[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.

A reappraisal of small- and large-fiber damage in carpal tunnel syndrome: New insights into the value of the EMLA test for improving diagnostic sensitivity.

OBJECTIVES: To reappraise the respective involvement of small- and large-fiber damage in carpal tunnel syndrome (CTS) and to determine the diagnostic sensitivity of autonomic tests compared to conventional nerve conduction study (NCS). METHODS: Thirty-two manual workers complaining of at least unilateral CTS were enrolled. They underwent clinical interview and completed the symptom severity scale of the Boston CTS Questionnaire (sssBCTQ) and the Neuropathic Pain Symptom Inventory (NPSI). In addition, transcarpal NCS was performed to investigate large sensory and motor fibers of the median nerve, while small autonomic fibers were assessed by recording sympathetic skin reflexes (SSR) at the palm and by grading skin wrinkling in response to eutectic mixture of local anesthetic (EMLA) cream application at the pulp of the index finger. For each neurophysiological variable, sensitivity and specificity values for the diagnosis of CTS were calculated and clinical correlations were studied. RESULTS: Among 64 hands examined, 36 were clinically symptomatic, while 22 were clinically asymptomatic and served as controls. Among all the neurophysiological variables studied, only the values of transcarpal sensory nerve conduction velocity and the EMLA test grade were found to be more altered in clinically symptomatic hands, with also a trend towards prolonged distal motor latency. Overall, for the diagnosis of clinically symptomatic CTS, NCS, SSR, and the EMLA test had a sensitivity of 66.7%, 22.2%, and 69.4%, respectively, and a specificity of 72.7%, 90.9%, and 50%, respectively. Combining NCS and the EMLA test led to a sensitivity of 88.9% and a specificity of 45.4%. The sssBCTQ (r=-0.34, P=0.009) and the total NPSI score (r=-0.41, P=0.001) correlated to a more altered EMLA test grade, but not to any NCS or SSR variables. In symptomatic hands, burning sensation was associated with more severe small-fiber lesion, while other pain and sensory symptoms were rather found to be reduced in case of large-fiber damage, evidenced by NCS alteration. CONCLUSIONS: This study confirms the discrepancy between conventional NCS results and clinical presentation of CTS, but still suggests a major involvement of Aß fibers in the positive sensory symptoms of CTS, excepting burning sensation. On the other hand, the EMLA test was found to correlate with clinical data and to be able to improve sensitivity of neurophysiological investigation in diagnosing CTS.

Peripheral nerve involvement in Fabry's disease: Which investigations? A case series and review of the literature.

BACKGROUND: Peripheral nerve system (PNS) involvement is common in Fabry's disease (FD), predominantly affecting the small nerve fibers that are difficult to investigate with conventional electrophysiological methods. PATIENTS AND METHODS: Eighteen patients followed for Fabry's disease underwent a prospective series of electroneurophysiological explorations, including a study of the cardiac parasympathetic autonomic nervous system (ANS) and electrochemical skin conductance (ESC) tests. Data were compared with those obtained in 18 matched healthy controls. RESULTS: All patients had at least one clinical sign suggestive of neuropathy: 16 reported an acrosyndrome and 12 had dyshidrosis. Cold hypoesthesia was found in 15 patients and heat hypoesthesia in 13. Electroneurophysiological investigations and study of the cardiac parasympathetic ANS were normal in all patients. The ESC was significantly lower in FD patients compared with controls. CONCLUSION: PNS involvement is common in FD and should be suspected in patients exhibiting an acrosyndrome, dyshidrosis and/or cold hypoesthesia. Conventional electrophysiological investigations are normal. New techniques, such as ESC, provide early diagnosis of small fiber involvement that currently requires more sophisticated tests difficult to apply in routine practice.

Measurement of electrochemical conductance of penile skin using Sudoscan®: A new tool to assess neurogenic impotence.

