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Introduction: Bullous pemphigoid (BP) is an autoimmune disease that typically presents with blisters, but sometimes early lesions may be eczematous, maculopapular, or urticarial. The aim of the present study was to highlight possible differences between typical bullous and non-bullous pemphigoid (NBP) and compare results with the literature. Material & methods: Patients receiving a diagnosis of BP between January 2000 and December 2019 were analyzed. Patients who developed a blister after 3 months from the onset of pruritus were considered as NBP. Demographic features, clinical findings at diagnosis and at 2-year follow-up, histological features, auto-antibodies titers, comorbidities and their treatment were retrieved. Categorical variables were evaluated for normal distribution using a histogram and a Q-Q plot. The χ2 and Fisher’s exact tests were used to compare categorical variables between the groups. Continuous variables were compared between the groups using analysis of variance and the independent-samples t test. For multivariate analysis, logistic regression was performed. Results: A total of 532 patients received a diagnosis of BP. A total of 122 patients were enrolled in the study; 63 were females, and the mean age at the diagnosis was 77.2 years (±11.9 SD). 98 were affected by BP and 24 were categorized as NBP. Mean time to diagnosis was 2.9 months (±5.8 SD) for BP and 30.4 months (±59.8 SD) for NBP (p = 0.0001). Skin manifestations in NBP patients were, in order of frequency: urticarial, papular or nodular, eczematous, and excoriations. Pruritus intensity was high but similar in the two groups (Numerical Rating Scale – NRS, 9.3 vs. 8.9). Seven out of 24 NBP patients (29%) never developed blisters; the other patients developed blisters after a mean follow-up time of 24.9 months (±54.9 SD). NBP patients had a more frequent history of myocardial infarction than BP patients (37.5 vs. 10.2%; p < 0.003). More NBP patients were taking diuretics than BP patients (66.7 vs. 49%; p = 0.03). NBP patients had a worse response to pruritus compared to BP patients at 2 years (NRS 3.7 vs. 11; p 0.001). Conclusions: NBP patients have a delayed diagnosis and may be at an increased risk of cardiovascular disease, especially myocardial infarction. Severely and persistently itchy skin disorders in aged patients should be investigated for BP diagnosis.

The mammalian target of rapamycin inhibitor (mTOR-I) Rapamycin, a drug widely used in kidney transplantation, exerts important anti-cancer effects, particularly in Kaposi's Sarcoma (KS), through several biological interactions. In this in vivo and in vitro study, we explored whether the activation of the autophagic pathway through the low-affinity receptor for nerve growth factor, p75NTR , may have a pivotal role in the anti-cancer effect exerted by Rapamycin in S. Our Kimmunohistochemistry results revealed a significant hyper-activation of the autophagic pathway in KS lesions. In vitro experiments on KS cell lines showed that Rapamycin exposure reduced cell viability by increasing the autophagic process, in the absence of apoptosis, through the transcriptional activation of p75NTR via EGR1. Interestingly, p75NTR gene silencing prevented the increase of the autophagic process and the reduction of cell viability. Moreover, p75NTR activation promoted the upregulation of phosphatase and tensin homolog (PTEN), a tumour suppressor that modulates the PI3K/Akt/mTOR pathway. In conclusion, our in vitro data demonstrated, for the first time, that in Kaposi's sarcoma, autophagy triggered by Rapamycin through p75NTR represented a major mechanism by which mTOR inhibitors may induce tumour regression. Additionally, it suggested that p75NTR protein analysis could be proposed as a new potential biomarker to predict response to Rapamycin in kidney transplant recipients affected by Kaposi's sarcoma.

The impact of cancer on death of elderly kidney transplant recipients has been extensively investigated, but with conflicting results. Unlike their younger counterparts, in elderly kidney transplant recipients cardiovascular and infectious disease may outweigh cancer in causing the patient’s death. Using competing risk analysis on a large retrospective cohort of kidney transplant recipients, we estimated the cause-specific cumulative incidence and hazard of death in different age categories and calculated standardized mortality ratios (SMRs) to compare mortality rates with the general population. Six thousand seven hundred eighty-nine kidney transplant recipients were followed-up for a median of 9 years. Ten years after transplantation, in transplant recipients aged 20–39, 40–59, and 60+, the cumulative incidence of cancer-related death was 0.6 (95% confidence interval [CI]: 0.3–1.0), 2.9 (2.3–3.6) and 5.3% (3.5–7.5), whereas the SMR was 9.1 (5.5–15.0), 2.0 (1.6–2.5), and 0.8 (0.6–1.0), respectively. At variance with young recipients, the hazard and the cumulative incidence of cardiovascular-related death in elderly recipients was well above that of cancer-related death. Relative to the general population, cancer-related death is increased in young but not in elderly kidney transplant recipients because of the more marked increased incidence of competing cause of death in the latter category.

