First case of canine visceral leishmaniasis in the midwestern of Santa Catarina State, Brazil / Primeiros casos de leishmaniose visceral canina no Meio-oeste do Estado de Santa Catarina, Brasil

Canine visceral leishmaniasis (CVL) caused by Leishmania (Leishmania) infantum is transmitted by phlebotomine sandflies and a major zoonotic disease in Brazil. Due to the southward expansion of the disease within the country and the central role of dogs as urban reservoirs of the parasite, we have investigated the occurrence of CVL in two municipalities Erval Velho and Herval d'Oeste in the Midwest region of Santa Catarina state. Peripheral blood samples from 126 dogs were collected in both cities and tested for anti-L. infantum antibodies by indirect enzymelinked immunosorbent assay (ELISA) and indirect immunofluorescence reaction (IIF) and for the presence of parasite DNA by polymerase chain reaction (PCR) in peripheral blood. From examined dogs, 35.71% (45/126) were positive for at least one of the three tests and two (1.6%) were positive in all performed tests. Twelve dogs (9.5%) were positive for both ELISA and IIF, while 21 dogs were exclusively positive for ELISA (16.7%), and 15 (11.9%) for IIF. L. infantum k-DNA was detected by PCR in 9 out of 126 dogs (7.1%) and clinical symptoms compatible with CVL were observed for 6 dogs. Taken together, these results indicate the transmission of CVL in this region, highlighting the needs for epidemiological surveillance and implementation of control measures for CVL transmission in this region.

A Leishmaniose Visceral Canina (LVC) causada pela Leishmania (Leishmania) infantum e transmitida por flebotomíneos e é uma das principais zoonoses do Brasil que se encontra em expansão em estados da região sul do país, sendo os cães o principal reservatório urbano do parasito. O presente estudo investigou a ocorrência de LVC em dois municípios, Erval Velho e Herval d'Oeste localizados no meio-oeste de Santa Catarina. Para tanto, amostras de sangue periférico de 126 cães foram coletadas em ambas as cidades e submetidas à detecção de anticorpos anti-L. infantum por meio de testes de ELISA e imunofluorescência indireta (IFI), bem com a detecção de k-DNA pela reação em cadeia de polimerase (PCR). Além disso, também foram observados os sintomas clínicos e as condições ambientais associadas a esses animais. Dos cães examinados, 35,7% (45/126) foram positivos para pelo menos um dos três testes, dois cães (1,6%) foram positivos em todos os três testes, 12 cães (9,5%) foram positivos tanto no ELISA quanto na IFI, enquanto 21 cães (16,7%) foram positivos para ELISA e 15 (11,9%) para o IFI. A amplificação do k-DNA de L. infantum foi positiva em 9 dos 126 cães (7,1%). Entre os cães positivos seis apresentaram um ou mais sintomas clínicos correlacionados com a LVC. Esses resultados confirmaram a ocorrência de LVC na região e destacaram a importância do monitoramento e implementação de medidas de controle para a LVC nessa região.

First case of canine visceral leishmaniasis in the midwestern of Santa Catarina State, Brazil / Primeiros casos de leishmaniose visceral canina no Meio-oeste do Estado de Santa Catarina, Brasil

Canine visceral leishmaniasis (CVL) caused by Leishmania (Leishmania) infantum is transmitted by phlebotomine sandflies and a major zoonotic disease in Brazil. Due to the southward expansion of the disease within the country and the central role of dogs as urban reservoirs of the parasite, we have investigated the occurrence of CVL in two municipalities Erval Velho and Herval d'Oeste in the Midwest region of Santa Catarina state. Peripheral blood samples from 126 dogs were collected in both cities and tested for anti-L. infantum antibodies by indirect enzyme linked immunosorbent assay (ELISA) and indirect immunofluorescence reaction (IIF) and for the presence of parasite DNA by polymerase chain reaction (PCR) in peripheral blood. From examined dogs, 35.71% (45/126) were positive for at least one of the three tests and two (1.6%) were positive in all performed tests. Twelve dogs (9.5%) were positive for both ELISA and IIF, while 21 dogs were exclusively positive for ELISA (16.7%), and 15 (11.9%) for IIF. L. infantum k-DNA was detected by PCR in 9 out of 126 dogs (7.1%) and clinical symptoms compatible with CVL were observed for 6 dogs. Taken together, these results indicate the transmission of CVL in this region, highlighting the needs for epidemiological surveillance and implementation of control measures for CVL transmission in this region.

