Pregnancies in patients with systemic lupus erythematosus during 2000-2018 in Finland: a case-control study.

OBJECTIVES: The aim was to investigate, how pregnancies proceed in patients with systemic lupus erythematosus (SLE) compared to their individually matched population controls. MATERIAL AND METHODS: Adult incident SLE patients were identified from the register of new special reimbursement decisions for SLE drugs in 2000-2014. For each patient, 1-3 randomly selected controls from the Population Register Centre were matched. Data regarding pregnancies were obtained from the Finnish Medical Birth Register, Care Register and Register of Congenital Malformations until 2018. The study utilized data from the Drug Purchase Register and educational information from Statistic Finland. RESULTS: A total of 163 deliveries for 103 mothers with SLE and 580 deliveries for 371 population controls were identified. The duration of pregnancies in SLE women was significantly shorter compared to controls (38.9 versus 39.6 weeks). There were more urgent Caesarean Sections. (15% versus 9%) and need for care at neonatal intensive care unit (NICU) (21% versus 11%) among deliveries in SLE mothers. No statistical difference was observed between SLE and control groups in the occurrence of preeclampsia or major congenital malformations. Gestational age was 2.5 weeks shorter when the mother experienced pre-eclampsia. Hydroxychloroquine was purchased by 30% of SLE mothers during pregnancy. CONCLUSION: The course of pregnancies in Finnish SLE patients seems to be quite moderate compared to controls, and no new safety issues were detected. The low utilization of hydroxychloroquine indicates that the benefits of the drug to pregnancy and disease course are not optimally recognized by specialists treating SLE mothers.

Depressive symptoms decrease health-related quality of life of patients with coronary artery disease and diabetes: a 12-month follow up study in primary care.

OBJECTIVE: Health-related quality of life (HRQoL) is a multidimensional patient-related outcome. Less is known about the role of depressive symptoms on HRQoL in chronic diseases. This follow-up study analyzed depressive symptoms' association with HRQoL change measured with 15D in patients with chronic diseases. DESIGN AND SETTING: A total of 587 patients from the Siilinjärvi Health Center, Finland were followed up due to the treatment of hypertension (HA), coronary artery disease (CAD) or diabetes (DM). Depressive symptoms were based on Beck Depression Inventory (BDI) (BDI ≥10 =depressive symptoms). HRQoL was assessed at the baseline and after 12 months. RESULTS: There were 244 patients with HA (mean age 70 years, 59% women); 103 patients (72 years, 38%) with CAD and 240 with DM (67 years, 52%). The change from baseline to the 12-month follow-up in 15D was significantly different between patients without and with depressive symptoms in CAD (p < 0.001) and DM (p = 0.024). In CAD with depressive symptoms, the change was -0.064 (95% CI: -0.094 to -0.035) and in DM -0.018 (95% CI: -0.037 to 0.001). In the 15 HRQoL dimensions of 15D, a depressive symptoms-related decrease was found in three dimensions with HA, in 9 with CAD and in 7 with DM. As a function of the BDI at baseline, the 15D score decreased significantly among patients with CAD and DM. CONCLUSIONS: Depressive symptoms impact negatively on future HRQoL among primary care patients with coronary artery disease and diabetes emphasizing that mood should be acknowledged in their care and follow-up. TRIAL REGISTRATION: Clinical Trials registration number: NCT02992431, registered December 14th 2016.

Health-related quality of life (HRQoL) is an important dimension of the quality and effectiveness of health care and an important predictor of mortality and morbidity.The main finding was that baseline depressive symptoms were associated with a decrease in the health-related quality of life after 12 months of follow-up, particularly in patients with coronary artery disease and diabetes.Beginning from the lowest scores, the severity of baseline depressive symptoms had a significant relationship with the level of deterioration in HRQoL among patients with coronary artery disease and diabetes.A significant decrease in HRQoL related to depressive symptoms was found in various different dimensions of HRQoL.

Inflammatory myositis-associated interstitial lung disease can be distinguished from that associated with other connective tissue diseases.

