Effects of tacrolimus ointment on facial eruption, itch, and scratching in patients with atopic dermatitis

The action of tacrolimus ointment on pruritus in atopic dermatitis is still unclear. In this open study we investigated both the relationship between the severity of eruptions and the degree of itch and scratching in patients with atopic dermatitis and the effects of topical tacrolimus on these symptoms. Seventy adults with moderate to severe atopic dermatitis with facial eruptions that were recalcitrant to topical steroids applied a 0.1% tacrolimus ointment twice per day after discontinuation of topical steroid. The eruption scores and an assessment of the itch and scratching were recorded for 12 weeks. Oral antihistamine was prescribed at least one month before the study and continued unchanged during the study in each patient. The percentage reduction in the score of itch and scratching after two weeks (n=59) was significantly higher than in the score of eruption. Although there was no significant relationship between the severity of the eruptions and the degree of itch and scratching during steroid application, a relationship became significant after four weeks (n=59) of tacrolimus use by a one-factor ANOVA analysis. This suggests that tacrolimus ointment is effective for the itch and scratching in cases where degrees might be discrepant from the severity of eruptions in patients with recalcitrant facial eruptions of AD.     

Some methods for evaluating clinical itch and their application for studying pathophysiological mechanisms.

Research on itch has been hampered by difficulties in measuring the itch sensation. A microcomputer-based system, where the patients themselves record their symptoms on portable data loggers can be used for quantitative measurements of clinical itch and for the detection of antipruritic effects of drugs. By using this system we have found that itch in atopic dermatitis is not inhibited by antihistamines but by cyclosporin A, a drug inhibiting cytokine production. Thus histamine is not a major pruritogen in atopic dermatitis. A hypothesis is proposed that cytokines are involved in itch in atopic dermatitis.     

Impact of acute stress on itch sensation and scratching behaviour in patients with atopic dermatitis and healthy controls

Patients with atopic dermatitis (eczema) often report that stress is a major factor to worsen their itchy skin. This study investigated the effects of acute stress on itch, urge to scratch, and scratching behavior in subjects with atopic dermatitis compared to healthy controls. Stress was created in a standardized way using the Trier Social Stress Test (TSST), where subjects were asked to perform a public speaking task and mental arithmetic. In a second control visit, instead of being stressed, subjects watched a non-stressful video of landscape scenes. Both subjects with atopic dermatitis and healthy subjects reported feeling stressed after the TSST. Interestingly, atopic dermatitis subjects who were more sensitive to stress also had higher eczema severity. Before and after the TSST or landscape video, cowhage (a plant that causes itch) was applied to the arm of each subject. Patients with atopic dermatitis reported less itch from cowhage and less urge to scratch after they had been stressed by the TSST. However, despite reporting less itch, they actually scratched their limbs significantly more when they were stressed. Healthy individuals did not have any difference in itch, urge to scratch, or scratching behavior in the stressful condition compared to the control landscape video condition. This study shows that acute stress can affect itch and scratching differently in chronic itch patients compared to healthy individuals. Stress led to more scratching in those with atopic dermatitis. Over time, this response to stress could lead to increased skin damage from scratching and therefore worse eczema and itch.     

Antipruritic effect of oral cyclosporin A in atopic dermatitis

The effect of ten days' treatment with cyclosporin A, 5 mg/kg/day, in 10 adults with atopic dermatitis was investigated using a double-blind, randomized, placebo-controlled, cross-over design. Evaluation was based on itch recording, clinical scoring and immunohistochemical examination of skin biopsy specimens. Cyclosporin A significantly reduced the itch intensity, the eczema score and the consumption of topical hydrocortisone. A significant decrease in serum magnesium and in the total number of blood eosinophils was seen. No other laboratory abnormalities were observed. In lesional skin, Cyclosporin A induced a relative decrease of CD3+ T cells in 5/10 patients, of HLA-DR+ cells in 6/10, and of interleukin-2-receptor positive (CD25+) cells in 4/10. However, these changes in phenotype expression did not seem necessary for itch relief. Relapse of clinical symptoms was seen within 2-30 days of completion of the Cyclosporin A course. The mechanism of the antipruritic effect remains unclear, but the present findings may support the hypothesis that 'pruritogenic cytokines', whose production is inhibited by Cyclosporin A, may be important in the pathogenesis of itch in atopic dermatitis.     

