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Tuberculin Skin Test (tuberculin + skin_test)
Selected AbstractsAntimicrobial treatment of presumed ocular tuberculosisACTA OPHTHALMOLOGICA, Issue 2007S KOUPRIANOFF Purpose: Uveitis secondary to a tuberculosis is rarely reported, even in a tertiary a care center. The prevalence of tuberculosis is low in Western Europe and its microbiological identification is difficult. However, anti tuberculosis treatment may be useful when the diagnosis of tuberculosis is presumed. Methods: The clinical records of patients with suspected tuberculosis uveitis referred to the Ophthalmology Department of the Grenoble University, between January 2005 and January 2007 were retrospectively analyzed. Patients were included in this series if they received a specific antituberculosis treatment. Results: This series included 10 patients (3M/7F, mean age 54.1). The clinical features of ocular inflammation were: bilateral panuveitis, episcleritis, bilateral posterior uveitis, and pars planitis. Tuberculin skin test, chest computerized tomography, BK sputum, and internal medicine consultation were performed for all patients. The diagnosis of presumed tuberculosis was based upon: history, thoracic imaging, and tuberculin skin test. None had extra-ocular symptoms. Sputum cultures were negative, 2 adenopathy biopsies confirmed the diagnosis. Nine patients received specific antituberculosis therapy, without systemic steroid therapy. All of them improved; no relapse occurred after 1 to 2 years after the end of therapy. In one case, tuberculosis specific therapy allowed to taper the systemic steroid therapy. Conclusions: The diagnosis of uveitis associated with tuberculosis is difficult since it depends on a spectrum of indirect signs. Bacteriological identification is rarely obtained. In presumed ocular tuberculosis, antituberculosis therapy may be useful to control intraocular inflammation, with or without steroid therapy. [source] Value of sonography for follow-up of mediastinal lymphadenopathy in children with tuberculosisJOURNAL OF CLINICAL ULTRASOUND, Issue 3 2007Joaquim Bosch-Marcet Abstract Purpose. To assess the clinical value of sonography for the follow-up of mediastinal lymphadenopathy in children diagnosed with pulmonary tuberculosis (TB). Methods. We conducted a retrospective review of the medical records of 21 children (9 boys, 12 girls) with a mean age of 6 years (range, 7.4 months to 18 years) who had a positive intradermal tuberculin skin test. All patients underwent thorough history-taking, physical examination, frontal and lateral chest radiographs, and sonographic study of the mediastinum. The mediastinum was accessed through the suprasternal and left parasternal approaches. The presence of 1 or more masses with an ovoid or round shape and hypoechoic appearance in the anterior or middle mediastinum was recorded. A comparison was made between the results of the sonographic examination of the mediastinum before administration of anti-TB agents and after 3 months of treatment. Results. Pulmonary radiographic findings were suggestive of TB in 17 patients and were uncertain in 4 patients. Sonographic examination, however, detected mediastinal lymphadenopathy in all patients. A comparison of pretreatment mediastinal sonograms with those obtained after 3 months of anti-TB treatment showed a marked reduction of lymph node involvement in 17 patients (80.9%). In the remaining 4 patients, mediastinal lymphadenopathy was still present. Conclusion. Mediastinal sonography appears to be a valuable tool for the diagnosis of TB and in the monitoring of response to treatment in children. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2007 [source] Tuberculosis in liver transplant recipients: A systematic review and meta-analysis of individual patient data,LIVER TRANSPLANTATION, Issue 8 2009Jon-Erik C. Holty Mycobacterium tuberculosis (MTB) causes substantial morbidity and mortality in liver transplant recipients. We examined the efficacy of isoniazid latent Mycobacterium tuberculosis infection (LTBI) treatment in liver transplant recipients and reviewed systematically all cases of active MTB infection in this population. We found 7 studies that evaluated LTBI treatment and 139 cases of active MTB infection in liver transplant recipients. Isoniazid LTBI treatment was associated with reduced MTB reactivation in transplant patients with latent MTB risk factors (0.0% versus 8.2%, P = 0.02), and isoniazid-related hepatotoxicity occurred in 6% of treated