Background: Acute onset of interstitial lung disease (ILD) has been described in patients with idiopathic inflammatory myositis (IIM), but controlled studies about this issue are sparse. The aim of this study was to compare disease onset, demographics, and high-resolution computed tomography (HRCT) patterns in IIM-ILD and other connective tissue disease (CTD)-ILDs. Methods: Clinical and radiological data of 22 IIM-ILD and 132 other CTD-ILD patients was retrospectively gathered from hospital registries between January 2000 and November 2019. Data was re-assessed and compared using a multivariate analysis. Results: Compared to other CTD-ILDs, the patients with IIM-ILD were younger (59.7 vs. 68.0 years, P=0.023), more often non-smokers (71.4% vs. 45.7%, P=0.029) and displayed radiological nonspecific interstitial pneumonia/organizing pneumonia (NSIP/OP) overlap pattern more frequently (27.3% vs. 1.5%, P<0.001). The onset of ILD was acute with patients needing intensive care significantly more often in IIM-ILD than in other CTD-ILDs (22.7% vs. 2.3%, P<0.001). In most patients ILD was diagnosed before or simultaneously with IIM presentation unlike in other CTD-ILDs (90.9% vs. 47.7%, P<0.001). In multivariate analysis, NSIP/OP overlap pattern, acute onset disease treated in intensive care unit and ILD preceding or being diagnosed simultaneously with CTD were significantly associated with IIM-ILD. The multivariate model, supplemented with age, had excellent diagnostic performance identifying IIM-ILD [area under curve (AUC) 0.845]. Conclusions: Unlike other CTD-ILDs, IIM-ILD often develops acutely, simultaneously with the systemic disease. Therefore, clinicians should consider IIM-ILD as an option of differential diagnosis in patients with acute ILD and promptly test muscle enzymes as well as comprehensive autoantibody tests.

Incidence of seropositive rheumatoid arthritis in population-based studies in Northern Savo, Finland, during 1980-2020.

The objective is to evaluate the incidence of seropositive rheumatoid arthritis (RA) over 40-year period in Northern Savo, Finland. Data on new seropositive RA patients according to the American College of Rheumatology (ACR) 1987 classification criteria were collected in 2020-2021. In 2020 data on tobacco exposure, patient-reported dental health and living in residences with fluoridated tap water were gathered. Incidence rates were estimated and age- and gender-adjusted to Northern Savo population. The results were compared with data acquired in studies from 1980, 1990, 2000, and 2010. In 2020, 46 seropositive RA patients (21 females and 25 males) were recorded. The crude incidence of seropositive RA fulfilling the ACR 87 criteria in 2020 was 22.3 (95% CI 16.3 to 29.8)/100 000 and age and gender-adjusted 22.3 (95% CI 15.9 to 28.8)/100 000. Tobacco exposure > 5 pack years occurred 18% of females and 56% of males. Only 16% of males were full dentate. A total of 242 incident seropositive RA (age ≥ 16 years, 55% females) were identified in all study years. No differences in the gender-specific incidence rates in each cohort or in incidence between the studies every 10 years were recorded. The incidence of seropositive RA decreased in the age group < 55 years, p = 0.003. There was no change in the incidence of seropositive RA between genders or the study years. A declining trend for occurrence of seropositive RA in the young and early middle-aged population may reflect change in risk factors.

Malignancies among newly diagnosed systemic lupus erythematosus patients and their survival.

The objective of this study was to evaluate the incidence of malignancies among newly diagnosed systemic lupus erythematosus (SLE) patients compared to reference individuals. Another aim was to assess the survival of SLE patients with malignancy compared to references with malignancy. Finnish adult (>17 years) newly diagnosed SLE patients were identified by their drug reimbursement decisions made during 1.1.2000-31.12.2014 from the register of the Social Insurance Institution. For each case, three population controls were individually selected by age, sex and place of residence. Overall, 1006 SLE patients (women 84%), with a mean age of 45.5 years (SD 16 years) and 3005 population controls were linked to Finnish Cancer Registry, and the information about incident malignancies was retrieved from the day the special reimbursement decision for SLE medication was accepted (index day, ID) until 31.12.2018 or until death. The patients diagnosed with malignancy were followed up until 31.12.2019 considering survival. During the follow-up, 85 SLE patients (women 78%) and 192 controls (women 78%) had developed one or more malignancy after the ID. The incidence rate ratio for any malignancy was 1.41 (95% CI 1.08-1.85). The most common malignancy in SLE patients was non-Hodgkin lymphoma, with twelve cases. SLE patients with malignancy had a lower adjusted 15-year survival than controls with malignancy, 27.1% versus 52.4%, and the adjusted hazard ratio for death was 1.68 (95% CI 1.17-2.43). Our results confirm that SLE patients have a higher risk for overall malignancy. The results also suggest that SLE patients with malignancy have lower survival than their references with malignancy.