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

Organ transplant recipients (OTRs) have a 100‐fold increased risk of cutaneous squamous cell carcinoma (cSCC). We prospectively evaluated the association between β genus human papillomaviruses (βPV) and keratinocyte carcinoma in OTRs. Two OTR cohorts without cSCC were assembled: cohort 1 was transplanted in 2003‐2006 (n = 274) and cohort 2 was transplanted in 1986‐2002 (n = 352). Participants were followed until death or cessation of follow‐up in 2016. βPV infection was assessed in eyebrow hair by using polymerase chain reaction–based methods. βPV IgG seroresponses were determined with multiplex serology. A competing risk model with delayed entry was used to estimate cumulative incidence of histologically proven cSCC and the effect of βPV by using a multivariable Cox regression model. Results are reported as adjusted hazard ratios (HRs). OTRs with 5 or more different βPV types in eyebrow hair had 1.7 times the risk of cSCC vs OTRs with 0 to 4 different types (HR 1.7, 95% confidence interval 1.1‐2.6). A similar risk was seen with high βPV loads (HR 1.8, 95% confidence interval 1.2‐2.8). No significant associations were seen between serum antibodies and cSCC or between βPV and basal cell carcinoma. The diversity and load of βPV types in eyebrow hair are associated with cSCC risk in OTRs, providing evidence that βPV is associated with cSCC carcinogenesis and may present a target for future preventive strategies., In two cohorts of organ transplant recipients, those with five and more different beta‐genus human papillomavirus types and high virus loads in eyebrow hairs subsequently develop significantly more cutaneous squamous cell carcinomas than others, suggesting that these virus types may increase the risk of cutaneous squamous cell carcinoma in these patients.

Primary cutaneous lymphomas (PCLs) are a rare group of extranodal non-Hodgkin lymphomas, and epidemiological data in Mediterranean countries are scarce.To investigate the incidence and characteristics of PCL in a single tertiary referral centre in Italy.A total of 141 PCL patients, seen over a 10-year follow-up period, were investigated.Incidence rate of PCL was 0.8 cases/100,000 person years. T-cell lymphoma represented 78.7% of all cases, the majority being early mycosis fungoides (MF) (64%; median age: 66 years), followed by lymphomatoid papulosis (LyP) (19%; median: age 48 years), and others (median age: 72 years), including eight cases of anaplastic large CD30+ T-cell lymphoma, four CD4+ small-medium pleomorphic T-cell lymphoproliferative disorder, four Sézary syndrome, one subcutaneous panniculitis-like T-cell lymphoma, one extranodal NK/T-cell lymphoma nasal-type, and one angioimmunoblastic T-cell lymphoma. B-cell lymphoma accounted for 21.3% of PCL, with 20 cases of cutaneous follicular centre B-cell (median age: 63 years), four primary cutaneous marginal zone, three primary cutaneous diffuse large B-cell, and three leg-type lymphoma. Complete remission within the first year after diagnosis occurred in 70.4% of MF, 61.9% of LyP, 78.9% of other T-cell lymphoma, and 93.1% of B-cell lymphoma cases. Based on a Cox proportional hazard regression model, age, gender, stage, and lactate dehydrogenase and β2-microglobulin blood levels did not predict clinical remission of MF or LyP.The incidence and characteristics of PCL in Italy are similar to those in other European countries. PCLs may be diagnosed at very early stages with good prognosis.

Neutrophilic figurate erythema (NFE) is a very rare inflammatory dermatosis, characterised by annular or polycyclic indurate lesions, and histologically by a perivascular and interstitial inflammatory cell infiltrate with numerous neutrophils and nuclear debris [1, 2]. NFE is a benign disorder that has been described both in infants and adults; the two forms are considered to have a distinct nature [1, 2]. Here, we describe a fifth case of NFE in adulthood and compare the characteristics between [...]