A Leishmaniose Visceral Canina (LVC) causada pela Leishmania (Leishmania) infantum e transmitida por flebotomíneos e é uma das principais zoonoses do Brasil que se encontra em expansão em estados da região sul do país, sendo os cães o principal reservatório urbano do parasito. O presente estudo investigou a ocorrência de LVC em dois municípios, Erval Velho e Herval d’Oeste localizados no meio-oeste de Santa Catarina. Para tanto, amostras de sangue periférico de 126 cães foram coletadas em ambas as cidades e submetidas à detecção de anticorpos anti-L. infantum por meio de testes de ELISA e imunofluorescência indireta (IFI), bem com a detecção de k-DNA pela reação em cadeia de polimerase (PCR). Além disso, também foram observados os sintomas clínicos e as condições ambientais associadas a esses animais. Dos cães examinados, 35,7% (45/126) foram positivos para pelo menos um dos três testes, dois cães (1,6%) foram positivos em todos os três testes, 12 cães (9,5%) foram positivos tanto no ELISA quanto na IFI, enquanto 21 cães (16,7%) foram positivos para ELISA e 15 (11,9%) para o IFI. A amplificação do k-DNA de L. infantum foi positiva em 9 dos 126 cães (7,1%). Entre os cães positivos seis apresentaram um ou mais sintomas clínicos correlacionados com a LVC. Esses resultados confirmaram a ocorrência de LVC na região e destacaram a importância do monitoramento e implementação de medidas de controle para a LVC nessa região.

First case of canine visceral leishmaniasis in the midwestern of Santa Catarina State, Brazil

Abstract Canine visceral leishmaniasis (CVL) caused by Leishmania (Leishmania) infantum is transmitted by phlebotomine sandflies and a major zoonotic disease in Brazil. Due to the southward expansion of the disease within the country and the central role of dogs as urban reservoirs of the parasite, we have investigated the occurrence of CVL in two municipalities Erval Velho and Herval dOeste in the Midwest region of Santa Catarina state. Peripheral blood samples from 126 dogs were collected in both cities and tested for anti-L. infantum antibodies by indirect enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence reaction (IIF) and for the presence of parasite DNA by polymerase chain reaction (PCR) in peripheral blood. From examined dogs, 35.71% (45/126) were positive for at least one of the three tests and two (1.6%) were positive in all performed tests. Twelve dogs (9.5%) were positive for both ELISA and IIF, while 21 dogs were exclusively positive for ELISA (16.7%), and 15 (11.9%) for IIF. L. infantum k-DNA was detected by PCR in 9 out of 126 dogs (7.1%) and clinical symptoms compatible with CVL were observed for 6 dogs. Taken together, these results indicate the transmission of CVL in this region, highlighting the needs for epidemiological surveillance and implementation of control measures for CVL transmission in this region.

Resumo A Leishmaniose Visceral Canina (LVC) causada pela Leishmania (Leishmania) infantum e transmitida por flebotomíneos e é uma das principais zoonoses do Brasil que se encontra em expansão em estados da região sul do país, sendo os cães o principal reservatório urbano do parasito. O presente estudo investigou a ocorrência de LVC em dois municípios, Erval Velho e Herval dOeste localizados no meio-oeste de Santa Catarina. Para tanto, amostras de sangue periférico de 126 cães foram coletadas em ambas as cidades e submetidas à detecção de anticorpos anti-L. infantum por meio de testes de ELISA e imunofluorescência indireta (IFI), bem com a detecção de k-DNA pela reação em cadeia de polimerase (PCR). Além disso, também foram observados os sintomas clínicos e as condições ambientais associadas a esses animais. Dos cães examinados, 35,7% (45/126) foram positivos para pelo menos um dos três testes, dois cães (1,6%) foram positivos em todos os três testes, 12 cães (9,5%) foram positivos tanto no ELISA quanto na IFI, enquanto 21 cães (16,7%) foram positivos para ELISA e 15 (11,9%) para o IFI. A amplificação do k-DNA de L. infantum foi positiva em 9 dos 126 cães (7,1%). Entre os cães positivos seis apresentaram um ou mais sintomas clínicos correlacionados com a LVC. Esses resultados confirmaram a ocorrência de LVC na região e destacaram a importância do monitoramento e implementação de medidas de controle para a LVC nessa região

First case of canine visceral leishmaniasis in the midwestern of Santa Catarina State, Brazil.

