Small fiber neuropathy is a common feature of Ehlers-Danlos syndromes

Abstract

Small fiber neuropathy is a common feature of Ehlers-Danlos syndromes ABSTRACT Objective: To investigate the involvement of small nerve fibers in Ehlers-Danlos syndrome (EDS).Methods: Patients diagnosed with EDS underwent clinical, neurophysiologic, and skin biopsy assessment. We recorded sensory symptoms and signs and evaluated presence and severity of neuropathic pain according to the Douleur Neuropathique 4 (DN4) and ID Pain questionnaires and the Numeric Rating Scale (NRS). Sensory action potential amplitude and conduction velocity of sural nerve was recorded. Skin biopsy was performed at distal leg and intraepidermal nerve fiber density (IENFD) obtained and referred to published sex-and age-adjusted normative reference values.Results: Our cohort included 20 adults with joint hypermobility syndrome/hypermobility EDS, 3 patients with vascular EDS, and 1 patient with classic EDS. All except one patient had neuropathic pain according to DN4 and ID Pain questionnaires and reported 7 or more symptoms at the Small Fiber Neuropathy Symptoms Inventory Questionnaire. Pain intensity was moderate (NRS $4 and ,7) in 8 patients and severe (NRS $7) in 11 patients. Sural nerve conduction study was normal in all patients. All patients showed a decrease of IENFD consistent with the diagnosis of small fiber neuropathy (SFN), regardless of the EDS type.Conclusions: SFN is a common feature in adults with EDS. Skin biopsy could be considered an additional diagnostic tool to investigate pain manifestations in EDS. Neurology ® 2016;87:155-159 GLOSSARY cEDS 5 classic Ehlers-Danlos syndrome; DN4 5 Douleur Neuropathique 4; EDS 5 Ehlers-Danlos syndrome; hEDS 5 hypermobility Ehlers-Danlos syndrome; IENFD 5 intraepidermal nerve fiber density; JHS 5 joint hypermobility syndrome; NRS 5 Numeric Rating Scale; SFN 5 small fiber neuropathy; SFN-SIQ 5 Small Fiber Neuropathy and Symptoms Inventory Questionnaire; SNAP 5 sensory nerve action potential; vEDS 5 vascular Ehlers-Danlos syndrome.

Gastrointestinal disorders in joint hypermobility syndrome/Ehlers‐Danlos syndrome hypermobility type: A review for the gastroenterologist

“…It should be noted however that other factors than musculoskeletal pain may contribute to chronic pain in patients with JHS/EDS‐HT. For example, a high prevalence of small fiber neuropathy has been reported in patients with JHS/EDS‐HT, resulting in neuropathic pain …”

Small‐fiber neuropathy: Expanding the clinical pain universe

“…5 The rates of IENFD decrease over time do not differ between idiopathic SFN, diabetic SFN, and impaired glucose tolerance SFN. 5 IENFD has been reported to be reduced also in other painful conditions, such as Guillain-Barré syndrome, 36 meralgia paraesthestica, 37 notalgia, 38 Ehlers-Danlos syndrome, 39 and fibromyalgia 40 and nonpainful disorders, such as Parkinson disease and related disorders, [41][42][43] Key points…”

“…IENFD has been reported to be reduced also in other painful conditions, such as Guillain‐Barré syndrome, meralgia paraesthestica, notalgia, Ehlers‐Danlos syndrome, and fibromyalgia and non‐painful disorders, such as Parkinson disease and related disorders, amyotrophic lateral sclerosis, critical illness, and peripheral arterial disease …”

Hypermobile Ehlers–Danlos syndrome (a.k.a. Ehlers–Danlos syndrome Type III and Ehlers–Danlos syndrome hypermobility type): Clinical description and natural history

“…Anatomic imaging (e.g., for impingement of the central spine or foraminal nerve roots) and functional electrodiagnostic studies (e.g., nerve conduction studies or electromyography) are often negative even in the face of subjective symptoms highly suggestive of a neuropathic etiology. Skin biopsy may reveal reduction of intradermal nerve fiber density, suggestive of small fiber neuropathy [Cazzato et al, ].…”