Itch in atopic dermatitis - pathophysiology and treatment

Pruritus is an essential feature of atopic dermatitis with a high impact on the quality of life. Although the pathophysiology of atopic dermatitis itch is not fully understood, recent studies have demonstrated that a variety of mechanisms contribute to the induction and maintenance of the symptom. For example, an increased number of cutaneous nerve fibers and neuropeptides were identified in atopic dermatitis skin. Histamine and histamine 4 receptor as well as interleukin 31 are novel key players identified in itch induction, in addition to inflammatory cells such as mast cells, eosinophils and lymphocytes. The new findings suggest that target-specific therapies are most likely to control atopic dermatitis itch. To date, only few therapies are available and controlled studies are pending.     

Topical E6005, a novel phosphodiesterase 4 inhibitor,attenuates spontaneous itch‐related responses in mice with chronic atopy‐like dermatitis

Atopic dermatitis is a chronic inflammatory cutaneous disease with difficult‐to‐treat pruritus. Although phosphodiesterase (PDE) 4 inhibitors have an anti‐inflammatory effect on inflammatory skin diseases, such as atopic dermatitis, their acute antipruritic activities remain unclear. Therefore, in this study, we examined whether E6005, a novel PDE4 inhibitor, has antipruritic activity in dermatitis, using a mouse model of atopic dermatitis (NC/Nga mice). A single topical application of E6005 inhibited spontaneous hind‐paw scratching, an itch‐associated response and spontaneous activity of the cutaneous nerve in mice with chronic dermatitis. The cutaneous concentration of cAMP was significantly decreased in mice with chronic dermatitis, and this decrease was reversed by topical E6005 application. These results suggest that E6005 increases the cutaneous concentration of cAMP to relieve dermatitis‐associated itching. Thus, E6005 may be a useful therapy for pruritic dermatitis such as atopic dermatitis.     

New therapies for controlling atopic itch

Chronic itch in atopic dermatitis markedly diminishes the quality of life of affected individuals. Sleep disturbance and impaired productivity in work due to chronic itch impose a socioeconomic burden. Conventional therapies for atopic dermatitis are capable of reducing atopic itch. However, the majority of patients are not satisfied with the antipruritic capacity of conventional treatments. In this review, we summarize recent progress in itch signaling in the skin, dorsal root ganglion and spinal cord. New therapies for controlling atopic itch are also discussed.     

Itch intensity evaluated in the German Atopic Dermatitis Intervention Study (GADIS): correlations with quality of life, coping behaviour and SCORAD severity in 823 children

The German Atopic Dermatitis Intervention Study (GADIS), which includes 823 children and adolescents, showed that age-related educational programmes are effective in the long-term management of atopic dermatitis. We investigated whether the itch severity obtained in the scoring of atopic dermatitis (SCORAD) correlates with quality of life and coping behaviour in children and parents. There were significant but low correlations between the severity of atopic dermatitis and the itch intensity. Itch and sleeplessness were significantly correlated. Significant correlations of itch with the coping behaviour and quality of life in parents of children with atopic dermatitis were measured. The coping and itching behaviour of children (8-12 years) and adolescents (13-18 years) had higher significant correlations with the itch compared with the parents' answers. Quality of life in children (8-12 years) and adolescents (13-18 years) showed a significant negative correlation with itch intensity. Quality of life, itch intensity and coping strategies should be considered when treating patients with atopic dermatitis.     

Rapid effects of olopatadine hydrochloride on the histamine-induced skin responses

Olopatadine hydrochloride is one of the second-generation nonsedating antihistamines that are used for treating allergic disorders such as urticaria, rhinitis, and atopic dermatitis. We examined the inhibitory effects of this drug on the flare and wheal responses induced by histamine iontophoresis at 30, 60, and 90 min after oral administration in a double-blind, cross-over, and placebo-controlled study. Olopatadine hydrochloride significantly inhibited the histamine-induced flare and wheal responses as early as 60 min after oral administration when compared with placebo. Significant inihibitory effects of olopatadine hydrochloride on the itch responses were seen at 90 min after administration. Thus, olopatadine hydrochloride exhibited a very rapid and potent antihistamine effect on the histamine-induced skin responses.     

