Immune Axonal Neuropathies Associated With Systemic Autoimmune Rheumatic Diseases

Abstract

Immune axonal neuropathies are a particular group of immune-mediated neuropathies that occasionally accompany systemic autoimmune rheumatic diseases such as connective tissue dissorders and primary systemic vasculitides. Apart from vasculitis of vasa nervorum, various other mechanisms are involved in their pathogenesis, with possible therapeutic implications. Immune axonal neuropathies have highly heterogeneous clinical presentation and course, ranging from mild chronic distal sensorimotor polyneuropathy to severe subacute mononeuritis multiplex with rapid progression and constitutional symptoms such as fever, malaise, weight loss and night sweats, underpinning a vasculitic process. Sensory neuronopathy (ganglionopathy), small fiber neuropathy (sensory and/or autonomic), axonal variants of Guillain-Barré syndrome and cranial neuropathies have also been reported. In contrast to demyelinating neuropathies, immune axonal neuropathies show absent or reduced nerve amplitudes with normal latencies and conduction velocities on nerve conduction studies. Diagnosis and initiation of treatment are often delayed, leading to accumulating disability. Considering the lack of validated diagnostic criteria and evidence-based treatment protocols for immune axonal neuropathies, this review offers a comprehensive perspective on etiopathogenesis, clinical and paraclinical findings as well as therapy guidance for assisting the clinician in approaching these patients. High quality clinical research is required in order to provide indications and follow up rules for treatment in immune axonal neuropathies related to systemic autoimmune rheumatic diseases.

Small fiber neuropathy as a complication of SARS-CoV-2 vaccinations

“…Genetic SFN is because of mutations in a number of genes, such as GLA (Fabry disease), TTR (transthyretin-related amyloidosis), or SNCA (alpha-synucleinopathy) and many others. Secondary causes of SFN prevail and include, for example, diabetes, renal failure, thyroid dysfunction, hypovitaminoses, acute infections (SARS-CoV-2,[ 8 ] borreliosis[ 9 ]), vaccinations (rabies, varicella, human papillomavirus, lyme, SARS-CoV-2),[ 8 10 ] auto-immune disease,[ 11 12 ] pure autonomic failure because of alpha-synuclein deposition,[ 13 ] sarcoidosis,[ 14 ] Sjögren syndrome,[ 15 ] Parkinson’s disease,[ 16 ] and many others. [ 17 ] SFN may go along with or without affection of large motor or sensory fibers.…”

Small fiber neuropathy

“…13,26 Toxins are known to cause SFN include alcohol, heavy metals (e.g., mercury), 27 platinumbased agents, taxanes, remdesivir, immune checkpoint inhibitors, 28 proteasome-inhibitors (e.g., bortezomib), N-hexane, resiniferatoxin, pyridoxine, nitrofurantoin, metronidazole, and several others. Autoimmune disease manifesting with SFN include monoclonal gammopathy; sarcoidosis, 24,29,30 rheumatic disease (mixed connective tissue disease, systemic vasculitis), 8,31,32 Sjögren syndrome, 33 anti-plexin D1-IgG antibodies in mice, 34 Behcet disease, 35 familial Mediterranean fever, 35 celiac disease, 36 primary systemic vasculitis, Guillain-Barre syndrome (GBS), chronic, inflammatory, demyelinating polyneuropathy (CIDP), lupus, AA, and AL amyloidosis, which can be associated with familial Mediterranean fever and hyperlipidemia, and acute, inflammatory SFN. 21 Neoplasms associated with SFN include keloids, 37 lymphoma, carcinoid, 18 and others.…”

Peripheral neuropathy: A neglected cause of disability in COPD – A narrative review

“…High-resolution nerve sonography and magnetic resonance imaging (MRI) could be used as diagnostic tools in peripheral neuropathies, as they are non-invasive and well tolerated. However, these are still scarcely used, mainly for immune-mediated neuropathies [87]. Nerve sonography also has the advantage of being relatively affordable, providing access to small fibers and peripheral nerves since they usually display a superficial course and rapidly assess the course of a long nerve [106].…”

“…basement membrane, narrowing of the lumen, pericytic mural debris, nerve capillary endothelial-cell hyperplasia, hypertrophy, nerve perineurium thickening[79](28)[31] Imaging High-resolution nerve sonography and magnetic resonance imaging (not available for clinical use)[87]. Autonomic testing composite autonomic scoring scale (CASS)[88] 3.1.1.2.…”