patients, with no reported deaths. The prevalence of active MTB infection in transplant recipients was 1.3%. Nearly half of all recipients with active MTB infection had an identifiable pretransplant MTB risk factor. Among recipients who developed active MTB infection, extrapulmonary involvement was common (67%), including multiorgan disease (27%). The short-term mortality rate was 31%. Surviving patients were more likely to have received 3 or more drugs for MTB induction therapy (P = 0.003) and to have been diagnosed within 1 month of symptom onset (P = 0.01) and were less likely to have multiorgan disease (P = 0.01) or to have experienced episodes of acute transplant rejection (P = 0.02). Compared with the general population, liver transplant recipients have an 18-fold increase in the prevalence of active MTB infection and a 4-fold increase in the case-fatality rate. For high-risk transplant candidates, isoniazid appears safe and is probably effective at reducing MTB reactivation. All liver transplant candidates should receive a tuberculin skin test, and isoniazid LTBI treatment should be given to patients with a positive skin test result or MTB pretransplant risk factors, barring a specific contraindication. Liver Transpl 15:894,906, 2009. © 2009 AASLD. [source] Mycobacterial infection and atopy in childhood: A systematic reviewPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 7 2007Charles C. Obihara The epidemiological relation between mycobacterial infection and the prevalence of atopic disease in humans is still unclear. This is in contrast to studies in murine models in which a clear suppression of atopic symptoms was observed after exposure to mycobacteria or mycobacterial products. We therefore wanted to provide a systematic overview of the published literature on the relationship between mycobacterial infection and atopic disease and to evaluate the causal relationship in a meta-analysis. The EMBASE and MEDLINE databases were searched systematically for papers published in the English literature (1966,2005) on the relation between mycobacterial infection and atopic disease. Original observational or interventional studies involving the paediatric population were included. Two authors independently reviewed articles for data on mycobacterial exposure and atopic disease outcome. Any differences were resolved by discussion. Of a total of 1201 hits, 23 studies (19 cross-sectionals, three case,controls and one prospective cohort) met the inclusion criteria. Only a minority of studies (40%) observed an association between mycobacterial infection and the prevalence of atopic disease outcome. In the meta-analysis, only studies containing data on mycobacterial exposure and atopic disease outcome variables were included. Only cross-sectional studies, in which the relation between a positive tuberculin skin test and allergic symptoms was studied, observed statistically significant negative correlation (odds ratio 0.63; 95% confidence interval: 0.51,0.79). The results of this review show that the evidence of the relationship of mycobacterial infection and atopic disease is based on observations of cross-sectional studies. In a meta-analysis, calculations showed a high level of heterogeneity (I2) within studies with similar design making it difficult to pool effects. This may partly be explained by differences in the type and definition of mycobacterial infection and lack of uniformity in the definition of atopy. The results show that only a minority of studies in the literature shows any evidence of inverse relationship between mycobacterial exposure and atopic disease outcome. The fact that the present epidemiological evidence on the relationship between mycobacterial infection and the development of atopic disease is based mainly on cross-sectional observational studies indicates the need for population-based prospective studies to address this issue. This issue needs to be addressed in view of recent suggestions to developing mycobacterial-based vaccines against atopic disease in the future. [source] Tuberculosis: Role of etiologic diagnosis and tuberculin skin testPEDIATRIC PULMONOLOGY, Issue S26 2004Luísa Pereira MD No abstract is available for this article. [source] Transmission of tuberculosis from adults to children in a Paris suburbPEDIATRIC PULMONOLOGY, Issue 3 2002Fouad Madhi MD Abstract Tuberculosis in children is often acquired by contact with a family or household member. The aim of our study was to evaluate risk factors for latent infection and active disease