The reproducibility of patch tests is an important determinant of the clinical value of this diagnostic procedure. The aim of the present study was to delineate comparatively the efficiency and reproducibility of identical test reagents from 2 different commercial sources. Purchased in duplicate from brial and Boots‐Hermal, 30 allergens from the European standard and an extension series were simultaneously applied to Finn Chambers ® and affixed next to each other. Out of 2070 paired patch tests in 71 patients, 97.2% presented with concordant‐negative results. 60 patch tests were classified as allergic with 95% concordant‐positive results. From these paired positive patches, a subgroup of 13 (22.8%) corresponding allergens presented with minor differences in the visible strength of the allergic reaction. Generated by cobalt chloride, formaldehyde and 2‐bromo‐2‐nitropropane‐1,3‐diol in 1 patient each, discordant results, i.e. 1 positive and 1 negative test in parallel, were found in only 5%. Taken together, we were able to demonstrate that patch test preparations from 2 different companies exhibited a high level of reproducibility. This standardized quality of test reagents from different suppliers provides useful information on several aspects of everyday practice.
While randomized, controlled trials have generated information about the safety and efficacy of imiquimod 5% cream in the treatment of actinic keratosis, still very little is known about the challenges and pitfalls of this therapy in the daily clinical routine.To mirror the full picture of the actinic keratosis imiquimod routine therapy, ie, patient profile, in-therapy decisions, tolerability, and satisfaction.The present observational, multicenter study included 463 patients from the offices of 93 non-hospital based Austrian dermatologists. Inclusion was solely based on the treatment decision of the dermatologist and the patient's will to participate. There were no specific interventions except suggested time points of visits with pre-defined documentation forms.The typical actinic keratosis patient was a male, aged 74 years, with a disease history of 5.7±5.3 years, who presented with 8.4±8.0 multiple pre-treated lesions at the face. More than 95% of the patients developed therapeutic skin responses (dominated by erythema and crusting), which led to a significant reduction of lesions from baseline to the end of the therapy. Notably, one-third of those patients prone to a second therapeutic course were submitted to another form of treatment. Post-imiquimod therapy comprised of antibiotic creams, topical steroids, and numerous emollients. Patients and dermatologists reported high satisfaction with the therapy including the cosmetic outcome.Our data show the high need for experience at the dermatologist side and information at the patient side. Moreover, the method of treatment for imiquimod-related skin reactions definitively asks for standardization. The study was registered at ClinicalTrials.gov (NCT01151956). Decision by ClinicalTrials.gov: Federal University Teaching Hospital, Feldkirch, Austria Protocol Record OBIMQ465-AK-08, Imiquimod and actinic keratoses: an observational study.
Summary Wund‐D.A.CH., as the umbrella organization of German‐speaking wound treatment societies, has currently developed a best practice recommendation for skin damage caused by body fluids, which is known as moisture‐associated skin damage (MASD) in English‐speaking countries. In this expert consensus, the diseases incontinence‐associated dermatitis (IAD), intertriginous dermatitis, including intertrigo, gram‐negative bacterial toe web infection and toxic contact dermatitis, including periwound and peristomal dermatitis are presented in a differentiated manner. A common feature of these clinical diseases is a deterioration of skin integrity due to prolonged exposure to body fluids such as urine, stool, sweat or wound exudate with associated physical‐irritative and/or chemical irritation. In addition, other comorbidities and cofactors play an important role. The diagnosis of these interdisciplinary and interprofessionally relevant MASD is difficult in everyday clinical practice because there are currently no uniform definitions and many relevant differential diagnoses. Effective strategies for the prevention and therapy of these skin diseases are, for example, continence management, use of efficient, absorbent aids with good retention as well as consistent skin protection and adequate skin care. Another important aspect is the education of patients and relatives about the origin, treatment and prevention of MASD.
Imiquimod (IMQ), a synthetic agonist to Toll-like receptor (TLR) 7, is being successfully used for the treatment of certain skin neoplasms, but the exact mechanisms by which this compound induces tumor regression are not yet understood. While treating basal cell carcinoma (BCC) patients with topical IMQ, we detected, by immunohistochemistry, sizable numbers of both myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) within the inflammatory infiltrate. Surprisingly, peritumoral mDCs stained positive for perforin and granzyme B, whereas infiltrating pDCs expressed tumor necrosis factor–related apoptosis-inducing ligand (TRAIL). The biological relevance of this observation can be deduced from our further findings that peripheral blood–derived CD11c+ mDCs acquired antiperforin and anti–granzyme B reactivity upon TLR7/8 stimulation and could use these molecules to effectively lyse major histocompatibility complex (MHC) class Ilo cancer cell lines. The same activation protocol led pDCs to kill MHC class I–bearing Jurkat cells in a TRAIL-dependent fashion. While suggesting that mDCs and pDCs are directly involved in the IMQ-induced destruction of BCC lesions, our data also add a new facet to the functional spectrum of DCs, ascribing to them a major role not only in the initiation but also in the effector phase of the immune response.
Immunoglobulin (Ig) heavy (H) and light (L) chain variable (V) region genes are assembled somatically during B-cell differentiation by stage-specific DNA rearrangements of multiple V, diversity (D, H chains only), and joining (J) germline gene segments (reviewed by Alt et al, 1986). Different combinations and imprecise joining of V, D and J elements, random insertion of nucleotides during the joining process (N regions), as well as somatic mutation, contribute to the generation of antibody diversity and ultimately determine the specificity (self or non-self antigen) of a given antibody. Murine lupus is characterised by high titres of circulating autoantibodies (AAb) leading to immune complex mediated lesions (Theofilopoulos and Dixon, 1985). We have previously shown, by means of restriction fragment length polymorphism analysis, that lupus mice and non-lupus mice of the same haplotypes share highly conserved H chain variable region loci (Kofler et al., 1985b). In the present study, we report a detailed analysis of nucleotide sequences corresponding to H and L chains of nine monoclonal AAb with different specificities frequently expressed during lupus disease (single stranded DNA, histone and various Ig isotypes). The following questions were addressed: Arc there any primary structures common to ail AAb regardless of their specificity, which might signal their autoreactive nature? Do AAb employ Ig genes in a restricted manner and are there unique Ig genes different from the germline pool used in the response to exogenous antigens? To what extent is self-specificity germline encoded or acquired during B-cell development?
With the projected expansion of the biosimilars market, there will be an increased propensity for the substitution of reference biological products with cheaper biosimilars for economic reasons (ie, non-medical switching). This will lower the cost per patient and should provide the benefit of wider access to biological therapies. However, it is essential that patients and clinicians fully understand the rationale for non-medical switching and its potential implications in terms of efficacy, safety, and immunogenicity. To date, clinical experience supports the use of biosimilars and a growing body of evidence from clinical trials and real world observational studies specifically supports clinical decision making around non-medical switching. Equally, as non-medical switching becomes more common, it is essential that pharmacovigilance systems adapt to handle the increasing volumes of data needed to effectively monitor the use of biosimilars and detect new signals. This will require a reduced reliance on registries, as well as streamlining and integration of existing systems to allow a frequent cycle of online reporting of adverse events by healthcare professionals, analysis by national authorities, and feedback to treating clinicians. This article considers the current use and future uptake of biosimilars from a clinical perspective.
