[Neuropathic pain as a symptom in autonomic neuropathies and other rare diseases : Small fiber neuropathy: its recognition, diagnosis, and treatment]. / Neuropathische Schmerzen als Symptom bei autonomen Neuropathien und anderen seltenen Erkrankungen : Kleinfaserneuropathie erkennen, diagnostizieren und behandeln.

BACKGROUND: Neuropathic pain is difficult to diagnose and treat. Small fiber neuropathy (SFN) flies under the radar of nerve conduction studies. OBJECTIVES: The importance of a structured patient history and physical examination in the context of neuropathic pain is emphasized. Describing SFN as an important cause, the authors consider rare but partially treatable differential diagnoses. They conclude that autonomic symptoms are frequently associated, often presenting with diverse symptoms. METHODS: A selective literature research to present SFN symptoms as well as differential diagnostic and therapeutic steps in the context of SFN and rare diseases focusing on the autonomic nervous system. RESULTS: Neuropathic pain significantly reduces quality of life. To shorten the time until diagnosis and to initiate therapy, the authors recommend a structured patient history including sensory plus and minus symptoms and non-specific autonomic signs. If the initial search for the cause is not successful, rare causes such as treatable transthyretin (ATTR) amyloidosis and Fabry's disease or autoimmune causes should be considered, particularly in the case of progressive and/or autonomic symptoms. CONCLUSION: The diagnosis and therapy of rare SFN requires interdisciplinary collaboration and, in many cases, a referral to specialized centers to achieve the best patient care.

[Small Fiber Neuropathy with Inadequate Response to Medical Therapy: Diagnosis of The Etiology of Small Fiber Neuropathy and Treatment Option].

Small-fiber neuropathy (SFN) has few significant laboratory findings and is difficult to diagnose. In 70% of the cases, the cause of SFN is unknown. Among the cases with known etiology, 50% are associated with diabetes, and the causes are autoimmune, amyloidosis, or multifactorial. In recent years, a specific autoantibody-positive group has been identified and has attracted attention because immunotherapy was successful in the autoantibody-positive SFN groups. In the cases reporting to our department, abnormalities could not be detected by various tests, including nerve conduction studies, and the response to symptomatic treatment was poor. An abnormality was identified in the current perception threshold test result, and a positive blood anti-plexin D1 antibody was detected via enzyme-linked immunosorbent assay. Therefore, autoimmune SFN was diagnosed, and plasma exchange therapy was remarkably effective. Subsequently, we aim to introduce general treatments for SFN and COVID-19-related SFN.

Peripheral neuropathy in sarcoidosis.

Peripheral nerve disorders in sarcoidosis consist of granulomatous neuropathy and non-granulomatous small fiber neuropathy (SFN), which differ in their underlying pathology, diagnostic methods and treatment. While granulomatous nerve involvement is rare in sarcoidosis, SFN is reported in over 40% of systemic cases. Distal symmetric polyneuropathy and asymmetric polyradiculoneuropathy are the most common presentations of granulomatous neuropathy, which typically responds to corticosteroids. In contrast, SFN is often manifested as non-length dependent pain and paresthesias that may improve with intravenous immune globulin or infliximab. Early recognition and treatment of sarcoidosis neuropathy can lead to improved outcomes and patient quality of life.

Small fiber neuropathy.

Small fiber neuropathy (SFN) is a peripheral nervous system disease due to affection of A-delta or C-fibers in a proximal, distal, or diffuse distribution. Selective SFN (without large fiber affection) manifests with pain, sensory disturbances, or autonomic dysfunction. Though uniform diagnostic criteria are unavailable, most of them request typical clinical features and reduced intra-epidermal nerve fiber density on proximal or distal skin biopsy. Little consensus has been reached about the treatment of SFN, why this narrative review aims at summarizing and discussing treatment options for SFN. Treatment of SFN can be classified as symptomatic, pathophysiologic, or causal. Prerequisites for treating SFN are an established diagnosis, knowledge about the symptoms and signs, and the etiology. Pain usually responds to oral/intravenous pain killers, antidepressants, anti-seizure drugs, or topical, transdermal specifications. Some of the autonomic disturbances respond favorably to symptomatic treatment. SFN related to Fabry disease or hATTR are accessible to pathogenesis-related therapy. Immune-mediated SFN responds to immunosuppression or immune-modulation. Several of the secondary SFNs respond to causal treatment of the underlying disorder. In conclusion, treatment of SFN relies on a multimodal concept and includes causative, pathophysiologic, and symptomatic measures. It strongly depends on the clinical presentation, diagnosis, and etiology, why it is crucial before initiation of treatment to fix the diagnosis and etiology. Due to the heterogeneous clinical presentation and multi-causality, treatment of SFN should be individualized with the goal of controlling the underlying cause, alleviating pain, and optimizing functionality.