Filler injection is widely used for facial rejuvenation. Global skin rejuvenation requires the precise sequential injections of different areas, but a standardized and reproducible method is lacking. The purpose of the study was to develop a new method for a precise measurement of the degree of facial defect before and after full-face rejuvenation with injectable fillers, so called facial filler (FAFI) grid.Three hundreds patients were included. There were 76 males and 224 females with a median age of 30.5 years. A grid of horizontal and vertical lines was drawn on the patients' face with a rigid meter and a surgical pen to identify some precise areas for sequential filler injections. The grid was also used to measure the defects and the corrections obtained. Three different formulations of hyaluronic acid were used for treating specific facial areas.Correction was judged adequate in 77% and 90% of cases by the physician and patients, respectively. Prevalence of adverse events was 8.8%, with mostly mild, with resolution in few weeks.FAFI grid proved to be helpful in guiding sequential injections for total facial rejuvenation.

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

Tessari G, Naldi L, Piaserico S, Boschiero L, Nacchia F, Forni A, Rugiu C, Faggian G, Dall’Olio E, Fortina AB, Alaibac M, Sassi F, Gotti E, Fiocchi R, Fagioli S, Girolomoni G. Incidence and clinical predictors of primary opportunistic deep cutaneous mycoses in solid organ transplant recipients: a multicenter cohort study. Clin Transplant 2010: 24: 328–333. © 2009 John Wiley & Sons A/S. Abstract: Background: Primary opportunistic deep cutaneous fungal infections may cause significant morbidity and mortality in solid organ transplant recipients (OTR), but no data exist about their incidence, timing, and clinical predictors in a long-term follow-up. Patients and methods: A series of 3293 consecutive OTR including 1991 kidney, 929 heart, and 373 liver transplant recipients were enrolled. Patients were regularly followed up since time at transplantation (mean 5.5 yr ±5.9 SD) and primary opportunistic fungal infections registered. Persons-year at risk (PYs), incidence rates (IR), incidence rate ratios (IRR), and 95% confidence intervals were computed. Results: Twenty-two cases of deep cutaneous mycoses were detected, (IR 1.2 cases per 1000 PYs) after a mean follow-up time since transplantation of 2.5 yr ± 2.0 SD (median 1.8 yr). Six patients had subsequent systemic involvement and three patients died of systemic dissemination. A higher risk for mycoses was observed in the first two yr after transplantation, (IRR 35.9, p

Summary 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 (30AE1% vs. 20AE6%, odds ratio 1AE65, 95% confidence interval 1AE16‐2AE35; P= 0AE005) 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.

Summary 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 (–765GC, and –1195AG) in the promoter region of the COX-2 gene (now PTGS2), and one common polymorphism in the 3′ UTR (8473TC) 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, −62CG, 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 –1195AG 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 8473TC, located in the 3′ UTR region of the gene, showed no association with NMSC risk after transplantation. Conclusions COX-2 common variants –765GC and –1195AG 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.

Identification of pre-transplant factors influencing delayed graft function (DGF) could have an important clinical impact. This could allow clinicians to early identify dialyzed chronic kidney disease (CKD) patients eligible for special transplant programs, preventive therapeutic strategies and specific post-transplant immunosuppressive treatments. To achieve these objectives, we retrospectively analyzed main demographic and clinical features, follow-up events and outcomes registered in a large dedicated dataset including 2,755 patients compiled collaboratively by four Italian renal/transplant units. The years of transplant ranged from 1984 to 2012. Statistical analysis clearly demonstrated that some recipients’ characteristics at the time of transplantation (age and body weight) and dialysis-related variables (modality and duration) were significantly associated with DGF development (p ≤ 0.001). The area under the receiver-operating characteristic (ROC) curve of the final model based on the four identified variables predicting DGF was 0.63 (95 % CI 0.61, 0.65). Additionally, deciles of the score were significantly associated with the incidence of DGF (p value for trend

Prurigo nodularis (PN) is a chronic, highly pruritic condition characterized by the presence of hyperkeratotic, excoriated, pruritic papules and nodules, with a tendency to symmetrical distribution. No reliable data exist about incidence and prevalence of PN in the general population, but it seems to be more frequent and more intense in females. PN may be associated with many dermatological and non-dermatological comorbidities, including psychiatric disease. Recent findings suggest a neuropathic origin of PN, with alterations in the dermal and epidermal small diameter nerve fibers. PN may have a tremendous impact on the quality of life, and few effective treatment options are available. Few randomized controlled trials (RCT) on the therapy of PN are available, demonstrating the efficacy of phototherapy alone or with psoralen, and of topical calcipotriol and topical steroids in occlusive medications. Thalidomide may be effective, but no RCT are available and its use is impractical due to the unfavorable safety profile. Gabapentin, pregabalin and the neurokinin receptor 1 antagonist, aprepitant, seem also to be effective in the therapy of PN, but RCTs are still lacking.

