Consensus statement on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: Localized scleroderma, systemic sclerosis and overlap syndromes.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present consensus provides an update to the 2017 European Dermatology Forum Guidelines, focusing on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, updated strategies for the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this consensus provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes.

Comorbidities, mortality and survival in patients with pyoderma gangrenosum: a Danish nationwide registry-nested case-control study.

BACKGROUND: Pyoderma gangrenosum (PG) is an ulcerative skin disease associated with comorbidities and increased mortality; however, the literature on this topic is scarce. OBJECTIVES: To investigate the mortality, prevalence and risk of comorbidities in patients with PG. METHODS: This nationwide registry nested case-control study included all inpatients and outpatients diagnosed with PG in tertiary dermatology centres in Denmark between 1 January 1994 and 31 December 2016. Each case was matched on date of birth and sex with 10 unique controls. The Danish National Patient Registry was used to identify all patients and to gather information on comorbidity. Information on age, sex, vital status and emigration was obtained from the Danish Civil Registration System. The outcomes were 19 different comorbidities and all-cause mortality. Prevalence was assessed from odds ratios (ORs) for specific comorbidities at the time of PG diagnosis. The risk of developing specific comorbidities and death was assessed using hazard ratios (HRs) obtained using the Cox proportional-hazards model. RESULTS: A total of 1604 patients with PG were matched with 16 039 controls. Some associations were known, e.g. inflammatory bowel disease [OR 19·15 (15·27-24·02), HR 6·51 (4·24-10·01)], while others have not been described previously, e.g. osteoporosis [OR 1·57 (1·22-2·02), HR 2·59 (2·08-3·22)]. Mortality was significantly increased among patients with PG [HR 2·79 (2·57-3·03)]. CONCLUSIONS: Patients with PG have increased mortality and an increased prevalence and risk of both previously reported and novel comorbidities that may have severe consequences if left undiagnosed. Our findings are mainly related to moderate and severe PG.

A comparison of nutrient uptake efficiency and growth rate between different macrophyte growth forms.

Aquatic macrophytes grow abundantly in many lowland streams and play a key role in ecosystem functioning, such as nutrient retention. In this study, we performed a microcosm experiment to quantify and compare the contribution of two freshwater macrophyte growth forms to nutrient cycling. We measured and compared inorganic nitrogen (NH4-N and NO3-N) and phosphorus (PO4-P) uptake kinetic parameters (Vmax and Cmin) in 12 submerged and seven amphibious plant species. We tested whether relative growth rate (RGR) was related to high Vmax and low Cmin, and quantified changes in nutrient uptake kinetic in a subset of six out of 19 plants species during the growth season. Uptake rates of NH4-N were higher in submerged compared to amphibious plants, whereas uptake rates of NO3-N were significantly higher in amphibious species; PO4-P uptake kinetics were not significantly different between the two growth forms. There were also significant seasonal differences in Vmax NH4-N rate among both submerged and amphibious species and in Vmax NO3-N among amphibious species. Highest uptake rates were observed in summer for both submerged and amphibious species. Overall, we found that nutrient uptake kinetics differed between the two growth forms within and between seasons. Consequently, the presence of both growth forms should extend the period of nutrient uptake across the year and enhance nutrient uptake within seasons. We conclude that higher functional diversity enhances annual nutrient uptake in streams and that stream restoration efforts should consider increasing the niche space available for both submerged and amphibious species.

Neonatal BCG vaccination and atopic dermatitis before 13 months of age: A randomized clinical trial.