Therapeutic plasma exchange for peripheral neuropathy associated with trisulfated heparan disaccharide IgM antibodies: A case series of 17 patients.

BACKGROUND: Small fiber neuropathy (SFN) can be associated with autoantibodies, including those of IgM class with specificity for the trisulfated heparan disaccharide (TS-HDS) antigen. We hypothesized that, as an IgM autoantibody-mediated disorder, TS-HDS-associated SFN symptoms may be reduced with therapeutic plasma exchange (TPE). STUDY METHODS: This was an observational analysis of all patients referred for TPE from 2018 to 2020 following laboratory confirmation of SFN with TS-HDS autoantibodies; a loading course of 3 to 5 procedures over 2 weeks was completed, with some patients returning for monthly procedures. The following data were collected: demographics, symptoms and duration, TS-HDS levels, skin biopsy results, reported responses to TPE, and TPE-associated adverse events. RESULTS: Of the 17 subjects, 12 (71%) were female and the mean age was 57.5 years (range 27-94). The most common reported symptom was lower extremity paresthesia (88% of subjects). The mean number of TPE procedures completed per subject was 9 (range 3-18), with 71% (12/17) reporting symptomatic improvement or slowed disease progression. About 15% of procedures were associated with an adverse event, with vasovagal reactions being the most common; 53% of patients had at least one adverse event. CONCLUSIONS: Given a reported symptomatic response rate of more than 70%, TPE may be a treatment option for individuals with autoimmune-mediated SFN associated with increased titers of TS-HDS IgM autoantibodies. Since TPE-associated adverse events appear common in this population, close monitoring during procedures is warranted.

Non-length-dependent small fiber neuropathy: Not a matter of stockings and gloves.

The clinical spectrum of small fiber neuropathy (SFN) encompasses manifestations related to the involvement of thinly myelinated A-delta and unmyelinated C fibers, including not only the classical distal phenotype, but also a non-length-dependent (NLD) presentation that can be patchy, asymmetrical, upper limb-predominant, or diffuse. This narrative review is focused on NLD-SFN. The diagnosis of NLD-SFN can be problematic, due to its varied and often atypical presentation, and diagnostic criteria developed for distal SFN are not suitable for NLD-SFN. The topographic pattern of NLD-SFN is likely related to ganglionopathy restricted to the small neurons of dorsal root ganglia. It is often associated with systemic diseases, but about half the time is idiopathic. In comparison with distal SFN, immune-mediated diseases are more common than dysmetabolic conditions. Treatment is usually based on the management of neuropathic pain. Disease-modifying therapy, including immunotherapy, may be effective in patients with identified causes. Future research on NLD-SFN is expected to further clarify the interconnected aspects of phenotypic characterization, diagnostic criteria, and pathophysiology.

Advances in the Management of Small Fiber Neuropathy.

Small fiber neuropathy (SFN) is a prevalent neurologic syndrome. Testing methods have emerged in recent years to better diagnose it, including autonomic tests and skin punch biopsy. SFN can present in a non-length-dependent fashion and can be mistaken for syndromes such as fibromyalgia and complex regional pain syndrome. SFN is caused by a variety of metabolic, infectious, genetic, and inflammatory diseases. Recently treatments have emerged for TTR amyloid neuropathy and Fabry disease, and novel biomarkers have been found both in genetic and inflammatory SFN syndromes. Ongoing trials attempt to establish the efficacy of intravenous immunoglobulin in inflammatory SFN syndromes.

Metabolic syndrome and peripheral neuropathy.

Diabetic peripheral neuropathy and metabolic syndrome (MetS) are both global health challenges with well-established diagnostic criteria and significant impacts on quality of life. Clinical observations, epidemiologic evidence, and animal models of disease have strongly suggested MetS is associated with an elevated risk for cryptogenic sensory peripheral neuropathy (CSPN). MetS neuropathy preferentially affects small unmyelinated axons early in its course, and it may also affect autonomic and large fibers. CSPN risk is linked to MetS and several of its components including obesity, dyslipidemia, and prediabetes. MetS also increases neuropathy risk in patients with established type 1 and type 2 diabetes. In this review we present animal data regarding the role of inflammation and dyslipidemia in MetS neuropathy pathogenesis. Several studies suggest exercise-based lifestyle modification is a promising treatment approach for MetS neuropathy.

