Association Between Atopic Dermatitis and Cardiovascular Disease: A Nationwide Register-based Case-control Study from Sweden.

The associations between atopic dermatitis (AD) and cardiovascular disease (CVD) are debated. The aim of this study was to investigate the association between AD and coronary artery disease or ischaemic stroke in a nationwide, register-based, case-control study (104,832 AD cases, 1,022,435 controls) based on linkage of Swedish national register data between 1968 and 2016. Patients were classified as having severe AD if they had received systemic pharmacotherapy for AD or had been treated in a dermatological ward with AD as the main diagnosis. Other AD was classified as non-severe. After multivariable adjustments for comorbidities and socioeconomic status, overall AD was associated with angina pectoris (adjusted odds ratio (aOR) 1.13, 95% confidence interval (CI) 1.08-1.19), but among males with severe AD this association was not found, compared with the general population. Male non-severe AD was associated with myocardial infarction (OR 1.15, 95% CI 1.07-1.23). Severe AD was associated with ischaemic stroke, with similar estimates in men and women (aOR 1.19, 95% CI 1.07-1.33). Subgroup analyses among women indicated smoking as an important risk factor among severe cases. Dia-betes mellitus, hyperlipidaemia, and hypertension were more prevalent in severe AD than in controls, and hyper-lipidaemia and hypertension were also more prevalent in non-severe AD than in controls. In conclusion, in this study, AD was associated with CVD, and this should be kept in mind, especially when managing patients with severe AD.

Shift in Occupational Risk for Basal Cell Carcinoma from Outdoor to Indoor Workers: A Large Population-based Case-control Register Study from Sweden.

Basal cell carcinoma (BCC) is the most common form of cancer worldwide. Exposure of the skin to ultraviolet (UV) radiation, from sunlight and other sources, is the most important risk factor. The aim of this large-scale case-control study was to determine which occupations are associated with increased risk of BCC in Sweden. The case cohort comprised 74,247 patients with BCC and the control cohort comprised 574,055 subjects linked to population-based registers. Compared with the occupational category of farmers, foresters and gardeners we observed elevated risks of BCC for almost all occupational categories studied. Legal workers with odds ratio (OR) 2.69 (95% confidence interval (CI) 2.36-3.06), dentists OR 2.69 (95% CI 2.35-3.08) and physicians OR 2.47 (95% CI 2.24-2.74) had the highest risk for both sexes taken together. In conclusion, there appears to have been a change in the risk of BCC from outdoor to indoor occupations in Sweden, possibly related to exposure to UV radiation during leisure activities exceeding occupational sun exposure as the main cause of BCC in Sweden.

[In case of pruritus, always consider scabies!]. / Vid klåda, tänk alltid på skabb!

In case of pruritus, always consider scabies! Scabies is an itching skin disease caused by the mite Sarcoptes scabiei which affects more than 100 million people worldwide. Regarded as a neglected tropical disease by the WHO, it is a major public health burden in endemic areas. As direct skin-to-skin contact is the main route of transmission family members and sexual partners are often affected. Typical presentation includes a severely pruritic rash with predilection for the extremities and the trunk. Definitive diagnosis relies on microscopic identification of the mites. Future, more efficient, diagnostic methods may include serological testing or PCR for S. scabiei DNA. A benzyl benzoate and disulfiram based lotion, Tenutex, is the treatment of choice in Sweden with topical permethrin or oral ivermectin being used in certain cases. Scabies is an important diagnosis to consider in all patients presenting with pruritus.

Suberythemal Sun Exposures at Swedish Schools Depend on Sky Views of the Outdoor Environments - Possible Implications for Pupils' Health.