in exposed children in a suburb of Paris. We examined medical records for the period 1997,2000 at six departmental centers for medical prevention in Val de Marne. Thirty-nine patients aged 18 years or more with M. tuberculosis -positive sputum samples, and living with children or adolescents, were identified. Ninety-one children, aged 3 months,17 years, were exposed to these index cases. All the children initially underwent a tuberculin skin test and chest radiography, and children with no criteria for latent infection or active disease at time of initial evaluation were asked to attend a second evaluation 3 months later. Overall, 20 of the 91 (22%) children were infected, including 4 children identified only at the second evaluation. Eight (40%) of the 20 infected children had active disease, including 2 of the 4 children identified at the second evaluation. The risk of infection was not influenced by the children's age, but was significantly associated with three characteristics of the adult cases, i.e., age younger than 40 years, presence of cavitary lesions, and smears with more than 100 bacilli per microscopic field. In conclusion, our results call for early examination of all exposed children, in order to prevent infection and progression to active disease, and for a routine second evaluation after the adult contact has ended. Pediatr Pulmonol. 2002; 34:159,163. © 2002 Wiley-Liss, Inc. [source] Tuberculin skin test positivity in pediatric allogeneic BMT recipients and donors in TurkeyPEDIATRIC TRANSPLANTATION, Issue 4 2007Betul Tavil Abstract:, The preliminary study was performed to determine the frequency of tuberculin skin test (TST) positivity among 26 patients and their donors screened by TST to investigate whether tuberculin positivity of a recipient or donor influenced the rate of tuberculosis disease, transplant-related events, and to evaluate the effectiveness of isoniazide (INAH) prophylaxis administered to those with positive TST. The frequency of TST positivity was 23% (n = 6) among recipients and also 23% (n = 6) among donors. Two recipients and five donors with positive TST received INAH prophylaxis for six months. Our use of INAH prophylaxis in transplant patients was very conservative because of the risk of drug interaction. The transplantation procedure was not postponed for either recipient or donor TST positivity. Despite the high frequency of tuberculosis in our country, we have not detected any case of tuberculosis in our center, either among the purified protein derivative-screened (n = 26) or non-screened (n = 128) patients except for disseminated tuberculosis infection because of BCG vaccination in two patients with severe combined immunodeficiency. In conclusion, TST positivity in either recipient or donor may not be a contraindication for bone marrow transplantation and the procedure may not be postponed. Pretransplantation TST screening may be needed in countries where tuberculosis is common in the general population. [source] Documented tuberculin skin testing among infliximab users following a multi-modal risk communication interventions,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 1 2006Deborah Shatin PhD Abstract Purpose Following its licensure, tuberculosis (TB) was reported as a potential adverse effect of infliximab. Subsequently, the product circular was changed to recommend tuberculin skin testing before patients received infliximab, which was reinforced by several risk communication efforts. The aim of this study was to evaluate patterns and predictors of documented tuberculin skin testing in patients before and after manufacturer, federal, and academic risk communications. Methods Patients administered infliximab were identified from 11 health plans located throughout the United States, and claims data were examined to determine whether the patients had received a tuberculin skin test. Patients were divided into three cohorts depending on the timing of their first infliximab treatment in relation to the risk communication efforts. Results The overall tuberculin skin testing rate doubled from 15.4% in the first cohort to 30.9% in the last cohort, while the rate of pre-infliximab treatment testing increased from 0 to 27.7% (Chi-squared test for trend, p,<,0.0001 for both). Tuberculin skin testing rates were significantly higher in women, those with a diagnosis of rheumatoid or psoriatic arthritis, and those with a rheumatologist as prescriber. After multivariable analysis, only rheumatologist remained significantly associated with