Methods
Study Design and Setting—We conducted a cross-sectional retrospective study using data-mining techniques to access information from the Clalit Health Services (CHS) database. Clalit Health Services is the largest health maintenance organization in Israel. It encompasses an extensive database with continuous real-time input from medical, administrative, and pharmaceutical computerized operating systems, which helps facilitate data collection for epidemiologic studies. A chronic disease register is gathered from these data sources and continuously updated and validated through logistic checks. The current study was approved by the institutional review board of the CHS (approval #0212-17-com2). Informed consent was not required because the data were de-identified and this was a noninterventional observational study.
Study Population and Covariates—Medical records of CHS enrollees were screened for the diagnosis of fibromyalgia, and data on prevalent cases of fibromyalgia were retrieved. The diagnosis of fibromyalgia was based on the documentation of a fibromyalgia-specific diagnostic code registered by a board-certified rheumatologist. A control group of individuals without fibromyalgia was selected through 1:2 matching based on age, sex, and primary care clinic. The control group was randomly selected from the list of CHS members frequency-matched to cases, excluding case patients with fibromyalgia. Age matching was grounded on the exact year of birth (1-year strata).
Other covariates in the analysis included pruritus-related skin disorders, including prurigo nodularis, neurotic excoriations, and LSC. There were 3 socioeconomic status categories according to patients' poverty index: low, intermediate, and high.26
Statistical Analysis—The distribution of sociodemographic and clinical features was compared between patients with fibromyalgia and controls using the χ2 test for sex and socioeconomic status and the t test for age. Conditional logistic regression then was used to calculate adjusted odds ratio (OR) and 95% CI to compare patients with fibromyalgia and controls with respect to the presence of pruritic comorbidities. All statistical analyses were performed using SPSS software (version 26). P<.05 was considered statistically significant in all tests.
Results
Our study population comprised 4971 patients with fibromyalgia and 9896 age- and sex-matched controls. Proportional to the reported female predominance among patients with fibromyalgia,27 4479 (90.1%) patients with fibromyalgia were females and a similar proportion was documented among controls (P=.99). There was a slightly higher proportion of unmarried patients among those with fibromyalgia compared with controls (41.9% vs 39.4%; P=.004). Socioeconomic status was matched between patients and controls (P=.99). Descriptive characteristics of the study population are presented in Table 1.
We assessed the presence of pruritus as well as 3 other pruritus-related skin disorders—prurigo nodularis, neurotic excoriations, and LSC—among patients with fibromyalgia and controls. Logistic regression was used to evaluate the independent association between fibromyalgia and pruritus. Table 2 presents the results of multivariate logistic regression models and summarizes the adjusted ORs for pruritic conditions in patients with fibromyalgia and different demographic features across the entire study sample. Fibromyalgia demonstrated strong independent associations with pruritus (OR, 1.8; 95% CI, 1.8-2.4; P<.001), prurigo nodularis (OR, 2.9; 95% CI, 1.1-8.4; P=.038), and LSC (OR, 1.5; 95% CI, 1.1-2.1; P=.01); the association with neurotic excoriations was not significant. Female sex significantly increased the risk for pruritus (OR 1.3; 95% CI, 1.0-1.6; P=.039), while age slightly increased the odds for pruritus (OR, 1.0; 95% CI, 1.0-1.04; P<.001), neurotic excoriations (OR, 1.0; 95% CI, 1.0-1.1; P=.046), and LSC (OR, 1.0; 95% CI, 1.01-1.04; P=.006). Finally, socioeconomic status was inversely correlated with pruritus (OR, 1.1; 95% CI, 1.1-1.5; P=.002).
Frequencies and ORs for the association between fibromyalgia and pruritus with associated pruritic disorders stratified by exclusion of pruritic dermatologic and/or systemic diseases that may induce itch are presented in the eTable. Analyzing the entire study cohort, significant increases were observed in the odds of all 4 pruritic disorders analyzed. The frequency of pruritus was almost double in patients with fibromyalgia compared with controls (11.7% vs 6.0%; OR, 2.1; 95% CI, 1.8-2.3; P<.0001). Prurigo nodularis (0.2% vs 0.1%; OR, 2.9; 95% CI, 1.1-8.4; P=.05), neurotic excoriations (0.6% vs 0.3%; OR, 1.9; 95% CI, 1.1-3.1; P=.018), and LSC (1.3% vs 0.8%; OR, 1.5; 95% CI, 1.1-2.1; P=.01) frequencies were all higher in patients with fibromyalgia than controls. When primary skin disorders that may cause itch (eg, pemphigus vulgaris, Darier disease, dermatitis, eczema, ichthyosis, psoriasis, parapsoriasis, urticaria, xerosis, atopic dermatitis, dermatitis herpetiformis, lichen planus) were excluded, the prevalence of pruritus in patients with fibromyalgia was still 1.97 times greater than in the controls (6.9% vs. 3.5%; OR, 2.0; 95% CI, 1.7-2.4; P<.0001). These results remained unchanged even when excluding pruritic dermatologic disorders as well as systemic diseases associated with pruritus (eg, chronic renal failure, dialysis, hyperthyroidism, hyperparathyroidism/hypoparathyroidism, hypothyroidism). Patients with fibromyalgia still displayed a significantly higher prevalence of pruritus compared with the control group (6.6% vs 3.3%; OR, 2.1; 95% CI, 1.7-2.6; P<.0001).