Usage of drugs for cardiovascular diseases is increased in systemic lupus erythematosus (SLE) patients already before diagnosis of SLE.

OBJECTIVES: Systemic lupus erythematosus (SLE) patients are considered as a high-risk population for cardiovascular diseases (CVDs). To explore whether their risk is increased already in preclinical episodes of the disease, we have studied the usage of CVD drugs in incident SLE cases five years before diagnosis of SLE compared to the population controls. METHODS: Adult SLE incident patients (age ≥18 years) from 2004 through 2014 were identified from a nationwide register. The date of granted reimbursement for SLE medication was defined as the date of diagnosis (index day). For each patient, three population controls were matched for age, sex and residence on the index day. The patients and controls were linked to the drug purchase register. All purchases of CVD drugs (Anatomical Therapeutic Chemical (ATC) - codes of C01-C04, C07-C09) and separately C10 were recorded in half-year periods over five years before the index day. RESULTS: A total of 653 SLE patients (mean age 45.7±15.9 years, 83% females) and 1924 population controls were found. Over five years before the index day, the proportion of SLE patients with purchased CVD drugs (46.7%) was greater compared to the controls (28.5%) (p<0.001). The relative risk for purchases started to increase more steeply during the last half-year period before SLE diagnosis. There was no significant difference in lipid-modifying agents between groups. CONCLUSIONS: Our finding that among SLE patients the use of CVD drugs was more common compared to their control population suggests increased CVD risk already before the diagnosis of SLE.

Randomized controlled study of the impact of a participatory patient care plan among primary care patients with common chronic diseases: a one-year follow-up study.

BACKROUND: Chronic diseases and multimorbidity are common in the ageing population and affect the health related quality of life. Health care resources are limited and the continuity of care has to be assured. Therefore it is essential to find demonstrable tools for best treatment practices for patients with chronic diseases. Our aim was to study the influence of a participatory patient care plan on the health-related quality of life and disease specific outcomes related to diabetes, ischemic heart disease and hypertension. METHODS: The data of the present study were based on the Participatory Patient Care Planning in Primary Care. A total of 605 patients were recruited in the Siilinjärvi Health Center in the years 2017-2018 from those patients who were followed up due to the treatment of hypertension, ischemic heart disease or diabetes. Patients were randomized into usual care and intervention groups. The intervention consisted of a participatory patient care plan, which was formulated in collaboration with the patient and the nurse and the physician during the first health care visit. Health-related quality of life with the 15D instrument and the disease-specific outcomes of body mass index (BMI), low density lipoprotein cholesterol (LDL-C), hemoglobin A1c (HbA1C) and blood pressure were assessed at the baseline and after a one-year follow-up. RESULTS: A total of 587 patients with a mean age of 69 years were followed for 12 months. In the intervention group there were 289 patients (54% women) and in the usual care group there were 298 patients (50% women). During the follow-up there were no significant changes between the groups in health-related quality and disease-specific outcomes. CONCLUSIONS: During the 12-month follow-up, no significant differences between the intervention and the usual care groups were detected, as the intervention and the usual care groups were already in good therapeutic equilibrium at the baseline. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02992431 . Registered 14/12/2016.

Mortality in SLE patients compared with population controls in Finland in years 2000-2015.