Clinical diagnosis and management of small fiber neuropathy: an update on best practice.

INTRODUCTION: Small fiber neuropathy (SFN) is a heterogeneous group of disorders affecting thin myelinated Aδ and unmyelinated C fibers. Common symptoms include neuropathic pain and autonomic disturbances, and the typical clinical presentation is that of a length-dependent polyneuropathy, although other distributions could be present. AREA COVERED: This review focuses on several aspects of SFN including etiology, clinical presentation, diagnostic criteria and tests, management, and future perspectives. Diagnostic challenges are discussed, encompassing the role of accurate and standardized assessment of symptoms and signs and providing clues for the clinical practice. The authors discuss the evidence in support of skin biopsy and quantitative sensory testing as diagnostic tests and present an overview of other diagnostic techniques to assess sensory and autonomic fibers dysfunction. The authors also suggest a systematic approach to the etiology including a set of laboratory tests and genetic examinations of sodium channelopathies and other rare conditions that might drive the therapeutic approach based on underlying cause or symptoms treatment. EXPERT OPINION: SFN provides a useful model for neuropathic pain whose known mechanisms and cause could pave the way toward personalized treatments.

Efficacy of Electrical Stimulation on Nerve Fiber Growth in Small Fiber Neuropathy.

OBJECTIVES: To define whether electrical nerve stimulation (ENS) therapy would promote intraepidermal nerve growth and nerve regeneration in patients with small fiber neuropathy (SFN). METHODS: This was a prospective study conducted on 8 subjects with previously diagnosed SFN. Nerve conduction testing, punch biopsies, and clinical examinations with a calculation of revised total neuropathy score were conducted on subjects before beginning ENS therapy and at 30 and 60 days after the start of ENS therapy. RESULTS: Clinical examination findings and intraepidermal nerve fiber density measurements on day 30 and day 60 did not show statistically significant changes in the treated group compared with the untreated group. CONCLUSIONS: Despite the success of previous animal studies, no meaningful nerve growth and regeneration in SFN was demonstrated with ENS therapy in this study. Studies of larger subject larger populations with longer duration of ENS treatment are warranted to confirm our findings.

Complex syndromes of chronic pain, fatigue and cognitive impairment linked to autoimmune dysautonomia and small fiber neuropathy.

Chronic fatigue syndrome, postural orthostatic tachycardia syndrome, complex regional pain syndrome and silicone implant incompatibility syndrome are a subject of debate among clinicians and researchers. Both the pathogenesis and treatment of these disorders require further study. In this paper we summarize the evidence regarding the role of autoimmunity in these four syndromes with respect to immunogenetics, autoimmune co-morbidities, alteration in immune cell subsets, production of autoantibodies and presentation in animal models. These syndromes could be incorporated in a new concept of autoimmune neurosensory dysautonomia with the common denominators of autoantibodies against G-protein coupled receptors and small fiber neuropathy. Sjogren's syndrome, which is a classical autoimmune disease, could serve as a disease model, illustrating the concept. Development of this concept aims to identify an apparently autoimmune subgroup of the disputable disorders, addressed in the review, which may most benefit from the immunotherapy.

Current Diagnosis and Treatment of Painful Small Fiber Neuropathy.

PURPOSE OF REVIEW: Small fiber neuropathy (SFN) could cause significant morbidity due to neuropathic pain and autonomic dysfunction. SFN is underdiagnosed and the knowledge on the condition is limited among general public and health care professionals. This review is intended to enhance the understanding of SFN symptoms, causes, diagnostic tools, and therapeutic options. RECENT FINDINGS: There is evidence of SFN in up to 40% patients with fibromyalgia. The causes of SFN are glucose metabolism defect, dysimmune, gluten sensitivity and celiac disease, monoclonal gammopathy, vitamin deficiencies, toxic agents, cancer, and unknown etiology. Auto-antibodies targeting neuronal antigens trisulfated heparin disaccharide (TS-HDS) and fibroblast growth factor 3 (FGFR3) are found in up to 20% of patients with SFN. Treatment of SFN includes treating the etiology and managing symptoms. SFN should be considered in patients with wide-spread body pain. The search for known causes of SFN is a crucial step in disease management.

