CD20, AIF-1, and TGF-beta in graft-versus-host disease: a study of mRNA expression in histologically matched skin biopsies.

Graft-versus-host disease is the leading cause of non-relapse mortality after allogeneic bone marrow transplantation. The cell-mediated immune mechanisms that underlie the pathogenesis of graft-versus-host disease remain unclear. In this study, 47 skin biopsies representing graft-versus-host disease grades 0-III, lichenoid, and sclerodermoid were included from 31 allogeneic bone marrow transplantation recipients. RNA from paraffin-embedded tissue was harvested. Transcript levels of the following markers were assessed and correlated with grade and survival: CD3, CD20, FoxP3, IL-17, gamma-interferon (IFN-gamma), transforming growth factor-beta (TGF-beta), IL-6, connective tissue growth factor (CTGF), allograft inflammatory factor-1(AIF-1), and IL-13. Levels of three markers significantly correlated with the length of survival (TGF-beta, correlation coefficient -20.8, P=0.016; AIF-1, 13.2, P=0.016; and CD20, 66, P=0.027). CD20 expression was limited to lichenoid cases. Levels of TGF-beta, AIF-1, and IFN-gamma appeared to correlate with histological progression, but did not reach statistical significance. Expression of FoxP3 correlated with worse survival, and approached statistical significance (P=0.053). Two potential mechanistic pathways were identified: the 'scleroderma' group (AIF-1 and TGF-beta) and the 'B-cell' group (CD20). Transcript levels of these markers were implicated in the progression from acute to chronic disease, and also correlated significantly with the duration of survival. Identification of these three markers may direct therapy selection with targeted agents, including the use of rituximab when B-lymphocytes are implicated.

Rhabdomyomatous mesenchymal hamartoma presenting on a digit.

Rhabdomyomatous mesenchymal hamartoma is a rare dermal lesion comprised of skeletal muscle, adipocytes and collagen. The vast majority has been described in very young patients on the head and neck. To our knowledge, there are only two reports of rhabdomyomatous mesenchymal hamartoma outside the head and neck region. Both of those lesions were located in the perianal area. We describe a rhabdomyomatous mesenchymal hamartoma in a 36-year-old man located on the great toe. Although rhabdomyomatous mesenchymal hamartoma is uncommon, it is important to be aware of this entity, its possible association with congenital syndromes and its potential for localization outside of the head and neck region.

Risk of skin cancer in the drug treatment of rheumatoid arthritis.

BACKGROUND: It is well established that rheumatoid arthritis (RA) is associated with an increased risk of lymphoproliferative disorders when compared to the general population. It remains unclear whether this risk is owing to underlying inflammation and immune dysregulation, effects of disease modifying medications or a combination of the two. With increasing use of targeted biologic therapies, including those that may theoretically interfere with innate tumor surveillance, there is increasing concern about the development of other malignancies. METHODS: The English language literature was searched to identify observational studies and clinical trials reporting incidence and relative risk of melanoma and non-melanoma skin cancer (NMSC) among RA patients. RESULTS/CONCLUSIONS: The numbers of melanomas reported were too small to draw conclusions regarding increased or decreased risk with underlying RA or commonly used medications. Relative incidence of NMSCs is difficult to assess given the lack of standardized reporting in the general population. No safety signal concerning skin cancer with RA or its therapies is at present identified.

Azelaic acid in the treatment of papulopustular rosacea: a systematic review of randomized controlled trials.

OBJECTIVE: To evaluate the clinical efficacy of topical 20% azelaic acid cream and 15% azelaic acid gel compared with their respective vehicles and metronidazole gel in the treatment of papulopustular rosacea. DATA SOURCES: Electronic searches of MEDLINE, EMBASE, BIOSIS, and SciSearch through July or August 2004 and the Cochrane Central Register of Controlled Trials through 2004 (issue 3). We performed hand searches of reference lists, conference proceedings, and clinical trial databases. Experts in rosacea and azelaic acid were contacted. STUDY SELECTION: Randomized controlled trials involving topical azelaic acid (cream or gel) for the treatment of rosacea compared with placebo or other topical treatments. Two authors independently examined the studies identified by the searches. Ten studies were identified, of which 5 were included (873 patients). DATA EXTRACTION: Two authors independently extracted data from the included studies, then jointly assessed methodological quality using a quality assessment scale. DATA SYNTHESIS: Because standard deviation data were not available for 4 of the 5 studies, a meta-analysis could not be conducted. Four of the 5 studies demonstrated significant decreases in mean inflammatory lesion count and erythema severity after treatment with azelaic acid compared with vehicle. None of the studies showed any significant decrease in telangiectasia severity. CONCLUSIONS: Azelaic acid in 20% cream and 15% gel formulations appears to be effective in the treatment of papulopustular rosacea, particularly in regard to decreases in mean inflammatory lesion count and erythema severity. Compared with metronidazole, azelaic acid appears to be an equally effective, if not better, treatment option.