BACKGROUND: Studies have suggested that Bacillus Calmette-Guérin (BCG) vaccination may reduce the risk of allergic diseases, including atopic dermatitis. METHODS: The Danish Calmette Study was conducted 2012-2015. Within 7 days of birth new-borns were randomised 1:1 to BCG or no BCG. Exclusion criteria were gestational age <32 weeks, birth weight <1000 g, known immunodeficiency or no Danish-speaking parent. Data were collected through telephone interviews and clinical examinations until 13 months. RESULTS: Clinical atopic dermatitis was diagnosed in 466/2,052 (22.7%) children in the BCG group and 495/1,952 (25.4%) children in the control group (RR = 0.90 [95% confidence intervals 0.80-1.00]). The effect of neonatal BCG vaccination differed significantly between children with atopic predisposition (RR 0.84 (0.74-0.95)) and children without atopic predisposition (RR 1.09 [0.88-1.37]) (test of no interaction, P = .04). CONCLUSION: Among children with atopic predisposition, the number-needed-to-treat with BCG to prevent one case of atopic dermatitis was 21 (12-76).

Submerged freshwater plant communities do not show species complementarity effect in wetland mesocosms.

It is a generally accepted theory that ecological functions are enhanced with increased diversity in plant communities due to species complementarity effects. We tested this theory in a mesocosm study using freshwater submerged plant beds to determine if increasing species number caused overyielding and species complementarity. We applied a maximum of four species in the plant beds corresponding to the typical species number in natural freshwater plant beds. We found no clear effects of species number (1-4) on biomass production and thus no conclusive overyielding and complementarity effect. This may be explained by low species differentiation among the four species in plant traits relevant for resource acquisition in freshwater, or that other species interactions, e.g. allelopathy, were inhibiting overyielding. The existing knowledge on species complementarity in aquatic plant communities is sparse and inconclusive and calls for more research.

Increased frequency of multiple sclerosis among patients with bullous pemphigoid: a population-based cohort study on comorbidities anchored around the diagnosis of bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is a disease of the elderly and may be associated with neurological and cardiovascular diseases and diabetes. Mortality rates strongly exceed those of the background population. OBJECTIVES: To investigate the frequency of comorbidities and their temporal relation to BP. METHODS: A register-based matched-cohort study on all Danish patients with a hospital-based diagnosis of BP (n = 3281). The main outcomes were multiple sclerosis (MS), Parkinson disease (PD), Alzheimer disease (AD), stroke, diabetes types 1 and 2, malignancies, ischaemic heart disease (IHD), hypertension and eventually death. RESULTS: At baseline, patients with BP had increased prevalences of MS [odds ratio (OR) 9·7, 95% confidence interval (CI) 6·0-15·6], PD (OR 4·2, 95% CI 3·1-5·8), AD (OR 2·6, 95% CI 1·8-3·5) and stroke (OR 2·7, 95% CI 2·4-2·9). Furthermore, malignancies, cardiovascular disease and diabetes were over-represented among patients with BP: type 1 diabetes (OR 3·1, 95% CI 2·5-3·8), type 2 diabetes (OR 2·3, 95% CI 2·0-2·6), malignancies (OR 1·3, 95% CI 1·1-1·4), IHD (OR 1·7, 95% CI 1·5-1·9) and hypertension (OR 2·0, 95% CI 1·8-2·2). During follow-up, the risk of MS was significantly higher among patients with BP [hazard ratio (HR) 9·4, 95% CI 4·9-18·0], even if events during the first year after diagnosis of BP were excluded (HR 5·1, 95% CI 2·3-11·3). Patients with BP had an average increased mortality rate of 2·04 (95% CI 1·96-2·13). CONCLUSIONS: We discovered a significantly increased frequency of MS among patients with BP. At the time of diagnosis, patients with BP had an excessive number of comorbidities and an increased mortality rate over the following years.

European dermatology forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 2: Scleromyxedema, scleredema and nephrogenic systemic fibrosis.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 2 of this guideline provides clinicians with an overview of the diagnosis and treatment of scleromyxedema, scleredema (of Buschke) and nephrogenic systemic sclerosis (nephrogenic fibrosing dermopathy).

European Dermatology Forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: localized scleroderma, systemic sclerosis and overlap syndromes.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this guideline provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes of systemic sclerosis with diseases of the rheumatological spectrum.

Venlafaxine and oxycodone effects on human spinal and supraspinal pain processing: a randomized cross-over trial.