More scheduled outdoor stay is increasingly advocated for school children. This study measured 2(nd) , 5(th) and 8(th) graders' erythemal UV-exposure in September, March and May at four Swedish schools. We related those exposures, as fractions of total available ambient radiation, to the schools outdoor environments differing in amount of shade, vegetation, and peripheral city-scape quantified as percentage of free sky view calculated from fish-eye photographs. Exposures correlated with the sky views (with exceptions in May) and were suberythemal. The exposures were also below the threshold limit of the International Commission on Non-Ionizing Radiation Protection (ICNIRP) for hazard evaluation of UVR but were potentially enough for adequate vitamin D formation according to a cited model calculation - as illustrated in the results and discussed. The school environments, typical in southern and middle Sweden, offer enough shade to protect children from overexposure during seasons with potentially harmful solar UV radiation. Pupils' outdoor stay may be extended during September and March. In May extended outdoor stay of the youngest pupils requires a more UVR-protective environment.

Similar anatomical distributions of childhood naevi and cutaneous melanoma in young adults residing in northern and southern Sweden.

BACKGROUND: Common melanocytic naevi are considered early biomarkers associated with risk of cutaneous malignant melanoma. We sought to investigate if residing at different latitudes in Sweden influences the population's anatomical distribution of naevi in children and melanoma in adults. METHODS: The nationwide Swedish Cancer Registry 1990-2012 gave cumulative number of invasive melanomas per body site, stratified by sex and age in northern (62-69 °N) (n=2823) and southern (55-58 °N) Sweden (n=24,115). A population-based cross-sectional study conducted in 2002 provided the allocation of naevi among 7-year-olds in northern (5695 naevi in 679 children) and southern Sweden (8392 naevi in 681 children). RESULTS: In 2012, northern Sweden had a two-fold lower melanoma incidence: 19.8/100.000 age-standardised population compared with 41.0/100.000 in the south. Similarly, a lower mean naevi density in children was demonstrated: 7.3 (standard deviation (SD) 5.4) in boys and 7.0 (4.7) in girls in the north versus 13.3 (8.4) in boys and 11.9 (8.5) in girls in the south. Across latitudes of residing, gender profiles and proportional body-site distributions of melanoma and naevi, respectively, were largely homogenous, but in southern Sweden slightly higher on the trunk; a body site associated with intermittent sun exposure. Childhood naevi distributions matched with melanomas in young and middle-aged adults. CONCLUSION: This large population-based study demonstrated that latitude of residing similarly affects the number and anatomical distribution of naevi in children and melanoma in adults. It supports a role of childhood naevi as predictors of overall and subsite risk of melanoma among young adults.

Cutaneous malignant melanoma in the Swedish organ transplantation cohort: A study of clinicopathological characteristics and mortality.

BACKGROUND: Risk of cutaneous melanoma is increased among organ transplant recipients (OTRs) but outcome has rarely been evaluated. OBJECTIVE: We sought to assess melanoma characteristics and prognosis among OTRs versus the general population. METHODS: Using Swedish health care registers, we identified melanomas in OTRs (n = 49) and in the general population (n = 22,496), given a diagnosis between 1984 and 2008 and followed up through December 31, 2012. Tumor slides of posttransplantation melanomas were reviewed. Odds ratios for comparison of histopathological characteristics and hazard ratios of melanoma-specific death were calculated. RESULTS: Among OTRs the trunk was the most common anatomic melanoma site (50% among female vs 51% among male) and 73% (n = 36) of all melanomas were histologically associated with a melanocytic nevus, 63% (n = 31) atypical/dysplastic. Compared with population melanomas, posttransplantation melanomas were more advanced at diagnosis (Clark level III-V: odds ratio 2.2 [95% confidence interval 1.01-4.7, P = .03], clinical stages III-IV: odds ratio 4.2 [1.6-10.8, P = .003]). Risk of melanoma-specific death was increased among OTRs: adjusted hazard ratio 3.0 (1.7-5.3, P = .0002). LIMITATIONS: Only posttransplantation melanoma slides were reviewed. CONCLUSIONS: Melanomas were more advanced at diagnosis and melanoma-specific survival was poorer in OTRs than in the general population. Prophylactic excision of truncal nevi among OTRs may be advised.

Changes in body-site distribution of common melanocytic naevi among 7-year-old Swedish children between 2002 and 2007.