Efficacy and problems associated with using a wet-wrap garment for children with severe atopic dermatitis

Use of a wet wrap for short-term relief of itch in children with severe atopic dermatitis has been advocated but objective determination of its efficacy has been difficult and many issues associated with its use are yet to be defined. We tested a new garment for the wet-wrap procedure in six patients with atopic dermatitis and objectively determined whether a 3-day usage could indeed relieve the distressing symptom of itch using a wrist motion monitor. The garments were effective in the short-term improvement of itching, severity of atopic dermatitis and quality of life in these children. Many issues associated with its use were identified. Clear instructions and individualized regimes (such as the choice of emollient, bathing ointment and topical corticosteroid) are essential for optimal outcome.     

Cromones in atopic dermatitis

Summary Three new cromones have been studied that are supposed to be better absorbed and to have a wider spectrum of anti-allergic activity than disodium cromoglycate. Pretreatment with i.d. injection of 10 g FPL 52758 significantly reduced the weal and flare reaction induced by specific antigen in 11 patients with atopic dermatitis. The weal and flare reaction was not reduced in the same patients when 1.5 mg of FPL 52758 was applied topically under occulusion for a 24-h period prior to challenge with antigen. The itch and slight pain caused by antigen injection was not experienced in the FPL 52758 pretreated areas.Preliminary clinical results were obtained with the cromone FPL 52757, but due to possible hepatotoxicity this trial was not completed. Another similar cromone without hepatotoxicity was used in a double blind within-patient study. Nine patients with mild to moderate atopic dermatitis were treated with FPL 57787 (5%) ointment and matching placebo ointment. No significant improvement was observed after 4 weeks of treatment with the cromone containing ointment.     

Failure of terfenadine in relieving the pruritus of atopic dermatitis

We report the results of a double-blind, placebo-controlled, cross-over study of terfenadine 120 mg twice daily for pruritus in atopic dermatitis. Twenty-eight subjects with chronic atopic dermatitis received both terfenadine 120 mg b.d. and placebo each for a period of 1 week. Response was recorded by the subjects using visual analogue scales for severity of pruritus twice daily for the last 4 days of each treatment phase. There was no benefit from terfenadine.     

咪唑斯汀治疗皮炎湿疹68例临床分析

目的评价咪唑斯汀治疗皮炎湿疹的临床疗效。方法118例皮炎湿疹患者随机分为两组,咪唑斯汀组68例口服咪唑斯汀10mg,氯雷他定组50例口服氯雷他定10mg,均1次/d。结果咪唑斯汀治疗急慢性湿疹和异位性皮炎3周有效率为90.7%,氯雷他定组为60.0%,两组差异有显著性(P<0.01);咪唑斯汀与氯雷他定对接触性皮炎的1周有效率均为100%,差异无显著性(P>0.05)。结论咪唑斯汀是治疗皮炎湿疹等过敏性疾病的理想药物。     

Effect of standard medication on quality of life of patients with atopic dermatitis