Severe pain is often treated with opioids. Antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) have also shown a pain relieving effect, but for both SNRI and opioids, the specific mode of action in humans remains vague. This study investigated how oxycodone and venlafaxine affect spinal and supraspinal pain processing. Twenty volunteers were included in this randomized cross-over study comparing 5-day treatment with venlafaxine, oxycodone and placebo. As a proxy of the spinal pain transmission, the nociceptive withdrawal reflex (NWR) to electrical stimulation on the sole of the foot was recorded at the tibialis anterior muscle before and after 5 days of treatment. For the supraspinal activity, 61-channel electroencephalogram evoked potentials (EPs) to the electrical stimulations were simultaneously recorded. Areas under curve (AUCs) of the EMG signals were analyzed. Latencies and AUCs were computed for the major EP peaks and brain source analysis was done. The NWR was decreased in venlafaxine arm (P = 0.02), but the EP parameters did not change. Oxycodone increased the AUC of the EP response (P = 0.04). Oxycodone also shifted the cingulate activity anteriorly in the mid-cingulate-operculum network (P < 0.01), and the cingulate activity was increased while the operculum activity was decreased (P = 0.02). Venlafaxine exerts its effects on the modulation of spinal nociceptive transmission, which may reflect changes in balance between descending inhibition and descending facilitation. Oxycodone, on the other hand, exerts its effects at the cortical level. This study sheds light on how opioids and SNRI drugs modify the human central nervous system and where their effects dominate.

Developmental milestones in children born post-term in the Danish National Birth Cohort: a main research article.

OBJECTIVE: To examine the timing of reaching developmental milestones in children born post-term. DESIGN: Cohort study. SETTING: The Danish National Birth Cohort: children born between 1997 and 2003. POPULATION: Data were obtained from a cohort of 92 892 pregnancies participating in the first pregnancy interview. All singletons born in gestational weeks 39-45 were identified. The study was then restricted to children who participated in an interview at the age of approximately 18 months and had information on at least one developmental milestone. We excluded children of mothers with chronic diseases from the final analysis. The remaining study population constituted of 43 915 singletons (27 503 born at term; 16 412 born post-term). METHODS: Logistic regression was used to calculate odds ratios of late achievement of these developmental milestones, adjusted for potential confounding factors. MAIN OUTCOME MEASURES: Achieving developmental milestones at the time of interview or at a certain age. RESULTS: More children born post-term achieved the assessed developmental milestones compared with children born at term (39-40 weeks). A test for trend for gestational ages 39, 40, and 41 weeks also showed a positive trend at achieving developmental milestones with gestational age at birth in nine out of 14 milestone items. CONCLUSIONS: Children born post-term appear to reach the main developmental milestones at an earlier age than children born at term. The association could also result from bias related to a longer time between conception and interviewing, misclassification of end points, or selection bias.

Cancer incidence among patients with a hospital diagnosis of pruritus: a nationwide Danish cohort study.

BACKGROUND: Pruritus is a frequent complaint in patients with cancer. However, no large study has examined pruritus as a marker of undiagnosed cancer. OBJECTIVES: To examine the association between inpatient, outpatient and emergency hospital diagnoses of pruritus and subsequent cancer diagnoses. METHODS: In this nationwide Danish cohort study, we used medical databases to identify all patients (n = 12,813) with a diagnosis of pruritus during the period 1978-2011 and followed them until a first-time cancer diagnosis, emigration, death or 31 December 2011. We computed standardized incidence ratios (SIRs) for cancer as the observed to expected number of cancers based on national cancer incidence rates. We calculated the 1-year absolute risk of cancer, treating death as a competing risk. RESULTS: The overall SIR of cancer was 1.13 [95% confidence interval (CI) 1.07-1.20]: 1.22 (95% CI 1.13-1.33) among men and 1.05 (95% CI 0.97-1.14) among women. The SIR was 1.20 (95% CI 1.08-1.33) among patients with a previous diagnosis of dermatological disease and 1.10 (95% CI 1.02-1.18) among patients without such a diagnosis. Both haematological and various solid cancers were observed at increased rates. Overall, the highest SIRs were observed during the first 3 months of follow-up, declining rapidly thereafter. The 1-year absolute risk of a cancer diagnosis was 1.63% and 155 patients with pruritus would have needed to be examined to detect one excess cancer. CONCLUSIONS: Pruritus may be a marker of occult cancer. Further studies are needed to assess the prognostic benefit of screening for cancer in patients with pruritus.

