This study has shown that the use of sericin cream can reduce UP in hemodialysis patients according to their VAS scores. Sericin cream can also significantly increase skin hydration and reduce skin irritation and skin pigmentation in patients. The molecular weight analysis of the sericin used in this study gave results that agree with those reported by Sprague, who indicated that sericin is a mixture of at least 15 different polypeptide chains ranging in size from 20–220 kDa . Similar to the earlier report by Kato et al., serine was the most abundant amino acid found in sericin .
Although antihistamines, anti-allergic agents and topical corticosteroids are commonly used to treat UP in ESRD patients, their effectiveness is sometimes limited [2, 8, 21, 22]. Alternative and effective treatments for intractable pruritus that generate low levels of adverse reactions, particularly in sensitive patients such as the ESRD group, must therefore be developed. This clinical study is the first to suggest that a sericin cream is beneficial for treating pruritus in hemodialysis patients. The benefits of this treatment apparently result from increases in skin hydration and suppression of pro-inflammatory cytokines, as shown in our earlier study [17, 23], thereby resulting in less skin irritation without any allergic reactions.
Pruritus associated with chronic kidney disease has been shown to be associated with elevated levels of C-reactive protein and other inflammatory cytokines. This evidence suggests that there is an inflammatory component in this form of pruritus . Some authors consider UP to be a skin manifestation of chronic inflammation . Recently, the “persistent microinflammation” theory, in which it is suggested that inflammation may be related to the genesis of UP, was proposed . The skin of ESRD patients with UP contains an increased number of mast cells, and these cells can release various substances such as histamine, interleukins (IL) and tumor necrosis factor (TNF) [27–30].
Pruritic skin can appear normal except for dryness; because the severity of pruritus is closely correlated with skin dryness , xerosis treatment normally begins with a topical agent such as a gentle moisturizing cream. Because sericin is well known for its moisturizing effect and its ability to reduce the generation of pro-inflammatory cytokines by fibroblasts, this study assessed the usefulness of sericin cream in treating UP. Evaluating the degree of pruritus was difficult because it is a subjective symptom; therefore, functional measurements of skin conditions known to be associated with pruritus, such as skin hydration and skin irritation, were considered to be objective indices. We found that both sericin cream and the cream base used to prepare the sericin cream increased the moisture content of the stratum corneum; however, the level of hydration was significantly higher in the skin treated with sericin cream. The side of the body treated with sericin cream had significantly lower levels of post-treatment dryness compared to pretreatment dryness and lower total dermatological severity scores in parameters such as skin pigmentation.
The pathogenesis of ESRD itself is associated with inflammation and oxidative stress, as reflected in studies of plasma biochemistry, including the levels of the cytokines IL and TNF-α [32–34], classic markers of inflammatory processes that are strongly affected by pathological conditions . These cytokines are upregulated in the plasma of ESRD patients [32, 36]. The skin inflammation associated with the release of IL and TNF-α is further complicated by the inflammatory lesions that occur secondary to scratching . Our results indicate that improvement in skin hydration and suppression of the release of pro-inflammatory cytokines in skin might be the mechanism by which sericin improves UP. Skin irritation, which can be caused by either skin inflammation or by scratching, was substantially reduced in the sericin group compared with the cream base group after 6 weeks of treatment. This result confirmed that sericin reduces skin irritation in patients with UP and suggested that it might be due to suppression of the inflammatory cytokines in skin. Similar results have been obtained in animal studies .
Secondary skin lesions that can result from the itch-scratch cycle include excoriations, hyperpigmentation, lichenification, prurigo nodules and scars . Chronic renal failure is usually accompanied by a variety of cutaneous manifestations; dermal manifestations, including hyperpigmentation, have also been reported, and these can exact a considerable toll on the quality of life [39–41]. Although skin pigmentation is not related to specific clinical symptoms, it has an important effect on patient satisfaction. Sericin has been reported to have activity against tyrosinase , an enzyme related to melanin production; as this study shows, treatment with sericin results in significant reduction in the skin color of patients.
The pruritus/mortality relationship may be strongly attributed to sleep disturbances, as previously mentioned in the DOPPS [8, 9, 42]. Many previous studies have found a strong association between inflammation, as measured by C-reactive protein or inflammatory cytokines, and sleep disturbances in dialysis patients [43–45]. The significant effects of pruritus on sleep, mood and social functioning require further investigation with the goal of improving the available treatments for this serious ESRD complication. We found that reduction in itching intensity from moderate to severe pruritus at the time of enrollment to mild pruritus after 6 weeks of treatment was associated with a better quality of life in all of the measured domains, including the mental, physical and kidney disease components. The KDQOL-SF score in the ESRD patients indicated improvements in several domains regarding the patients’ quality of life, particularly pain and sleep, which are relevant to itching. A better quality of sleep may reflect some degree of relief from itching achieved through the treatments.
This study has certain limitations. First, the study design was an in-subject controlled study; it cannot be determined whether the improvements in the itching evaluation and the quality of life were from the sample (sericin cream) or the placebo (cream base). Moreover, due to the in-subject controlled design, the biochemical parameters could not be evaluated at the end of the study. Second, the study included a small number of patients, and these were followed for a relatively short time. A long-term study with a larger sample size is necessary. In addition to studies of hemodialysis patients, similar studies of other ESRD patients, such as peritoneal dialysis and kidney transplant patients, are also necessary to confirm the findings presented here.