Patients with atopic dermatitis present with debilitating symptoms, including pruritus and subsequent excoriation, which significantly reduces their quality of life (QOL). At present, the standard therapy for atopic dermatitis constitutes a topical steroid and/or a topical immunomodulator, an emollient and an oral antihistamine, although few studies have reported the effect of this treatment regimen on QOL. The current study aimed to verify the efficacy of the standard therapy for both clinical symptom severity and patient QOL, assessed using the validated Skindex-16 questionnaire. Atopic dermatitis patients receiving the standard therapy (n=771) were enrolled in the current phase IV, multicenter, 12-week, open-label study. The Rajka and Langeland scale (used to rate the severity of atopic dermatitis symptoms) and the Skindex-16 QOL questionnaire were completed at weeks 0 (baseline), 4 and 12. Of 415 patients completing the questionnaire at all time points (per-protocol population), 95.2% were prescribed the antihistamine fexofenadine HCl 60 mg. There were significant improvements in symptoms, emotions and functioning scale scores at weeks 4 and 12 compared with baseline (P<0.005). Discomfort associated with itching, as assessed by item 1 on the Skindex-16, improved over the treatment period (score decreased by >or=1 and >or=2 in 75.2% and 50.9% of patients, respectively). Significant (P<0.005) improvements from baseline in global scores were also observed at weeks 4 and 12, and for week 12 compared with week 4. Severity scores improved significantly (P<0.005) from weeks 0-4 and from weeks 4-12. The standard therapy was generally well tolerated with only mild adverse events reported (0.5%). These data suggest that patients with atopic dermatitis and associated pruritus experience significant improvements in both symptom severity and QOL when receiving standard therapy.     

Electrode design for skin electroporation with minimal nerve stimulation

Itch is one of the major symptoms of various skin diseases. Although specific neuronal pathways for itch were identified both peripherally and centrally, they still fail to explain itchy skin observed in patients with chronic pruritus. In this study, sensitivity to itchy and painful stimuli in patients with atopic dermatitis was investigated. Histamine-prick evoked enormous itch in their lesional skin, while less itch in their non-lesional skin than healthy subjects. Flare reaction was not significantly different between their non-lesional and lesional skin, rather smaller than healthy subjects. Mechanical (pin-pricks), electrical, heat and chemical (injection of pH3 solution) stimuli evoked intense itch in their lesional skin and partly also in their non-lesional skin, while only pain in healthy subjects. Itch was also, but not intensely, evoked in healthy subjects by injection of pH3 solution after sufficient histamine stimuli. These results confirm the presence of itchy skin with hyperkinesis (excessive itch by itchy stimuli) and allokinesis (itch by non-itchy stimuli) in patients with atopic dermatitis, which is so intense that painful stimuli cannot suppress but evoke itch, and suggest that neuronal sensitization is involved in their itch not only peripherally but also centrally.     

Non‐corticosteroid adherence and itch severity influence perception of itch in atopic dermatitis

Topical corticosteroid phobia is an important problem in the treatment of atopic dermatitis as it can affect the ability to control disease severity and itch by reducing treatment adherence. Topical corticosteroid phobia often ends up even non‐corticosteroid adherence. As such, non‐corticosteroid adherence, disease severity and itch are likely to be associated with each other, but their relationship has yet to be thoroughly investigated. Thus, the purpose of this study is to investigate it in atopic dermatitis. Using data from 1190 participants in an Internet survey, we identified 255 non‐corticosteroid users and 225 with moderate to severe itch who were defined as non‐corticosteroid adherents. Corticosteroid users with the same itch categories (n = 878) served as controls. We also examined how itch severity affects the perception of itch in atopic dermatitis. Unexpectedly, non‐corticosteroid adherents were less sensitive to the conditions to elicit itch such as perspiring, commuting homeward, drinking alcohol and wearing woolen clothes compared with the control. We also found that patients with severer itch were more sensitive to itch during/after bathing, when lying in bed, commuting homeward, studying/working, drinking alcohol, undressing, getting up in the morning, after a meal, ingesting piquant foods and when they were unoccupied, angry, busy, nervous, sad or enjoying themselves. In conclusion, we found that non‐corticosteroid adherence and itch severity influence perception of itch in atopic dermatitis and discuss possible mechanisms underlying these results. The information obtained in this study may be useful for communication with and education of atopic dermatitis patients and their treatment in outpatient clinics.     

Neuroimmune interactions in chronic itch of atopic dermatitis

Itch is a defining symptom of atopic dermatitis. Crosstalk between keratinocytes, the immune system and non-histaminergic sensory nerves is responsible for the pathophysiology of chronic itch in atopic dermatitis. An expanding understanding of the contribution of the nervous system and its interaction with immune pathways in atopic itch are helping to identify new therapeutic strategies.