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.

Background Prevalence and causes of allergic contact dermatitis (ACD) in children vary with time and geographical area. Objective This study aimed to determine the relevant allergens causing ACD in children and the relation between ACD and atopic dermatitis (AD). Methods A cohort study on 349 children (0-15 years old) patch tested over a 7-year period was conducted. Results Patch test results were positive for at least 1 allergen in 69.3% of patients and were relevant in 69.8%. The highest sensitization rate (76.7%) was observed in children who are 0 to 5 years old (n = 86, 64% females), followed by the group of 6- to 10-year olds (70%, n = 157, 47.8% females), whereas 62.3% of 11- to 15-year-old children (n = 106, 59.4%) were sensitized. The most frequent allergens were nickel (16.3%), cobalt (6.9%), Kathon CG (5.4%), potassium dichromate (5.1%), fragrance mix (4.3%), and neomycin (4.3%). Body areas mostly affected were upper limbs and hands (31%). Approximately one third of children also had AD. Allergic contact dermatitis was more widespread in children with AD. Patch tests resulted positive in 55.3% (50% relevant) of AD compared with 76.9% (77.5% relevant) of the children without AD. Sensitizers were similar to children without AD. Conclusions Very young children showed a high rate of relevant positive patch test reactions to common haptens. Allergic contact dermatitis may easily coexist with AD.

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.

Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae. We describe the case of a 20-year-old man from India living in Italy since 2003, who presented with erythematous papules and nodules distributed on his arms, legs, and face in 2006. He also had episodes of high fever, polyarthritis, and episcleritis. Sarcoidosis was suspected on the basis of elevated angiotensin-converting enzyme and bronchoalveolar lavage fluid, and the patient was treated with corticosteroids for about a year. A flare of the disease occurred each time corticosteroid was tapered or suspended. An autoinflammatory disease was then suspected and treated with immunosuppressant. Only the third deep skin biopsy revealed the presence of M. leprae. The lack of clinical suspicion and the unfamiliarity with the histology of leprosy delayed diagnosis and treatment. Leprosy should be considered in the differential diagnoses of patients presenting with rheumatic and cutaneous manifestations especially when they come from countries where the disease is endemic.

Cyclosporin (CsA) and azathioprine (AZA) are useful immunosuppressive drugs in the management of kidney and liver transplant recipients. We investigated urinary mutagenicity in three groups of kidney transplant recipients after different immunosuppressive protocols. Urinary mutagenicity was detected in a base-pair strain, E. coli WP2uvrA, in a liquid incubation assay. No mutagenic activity was detected in the urines of patients treated with CsA (4.5 mg/kg); 85% of the urines in the second group treated with AZA (1.26 mg/kg) showed high mutagenic activity, whereas mutagenic activity was found in 40% of the urines of subjects treated with CsA and AZA (3.89 mg/kg + 1.15 mg/kg). These data suggest that immunosuppressive therapy with AZA carries a high risk of urinary mutagenicity, while immunosuppressive combined treatment with CsA and AZA significantly reduces this risk.

Objective To compare the long-term risk of primary nonmelanoma skin cancer (NMSC) and the risk of subsequent NMSC in kidney and heart transplant recipients. Design Partially retrospective cohort study. Setting Two Italian transplantation centers. Patients The study included 1934 patients: 1476 renal transplant recipients and 458 heart transplant recipients. Main Outcome Measures Cumulative incidences and risk factors of the first and subsequent NMSCs. Results Two hundred patients developed a first NMSC after a median follow-up of 6.8 years after transplantation. The 3-year risk of the primary NMSC was 2.1%. Of the 200 patients with a primary NMSC, 91 (45.5%) had a second NMSC after a median follow-up after the first NMSC of 1.4 years (range, 3 months to 10 years). The 3-year risk of a second NMSC was 32.2%, and it was 49 times higher than that in patients with no previous NMSC. In a Cox proportional hazards regression model, age older than 50 years at the time of transplantation and male sex were significantly related to the first NMSC. Occurrence of the subsequent NMSC was not related to any risk factor considered, including sex, age at transplantation, type of transplanted organ, type of immunosuppressive therapy, histologic type of the first NMSC, and time since diagnosis of the first NMSC. Histologic type of the first NMSC strongly predicted the type of the subsequent NMSC. Conclusions Development of a first NMSC confers a high risk of a subsequent NMSC in transplant recipients. Intensive long-term dermatologic follow-up of these patients is advisable.

