Small-fiber polyneuropathy (SFPN), a common underlying diagnosis in syndromes involving unexplained chronic pain and multi-system symptoms

Background Syndromes involving unexplained chronic widespread pain (CWP) and multi-system symptoms are common, with 15% prevalence for fibromyalgia alone. They more often affect females and cause disability and high costs [1-3]. Other common syndromes include chronic fatigue, seronegative Lyme, and Gulf War Illness. Fragmentary syndromes include TMJD, POTS, CRPS, irritable bowel). These syndromes are particularly devastating in children and young adults, where they interfere with education and development and disrupt entire families [4-6]. SFPN is known to cause CWP and multi-system complaints in older adults. Unlike the syndromes above, SFPN can be objectively diagnosed by measuring innervation in lowerleg skin biopsies, and autonomic functions testing (AFT) of heart rate, blood pressure and sweating [7]. SFPN has several established causes including diabetes, infections, cancer, and toxins. Many causes are diagnosable, treatable, and sometimes curable [8]. Our work suggests that unrecognized SFPN contributes to several syndromes involving CWP and multi-organ symptoms.