Differential expression of interferon-induced genes and other tissue-based biomarkers in acute graft-versus-host disease vs. lupus erythematosus in skin.

BACKGROUND: In both acute graft-versus-host disease (GVHD) and lupus erythematosus (LE), the patient's own tissues are subjected to immunological assault via complex mechanisms influenced by interferon (IFN) and other cytokines. Although not typically confused clinically, these entities have overlapping histopathological findings in the skin. AIM: To assess whether GVHD can be differentiated from LE using molecular methods on skin specimens. METHODS: We developed a quantitative reverse transcription PCR assay based on previously identified tissue-based biomarkers of cutaneous GVHD, and compared gene expression in GVHD with that in LE. RESULTS: Both entities showed robust expression of IFN-induced genes and of genes encoding proteins involved in antigen presentation, cell signalling and tissue repair. Levels of gene expression differed significantly in GVHD compared with LE, particularly those of IFN-induced genes such as MX1, OAS3, TAP1 and STAT3 (P < 0.01). Three logistic regression models could differentiate the two entities with a high degree of certainty (receiver operating characteristic area under the curve of 1.0). CONCLUSION: The study demonstrates the feasibility of distinguishing between microscopically similar inflammatory dermatoses using tissue-based molecular techniques.

Coping as a mediator of stress and psychotic-like experiences.

BACKGROUND: There is evidence that individuals along the whole psychosis continuum have increased responsiveness to stress; however, coping responses to stressors have not been extensively explored in subthreshold psychotic symptoms. METHODS: In 454 undergraduates, psychotic-like experiences (PLEs) were evaluated using the positive items of the Prodromal Questionnaire. Perceived stress and traumatic life events were assessed using the Life Events Checklist and Perceived Stress Scale, and coping was measured using the Brief COPE. We also examined whether different coping styles mediated the relationship between perceived stress and PLEs, as well as whether different coping styles mediated the relationship between traumatic life events and PLEs. RESULTS: Both number of traumatic life events and current level of perceived stress were significantly associated with PLEs. These relationships were both mediated by higher levels of maladaptive coping. CONCLUSIONS: Results have the potential to inform treatment strategies, as well as inform targets for exploration in longitudinal studies of those at risk for psychosis.

Simple sample processing enhances malaria rapid diagnostic test performance.

Lateral flow immunochromatographic rapid diagnostic tests (RDTs) are the primary form of medical diagnostic used for malaria in underdeveloped nations. Unfortunately, many of these tests do not detect asymptomatic malaria carriers. In order for eradication of the disease to be achieved, this problem must be solved. In this study, we demonstrate enhancement in the performance of six RDT brands when a simple sample-processing step is added to the front of the diagnostic process. Greater than a 4-fold RDT signal enhancement was observed as a result of the sample processing step. This lowered the limit of detection for RDT brands to submicroscopic parasitemias. For the best performing RDTs the limits of detection were found to be as low as 3 parasites per µL. Finally, through individual donor samples, the correlations between donor source, WHO panel detection scores and RDT signal intensities were explored.

Cutaneous vasculitis update.

The classification of cutaneous vasculitis and its general principles, including clinical patterns, pathogenesis, and causes, are reviewed in this article. Several types of cutaneous vasculitis are discussed in detail, including Henoch-Schonlein purpura, erythema elevatum diutinum, and cutaneous polyarteritis nodosum. The approach to treatment for cutaneous vasculitis also is reviewed.

The impact of child sexual abuse and stigma on methods of coping with sexual assault among undergraduate women.

OBJECTIVE: The aim of the current study was to determine whether a prior history of child sexual abuse increased the likelihood of using disengagement methods of coping with a sexual assault that had occurred within the past year. Once this was established, a mediational model was tested in which it was hypothesized that specific traumagenic dynamics and changed world views would mediate the association between child and/or adolescent sexual abuse and increased use of disengagement coping methods in response to a recent sexual assault. METHOD: One thousand and fifty women undergraduates from a New England state university completed a survey for research credit. Respondents were asked detailed questions regarding experiences of sexual assault within the past year, histories of child and/or adolescent sexual abuse, traumagenic dynamics, and world assumptions. Analyses were based on 106 participants who had experienced a sexual assault within the past year. RESULTS: Sexually assaulted young women with a history of child sexual abuse used more disengagement methods of coping to deal with the adult sexual assault than women without this history. In addition, the relationship between prior sexual abuse and the use of disengagement coping strategies was mediated by feelings of stigma, but not by feelings of betrayal and powerlessness or beliefs in the meaningfulness and benevolence of the world. CONCLUSIONS: This is the first study to find that sexually revictimized young women may be particularly at-risk of relying on disengagement methods of coping with sexual assault. Furthermore, this association is mediated by feelings of shame or stigma. Directions for further research and clinical implications are discussed.

