Summary Background  Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is an effective treatment for multiple actinic keratoses (AKs). Pain, however, is a major side‐effect.

BACKGROUND:In 16 patients with revised metal-on-metal arthroplasty and peri-implant lymphocytic inflammation, we verified the role of metal hypersensitivity by patch testing (PT) and lymphocyte transformation test (LTT).METHODS:In the 16 patients with lymphocyte dominated periprosthetic inflammation, allergy history was obtained by a questionnaire, specific serum IgE to aeroallergens was measured to assess atopy, PT to standard and metal series was performed and metal sensitivity was further assessed by LTT using blood mononuclear cells.RESULTS:Revision surgery was performed because of pain (8/16), osteolysis (4/16), dislocation (3/16) and loosening of the stem (1/16). Histological examination showed perivascular infiltrates of T lymphocytes, high endothelial venules, fibrin exudation and accumulation of macrophages with drop-like inclusions. Five patients had a history of cutaneous metal allergy and atopy was found in 25% of the patients. In 13/16 patients (81%), systemic metal sensitivity was found based on PT and/or LTT. Patch test reactions were seen in 11/16 patients (69%; partly multiple reactions/patient): 7/16 to Cobalt (Co), 7/16 to Chromium (Cr), 4/16 to Nickel (Ni), and one each to Molybdenum (Mo) and Manganese (Mn). Ten of 16 patients (62%) showed enhanced LTT reactivity to metals: 7/16 to Ni, 7/16 to Co, 5/16 to Cr, 5/16 to Mo and 4/16 to Mn.CONCLUSIONS:The lymphocyte dominated peri-implant inflammation may well reflect an allergic hyper-reactivity in these patients, given the high rate of concomitantly found metal allergy. Despite the overall incidence of metal implant allergy being low, allergic reactions should be included as differential diagnosis in failed metal-on-metal arthroplasty.

hShroom1 (hShrm1) is a member of the Apx/Shroom (Shrm) protein family and was identified from a yeast two-hybrid screen as a protein that interacts with the cytoplasmic domain of melanoma cell adhesion molecule (MCAM). The characteristic signature of the Shrm family is the presence of a unique domain, ASD2 (Apx/Shroom domain 2). mRNA analysis suggests that hShrm1 is expressed in brain, heart, skeletal muscle, colon, small intestine, kidney, placenta and lung tissue, as well a variety of melanoma and other cell lines. Co-immunoprecipitation and bioluminescence resonance energy transfer (BRET) experiments indicate that hShrm1 and MCAM interact in vivo and by immunofluorescence microscopy some co-localization of these proteins is observed. hShrm1 partly co-localises with beta-actin and is found in the Triton X-100 insoluble fraction of melanoma cell extracts. We propose that hShrm1 is involved in linking MCAM to the cytoskeleton.

BACKGROUND:Non-healing leg ulcers represent a treatment problem. OBJECTIVE:Investigate grafting of autologous suction blister roofs as treatment. METHODS:Twenty-nine chronic, non-healing leg ulcers of various aetiologies in 18 inpatients were treated by autologous epidermal grafting using the roofs of suction blisters. RESULTS:55% of ulcers completely healed 2 to 6 weeks after grafting. A 50-90% reduction in size was documented in 34% and no change was observed in 11% of ulcers. Twelve weeks after grafting, 89% of ulcers were healed completely. In most ulcers, we observed a stimulation of reepithelialization from the wound edge ('edge effect') and an accelerated formation of healthy granulation tissue. During a follow-up period of 12 months, 90% of the ulcers remained healed. CONCLUSION:Grafting of autologous suction blister roofs is an effective treatment option for non-healing leg ulcers. The advantages of the method are its lack of pain, low costs and immediate availability.

BACKGROUND:Acne inversa (hidradenitis suppurativa) is a chronic inflammatory and cicatricial disorder that affects skin areas rich in apocrine glands and terminal hairs, such as perineum and axillae. The exact pathogenesis of the disease is not well understood and the mechanisms by which bacterial superinfection contributes to the disease progression are not clear. Toll-like receptors (TLRs) expressed by inflammatory cells play a crucial role in the innate immune response to bacteria.OBJECTIVES:We sought to investigate the role of TLR2 in the pathogenesis of acne inversa.METHODS:We investigated the expression of TLR2 using real-time polymerase chain reaction analysis and immunohistochemical stainings of tissue samples from patients with acne inversa. Furthermore, we phenotypically characterized the infiltrating cells and their expression of TLR2.RESULTS:Compared with normal skin, a highly increased in situ expression of TLR2 in acne inversa skin lesions was found at both the mRNA and the protein level. The most abundant cells in the dermal infiltrate of acne inversa were CD68+ macrophages, CD209+ dendritic cells (DCs) and CD3+ T cells. CD19+ B cells and CD56+ natural killer cells were found only in small numbers. Double staining with fluorescence-labelled antibodies showed that TLR2 was expressed by infiltrating macrophages (CD68+) and DCs (CD209+). Flow cytometric analysis of isolated infiltrating cells further confirmed surface expression of TLR2 by macrophages and DCs.CONCLUSIONS:These data indicate that the enhanced expression of TLR2 by infiltrating macrophages and DCs may contribute to the pathogenesis of inflammatory lesions of acne inversa.