Canine visceral leishmaniasis (CVL) caused by Leishmania (Leishmania) infantum is transmitted by phlebotomine sandflies and a major zoonotic disease in Brazil. Due to the southward expansion of the disease within the country and the central role of dogs as urban reservoirs of the parasite, we have investigated the occurrence of CVL in two municipalities Erval Velho and Herval d'Oeste in the Midwest region of Santa Catarina state. Peripheral blood samples from 126 dogs were collected in both cities and tested for anti-L. infantum antibodies by indirect enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence reaction (IIF) and for the presence of parasite DNA by polymerase chain reaction (PCR) in peripheral blood. From examined dogs, 35.71% (45/126) were positive for at least one of the three tests and two (1.6%) were positive in all performed tests. Twelve dogs (9.5%) were positive for both ELISA and IIF, while 21 dogs were exclusively positive for ELISA (16.7%), and 15 (11.9%) for IIF. L. infantum k-DNA was detected by PCR in 9 out of 126 dogs (7.1%) and clinical symptoms compatible with CVL were observed for 6 dogs. Taken together, these results indicate the transmission of CVL in this region, highlighting the needs for epidemiological surveillance and implementation of control measures for CVL transmission in this region.

Impact of 3 Major Maintenance Immunosuppressive Protocols on Long-term Clinical Outcomes: Result of a Large Multicenter Italian Cohort Study Including 5635 Renal Transplant Recipients.

BACKGROUND: Although optimization of immunosuppressive schemes in renal transplantation have minimized acute posttransplant complications, long-term outcomes are still not optimal and most of the chronic graft damage is drug-related. Therefore, to define the best long-term maintenance immunosuppressive regimen is of major importance in renal transplantation. To assess this objective, we undertook a large, multicenter cohort study in Italy. METHODS: We retrospectively analyzed data of 5635 patients (enrolled from 1983 to 2012) and we assessed the impact of 3 major immunosuppressive regimens (calcineurin inhibitors+antimetabolites+corticosteroids [CNI+ANT+CS] vs CNI+mammalian target-of-rapamycin (mTOR) inhibitors+CS [CNI+mTOR-I+CS] vs CNI+CS) on long-term clinical outcomes by employing several statistical algorithms. RESULTS: The overall difference in the incidence of outcome over time was not statistically different within the first 5 years of follow-up (P = .13); however, it became significant at 10 years and 20 years (P < .01), with the CNI+CS group showing the lowest cumulative incidence of outcome. Compared with the CNI+ANT+CS group, the CNI+mTOR-I+CS group patients had a significantly higher risk of outcome (hazard ratio [HR], 1.30; P = .024); the difference remained significant and even increased in magnitude after adjustment for potential confounders (HR, 1.38; P = .006). Similarly, patients in the CNI+CS group had a significantly higher risk of the outcome (HR, 1.64; P < .001). CONCLUSION: Our data confirm that CNI+ANT+CS is the "gold standard" therapy in renal transplantation, but, whenever required, the introduction of mTOR-Is instead of ANT may not dramatically modify major clinical outcomes. The use of mTOR-I could be a valuable pharmacologic tool to minimize CNI complications and insure adequate immunosuppression.

Opportunistic deep cutaneous mycoses in solid organ transplant recipients.

Invasive fungal infections are a major cause of morbidity and mortality among organ transplant recipients, despite many progresses concerning diagnosis, preventions and treatment. Risk factors for invasive fungal infections in transplanted recipients include type and severity of immunosuppression, especially in life-saving organs as lung or liver, older age at transplantation, and technical complexity of surgery, living in endemic areas or exposure to a contaminated environment. Superficial fungal infections are caused by Candida, Dermatophytes, and Malassezia. In invasive mycoses, skin lesions may occur as a consequence of the systemic dissemination of invasive mycoses, or after direct inoculation in the skin. Aspergillosis, cryptococcosis, Zygomycoses, dark mould infections, fusariosis and infections attributable to Scedosporium and Pseudallescheria species are the most common etiological agents. Cutaneous manifestations of fungal infection are not specific, and a high degree of suspicion is required, and prompt biopsy for histology and culture is needed. Therapy with lyposomal amphotericin B and new triazoles are effective.

Opportunistic deep cutaneous mycoses in solid organ transplant recipients.

