158 of the heart is likely being underdiagnosed. Thus, a prospective study that systematically evaluates cardiac autonomic dysfunction and carvedilol treatment in patients with sarcoidosis and cardiac symptoms could offer new insights about prevalence of cardiac autonomic dysfunction and treatment effects. Finally, adequate treatment for SFN is currently lacking. Therefore, treating the underlying condition is assumed to be the most effective strategy.31,51 Results for the effects of immunoglobulin on sarcoidosis-associated SFN are contradictory.35,37,52 Although intravenous immunoglobulin (IVIG) treatment was not effective for idiopathic SFN34 or in our study cohort, some case series showed positive effects of sarcoidosis treatment on SFN related symptoms.5,36 Given the fact that the pathophysiology of SFN remains unclear and it can occur secondary to a wide range of conditions, idiopathic SFN may arise from entirely different mechanisms than when it occurs secondary to sarcoidosis. The inconsistent positive findings regarding IVIG-treatment in sarcoidosis-associated SFN in the literature,5,36 in combination with the lack of prospective studies, contribute to uncertainty in this area. A prospective study in this population could provide the clarity needed to address these uncertainties. Moreover, interest in alternative non-pharmacologic treatment options is growing. For example mindfullness-based cognitive treatment, whole-body cryotherapy, transcutaneous stimulation and repetitive transcranial stimulation are already investigated and might be the solution to improve the HRQL.27,53,54 In conclusion, as SFN is highly prevalent in patients with sarcoidosis, future research should focus on validating TTT NOAs, improving the IENFD protocol, improving the guidelines for cardiac sarcoidosis, and improving treatment strategies for cardiac autonomic dysfunction and SFN. In addition, investigating the pathophysiology of (intermittent) pain in patients with SFN, may lead to the exploration of entirely new diagostic domains. Key issues of this thesis Intermittent pain symptoms cannot be quantified with current diagnostic methods. CCM did not add value for diagnosing sarcoidosis-associated SFN. TTT NOAs was the only method which could diagnose SFN and was the only method which measured Aδ-nerve fibers. Patients with sarcoidosis and SFN experience more often and more severe fatigue, restless legs, pain and cognitive impairment. Although sarcoidosis-associated severe fatigue and cognitive impairment cannot be cured or adequately treated at the moment, other symptoms, such as pain and RLS, might be. 10 165 10
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