Small-fiber neuropathy (SFN) in sarcoidosis; treatment via TNF-alpha, role of palmitoylethanolamide

Sarcoidosis is a chronic inflammatory illness and small-fiber neuropathy (SFN) is one of the disabling and often chronic manifestations of the disease. SFN presents with peripheral pain and symptoms of autonomic dysfunction. The character of the pain can be burning or shooting. Besides, allodynia and hyperesthesia can exist.

Symptoms small fibre neuropathy

Symptoms small fibre neuropathy

Diagnosis is usually made on the basis of clinical features, in combination with abnormal specialized tests. The aim of treatment is often to reduce pain; however, total pain relieve is seldom achieved. The role of TNF-α in the pathogenesis of SFN in sarcoidosis appears interesting to explore.

Palmitoylethanolamide is known to reduce TNF-alpha’s negative effects and is an analgesic. It might be a good therapeutic option in small fibre neuropathy (in sarcoidosis).

Small-fiber neuropathy (SFN) is a peripheral nerve disorder that selectively affects thinly myelinated Aδfibers and unmyelinated C fibers. Small nerve fibers are involved in both somatic and autonomic function. As a result, patients with SFN may present with symptoms of neuropathic pain (NP) and autonomic dysfunction.

Damage to or loss of small somatic nerve fibers results in burning pain, tingling, or numbness that typically affects the limbs in a distal to proximal gradient. Symptoms are usually worse at night and often affect sleep. People sometimes sleep with the feet uncovered because they can not bear the touch of the sheets. Besides, walking may be difficult due to pain by the pressure on the floor. When autonomic fibers are affected, patients may experience dry eyes, dry mouth, orthostatic dizziness, constipation, bladder incontinence, sexual dysfunction, hyperhidrosis or hypohidrosis, or red or white skin discoloration. Finally restless legs syndrome may be present, characterized by disagreeable leg sensations that usually occur prior to sleep onset and cause an almost irresistible urge to move.

Most patients suffer from length-dependent small-fiber neuropathy (LD-SFSN): symptoms and signs start to develop in the toes and feet, symptoms gradually progress to involve distal legs, fingertips, and hands. Non-length-dependent small-fiber neuropathy (NLD-SFSN) is not as common as LD-SFSN and patients develop complaints in a patchy distribution. This can include face, upper limbs, or trunk before the lower limbs are affected. The NLD-SFSN is more seen in women and presents at a younger age.

TNF-alpha and SFN

The pathogenetic role of oxidative stress, inflammatory cytokines such as TNF-α, and neuropeptides such as substance P (SP) are interesting to explore as a common final pathway in SFN in several immune-mediated inflammatory diseases. We described a patient with severe SFN who showed spectacular improvement after treatment with anti-TNF-α therapy [20]. This case supports the idea that TNF-α may be a crucial cytokine in the pathogenesis of SFN related to sarcoidosis and presumably in SFN related to other immune-mediated inflammatory diseases as well. Theoretical support for the effect of anti-TNF-α therapy on SFN may be found in the following. First, TNF-α plays an important role in immune-mediated neuropathies such as Guillain-Barré syndrome, in which small nerve fibers are also involved. Elevated serum concentration of TNF-α shows a positive correlation with neuropathy severity in patients with Guillain-Barré syndrome. Furthermore, the decrease in serum TNF-α and increase in serum soluble TNF receptors show a positive correlation with neuropathy recovery in those patients. Second, pharmacological and physiological studies report that proinflammatory cytokines such as TNF-α are strongly involved in the generation and maintenance of neuropathic pain.

Usual treatments in sarcoidosis such as prednisone and methotrexate do not appear beneficial in sarcoidosis-related SFN (personal experience). SFN is disabling for patients and the pain is often difficult to treat.

As the role of TNF-α in the pathogenesis of SFN in sarcoidosis appears interesting to explore, anti-TNF therapy might be beneficial in the treatment of SFN in sarcoidosis. A recent therapeutic development has been the availability of agents that directly inactivate the proinflammatory cytokine TNF-α. Those are expensive drugs with possible severe side effects including opportunistic infection. The remarkable distinction is palmitoylethanolamide, which is available as a food supplement and does not cost much.

Therefore palmitoylethanolamide should be considered, in a dose up to 30 mg / kg bodyweight.

Based on:

Pain Research and Treatment
Volume 2012 (2012), Article ID 256024, 6 pages
Review Article: Sarcoidosis and Pain Caused by Small-Fiber Neuropathy, by
Lara Heij, Albert Dahan,1 and Elske Hoitsma

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