Impact of PCOS on early embryo cleavage kinetics.

This study investigated whether polycystic ovary syndrome (PCOS) affected early embryo development assessed by time-lapse analysis of embryo kinetics from fertilization to the blastocyst stage. This was a prospective cohort study of two pronuclei (2PN) embryos from 25 hyperandrogenic PCOS patients (110 2PN embryos), 26 normoandrogenic PCOS patients (140 2PN embryos) and 20 healthy, regularly cycling women (controls, 97 2PN embryos). Patients underwent the same baseline evaluation and the same ovarian stimulation from April 2010 to February 2013. Oocytes were fertilized by intracytoplasmic sperm injection and incubated in an EmbryoScope with pictures taken every 20 min in seven focal planes. Time to 2PN breakdown, first cleavage and cleavage to 3, 4, 5, 6, 7 and 8 cells, morula and blastocyst (t2, t3, t4, t5, t6, t7, t8, t(M), t(B)) were annotated. Differences in embryo kinetics between groups were assessed by mixed modelling. Compared with controls, embryos from hyperandrogenic PCOS patients were significantly delayed at 2PN breakdown, t2, t3, t4 and t7 but not at t5, t6, t8, t(M) or t(B). Embryos from hyperandrogenic PCOS women had developed slower from fertilization to the 8-cell stage compared with embryos from controls.

Self-reported skin morbidities and health-related quality of life: a population-based nested case-control study.

BACKGROUND: Impaired dermatological health-related quality of life (HRQoL) has been observed in hospital-based studies, but little is known on a population-based level. OBJECTIVE: To investigate self-reported dermatological HRQoL in the general population. METHODS: Hidradenitis suppurativa, psoriasis, pimples, hand rash or atopic eczema were identified using questionnaires in a 15,177 person population sample. A nested case-control study of 180 cases and 259 controls was made using the Dermatology Life Quality Index (DLQI), Skindex-29 and EQ-5D. RESULTS: Cases had higher scores in DLQI and Skindex-29 and a lower score in EQ-5D, suggesting lower HRQoL. Adjusting for age and sex, the differences in Skindex-29 and DLQI were significant (p < 0.001). CONCLUSIONS: Persons with self-reported skin morbidity had lower HRQoL than the general population. The impairment is not as significant as in studies of hospital-based cases, but considering the high prevalence of skin diseases it may still represent a significant burden of disease on society in aggregate.

The impact of comorbidity and stage on prognosis of Danish melanoma patients, 1987-2009: a registry-based cohort study.

BACKGROUND: Comorbid conditions may play an important role in the prognosis of melanoma patients but have received little attention. METHODS: Using data from Danish registries, we identified patients diagnosed with melanoma from 1987 to 2009. We estimated the prevalence of comorbidity and calculated mortality rate ratios and interaction risks between melanoma and comorbidity. For every melanoma patient, 10 individuals were selected for comparison. Individuals in the comparison cohort were matched to their corresponding melanoma patients on age, gender, and exact prevalent comorbidities. RESULTS: We included 23 476 patients, 81% of whom had no comorbidity. Higher prevalence of comorbidity was associated with more advanced cancer stage. The standardised mortality rate increased with increasing level of comorbidity in both cohorts and was consistently higher among melanoma patients. Melanoma and comorbidity interacted to increase the mortality rate. The highest proportional excess was seen in melanoma patients with comorbidity score 3, in whom interaction accounted for 77 deaths per 1000 person-years (40% of the total rate). We stratified by cancer stage and found that the interaction was markedly concentrated in patients with distant metastases. CONCLUSION: Interaction between melanoma and comorbidity was primarily concentrated in patients with distant metastases, which raises the possibility that comorbidity is associated with delay of melanoma diagnosis, advanced cancer stage, and less aggressive melanoma treatment.

