Itch in Atopic Dermatitis - What Is New?

Atopic dermatitis (AD) is among the most frequent inflammatory skin diseases in humans, affecting up to 20% of children and 10% of adults in higher income countries. Chronic pruritus is a disease-defining symptom of AD, representing the most burdensome symptom for patients. Severe chronic pruritus causes significant sleep disturbances and impaired quality of life, as well as increased anxiety, depression and suicidal behavior. Until recently, skin care, topical corticosteroids, and calcineurin-inhibitors were primarily used to treat mild to moderate AD, while phototherapy and immunosuppressive agents such as corticosteroids, cyclosporine, and methotrexate were used to treat patients with moderate to severe AD. The potential short- and long-term adverse events associated with these treatments or their insufficient therapeutic efficacy limited their use in controlling pruritus and eczema in AD patients over longer periods of time. As our understanding of AD pathophysiology has improved and new systemic and topical treatments have appeared on the market, targeting specific cytokines, receptors, or their intracellular signaling, a new era in atopic dermatitis and pruritus therapy has begun. This review highlights new developments in AD treatment, placing a specific focus on their anti-pruritic effects.

Quality of Life, Anxiety, and Depression in Patients With Early-Stage Mycosis Fungoides and the Effect of Oral Psoralen Plus UV-A (PUVA) Photochemotherapy on it.

Background: Little is known about psychological discomfort and quality of life (QoL) in early stage mycosis fungoides (MF) and the effect of psoralen plus UV-A (PUVA) on it. Objective: To evaluate QoL, anxiety, and depression with validated instruments in early stage MF patients and whether PUVA treatment improves it. Methods: Patients with stage IA to IIA MF were treated with PUVA twice weekly for 12-24 weeks, followed by maintenance treatment or not, in a prospective randomized clinical trial. Patients completed a questionnaire on DLQI as well as the Hospital Anxiety and Depression Scale (HADS) prior to therapy, after their last PUVA exposure, and after the PUVA maintenance or observance phase. Results: For 24 patients with early stage MF, completed questionnaires were available and analyzed. Prior to treatment, 17% reported strong (DLQI > 10) and 29% moderate impairment (DLQI 6-10) in QoL; 33% of patients reported HADS scores indicating anxiety, and 21% reported scores indicating depression. PUVA significantly improved overall QoL by reducing mean DLQI scores by 58.6% (p = 0.003), HADS-A by 30% (p = 0.045), and HADS-D by 44% (p = 0.002). Improvements in QoL and psychological well-being seemed to be sustained, irrespective of maintenance treatment or not. Limitations: Small sample size. Conclusions: PUVA sustainably improves QoL and psychological well-being in patients with early stage MF. Clinical trial registration: ClinicalTrials.gov identifier: NCT01686594.

Is there still a role for UV therapy in itch treatment?

Itching is a frequent and greatly distressing symptom related to many skin and systemic diseases. New insights into the pathophysiology of itchy skin and potentially involved mediators have increased the interest in and development of new treatments that specifically act on targets involved in the transmission and perception of itching. Phototherapy has long been known and used as an effective treatment for various kinds of chronic itching. However, despite its well-known beneficial effects, the mechanisms behind the antipruritic effect of phototherapy are less well-known. In addition, phototherapy requires the use of expensive equipment in dermatology offices, patients must undergo repeated treatments and no large, randomized, controlled trials have yet supported the antipruritic effect of UV. Therefore, phototherapy is rarely recommended as a treatment method for chronic pruritic diseases or only used as a last recourse. However, the wide range of pruritic conditions that can be successfully treated with phototherapy, together with its low acute side effects, extremely low frequency of interactions with other medications, possibilities to combine phototherapy with other treatment modalities and the fact that patients of almost all ages-from childhood to old age, including women during pregnancy or lactation-can be treated make UV therapy advantageous over other treatments of chronic pruritus. Thus, despite the development of new targeted therapies against pruritus, UV therapy is neither outdated nor the 'last recourse', but should be considered early on in the treatment of chronic pruritus.

The Antipruritic Effect of Phototherapy.