Invasive fungal infections are a major cause of morbidity and mortality among organ transplant recipients, despite many progresses concerning diagnosis, preventions and treatment. Risk factors for invasive fungal infections in transplanted recipients include type and severity of immunosuppression, especially in life-saving organs as lung or liver, older age at transplantation, and technical complexity of surgery, living in endemic areas or exposure to a contaminated environment. Superficial fungal infections are caused by Candida, Dermatophytes, and Malassezia. In invasive mycoses, skin lesions may occur as a consequence of the systemic dissemination of invasive mycoses, or after direct inoculation in the skin. Aspergillosis, cryptococcosis, Zygomycoses, dark mould infections, fusariosis and infections attributable to Scedosporium and Pseudallescheria species are the most common etiological agents. Cutaneous manifestations of fungal infection are not specific, and a high degree of suspicion is required, and prompt biopsy for histology and culture is needed. Therapy with lyposomal amphotericin B and new triazoles are effective.

Incidence of primary and second cancers in renal transplant recipients: a multicenter cohort study.

Limited data exist about cancer prognosis and the development of second cancers in renal transplant recipients. In a retrospective cohort study on 3537 patients incidence rates of the first and, if any, of a second cancer, and standardized incidence ratios [SIR (95% CI)] were computed. Two hundred and sixty-three (7.5%) patients developed a NMSC, and 253 (7.2%) another type of cancer after a median follow-up of 6.5 and 9.0 years, respectively. A statistically significant excess risk, if compared to an age- and sex-matched reference general population, was observed for Kaposi sarcoma and NMSC, followed by non-Hodgkin lymphoma and carcinoma of cervix uteri; a small number of unusual cancers such as tumors of the salivary glands, small intestine and thyroid also were detected at a level worthy of additional scrutiny. Ten-year survival rate of all noncutaneous cancers was 71.3%, with lower rates for lung carcinoma and non-Hodgkin lymphoma (0% and 41.7%, respectively). Patients with NMSC had an increased risk of developing a second NMSC [SIR 8.3 (7.0-10.0)], and patients with a primary noncutaneous cancer had increased risk of developing a second noncutaneous cancer [SIR 1.8 (1.2-2.8)], if compared to the whole cohort. Our study underscore that the high risk of primary and second cancer in renal transplant recipients, including unusual cancers.

Clinical and diagnostic features of in situ melanoma and superficial spreading melanoma: a hospital based study.

BACKGROUND: Despite the incidence of in situ melanoma is continuously rising; few studies have investigated its clinical and diagnostic features. OBJECTIVE: To investigate clinical and diagnostic features of in situ melanoma compared to superficial spreading melanoma (SSM). METHODS: This is a hospital based, case-control study. Ninety consecutive patients with an in situ melanoma and 90 age and gender matched patients with SSM were enrolled. Main outcome measures were differences in clinical signs that aroused suspicion of in situ melanoma, detection modalities (self-detection vs. incidental detection by a physician), factors conditioning time between first noticing the suspect lesions and the physician visit. RESULTS: Median diameter of in situ melanoma was smaller than SSM (7.5 vs. 9.0 mm, P < 0.024), and 47.8% of in situ melanomas were smaller than 6 mm, in contrast to 25.6% of SSM (P < 0.002). In situ melanoma was mainly detected by a dermatologist (Odds Ratio 2.95 P = 0.018), and in patients with more than 10 melanocytic naevi (Odds Ratio 3.12, P = 0.008). Clinical factors independently associated to early request of dermatological consultation were age older than 45 years (Odds ratio 3.47, P = 0.002) and location of lesion in a difficult observation skin site (Odds ratio 4.20, P = 0.001), but not Breslow's thickness. CONCLUSIONS: Our findings show that in situ melanoma and SSM share similar clinical characteristics and early warning signs. However, in situ melanoma is smaller in size than SSM. This may have important implications for early diagnosis and prevention strategies.

A case-control study of betapapillomavirus infection and cutaneous squamous cell carcinoma in organ transplant recipients.

