A structured list of laboratory tests for screening the possible causes of small fiber neuropathy in clinical practice.

Small fiber neuropathies (SFN) are increasingly recognized as the cause of various sensory and autonomic disorders. Different tests exist to enable the objective diagnosis of SFN, but these tests generally do not identify a possible etiology. However, finding the cause of SFN is the best way to implement effective treatment. Thus, the etiological assessment must be as exhaustive as possible so as not to miss a curable cause of SFN. This search is based primarily on patient's history and clinical examination but may also require additional laboratory investigations. The objective of this article is to provide recommendations to help practitioners rationalize these investigations, mainly blood tests, with the aim of identifying the possible cause of SFN in a given patient. The first-line blood tests we generally recommend help identify two main categories of possible etiologies of SFN: firstly, metabolic and endocrine causes (diabetes, prediabetes, metabolic syndrome, insulin resistance, vitamin B disorders, renal or hepatic insufficiency, and thyroid diseases), and secondly, immunological, inflammatory, and infectious causes (autoimmune connective tissue diseases, celiac disease, monoclonal gammopathy, sarcoidosis, and viral infections). As a second-line approach, we propose complementary investigations that should be considered in more specific clinical situations. An algorithm is presented, summarizing the sequence of investigations to be performed to guide clinicians in their diagnostic approach to SFN.