Delusional infestation: It is the brain that itches and not the skin

Delusional infestation (DI) is a rare condition, in which patients often experience severe itch due to the belief that they are infested with living or non-living pathogens, which cannot be confirmed by physical and additional examination.1 The estimated incidence is between 2 and 30 per 1,000,000 people per year.2 Between the physician and the patient, there is often a difference of opinion about the origin of the itch. The physician also considers a psychogenic origin, while the patient is convinced that the itch is in the skin. The aetiology and pathogenesis of itch are complex. It is known that both acute and chronic stress can significantly affect itch in healthy individuals by both central and peripheral activation of the hypothalamic–pituitary–adrenal (HPA) axis and sympathetic nervous system.3 Skin cells express various neuropeptides and hormones in response to stress, including the fully functional analog of the HPA axis. Stress-induced changes in the levels of neuroendocrine mediators may lead to the activation of the immune response and release of various cytokines that mediate the sensation of itch. Among the many known pruritogens, Th2 cytokines interleukin-4 and interleukin-13, interleukin-31, and thymic stromal lymphopoietin are particularly important mediators that signal through shared Janus kinase pathways.4 In patients with psychiatric disease, like patients suffering from DI, one would not expect inflammation or cytokine release in the skin. Interestingly, several studies show elevated pro-inflammatory cytokines in blood of patients suffering from early schizophrenia, first episode psychosis and depression.5 It is speculated that this may play a role in the onset, development and therefore the pathogenesis of psychiatric disorders.5, 6 It is therefore conceivable that stress-induced overexpression of cytokines may cause pruritus in patients with DI. Moreover, the possibility that the itch is caused by an undiagnosed disease associated with aberrant immunity should be considered. In addition, it is also possible that the long-term scratching of patients suffering from delusional infestation may induce an inflammatory reaction in the skin and therefore a cytokine release. Currently, it is unknown if there are increased levels of pro-inflammatory cytokines in the skin of patients suffering from DI. A difference in pro-inflammatory cytokines in patients suffering from DI compared to healthy individuals without pruritus, or even patients with pruritus caused by other diseases, may shed light on the pathogenesis of pruritus in DI, in particular whether it is psychogenic or somatic in origin. To investigate whether patients with DI have an altered immunological response in the skin, we compared the skin levels of relevant cytokines in patients suffering from DI and healthy controls (HC). Fifteen HC and 19 patients clinically diagnosed with DI by an expert panel of a psychiatrist and two dermatologists were included. No major skin abnormalities except for some small excoriations and dry skin were observed in the patients. The levels of cytokines of different signature (Figure 1) were determined in the stratum corneum (SC) collected by minimal invasive tape stripping. The samples were obtained from the back between the shoulder blades as this body location is less likely to be scratched. As shown in Figure 1, we found no significant difference in cytokine levels between patients with DI and HC. This suggests that the itch experienced in patients with DI is likely not caused by an inflammatory skin condition which in previous studies did show altered SC profiles of the same immunological markers.7 It is therefore likely that psychological factors in particular play an important role in symptoms in patients with DI. Therapy should therefore focus on the psychological cause where antipsychotics are the cornerstone of therapy. None. None declared. According to the Dutch IRB criteria (WMO), approval was not required.