54 with neurosarcoidosis and a case series of patients with Sjögren’s syndrome and SFN reported increased cognitive failure.8,10 Sjögren’s syndrome shares similar immunologic and histopathological features with sarcoidosis and is therefore of much interest.11 Restless legs syndrome (RLS) is a common movement disorder characterized by uncomfortable and sometimes painful sensations in the legs with a diurnal variation and a (partial) release with movement.12 RLS is a relative uniform disorder, and the severity of the basic symptoms is strongly related with the impact on quality of life.13 Data about RLS in sarcoidosis is limited with prevalence of RLS in sarcoidosis ranging from 0-50%.14,15 Although no data on RLS in patients with sarcoidosis with SFN is available, data suggesting an association between SFN and RLS is growing.16–19 It is unknown whether the presence of SFN in patients with sarcoidosis affects the prevalence and severity of fatigue, RLS, pain and cognitive impairment. Therefore, we investigated the prevalence and severity of these symptoms in healthy controls, patients with sarcoidosis without SFN and patients with sarcoidosis with SFN. Additionally, the association between these symptoms was investigated. Methods Design This was a cross-sectional, prospective observational study between January 2021 – September 2022. Healthy controls were recruited from partners of patients with sarcoidosis and colleagues from our hospital. Furthermore, patients with sarcoidosis with and without symptoms of SFN between 18-75 years were approached at the outpatient clinic of the St. Antonius hospital, a tertiary referral center for sarcoidosis and other interstitial lung diseases (ILD) in the Netherland. Sarcoidosis was diagnosed based on the criteria of the American Thoracic Society/European Respiratory Society.1 Exclusion criteria were vitamin B12 deficiency, glucose intolerance, diseases affecting sensory nerve function, signs of polyneuropathy, other diseases with a risk for developing (poly) neuropathy or SFN, pregnancy, mental health problems, language barrier, rheumatoid arthritis, and excessive alcohol intake as judged by the treating lung physician. Neuropathy Assessment Neuropathy assessment was performed according to the updated Besta criteria,20 the most widely recognized and standardized criteria for diagnosing SFN. Symptoms and clinical signs matching with a diagnosis of SFN as described in the diagnostic criteria were established. Large fiber dysfunction was assessed with sensory and motor nerve conduction studies at the tibial and peroneal nerves. Nerve conduction velocity, compound muscle action potential and sensory nerve action potential were examined with surface recording electrodes with standard placement. A diagnosis of “probable SFN” was made during a consultation at the neurologist based on symptoms and clinical signs during physical examination, in combination with normal nerve conduction studies according to the current diagnostic criteria.20 Patients with sarcoidosis and a diagnosis of probable SFN are called patients with sarcoidosis with SFN in this article. The group of patients with “no SFN” consist of patients without symptoms of SFN and patients with symptoms suggesting SFN but without clinical signs of SFN.20 Fatigue Assessment Scale The fatigue assessment scale (FAS) is a questionnaire developed to assess fatigue.21 The questionnaire consists of 10 questions on a 5-point Likert scale. Consequently, the FAS-score can range between 1050. FAS-scores below 22 indicate no fatigue, scores between 22-34 indicates mild-to-moderate fatigue and above 34 indicates severe fatigue.22 To simplify our results, we defined no fatigue (FAS<22) and fatigue (FAS≥22) for determining the prevalence. The median score per group was used to determine the severity of fatigue. 3 57 3
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