Primary opportunistic deep cutaneous fungal infections may cause significant morbidity and mortality in solid organ transplant recipients (OTR), but no data exist about their incidence, timing, and clinical predictors in a long-term follow-up. Patients and methods: A series of 3293 consecutive OTR including 1991 kidney, 929 heart, and 373 liver transplant recipients were enrolled. Patients were regularly followed up since time at transplantation (mean 5.5 yr ±5.9 SD) and primary opportunistic fungal infections registered. Persons-year at risk (PYs), incidence rates (IR), incidence rate ratios (IRR), and 95% confidence intervals were computed. Results: Twenty-two cases of deep cutaneous mycoses were detected, (IR 1.2 cases per 1000 PYs) after a mean follow-up time since transplantation of 2.5 yr ± 2.0 SD (median 1.8 yr). Six patients had subsequent systemic involvement and three patients died of systemic dissemination. A higher risk for mycoses was observed in the first two yr after transplantation, (IRR 35.9, p < 0.0001), in renal transplant recipients (IRR 5.1 p = 0.030), and in patients transplanted after the age of 50 (IRR 11.5 p = 0.020). Conclusions: Primary deep cutaneous opportunistic mycoses in OTR occur mainly in the first two yr after transplantation, in renal transplant recipients, and in older patients.

Chronic pruritus is a major and distressing symptom of many cutaneous and systemic diseases and can significantly impair the patient's quality of life. Pruritus perception is the final result of a complex network involving dedicated nerve pathways and brain areas, and an increasing number of peripheral and central mediators are thought to be involved. Itch is associated with most cutaneous disorders and, in these circumstances, its management overlaps with that of the skin disease. Itch can also occur without associated skin diseases or primary skin lesions, but only with nonspecific lesions secondary to rubbing or scratching. Chronic itch with no or minimal skin changes can be secondary to important diseases, such as neurologic disorders, chronic renal failure, cholestasis, systemic infections, malignancies, and endocrine disorders, and may also result from exposure to some drugs. The search for the cause of pruritus usually requires a meticulous step-by-step assessment involving careful history taking as well as clinical examination and laboratory investigations. Few evidence-based treatments for pruritus are available. Topical therapy, oral histamine H(1) receptor antagonists, and phototherapy with UV radiation can target pruritus elicitation in the skin, whereas antiepileptic drugs, opioid receptor antagonists, and antidepressants can block signal processing in the CNS.

Summary 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 ≥ 75% reduction of vitiligo lesions at 12 weeks (χ2 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.

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.

Solid organ transplant recipients are at higher risk of non-melanoma skin cancer (NMSC), especially basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Genetic alterations in the production of detoxifying enzymes such as glutathione S-transferase (GST) and CYP1A1 may enhance this risk. We investigated the frequency of GST genotypes (GSTM1, GSTM3, GSTT1 and GSTP1) and CYP1A1 in 239 transplant recipients: 107 cases with NMSC and 132 controls free from NMSC matched for type of transplanted organ, duration of transplantation, sex and age. Allele GSTP1*A was associated with a higher risk of NMSC [odds ratio (OR) 1.7 (1.1-2.5); P = 0.017]. Homozygosity for allele GSTP1 Val(105) was lower in cases [OR 0.3 (0.1-0.8); P = 0.012], especially in patients with SCC [OR 0.1 (0.0-0.7); P = 0.012]. A higher risk of BCC was found in patients with GSTM1 null/null [null/null versus A + B, OR 3.1 (1.4-6.8); P = 0.003]. Analysis of allelism and interaction between allelic variants showed significant association between combined GSTM1 and CYP1A1 Val(462) genotypes, where individuals homozygous for the risk allele GSTM1 null and carrying also the allele CYP1A1 Val(462), show a higher risk of developing NMSC [OR 4.5 (1.1-21.4); P = 0.03], especially SCC [OR 6.5 (1.4-34.4); P = 0.01]. GSTP1 polymorphisms are associated with both BCC and SCC risk. GSTM1 polymorphisms seem to be involved in BCC risk, while GSTM1 null/null genotype combined with CYP1A1 allele Val(462) are associated with a higher risk for SCC, indicating that allelism and/or interactions between allelic variants at other loci may also influence the risk of NMSC, particularly SCC.