Antifibrotic effect after low-dose imatinib mesylate treatment in patients with nephrogenic systemic fibrosis: an open-label non-randomized, uncontrolled clinical trial.

BACKGROUND: Nephrogenic systemic fibrosis is a disease affecting the connective tissue of the skin and internal organs in patients with renal failure. No effective treatments are available. OBJECTIVES: To investigate if the tyrosine kinase inhibitor, imatinib mesylate was effective in patients with moderate to severe nephrogenic systemic fibrosis. METHODS: Among 25 patients with nephrogenic systemic fibrosis evaluated for the study from 1 October 2009 to 1 December 2010, four were included. They were treated with oral imatinib mesylate at a start dose of 400 mg/day. MAIN OUTCOME MEASURE: Reduction of skin fibrosis and increase in joint mobility evaluated by the modified Rodnan skin score and a goniometer. RESULTS: In two patients, the imatinib mesylate dose was reduced to 200 mg/day and in one patient to 100 mg/day. Two patients were treated for 24 weeks, one patient for 16 weeks and one patient for 4 weeks. Three patients experienced tethering of their skin which lessened with reduction in modified Rodnan skin score from 24 to 20, 24 to 17 and 21 to 14 but with very limited changes in joint mobility. The fourth patient discontinued the treatment due to a complicating infection. CONCLUSION: Imatinib mesylate may be an effective drug in the treatment of skin fibrosis in moderate to severe NSF cases, even at reduced doses. We found a positive clinical effect on the skin, but no convincing improvement of the joint mobility. Only few patients could be recruited limiting the interpretation and conclusions of the results.

Revisiting the passive biocover system at Klintholm landfill, six years after construction.

A biocover system was established at Klintholm landfill in Denmark in 2009 to mitigate methane emissions, and the system exhibited high mitigation efficiency during the first year after implementation. The biocover system was revisited in 2016/2017, and a series of field and laboratory tests were carried out to evaluate functionality about six years after establishment. Three field campaigns were executed in three different barometric pressure conditions, namely increasing, stable and decreasing. Local surface flux measurements and gas concentration profiles in the methane oxidation layer showed that barometric pressure changes had a significant effect on gas emission and methane oxidation. Elevated concentrations of oxygen were observed in the gas distribution layer, and field data showed that significant methane oxidation took place in this location. This finding was verified in laboratory-based methane oxidation incubation tests. Temperatures higher than ambient temperature were observed throughout the methane oxidation layer, with average temperatures ranging between 13 and 27 °C, even in the coldest month of the year. Field measurements showed that total methane emissions from the whole landfill cell were at the same level or lower than measurements performed in 2009/2010 after implementation of the biocover system, and laboratory tests showed methane oxidation potential approximately equal to former tests. In spite of an inhomogeneous distribution of landfill gas load to the methane oxidation layer, the performance of the biocover system had not declined over the 6-7 years since its establishment, even though no maintenance had been carried out in the intervening years.

Nephrogenic systemic fibrosis is found only among gadolinium-exposed patients with renal insufficiency: a case-control study from Denmark.

BACKGROUND: Nephrogenic systemic fibrosis (NSF) is a systemic fibrosing disease associated with exposure to gadolinium-based contrast agents (GBCA) in patients with renal insufficiency. OBJECTIVES: To report the prevalence of NSF in a well-defined cohort of patients with renal insufficiency exposed to GBCA, to investigate if GBCA-unexposed controls showed signs of NSF and to evaluate selected risk factors among NSF cases and GBCA-exposed controls. METHODS: A study among GBCA-exposed patients with renal insufficiency (n=565) was conducted to identify cases of NSF. The NSF cases found were age and sex matched and clinically compared with GBCA-exposed and unexposed patients with renal insufficiency in a case-control study. RESULTS: We identified 17 NSF cases. No signs of NSF were observed among the controls. The prevalence of NSF was 4·7%, highest among patients with chronic kidney disease (CKD) stage 5 exposed to GBCA and undergoing haemodialysis or peritoneal dialysis. Three NSF cases were identified among patients with CKD stage 3 and 4. Three patients developed NSF after macrocyclic GBCA exposure. NSF cases had a tendency to have higher serum phosphate concentrations than GBCA-exposed controls. CONCLUSIONS: Our study supports the view that GBCA is a major risk factor for NSF. Importantly, we found that patients with CKD stage 3 and 4 can be at risk of NSF. NSF may also be triggered by macrocyclic GBCA. Further, we observed a trend for higher phosphate levels in NSF cases compared with controls. The important findings drawn from this case-control study indicate that NSF is not an overlooked condition among patients with renal insufficiency not exposed to GBCA.

