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Journal: The British journal of dermatology

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Anti-drug antibodies (ADAs) against biologic agents may be clinically significant and potentially alter a biologic drug’s treatment efficacy. This systematic review aims to 1) determine the prevalence of ADAs against infliximab, etanercept, adalimumab, and ustekinumab in psoriasis patients; 2) ascertain whether ADAs are associated with changes in drug efficacy; and 3) explore the use of concomitant methotrexate to prevent ADA formation. Through a systematic search using MEDLINE and EMBASE from January 29, 1950 to March 29, 2013, we identified 25 studies that met the inclusion criteria. Of 7,969 psoriasis patients, 950 patients tested positive for ADAs. Antibodies against infliximab, etanercept, adalimumab, and ustekinumab were reported in 5.4%-43.6%, 0.0%-18.3%, 6.6%-44.8%, and 3.8%-5.5% of patients, respectively. Anti-infliximab antibodies were associated with lower serum infliximab concentrations in three studies and decreased treatment response in five studies. ADAs against etanercept were non-neutralizing and not associated with any apparent effects on clinical response. Anti-adalimumab antibodies were associated with lower serum adalimumab concentrations in three of five studies and reduced clinical efficacy in four studies. Two of six studies reported that anti-ustekinumab antibodies were associated with lower PASI responses, and three ustekinumab studies noted that most of these antibodies were neutralizing. Although the use of concomitant methotrexate with biologic agents to prevent ADA formation in other immune-mediated diseases is promising, their use in psoriasis is sparse. ADA development remains a challenge with biologic therapies and therefore should be considered in psoriasis patients who experience diminished treatment response. This article is protected by copyright. All rights reserved.

Concepts: Monoclonal antibodies, Rheumatoid arthritis, Infliximab, Ankylosing spondylitis, Psoriatic arthritis, Psoriasis, Etanercept, Adalimumab

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Background  Lichen sclerosus (LS) is a chronic inflammatory skin disorder that typically affects the anogenital area. It presents with ivory-white atrophic patches or plaques with associated telangiectasia and occasional purpura. It has rarely been described as affecting abdominal stomas. Objectives  To investigate possible aetiological factors responsible for the development of this condition. Methods  All patients with peristomal LS were identified at a specialist stoma dermatology clinic and studied using a standardized pro forma. Results  We identified 12 patients with peristomal LS. The mean age was 72·3 years (range 47-85 years). With the exception of one patient, all our other patients had urostomies. Treatment was effective in the majority of cases. Conclusions  Peristomal LS, in our experience, is most commonly found around urostomies, and we speculate that in addition to the possible role of local trauma and occlusion, certain - as yet unidentified - constituents in the urine possibly play a role in its aetiology. It tends to respond well to corticosteroids and has not been associated with malignant transformation.

Concepts: Medicine, Patient, Hospital, Effect, Affect, Play, Etiology, Pro forma

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Summary Background  Dermoscopy is useful in evaluating skin tumours, but its applicability also extends into the field of inflammatory skin disorders. Discoid lupus erythematosus (DLE) represents the most common subtype of cutaneous lupus erythematosus. While dermoscopy and videodermoscopy have been shown to aid the differentiation of scalp DLE from other causes of scarring alopecia, limited data exist concerning dermoscopic criteria of DLE in other locations, such as the face, trunk and extremities. Objective  To describe the dermoscopic criteria observed in a series of patients with DLE located on areas other than the scalp, and to correlate them to the underlying histopathological alterations. Methods  DLE lesions located on the face, trunk and extremities were dermoscopically and histopathologically examined. Selection of the dermoscopic variables included in the evaluation process was based on data in the available literature on DLE of the scalp and on our preliminary observations. Analysis of data was done with SPSS analysis software. Results  Fifty-five lesions from 37 patients with DLE were included in the study. Perifollicular whitish halo, follicular keratotic plugs and telangiectasias were the most common dermoscopic criteria. Statistical analysis revealed excellent correlation between dermoscopic and histopathological findings. Notably, a time-related alteration of dermoscopic features was observed. Conclusions  The present study provides new insights into the dermoscopic variability of DLE located on the face, trunk and extremities.

