Comment
A wide range of skin manifestations have been associated with fibromyalgia, but the exact mechanisms remain unclear. Nevertheless, it is conceivable that autonomic nervous system dysfunction,28-31 amplified cutaneous opioid receptor activity,32 and an elevated presence of cutaneous mast cells with excessive degranulation may partially explain the frequent occurrence of pruritus and related skin disorders such as neurotic excoriations, prurigo nodularis, and LSC in individuals with fibromyalgia.15,16 In line with these findings, our study—which was based on data from the largest health maintenance organization in Israel—demonstrated an increased prevalence of pruritus and related pruritic disorders among individuals diagnosed with fibromyalgia.
This cross-sectional study links pruritus with fibromyalgia. Few preliminary epidemiologic studies have shown an increased occurrence of cutaneous manifestations in patients with fibromyalgia. One chart review that looked at skin findings in patients with fibromyalgia revealed 32 distinct cutaneous manifestations, and pruritus was the major concern in 3.3% of 845 patients.15
A focused cross-sectional study involving only women (66 with fibromyalgia and 79 healthy controls) discovered 14 skin conditions that were more common in those with fibromyalgia. Notably, xerosis and neurotic excoriations were more prevalent compared to the control group.16
The brain and the skin—both derivatives of the embryonic ectoderm33,34—are linked by pruritus. Although itch has its dedicated neurons, there is a wide-ranging overlap of brain-activated areas between pain and itch,6 and the neural anatomy of pain and itch are closely related in both the peripheral and central nervous systems35-37; for example, diseases of the central nervous system are accompanied by pruritus in as many as 15% of cases, while postherpetic neuralgia can result in chronic pain, itching, or a combination of both.38,39 Other instances include notalgia paresthetica and brachioradial pruritus.38 Additionally, there is a noteworthy psychologic impact associated with both itch and pain,40,41 with both psychosomatic and psychologic factors implicated in chronic pruritus and in fibromyalgia.42 Lastly, the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system are altered in both fibromyalgia and pruritus.43-45
Tey et al45 characterized the itch experienced in fibromyalgia as functional, which is described as pruritus associated with a somatoform disorder. In our study, we found a higher prevalence of pruritus among patients with fibromyalgia, and this association remained significant (P<.05) even when excluding other pruritic skin conditions and systemic diseases that can trigger itching. In addition, our logistic regression analyses revealed independent associations between fibromyalgia and pruritus, prurigo nodularis, and LSC.
According to Twycross et al,46 there are 4 clinical categories of itch, which may coexist7: pruritoceptive (originating in the skin), neuropathic (originating in pathology located along the afferent pathway), neurogenic (central origin but lacks a neural pathology), and psychogenic.47 Skin biopsy findings in patients with fibromyalgia include increased mast cell counts11 and degranulation,48 increased expression of δ and κ opioid receptors,32 vasoconstriction within tender points,49 and elevated IL-1β, IL-6, or tumor necrosis factor α by reverse transcriptase-polymerase chain reaction.12 A case recently was presented by Görg et al50 involving a female patient with fibromyalgia who had been experiencing chronic pruritus, which the authors attributed to small-fiber neuropathy based on evidence from a skin biopsy indicating a reduced number of intraepidermal nerves and the fact that the itching originated around tender points. Altogether, the observed alterations may work together to make patients with fibromyalgia more susceptible to various skin-related comorbidities in general, especially those related to pruritus. Eventually, it might be the case that several itch categories and related pathomechanisms are involved in the pruritus phenotype of patients with fibromyalgia.
Age-related alterations in nerve fibers, lower immune function, xerosis, polypharmacy, and increased frequency of systemic diseases with age are just a few of the factors that may predispose older individuals to pruritus.51,52 Indeed, our logistic regression model showed that age was significantly and independently associated with pruritus (P<.001), neurotic excoriations (P=.046), and LSC (P=.006). Female sex also was significantly linked with pruritus (P=.039). Intriguingly, high socioeconomic status was significantly associated with the diagnosis of pruritus (P=.002), possibly due to easier access to medical care.
There is a considerable overlap between the therapeutic approaches used in pruritus, pruritus-related skin disorders, and fibromyalgia. Antidepressants, anxiolytics, analgesics, and antiepileptics have been used to address both conditions.45 The association between these conditions advocates for a multidisciplinary approach in patients with fibromyalgia and potentially supports the rationale for unified therapeutics for both conditions.