Cutaneous involvement by angioimmunoblastic T-cell lymphoma with remarkable heterogeneous Epstein-Barr virus expression.

INTRODUCTION: Initially described as an abnormal immune reaction, most cases of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD)-like T-cell infiltrates are now regarded as a peripheral T-cell lymphoma (AILD T-NHL). AILD T-NHL is characterized clinically with constitutional symptoms, generalized lymphadenopathy, hepatosplenomegaly, skin rash, and polyclonal hypergammaglobulinemia. Epstein-Barr virus (EBV) is frequently detected in involved lymph nodes, but the presence of EBV in cutaneous infiltrates of AILD T-NHL has rarely been examined. We present a patient with AILD T-NHL with cutaneous involvement that shows marked heterogeneity of EBV expression in the lymph node and skin biopsies, and review the histological findings of AILD T-NHL in the skin. METHODS: Two skin biopsies of a diffuse maculopapular rash and a lymph node were examined and immunophenotyped. In situ hybridization for detection of EBV in the lymph node and skin biopsies was utilized. In order to attempt to delineate which lymphocytes were EBV positive, skin biopsies were dual labeled with CD3, CD45RO, CD20 and EBV. The skin biopsies and lymph node were submitted for gene rearrangement studies by polymerase chain reaction (PCR). Capillary electrophoresis of fluorescently labeled PCR products was utilized for PCR product quantitation. RESULTS: The histological features of the lymph node were diagnostic of AILD T-NHL and a T-cell clone was identified by PCR. The skin biopsies showed an atypical superficial and deep perivascular polymorphous infiltrate consistent with cutaneous involvement by AILD T-NHL. Both skin biopsies showed the same clonal T-cell receptor gene rearrangement as the lymph node. In situ hybridization of the lymph node and one skin biopsy showed a few scattered EBV-positive lymphocytes (<1% of the infiltrate). A second skin biopsy revealed 40-50% of the lymphocytes as EBV positive. Dual staining for CD20 and EBV identified a minority of EBV-infected lymphocytes as B-cells, but most of the EBV-positive cells lacked staining for CD3 and CD45RO. CONCLUSIONS: In our patient, the same T-cell receptor gene rearrangement was found by PCR in all three biopsy sites. Most cases of AILD T-NHL contain only a few EBV-positive cells, but in our patient the extent of EBV expression ranged from <1% to 40-50% of the AILD T-NHL cutaneous infiltrate. To our knowledge, this case is the most extensive and heterogeneous expression of EBV in cutaneous AILD T-NHL to date.

Clinicopathologic, immunophenotypic, and molecular characterization of primary cutaneous follicular B-cell lymphoma.

OBJECTIVE: To determine the clinicopathologic, immunophenotypic, and molecular characteristics of primary follicular cutaneous B-cell lymphoma (CBCL) as defined by the revised European-American lymphoma classification. DESIGN: A retrospective survey of the medical records, an immunohistochemical study of archival biopsy specimens. and molecular studies of preserved DNA of all patients with follicle center lymphoma-follicular (FCL-F) primary CBCL from 1987 to 1997. SETTING: A single-center outpatient specialty clinic at an academic medical center. PATIENTS: Twenty-one patients (68% of all new primary CBCL cases), including 14 men and 7 women (age range, 33-88 years; mean, 55 years). RESULTS: The head and neck region was the most frequent primary site. Following treatment, recurrences were relatively frequent, but the overall mortality rate during 1.0 to 11.3 years (mean, 6.3 years) of follow-up was 4.8%. Immunohistochemical analysis for B- and T-cell lineages was helpful in enhancing the folliclelike structures. CD10, bcl-2, and CD43 were expressed by the neoplastic cells in 9 (47%) of 19 cases, 4 (21%) of 19 cases, and 2 (13%) of 16 cases, respectively. Immunohistochemical detection of cytoplasmic immunoglobulin light chains, using steaming in EDTA as the antigen-retrieval technique, was successful in 12 (71%) of 17 cases. The Ig heavy-chain gene rearrangements, using the Southern blot technique, detected clonality in 17 (94%) of 18 cases. The bcl-2 gene rearrangements were detected in only 2 (13%) of 15 of the primary cutaneous FCL-F cases, compared with 9 (75%) of 12 of the primary nodal FCL-F cases (P =.002). CONCLUSIONS: Primary cutaneous FCL-F is a relatively common subtype of CBCL, with a relatively indolent course. It has many features in common with primary nodal FCL-F, except for low rates of bcl-2 expression and bcl-2 gene rearrangements.