We examined the association between betapapillomavirus (betaPV) infection and cutaneous squamous cell carcinoma (SCC) in organ transplant recipients. A total of 210 organ transplant recipients with previous SCC and 394 controls without skin cancer were included. The presence of 25 betaPV types in plucked eyebrow hairs was determined using a human papillomavirus (HPV) DNA genotyping assay, and antibodies for the 15 most prevalent betaPV types were detected using multiplex serology. We used multivariate logistic regression models to estimate associations between various measures of betaPV infection and SCC. BetaPV DNA was highly prevalent (>94%) with multiple types frequently detected in both groups. We found a significant association between SCC and the concordant detection of both antibodies and DNA for at least one betaPV type (adjusted OR 1.6; 95% CI 1.1;2.5). A borderline-significant association with SCC was found for HPV36 (adjusted OR 2.4; CI 1.0;5.4), with similar associations for HPV5, HPV9 and HPV24. These data provide further evidence of an association between betaPV infection and SCC in organ transplant recipients. Confirmation of a betaPV profile predictive of risk for SCC may pave the way for clinically relevant pretransplant HPV screening and the development of preventive and therapeutic HPV vaccination.

PTCH1 gene haplotype association with basal cell carcinoma after transplantation.

BACKGROUND: Basal cell carcinoma (BCC) is 10 times more frequent in organ transplant recipients (OTRs) than in the general population. Factors in OTRs conferring increased susceptibility to BCC include ultraviolet radiation exposure, immunosuppression, viral infections such as human papillomavirus, phototype and genetic predisposition. The PTCH1 gene is a negative regulator of the hedgehog pathway, that provides mitogenic signals to basal cells in skin. PTCH1 gene mutations cause naevoid BCC syndrome, and contribute to the development of sporadic BCC and other types of cancers. Associations have been reported between PTCH1 polymorphisms and BCC susceptibility in nontransplanted individuals. OBJECTIVES: To search for novel common polymorphisms in the proximal 5' regulatory region upstream of PTCH1 gene exon 1B, and to investigate the possible association of PTCH1 polymorphisms and haplotypes with BCC risk after organ transplantation. METHODS: Three PTCH1 single nucleotide polymorphisms (rs2297086, rs2066836 and rs357564) were analysed by restriction fragment length polymorphism analysis in 161 northern Italian OTRs (56 BCC cases and 105 controls). Two regions of the PTCH1 gene promoter were screened by heteroduplex analysis in 30 cases and 30 controls. RESULTS: Single locus analysis showed no significant association. Haplotype T(1686)-T(3944) appeared to confer a significantly higher risk for BCC development (odds ratio 2.98, 95% confidence interval 2.55-3.48; P = 0.001). Two novel rare polymorphisms were identified at positions 176 and 179 of the 5'UTR. Two novel alleles of the -4 (CGG)(n) microsatellite were identified. No association of this microsatellite with BCC was observed. CONCLUSIONS: Haplotypes containing T(1686)-T(3944) alleles were shown to be associated with an increased BCC risk in our study population. These data appear to be of great interest for further investigations in a larger group of transplant individuals. Our results do not support the hypothesis that common polymorphisms in the proximal 5' regulatory region of the PTCH1 gene could represent an important risk factor for BCC after organ transplantation.

Randomized controlled trial comparing the effectiveness of 308-nm excimer laser alone or in combination with topical hydrocortisone 17-butyrate cream in the treatment of vitiligo of the face and neck.

BACKGROUND: Vitiligo is a pigmentary disorder which may have disfiguring consequences. Its treatment remains a challenge. OBJECTIVES: We designed a parallel-group randomized controlled trial to compare the effectiveness of 308-nm excimer laser alone or in combination with topical hydrocortisone 17-butyrate cream in patients with vitiligo unresponsive to previous treatment with topical steroids or narrow-band ultraviolet (UV) B phototherapy. METHODS: Consecutive patients aged 18-75 years with nonsegmental vitiligo localized on the face and/or neck lacking response to previous conventional treatment were eligible. In total, 84 patients (44 women and 40 men, mean age 44 years) were randomized to 308-nm excimer laser phototherapy twice weekly alone or in combination with topical hydrocortisone 17-butyrate cream twice daily for three periods of 3 weeks followed by a 1-week steroid-free interval. The primary outcome was a reduction of at least 75% of the overall lesional areas as judged by automatic image analysis on reflected UV photographs, conducted blind to treatment assignment, at 12 weeks compared with baseline. Secondary outcomes were clearance, and improvements on Physician's Global Assessment (PGA) and Skindex-29 scores. RESULTS: A total of 76 (90%) patients completed the study. In an intention-to-treat analysis, seven [16.6%; 95% confidence interval (CI) 5.3-27.8%] patients in the excimer monotherapy arm and 18 (42.8%; 95% CI 27.8-57.8%) in the combination arm showed > or = 75% reduction of vitiligo lesions at 12 weeks (chi(2) test 6.89, P = 0.0087). Clearance was observed in two (4.7%; 95% CI 1.6-11.2%) and nine (21.4%; 95% CI 9.0-33.8%) patients, respectively (Fisher's exact test P = 0.04). A significant difference also emerged for PGA scores, while no difference was documented for Skindex-29. CONCLUSIONS: Recalcitrant vitiligo of the face and neck may benefit from the combination of excimer laser phototherapy with topical hydrocortisone 17-butyrate cream.

