Evidence Corner: Taking Itch Seriously

Dear Readers,

Itching (pruritus) of a wound, scar, or dermatologic disorder can negatively impact a patient’s quality of life, resulting in injurious scratching¹ or impeded rehabilitation.² Like pain, itch can cause the sufferer to lose sleep and appetite or even consider suicide.^3,4 Clinical measures of pruritus have proved reliable and valid in individuals with burn wounds, dermatologic conditions, or urticaria^5-7 or resulting scars,² allowing studies to clarify its impact on human experience and compare the effects of interventions to reduce itching. This Evidence Corner explores the effects on pruritus of interventions applied at 2 very different stages of wound healing: the first during early healing stages after hemorrhoidectomy⁸ and the other in postburn hypertrophic scarring with contracture.⁹ Each condition generates distressing levels of pruritus from which patients eagerly seek relief. 

Reference: Giannini I, Pecorella G, Pennisi D, Santangelo G, Digennaro R, Latorre F, Giuliani G, Altomare DF. Control of post-hemorrhoidectomy symptoms and wound healing by triclosan: a randomized, double-blind, controlled trial. Minerva Chir. 2014;69(2):75–82.

Rationale: Commonly performed procedures for removing Grade III or IV hemorrhoids often result in prolonged postop wound healing, itching, and pain. 

Objective: Conduct a double-blind, randomized clinical trial (RCT) exploring the safety and efficacy of hemorrhoidectomy wound cleansing with triclosan as compared with sodium hypochlorite.

Methods: All patients undergoing Grade III or IV hemorrhoidectomy by diathermy or Ligasure (Medtronic, Minneapolis, MN) technique in an Italian university hospital emergency department received analgesics and a fiber-rich diet in addition to being randomly assigned to have their wounds cleansed postoperatively for up to 21 days with a commercially available triclosan solution (n = 55) or sodium hypochlorite (n = 58). On postoperative days 7, 14, and 21, anal pain, itch, and bleeding or secretions were assessed by observers blinded to the treatment group using a visual analogue scale (VAS). Healing time was recorded as the first day with no bleeding or secretion. The 2 groups’ demographics and hemorrhoid severity were compared at baseline. Patient-reported outcomes were compared at all 3 time points postoperatively, with significance set at P ≤ .05.

Results: Both groups were comparable at enrollment on severity of hemorrhoids, hemorrhoidectomy technique, and demographics. Patients whose hemorrhoidectomy sites were cleansed with triclosan epithelized faster (P = .05) and with less itch (P = .01), pain (P < .0001), and bleeding or secretion (P = .003) as compared with those cleansed with sodium hypochlorite. 

Authors’ Conclusions: Triclosan was safe and effective in cleansing hemorrhoidectomy sites and reduced the intensity of postoperative complications compared with cleansing the sites with sodium hypochlorite.

Reference: Wu J, Xu R, Zhan R, Luo G, Niu X, Liu Y, Lee BT, Flury M, Wong CH, Fok M, Lau JY. Effective symptomatic treatment for severe and intractable pruritus associated with severe burn-induced hypertrophic scars: a prospective, multi- center, controlled trial. Burns. 2016; 42(5): 1059–1066.

Rationale: Most patients receive little relief from severe intractable pruritus associated with postburn hypertrophic scars.

Objective: Conduct a prospective RCT comparing the antipruritic effects of topically applied gauze alone or gauze impregnated with a guar gum gel with or without an oil-in-water nanoemulsion of peppermint oil, menthol, and methyl salicylate on patients with severely pruritic postburn hypertrophic scars.

Methods: After pilot evaluations of formulations designed to reduce cutaneous pruritus and appropriate statistical power determinations, 3 Chinese burn centers enrolled 74 individuals in a RCT to evaluate safety and efficacy of the most promising formulation (CQ-01). Patients included were aged 16 to 65 years, each with at least 3 postburn hypertrophic scar areas formed during the first year following burn injury and averaging more than 50 cm²  in area. To qualify for study, each scar area elicited pruritus so severe that it interfered with sleep and/or caused depression or suicidal thoughts reflected by patient-reported scores >40 on the 0–100 JW VAS for pruritus. Patients were excluded if they were pregnant, had conditions rendering them incapable of understanding or following study instructions, or if they had conditions such as eczema, diabetes, immunological, renal, hepatic, or oncologic disorders that could affect outcome responses. Three similar pruritic areas on each qualifying subject were randomized to receive 24 hours of topical treatment with either the CQ-01 formula or its placebo (each 0.2 g of gel/cm²) covered with CQ-01 gel-impregnated gauze or gauze alone. The primary outcome was JW score assessed at 0.5, 1, 3, 6, 12, and 24 hours after application, then daily for 7 additional days after the initial day of treatment. Safety was measured as any form of irritation response to the topical treatment during the 24-hour application. Irritation led to discontinued treatment, though all subjects were encouraged to continue reporting their day 2 to 7 JW pruritus scores to investigators unaware of treatment assigned to each site. True double blinding was challenged by differences in scent and sensations of gel application. Planned comparisons of JW scores during the study were performed comparing pruritus reported for all 3 treatments throughout the 8-day study, with statistical significance set at P < .05.

Results: Among those who completed all JW assessments per protocol (n = 70), after 3 hours of treatment, itch dropped from an initial severe, intractable level of pruritus, causing depression and lack of sleep (mean, 80 JW score), for all 3 treatment sites to 73 JW score in response to gauze alone, 62 JW score for placebo gel, and 44 JW score for CQ-01 gel. Pruritus differences were significant from hour 3 of treatment through study day 8 between CQ-01 gel-impregnated gauze or gauze alone or through day 7 for CQ-01 gel compared with placebo gel (P < .01). Pruritus was reduced by the placebo gel compared with gauze alone for 5 days (P < .05). Irritation lasting < 1 hour after removal was reported after 3 minutes to 2 hours of CQ-01 treatment by 6 patients, 4 of whom could no longer rate JW pruritus due to mild irritation; thus, they were omitted from the study per protocol analysis of pruritis outcomes. On a subset of 10 patients, similar successive 24-hour applications of CQ-01 had undiminished effects persisting for at least 3 days after one 24-hour treatment. Subsequent similar studies showed that a cream formulation had similar initial antipruritic efficacy with no lasting effect after 24 hours. A low water-vapor-transmission-rate silicone gel sheet did not significantly reduce JW scores.

Authors’ Conclusions: The CQ-01 formulation has a promising clinical profile in meeting important unmet medical needs to address pruritus in patients with burn scars.

Both studies report significant efficacy and safety of topical agents in reducing patient-reported pruritus in fresh surgical wounds⁸ or hypertrophic scars occurring during the first year following injury.⁹ These antipruritic effects were not permanent but do offer promise of significant transient relief — even with a placebo guar gum-based hydrogel. One 24-hour application suppressed severe pruritus of hypertrophic burn scars for up to 8 days, but average pruritus ratings remained sufficiently severe to limit sleep.⁹ Mechanism(s) of action remain to be explored, but pruritus can be temporarily suppressed by at least 2 topical formulations.^8,9 This raises the question as to whether acute radiation dermatitis, eczema, shingles, poison ivy, or other pruritic conditions may also respond to one or both of these formulations, or is their antipruritic efficacy specific to the indications described here? Efficacy of the CQ-01 hydrogel was unrelated to burn location, duration of healing, or time after healing.⁹ Further research is needed to explore other formulations and effects on less severe pruritus. Although many questions remain to be answered, these studies^8,9 represent important advances in managing pruritus. 

This article was not subject to the WOUNDS peer-review process.