OBJECTIVES: To investigate the value of electrochemical skin conductance (ESC) measurement at penile level using Sudoscan® for the diagnosis of neurogenic impotence in diabetics. METHODS: The following neurophysiological parameters were assessed in 25 male diabetics who complained of impotence and 25 age-matched normal male subjects without erectile dysfunction (age range: 29-70 years): ESC, sympathetic skin responses (SSR), warm detection thresholds (WDT), and cold detection thresholds (CDT) for the penis and the feet, vibration detection thresholds (VDT) for the penis, and sensory nerve conduction study of the dorsal nerve of the penis (DNP) with sensory nerve action potential (SNAP) recording. RESULTS: Diabetic patients with impotence differed from controls with regard to most neurophysiological results at both penile and foot levels. Among penile innervation variables in the group of impotent diabetics, penile ESC was found to be the most frequently abnormal (80% of patients), followed by penile WDT, CDT, and DNP-SNAP amplitude (52% of patients), and then penile SSR amplitude and VDT (44% of patients). Various combinations of abnormalities were observed: penile ESC was the only abnormal test in 2 patients, while all tests were abnormal in 2 patients and remained normal in only one patient. CONCLUSION: Erectile dysfunction is common in diabetic men, but the diagnosis of a neurogenic origin is challenging. This study showed that ESC measurement using Sudoscan® is feasible and more sensitive than SSR recordings to show penile sympathetic innervation impairment. This new test should be further studied to better define its diagnostic accuracy and clinical correlates.

Diagnosis of small fiber neuropathy: A comparative study of five neurophysiological tests.

The diagnosis of small fiber neuropathy (SFN) is a challenge for clinical neurophysiology. Conventional nerve conduction studies are inappropriate for this purpose and therefore various neurophysiological tests have been proposed. In this study, we compared the diagnostic value of five of these tests in 87 patients with clinically definite (n=33) or possible (n=54) SFN related to amyloid neuropathy secondary to transthyretin gene mutation or monoclonal gammopathy (n=30), primary Sjögren's syndrome (n=20), Fabry's disease (n=2), or unknown cause (n=35). Neurophysiological tests included quantitative sensory testing with determination of warm and cold detection thresholds (WDT, CDT), recording of laser-evoked potentials (LEP) and sympathetic skin responses (SSRs), and measurement of electrochemical skin conductance (ESC) using Sudoscan(®) device. All tests were performed at the four extremities (hands and feet). All patients with clinically definite SFN and 70% of the patients with possible SFN had at least one abnormal test. The LEP was the most sensitive test (altered in 79% of the patients with at least one abnormal test), followed by ESC (61%), WDT (55%), SSR (41%), and CDT (32%). The combination of LEP, assessing A-delta sensory fibers, WDT, assessing sensory C fibers, and ESC, assessing autonomic C fibers, appears a relevant approach for the diagnosis of SFN. Compared to SSR and CDT, these three tests, LEP, WDT, and ESC, had a significantly better diagnostic sensitivity and their combination further improved diagnostic accuracy.

[What's new in clinical dermatology?]. / Quoi de neuf en dermatologie clinique?

Significant advances have been performed in cutaneous adverse reactions leading to primary prevention strategy and implication of new signaling pathways. Histological features of DRESS and methotrexate toxicity are detailed. New emerging infectious agents are reported including Zika Virus, an arbovirus which can be confused with dengue or chikungunya, a new cowpox virus transmitted by domestic cat leading to lymphadenitis, Spirurina type X larva transmitted in Japan by eating raw squid or fish. Malignancies in pemphigus and pemphigoid are emphasized. Expert recommandations are developped on definitions, diagnosis and disease activity of mucous membrane pemphigoid, bubllous pemphigoid and pemphigus. Psoriasis and cardiometabolic association are discussed. This risk association appears higher in hidradenitis suppurativa, which seems more frequent in patients of African ancestry. IgG4-related disease is an immune mediated entity characterized by fibroinflammatory lesions often misdiagnosed. Pruritus, heat sensations, numbness could be recognized as a small-fiber neuropathy symptoms. Burden impact in common dermatosis is demonstrated and should be integrated in our daily practice.

[Normal skin biopsy as a tool for extra-cutaneous disorders]. / Indications extra-cutanées de la biopsie de peau normale.

Biopsies of apparently healthy skin can contribute to the diagnosis of an internal disorder in a patient or in the detection of a potential disease carrier. Herein, we review those diseases for which dermatologists may be asked to perform a biopsy on normal skin where analysis by optical microscopy, immunofluorescence or electronic microscopy may result in diagnosis of an "internal" disease. Diseases for which biopsies are required for cell cultures (e.g. fibroblasts cultures), clonality testing or chromosomal analysis are not discussed here.