Clinical Manifestations, Pathogenesis, Diagnosis and Treatment of Peripheral Neuropathies in Connective Tissue Diseases: More Diverse and Frequent in Different Subtypes than Expected

Abstract

Purpose of review: To discuss and summarize recent findings in peripheral neuropathy (PN) related to connective tissue diseases (CTD) including its prevalence, clinical manifestations, pathogenesis, diagnosis and treatment. Recent findings: Although PN is a common complication in CTD and has been well studied, recent research has shown that PN is more diverse and frequent in different subtypes of CTD than was expected. The incidence of PN in Sjögren’s syndrome and rheumatoid arthritis (RA) varies according to different disease subtypes, and the pathogenesis of neuropathic pain in different subtypes of eosinophilic granulomatosis with polyangiitis (EGPA) may also differ. Neurogenic inflammation, autoantibody-mediated changes, ischemia of the vascular wall and metabolic mechanisms have been shown to contribute to the pathogenesis of PN in CTD. Moreover, allergic inflammation has been recently identified as a possible new mechanism producing peripheral neuropathic pain associated with MPO-ANCA negative EGPA patients. Glucocorticoids are routinely used to relieve pain caused by PN. However, these steroids may cause hyperalgesia, exacerbate neuropathic pain, and activate the early phase of pain induction and produce hyperalgesia. Recently, neuroactive steroids, such as progesterone, tetrahydroprogesterone and testosterone, have been shown to exert protective effects for several PN symptoms, and in particular neuropathic pain. Neuroactive steroids will be an interesting topic for future research into PN in CTD. Summary: It is essential for the diagnosis and treatment of PN in CTD to be updated. Timely diagnosis, appropriate treatments, and multidisciplinary care are essential to minimize morbidity and decrease the risk of permanent neurologic deficits. Further studies are needed to guide diagnosis and treatment.

Successful treatment with spinal cord stimulation for pain due to eosinophilic granulomatosis with polyangiitis: a case report

“…Two hypothetical mechanisms are suggested as follows: (1) eosinophils interrupt blood circulation by clogging the small vessels that supply the terminal nerves and (2) eosinophils induce toxicity by releasing proteins within the eosinophilic-specific granules into the extracellular milieu [4,5]. Thus, EGPA frequently causes mononeuritis multiplex, and the symptoms are severe in some cases and require aggressive immunosuppressive therapies [8].…”

“…The manifestations are wide-ranging, both those induced by eosinophilic non-vasculitis, such as asthma, rhinosinusitis, peripheral and tissue eosinophilia, and cardiomyopathy, and that induced by vasculitis, such as purpura, glomerulonephritis, and mononeuritis multiplex [3]. The prevalence of peripheral neuropathy in EGPA patients is reportedly between 46 and 77% [4,5]. Peripheral neuropathy in EGPA patients is characterized by polyneuropathy and mainly affects the lower extremities, with peroneal nerve involvement being the most frequent and severe [4].…”

“…The prevalence of peripheral neuropathy in EGPA patients is reportedly between 46 and 77% [4,5]. Peripheral neuropathy in EGPA patients is characterized by polyneuropathy and mainly affects the lower extremities, with peroneal nerve involvement being the most frequent and severe [4]. The main manifestations of motor neuropathy are foot drop and muscle weakness, and sensory neuropathy is distributed mostly asymmetrically in the distal limbs [4].…”

“…Although the mechanisms underlying the pain relief induced by spinal cord stimulation (SCS) are still not fully understood, this approach has been used in a variety of pathological states, including conditions involving peripheral neuropathic pain, such as complex regional pain syndrome, failed back surgery syndrome, diabetic neuropathy, ischemic pain, and postherpetic neuralgia [7]. Pain in EGPA patients is peripheral neuropathy induced by vasculitis of the small vessels that supply the terminal nerves [4]. Therefore, we speculated that SCS might be effective for pain of EGPA.…”