Drug hypersensitivity reactions involving skin

Immune reactions to drugs can cause a variety of diseases involving the skin, liver, kidney, lungs, and other organs. Beside immediate, IgE-mediated reactions of varying degrees (urticaria to anaphylactic shock), many drug hypersensitivity reactions appear delayed, namely hours to days after starting drug treatment, showing a variety of clinical manifestations from solely skin involvement to fulminant systemic diseases which may be fatal. Immunohistochemical and functional studies of drug-specific T cells in patients with delayed reactions confirmed a predominant role for T cells in the onset and maintenance of immune-mediated delayed drug hypersensitivity reactions (type IV reactions). In these reactions, drug-specific CD4+ and CD8+ T cells are stimulated by drugs through their T cell receptors (TCR). Drugs can stimulate T cells in two ways: they can act as haptens and bind covalently to larger protein structures (hapten-carrier model), inducing a specific immune response. In addition, they may accidentally bind in a labile, noncovalent way to a particular TCR of the whole TCR repertoire and possibly also major histocompatibility complex (MHC)-molecules - similar to their pharmacologic action. This seems to be sufficient to reactivate certain, probably in vivo preactivated T cells, if an additional interaction of the drug-stimulated TCR with MHC molecules occurs. The mechanism was named pharmacological interaction of a drug with (immune) receptor and thus termed the p-i concept. This new concept may explain the frequent skin symptoms in drug hypersensitivity to oral or parenteral drugs. Furthermore, the various clinical manifestations of T cell-mediated drug hypersensitivity may be explained by distinct T cell functions leading to different clinical phenotypes. These data allowed a subclassification of the delayed hypersensitivity reactions (type IV) into T cell reactions which, by releasing certain cytokines and chemokines, preferentially activate and recruit monocytes (type IVa), eosinophils (type IVb), or neutrophils (type IVd).

The choice of anesthesia influences oxidative energy metabolism and tissue survival in critically ischemic murine skin

In surgical animal studies anesthesia is used regularly. Several reports in the literature demonstrate respiratory and cardiovascular side effects of anesthesiologic agents. The aim of this study was to compare two frequently used anesthesia cocktails (ketamine/xylazine [KX] versus medetomidine/climazolam/fentanyl [MCF]) in skin flap mouse models. Systemic blood values, local metabolic parameters, and surgical outcome should be analyzed in critical ischemic skin flap models. Systemic hypoxia was found in the animals undergoing KX anesthesia compared with normoxia in the MCF group (sO(2): 89.2% +/- 2.4% versus 98.5% +/- 1.2%, P < 0.01). Analysis of tissue metabolism revealed impaired anaerobic oxygen metabolism and increased cellular damage in critical ischemic flap tissue under KX anesthesia (lactate/pyruvate ratio: KX 349.86 +/- 282.38 versus MCF 64.53 +/- 18.63; P < 0.01 and glycerol: KX 333.50 +/- 83.91 micromol/L versus MCF 195.83 +/- 29.49 micromol/L; P < 0.01). After 6 d, different rates of flap tissue necrosis could be detected (MCF 57% +/- 6% versus KX 68% +/- 6%, P < 0.01). In summary we want to point out that the type of anesthesia, the animal model and the goal of the study have to be well correlated. Comparing the effects of KX and MCF anesthesia in mice on surgical outcome was a novel aspect of our study.

High numbers of DC-SIGN+ dendritic cells in lesional skin of cutaneous T-cell lymphoma

The role of dendritic cells (DCs) in disease progression of primary cutaneous T-cell lymphoma (CTCL) is not well understood. With their unique ability to induce primary immune responses as well as immunotolerance, DCs play a critical role in mediation of anti-tumor immune responses. Tumor-infiltrating DCs have been determined to represent important prognostic factors in a variety of human tumors.

