Bernt Lindelöf

Risk of cancer in patients with dermatomyositis or polymyositis : a population-based study

BACKGROUND An association between polymyositis and cancer was first proposed in 1916, but the existence of the association has been disputed. An association between dermatomyositis and cancer is better accepted, but its magnitude is not known. METHODS We undertook a study to provide accurate estimates of the risk of cancer in patients with dermatomyositis or polymyositis. We studied the incidence of cancer and the rate of mortality from cancer in a population-based cohort of 788 patients with dermatomyositis or polymyositis in Sweden from 1963 through 1983. The results were compared with those for the general population. RESULTS Among the 396 patients with polymyositis, 42 cancers were diagnosed at the same time or after polymyositis was diagnosed in 37 patients (9 percent). The relative risk of cancer was 1.8 (95 percent confidence interval, 1.1 to 2.7) in the male patients and 1.7 (95 percent confidence interval, 1.0 to 2.5) in the female patients. Eighty-four males and 85 females died, and in 24 of these cases (14 percent) cancer was the principal cause of death. The mortality ratio (the rate of mortality from cancer in these patients as compared with that in the general population) was 0.90 (95 percent confidence interval, 0.6 to 1.4). Among the 392 patients with dermatomyositis, 61 cancers were diagnosed at the same time or after dermatomyositis was diagnosed in 59 patients (15 percent). The relative risk of cancer was 2.4 (95 percent confidence interval, 1.6 to 3.6) in the male patients and 3.4 (95 percent confidence interval, 2.4 to 4.7) in the female patients. Fifty-seven males and 110 females died, and in 67 of these cases (40 percent) cancer was the principal cause of death (mortality ratio, 3.8; 95 percent confidence interval, 2.9 to 4.8). CONCLUSIONS The risk of cancer is increased in patients with polymyositis or dermatomyositis. In patients with dermatomyositis there is also a higher rate of mortality from cancer.

Cancer risk following organ transplantation: a nationwide cohort study in Sweden

A substantial excess risk of lymphomas and nonmelanoma skin cancer has been demonstrated following organ transplantation. Large sample size and long follow-up time may, however, allow more accurate risk estimates and detailed understanding of long-term cancer risk. The objective of the study was to assess the risk of cancer following organ transplantation. A nationwide cohort study comprising 5931 patients who underwent transplantation of kidney, liver or other organs during 1970–1997 in Sweden was conducted. Complete follow-up was accomplished through linkage to nationwide databases. We used comparisons with the entire Swedish population to calculate standardised incidence ratios (SIRs), and Poisson regression for multivariate internal analyses of relative risks (RRs) with 95% confidence intervals (CI). Overall, we observed 692 incident first cancers vs 171 expected (SIR 4.0; 95% CI 3.7–4.4). We confirmed marked excesses of nonmelanoma skin cancer (SIR 56.2; 95% CI 49.8–63.2), lip cancer (SIR 53.3; 95% CI 38.0–72.5) and of non-Hodgkins lymphoma (NHL) (SIR 6.0; 95% CI 4.4–8.0). Compared with patients who underwent kidney transplantation, those who received other organs were at substantially higher risk of NHL (RR 8.4; 95% CI 4.3–16). Besides, we found, significantly, about 20-fold excess risk of cancer of the vulva and vagina, 10-fold of anal cancer, and five-fold of oral cavity and kidney cancer, as well as two- to four-fold excesses of cancer in the oesophagus, stomach, large bowel, urinary bladder, lung and thyroid gland. In conclusion, organ transplantation entails a persistent, about four-fold increased overall cancer risk. The complex pattern of excess risk at many sites challenges current understanding of oncogenic infections that might become activated by immunologic alterations.

Increased risk for cardiovascular mortality in psoriasis inpatients but not in outpatients

We have conducted a historical cohort study to assess cardiovascular mortality among psoriasis patients. Using the Swedish Inpatient Registry, we selected 8991 patients hospitalized for psoriasis at dermatological wards. To represent an outpatient cohort, 19,757 members of the Swedish Psoriasis Association were selected. Mortality from cardiovascular diseases was compared with the general population. We found no increased cardiovascular mortality among outpatients with psoriasis (standardized mortality ratio, SMR 0.94; 95% confidence interval, CI: 0.89–0.99). The overall risk among inpatients admitted at least once was increased by 50%(SMR 1.52; 95% CI: 1.44–1.60). The excess risk increased with increasing number of hospital admissions (p for trend <0.001). Cardiovascular mortality was higher among those admitted at younger ages (p for trend <0.001; SMR 2.62, 95% CI: 1.91–3.49, for patients aged 20 to 39 years at first admission). Young age at first admission appeared to further increase the risk among those who were repeatedly admitted. We conclude that a diagnosis of psoriasis per se does not appear to increase the risk for cardiovascular mortality. Severe psoriasis, however, here measured as repeated admissions, and early age at first admission, is associated with increased risk for cardiovascular death.

PUVA and cancer: a large-scale epidemiological study.