tuberculin skin testing. Conclusions Although the tuberculin skin testing rate was relatively low overall, tuberculin skin testing doubled over 30 months of ongoing risk communication efforts and under ascertainment likely occurred. We also found variation in the tuberculin skin testing rate associated with physician specialty. This study demonstrates a significant change in patient care following risk communication efforts. Copyright © 2005 John Wiley & Sons, Ltd. [source] Job-related risk of latent tuberculosis infection in a homogeneous population of hospital workers in a low incidence area,AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 4 2009Alberto Franchi MD Abstract Background Few comprehensive tuberculin surveys were carried out in a homogeneous population of health care workers (HCWs) in a low incidence area to assess the risk of tuberculosis (TB) infection by different occupational groups and units. Methods Community and occupational factors and tuberculin skin test (TST) reactivity were determined in 1,755 HCWs. Results The overall prevalence of tuberculin reactivity was 6%. Predicting factors for TST reactivity were age >47 years (OR,=,2.88), history of household TB contact (OR,=,2.41), years of work as HCW (OR,=,2.57), physician (OR,=,1.88), and working in microbiology (OR,=,4.94), dialysis/nephrology (OR,=,2.00), gynecology/obstetrics (OR,=,2.01). In a multiple regression model working in microbiology [OR,=,4.16 (1.27,13.6)], dialysis/nephrology [OR,=,2.52 (1.36,4.65)], gynecology/obstetrics [OR,=,2.46 (1.24,4.86)] and age >47 years [OR,=,1.98 (1.14,3.46)] were significant predictors for infection. Conclusions A higher risk of latent infection can be demonstrated in well-defined groups of HCWs. Am. J. Ind. Med. 52:297,303, 2009. © 2009 Wiley-Liss, Inc. [source] Latest news and product developmentsPRESCRIBER, Issue 23-24 2007Article first published online: 8 JAN 200 Cervical cancer risk falls after COC use ends Combined oral contraceptives (COCs) are associated with a slight increase in the risk of cervical cancer but this diminishes with time after use ends, an international study has shown (Lancet 2007;370:1609,21). Analysis of data for 16 573 women with and 35 509 women without cervical cancer confirmed that using a COC for 10 years between the ages of 20 and 30 increases the incidence of invasive cervical cancer from 3.8 to 4.5 per 1000 by age 50. However, the excess risk disappears 10 years after cessation of use. , A new analysis of the US Nurses' Health Study suggests that protection against ovarian cancer does not persist beyond 20 years after cessation of COC use. This study also showed that tubal ligation is associated with reduced risk of ovarian cancer (Am J Epidemiol 2007; 166;894,901). Pharmaceutical services fund moves to PCTs The ,global sum' that provides central funding for NHS pharmaceutical services is being shifted to PCTs. The Government has included legislation for the change in the recent Health and Social Care Bill. The fund pays the fees and allowances for pharmacy contractors and appliance contractors. The Government says this is a ,natural progression and in keeping with moves to devolve NHS funds to the frontline' that will enable PCTs to manage pharmacy services better by ,encouraging best prescribing practice'. Fewer fluoroquinolones in the community Restricting prescribing of fluoroquinolone antibacterials does not increase hospital admissions for infection among older people, say Canadian researchers (Am J Med 2007;120:893,900). Their analysis of an Ontario medical database shows that, in a community where fluoroquinolones were the most widely prescribed antibacterials, a one-third reduction in prescribing was not followed by an increase in hospital admissions for infectious episodes in the over,65s. On the contrary, there was a 32 per cent reduction in admissions for gastrointestinal conditions. FDA reports increased TB risk with infliximab The US Food and Drug Administration has published an analysis of cases of TB associated with infliximab (Remicade) detected via its spontaneous adverse event reporting scheme (Ann Intern Med 2007;147: 699,702). In 2001 the FDA placed a warning about the risk of TB on product labelling for infliximab and advised testing for TB before initiating treatment. This analysis of 130 cases of TB since reported in patients treated with infliximab found that 45 per cent had developed extra-pulmonary disease; risk factors included use of immunosuppressants (including methotrexate), a history of