Persistent itching is very stressful for those affected and can lead to enormous suffering. A careful diagnostic clarification of chronic pruritus is the basis for a goal-oriented treatment. It remains to be seen which of the active ingredients currently being tested in clinical trials will clear the approval hurdle. The results to date are promising – this is particularly true for chronic prurigo, which is characterized by severely itchy skin nodules.
If itching symptoms persist for longer than 6 weeks, the condition is referred to as chronic pruritus. This can occur in the context of various diseases. Treatment continues to be a challenge. The underlying mechanism is thought to be peripheral sensitization of cutaneous nerve fibers by inflammatory mediators. However, there are still many unanswered questions. For the management of chronic pruritus, the corresponding s2k guideline provides helpful guidance. Apart from dermatoses, pruritus symptoms also occur in the context of various internal and neurological-psychiatric diseases (overview 1-3) . Chronic prurigo represents a chronified special form. “Chronic prurigo is a disease in its own right, which represents a major problem for our patients,” explains Prof. Martin Metz, MD, Clinic for Dermatology, Venereology and Allergology, Charité, Universitätsmedizin Berlin, on the occasion of the SGDV Annual Meeting 2021 [1]. Recently, a new international guideline was published by the International Forum for the Study of Itch (IFSI) (box) [2]. “This is the first ever guideline on chronic prurigo,” Prof. Metz said. Nowadays, this complex entity is thought to develop through neuronal sensitization and the emergence of an itch-scratch cycle.
Record severity of pruritus and impaired quality of life
According to the Global Burden of Diseases study, chronic pruritus is one of the 50 central and highly burdensome diseases [3]. The quality of life of patients with persistent itching is often significantly reduced – many suffer from depression, sleep disturbances and reducedperformance. Loss of employment and restrictions on participation in non-work social life may occur [4]. In addition to pruritus-specific history and clinical examination, the current guideline recommends the use of questionnaires. For this purpose, several validated tools are now available to assess the severity of pruritus (NRS, VAS)* and quality of life limitations (DLQI, ItchyQoL) as well as possible affective symptoms (HADS) [4,5].
* NRS=Numerical Rating Scale, VAS=Visual Analog Scale
Is there a systemic disease or not?
Laboratory diagnostic tests serve as a further pillar of diagnostics. The following parameters should be determined as part of a screening: Differential blood count, CRP, ferritin, liver parameters (bilirubin, liver enzymes, alkaline phosphatase). Renal parameters (creatinine, urea, GFR, potassium), glucose levels to rule out diabetes, and LDH and TSH. In addition, if one has a clinical suspicion, further clarifications may be useful, such as determination of total IgE, skin biopsies, X-ray, abdominal ultrasonography, the speaker said. These clarifications should be carried out in interdisciplinary cooperation with the respective other specialist disciplines.
As a basis for the therapy decision, the current s2k guideline on chronic pruritus proposes a grouping into the following three categories [1,4] (Fig. 1) :
1) Chronic pruritus on primary altered skin, 2) Chronic pruritus on primary unchanged skin, 3) Chronic pruritus with scratch lesions. Under the first group among other things itching is subsumed as Begleitsymptom in the context of hepatobiliären, nephrological or neurological illnesses as well as Pruritus of medicament-induced Genese, explains Professor Metz. The category “chronic pruritus with scratch lesions” is assigned in particular to chronic prurigo – according to current understanding a secondary reaction pattern in chronic pruritus [6,7].
Current treatment options are limited
There is no universal, uniform therapy for chronic pruritus due to the diversity of possible underlying causes [4]. If it is known as a concomitant of which disease the itching symptoms occur, specific therapy recommendations can be resorted to. For example, rifampicin (150-600 mg/day) or naltrexone (25-50 mg/day) are mentioned for liver disease [8]. In the case of chronic pruritus of unclear causes, active substances from other areas, i.e. with a different main indication area, are also used in addition to antihistamines as first-line medication [1]. These include second-line gabapentin (up to 3600 mg/day) or pregabalin (up to 600 mg/day) and third-line SSRIs (e.g., sertraline 25-50 mg/day, morning). If none of these options are viable or goal-directed, therapy may be attempted with mirtazapine (15 mg/day) or naltrexone (50-150 mg/day). In addition, light therapy (UVB 311 nm) is mentioned as a treatment alternative.
The various etiology-dependent treatment options are summarized in the guideline. An individual treatment plan, taking into account the appropriate itch-relieving measures in each case, is useful.
Several drug candidates in the pipeline
It is becoming apparent that the drug spectrum for the therapy of chronic pruritus will expand in the not too distant future. In recent years, intensive research efforts have yielded significant advances and identified several mediators and targets for targeted pharmacologic therapy of pruritus. Many of these have a directly anti-pruritic approach, explains Prof. Metz. Among the promising representatives in advanced phases of clinical development are the monoclonal antibodies lebrikizumab (anti-IL-13), tralokinumab (anti-IL-13) and nemolizumab (anti-IL-31), as well as the JAK inhibitors baricitinib, abrocitinib and upadacitinib, which belong to the “small molecules”. These agents have achieved remarkable reductions in itch symptomatology in clinical trials, with clinical improvement of up to 4 points on the NRS scale, the speaker explained. There were also some data specifically related to chronic prurigo, he said. In one of the clinical trials of nemolizumab, the proportion of patients with a reduction of at least 4 points in the NRS scale in the verum condition as early as 4 weeks after baseline was a substantial 59% compared with 31% on placebo [9]. There are also encouraging data on dupilumab: this antibody, which inhibits the signaling pathways of IL-4 and IL-13, achieved significant itch relief in several case reports, even in patients whose itch symptoms were not due to atopic dermatitis [10].
Congress: SGDV Annual Meeting
Literature:
- Metz M: Diagnostics and treatment in chronic pruritus. Prof. Martin Metz, MD, SGDV Aug. 25-27, 2021.
- Stand S, et al: Itch 2020, 5 (Issue 4), p e42.
- Hay RJ, et al: J Invest Dermatol 2014; 134: 1527-1534.
- Stand S, et al: JDDG 2017; 15: 860-873.
- Verweyen E, et al: Acta Derm Venereol 2019; 99(7): 657-663.
- UKM; www.ukm.de/index.php?id=8868.
- Pereira MP, et al: J Eur Acad Dermatol Venereol 2017, https://doi.org/10.1111/jdv.14570
- Düll MM, et al: Curr Gastroenterol Rep 2019; 21(9): 48.
- Stand S, et al: N Engl J Med 2020; 382(8): 706-716.
- Calugareanu A, et al; J Eur Acad Dermatol Venereol 2020; 34(2): e74-e76.
- Stand S: International guideline Chronic prurigo: first step towards structured care. P 191. JDDG 2021; 19(IssueS2): 25-142.
DERMATOLOGIE PRAXIS 2021; 31(5): 29-30 (published 7/10/21, ahead of print).
