Investigation of nerve fibers in the skin by biopsy: technical aspects, indications, and contribution to diagnosis of small-fiber neuropathy

Raicher, Irina; Ravagnani, Luís Henrique Casartelli; Correa, Silene Gomes; Dobo, Cristine; Mangueira, Cristóvão Luis Pitangueira; Macarenco, Ricardo Silvestre e Silva

doi:10.31744/einstein_journal/2022MD8044

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MEDICAL DEVELOPMENTS • Einstein (São Paulo) 20 • 2022 • https://doi.org/10.31744/einstein_journal/2022MD8044 copy

Investigation of nerve fibers in the skin by biopsy: technical aspects, indications, and contribution to diagnosis of small-fiber neuropathy

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Skin biopsy with investigation of small-diameter nerve fibers in human epidermis and dermis has been proven to be a useful method for confirming small-fiber neuropathy. In medical practice, small-fiber neuropathy is increasingly recognized as a leading cause of neuropathic pain. It is a prevalent complaint in medical offices, brought by patients often as a “painful burning sensation”. The prevalence of neuropathic pain is high in small-fiber neuropathies of different etiologies, especially in the elderly; 7% of population in this age group present peripheral neuropathy. Pain and paresthesia are symptoms which might cause disability and impair quality of life of patients. The early detection of small-fiber neuropathy can contribute to reducing unhealthy lifestyles, associated to higher incidence of the disease.

Biopsy; Skin; Nerve fibers; Small fiber neuropathy; Diabetes mellitus; Diabetic neuropathies; Fabry disease; Neuralgia, postherpetic; HIV; Rheumatic diseases; Drug therapy

Indication	Finding	References
Diabetic neuropathy	Diabetes induces early degeneration of nerve fibers in the skin correlated with the duration and severity of the condition	Kennedy et al.⁽¹⁶⁾ Pittenger et al.⁽¹⁷⁾ Sorensen et al.⁽¹⁸⁾
Diabetic neuropathy	Individuals with diabetes have slower regeneration, even with no evidence of neuropathy	Polydefkis et al.⁽¹⁹⁾
Diabetic neuropathy	Studies from North America and Europe have shown different results on the effect of glucose intolerance on intraepidermal fiber loss	Smith et al.⁽¹¹⁾ Sumner et al.⁽²⁰⁾ Løseth et al.⁽²¹⁾ Nebuchennykh et al.⁽²²⁾ Vlckova-Moravcova et al.⁽²³⁾
Small-fiber neuropathy	A skin biopsy is the most sensitive method for diagnosing small-fiber neuropathy	Periquet et al.⁽²⁴⁾ Devigili et al.⁽²⁵⁾ Scherens et al.⁽²⁶⁾
Small-fiber neuropathy	The progressive nature of idiopathic small-fiber neuropathy is demonstrated by repeated skin biopsies	Lauria et al.⁽²⁷⁾
Small-fiber neuropathy	There are length-dependent and non-length-dependent small-fiber neuropathies	Holland et al.⁽²⁸⁾ Lauria et al.⁽²⁹⁾ Uçeyler et al.⁽³⁰⁾
Inflammatory demyelinating neuropathy	Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy may present with loss of intraepidermal nerve fibers	Chiang et al.⁽³¹⁾ Pan et al.⁽³²⁾
Inflammatory demyelinating neuropathy	Anti-MAG neuropathy may show IgM deposits in dermal myelinated nerve fibers	Lombardi et al.⁽³³⁾ Stalder et al.⁽³⁴⁾
Vasculitic neuropathy	Reduced cutaneous innervation may correlate with the severity of the vasculitic neuropathy, even in the absence of sensory symptoms.	Tseng et al.⁽¹²⁾
Vasculitic neuropathy	The presence of skin vasculitis may indicate a non-systemic vasculitic neuropathy with good sensitivity and specificity.	Uçeyler et al.⁽¹³⁾
HIV neuropathy	Intraepidermal fiber density is length-dependently reduced in HIV when the patient shows signs of neuropathy regardless of symptoms	Herrmann et al.⁽³⁵⁾
Hereditary neuropathy	Evaluation of dermal myelinated fibers may show changes in the molecular architecture of the axolemma	Li et al.⁽³⁶⁾ Sabet et al.⁽³⁷⁾
Hereditary neuropathy	Dermal myelinated fibers in Charcot-Marie-Tooth 1A have internodal length shortening	Saporta et al.⁽³⁸⁾
Hereditary neuropathy	Intraepidermal nerve fiber losses in Fabry disease, Friedreich’s ataxia, and familial dysautonomia (Riley-Day syndrome)	Scott et al.⁽³⁹⁾ Nolano et al.⁽⁴⁰⁾ Hilz et al.⁽⁴¹⁾ Torvin Møller et al.⁽⁴²⁾
Autonomic neuropathy	A peculiar pattern of cutaneous denervation characterizes rare conditions, such as congenital insensitivity to pain with anhidrosis, cold-induced sweating syndrome, and “Ross Syndrome”	Nolano et al.⁽⁴⁰⁾ Nolano et al.⁽⁴³⁾ Di Leo et al.⁽⁴⁴⁾
Nerve regeneration	The chemical model with topical capsaicin can be used to study the degenerative and regenerative properties of epidermal nerve fibers	Simone et al.⁽⁴⁵⁾ Nolano et al.⁽⁴⁶⁾ Nodera et al.⁽⁴⁷⁾ Polydefkis et al.⁽¹⁹⁾ Hahn et al.⁽⁴⁸⁾

Instituto Israelita de Ensino e Pesquisa Albert Einstein Avenida Albert Einstein, 627/701 , 05651-901 São Paulo - SP, Tel.: (55 11) 2151 0904 - São Paulo - SP - Brazil
E-mail: revista@einstein.br

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[1] Corresponding author: Irina Raicher Avenida Albert Einstein, 627/701 - Morumbi Laboratório Patologia Cirúrgica 2^nd floor, building E Zip code: 05652-900- São Paulo, SP, Brazil E-mail: irina.raicher@einstein.br