Biopsy-Proven Small-Fiber Neuropathy in Primary Sjögren's Syndrome: Neuropathic Pain Characteristics, Autoantibody Findings, and Histopathologic Features.

OBJECTIVE: Painful small-fiber neuropathies (SFNs) in primary Sjögren's syndrome (SS) may present as pure or mixed with concurrent large-fiber involvement. SFN can be diagnosed by punch skin biopsy results that identify decreased intra-epidermal nerve-fiber density (IENFD) of unmyelinated nerves. METHODS: We compared 23 consecutively evaluated patients with SS with pure and mixed SFN versus 98 patients without SFN. We distinguished between markers of dorsal root ganglia (DRG) degeneration (decreased IENFD in the proximal thigh versus the distal leg) versus axonal degeneration (decreased IENFD in the distal leg versus the proximal thigh). RESULTS: There were no differences in pain intensity, pain quality, and treatment characteristics in the comparison of 13 patients with pure SFN versus 10 patients with mixed SFN. Ten patients with SFN (approximately 45%) had neuropathic pain preceding sicca symptoms. Opioid analgesics were prescribed to approximately 45% of patients with SFN. When compared to 98 patients without SFN, the 23 patients with SFN had an increased frequency of male sex (30% versus 9%; P < 0.01), a decreased frequency of anti-Ro 52 (P = 0.01) and anti-Ro 60 antibodies (P = 0.01), rheumatoid factor positivity (P < 0.01), and polyclonal gammopathy (P < 0.01). Eleven patients had stocking-and-glove pain, and 12 patients had nonstocking-and-glove pain. Skin biopsy results disclosed patterns of axonal (16 patients) and DRG injury (7 patients). CONCLUSION: SS SFN had an increased frequency among male patients, a decreased frequency of multiple antibodies, frequent treatment with opioid analgesics, and the presence of nonstocking-and-glove pain. Distinguishing between DRG versus axonal injury is significant, especially given that mechanisms targeting the DRG may result in irreversible neuronal cell death. Altogether, these findings highlight clinical, autoantibody, and pathologic features that can help to define mechanisms and treatment strategies.

Small-Fiber-Neuropathien.

Small fiber neuropathies (SFN) comprise a clinical syndrome typically associated with acral burning pain, where the pathophysiological processes affect the thinly myelinated A-delta and the unmyelinated C nerve fibers. Neurological examination thus reveals merely thermal sensory deficits. Nerve conduction studies in SFN are normal to marginally abnormal. To underpin suspicion of SFN, special psychophysical and neurophysiological examinations or a skin punch biopsy are needed. The search for the etiology of SFN is crucial and most frequently reveals diabetes mellitus or impaired glucose tolerance. Mutations in genes encoding voltage-gated sodium channels and other genetic alterations are being increasingly reported. Treatment depends on the underlying disease and follows the guidelines on the treatment of neuropathic pain.

Facts and myths pertaining to fibromyalgia.

Fibromyalgia (FM) is characterized by chronic widespread pain, unrefreshing sleep, physical exhaustion, and cognitive difficulties. It occurs in all populations throughout the world, with prevalence between 2% and 4% in general populations. Definition, pathogenesis, diagnosis, and treatment of FM remain points of contention, with some even contesting its existence. The various classification systems according to pain medicine, psychiatry, and neurology (pain disease; persistent somatoform pain disorder; masked depression; somatic symptom disorder; small fiber neuropathy; brain disease) mostly capture only some components of this complex and heterogeneous disorder. The diagnosis can be established in most cases by a general practitioner when the symptoms meet recognized criteria and a somatic disease sufficiently explaining the symptoms is excluded. Evidence-based interdisciplinary guidelines give a strong recommendation for aerobic exercise and cognitive behavioral therapies. Drug therapy is not mandatory. Only a minority of patients experience substantial symptom relief with duloxetine, milnacipran, and pregabalin.