TB and time spent in an endemic area. Of 67 cases in which treatment was initiated after the warning was issued, 34 with a negative tuberculin skin test developed TB after receiving infliximab. MHRA announces anticounterfeit strategy The UK is a transit point, distribution hub and end-user of counterfeit medicines, says the MHRA in its first anti-counterfeiting strategy (www.mhra.gov.uk). Counterfeits have been detected in the legitimate supply chain with increasing frequency since 2004, resulting in nine batch recalls and a further five incidents detected at wholesale level. The MHRA's proposed approach includes: communication to raise awareness of the risk and facilitate reporting, collaboration with the WHO, the industry and law enforcement agencies, and targeted surveillance, prosecution and regulation. Evidence lacking for choosing DMARD There is insufficient evidence to choose one DMARD or biological agent over another in patients with RA, US investigators say (www.annals.org/cgi/content/abstract/0000605,20080115000192v1). Their systematic review of meta-analyses and intervention and observational trials found no evidence of differences among DMARDs or anti-TNF agents. Mono-therapy with an anti-TNF agent was associated with superior radiographic but not clinical outcomes; methotrexate plus an anti-TNF agent was superior in clinical and functional terms to either drug given alone. Be alert to psychiatric ADRs with rimonabant Clinicians should remain alert for the development of anxiety, depression and an increased risk of suicide with rimonabant (Acomplia), say Danish investigators (Lancet 2007;370:1706,13). Their meta-analysis of four randomised trials involving a total of 4105 patients showed that rimonabant was associated with an increased risk of serious adverse events (odds ratio 1.4; number needed to harm, NNH, 59), including a 2.5,fold increased risk of depression (NNH 49) and a threefold increased risk of anxiety (NNH 166). Following a warning from the FDA of an increased risk of suicide with rimonabant, the authors say their findings indicate a need for ,increased alertness by physicians to these potentially severe psychiatric adverse reactions'. New strategy for NHS medicines information The UK Medicines Information Service (www.ukmi.nhs.uk) has published its new management strategy setting out how it will respond to recent developments in the NHS. Developments include greater access to information for patients, support for nontraditional prescribers and new commissioning arrangements. New antiretroviral Maraviroc (Celsentri) is the first CCR5 antagonist to be introduced for the treatment of HIV infection. CCR5 is one of two co-receptors to which the HIV virus must attach to achieve cell entry. Maraviroc is licensed for use by treatment-experienced patients in whom only CCR5-tropic HIV-1 is detectable. The recommended dose ranges from 150 to 600mg twice daily depending on interactions with concurrent medication. Dimeticone superior Dimeticone 4 per cent lotion (Hedrin) is superior to malathion 0.5 per cent in the eradication of head lice, a UK study in 58 children and 15 adults has shown (PLoS ONE 2007;2: e1127. doi:10.1371/journal.pone. 0001127). Two applications of dimeticone lotion one week apart cleared active infestation in 70 per cent of participants compared with 33 per cent in those who used a single application of malathion. Copyright © 2007 Wiley Interface Ltd. [source] Use of QuantiFERON® -TB Gold to investigate tuberculosis contacts in a high schoolRESPIROLOGY, Issue 1 2007Kazue HIGUCHI Background and objective: QuantiFERON® -TB Gold (QFT-G) was employed in a contact investigation in a high school to evaluate its performance in adolescents. Methods: Students of the same school grade as the index case were screened with tuberculin skin test (TST) and CXR examination as an initial contact investigation. QFT-G was performed for students demonstrating a positive TST (erythema larger than 30 mm). Results: Of 349 students whose TST was completed, 95 had positive TST responses, although the distribution of TST responses was similar for both high and low exposure groups. In contrast, only four of the 88 TST-positive students tested with QFT-G were positive by this test, and three of these were from the high exposure group. Chemoprophylaxis was provided to only those four QFT-G-positive students. Follow up of the 91 students who were TST-positive, but QFT-G-negative (or not tested), for more than 3.5 years revealed that none have developed active tuberculosis. Conclusions: QFT-G appears more specific than TST as contacts with positive TST and negative QFT-G responses were not offered prophylaxis and none developed tuberculosis during 3.5 years of follow up. The replacement of TST with QFT-G, or perhaps combined use of TST and QFT-G, may be more useful in diagnosing true infection and thus reducing the number of subjects indicated for chemoprophylaxis. [source] 2263: Analysis of the utility of QuantiFERON-TB GoldTM in tube and measurement of IFN, release by peripheral mononuclear cells in response to different mycobacterium antigen in the work-up of patients with uveitisACTA OPHTHALMOLOGICA, Issue 2010D MAKHOUL Purpose Tuberculosis remains an important cause of infectious uveitis and immune reaction against mycobacteria may contribute to the development of certain forms of autoimmune uveitis. Moreover, many non-infectious uveitis patients are treated with immunomodulatory treatment. The evaluation of tuberculosis immunity is thus an important aspect in the work-up of patients with uveitis. In this work, we would like to investigate the usefulness of different methods of tuberculosis immunity testing in a series of patients with intraocular inflammation. Methods Patients with uveitis will undergo a standard diagnosis procedure, including a chest Xray. Quantiferon TB Gold in Tube (QFT) and tuberculin skin test (TST) will be performed. IFN, production by mononuclear cells in response to PPD and to HBHA will be measured by ELISA. Results Thirty-two patients have already been recruited. Sixteen had a negative QFT and a negative TST. In two of them, mononuclear cells produce IFN, in response to PPD (but not to HBHA) and in 1 in response to HBHA (but not to PPD). In 11 patients QFT and TST were positive. In this group, IFN, response to PPD was observed in 82% but only in 50% in response to HBHA. Discordant results between QFT and TST were observed in 5 patients. One had a positive QFT and a negative TST and 4 had a positive TST and a negative QFT. In this group IFN, response to PPD or HBHA was not observed. Conclusion Discordant results between QuantiFERON-TB Gold and TST were observed in 15 % of uveitis patients. Analysis of the IFN, production in response to PPD and to HBHA seems to add important information in both concordant and discordant group. [source] Antimicrobial treatment of presumed ocular tuberculosisACTA OPHTHALMOLOGICA, Issue 2007S KOUPRIANOFF Purpose: Uveitis secondary to a tuberculosis is rarely reported, even in a tertiary a care center. The prevalence of tuberculosis is low in Western Europe and its microbiological identification is difficult. However, anti tuberculosis treatment may be useful when the diagnosis of tuberculosis is presumed. Methods: The clinical records of patients with suspected tuberculosis uveitis referred to the Ophthalmology Department of the Grenoble University, between January 2005 and January 2007 were retrospectively analyzed. Patients were included in this series if they received a specific antituberculosis treatment. Results: This series included 10 patients (3M/7F, mean age 54.1). The clinical features of ocular inflammation were: bilateral panuveitis, episcleritis, bilateral posterior uveitis, and pars planitis. Tuberculin skin test, chest computerized tomography, BK sputum, and internal medicine consultation were performed for all patients. The diagnosis of presumed tuberculosis was based upon: history, thoracic imaging, and tuberculin skin test. None had extra-ocular symptoms. Sputum cultures were negative, 2 adenopathy biopsies confirmed the diagnosis. Nine patients received specific antituberculosis therapy, without systemic steroid therapy. All of them improved; no relapse occurred after 1 to 2 years after the end of therapy. In one case, tuberculosis specific therapy allowed to taper the systemic steroid therapy. Conclusions: The diagnosis of uveitis associated with tuberculosis is difficult since it depends on a spectrum of indirect signs. Bacteriological identification is rarely obtained. In presumed ocular tuberculosis, antituberculosis therapy may be useful to control intraocular inflammation, with or without steroid therapy. [source] Mycobacterium tuberculosis infection may protect against allergy in a tuberculosis endemic areaCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2006C. C. Obihara Summary Background Epidemiological studies have shown an inverse relation of mycobacterial infection and the frequency of allergic diseases and asthma. Recent evidence suggests that allergic