Apheresis in the treatment of recalcitrant atopic dermatitis: case series and review of the literature

Background

Atopic dermatitis is a chronic disabling inflammatory skin disorder, typically characterized by intensely itching, oozing, crusted, eroded vesicles or papules developing on erythematous plaques. Conventional treatments, both topical and systemic, may produce unsuccessful and unsatisfactory results.

Objectives

we aimed to assess the efficacy of apheretic treatments in patients with severe, recalcitrant AD, in particular, the pruritic component.

Patients and methods

four patients affected by recalcitrant and debilitating atopic dermatitis, who had previously received conventional topical and systemic therapies with poor clinical improvement, were treated with extracorporeal photopheresis or therapeutic plasma exchange.

Results

a satisfactory response to apheresis was observed with a reduction of pruritus and skin lesions.

Conclusion

In our experience, apheretic therapies might be used as monotherapy but, more effectively, in combination with topical and/or systemic treatments. Indeed, they proved to be a safe “enhancer” for increasing the efficacy of conventional therapeutics.

     

Diagnostic criteria for atopic dermatitis: a systematic review

BACKGROUND: Atopic dermatitis (AD) has a wide spectrum of dermatological manifestations and despite various validated sets of diagnostic criteria that have been developed over the past decades, there is disagreement about its definition. Nevertheless, clinical studies require valid diagnostic criteria for reliable and reproducible results. OBJECTIVE: To summarize the evidence concerning the validity of diagnostic criteria for AD. METHODS: All data sources were identified through searches on Medline, Embase and Cochrane databases. The Quality Assessment of Diagnostic Accuracy tool (QUADAS) was used. Results are presented in a receiver operating characteristic (ROC) plot. RESULTS: Out of the 20 articles that met the criteria, 27 validation studies were identified. In two studies concerning Hanifin and Rajka diagnostic criteria sensitivity and specificity ranged from 87.9% to 96.0% and from 77.6% to 93.8%, respectively. Nineteen validation studies of the U.K. diagnostic criteria showed sensitivity and specificity ranging from 10% to 100% and 89.3% to 99.1%, respectively. Three validation studies concerning the Schultz-Larsen criteria showed sensitivity from 88% to 94.4% and specificity from 77.6% to 95.9%. In one article concerning the criteria of Diepgen, the sensitivity ranged from 83.0% to 87.7% and the specificity from 83.9% to 87.0%. One article studied the Kang and Tian criteria and reported 95.5% sensitivity and 100% specificity. One article validating the International Study of Asthma and Allergies in Childhood (ISAAC) criteria showed a positive and negative predictive value of 48.8% and 91.1%, respectively. CONCLUSION: With this systematic review of the existing sets of diagnostic criteria for AD a varying number of validation studies with varying methodological quality was found. The U.K. diagnostic criteria are the most extensively validated. However, improvement of methodological design for validation studies and uniformity in well-validated and applicable diagnostic criteria are needed to improve future intervention studies and to compare study results.     

Omalizumab for the treatment of atopic dermatitis

Atopy is almost always associated with an elevated immunoglobulin (Ig) E production. Omalizumab is a monoclonal anti-IgE antibody that is currently indicated for the treatment of cases of asthma that satisfy certain criteria. A number of studies have been published on the usefulness of omalizumab in the treatment of atopic dermatitis, and the results have been variable. We present our experience in the treatment of 9 patients with severe atopic dermatitis refractory to at least 2 systemic drugs. All patients reported a decrease in pruritus and an improvement in quality of life. Good control of the skin disease was achieved with omalizumab in monotherapy in 2 patients, and there was a slight improvement in the eczematous lesions in 4 patients. Those patients who also had asthma achieved good control of their respiratory symptoms and did not require additional therapy. Omalizumab is a well-tolerated and safe drug that can be useful for the treatment of severe atopic dermatitis refractory to other systemic therapies. This monoclonal anti-IgE antibody is a major therapeutic advance as it opens the door to the management of atopic dermatitis using systemic immunomodulating therapies.     

Phototherapy in the management of atopic dermatitis: a systematic review

BACKGROUND/PURPOSE: Atopic dermatitis (AD) is a common and extremely burdensome skin disorder with limited therapeutic options. Ultraviolet (UV) phototherapy is a well tolerated, efficacious treatment for AD, but its use is limited by a lack of guidelines in the optimal choice of modality and dosing. Given this deficit, we aim to develop suggestions for the treatment of AD with phototherapy by systematically reviewing the current medical literature. METHODS: Data sources: All data sources were identified through searches of MEDLINE via the Ovid interface, the Cochrane Central Register of Controlled Trials, and a complementary manual literature search. STUDY SELECTION: Studies selected for review met these inclusion criteria, as applied by multiple reviewers: controlled clinical trials of UV phototherapy in the management of AD in human subjects as reported in the English-language literature. Studies limited to hand dermatitis and studies in which subjects were allowed unmonitored use of topical corticosteroids or immunomodulators were excluded. DATA EXTRACTION: Included studies were assessed by multiple independent observers who extracted and compiled the following data: number of patients, duration of treatment, cumulative doses of UV radiation, adverse effects, and study results. Data quality was assessed by comparing data sets and rechecking source materials if a discrepancy occurred. RESULTS: Nine trials that met the inclusion criteria were identified. Three studies demonstrated that UVA1 is both faster and more efficacious than combined UVAB for treating acute AD. Two trials disclosed the advantages of medium dose (50 J/cm(2)) UVA1 for treating acute AD. Two trials revealed the superiority of combined UVAB in the management of chronic AD. Two additional studies demonstrated that narrow-band UVB is more effective than either broad-band UVA or UVA1 for managing chronic AD. CONCLUSION: On the basis of available evidence, the following suggestions can be made: phototherapy with medium-dose (50 J/cm(2)) UVA1, if available, should be used to control acute flares of AD while UVB modalities, specifically narrow-band UVB, should be used for the management of chronic AD.     