There is concern about the long-term carcinogenic effects of psoralen and ultraviolet A radiation (PUVA) therapy for treatment of skin disorders. A study of 4799 Swedish patients (2343 males, 2056 females; mean age at first treatment 45.3 years, range 6-93; mean follow-up 6.9 years males, 7.2 years females) who received PUVA between 1974 and 1985 showed a dose-dependent increase in the risk of squamous cell cancer of the skin. Male patients who had received more than 200 treatments had over 30 times the incidence of squamous cell cancer found in the general population. Significant increases (p less than 0.05) were also found in the incidences of respiratory cancer in males and females, pancreatic cancer in males, and kidney and colonic cancer in females. This study confirms previous reports of a dose-dependent increase in the incidence of squamous cell cancer in patients treated with PUVA.

PUVA and cancer risk : the Swedish follow-up study

There is concern about the long‐term carcinogenic effects of psoralen and ultraviolet A radiation (PUVA) for treatment of skin disorders. Many authors have found an increased risk for cutaneous squamous cell carcinoma (SCC). Except in anecdotal reports, malignant melanoma had not been observed in patients treated with PUVA until recently. In the U.S.A., a 16‐centre prospective study of 1380 patients showed for the first time that there might also be an increased risk for malignant melanoma in patients treated with high cumulative dosages of PUVA. We have therefore followed up the Swedish PUVA cohort until 1994. This cohort had previously been followed up until 1985. Information from 4799 Swedish patients (2343 men, 2456 women) who had received PUVA between 1974 and 1985 was linked to the compulsory Swedish Cancer Registry in order to identify individuals with cancer. The average follow‐up period was 15.9 years for men and 16.2 for women. We did not find any increased risk for malignant melanoma in our total cohort of 4799 patients treated with PUVA or in a subcohort comprising 1867 patients followed for 15–21 years. For cutaneous SCC there was an increase in the risk: the relative risk was 5.6 (95% confidence interval, CI 4.4–7.1) for men and 3.6 (95% CI 2.1–5.8) for women. Significant (P < 0.05) increases were also found in the incidence of respiratory cancer in men and women and of kidney cancer in women. In conclusion, we did not find any increased risk for malignant melanoma in our patients treated with high doses of PUVA and followed up for a long time. We confirm previous reports of an increase in the incidence of cutaneous SCC in patients treated with PUVA, and recommend that patients should be carefully selected for PUVA and rigorously followed up.

Cutaneous Human Papillomaviruses Found in Sun-Exposed Skin: Beta-papillomavirus Species 2 Predominates in Squamous Cell Carcinoma

BACKGROUND A spectrum of cutaneous human papillomaviruses (HPVs) is detectable in nonmelanoma skin cancers, as well as in healthy skin, but the significance that the presence of these types of HPV DNA has for the pathogenesis of skin cancer remains unclear. METHODS We studied 349 nonimmunosuppressed patients with skin lesions (82 with squamous cell carcinomas, 126 with basal cell carcinomas, 49 with actinic keratoses, and 92 with benign lesions). After superficial skin had been removed by tape, paired biopsy samples--from the lesion and from healthy skin from the same patient--were tested for HPV DNA. Risk factors for HPV DNA were analyzed in multivariate models. RESULTS Overall, 12% of healthy skin samples were positive for HPV DNA, compared with 26% of benign lesions, 22% of actinic keratoses, 18% of basal cell carcinomas, and 26% of squamous cell carcinomas. HPV DNA was associated with sites extensively exposed to the sun, both for the lesions (odds ratio [OR], 4.45 [95% confidence interval {CI}, 2.44-8.11]) and for the healthy skin samples (OR, 3.65 [95% CI 1.79-7.44]). HPV types of Beta-papillomavirus species 2 predominate in squamous cell carcinomas (OR, 4.40 [95% CI, 1.92-10.06]), whereas HPV types of Beta-papillomavirus species 1 are primarily found in benign lesions (OR, 3.47 [95% CI, 1.72-6.99]). CONCLUSIONS Cutaneous HPV types are primarily detected at sites extensively exposed to the sun. HPV types of Beta-papillomavirus species 2, but not of species 1, are associated with squamous cell carcinoma.

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, SIRcancer excl SCC 2.4 (95% CI, 2.2–2.5); SIRSCC 121 (95% CI, 116–127). Cancer risks were most increased among heart and/or lung recipients SIRcancer excl SCC 3.3 (95% CI, 2.8–4.0); SIRSCC 198 (95% CI, 174–224), followed by kidney SIRcancer excl SCC 2.3 (95% CI, 2.1–2.4); SIRSCC 121 (95% CI, 116–127) and liver recipients SIRcancer excl SCC 2.3 (95% CI, 1.9–2.8); SIRSCC 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.

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.

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.

Chronic urticaria and cancer: an epidemiological study of 1155 patients.

To evaluate the possible association of malignant disease with chronic urticaria 1155 consecutive cases with chronic urticaria were reviewed. The Swedish Cancer Registry, Stockholm, was searched for records reporting malignancies in the study population (1958–1984), and the expected number of malignancies was calculated on the basis of age‐ and sex‐standardized incidence data. A malignancy was diagnosed in 36 patients with urticaria and the expected number of malignancies was 41. In 23 patients the malignancy appeared during the same year as the onset of urticaria or later. The expected number was 25.6. We conclude that chronic urticaria is not statistically associated with malignancy in general.