An observational population-based study conducted among 2 sets of 7-year-old children in Sweden in 2002 and 2007 revealed evidence of improved sun protection, also reflected in a significant reduction in the total number of melanocytic naevi. Based on these data-sets, the aim of the current study was to determine whether the overall reduction in naevi had impacted differently on body sites based on their main pattern of sun exposure. In 2002, median naevi counts/m2 were highest on intermittently sun-exposed sites: 13.8 (95% CI 8.0-22.7) compared with chronically sun-exposed sites: 11.0 (95% CI 0.0-20.5). In 2007, median naevi counts/m2 on intermittently sun-exposed body sites were significantly lower: 8.7 (95% CI 4.7-15.2), p < 0.0001, while on chronically exposed sites median naevi counts/m2 were unaltered: 10.3 (95% CI 0.0-14.4), p = 0.9313. Changes were most evident among boys. Future research can evaluate whether this shift in naevi distribution in Swedish children translates into a reduction in cutaneous melanomas on intermittently sun-exposed body sites.

Mobile teledermatology is a valid method to estimate prevalence of melanocytic naevi in children.

The prevalence of melanocytic naevi in children correlates with sun exposure and may serve as an objective population risk indicator of future melanoma incidence. The aim was to investigate if mobile teledermatology could offer a valid methodology compared with standard manual, face-to-face counting of naevi on the back of children. Ninety-seven children aged 7-16 years were enrolled. One dermatologist performed manual naevi counting and imaging of the child's back using an iPhone 4S comprising a safe-coded mobile application. Two other dermatologists independently counted naevi from the images. Cohen's weighted kappa (κw) coefficient demonstrated substantial agreement for both dermatologists: κw = 0.69 (0.57-0.81 [95% confidence intervals]) and κw = 0.78 (0.70-0.86), compared with the manual assessment. Inter-rater reliability was also substantial (κw = 0.80 [0.73-0.87]). Use of mobile teledermatology proved valid for estimating naevi prevalence on the back and could provide a more feasible methodology following trends in sun exposure in children.

Does urticaria risk increase in patients with celiac disease? A large population-based cohort study.

BACKGROUND: Case reports and smaller case-control studies suggest an association between celiac disease (CD) and urticaria but risk estimates have varied considerably across studies and as yet there are no studies on CD and the risk of future urticaria. OBJECTIVE: To examine the association between CD and urticaria. METHODS: We identified 28,900 patients with biopsy-verified CD (equal to Marsh stage 3) and compared them with 143,397 age- and sex-matched controls with regards to the risk of urticaria and chronic urticaria (duration ≥6 weeks). Hazard ratios (HRs) were estimated using a Cox regression model. RESULTS: During follow-up, 453 patients with CD and no previous diagnosis of urticaria developed urticaria (expected n = 300) and 79 of these 453 had chronic urticaria (expected n = 41). The corresponding HRs were 1.51 for any urticaria (95%CI = 1.36-1.68) and 1.92 for chronic urticaria (95%CI = 1.48-2.48). The absolute risk for urticaria in CD was 140/100,000 person-years (excess risk = 47/100,000 person-years). Corresponding figures for chronic urticaria were 24/100,000 person-years and 12/100,000 person-years. Patients with CD were also at increased risk of having both urticaria (odds ratio, OR = 1.31; 95%CI = 1.12-1.52) and chronic urticaria (OR = 1.54; 95%CI = 1.08-2.18) prior to the CD diagnosis. CONCLUSION: This study suggests that CD is associated with urticaria, especially chronic urticaria.

Risk of skin cancer and other malignancies in kidney, liver, heart and lung transplant recipients 1970 to 2008--a Swedish population-based study.