Anti-tumour necrosis factor-alpha therapy increases body weight in patients with chronic plaque psoriasis: a retrospective cohort study.

UNLABELLED: BACKGROUND Chronic plaque psoriasis is associated with overweight or obesity. Anti-tumour necrosis factor-alpha (anti-TNF-alpha) treatments are now frequently used in psoriasis management. TNF-alpha is deeply involved in body weight homeostasis, which may be affected by TNF-alpha-targeted therapy. OBJECTIVE: To investigate whether anti-TNF-alpha treatments is associated with changes in body weight in patients with chronic plaque psoriasis. METHODS: We performed a retrospective controlled analysis comparing the variations in body weight and body mass index (BMI) in three closed cohorts of psoriatic patients during a 6-month treatment with etanercept (N = 58), infliximab (N = 40) or methotrexate (N = 43). RESULTS: We observed a body weight increment of 1.5 +/- 2.7 kg (mean +/- SD; P = 0.0002) and 2.5 +/- 3.3 kg (P = 0.004) in patients treated with etanercept and infliximab, respectively. In contrast, a non-significant change (0.6 +/- 1.4 kg; P = 0.4) was measured in patients treated with methotrexate. The BMI increased with 0.5 +/- 0.5 (P = 0.01) and 0.8 +/- 1 (P = 0.003) points in patients treated with etanercept and infliximab, respectively, whereas it did not change (< 0.2 +/- 0.5; P = 0.06) in patients treated with methotrexate. About one fourth of patients experienced a 4- to 10-kg weight gain. Differences in body weight variations among patients treated with anti-TNF-alpha therapies and methotrexate were statistically significant (P = 0.0005). We could not identify clinical parameters predicting this phenomenon. CONCLUSIONS: Patients with psoriasis treated with long-term anti-TNF-alpha therapies may manifest a body weight gain. This effect should be taken into account in the global approach to patients with psoriasis.

Association of functional gene variants in the regulatory regions of COX-2 gene (PTGS2) with nonmelanoma skin cancer after organ transplantation.

BACKGROUND: Overexpression of cyclooxygenase-2 (COX-2), resulting in excessive prostaglandin production, has been observed in human epidermal keratinocytes after ultraviolet B injury, in squamous cell skin carcinoma (SCC), in actinic keratoses, and in the early stages of carcinogenesis in a wide variety of tissues. The dysregulation of COX-2 expression can in part be due to functional changes affecting regulatory elements in the promoter or 3' untranslated region (UTR) of the gene. Two common polymorphisms (-765G-->C, and -1195A-->G) in the promoter region of the COX-2 gene (now PTGS2), and one common polymorphism in the 3' UTR (8473T-->C) have been described, and reported as associated with various malignancies. OBJECTIVES: To determine if common known polymorphisms in the regulatory region of the COX-2 gene (PTGS2) can be associated with nonmelanoma skin cancer (NMSC) predisposition after organ transplantation, to evaluate if cancer risks are associated with specific COX-2 gene (PTGS2) haplotypes containing these polymorphisms, and to identify possible new genetic polymorphisms in the proximal 5' or 3' regulatory regions of the gene associated with disease. METHODS: The frequency of the three polymorphisms was determined in 240 Northern Italian transplant recipient patients (107 cases and 133 controls) with polymerase chain reaction-restriction fragment length polymorphism analysis. The proximal 5' and 3' regulatory regions of the gene were screened by heteroduplex analysis. RESULTS: Stratification by age at transplant and type of tumours [SCC or basal cell carcinoma (BCC)] demonstrated that allele -765C represented a protective factor in BCC cases undergoing transplantation before 50 years of age (CC + CG vs. GG, Fisher exact test P = 0.003). One rare polymorphism, -62C-->G, was detected in the 5' flanking region. The allele frequency of -62G was 0.019, and no difference in genotype between cases and controls was observed. No other variants were found, suggesting that sequence variations in these regions are not likely to contribute to NMSC risk in this population. Haplotype analysis showed that the haplotype containing all major alleles represents a protective factor in patients with SCC undergoing transplantation after 50 years of age [P = 0.009; OR = 0.37 (0.18-0.79)] and that variant -1195A-->G may represent a risk factor in this subgroup of patients [P = 0.01; OR = 4.77 (1.47-16.41)]. Haplotype analysis in patients with BCC revealed that variant -765C might be a protective factor in patients undergoing transplantation before 50 years of age. Variant 8473T-->C, located in the 3' UTR region of the gene, showed no association with NMSC risk after transplantation. CONCLUSIONS: COX-2 common variants -765G-->C and -1195A-->G appear to be associated with risk of NMSC, although in different ways in the SCC and BCC subgroups, indicating that environmental and genetic risk factors may play different roles in the outcome leading to these two phenotypes.