La fibromialgia (FM) se caracteriza por dolor crónico generalizado, sueño no reparador, agotamiento físico y dificultades cognitivas. Ella se presenta en todas las poblaciones a través del mundo, con una prevalencia entre el 2% y el 4% en la población general. La definición, la patogénesis, el diagnóstico y el tratamiento de la FM constituyen puntos de discusión, con algunos autores que incluso dudan de su existencia. Los diversos sistemas de clasificación de acuerdo con la medicina, la psiquiatría y la neurología del dolor (patología dolorosa, trastorno de dolor somatomorfo persistente, depresión enmascarada, trastorno de síntoma somático, neuropatía de fibra pequeña, enfermedad cerebral) en su mayoría incorporan sólo algunos componentes de este complejo y heterogéneo trastorno. En la mayoría de los casos un médico general puede establecer el diagnóstico, cuando los síntomas reúnen criterios reconocidos y se excluye una enfermedad somática que pueda explicar suficientemente dichos síntomas. Las guías interdisciplinarias basadas en la evidencia entregan una sólida recomendación respecto al ejercicio aeróbico y las terapias cognitivo conductuales. La terapia farmacológica no es obligatoria. Sólo una minoría de los pacientes presenta un alivio sintomático significativo con duloxetina, milnacipran y pregabalina.

La fibromyalgie (FM) se caractérise par des douleurs chroniques généralisées, un sommeil non réparateur, un épuisement physique et des difficultés cognitives. Elle survient dans toutes les populations du monde, avec une prévalence entre 2 % et 4 % de la population générale. La définition, la pathogenèse, le diagnostic et le traitement de la FM restent un point de discorde, quelques-uns contestant même son existence. Les systèmes de classification variés selon la médecine, la psychiatrie et la neurologie de la douleur, (pathologie douloureuse ; trouble douloureux somatoforme persistant ; dépression masquée ; trouble à symptomatologie somatique ; neuropathie des petites fibres ; maladie cérébrale) n'appréhendent principalement que quelques composantes de ce trouble complexe et hétérogène. Le diagnostic peut être établi dans la plupart des cas par un généraliste quand les symptômes rencontrés remplissent les critères et quand une maladie somatique capable d'expliquer les symptômes est exclue. Des recommandations interdisciplinaires fondées sur des éléments probants recommandent fortement les exercices aérobiques et les thérapies cognitivo-comportementales. Le traitement médicamenteux n'est pas obligatoire. Seule une minorité de patients sont soulagés par la duloxétine, le milnacipran et la prégabaline.

[Small fiber neuropathy]. / La neuropathie des petites fibres.

Small fiber neuropathy (SFN) is still unknown. Characterised by neuropathic pain, it typically begins by burning feet, but could take many other expression. SFN affects the thinly myelinated Aδ and unmyelinated C-fibers, by an inherited or acquired mechanism, which could lead to paresthesia, thermoalgic disorder or autonomic dysfunction. Recent studies suggest the preponderant role of ion channels such as Nav1.7. Furthermore, erythromelalgia or burning mouth syndrome are now recognized as real SFN. Various aetiologies of SFN are described. It could be isolated or associated with diabetes, impaired glucose metabolism, vitamin deficiency, alcohol, auto-immune disease, sarcoidosis etc. Several mutations have recently been identified, like Nav1.7 channel leading to channelopathies. Diagnostic management is based primarily on clinical examination and demonstration of small fiber dysfunction. Laser evoked potentials, Sudoscan®, cutaneous biopsy are the main test, but had a difficult access. Treatment is based on multidisciplinary management, combining symptomatic treatment, psychological management and treatment of an associated etiology.

Small fibre neuropathy.

PURPOSE OF REVIEW: To provide a review on the state-of-art of clinical features, diagnostics, genetics and treatments of small fibre neuropathy (SFN). RECENT FINDINGS: The spectrum of clinical features has been widened from the classical presentation of burning feet as length-dependent SFN to that of small fibre dysfunction and/or degeneration associated with focal, diffuse and episodic neuropathic pain syndromes. The involvement of small nerve fibres in neurodegenerative diseases has been further defined, challenging the relationship between neuropathic pain symptoms and small fibre loss. The clinical reliability of skin biopsy has been strengthened by the availability of normative values for both the immunohistochemistry techniques used and their comparison, and by side and short-term follow-up analyses. Corneal confocal microscopy has implemented its diagnostic potentiality because of the availability of age-adjusted and sex-adjusted normative values. Genetic studies expanded the panel on genes involved in SFN because of the discovery of new mutations in SCN10A and SCN11A, besides the first found in SCN9A, and identification of mutations in COL6A5 in patients with itching. SUMMARY: In the last 5 years, the chapter of SFN has been widened by new clinical and genetics descriptions leading to a more comprehensive approach to patients in clinical practice and research.