Concepts: Systemic lupus erythematosus, Lupus erythematosus, Discoid lupus erythematosus

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BACKGROUND: The initial pathology in hidradenitis suppurativa / acne inversa (HS) takes place in the folliculopilosebaceous unit (FPSU) and its surrounding tissue. The process involves follicular hyperkeratosis, inflammation and perifolliculitis. Identification of the exact origin of inflammation may shed new light on the pathogenesis and aetiology of the disease. OBJECTIVES: To study the morphology of the basement membrane zone (BMZ) in patients with HS. METHODS: Operative specimens obtained from 20 patients diagnosed with HS were cut stepwise. Within each specimen focus was set on heavily involved HS regions (centre) and clinically uninvolved regions (border). All (n=65) were stained with Periodic Acid Schiff (PAS) to visualise the epithelial support structures (basement membrane zone, BMZ) of the FPSU, the sinus tracts (ST) and the interfollicular epidermis (BM). The intensity of BMZ PAS staining was graded 0-4+. RESULTS: Compared to axillary skin of human controls the sebofollicular junction in HS patients was found to be almost devoid of PAS positive material (0/1+) in both the border and centre lesions of HS, whereas STs and BMs showed uniformly 2-3+ positivity irrespective of inflammation present. The distribution of inflammatory cells around the sebofollicular junction occurred predominantly in areas of BMZ thinning CONCLUSIONS: BMZ PAS-positivity of clinically uninvolved FPSUs of HS patients appears to be wispy or missing entirely. It is speculated that this may explain the apparent fragility of the sebofollicular junction. There is an increased concentration of inflammatory cells adjacent to these areas, whilst inflammatory cells are scarce in areas where the PAS material is intact. It is hypothesised that the PAS gap identifies areas susceptible to leakage, trauma and rupture, leading to release of materials that trigger inflammatory mediators, and the seeding of the dermis with free-living stem cells generating benign but invasive epithelialised sinuses, spreading horizontally in the dermis.

Concepts: Inflammation, Pathology, Epithelium, Skin, Epidermis, Fistula, Hidradenitis suppurativa, Abscess

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BACKGROUND: small diameter melanocytic lesions represent a diagnostic challenge for clinicians since they do not follow the ABCD rule and do not always display reliable histopathologic criteria OBJECTIVES: The aim of the study was to analyze the confocal features of small diameter lesions (naevi and melanomas with diameter ≤ 5 mm) to determine whether they show specific morphologic criteria PATIENTS AND METHODS: 24 melanomas and 72 naevi were subjected to dermoscopic and confocal evaluation along with histopathology. Significant dermoscopic and confocal differences between melanomas and naevi were evaluated by means of Pearson’s Chi-square. Odds ratios and 95% confidence interval were calculated for each parameter. Binary logistic regression was calculated to identify the RCM independently significant features for melanoma diagnosis. RESULTS: The 7-point checklist dermoscopic score was ≥ 3 in 22 melanomas and in 33 naevi. The combination of cells' pleomorphism and architectural disorder (i.e. non specific pattern or irregular junctional nests upon confocal examination) are the most striking criteria for consistent small melanoma diagnosis. Presence of atypical cells, >5 atypical cells per mm(2) and roundish atypical cells at DEJ showed the highest odds ratios values. From logistic regression presence of > 5 pagetoid cells per mm(2) , tangled lines within the epidermis, atypical roundish cells at DEJ resulted to be the three independent confocal parameters that characterized small melanomas. CONCLUSIONS: small melanomas frequently reveal specific dermoscopic and confocal features. Moreover the combination of dermoscopy and RCM can lead to a correct diagnosis of a quote of naevi that share some morphologic aspects with melanomas.

Concepts: Regression analysis, Logit, Logistic regression, Melanoma, Melanin, Melanocyte, Dysplastic nevus, Dermatoscopy

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Background  Lipoxins are potential anti-inflammatory mediators and serve as an endogenous ‘braking signal’ in the inflammatory process. Accumulating evidence has indicated the efficacy of lipoxin A(4) (LXA(4) ) and its analogs in the treatment of many animal models of inflammatory diseases. Objectives  This study investigates the efficacy and safety of 15(R/S)-methyl-lipoxin A(4) in the topical treatment of infantile eczema. Patients and methods  In this two-centre, double-blind, placebo-controlled, randomized, parallel-groups comparative study, 60 patients were randomly assigned to receive either the 15(R/S)-methyl-lipoxin A(4) cream, mometasone furoate (Eloson, Schering-Plough, Shanghai, China) or placebo for 10 days. The efficacy was determined using the Severity Scale Score (SSS), Eczema Area and Severity Index (EASI) and the Infants' Dermatitis Quality of Life Index (IDQOL). Safety was monitored by physical examination, laboratory investigation and documentation of clinical adverse events. Results  The treatment of eczema with 15(R/S)-methyl-LXA(4) cream significantly relieved the severity, induced a recovery, and improved the quality of life of the patients, as demonstrated by significantly reduced SSS, EASI and IDQOL, respectively, in a way similar to the efficacy of Eloson. All safety parameters remained within normal limits. No clinical adverse event was found in the three patient groups. Conclusions  15(R/S)-methyl-LXA(4) was well tolerated, and significantly reduced the severity of eczema. The results of this small exploratory study suggest that 15(R/S)-methyl-LXA(4) warrants further investigation in the treatment of eczema.