Phototherapy is widely used to treat inflammatory skin diseases such as psoriasis and atopic dermatitis. Repeated suberythemogenic doses of UV-light reduce inflammation in these diseases and ultimately may lead to a complete disappearance of cutaneous symptoms for weeks or months. Chronic pruritus is an important and highly distressing symptom of many of these inflammatory skin diseases. Interestingly, pruritus is also reduced or completely abolished by UV-treatment of psoriasis and atopic dermatitis, and sometimes reduction of pruritus is the first indication for skin improvement by phototherapy. The cutaneous nervous system is an integral part of skin anatomy, and free nerve endings of sensory cutaneous nerve fibers reach up into the epidermis getting in close contact with epidermal cells and mediators from epidermal cells released into the intercellular space. Stimulation of "pruriceptors" within this group of sensory nerve fibers generates a neuronal signal eventually transmitted via the dorsal root and the spinal cord to the brain, where it is recognized as "itch". UV-light may directly affect cutaneous sensory nerve fibers or, via the release of mediators from cells within the skin, indirectly modulate their function as well as the transmission of itch to the central nervous system inducing the clinically recognized antipruritic effect of phototherapy.

[Importance of phototherapy in the treatment of chronic pruritus]. / Stellenwert der Phototherapie in der Behandlung des chronischen Pruritus.

Phototherapy and photochemotherapy (PUVA) are important treatment modalities in inflammatory skin diseases such as psoriasis and atopic dermatitis as well as in cutaneous T­cell lymphoma (e.g., mycosis fungoides/Sezary syndrome). Many of these skin diseases are accompanied by distracting pruritus. In addition, patients may suffer from intense pruritus in systemic diseases of the kidney and liver as well as of the endocrine and hematopoietic system. UV-light during phototherapy is capable of not only improving the inflammatory skin lesions but also of reducing the pruritus in skin and systemic diseases. The significant antipruritic effect, the usually low rate of well-known side effects, as well as the possibility to treat adults of any age, pregnant and lactating women, and under certain circumstances also children, make phototherapy a valuable treatment option for pruritus of various origin. Thus, the use of phototherapy should be considered early in the course of antipruritic therapy, when topical treatment modalities are insufficient to significantly improve pruritus.

Retrospective long-term follow-up in patients with chronic palmoplantar dermatoses after good response to bath PUVA therapy.

BACKGROUND: Numerous studies have confirmed the short-term effectiveness of 8-methoxypsoralen bath PUVA therapy in patients with chronic palmoplantar dermatoses; however, little is known about long-term results. PATIENTS AND METHODS: In this retrospective study we examined the long-term results in 79 patients (mean age: 48 years) with chronic palmoplantar dermatoses who were treated with bath PUVA three times a week over an 8-year period. A good clinical response (a reduction of more than 50% of the skin lesions) occurred after a mean of 23 treatments and a mean cumulative UVA dose of 39 J/cm(2) in 51 patients (65%). In 2007 a questionnaire was sent to these 51 patients to assess the long-term outcome. RESULTS: With bath PUVA treatment, the best results were found in patients with hyperkeratotic eczema (17/22; 77% good clinical response) followed by patients with palmoplantar psoriasis (26/41; 63%) and patients with dyshidrotic eczema (8/16; 50%). Thirty-four patients (67%) answered the questionnaire after a mean follow-up interval of 4.3 years (10-87 months). Among these patients, 36% reported an improved course of disease after PUVA therapy with reduced frequency and/or intensity of the skin rash, and 29% of patients reported continued complete clearance. 79% of our patients reported a long-term reduction in the use of topical corticosteroids during the follow-up period (mean: 4.3 years). In addition, 67% of patients reported a lasting improvement in quality of life. CONCLUSIONS: These data show that bath PUVA may have a long-term, beneficial influence on the course of disease in a majority of patients with recalcitrant chronic palmoplantar dermatoses.

Narrowband UV-B phototherapy, alefacept, and clearance of psoriasis.