Organ transplant recipients are at increased risk of a wide range of malignancies, especially cutaneous squamous cell carcinomas (SCC). Few previous population-based studies have quantified and compared cancer risks according to graft type and with long-term follow-up. Using nationwide Swedish registers, we identified 10,476 recipients transplanted from 1970 to 2008 and followed them for cancer occurrence. Relative risks of cancer in comparison with the general population were expressed as standardized incidence ratios (SIR) and within the transplanted cohort as incidence rate ratios (IRR). During a total follow-up of 93,432 person-years, patients were diagnosed with 1,175 cancers excluding SCC, and with 2,231 SCC, SIR(cancer excl SCC) 2.4 (95% CI, 2.2-2.5); SIR(SCC) 121 (95% CI, 116-127). Cancer risks were most increased among heart and/or lung recipients SIR(cancer excl SCC) 3.3 (95% CI, 2.8-4.0); SIR(SCC) 198 (95% CI, 174-224), followed by kidney SIR(cancer excl SCC) 2.3 (95% CI, 2.1-2.4); SIR(SCC) 121 (95% CI, 116-127) and liver recipients SIR(cancer excl SCC) 2.3 (95% CI, 1.9-2.8); SIR(SCC) 32 (95% CI, 24-42). During follow-up, risk of cancer excluding SCC remained stable while risk of SCC tripled over 20 years irrespective of graft type, partly due to a subgroup of patients developing new SCCs at a rapidly increasing rate. In summary, post-transplant cancer risk varied by transplanted organ and by cancer site, with the bulk of the excess risk driven by an exceptionally high and accelerating risk of SCC. These findings underscore the importance of regular skin screening in organ transplant recipients.

No association between infections, HLA type and other transplant-related factors and risk of cutaneous squamous cell carcinoma in solid organ transplant recipients.

Recipients of solid organ transplants are at a markedly increased risk of cutaneous squamous cell carcinoma (SCC). We investigated potential associations between post-transplant infections, HLA type, and other transplant-related factors and risk of SCC, taking immuno-suppressive treatment into account. A population-based case-control study was conducted. All patients who developed SCC during follow-up (1970-1997) were eligible as cases (n = 207). Controls (n = 189) were individually matched to the cases on age and calendar period of transplantation. Detailed exposure information was collected through an extensive, blinded review of medical records. Odds ratios were computed with conditional logistic regression. There were no significant associations with any infectious agents, or with number and timing of infections, specific HLA-type, donor characteristics, or other transplant characteristics and risk of post-transplant SCC. These results suggest that risk of post-transplant SCC is neither closely related to specific post-transplant infectious disorders, nor to the infectious load or specific HLA types.

Previous extensive sun exposure and subsequent vitamin D production in patients with basal cell carcinoma of the skin, has no protective effect on internal cancers.

BACKGROUND: It has been suggested that sunlight through production of vitamin D might have a protective effect on a number of internal cancers. Consequently, in spite of the well known skin cancer risks, some researchers advocate more exposure to ultraviolet radiation, supported by the solarium industry. We estimated the risk of internal cancer before the patient contracted a basal cell carcinoma (BCC) of the skin, the most common cancer in white populations and strongly associated with extensive sun exposure. METHODS: A nested case control study was undertaken in the whole Swedish population. 115,016 patients with BCC and 987,893 controls were linked to population based registers. FINDINGS: The cases had an increased risk of getting another form of cancer before the BCC diagnosis: odds ratio (OR)=1.84; 95% confidence interval (CI) 1.81-1.86. This risk was mainly due to skin cancer: OR=4.95; 95% CI 4.81-5.09 but also non-skin cancer risk was elevated: OR=1.37; 95% CI 1.35-1.39. We adjusted the estimates for age, level of income, occupational status in national censuses, place of living and sex, where appropriate. Of the cancers specifically suggested to be related to vitamin D status: colon, prostate, breast, and ovary cancer, all had slightly increased ORs whilst for pancreatic and gastric cancer no increased OR was found. INTERPRETATION: Patients with BCC, a proxy for extensive sun exposure, run an increased risk of other forms of cancer prior to the diagnosis of BCC. The findings in this study contradict that vitamin D production through extensive sun exposure has any protective effect on internal cancer but emphasise the increased risk for skin cancer.

Psoriasis in a nationwide cohort study of patients with celiac disease.