Concepts: Inflammation, Clinical trial, Asthma, Anti-inflammatory, Clinical research, Eczema, Dermatitis, Lipoxin

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Ectodermal dysplasias (EDs) are a large group of heritable complex conditions with more than 200 members and common clinical characteristics of anomalies of the hair, teeth, nails, and sweat glands with or without involvement of other organs (1) . Anhidrotic or hypohidrotic ectodermal dysplasia (EDA/ HED) is the most common form of EDs which is characterized by the clinical triad of hypotrichosis (sparse hair), abnormal or missing teeth (anodontia or hypodontia), and deficient sweating (hypohidrosis or anhidrosis) (2) . Different modes of inheritance have been described for HED. X-linked HED (OMIM: 305100) is caused by mutations in ectodysplasin A gene (EDA1), whereas mutations in the EDA receptor (EDAR) and EDAR-associated death domain (EDARADD) genes result in autosomal dominant (OMIM:129490) and autosomal recessive (OMIM: 224900) forms (3) .

Concepts: DNA, Genetics, Mutation, Point mutation, Genodermatoses, Hypohidrotic ectodermal dysplasia, Ectodermal dysplasia, EDA

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Palmoplantar pustulosis is characterized by sterile pustules with hyperkeratosis, erythema, scaling, and fissuring on the palms and soles.(1) It has been reported to be more frequent in middle-aged women, smokers, and diabetic patients(2) , and it is increasingly reported as a paradoxical reaction to antitumor necrosis factor alpha (anti-TNF) biological agents.(3, 4.) It can present itself alone (PPP), or in association with psoriasis vulgaris (palmoplantar pustular psoriasis, PPPP).

Concepts: Ultraviolet, Tumor necrosis factor-alpha, Psoriatic arthritis, Psoriasis, Etanercept, Pustulosis palmaris et plantaris, Ustekinumab, Adalimumab

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Background  Photodynamic therapy (PDT) and laser ablation (LA) are frequently used treatment options for multiple actinic keratoses (AK), yet they have not been compared head to head. Objectives  To compare PDT and carbon dioxide (CO(2) ) LA in the management of multiple AK using objective and subjective outcome measures. Methods  A single-centre, randomized, two-treatment half-side comparative study of PDT vs. CO(2) LA was performed. Patients with at least four bilateral (e.g., scalp, forearms) AK were included. The primary outcome measure was the reduction of AK 3 months (v3) after therapy. Secondary outcome measures included the reduction of AK 4 weeks (v2) after therapy, decrease of epidermal p53 and Ki-67 protein expression, micromorphological changes as assessed by optical coherence tomography (OCT) in vivo, and investigators' and patients' satisfaction scoring. Results  In total, 20 patients (18 men and 2 women) completed the study. Both treatments reduced AK quantity significantly. On v3, relative reduction of AK quantity was significantly higher following PDT (P = 0·0362). Ki-67 and p53 protein expression was reduced significantly from baseline (Ki-67, median 49·5%; p53, median 64·8%) to v2 by both procedures (PDT, median 18·5%, P < 0·0001; LA, median 16·2%, P < 0·0001). AK features as assessed by OCT imaging were also significantly reduced by both procedures. The investigators and patients rated the side-effects and inconveniences of PDT as more severe, but both overall preferred PDT due to the superior clinical outcome. Conclusions  CO(2) LA and PDT are both effective therapy options for multiple AK, yet PDT seems to be superior in terms of AK reduction and participants' and investigators' overall satisfaction.

Concepts: Photosynthesis, Carbon dioxide, Redox, Laser, Nitrogen, Carbon, Optical coherence tomography, Actinic keratosis