Small fiber neuropathy: a disabling and underrecognized syndrome.

PURPOSE OF REVIEW: To discuss cause, clinical manifestations, diagnostics, and treatment of small fiber neuropathy (SFN). The diagnosis is difficult and can be easily missed. RECENT FINDINGS: SFN causes high morbidity with disabling symptoms and impact on quality of life. Patients may benefit from being diagnosed with SFN, even if no underlying cause is identified and no specific treatment is yet available. Recently, genetic mutations as a possible cause of SFN were identified. Clinical diagnostic criteria have been proposed, but no gold standard exists, and each test has its limitations. The diagnosis requires a combination of typical symptoms, abnormal neurologic findings, and absence of large fiber involvement. Clinicians should be aware of overlapping symptoms of SFN and fibromyalgia. Treatment is often difficult, even when the underlying cause is identified and appropriately treated. Usually, only symptomatic relief of complaints is available. SUMMARY: Awareness of SFN and related symptoms is of great clinical relevance. Guidelines for appropriate diagnostic workup using a stepwise approach involving a combination of tests are warranted. Even if no treatment is available, patients may benefit from timely recognition of SFN.

Efficacious Dorsal Root Ganglion Stimulation for Painful Small Fiber Neuropathy: A Case Report.

Small fiber neuropathy is a disorder of the peripheral nerves with typical symptoms of burning, sharp, and shooting pain and sensory disturbances in the feet. Pain treatment depends principally on the underlying etiology with concurrent administration of antidepressants, anticonvulsants, opioids, and topical treatments like capsaicin and local anesthetics. However, treatments for pain relief in these patients frequently fail. We describe the first case of intractable painful small fiber neuropathy of the foot successfully treated with spinal cord stimulation of the left L5 dorsal root ganglion.A 74-year-old man presented at our clinic with severe intractable pain, dysesthesia, and allodynia of the left foot caused by idiopathic small fiber neuropathy, confirmed by skin biopsy. His pain score was 8 on a standard 0 - 10 numeric rating scale. As the pain was not satisfactorily controlled by conventional therapy, dorsal root ganglion stimulation was proposed to the patient and, after informed consent, a specifically designed percutaneous stimulation lead was placed over the left L5 dorsal root ganglion and connected to an external neurostimulator. After a positive trial of 10 days, a permanent neurostimulator was implanted. Twenty months post-implantation the patient continued to experience stimulation-induced paresthesia covering the entire pain area and reported a pain rating of 4.Results from the case report demonstrate that the dorsal root ganglion is a promising neural stimulation target to treat neuropathic pain due to intractable small fiber neuropathy. Prospective controlled studies are warranted to confirm the efficacy of this treatment as an option for the aforementioned condition.Key words: Dorsal root ganglion stimulation, small fiber neuropathy, neuropathic pain.

Small Fiber Neuropathy in Children: Two Case Reports Illustrating the Importance of Recognition.

Small fiber neuropathy (SFN) is a debilitating condition that often leads to pain and autonomic dysfunction. In the last few decades, SFN has been gaining more attention, particularly in adults. However, literature about SFN in children remains limited. The present article reports the cases of 2 adolescent girls diagnosed with SFN. The first patient (14 years of age) complained about painful itch and tingling in her legs, as well as dysautonomia symptoms for years. She also reported a red/purple-type discoloration of her legs aggravated by warmth and standing, compatible with erythromelalgia. The diagnosis of SFN was confirmed by a reduced intraepidermal nerve fiber density (IENFD) in skin biopsy sample. No underlying conditions were found. Symptomatic neuropathic pain treatment was started with moderate effect. The second patient (16 years of age) developed painful sensations in both feet and hands 6 weeks after an ICU admission for diabetic ketoacidosis, which included dysautonomia symptoms. She also exhibited some signs of erythromelalgia. The patient was diagnosed with predominant SFN (abnormal IENFD and quantitative sensory testing) as well as minor large nerve fiber involvement. Treatment with duloxetine, combined with a rehabilitation program, resulted in a marked improvement in her daily functioning. Although the SFN diagnosis in these 2 cases could be established according to the definition of SFN used in adults, additional diagnostic tools are needed that may be more appropriate for children. Additional information about the course of SFN in children may result in better treatment options.