Chronic prurigo is characterized by an “itch-scratch cycle” and is often associated with high levels of distress. The International Forum for the Study of Itch (IFSI) suggests a stage-adapted multimodal therapeutic approach, and the range of recommended treatment options has recently expanded.
Chronic pruritus can occur at any age and affect different groups of patients [1]. A common characteristic is that pruritic patients contribute to the maintenance or enhancement of inflammatory processes by prolonged or intense scratching, which in turn promote pruritus. Peripheral and central sensitization to the chronic itch maintains this vicious circle, according to Prof. Martin Metz, MD, Clinic for Dermatology, Venereology and Allergology, Charité Universitätsmedizin Berlin (D) [2]. A diagnosis of chronic prurigo can be made if itching persists for at least 6 weeks, there are signs of repeated scratching (e.g., excoriations and scars), and multiple localized or generalized pruriginous lesions are present [3]. “Chronic prurigo is a disease in its own right,” the speaker emphasized [2]. This is supported by a broad evidence base, he said. Chronic nodular prurigo (prurigo nodularis) is the most common, with nodules ranging in size from a few millimeters to a few centimeters occurring mostly on the extremities [1]. The symptoms may result in sleep disturbances, depression, and anxiety [1].
Breaking the itch-scratch cycle – IFSI guidelines provide guidance
The Prurigo Activity and Severity Score (PAS) can be used to assess the severity and extent of chronic prurigo. This medical survey form is used to assess the spread, severity, number, activity, and healing of lesions [5]. Other measurement tools that can be used include the prurigo activity score or the prurigo control test, as well as questionnaires to assess quality of life [2]. The primary treatment goal is to break the itch-scratch cycle so that the scratch marks can heal, which in turn further reduces the itch until eventually the itch and nodules of prurigo nodularis disappear completely. The current International Forum for the Study of Itch (IFSI) treatment guideline recommends using a multimodal approach that includes general strategies to control pruritus, treatment of potentially pruritogenic comorbidities, and therapy of pruritogenic lesions (Fig. 1) . Topical and systemic antipruritic agents should be used in a stage-adapted manner. The duration of each treatment step depends on the extent of chronic prurigo, the severity of itching, previous treatments, and the patient’s psychological distress.
Systemic treatment is often required
“We have to do systemic therapy in almost all patients with prurigo,” Prof. Metz reported, adding, “Gabapentin and SSRI are the drugs we use the most” [2]. Selective serotonin reuptake inhibitors (SSRIs) or the anticonvulsant gabapentin relieve symptoms in some prurigo patients, but by no means in all. “Unfortunately, even with that, we don’t get many patients under control,” the speaker stated. But there is hope: the IFSI guidelines suggest the biologics dupilumab and nemolizumab as treatment options for severe cases in stage 4. Thus, the recognition that the cytokines IL-4, IL-13 and IL-31 play a pathophysiologically important role has now borne fruit: both dupilumab (anti-IL4/13 receptor antibody) and nemolizumab (anti-IL-31 receptor antibody) showed very promising results in clinical trials. With dupilumab, 37.2% of patients in the PRIME-2 trial achieved a clinically meaningful reduction in itch since baseline at week 12, compared to 22.0% in the placebo group (p=0.0216) [8–10]. At week 24, the corresponding values were 57.7% and 19.5%, respectively (p<0.0001), thus almost three times as many study participants in the verum condition achieved clinically significant itch reduction after this period [8–10]. Appearance-free or near-appearance-free skin at week 24 was achieved by 44.9% of dupilumab-treated patients versus 16% on placebo (p<0.0001).
In the USA, dupilumab has already received FDA approval for the indication of prurigo nodularis [7]. In Europe, official approval is currently limited to other indications. However, according to the current European guideline, off-label use of dupilumab can be considered in chronic nodular prurigo [1]. Nemolizumab is not yet on the market in Germany, Austria and Switzerland. But there are positive phase II data for the chronic prurigo indication and phase III data are expected soon. In the phase II study, nemolizumab resulted in a 4.5 point (-53.0%) reduction in itch in patients with moderate to severe prurigo nodularis at week 4 compared to baseline, compared to 1.7 points (-20.2%) with placebo (p<0.001) [4].
Kongress: Schweizerische Gesellschaft für Dermatologie und Venerologie (SGDV)
Literature:
- Ständer S, et al.: S2k Leitlinie: Diagnostik und Therapie des chronischen Pruritus. J Dtsch Dermatol Ges 2022; 20(10): 1386–1402.
- “Never ending itch – addressing clinical challenges in prurigo nodularis,” Prof. Martin Metz, MD, SGDV Annual Meeting Nov. 9-11, 2022.
- Pereira MP, et al: EADV Task Force Pruritus group members. European academy of dermatology and venereology European prurigo project: expert consensus on the definition, classification and terminology of chronic prurigo. J Eur Acad Dermatol Venereol 2018; 32(7): 1059-1065.
- Stand S, et al: Trial of nemolizumab in moderate-to-severe prurigo nodularis. N Engl J Med 2020; 382(8): 706-716.
- Pölking J, et al: Journal of the European Academy of Dermatology and Venereology 2018; 32(10): 1754-1760.
- Ständer S, et al: IFSI-guideline on chronic prurigo including prurigo nodularis. Itch 5(4):p e42, October-December 2020.
DOI: 10.1097/itx.0000000000000042 - “FDA approves first treatment for prurigo nodularis,” www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-prurigo-nodularis, (last accessed, Jan. 30, 2023).
- Lönndahl L, et al: Dupilumab significantly reduces symptoms of prurigo nodularis and depression: a case series. Acta Derm Venereol 2022; 102: adv00754XX.
- “Study of dupilumab for the treatment of patients with prurigo nodularis, inadequately controlled on topical prescription therapies or when those therapies are not advisable (PRIME2)”. https://ClinicalTrials.gov/show/NCT04202679, (last accessed Jan. 30, 2023)
- “Dupixent® (dupilumab) is the first biologic to significantly reduce itch and skin lesions in phase 3 trial for prurigo nodularis, demonstrating the role of type 2 inflammation in this disease,” Sanofi, October 22, 2021.
DERMATOLOGIE PRAXIS 2023; 33(1): 20–21