Prevalence of metabolic syndrome in patients with psoriasis: a hospital-based case-control study.

BACKGROUND: Psoriasis is a chronic inflammatory disease associated with an increased cardiovascular risk. Metabolic syndrome is a significant predictor of cardiovascular events. OBJECTIVE: To investigate the prevalence of metabolic syndrome in patients with psoriasis. METHODS: We performed a hospital-based case-control study on 338 adult patients with chronic plaque psoriasis and 334 patients with skin diseases other than psoriasis. RESULTS: Metabolic syndrome was significantly more common in psoriatic patients than in controls (30.1% vs. 20.6%, odds ratio 1.65, 95% confidence interval 1.16-2.35; P = 0.005) after the age of 40 years. Psoriatic patients also had a higher prevalence of hypertriglyceridaemia and abdominal obesity, whereas hyperglycaemia, arterial hypertension and high-density lipoprotein cholesterol plasma levels were similar. Although psoriasis patients were more frequently smokers, the association of psoriasis with metabolic syndrome was independent from smoking. There was no correlation between severity of psoriasis and prevalence of metabolic syndrome. Psoriatic patients with metabolic syndrome were older and had a longer disease duration compared with psoriatic patients without metabolic syndrome. CONCLUSION: Psoriatic patients have a higher prevalence of metabolic syndrome, which can favour cardiovascular events. We suggest psoriatic patients should be encouraged to correct aggressively their modifiable cardiovascular risk factors.

Mechanisms of immune-mediated skin diseases: an overview.

The skin is a frequent site of pathological immune responses that can take place in the dermal and/or the epidermal compartments.These immunopathological reactions often occur towards innocuous antigens and may be the result of T cell-dependent and/or autoantibody dependent mechanisms. Defective immune regulation is increasingly recognized as very relevant in many skin and systemic immune-mediated disorders. In some instances (e.g., psoriasis and atopic dermatitis) genetic predisposition can affect also the capacity of keratinocytes to initiate or perpetuate inflammatory responses. A more precise understanding of the molecular and cellular mechanisms underlying each disorder may allow the identification of novel targets for more effective therapeutic strategies.

Cutaneous plasmacytoma in a hemodialysis patient.

BACKGROUND: Extramedullary plasma cell dyscrasias are rare. CASE REPORT: We report a case of a 56-year-old male Caucasian hemodialysis patient with cutaneous plasmacytoma. The diagnosis was made a few months after surgical removal of his renal graft due to chronic rejection. Investigations for the presence of an associated myeloma were negative. He underwent local radiotherapy with complete resolution of the skin lesion. CONCLUSIONS: Nephrologists should be aware that the frequency of post-transplant lymphoproliferative disorders is increasing in the dialysis population, especially in those previously or currently treated with immunosuppressive drugs.

Lethal systemic dissemination from a cutaneous infection due to Curvularia lunata in a heart transplant recipient.

A 69-year-old male heart transplant recipient, being treated with Cell Cept, FK 506 and methylprednisolone had multiple deep brown skin nodules and nodes, on the upper right arm. Skin biopsy and culture detected a strain of Curvularia lunata. The infection disseminated to the whole skin surface, oral mucosa, upper third of the oesophagus and to the lungs. Therapy with antibiotics and antifungal drugs was ineffective. The patient died of sepsis. We did not find any other case of systemic dissemination from a skin infection due to C. lunata among heart transplant recipients. We feel that heart transplant recipients need adequate education to prevent situations that would put them at risk for infection and to seek medical advice immediately for an early diagnosis and an effective therapy.