Beard dermatitis due to para-phenylenediamine use in Arabic men.

The most common active ingredient in hair coloring is para-phenylenediamine (PPDA), which can produce contact dermatitis, particularly in persons who dye their scalp hair and in hairdressers. We have identified another group of patients also at risk, namely men from Arab countries, who commonly grow beards and dye them. We searched the computerized patient database at the Mayo Clinic for patients with beard dermatitis associated with dye use. Eight Arabic men presented to the Mayo Clinic between 1994 and 1999 with beard dermatitis and a positive patch test to PPDA. The lesions were described as pruritic, erythematous, papular eruptions that developed in the jaw area after each application of beard dye. The symptoms subsided after the patients discontinued use of the PPDA-containing dye and received treatment with topical corticosteroids. Allergic contact dermatitis in the beard area due to PPDA occurs in Arabic men as a result of their propensity to dye their beards.

Child sexual abuse prevention programs: do they decrease the occurrence of child sexual abuse?

OBJECTIVE: The primary goal of the current study was to determine whether rates of child sexual abuse differed among undergraduate women who either had or had not participated in a sexual abuse prevention program during childhood. A secondary goal was to determine whether differences emerged in sexual satisfaction or avoidance of sexual activity between those women who had or had not participated in such a program. METHOD: Eight hundred and twenty-five women undergraduates from a New England state university filled out a survey on "sexual experiences" for research credit. Respondents were asked detailed questions regarding past histories of child sexual abuse and participation in school-based prevention programs during childhood. Additionally, they responded to questions about their current sexual satisfaction and sexual behaviors. RESULTS: Sixty-two percent of the sample reported having participated in a "good touch-bad touch" sexual abuse prevention program in school. Eight percent of respondents who reported ever having had a prevention program also reported having been subsequently sexually abused, compared to 14% of respondents who did not ever have a prevention program. No differences were found in adult sexual satisfaction or on behavioral measures of sexual activity between those respondents who had and had not participated in a prevention program. CONCLUSIONS: This is the first study to find that school-based child sexual abuse prevention programs are associated with a reduced incidence of child sexual abuse. Additionally, contrary to concerns voiced in the literature, there was no evidence that prevention programs are associated with decreased sexual satisfaction or avoidance of sex in adulthood. Implications of the results for further study are discussed.

Foreign bodies in sarcoidosis.

Sarcoidosis is a multisystem disease of unknown etiology. The demonstration of polarizable foreign bodies in cutaneous granulomas is generally thought to exclude a diagnosis of sarcoidosis. Nevertheless. some investigators have reported systemic sarcoidosis with cutaneous manifestations in which polarizable particles were associated with granuloma formation in the skin. We searched the biopsy specimens of granulomatous lesions from 50 patients with cutaneous sarcoidosis using polarization microscopy to estimate the frequency of polarizable foreign bodies in cutaneous lesions of sarcoidosis. Using electron probe microanalysis, we sought to determine what elements compose these foreign bodies. Polarizable foreign bodies were found in the granulomatous skin lesions of 12 of 50 patients with cutaneous sarcoidosis. All 12 patients also had at least one other granulomatous systemic lesion, and 4 had biopsy specimens of a systemic lesion available for review. Polarizable foreign bodies were found in two cases. The elements identified were calcium, phosphorus, silicon, and aluminum. Polarizable foreign bodies were found in cutaneous sarcoidosis far more often than expected. Foreign bodies were also found in granulomatous systemic lesions. The foreign body may serve as an inciting stimulus for granuloma formation in selected cases of sarcoidosis.

Necrobiotic xanthogranuloma: long-term outcome of ocular and systemic involvement.

