Small Fiber Neuropathy for the Rheumatologist

Skin biopsy should be avoided when the source of neuropathy is already clear, such as in a mixed fiber neuropathy or when there are symptoms beyond those attributable to small fiber neuropathy, such as loss of deep tendon reflexes or weakness.³

Management

Management of small fiber neuropathy focuses on symptomatic control of neuropathic pain, primarily with antidepressants, anti-epileptics and sometimes opiates. “Among antidepressants, tricyclic and [serotonin and norepinephrine reuptake inhibitors] have demonstrated efficacy while [selective serotonin reuptake inhibitors] have not,” says Dr. Polydefkis. “Among antiepileptics, gabapentin and pregabalin are generally preferred over carbamazepine, lamotrigine or phenytoin, which have shown efficacy but require monitoring or have high rates of adverse events. Tramadol can be helpful in patients who tolerate sporadic treatment. The agent or combination of agents selected is based on a patient’s concomitant medical issues.”

Intravenous immunoglobulin (IVIG) “is not an accepted symptomatic treatment for small fiber neuropathy,” he says, but it may be used in rheumatic conditions associated with small fiber neuropathy. In a double-blind, randomized controlled study of patients with idiopathic small fiber neuropathy, Geerts et al. demonstrated no clinically relevant benefit of IVIG, which was not only expensive, but had risk of adverse events.⁶ However, case reports and small series have demonstrated success with IVIG in Sjögren’s disease-related small fiber neuropathy.⁷

In Sum

Rheumatologists should be familiar with small fiber neuropathy, particularly in patients with underlying Sjögren’s disease. Definitive diagnosis requires a cutaneous nerve biopsy. Management primarily involves relieving neuropathic pain through various medications, with an approach tailored to the patient. Data on the role of immunosuppression in small fiber neuropathy are limited.

Michael Cammarata, MD, is a second-year rheumatology fellow at Johns Hopkins University School of Medicine, Baltimore.

References

1. Seeliger T, Dreyer HN, Siemer JM, et al. Clinical and paraclinical features of small fiber neuropathy in Sjögren’s syndrome. J Neurol. 2023 Feb;270(2):1004–1010.
2. Terkelsen AJ, Karlsson P, Lauria G, et al. The diagnostic challenge of small fibre neuropathy: Clinical presentations, evaluations, and causes [published correction appears in Lancet Neurol. 2017 Dec;16(12):954]. Lancet Neurol. 2017 Nov;16(11):934–944.
3. Saperstein DS. Small fiber neuropathy. Neurol Clin. 2020 Aug;38(3):607–618.
4. McCoy SS, Baer AN. Neurological complications of Sjögren’s syndrome: Diagnosis and management. Curr Treatm Opt Rheumatol. 2017 Dec;3(4):275–288.
5. Bailly F. The challenge of differentiating fibromyalgia from small-fiber neuropathy in clinical practice. Joint Bone Spine. 2021 Dec;88(6):105232.
6. Gibbons CH, Klein C. IVIG and small fiber neuropathy: The ongoing search for evidence. Neurology. 2021 May 18;96(20):929–930.
7. Rist S, Sellam J, Hachulla E, et al. Experience of intravenous immunoglobulin therapy in neuropathy associated with primary Sjögren’s syndrome: A national multicentric retrospective study. Arthritis Care Res (Hoboken). 2011 Sep;63(9):1339–1344.