Fibromyalgia and small‐fiber polyneuropathy: What's in a name?

Farhad, Khosro; Oaklander, Anne Louise

doi:10.1002/mus.26179

Cited by 19 publications

(20 citation statements)

References 21 publications

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“…Sweating is controlled by sympathetic non-myelinated C-fibers and deficiencies therein may occur due to alterations in these nerve fibers [ 26 , 34 ]. Small (intraepidermal unmyelinated nerve fibers) and even large peripheral nerve fiber neuropathy, usually in distal body parts, has been observed in a proportion of FMS patients, leading to a lower density of these fibers in comparison with healthy individuals [ 5 , 6 , 45 – 48 ]. A recent study in a large cohort of patients with FMS applied different tests for multidimensional characterization of neuropathy, observing indications of widespread small nerve fiber dysfunction and damage and identifying patient subgroups in relation to the extent and pattern of this damage [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

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Reduced activity, reactivity and functionality of the sympathetic nervous system in fibromyalgia: An electrodermal study

Paso

Coba

2020

PLoS ONE

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Alterations in autonomic activity are well established in fibromyalgia syndrome (FMS). Previous studies found reduced parasympathetic activity and sympathetic reactivity to physical and stress manipulations. However, sympathetic activity at rest has not been well studied in FMS. Sweating is exclusively controlled by sympathetic mechanisms. In this study, skin conductance (SC), as an indirect measure of sweating, was analyzed in 45 women with FMS and 38 healthy women. Tonic SC levels were recorded during a 4-minute rest period, and a breathing maneuver consisting of deep breathing with posterior breath holding was used to evoke SC responses. Associations of tonic SC with state anxiety and body temperature, measured in the hand, were explored to determine sweat functionality. The results showed reduced tonic SC levels, with a less marked decrease in SC during the recording period, and blunted SC reactivity to the breathing manipulation in FMS patients relative to healthy participants. Positive associations of SC with state anxiety and body temperature were observed in healthy participants, but these associations were absent in FMS patients. These results indicate alterations of sweating in FMS, suggesting reduced tonic and reactivity sympathetic influences. Furthermore, the absence of associations between SC levels and state anxiety and body temperature in the patient sample suggested a loss of functionality of the autonomic nervous system in FMS. Diminished autonomic regulation in FMS would reduce the ability to cope with environmental demands, thus favoring increases in stress and pain levels. Finally, the observed reduction in sweating is in accordance with evidence of small nerve fiber neuropathy in FMS.

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Section: Discussionmentioning

confidence: 99%

“…The etiology and pathophysiology of FMS are largely unknown, and there are no specific somatic signs of the disease. Most etiological models propose that FMS pain arises from central nervous system sensitization [ 2 – 4 ] and/or peripheral small fiber neuropathy [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Reduced activity, reactivity and functionality of the sympathetic nervous system in fibromyalgia: An electrodermal study

Paso

Coba

2020

PLoS ONE

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“…Nearly half of patients with fibromyalgia have evidence of reduced IENFD on skin biopsy, and emerging evidence indicates that nearly a third of patients have a distal large fiber neuropathy as indicated by low medial plantar responses 93. It is unclear whether patients who have fibromyalgia with and without small fiber pathology are clinically distinguishable,94 although some researchers report that paresthesia and autonomic involvement may predict the presence of small fiber dysfunction 95. One prospective study compared 30 patients with fibromyalgia with 34 age and sex matched healthy controls in terms of clinical examination, quantitative sensory testing, skin biopsy, blood and cutaneous miRNA isolation.…”

Section: Differential Diagnosis Of Small Fiber Neuropathiesmentioning

confidence: 99%

Diagnosis and management of sensory polyneuropathy

Gwathmey

Pearson

2019

BMJ

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Sensory polyneuropathies, which are caused by dysfunction of peripheral sensory nerve fibers, are a heterogeneous group of disorders that range from the common diabetic neuropathy to the rare sensory neuronopathies. The presenting symptoms, acuity, time course, severity, and subsequent morbidity vary and depend on the type of fiber that is affected and the underlying cause. Damage to small thinly myelinated and unmyelinated nerve fibers results in neuropathic pain, whereas damage to large myelinated sensory afferents results in proprioceptive deficits and ataxia. The causes of these disorders are diverse and include metabolic, toxic, infectious, inflammatory, autoimmune, and genetic conditions. Idiopathic sensory polyneuropathies are common although they should be considered a diagnosis of exclusion. The diagnostic evaluation involves electrophysiologic testing including nerve conduction studies, histopathologic analysis of nerve tissue, serum studies, and sometimes autonomic testing and cerebrospinal fluid analysis. The treatment of these diseases depends on the underlying cause and may include immunotherapy, mitigation of risk factors, symptomatic treatment, and gene therapy, such as the recently developed RNA interference and antisense oligonucleotide therapies for transthyretin familial amyloid polyneuropathy. Many of these disorders have no directed treatment, in which case management remains symptomatic and supportive. More research is needed into the underlying pathophysiology of nerve damage in these polyneuropathies to guide advances in treatment.

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“…In a recent publication, Farhad and Oaklander reported that up to 40% of patients with fibromyalgia met the best available diagnostic criteria for “initially idiopathic” small‐fiber polyneuropathy. The authors suggested that, unlike syndromes such as fibromyalgia, diseases such as SFN can be objectively diagnosed, their biological causes can be identified and tracked, and, sometimes they can be prevented or cured .…”

Section: Discussionmentioning

confidence: 99%

Small‐fiber neuropathy associated with autoinflammatory syndromes in children and adolescents

et al. 2020

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Introduction Small‐fiber neuropathy is rare in children. It has been associated with several autoimmune disorders, but there are no reports of an autoinflammatory etiology. Methods The data of four children/adolescents presenting with erythromelalgia and neuropathic pain from 2014 to 2019 were collected retrospectively from the electronic database of a pediatric medical center. Results Results of clinical and/or electrophysiological evaluation excluded large nerve fiber involvement. Skin biopsy results confirmed small‐fiber neuropathy. According to genetic analysis, two patients were heterozygous and one was homozygous for mutations in the familial Mediterranean fever (MEFV) gene. Behcet disease was diagnosed in the fourth patient. Treatment with anti–interleukin‐1 agents, intravenous immunoglobulin, and glucocorticoids was beneficial. Discussion The diagnosis of small‐fiber neuropathy should be considered in children/adolescents presenting with erythromelalgia. A thorough investigation is required to reveal the underlying disorder. Clinicians should be alert to the peripheral neurological manifestations of autoinflammatory syndromes because effective treatments are available.

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Fibromyalgia and small‐fiber polyneuropathy: What's in a name?

Cited by 19 publications

References 21 publications

Reduced activity, reactivity and functionality of the sympathetic nervous system in fibromyalgia: An electrodermal study

Reduced activity, reactivity and functionality of the sympathetic nervous system in fibromyalgia: An electrodermal study

Diagnosis and management of sensory polyneuropathy

Small‐fiber neuropathy associated with autoinflammatory syndromes in children and adolescents

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