中外特应性皮炎诊疗指南比较

特应性皮炎是一种炎症性、瘙痒性和慢性复发性皮肤病,其治疗强调根据病情制定长期的综合方案。i治疗方案的重要内容包括基础治疗、药物治疗和健康教育。以循证医学文献、专家讨论意见为基础的诊断和治疗指南是制定治疗方案的最佳依据。本文概述目前国内外重要的6项指南中关于特应性皮炎诊断和治疗意见的异同和强调的理念。     

Kaposi's sarcoma in an atopic dermatitis patient: a case report and a review of literature

A 7-year-old girl suffering from atopic dermatitis developed multiple lesions of Kaposi's sarcoma, which could not be categorized under any one of the four known types of Kaposi's sarcoma (classic, human immunodeficiency virus-associated, endemic, or iatrogenic). We propose that atopic dermatitis may cause susceptibility to human herpes virus 8 infection, which is related to the pathogenesis of Kaposi's sarcoma.     

Skin absorption through atopic dermatitis skin: a systematic review

Patients with atopic dermatitis (AD) have skin barrier impairment in both lesional and nonlesional skin. They are typically exposed daily to emollients and intermittently to topical anti‐inflammatory medicaments, thereby increasing the risk of developing contact allergy and systemic exposure to chemical ingredients found in these topical preparations. We systematically searched for studies that investigated skin absorption of various penetrants, including medicaments, in patients with AD, but also in animals with experimentally‐induced dermatitis. We identified 40 articles: 11 human studies examining model penetrants, 26 human studies examining AD drugs, and three animal studies. We conclude that patients with AD have almost twofold increased skin absorption compared with healthy controls. There is a need for well‐designed epidemiological and dermatopharmacokinetic studies that examine to what extent AD causes patients to be systemically exposed to chemicals compared with nonatopic dermatitis.     

The role of the skin microbiome in atopic dermatitis: a systematic review

Dysbiosis is a hallmark of atopic dermatitis (AD). The composition of skin microbiome communities and the causality of dysbiosis in eczema have not been well established. The objective of this review is to describe the skin microbiome profile in AD and address whether there is a causal relationship between dysbiosis and AD. The protocol is registered in PROSPERO (CRD42016035813). We searched PubMed, Embase, Scopus and ClinicalTrials.gov for primary research studies applying culture‐independent analysis on the microbiome on AD skin of humans and animal models. Two authors independently screened the full text of studies for eligibility and assessed risk of bias. Because of heterogeneity no quantitative synthesis was done. Of 5735 texts, 32 met the inclusion criteria (17 published: 11 human and six animal studies). The studies varied in quality and applied different methodology. The skin in AD had low bacterial diversity (lowest at dermatitis‐involved sites) and three studies showed depletion of Malassezia spp. and high non‐Malassezia fungal diversity. The relative abundance of Staphylococcus aureus and Staphylococcus epidermidis were elevated and other genera were reduced, including Propionibacterium. A mouse study indicated that dysbiosis is a driving factor in eczema pathogenesis. The data are not sufficiently robust for good characterization; however, dysbiosis in AD not only implicates Staphylococcus spp., but also microbes such as Propionibacterium and Malassezia. A causal role of dysbiosis in eczema in mice should encourage future studies to investigate if this also applies to humans. Other important aspects are temporal dynamics and the influence of methodology on microbiome data.     

Zinc and atopic dermatitis: a systematic review and meta‐analysis

Zinc plays a central role in skin integrity via barrier and immune mechanisms and may also be relevant in the pathogenesis of atopic dermatitis (AD). However, little is known about the relationship between zinc and AD. We performed a systematic review to determine (i) the association between zinc levels or zinc deficiency and AD and (ii) the efficacy of oral zinc supplementation in the treatment of AD. We searched PubMed, Scopus, Web of Science and article references for observational studies on zinc levels or zinc deficiency in participants with AD vs. controls and for randomized control trials (RCTs) on zinc supplementation in AD. For observational studies, we calculated pooled standardized mean differences (SMDs) or odds ratios (ORs) along with 95% confidence intervals (CIs) using a random effects model. We included 14 observational studies and two RCTs. The pooled SMD demonstrated significantly lower serum (SMD 0.66, 95% CI 0.21–1.10, P = 0.004), hair (SMD 0.95, 95% CI 0.38–1.52, P = 0.001) and erythrocyte (SMD 0.95, 95% CI 0.38–1.52, P = 0.001) zinc levels in participants with AD compared to controls. Pooled unadjusted data from three studies showed a non‐significant increased odds of AD in those with zinc deficiency compared with those without zinc deficiency (OR = 1.50, 95% CI 0.71–3.16, P = 0.28). One RCT of oral zinc supplementation among AD patients with zinc deficiency showed improvement in extent and severity of AD, while another RCT among all AD patients showed no significant improvement. All the studies were of low or moderate quality. We conclude that low serum, hair and erythrocyte zinc levels are associated with AD. However, the poor quality of included studies makes interpretation of these results problematic. High‐quality observational studies are needed to confirm the association between low zinc levels and AD, and RCTs are required to evaluate the merit of zinc supplementation for the treatment or prevention of AD.     

