Hlubocky Ales, Wellik Kay, Ross Mark A, Smith Benn E, Hoffman-Snyder Charlene, Demaerschalk Bart M, Wingerchuk Dean M
Department of Neurology, Mayo Clinic College of Medicine, Scottsdale, AZ 85259, USA.
Neurologist. 2010 Jan;16(1):61-3. doi: 10.1097/NRL.0b013e3181c9c303.
Patients with lower extremity sensory symptoms and pain but without clinical or standard neurophysiological examination abnormalities may have a small fiber neuropathy. Skin biopsy with intraepidermal nerve fiber density (IENFD) assessment has been promoted as a diagnostic tool for such patients.
To evaluate the diagnostic utility of skin biopsy with IENFD in patients with suspected small fiber neuropathy.
The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario, structured question, search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of neuromuscular neurology.
One primary article was selected for review. A retrospective study using skin biopsy with IENFD detected abnormalities in 88.1% of 67 patients who had symptoms suggestive of sensory neuropathy but normal nerve conduction studies compared with 10% of healthy controls. Skin biopsy was more often abnormal in this setting than either the clinical examination (signs of small fiber impairment) or quantitative sensory testing but formal evaluation of sensitivity and specificity are compromised by inclusion of the diagnostic tests within the definition of the reference standard. Skin biopsy with IENFD was abnormal in 81% of patients clinically diagnosed with mixed large and small fiber neuropathy, 0/22 patients with large fiber neuropathy and 0/16 patients with nonperipheral neuropathic disorders.
Detection of reduced IENFD using skin biopsy may be sensitive and specific for clinically-defined syndromes consistent with small fiber neuropathy. Skin biopsy appears to have greater diagnostic utility than the neurologic examination and quantitative sensory testing, both of which rely heavily on subjective patient perception. Prospective studies that evaluate quantitative methodology (rather than modalities that rely on patient report) and do not include the diagnostic tests in the reference standard are needed. Consensus is needed regarding a reference standard definition for small fiber neuropathy.
下肢有感觉症状和疼痛但临床或标准神经生理学检查无异常的患者可能患有小纤维神经病变。表皮内神经纤维密度（IENFD）评估的皮肤活检已被推荐作为此类患者的诊断工具。
评估IENFD皮肤活检在疑似小纤维神经病变患者中的诊断效用。
通过制定结构化的严格评价主题来实现该目标。这包括临床病例、结构化问题、检索策略、严格评价、结果、证据总结、评论和最终结论。参与者包括顾问和住院神经科医生、医学图书馆员、临床流行病学家以及神经肌肉神经病学领域的内容专家。
选择了一篇主要文章进行综述。一项使用IENFD皮肤活检的回顾性研究发现，67例有感觉神经病变症状但神经传导检查正常的患者中，88.1%存在异常，而健康对照组中这一比例为10%。在这种情况下，皮肤活检比临床检查（小纤维损伤体征）或定量感觉测试更常出现异常，但由于在参考标准定义中纳入了诊断测试，敏感性和特异性的正式评估受到影响。在临床诊断为混合性大纤维和小纤维神经病变的患者中，81%的患者IENFD皮肤活检异常，22例大纤维神经病变患者中0例异常，16例非周围神经病变患者中0例异常。
使用皮肤活检检测IENFD降低对于临床定义的与小纤维神经病变一致的综合征可能具有敏感性和特异性。皮肤活检似乎比神经学检查和定量感觉测试具有更大的诊断效用，后两者都严重依赖患者的主观感受。需要进行前瞻性研究来评估定量方法（而不是依赖患者报告的方式），并且在参考标准中不包括诊断测试。需要就小纤维神经病变的参考标准定义达成共识。