Skin cancers in renal transplant recipients: A description of the renal transplant cohort in Bern

BACKGROUND/AIMS: Skin tumours, in particular squamous-cell carcinomas (SCC), are the most common malignant conditions developing in transplant recipients. The aim of this study is to investigate the frequency and type of skin cancer in patients receiving immunosuppressive therapy after organ transplantation. METHODS: Multivariate logistic regression analysis was performed on data of 243 renal transplant patients who attended the dermatology outpatient clinic for the first time after transplantation in the period January 2002-October 2005. RESULTS: We found an increased risk of actinic keratosis (AK) and SCC in renal transplant recipients with a basal cell carcinoma (BCC) / SCC ratio of 1:7. Older patients had AK more frequently (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.06-1.15; p <0.0001) and SCC (OR 1.14, CI 1.07-1.22; p <0.0001) than younger patients. Men had AK (OR 0.19, CI 0.08-0.45; p = 0.0002) and SCC (OR 0.25, CI 0.07-0.89; p = 0.0332) more frequently than women. The duration of immunosuppressive therapy correlated significantly with the numbers of AKs (OR 1.15, CI 1.08-1.24; p <0.0001) and SCCs (OR 1.16, CI 1.05-1.28; p = 0.0025), and patients with fair skin had more AKs (OR 0.31, CI 0.14-1.24; p <0.0001) and SCCs (OR 0.11, CI 0.02-0.52; p = 0.0054) than darker skinned patients. We could not identify any specific immunosuppressive drug as a distinct risk factor for AK or non-melanoma skin cancer (NMSC). CONCLUSION: Skin cancers are increased in the renal transplant population. Main risk factors for skin cancers are fair skin type and long duration of immunosuppressive therapy. A follow-up programme is necessary for early detection of skin cancer and precancerous conditions. Preventive strategies should include specialist dermatological monitoring and self-examination.

Internet based health promotion campaign against skin cancer - Results of www.skincheck.ch in Switzerland

Conventional skin cancer prevention programs appeal to limited populations, and the middle aged male population responds less frequently. Our objective was to establish a complementary health promotion campaign tool for skin cancer prevention. Internet-based education, instruction for self assessment and teledermatological evaluation of skin lesions by an expert commission of dermatologists was used. Compliance and clinical diagnosis was assessed in a subgroup. 12,000 users visited the educational website. There was strong interest among the middle aged male population (53% (N = 262): male; mean age: 42). 28.5% of examined lesions (N = 494) were considered suspicious. Email requests, sent to the group whose lesions where considered suspicious, were answered by 46.0% of females (N = 29) and 59.7% of males (N = 46) with a female distribution predominantly in younger ages (52.6% of females with known age: < 30 years). Males were predominantly represented over 30 years (86.2% of all males). According to user's declarations, at least 8 (8.5%) malignant lesions (1 melanoma in situ, 1 squamous cell carcinoma, 4 basal cell carcinomas, 2 malignant lesions without declared diagnosis) were finally diagnosed by physicians. We conclude that internet-based, interactive, educational programs, in addition to existing health promotion campaigns, can enhance public participation in the middle aged male population in skin cancer prevention.

Organ-specific eosinophilic disorders of the skin, lung, and gastrointestinal tract

Eosinophils are multifunctional leukocytes that increase in various tissues in patients with a variety of disorders. Locally, they can be involved in the initiation and propagation of diverse inflammatory responses. In this review the clinical association of eosinophils with diseases of the skin, lung, and gastrointestinal tract is summarized. An approach to determining the causal role of eosinophils in these diseases is presented. Recent findings concerning molecular diagnosis, cause, and treatment are discussed.

[The thoracoscopic talc pleurodesis with intraoperative pleural biopsy - a retrospective analysis in patients with malignant pleural effusion]

The thoracoscopic pleurodesis with talc is an established therapy in case of malignant pleural effusion. With the instillation of talc a -localised inflammation is induced. However, some-times it turns into a severe systemic reaction. In this study of the postoperative course, the -question is examined whether a pleural biopsy is an additional risk factor for morbidity and mortality after talc pleurodesis.