OBJECTIVE: To determine whether the addition of 311-nm narrowband UV-B (NB UV-B) phototherapy accelerates and improves the therapeutic efficacy of alefacept, a biological antipsoriatic drug approved for the treatment of moderate to severe psoriasis. DESIGN: Randomized half-body comparison study. SETTING: Ambulatory section of a university hospital photodermatology unit. PATIENTS: Fourteen patients with moderate to severe psoriasis. INTERVENTIONS: All patients were treated with 7.5 mg of intravenous alefacept once weekly for 12 weeks. Three times each week, a randomly selected body half (left or right) was treated with NB UV-B light until complete remission, defined as a reduction in the Psoriasis Area Severity Index (PASI) to 3 or lower, was achieved on the irradiated body half. MAIN OUTCOME MEASURES: Modified PASI, self-assessed visual analogue scale rating of skin lesions, and self-assessed therapeutic efficacy. RESULTS: After 12 weeks of treatment, the mean PASIs on UV-irradiated and nonirradiated body halves were significantly reduced by 81% and 62%, respectively (P < .001). From week 3 to week 12, the mean PASI was significantly lower on UV-irradiated body halves than on nonirradiated body halves (P < .001). At week 12, PASI reductions of greater than 75% had been achieved significantly more often on UV-irradiated body halves (86%, 12 of 14) than on nonirradiated body halves (43%, 6 of 14), and complete remission had been achieved significantly more often on UV-irradiated body halves (43%, 6 of 14) than on nonirradiated body halves (0 of 14) (McNemar test P = .03). CONCLUSIONS: In this randomized half-side comparison of alefacept with and without phototherapy for psoriasis, alefacept with NB UV-B phototherapy accelerated and improved the clearance of psoriasis. This suggests a promising future for this combination as antipsoriatic therapy.

Reduction of treatment frequency and UVA dose does not substantially compromise the antipsoriatic effect of oral psoralen-UVA.

BACKGROUND: The carcinogenic potential of 8-methoxypsoralen photochemotherapy (psoralen-UVA [PUVA]) is correlated with the total number of treatments and cumulative UVA dose applied during oral PUVA therapy. OBJECTIVE: We sought to determine whether reducing treatment frequency and UVA dose affects the therapeutic efficacy of oral PUVA for patients with chronic plaque psoriasis. METHODS: This was a prospective, randomized, half-side study performed in a photodermatology department in a dermatology hospital. Eighteen consecutive patients with chronic plaque psoriasis received paired PUVA regimens (0.5 minimal phototoxic dose [MPD] 4 times/wk vs 1 MPD twice/wk, 0.5 MPD twice/wk vs 1 MPD twice/wk, and 0.5 MPD twice/wk vs 0.75 MPD twice/wk). The PUVA regimens were assessed for reduction of Psoriasis Area and Severity Index (PASI) score and the number of treatments and cumulative UVA dose required to reduce PASI score to defined end points (ie, PASI reductions of 25%, 50%, and 75%) or to induce complete remission (PASI < 3). RESULTS: Reducing the number of treatments while maintaining the same UVA dose per week did not reduce overall therapeutic efficacy. Reducing the number of treatments to twice a week and reducing the UVA dose from 1 MPD to 0.75 or 0.5 MPD per treatment only slightly affected intermediate therapeutic efficacy (between the second and seventh weeks of therapy) but had no effect on final clearance rates. The time to complete clearance did not significantly differ between regimens. The mean cumulative UVA dose was significantly lower for the least intensive dose regimen (0.5 MPD twice/wk) than for the more intensive regimens. CONCLUSIONS: Reducing treatment frequency and UVA dose does not substantially compromise the therapeutic efficacy of PUVA.

Repeated subinflammatory ultraviolet B irradiation increases substance P and calcitonin gene-related peptide content and augments mustard oil-induced neurogenic inflammation in the skin of rats.

The cutaneous neurosensory system is suggested to be involved in the pathophysiology of pruritus and skin diseases such as psoriasis. We investigated if repeated subinflammatory doses of ultraviolet B (UVB) irradiation similar to those used to treat pruritus or psoriasis would affect the cutaneous neurosensory system. Sprague-Dawley rats were irradiated thrice weekly for 2-4 weeks with subinflammatory doses of UVB. Three days after the last UVB exposure: (i), the skin contents of substance P (SP), calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF) were quantified; (ii), the skin nerve fiber density was observed; and (iii), the effect of UVB on mustard oil-induced neurogenic inflammation was determined. UV exposure significantly increased SP and CGRP content and mustard oil-induced neurogenic inflammation in UV-irradiated but not non-irradiated skin; however, it did not affect cutaneous NGF content or overall nerve fiber density. These data suggest that repeated subinflammatory UVB irradiation locally increases the content of cutaneous SP and CGRP by an increase of neuropeptide content of nerve fibers rather than by an increase of overall nerve fiber density.