Earlier studies on the association between celiac disease (CD) and psoriasis show contradictory results. The purpose of this study was to assess the risk of psoriasis in patients with biopsy-verified CD. Through 28 pathology departments in Sweden, we identified individuals with CD diagnosed between 1969 and 2008 (Marsh 3: villous atrophy; n = 28,958 unique individuals). We then used Cox regression to compare individuals with CD with 143,910 sex- and age-matched controls regarding their risk of psoriasis. CD was a risk factor for future psoriasis (hazard ratio (HR) = 1.72; 95% confidence interval (CI) = 1.54-1.92; during follow-up, 401 individuals with CD and 1,139 controls had a diagnosis of psoriasis). The absolute risk of future psoriasis in patients with CD was 135/100,000 person-years (excess risk = 57/100,000). In all, 42% of all psoriasis in patients with CD could be attributed to the underlying CD. Moreover, in children we saw a positive association between CD and psoriasis (HR = 2.05; 95% CI = 1.62-2.60). The association between CD and psoriasis seems to be independent of a temporal relationship, as we also found a positive association between CD and psoriasis before CD diagnosis (odds ratio = 1.91; 95% CI = 1.58-2.31). In conclusion, individuals with CD were at increased risk of psoriasis both before and after CD diagnosis.

Differences in the peritumoural inflammatory skin infiltrate between squamous cell carcinomas in organ transplant recipients and immunocompetent patients.

Organ transplant recipients (OTR) have a greatly increased risk (up to 100 times) of developing squamous cell carcinomas (SCC) in the skin. This is attributed specifically to chronic immunosuppression, causing dysfunctional viral defence and tumour protection. To investigate the possible link between increasing risk of SCCs and type of inflammation in these tumour-prone patients, we analysed the peritumoural infiltrates with regard to cell types and densities. Seven SCCs from immunosuppressed OTR and 14 SCCs from immunocompetent patients were immun-histochemically stained for CD3, CD4, CD8, CD56, CD20, CD138, CD14, CD68, CD1a. Cell counts were performed with the aid of computer-based image analysis of > 100,000 cells. When comparing the percentage distributions, significant differences were detected (outlined as median values (min-max)): T cells (CD3+): OTR 57% (35-78), controls 68% (48-80), p = 0.036; plasma cells (CD138+): OTR 2% (0.7-7), controls 0.2% (0-1.2), p = 0.001; mono-cytes (CD14+): OTR 3.2% (1.1-5.6), controls 9.3% (2.2-17.2), p = 0.014. Surprisingly, no differences in cell densities, i.e. cells/mm2 tumour section area, were detected between the 2 groups. In conclusion, we found that the peritumoural infiltrates in immunosuppressed compared with immunocompetent patients differ in cellular composition, inferring a more tumour-submissive environment in OTR. However, cellular densities were equal, suggesting deviating cellular functionality in OTR.

Immunosuppressive treatment after solid organ transplantation and risk of post-transplant cutaneous squamous cell carcinoma.

BACKGROUND: The risk of cutaneous squamous cell carcinoma (CSCC) is found to be substantially increased after organ transplantation. The association with specific immunosuppressive regimens has been previously investigated, but results are not concordant. We aimed to clarify the relationship between separate immunosuppressive drugs, drug load, timing and risk of post-transplant CSCC. METHODS: A population-based nested case-control study was performed in the Swedish organ transplantation cohort (n = 5931). All patients who developed CSCC during the follow-up (1970-97) were eligible as cases (n = 207). Controls (n = 189) were randomly selected from the cohort and individually matched to the cases on follow-up time, age at and calendar period of transplantation. Exposure information was collected through extensive and standardized review of medical records. RESULTS: The median time to CSCC was 6.7 years. Post-transplant azathioprine (Aza) treatment considerably increased the risk of CSCC during all time periods analysed, and the risk augmented with increasing dose and duration. Patients who after the entire follow-up period had received a high accumulated dose of Aza had an 8.8-fold increased risk of CSCC in multivariate analysis (P < 0.0001), compared to patients never treated with Aza. Additionally, a high accumulated dose of corticosteroids during the same period conferred a 3.9-fold elevated risk of CSCC (P = 0.09), compared to the lowest accumulated dose of corticosteroids. Cyclosporine treatment was not associated with the risk of CSCC post-transplantation. CONCLUSIONS: This study provides evidence that Aza treatment, but not cyclosporine treatment, is strongly associated with post-transplant CSCC risk. The results suggest that the risk of CSCC after organ transplantation is not only an effect of the immunosuppressive load per se.