Effectiveness of prevention programmes for hand dermatitis: a systematic review of the literature

Hand dermatitis is a prevalent disease with an episodic, chronic character. The use of medical resources is high and is often related to reduced (work) functioning. The burden is therefore high for patients and society. Management of hand dermatitis is often unsatisfactory, and for this reason prevention is important. The effectiveness of prevention programmes is, however, unknown. This study evaluates if comprehensive prevention programmes for hand dermatitis, that include worker education as an element, are effective on occurrence, adherence to preventive measures, clinical outcomes and costs compared to usual care or no intervention. The literature was systematically searched using PubMed and Embase, from the earliest to January 2010 for relevant citations. The methodological quality was assessed by two reviewers using the Cochrane criteria. The GRADE approach was used to determine the level of evidence. After reading the full text articles, 7 publications met our inclusion criteria. We found that there is moderate evidence for the effect of prevention programmes on lowering occurrence and improving adherence to preventive measures, and low evidence for the effect on improving clinical outcomes and self-reported outcomes. No studies reporting on costs were found. It can be concluded that there is moderate evidence for the effectiveness of prevention programmes of hand dermatitis versus usual care or no intervention. However, more high quality studies including cost-effectiveness are needed.     

The socioeconomic impact of atopic dermatitis in the United States: a systematic review

Abstract:  The aim of this study was to review studies examining the direct and indirect costs of atopic dermatitis in the United States. A search was performed using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the International Agency for Health Technology Assessment (INAHTA) database, and the Cochrane Library. All abstracts were reviewed for the following criteria: original cost data, studies performed in the United States, and English language. The search yielded 418 papers. Fifty-nine papers were reviewed in detail, and four studies were found that met the inclusion criteria. These cost-identification analyses estimated the cost of atopic dermatitis heterogeneously and could not be compared directly. National cost estimates ranged widely, from $364 million to $3.8 billion US dollars per year. The cost of atopic dermatitis is significant and will likely increase in proportion to increasing disease prevalence. Measurement of the cost of atopic dermatitis in the United States has been limited to direct cost-identification analyses, with few studies measuring the indirect cost of disease.     

A systematic review of the safety of topical therapies for atopic dermatitis

BACKGROUND: The safety of topical therapies for atopic dermatitis (AD), a common and morbid disease, has recently been the focus of increased scrutiny, adding confusion as how best to manage these patients. OBJECTIVES: The objective of these systematic reviews was to determine the safety of topical therapies for AD. METHODS: Databases searched included: OVID Medline, Medline In-Process and Other Non-Indexed Citations, Embase, and the Cochrane Central Register of Controlled Trials. In addition to the articles identified by this search, investigators were also referred to a list of links (most recently updated 25 September 2005) to recent Food and Drug Administration (FDA) studies, reports and meetings regarding the topical calcineurin inhibitors for further potential references. Only fully published papers available in English and data obtained from FDA sites were included. Furthermore, the criteria for inclusion and exclusion for each systematic review were further evaluated at a meeting of all of the content and evidence-based medicine experts participating in this process and alteration of the inclusion criteria was done at that time when it was felt necessary to avoid inclusion of lower-quality data in the review. Qualitative review of the abstracted data was performed and reviewed at a meeting of all of the content and evidence-based medicine experts. RESULTS: While systemic exposure to these topical agents does occur, physiological changes appear to be uncommon and systemic complications rare and have only been found with use of topical corticosteroids. CONCLUSIONS: Based on the data that are available the overall safety of AD therapies appears to be good with the only documented systemic side-effects of therapy those occasionally seen with use of topical corticosteroids.     

类风湿性嗜中性皮炎一例并文献复习

报道1例类风湿性嗜中性皮炎并复习相关文献。患者,女,60岁。四肢红斑、丘疹、结节痛1年余,加重伴水疱、脓疱1周。患者确诊类风湿关节炎3年余,类风湿因子阳性。三次组织病理示表皮表现不一,真皮浅中层均可见较多弥漫中性粒细胞浸润,可见核尘,并可见少量淋巴细胞浸润,血管内皮肿胀伴红细胞外溢,未见血管炎改变。DIF阴性。诊断：类风湿性嗜中性皮炎。结合病例及相关文献,对此病发病机制、临床及病理、治疗等进行综合分析。