Granzyme B: A novel therapeutic target for treatment of atopic dermatitis.

Granzyme B is a serine protease that can play multiple roles in intracellular and extracellular perforin-dependent or non-perforin-dependent mechanisms. Granzyme B has been found to be an important factor involved in the pathogenesis of atopic dermatitis and is increased in both skin lesions and peripheral blood of atopic dermatitis patients. In this article, we review the correlation between granzyme B and atopic dermatitis to provide a novel therapeutic targeting option for clinical treatment of the latter.

JAK inhibitors and monoclonal antibodies for the treatment of atopic dermatitis: effectiveness and value.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, The Donaghue Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from AbbVie, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Sun Life Financial, uniQure, and United Healthcare. Agboola, Herron-Smith, Nhan, Rind, and Pearson are employed by ICER. Through their affiliated institutions, Atlas, Brouwer, Carlson, and Hansen received funding from ICER for the work described in this summary.

Phototherapy for atopic dermatitis.

BACKGROUND: The aim of these guidelines is to review the available published literature regarding the effectiveness of phototherapy and photochemotherapy in atopic dermatitis and put forward recommendations regarding their use in atopic dermatitis. MATERIALS AND METHODS: A literature search was performed to collect data from PubMed, EMBASE, and the Cochrane Library published till March 2014. Keywords used were "phototherapy", "photochemotherapy", "NB-UVB", "BBUVB", "PUVA", "UVA1", "atopic dermatitis", and "atopic eczema". Systematic reviews, meta-analysis, national guidelines, randomized controlled trials, prospective open label studies, and retrospective case series in English literature mentioning use of above-mentioned keywords were reviewed. RESULTS: Six hundred and eighty eight studies were evaluated, 38 of which fulfilled the criteria for inclusion in the guidelines. CONCLUSIONS AND RECOMMENDATIONS: Both UV1 and narrow-band UVB are effective in significantly decreasing the eczema severity although UV1 may be preferred in acute flares and narrow-band UVB in chronic eczema, especially in adults (Level of evidence 1+, Grade of recommendation A). Among various doses of UVA1, medium dose UVA1 may be preferred over others as its efficacy is similar to high dose and better than low dose UVA1 phototherapy. Narrow-band UVB is preferred to broad-band UVB (Level of evidence 1+, Grade of recommendation A). Medium-dose UVA1 is similar in efficacy to narrow-band UVB (Level of evidence 1+, Grade of recommendation A). In children, despite its efficacy, narrow-band UVB phototherapy should be used only as a second line therapy due to its potential for long-term adverse effects (Level of evidence 2+, Grade of recommendation B).

Evaluation of hypothalamic-pituitary-adrenal axis in patients with atopic dermatitis.

BACKGROUND: Most of the research on atopic dermatitis (AD) has focused on the pathophysiological role of the immune system in AD, and the role of endocrine signals in the pathology of AD has not been explored. Current research has shown a link between the neuroendocrine and immune functions. AIM: The aim was to measure the serum basal cortisol levels and cortisol levels following a low-dose ACTH stimulation test in patients with AD before and after treatment with corticosteroids. METHODS: Three groups of patients with AD were evaluated: mild, moderate, and severe. Basal cortisol levels following an ACTH stimulation test were measured before and after treatment with topical steroids when an improvement in the disease activity by 75% as determined by the SCORAD index was observed. RESULTS: Eighteen patients of the severe group at baseline showed an impaired hypothalamic-pituitary-adrenal (HPA) axis with cortisol levels <250 nmol/l during their first visit. A total of 13 of 18 patients regained their HPA axis activity when the baseline cortisol was measured after using topical corticosteroids which resulted in 75% improvement in the disease activity. CONCLUSIONS: The disease activity rather than the use of topical corticosteroids is responsible for the low basal levels in patients with severe AD.

Atopic dermatitis in infants and children in India.

Atopic dermatitis (AD) is a chronic relapsing eczematous skin disease characterized by pruritus and inflammation and accompanied by cutaneous physiological dysfunction, with a majority of the patients having a personal or family history of "atopic diathesis." The term "atopic diathesis" refers to the presence of allergic rhinitis, bronchial asthma or AD. The universal occurrence of AD is no longer debated. However, published material about its natural history, etiopathogenesis, epidemiology, clinical patterns and management leave a lot to be known in the Indian scenario. In the present write-up, we will try to explore the wealth of knowledge about the disease available in our country and try to unfurl the complex interplay of different factors that are implicated for the development of this condition. The diagnosis of AD is based on a constellation of signs and symptoms. There is no laboratory "gold standard" for the diagnosis of AD. In a majority of the cases, the diagnosis is quite easy. Topical corticosteroids form the mainstay of topical treatment and, along with emollient, are able to control the condition in more than 80% of the cases. However, as use of long-term topical corticosteroid has the potential to produce local and systemic adverse effects, topical tacrolimus has come up as a useful molecule for the long-term control of the disease.

