**5. Topical Treatments**

Topical treatment with skin emollient contained high water to hydrate stratum corneum is considered as a primary therapy for UP in CKD patients. In order to avoid any allergic reaction, emollients without perfumes or other additives is preferable [43,90].

#### **5.1. Skin Emollients**

Because xerosis plays at least an adjuvant role in the development of UP, emollients are a mainstay in the treatment. It has been suggested by several researchers that the use of emollients with high water content should be the first-line treatment [91,92]. The benefit of using emollients to treat dry skin in patients with UP has been reported by Morton et al. and others [9,43,93]. A pilot study on the use of urea 10% lotion with dexpanthenol, a moisturizer, showed significant improvement in skin itch [20]. The study by Balaskas *et al.* of 100 patients using glycerol and paraffin, showed a 75% improvement in UP and hence quality of life (*p*<0.001) [94]. The addition of endocannabinoids to creams containing structured physiolog‐ ical lipids demonstrated good efficacy and tolerance in a clinical study [61,95].

### **5.2. Sericin Cream**

Sericin, a biopolymer with a high molecular weight, is a water-soluble protein that is obtained from the silkworm (*Bombyx mori*). Sericin is characterized by the presence of 32% serine, which is the main amino acid of the natural moisture factor (NMF) in human skin; therefore, sericin has excellent moisturizing properties that may be helpful for treating hypohidrosis. Sericin also demonstrates many biological activities and has been widely studied for potential use in medicines and biomaterials [96-100]. Moreover, sericin can significantly decrease the levels of the pro-inflammatory cytokines TNF-α and IL-1β in sericin-treated wounds in rats 7 days after an injury, compared with the levels found in normal saline-soaked wounds and cream basetreated wounds [101]. As previously mentioned, the immune-inflammatory hypothesis considers UP a dermatologic manifestation of chronic inflammation and treats the condition as a possible result of derangements in the immune system that are based on a pro-inflamma‐ tory pattern. Based on this reasoning, sericin was investigated for relieving UP. An in-subject, randomized, double-blind, placebo-controlled experimental study was designed to investigate the effects of sericin cream (concentration 8%) versus the cream base (placebo) applied twice daily for 6 weeks in reducing the symptoms of UP (itching, dryness and redness) and skin pigmentation in 47 subjects with stable maintenance hemodialysis [102]. The results showed that sericin reduces pruritus in patients with UP. The use of sericin cream significantly increased the level of skin hydration after 6 weeks of treatment compared to baseline and to the use of the cream base. The use of sericin cream also significantly reduced the level of skin irritation and pigmentation after 6 weeks of treatment compared to baseline, while use of the cream base reduced skin pigmentation slightly but not significantly. Patients' quality of life was also assessed using the Thai version of the KDQOL-SF Version 1.3, and the results showed a better quality of life in all of the measured domains, including sleep and mood/emotional distress after the treatment period. When the mean score on the enrollment day was compared with the mean score on the day after the completion of treatment, significant differences were found in some domains, including pain, the symptoms/problems list in kidney disease, the effect of kidney disease on daily life and sleep, the most relevant parameter for itching. The overall score increased from 60.00 at the time of enrollment to 61.95 after 6 weeks of treatment, although this difference was not statistically significant. The results of this study suggest that sericin cream may be a good choice for treating pruritus in hemodialysis patients. Because sericin is obtained from natural sources that have high biocompatibility, it may cause fewer allergic reactions and lower resistances compared to other chemical substances.

#### **5.3. Capsaicin**

the thermal therapy group compared with the non-thermal therapy group, even though there was no significant differences between groups [88]. The result implied that thermal therapy

Stimulation of the sweat glands with a sauna has shown benefits, perhaps through augmented excretion of hypothetical pruritogen [89]. However, such treatment may cause major compli‐

Topical treatment with skin emollient contained high water to hydrate stratum corneum is considered as a primary therapy for UP in CKD patients. In order to avoid any allergic reaction,

Because xerosis plays at least an adjuvant role in the development of UP, emollients are a mainstay in the treatment. It has been suggested by several researchers that the use of emollients with high water content should be the first-line treatment [91,92]. The benefit of using emollients to treat dry skin in patients with UP has been reported by Morton et al. and others [9,43,93]. A pilot study on the use of urea 10% lotion with dexpanthenol, a moisturizer, showed significant improvement in skin itch [20]. The study by Balaskas *et al.* of 100 patients using glycerol and paraffin, showed a 75% improvement in UP and hence quality of life (*p*<0.001) [94]. The addition of endocannabinoids to creams containing structured physiolog‐

Sericin, a biopolymer with a high molecular weight, is a water-soluble protein that is obtained from the silkworm (*Bombyx mori*). Sericin is characterized by the presence of 32% serine, which is the main amino acid of the natural moisture factor (NMF) in human skin; therefore, sericin has excellent moisturizing properties that may be helpful for treating hypohidrosis. Sericin also demonstrates many biological activities and has been widely studied for potential use in medicines and biomaterials [96-100]. Moreover, sericin can significantly decrease the levels of the pro-inflammatory cytokines TNF-α and IL-1β in sericin-treated wounds in rats 7 days after an injury, compared with the levels found in normal saline-soaked wounds and cream basetreated wounds [101]. As previously mentioned, the immune-inflammatory hypothesis considers UP a dermatologic manifestation of chronic inflammation and treats the condition as a possible result of derangements in the immune system that are based on a pro-inflamma‐ tory pattern. Based on this reasoning, sericin was investigated for relieving UP. An in-subject,

ical lipids demonstrated good efficacy and tolerance in a clinical study [61,95].

cations in fluid balance due to unquantifiable insensible water loss.

emollients without perfumes or other additives is preferable [43,90].

may have therapeutic benefits for UP.

**5. Topical Treatments**

**5.1. Skin Emollients**

**5.2. Sericin Cream**

**4.7. Sauna**

26 Updates in Hemodialysis

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), an extract from capsicum or common pepper plant, can be used as a main ingredient in cream for the treatment of painful disorders including postherpetic neuralgia, cluster headaches, diabetic neuropathy, osteoarthritis and phantom limb [103,104]. Capsaicin blocks pain and itching by depleting and preventing the re-accumulation of substance P from local type C sensory nerve terminals [89,104]. After using 0.025% capsaicin cream for the treatment of UP in long-term dialysis patients, the results indicated that significant alleviation of pruritus was found with no serious adverse reaction [105,106]. Although topical capsaicin might be useful for the treatment of localized disease, it is impractical for large areas or generalized pruritus.

#### **5.4. Tacrolimus**

Tacrolimus is an immunomodulator targeting mainly at the T helper cells. It blocks the differentiation of Th1-type lymphocytes, and therefore, suppresses the production of IL-2. Due to these mechanisms, it was suggested that it might be beneficial in the treatment of UP. An observational study of 3 cases of severe UP in patients on peritoneal dialysis indicated a shortterm efficacy of 0.03% tacrolimus ointment over 7 days. However, the use of this agent was not extended longer because of the potential carcinogenic effect of systemic tacrolimus [107], which resulted in an FDA black-box warning that was issued in 2006 against the prolonged topical use of tacrolimus creams and ointments. Nevertheless, some studies failed to demon‐ strate any efficacy of the topical calcineurin inhibitor in patients with UP [108,109].