Patient safety incidents involving transdermal opioids: data from the Danish Patient Safety Database.

Background Transdermal opioids are widely used among elderly adults with chronic pain. However, transdermal patches may be involved in a significant proportion of opioid-related patient safety incidents, as the application process includes several subprocesses, each associated with an individual risk of error. Objective The aim was to obtain specific knowledge on patient safety incidents related to transdermal opioid treatment within both the primary care sector and the hospital sector in Denmark. Setting The study is descriptive with data provided by the Danish Patient Safety Database. Methods We manually retrieved all patient safety incidents concerning transdermal opioids reported for 2018 from (1) the hospital sector and (2) the primary care sector. Study data were collected and managed using REDCap electronic data capture tools. Main outcome measure The available information for each incident was sorted into the following categories: location, medication process, type of problem, outcome at time of reporting, and outcome classification. Results A total of 866 patient safety incidents involving transdermal opioids were reported to the Danish Patient Safety Database in 2018. No fatal incidents were present in the database. In 386 cases, the incidents were reported as harmful, and these 386 cases were analysed. Most reports came from the primary care sector (nursing home, home care or social housing). The majority of incidents were related to the administration of the patch in the medication process, and the most prevalent problem was the omission of doses. Conclusion This study has demonstrated that the administration of transdermal opioids is challenging and may cause harm, particularly in the primary care sector. To improve patient safety, optimized systems, including guidelines on drug management and the continuing education of healthcare personnel in transdermal opioid management, are necessary. These guidelines should preferably incorporate reminders and checklists, since the omission of doses was the most reported problem.

Systemic sclerosis and the risk of cancer: a nationwide population-based cohort study.

BACKGROUND: Earlier studies reported an increased cancer risk among patients with systemic sclerosis. Study size limitations and paucity of population-based study designs may have resulted in imprecise risk estimates. OBJECTIVES: To assess cancer risk among patients with systemic sclerosis in a nationwide follow-up study. METHODS: Patients with a first diagnosis of systemic sclerosis from 1977 to 2006 were identified from the nationwide Danish National Registry of Patients (DNRP), whose records encompass all hospitalizations and outpatient visits. Patients' DNRP records were linked to the Danish Cancer Registry. We compared their cancer incidence with that expected from cancer incidence in the general population, calculating standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). RESULTS: Two thousand and forty patients with systemic sclerosis were identified and followed for 16,003 person-years, with a median follow-up time of 6·4 years (interquartile range 2·2-11·5). Among these patients, 222 cases of cancer were identified. The overall SIR for cancer was 1·5 (95% CI 1·3-1·7), with a gender-specific SIR of 2·2 (95% CI 1·7-2·8) for men and 1·3 (95% CI 1·1-1·6) for women. The most frequent cancers were smoking- and alcohol-related cancers including lung cancer (SIR = 1·6, 95% CI 1·2-2·0), haematological cancers (SIR = 2·5, 95% CI 1·5-4·0) and immune-related cancers (SIR = 1·4, 95% CI 1·0-1·9). CONCLUSIONS: Systemic sclerosis is a risk factor for cancer, particularly smoking- and alcohol-related cancers. Men with systemic sclerosis generally are at higher cancer risk than women. Both primary and secondary cancer preventive measures are needed in the care of patients with systemic sclerosis.