Administration of Ag85B showed therapeutic effects to Th2-type cytokine-mediated acute phase atopic dermatitis by inducing regulatory T cells.

Increase in the number of patients with atopic dermatitis (AD) has been recently reported. T helper (Th) cells that infiltrate AD skin lesions are Th2-type dominant; reduced exposure to environmental Th1-cytokine-inducing microbes is believed to contribute to the increased number of AD patients. Regulatory type immune responses have been also associated with the occurrence of AD. It has been reported that antigen 85B (Ag85B) purified from mycobacteria is a potent inducer of Th1-type immune response in mice as well as in humans. In this study, we have examined the effect of plasmid DNA encoding Ag85B derived from Mycobacterium kansasii on AD skin lesions induced by oxazolone (OX) application. Th2-cytokine mediated mouse AD model with immediate type response followed by a late phase reaction was developed by repeated applications of low-dose OX to sensitized mice. Mice were immunized with plasmid DNA encoding cDNA of Ag85B before OX sensitization or during repeated elicitation phase. Both therapies were associated with significant suppression of immediate type response, clinical appearance, dermal cell infiltration, reduced IL-4 production, and augmented IFN-gamma mRNA expression compared to placebo-treated mice. Additionally, increased number of Foxp3(+) regulatory T cells were observed in the skin sections in Ag85B treated mice. The results of this study suggest that Ag85B DNA vaccine is a potential therapy for Th2 type dermatitis.

Evening primrose oil is effective in atopic dermatitis: a randomized placebo-controlled trial.

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing, itchy dermatosis of multifactorial origin, which commonly starts in childhood. Defective metabolism of essential fatty acids leading to relative dominance of pro-inflammatory prostaglandins (PGE2 and PGF2) has been reported as an important factor in the pathogenesis of AD. Evening primrose oil (EPO) as a source of gamma-linolenic acid (GLA) has been of interest in the management of AD. AIM: To evaluate the efficacy and safety of EPO in atopic dermatitis in our patients. METHODS: Consecutive new out-patient department (OPD) patients of a referral hospital in Kolkata clinically diagnosed as having AD were randomly allocated to two groups. To the first group, evening primrose oil was supplied as 500-mg oval clear unmarked capsules, while placebo capsules identical in appearance and containing 300 mg of sunflower oil were given to the other group. Treatment continued for a period of 5 months. With pre-designed scoring system (based on four major parameters: extent, intensity, itching, and dryness), clinical evaluation was done at baseline and subsequent monthly visits. Data of the first 25 patients from each group who completed the 5 months of trial were compiled and analyzed. RESULTS: At the end of the fifth month, 24 (96%) patients of EPO group and 8 (32%) patients of placebo group showed improvement. There was significant difference in outcome of treatment between two groups (P<0.00001). No significant adverse effect was reported by any patient/guardian at any point of assessment. CONCLUSION: Evening primrose oil is a safe and effective medicine in management of AD. However, since not all researchers across the world have found the same good result, further large trials on Indian patients are needed.

Efficacy and safety of combination ointment "fluticasone propionate 0.005% plus mupirocin 2.0%" for the treatment of atopic dermatitis with clinical suspicion of secondary bacterial infection: an open label uncontrolled study.

BACKGROUND: The skin of patients with atopic dermatitis is colonized with Staphylococcus aureus. Reduction of bacterial colonization has been reported to be effective in the treatment of atopic dermatitis. AIM: To assess the efficacy and safety of a combination of fluticasone propionate 0.005% and mupirocin 2.0% ointment twice daily for 2 weeks in patients with atopic dermatitis clinically suspected of secondary bacterial infection. METHODS: An open-label, non-randomized study of 122 patients (64 males and 58 females) from 20 centers was conducted. Atopic dermatitis was diagnosed by clinical assessment and scoring was done on the visual analogue scale (VAS). Clinical evaluation of the lesions was done on day 1 (baseline), day 8 and on day 15 of study visits. RESULTS: At baseline, many patients had moderate itching (41.8%), moderate dryness (41.8%) and mild weeping lesions (49.2%). The baseline proportions of the clinicians' global impressions (CGI) scale for mild, moderate and severe atopic dermatitis lesions were 19.7%, 55.7% and 12.2% respectively. At the end of the treatment period, 67.2% patients had mild disease, whereas only 9% and 0.8% patients had moderate and severe disease respectively. At baseline, only 33.65% patients were comfortable with the existing lesions when assessed on visual analog scale (VAS). However, after the treatment, this proportion increased to 51.77% and 78.60% patients on day 8 and on day 15 respectively. CONCLUSION: Twice daily topical application of a fluticasone propionate 0.005% and mupirocin 2.0% ointment is an effective and safe therapeutic regimen in atopic dermatitis.