BACKGROUND:Atopic dermatitis (AD) is based on a genetic predisposition, but environmental factors may trigger skin inflammation. According to the hygiene hypothesis, decreased exposure to microbial products in early childhood does not allow sufficient maturation of the immune system that is associated with an increased risk of atopic sensitization.OBJECTIVES:The effect of lipopolysaccharide (LPS) on the cytokine production of peripheral blood mononuclear cells (PBMC) of AD patients and nonatopic controls was studied.PATIENTS AND METHODS:PBMC were isolated from heparinized blood of 10 patients with AD and 10 nonatopic individuals, suspended in culture medium and stimulated with LPS. Cytokine levels in the supernatants were measured by immunoassays. Results Upon stimulation with LPS, PBMC from AD patients produced significantly higher amounts of tumour necrosis factor-alpha, interferon-gamma and interleukin (IL)-10 compared with control PBMC. LPS stimulation blocked the increased spontaneous production of IL-4 and IL-5 by PBMC from AD patients, but had no effect on IL-13 production.CONCLUSIONS:These results demonstrate that the effects of LPS stimulation depend on both the type of cytokine and the origin of PBMC. Endotoxin exposure is suggested to modulate the disease course of AD.

Bei einer Reihe von Erkrankungen, die durch eine Eosinophilie charakterisiert sind, findet man erhöhte Spiegel von Interleukin- (IL-)5 im Blut und/oder Gewebe. IL-5 spielt eine wichtige Rolle in der Regulierung von Produktion, Differenzierung, Rekrutierung, Aktivierung und Überleben eosinophiler Granulozyten. Daher stellt die Neutralisation von IL-5 durch blockierende Antikörper einen vielversprechenden neuen Ansatz in der Therapie dieser Erkrankungen dar. Erste klinische Studien zeigten, dass es nach Applikation von Anti-IL-5-Antikörpern zu einem raschen Abfall der Eosinophilenzahlen im peripheren Blut kommt. Eine Abnahme der Beschwerden wurde bei der lymphozytären Form hypereosinophiler Syndrome, bei eosinophiler Ösophagitis und bei chronischer Rhinitis mit nasaler Polyposis beobachtet. Im Gegensatz dazu zeigte eine Anti-IL-5-Antikörper-Behandlung von Patienten mit Asthma bronchiale oder mit atopischem Ekzem nicht den erwarteten klinischen Effekt. Zukünftige Studien werden zeigen, bei welchen eosinophilen Erkrankungen eine Anti-IL-5-Therapie wirksam ist und welche Patientengruppen auf diese Therapie ansprechen.

In a number of diseases with eosinophilia, elevated interleukin (IL)-5 levels are detected in the peripheral blood and/or tissues. IL-5 plays an important role in regulating the production, differentiation, recruitment, activation, and survival of eosinophils. Therefore, neutralizing IL-5 by blocking antibodies seems a promising approach in the treatment of eosinophilic diseases. Clinical trials have demonstrated that anti-IL-5 therapy results in a rapid decrease in peripheral blood eosinophil numbers. Moreover, improvement of symptoms in patients with lymphocytic variants of hypereosinophilic syndromes, in eosinophilic esophagitis and chronic rhinitis with nasal polyposis has been observed. In contrast, in patients with bronchial asthma or atopic eczema, anti-IL-5 therapy showed only moderate or no clinical effects. Future studies will have to identify those eosinophilic diseases in which anti-IL-5 antibodies are effective, perhaps with the help of newly developed biomarkers.

Allergic contact dermatitis is a T cell mediated, antigen-specific inflammatory reaction of the skin due to repeated epicutaneous exposure to antigens. Immunologically it is divided into 2 phases, induction and elicitation phase. During the first phase which is clinically silent, naïve T cells are activated and differentiate into antigen-specific memory T cells. During the elicitation phase, after recontact with the same antigen, memory T cells are activated and exert direct and indirect cytotoxic effects towards cells of the skin. In this review we summarize immunological mechanisms leading to allergic contact dermatitis.