inflammation may be inhibited in the presence of chronic and persistent infections, such as that by Mycobacterium tuberculosis (MTB). The relation of tuberculin skin test (TST) size, an accepted marker of MTB infection and the frequency of allergic disease symptoms has not been reported from an area where MTB infection is endemic. Objective To investigate the association of TST and allergic disease symptoms, in children living in a tuberculosis (TB) endemic area. Methods In this cross-sectional study, 841 children aged 6,14 years from randomly selected household addresses in two poor communities of Cape Town, South Africa, were investigated with TST and standardized International Study on Asthma and Allergies in Childhood-based questionnaire on allergic disease symptoms. Results Children with positive TST (10 mm) were significantly less likely to have allergic disease symptoms, in particular allergic rhinitis (AR) (adjusted odds ratio 0.43; 95% confidence interval 0.24,0.79) than those with negative TST. This association remained significant after adjusting for possible confounders and correcting for the effect of clustering (>1 child per household address) in the sample. There was a significant inverse linear trend in the relation of TST size in millimetre and the frequency of allergic disease symptoms, in particular AR (P<0.001). Conclusions These results of inverse association of strong TST reaction and allergic disease symptoms in children from a TB endemic area are in support of the hypotheses that allergic inflammation may be inhibited by chronic infections, such as MTB. [source] In vitro culture of skin-homing T lymphocytes from inflammatory skin diseasesEXPERIMENTAL DERMATOLOGY, Issue 5 2005Karen Bang Abstract:, We, in this study, describe how T lymphocytes in a skin biopsy can proliferate in vitro for up to 3 months by using T-cell growth factors , interleukin-2 (IL-2) and IL-4 yielding approximately 100,160 million T lymphocytes within 1 month. We established cell lines from three tuberculin skin tests, four positive patch tests, 15 of 16 biopsies from atopic dermatitis (AD), 15 of 19 biopsies from mycosis fungoides (MF), 12 of 24 biopsies from psoriasis vulgaris, which was significantly less than AD (P < 0.05), and with a reduced cumulative number of lymphocytes (P < 0.05). Omitting IL-2 and IL-4 led to immediate halt of proliferation. Blood mononuclear cells from patients and biopsies from healthy persons never gave cell lines. All cells were T lymphocytes expressing CD45RO+, HLA-DR+ and CD150. The CD7 expression was significantly increased in cell lines from AD (P < 0.05). T-cell receptor ,-chain studies by using reverse transcription-polymerase chain reaction showed that all T lymphocytes had access to the skin compartment. Single-stranded conformational analysis showed clonally expanded T cells numbering between 40 and 60 clones. After approximately 2 months of growth, the mean CD4+ : CD8+ ratio was for AD 1.20, MF 0.65 and psoriasis 0.85. Patients with AD treated with cyclosporin-A had almost no growth of CD8+ cells in vitro. Our findings indicate a changed homeostasis among skin-homing lymphocytes for in vitro culture. Our culture system of skin-homing T lymphocytes leads to a prominent cellular expansion allowing for a range of studies of in vivo activated skin T lymphocytes. [source] Cutaneous sarcoid-like granulomas with alveolar hemorrhage and c-ANCA PR-3INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 9 2004Natividade Rocha MD A 28-year-old woman, employed as a leather factory worker, noted asymptomatic, well-delimited plaques on both knees, 6 years ago. The plaques were violaceous with a smooth surface. One appeared over a post-traumatic scar from childhood (Fig. 1). Two years later, she began to complain of symptoms suggestive of polyarthritis, first of the small joints of the hands (proximal interphalanges) and then of the larger joints (wrists, elbows, and knees). She was diagnosed with rheumatoid arthritis and began treatment with nonsteroidal anti-inflammatory drugs for 1 month without any change. Deflazacort, 12 mg/day, and hydroxychloroquine, 400 mg/day, were administered for 3 months, with improvement of her articular complaints, but not her skin lesions. Figure 1. Well-delimited, violaceous plaques with a smooth surface on the knees, one over an old post-traumatic scar One year later, she complained of dysphonia, which remitted spontaneously after some weeks. After one additional year, she noted papules, with similar characteristics to