2 will provide an overview of the current literature regarding small fiber neuropathy. First, diagnostic methods currently in use will be evaluated concerning their corresponding physiologic mechanisms. Additionally, a systematic literature review will be performed to identify diagnostic accuracy of all methods. Chapter 3 will highlight the high rates of fatigue, restless legs syndrome, pain and cognitive impairment in patients with sarcoidosis-associated small fiber neuropathy compared with patients with sarcoidosis without small fiber neuropathy. Additionally, the correlation between these nonorgan specific symptoms will be established. Chapter 4 will use the new SFNPQ questionnaire to assess pain at cutaneous, muscular and joint pain in patients with sarcoidosis. A distinction will be made between pain in the head, thorax, arms, hands, back/abdomen, legs, and feet. Chapter 5 will indicate the diagnostic performance of thermal threshold testing (TTT). The strengths and limitations of this method will be evaluated, and a proposal is made to select the best parameters and measuring sites. Chapter 6 will compare multiple analysis methods to assess corneal nerve fiber length (CNFL) from corneal confocal microscopy images. Additionally, CNFL will be compared among healthy controls, sarcoidosis patients without SFN and sarcoidosis patients with established SFN. Chapter 7 will use the new SFNPQ questionnaire to identify non-length-dependent, length-dependent, intermittent or continuous SFN symptoms in sarcoidosis patients. Additionally, the association between symptom phenotype and different diagnostic modalities will be investigated. Chapter 8 will investigate the effects of treating the underlying disease of SFN. In this study the effects of infliximab on sarcoidosis activity and small fiber neuropathy-associated symptoms will be assessed. Patients with sarcoidosis, at least 3 months on infliximab treatment and high scores on the small fiber neuropathy screening list (SFNSL) will be included. Chapter 9 will reveal the clinical characteristics of patients with sarcoidosis referred for assessment of cardiac involvement and further analysis with an Iodine-123 meta-iodobenzylguanidine (123I-MIBG) scintigraphy to rule out autonomic dysfunction of the heart. Furthermore, the effectiveness of the beta-blocker carvedilol on patients with impaired parasympathetic activity will be determined. Chapter 10 will provide a summary, a general discussion on the results of this thesis and directions for future research. 1 15 1
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