Publisher Summary The human skin is the largest organ of the body that provides a protective barrier to ensure that exogenous noxious agents do not affect the homeostasis of the organism. Knowledge of skin immunological defense mechanisms is advancing rapidly and provides new insights into the normal homeostasis of this vital organ, improving the understanding of various disease processes. Structure–function correlations are being expanded to include detailed molecular dissection of the events that are principally responsible for the skin immune system (SIS), and which guide the coordinated intercellular interplay crucial for immune surveillance involving the skin. For the understanding of cutaneous immunology, it is essential to keep in mind what distinguishes the skin from other organs. From such a platform of specific immunophysiology of the skin its dysregulations as it knows them in the form of a surprisingly large number of inflammatory and immunodermatological diseases can be understood.

A superficial spreading melanoma (Breslow thickness 0.4 mm) was diagnosed in a 65-year-old candidate for heart transplantation due to refractory end stage heart failure. After extensive review of the literature (USA and Europe), no clear guidelines about the management of candidates for transplantation with a previous diagnosis of melanoma were found. As this patient had a 5-year probability of survival higher than 95% and heart transplantation was necessary for saving his life, the final decision was to perform the transplantation. Unfortunately, the patient died of heart failure before a suitable heart became available. This case stresses the need for early and continuous dermatological evaluation of all candidates for solid organ transplantation. Clear guidelines for screening of skin cancer before transplantation are needed.

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.

BACKGROUND Organ transplant recipients are at an increased risk of nonmelanoma skin cancer. Few data concern heart transplantation and populations from southern Europe. METHODS A total of 1,329 patients who received their first kidney (1,062 subjects) or heart allograft (267 subjects) were included in a partly retrospective cohort study to evaluate the risk of skin cancer. The incidence rate per 1,000 person-years and the cumulative incidence were computed. Standardized morbidity ratio was estimated by comparison with Italian cancer registry data. To analyze the role of potential prognostic factors, Cox's regression method was used. RESULTS The overall incidence rate of nonmelanoma skin cancer was 10.0 cases per 1,000 posttransplant person-years (95% confidence interval 8.2-11.7). This estimate was far higher than expected in the general population. The overall risk of developing skin cancer increased from a cumulative incidence of 5.8% after 5 posttransplant years to an incidence of 10.8% after 10 years of graft survival. In a Cox proportional hazard risk model, the most important factors that appeared to favor the development of skin cancer were age at transplantation and sex. After adjustment for age at transplantation and sex, no definite increased risk was documented among heart as compared with kindney transplant recipients. CONCLUSIONS Our study confirms the increased risk of nonmelanoma skin cancer among organ transplant recipients in a southern European population.

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We have investigated some possible risk factors for cutaneous warts in a consecutive group of renal transplant recipients treated with three different immunosuppressive regimens: prednisolone + azathioprine (PA), prednisolone + azathioprine + cyclosporin (PAC), prednisolone + cyclosporin (PC). Kaplan and Meier analysis showed an earlier onset of warts in the PAC and PC groups than in the PA group (p0.0001), which might be related to the different immunosuppressive action of the pharmacological treatments including cyclosporin. Seven patients had skin cancer: 4 of them also had multiple warts on the cancer site. In 2 patients, histological examination demonstrated the neoplastic transformation of a wart. Maintenance posology of azathioprine, cyclosporin and prednisolone may be an important risk factor for cutaneous warts; on the other hand HLA-B mismatch and HLA-A11 seem to have no effect.

We present a review of the current literature on skin diseases in renal transplant recipients (RTR) and the results of a 5-year follow-up of 285 patients. Many skin diseases are only an aesthetic and functional cause for interest, but HPV infections and skin cancers are significantly more frequent in RTR than in immunocompetent subjects and can affect a patient's prognosis. For this reason, we feel dermatological surveillance of RTR is necessary for early diagnosis and treatment of all high-risk lesions.

Udgivelsesdato: 2007-Oct Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith Disease, is a rare cancer-associated genodermatosis with an autosomal dominant inheritance. Affected patients suffer from recurrent skin lesions, which clinically and histologically resemble keratoacanthomas or well-differentiated squamous cell carcinomas, but which, if left, undergo spontaneous regression, leaving pronounced scarring. The majority of MSSE cases previously described were of Scottish ancestry and all shared the same at-risk haplotype, suggesting that this disorder was caused by a founder mutation. The candidate locus for MSSE lies in a region of