Japanese guidelines published in the Journal of Dermatology offer up-to-date and evidence-based recommendations for clinicians on the treatment of cutaneous pruritus. The guidance statement is an update from a 2012 guideline statement on generalized pruritus, with the new guidelines providing recommendations supposedly more applicable to real-world clinical practice.

Treatment Recommendations

Aside from outlining the definition and classification of cutaneous pruritus and discussing the laboratory tests to assess the condition, the guideline committee delved into 14 key clinical questions regarding the treatment of cutaneous pruritus:


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· Moisturizers: The guideline indicates moisturizers may reduce itch for generalized pruritus in patients with dry skin, but the efficacy of moisturizers in patients without dry skin is still uncertain given the paucity of data in this area. Likewise, the guideline authors state that if topical moisturizers provide little to no relief, it is recommended to switch the patient to other treatments (Level of Recommendation: B).

· Antihistamines: Currently, no studies with a high level of evidence can support the recommendation to use antihistamines for cutaneous pruritus, according to the guideline authors. There are also no randomized studies on antihistamines for generalized pruritus, but there is a randomized trial that has assessed the antipruritic effects of antidepressant doxepin. The guideline authors state that antihistamines may still be considered, despite the lack of sufficient clinical evidence to demonstrate their efficacy (Level of Recommendation: C1).

· Topical steroids: There is also currently a lack of reports with high levels of evidence demonstrating the effects of topical steroids on cutaneous pruritus. In contrast, reports with Evidence Level 2 have discussed the use of topical steroids in anogenital pruritus. Eczematous lesions were included these reports, however, prompting the guideline committee to recommend topical steroids only if the patient has secondary eczematous lesions (Level of Recommendation: B).

· Topical crotamiton: The guidelines state topical crotamiton can be considered in cutaneous pruritus but note the lack of studies with high levels of evidence on crotamiton’s antipruritic effects (Level of Recommendation: C1). The authors add that insurance doesn’t cover topical crotamiton, preventing its broader use in the population.

· Ultraviolet (UV) light therapy: Recent case reports suggest broadband UV-B may be a potentially effective treatment modality for generalized pruritus associated with renal dysfunction (Level of Recommendation: B). Other published studies have demonstrated the utility of narrowband UV-B and UV-A, but these reports feature low levels of evidence (Level of Recommendation: C1). In addition, there are currently no studies with high levels of evidence that have demonstrated the efficacy of UV light therapy for generalized/localized pruritus. Similar to topical crotamiton, UV light is also not covered by insurance for the purposes of treating pruritus.

· Topical/oral immunosuppressants: There is also a lack of clinical evidence demonstrating the usefulness of topical and oral immunosuppressants in pruritus. As such, the guideline authors state immunosuppressants are not recommended for cutaneous pruritus (Level of Recommendation: C1). In addition to topical crotamiton and UV light therapy, the Japanese guideline authors state immunosuppressants for pruritus are not covered by insurance.

· Anti-anxiety and antidepressant drugs: In cases resistant to other therapies, the guideline committee state anti-anxiety and antidepressant agents may be considered. In contrast, the guideline authors suggest these agents should not be given to patients if the clinician is unfamiliar with how to administer them. The levels of evidence for these recommendations are C1 for clinicians who are skilled in their use and C2 for clinicians not skilled in their use.

· Oral nalfurafine hydrochloride: There are no published epidemiological studies that have evaluated the efficacy of nalfurafine hydrochloride for generalized pruritus associated with conditions other than chronic liver diseases and hemodialysis. As such, the guideline recommends nalfurafine hydrochloride for patients with hemodialysis patients and patients with chronic liver diseases (Level of Recommendation: B) but not in patients with pruritus associated with other conditions, given the lack of available evidence (Level of Recommendation: C2).

· Reserpine: Insufficient evidence exists to support the efficacy and safety of reserpine in pruritus. Although the agent possesses antipruritic action, the guideline does not recommend reserpine given the lack of available data (Level of Recommendation: C2).

· Pregabalin: The guideline states that “good evidence” exists to support the efficacy of pregabalin for dialysis-associated generalized pruritus. Likewise, there are also case reports and case series that have demonstrated the efficacy of the gabapentinoid for generalized pruritus associated with other conditions. While insurance in Japan does not cover pregabalin, the guideline authors state the therapy could be considered a good treatment option for cutaneous pruritus (Level of Recommendation: C1).

· Gabapentin: Similar to pregabalin, there is “good evidence” to suggest gabapentin is effective for pruritus, suggesting the therapy may also be considered in this setting (Level of Recommendation: C1).

· Kampo medicines: The use of Kampo medicines, or traditional Japanese medicines, may be considered in cases of resistant disease (Level of Recommendation: C1). Certain Kampo medicines include Orengedokuto and Goshajinkigan, Tokiinshi, as well as Hachimijiogan and Rokumigan.

· Neurotropin: Neurotropin consists of extracts from inflamed skin tissue of rabbits inoculated with vaccinia virus. The guideline cites some evidence to suggest its benefit in pruritus and recommends its use in resistant cases (Level of Recommendation: C1).

Reference

Satoh T, Yokozeki H, Murota H, et al. 2020 guidelines for the diagnosis and treatment of cutaneous pruritus. J Dermatol. Published online July 20, 2021. doi:10.1111/1346-8138.16066