the plaques, on the elbows, and two well-delimited orange-to-brown plaques on the forehead (Fig. 2). Figure 2. Orange,brown plaques symmetrically placed on the forehead During the fifth year of the disease, she was referred for the first time to a dermatologist, who biopsied one of the knee lesions. The histologic result was compatible with "sarcoid granuloma." At that time, she presented with skin lesions as her only complaint. Sarcoidosis was suspected based on a chest X-ray, which revealed hilar lymphadenopathy and diffuse accentuation of the interstitium. In November 2000, she suddenly developed fever (40 °C), cough with hemoptysis, dysphonia, and subcutaneous nodules on the palmar surface of the fingers of both hands that were painless, well-delimited, 5 mm in diameter, and firm (Fig. 3). She reported a weight loss of 12 kg in the previous 3 months. Pulmonary condensation was found on auscultation, and she had palpable hepatomegaly. Peripheral lymphadenopathy was not present. Figure 3. Painless, well-delimited, firm subcutaneous nodules on the palmar surface of the fingers Laboratory investigations revealed normochromic, normocytic anemia (hemoglobin, 7.7 g/dL), iron deficit, a white blood cell count of 16,000/µL with neutrophilia, an erythrocyte sedimentation rate of 130 mm/h, elevation of liver enzymes, a slight increase in angiotensin-converting enzyme (ACE) level (72 U/L), hypergammaglobulinemia (IgG, 3350 mg/dL), antinuclear antibody (ANA) of 1 : 320, and a slight increase in CD4 and decrease in CD8 lymphocytes with normal cellular morphology in blood. Renal function, urine sediment, urine and serum calcium, complement (C4), dsDNA, antimitochondrial antibody, direct and indirect Coombs test, antineutrophil cytoplasmic antibody (ANCA), tuberculin skin tests, viral markers of hepatitis B, C, and human immunodeficiency virus (HIV), electrocardiogram (ECG), ophthalmic examinations, and culture for infectious agents in blood and sputum were all normal or negative. Computed tomography (CT) scan showed an infiltrate in the upper right pulmonary lobule with a central cavity and bilateral hilar lymphadenopathy (Fig. 4). Homogeneous hepatosplenomegaly was present. The bronchoalveolar lavage (BAL) showed a slight lymphocytic increase predominantly of CD8 cells and hemosiderosis. Stains for infectious agents, including acid-fast bacillus, fungi, Mycoplasma, and Legionella, were negative. Three biopsies from the forehead, elbows, and knees showed well-formed noncaseating epithelioid cell granulomas with giant cells of the Langhans type in the dermis, suggestive of sarcoidosis (Figs 5 and 6). A fourth biopsy from a finger nodule demonstrated inflammatory infiltration of the dermis and necrosis with cellular debris. Vasculitis was not seen (Fig. 7). Figure 4. Computed tomography scan showing an infiltrate in the upper right pulmonary lobule with a central cavity Figure 5. Beneath a flattened epidermis, several sarcoid granulomas composed of epithelioid histiocytes and several multinucleated giant cells of Langhans type can be seen (hematoxylin and eosin, ×10) Figure 6. Less well-formed sarcoid granulomas in a hyperkeratotic area, surrounded by a sparse rim of lymphocytes (hematoxylin and eosin, ×20) Figure 7. Foci of necrosis and fibrinoid degeneration with some neutrophil infiltration and nuclear dusting (hematoxylin and eosin, ×40) The patient was treated with a broad-spectrum empirical antimicrobial (levofloxacin, 500 mg daily intravenously) over 12 days, with prompt improvement in her symptoms and remission of the forehead and finger lesions. Nevertheless, on the first evaluation after hospitalization, the CT scan showed persistence of the pulmonary cavity (Fig. 8). A repeat ANCA determination was positive (cytoplasmic pattern, c-ANCA) at 1 : 640 by indirect immunofluorescence (IIF). Antiproteinase-3 antibody was demonstrated at 78 by enzyme-linked immunosorbent assay (ELISA). Figure 8. Computed tomography scan showing persistence of the pulmonary cavity She underwent an open lung biopsy which revealed intra-alveolar hemorrhage and scanty noncaseating epithelioid cell granulomas of the sarcoidosis type in the peripheral blood vessels without vasculitis. A diagnosis of Wegener's granulomatosis was made and she began prednisolone (1 mg/kg/day) and oral cyclophosphamide (2 mg/kg/day). One year later, she is asymptomatic, the skin lesions have completely remitted, c-ANCA is negative, and the CT scan shows partial regression of the pulmonary cavity. [source] | ||||||||||||||||||||||