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Three patients with chronic vulvar pruritus successfully treated with cold atmospheric pressure plasma

Chronic vulvar pruritus (cVP) is a common and bothersome symptom associated with a high burden of disease caused by various dermatological and non-dermatological conditions [1]. Although the European Guideline for the management of vulval conditions [2] provides recommendations on the treatment of some itchy conditions such as eczema, psoriasis, lichen sclerosus, and lichen simplex chronicus, according to our experience treatment of cVP is often challenging and unsatisfactory in clinical routine. Plasma medicine is an emerging field that comprises the application of physical plasma (e.g. cold plasma at atmospheric pressure conditions) for therapeutic purposes [3]. For cold atmospheric plasma (CAP), the fourth state of matter is generated by supplying electrical energy to inert gases such as nitrogen, helium or argon [4]. CAP comprises a multitude of active components including ions, electric fields, UV-radiation and reactive oxygen/nitrogen species resulting in synergistic antimicrobial, anti-inflammatory, antipruritic, tissue-stimulating, blood flow-enhancing, and proapoptotic effects [3, 5]. CAP is approved for the treatment of chronic (leg) ulcers in many countries [6], but has also been tested in clinical pilot studies or case-control studies for the treatment of several other dermatological conditions including atopic dermatitis, psoriasis, ichthyosis, skin tumors or scars [3]. In particular, CAP has been reported to reduce itch in various pruritic conditions [3, 7]. Against this background and based on the rationale summarized in Figure 1, we hypothesized that CAP might also have the potential to decrease itch intensity in cVP. To our knowledge, this hypothesis has not yet been addressed in the medical literature. Hence, we treated three patients, of whom two suffered from lichen sclerosus and one from lichen simplex chronicus, with CAP using PlasmaDerm® FLEX9060 (CINOGY System GmbH, Duderstadt, Germany) as an add-on treatment. The regimen comprised three sessions per week over six weeks with an application Clinical Letter time of 90 seconds per session (Figure 2a). All three patients had a long-term history for cVP and suffered from high itch intensities resistant to topical and systemic treatments (Table S1, online Supplement Information). Mean itch intensity during the past seven days rated on a 0–10 Numerical Rating Scale (NRS, 0: no itch, 10: worst itch imaginable) was assessed at baseline, after two, four and six weeks of CAP treatment. Topical and systemic treatment remained unchanged two weeks before until six weeks after the initiation of CAP treatment. As shown in Figure 3, the itch intensity was already significantly reduced after two weeks (mean NRS 7 ± 1.0 vs. 3.3 ± 1.5, paired sample t-test P = 0.02) and all patients reported an additional itch reduction in the following four weeks. In contrast to the significant reduction of itch, the clinical signs improved only slightly as exemplified by patients 1 and 2 (Figure 2b). This mismatch may be explained by the fact that several itch pathways involved in cVP may be targeted by CAP irrespective of a visible improvement of the inflammation involved in lichen sclerosus or lichen simplex chronicus. Moreover, it is conceivable that the anti-pruritic effects of CAP preceded the visible improvement that is usually achieved by anti-inflammatory effects. Apart from mild local sensations during the 1.5 minutes of application, no other side effects were reported (Table S1, online Supplement Information) indicating that CAP treatment was well-tolerated and safe during our observation period. We conclude that the itch reduction reported by our three patients with cVP treated with CAP aligns with the anti-pruritic properties of CAP reported for other itchy conditions. These promising results may rationalize further investigation of the effect of CAP treatment on cVP in a standardized study protocol (ideally with sham applications as placebo control), including histological work-up, cytokine and chemokine gene expression and assessments of itch-related quality of life.