PURPOSE: To report long-term outcomes of patients with necrobiotic xanthogranuloma, to investigate the propriety of therapeutic surgical excision or debulking, and to study tissue specimens by immunoperoxidase staining and in situ hybridization. METHODS: Medical records of all patients at the Mayo Clinic, Rochester, Minnesota, with necrobiotic xanthogranuloma between 1980 and 1997 were reviewed. A follow-up letter was sent to each patient inquiring about the current status of the lesions, the treatment regimen, and associated systemic diseases. RESULTS: The average age (+/- standard deviation) of the 15 men and 11 women was 56.8 +/- 14.8 years. Of the 26 patients, 21 (81%) had lesions of the ocular adnexa. Ulceration of the lesions occurred in 11 patients (42%). The lesions recurred after surgical removal in 11 patients (42%) and on prior incision sites from unrelated operations in three patients (12%). The average duration of follow-up from the appearance of characteristic skin lesions was 10 +/- 6.1 years. Four patients had multiple myeloma, five had a plasma cell dyscrasia, and one had a lymphoproliferative disorder during this period. Time to development of associated malignancy ranged from 8 years before the skin lesions to 11 years after the skin lesions. Overall survival was 100% at 10 years and 90% at 15 years (95% confidence limit, 0.73 to 1.00). Immunoperoxidase stains demonstrated that most histiocytes are not of Langerhans cell lineage. Monoclonal immune globulins were not identified in tissue specimens. CONCLUSION: Care of patients with necrobiotic xanthogranuloma should include avoidance of surgical removal, if possible, and lifelong follow-up to detect the development of associated malignancy.

The epidemiology of psoriatic arthritis in Olmsted County, Minnesota, USA, 1982-1991.

OBJECTIVE: To determine the incidence, prevalence, and outcomes of psoriatic arthritis (PsA) in a geographically defined community. METHODS: Using the Rochester Epidemiology Project computerized medical record system, we screened all records of Olmsted County, Minnesota, residents with any diagnosis consistent with psoriasis and/or PsA made between January 1, 1982 and December 31, 1991. Medical records were reviewed using a pretested data collection form. Only those cases of psoriasis where the diagnosis was confirmed by a dermatologist were included. PsA was defined as inflammatory arthritis associated with a definite diagnosis of psoriasis. All identified cases were followed until death, migration from the county, or January 1, 1992. Cases with seropositive rheumatoid arthritis, systemic lupus erythematosus, crystal induced arthritis, Reiter's syndrome, arthritis associated with inflammatory bowel diseases, and inflammatory osteoarthritis were excluded. Clinical characteristics were described using summary statistics. Age and sex adjusted incidence and prevalence rates were calculated. Survival was estimated using the Kaplan-Meier method. RESULTS: We reviewed the records of 1844 patients with a diagnosis of psoriasis. In 1056 of these, the diagnosis was confirmed by a dermatologist. Among these 1056 psoriasis cases, we identified 66 cases (34 female, 32 male) of PsA first diagnosed between 1982 and 1991. The average age and sex adjusted incidence rate per 100,000 US population was 6.59 (95% confidence interval, CI, 4.99, 8.19) and the prevalence on January 1, 1992, was about one per 1000 (95% CI 0.81, 1.21). The average age at diagnosis was 40.7 years. At diagnosis, 91, 3, and 6% of cases had oligoarthritis, polyarthritis, and spondylitis, respectively. Over the 477.8 person-years of followup, 25 developed extraarticular manifestations (enthesitis, n = 15; ocular inflammation, n = 11; urethritis, n = 9), 10 patients received disease modifying antirheumatic drug treatment (methotrexate, n = 7; sulfasalazine, n = 5; intramuscular gold, n = 1; oral gold, n = 1), 3 received corticosteroids, and 5 had surgical interventions (synovectomy, n = 3; arthroplasty, n = 1; other reconstructive surgery, n = 2). Survival was not significantly different from the general population (p = 0.546). CONCLUSION: Unlike results from previous referral based studies, our findings indicate that PsA is a mild, uncommon inflammatory arthritis, not associated with a significant increase in mortality.

An examination of antecedent traumas and psychiatric comorbidity among male inmates with PTSD.

Despite substantially higher rates of posttraumatic stress disorder (PTSD) among male inmates than among men in the general population, there is a dearth of research on PTSD among incarcerated men. The current study addresses traumatic events that precede PTSD and psychiatric disorders that are comorbid with PTSD in an inmate sample. Seeing someone seriously injured or killed, being sexually abused, and being physically assaulted were the three most commonly reported antecedent traumas to PTSD. Lifetime and current rates of mood disorders, anxiety disorders, and antisocial personality disorder were elevated among inmates with a diagnosis of PTSD. Two hundred and thirteen inmates participated in the study. Sixty-nine participants (33%) met lifetime DSM-III-R criteria for PTSD, and 45 (21%) met current criteria. The findings are compared with general population samples, and implications of the findings are discussed.