Histopathologic diagnosis of chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: II. Pathology Working Group Report.

This consensus document provides an update for pathologists and clinicians about the interpretation of biopsy results and use of this information in the management of hematopoietic cell transplantation patients. Optimal sampling and tissue preparation are discussed. Minimal criteria for the diagnosis of graft-versus-host disease (GVHD) are proposed, together with specific requirements for the diagnosis of chronic GVHD. Four final diagnostic categories (no GVHD, possible GVHD, consistent with GVHD, and definite GVHD) reflect the integration of histopathology with clinical, laboratory, and radiographic information. Finally, the Working Group developed a set of worksheets to facilitate communication of clinical information to the interpreting pathologist and to aid in clinicopathologic correlation studies. Forms are available at . The recommendations of the Working Group represent a consensus opinion supplemented by evaluation of available peer-reviewed literature. Consensus recommendations and suggested data-capture forms should be validated in prospective clinicopathologic studies.

Reliability and validity of a histologic score as a marker for skin cancer chemoprevention studies.

OBJECTIVE: To develop a reliable and valid scoring system for grading skin biopsies from actinic keratosis (AK) and sun-damaged skin for use in evaluating the efficacy of skin cancer chemopreventive agents. STUDY DESIGN: A panel of dermatopathologists developed histologic criteria and diagnostic definitions for the progression of lesions from early AK to AK. The criteria were then applied to a sample of 335 histologic slides from an ongoing chemoprevention study. A 10% sample of 35 slides was reread in order to assess intrarater reliability. RESULTS: Six of the 7 criteria demonstrated high reliability (> 85%). The total histologic score, calculated using the 6 criteria, was found to significantly differentiate between (blinded) biopsy location (normal, pre-AK, AK and adjacent to squamous cell carcinoma) and histologic diagnosis (normal, pre- or early AK, AK and squamous cell carcinoma). CONCLUSION: The total histologic score, having demonstrated reliability on repeated readings and validity in its association with biopsy location and histologic score, is a reliable and valid end point for judging the efficacy of agents in skin cancer chemoprevention studies. Additional interrater reliability tests utilizing larger test sets and a rigorous statistical design should be undertaken to establish its portability.

A skin cancer education initiative at a professional baseball game and results of a skin cancer survey.

BACKGROUND: It is important to develop an understanding of what the public knows about skin cancer and what sun safety precautions they are taking. Research on the evaluation of skin cancer education targeting adults is minimal. AIM: To assess the knowledge and behavior related to skin cancer and sun exposure, and to determine if an informal interaction between dermatologists and the public could promote skin cancer awareness and precautions. METHODS: In May 2000, a dermatologist-staffed educational booth was set up at an Indianapolis Indians baseball game. Attendees were educated through discussions and handouts. Attendees completed a self-administered questionnaire prior to this interaction and a mailed follow-up questionnaire in August 2000. RESULTS: One hundred and thirty-six attendees participated in May, and 60 completed the second questionnaire in August. The May results revealed that 92% believed that sun exposure caused skin cancer; 37% used sunscreens "sometimes" and 29%"never." There was a significant decrease in the number of hours spent outdoors per week during the summer of 2000 compared to 1999. CONCLUSIONS: Frequent and unprotected sun exposure occurs despite awareness of the adverse effects. Although the number of subjects in our study was small, informal education at public events has the potential to influence behavior.

Awareness of the risks of tanning lamps does not influence behavior among college students.

HYPOTHESIS: Awareness of the risks of artificial tanning influences tanning behavior among college students. OBJECTIVE: To correlate the prevalence of tanning lamp use, the perceived benefits and risks associated with UV exposure, and knowledge about skin cancer among university students. DESIGN: A survey was designed and administered to college students seeking "walk-in" care at a university student health center from September 7, 1999, through September 30, 1999. SETTING: A large midwestern public university student health center. PARTICIPANTS: Undergraduate and graduate students attending the student health center for any medical condition. INTERVENTION: None. MAIN OUTCOME MEASURE: Completion of the survey. RESULTS: Of the surveyed students, 47% had used a tanning lamp during the preceding 12 months. Female students were more common users than male students. Of the students surveyed, 39% reported never having used tanning lamps. More than 90% of users of tanning lamps were aware that premature aging and skin cancer were possible complications of tanning lamp use. CONCLUSIONS: Despite adequate knowledge of the adverse effects of UV exposure, university students freely and frequently use tanning lamps, primarily for desired cosmetic appearance. To alter this risky behavior will require a fundamental change in the societal belief that tans are attractive and healthy.