Virtobot--a multi-functional robotic system for 3D surface scanning and automatic post mortem biopsy

The Virtopsy project, a multi-disciplinary project that involves forensic science, diagnostic imaging, computer science, automation technology, telematics and biomechanics, aims to develop new techniques to improve the outcome of forensic investigations. This paper presents a new approach in the field of minimally invasive virtual autopsy for a versatile robotic system that is able to perform three-dimensional (3D) surface scans as well as post mortem image-guided soft tissue biopsies.

Diagnosis of fatal pulmonary fat embolism with minimally invasive virtual autopsy and post-mortem biopsy

We report a case of a 78-year-old female with a proximal femur fracture caused by an accidental fall who died suddenly 1h after orthopaedic prosthesis insertion. Post-mortem computed tomography (CT) scan and histological examination of samples obtained with post-mortem percutaneous needle biopsies of both lungs were performed. Analysis of the medical history and the clinical scenario immediately before death, imaging data, and biopsy histology established the cause of death without proceeding to traditional autopsy. It was determined to be acute right ventricular failure caused by massive pulmonary fat embolism. Although further research in post-mortem imaging and post-mortem tissue sampling by needle biopsies is necessary, we conclude that the use of CT techniques and percutaneous biopsy, as additional tools, can offer a viable alternative to traditional autopsy in selected cases and may increase the number of minimally invasive forensic examinations performed in the future.

Diagnostic performance and accuracy of 3-D spoiled gradient-dual-echo MRI with water- and fat-signal separation in liver-fat quantification: comparison to liver biopsy

To prospectively evaluate a 3-dimensional spoiled gradient-dual-echo (3D SPGR-DE) magnetic resonance imaging (MRI) sequence for the qualitative and quantitative analysis of liver fat content (LFC) in patients with the suspicion of fatty liver disease using histopathology as the standard of reference.

Postmortem imaging-guided biopsy as an adjuvant to minimally invasive autopsy with CT and postmortem angiography: a feasibility study

Although postmortem CT suffices for diagnosing most forms of traumatic death, the examination of natural death is, to date, very difficult and error prone. The introduction of postmortem angiography has led to improved radiologic diagnoses of natural deaths. Nevertheless, histologic changes to tissues, an important aspect in traditional examination procedures, remain obscure even with CT and CT angiography. For this reason, we examined the accuracy of a minimally invasive procedure (i.e., CT angiography combined with biopsy) in diagnosing major findings and the cause of death in natural deaths.

[A dead man with a light reddish skin]

A 40-year-old man was found dead in his bathroom with a light reddish skin. The cause of death was asphyxia due to CO-intoxication.

Recurrent non-melanoma skin cancer: remission of field cancerization after conversion from calcineurin inhibitor- to proliferation signal inhibitor-based immunosuppression in a cardiac transplant recipient

Non-melanoma skin cancers (NMSCs) are the most common malignancies after solid organ transplantation. Their incidence increases with time after transplantation. Calcineurin-inhibitors (CNIs) and azathioprine are known as skin neoplasia-initiating and -enhancing immunosuppressants. In contrast, increasing clinical experience suggests a relevant antiproliferative effect of mammalian target of rapamycin inhibitors, also named proliferation signal inhibitors (PSIs). We report the case of a cardiac allograft recipient with an impressive and consolidated reduction of recurrent NMSC, observed after conversion from CNI-therapy to a PSI-based protocol.

Air suctioning during colon biopsy forceps removal reduces bacterial air contamination in the endoscopy suite

Bacterial contamination of endoscopy suites is of concern; however studies evaluating bacterial aerosols are lacking. We aimed to determine the effectiveness of air suctioning during removal of biopsy forceps in reducing bacterial air contamination.

Detection of Merkel cell polyomavirus in epidermodysplasia-verruciformis-associated skin neoplasms

BACKGROUNd: Epidermodysplasia verruciformis (EV) is a rare genodermatosis that is characterized by susceptibility to infection with specific human papillomavirus (HPV) genotypes. Among polyomaviruses, the novel Merkel cell polyomavirus (MCPyV) has been found in different epithelial skin neoplasias.