OBJECTIVE: To estimate the risk of mortality in the Finnish incident SLE cohort in a 16-year period compared with the general population. METHODS: Adults with new-onset SLE between 1 January 2000 and 31 December 2014 identified from the national drug reimbursement register and their individually matched controls from the Population Register Centre were followed up until death or 31 December 2015. Data on deaths were retrieved from the national causes of death register. Comorbidities and education were obtained by linkage to the other national registries. RESULTS: A total of 1006 patients with incident SLE and 3005 population controls were found (mean follow-up 8.6 years). Of these, 98 SLE patients subsequently died. Their 5 -, 10-, and 15-year survival rates were 95.0% (95% CI: 93.3, 96.2), 88.8% (86.2, 91.0), and 82.1% (77.6, 85.8), respectively. Crude hazard ratio (HR) was 1.61 (95% CI: 1.26, 2.06), adjusted for education level was almost the same 1.61 (95% CI: 1.26, 2.05). After adjustment for comorbidities and education at baseline, the difference in mortality disappeared: HR 1.14 (95% CI: 0.88, 1.48). The leading causes of death were cardiovascular diseases (CVDs) (33%), malignancies (27%) and neurological diseases (10%). Subhazard ratio for CVD deaths was 1.28 (95% CI: 0.85, 1.93), adjusted for comorbidities and education 0.88 (95% CI: 0.56, 1.39). CONCLUSIONS: These results suggest that the increased mortality in SLE patients is highly associated with comorbidities present at diagnosis. This underlines the importance to screen and treat comorbidities and disease actively without delays.

Multimorbidity among incident Finnish systemic lupus erythematosus patients during 2000-2017.

The objective of the study was to examine the risk of other morbidities among patients with systemic lupus erythematosus (SLE). A total of 1006 adult new-onset SLE patients were identified during 1.1.2000- 31.12.2014 from the register of Social Insurance Institution. For each case three general population controls matched according to age, sex and place of residence at the index day were sampled from the population register. Both groups were followed up from the index date until the end of 2017 or until death. The national register on specialized care was explored to gather broadly their 12 organ-specific morbidities, which were found among 91.2% of SLE patients and 66.7% of comparators. The rate ratio (RR) was elevated in almost all disease groups. Musculoskeletal, cardiovascular and genitourinary conditions were the most common comorbidities with RRs of 1.82 (1.68 to 1.97), 1.91 (1.76 to 2.08) and 1.91 (1.73 to 2.09), respectively. Men with SLE had a significantly higher risk for diseases of the genitourinary system and endocrine, nutritional and metabolic diseases compared to women with SLE. The risk of concurrent morbidities is essential to note in the care of SLE patients.

Metabolic Syndrome, Disease Activity, and Adipokines in Patients With Newly Diagnosed Inflammatory Joint Diseases.

OBJECTIVE: To investigate metabolic syndrome (MetS), disease activity, and adipokine levels among patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and undifferentiated arthritis (UA) at the time of diagnosis and after 1 year of follow-up. METHODS: Patients with inflammatory joint diseases participating in the Northern Savo 2010 population-based longitudinal epidemiological study were evaluated for components of MetS (by National Cholesterol Education Program's Adult Treatment Panel III) and clinical parameters of disease activity. The adipokines adiponectin, adipsin, resistin, and leptin were measured at baseline and after 1 year of treatment with disease-modifying antirheumatic drugs. RESULTS: Among 176 patients, MetS was detected in 42% of RA, 36% of SpA, and 51% of UA patients. Metabolic syndrome was associated with higher disease activity as measured by patient global assessment in RA and UA patients and increased pain in RA patients. Leptin levels were increased in patients with MetS, showing a linearly increasing trend with the number of components of MetS in SpA and UA, but not in RA. In RA patients, decrease in disease activity correlated with decrease in leptin levels. Resistin did not associate with MetS, but a decrease in resistin correlated with decrease in disease activity in RA and UA. In SpA, increased adiponectin level correlated with relief in disease activity, but not with MetS. CONCLUSIONS: Metabolic syndrome was common in patients with newly diagnosed arthritides and associated with higher disease activity and increased leptin levels. Resistin responded to treatment of arthritis in RA and UA, leptin in RA, and adiponectin in SpA.

Relationship between patient activation measurement and self-rated health in patients with chronic diseases.

BACKGROUND: In the aging population, chronic diseases and multimorbidity are common. Therefore, it is important to engage patients in their self-care. The aim of this study was to analyze the relationship between activity in self-care and self-rated health among primary care patients with chronic diseases. METHODS: The data of the present study were derived from a research project on the Participatory Patient Care Planning in Primary Care (4PHC). A total of 605 patients were recruited in the Siilinjärvi Health Center from those patients who were being monitored due to the treatment of hypertension, ischemic heart disease or diabetes. We evaluated the level of patient's activity in self-care with the Patient Activation Measurement (PAM). Self-rated health (SRH) was measured with the 5-item Likert scale. An adjusted hypothesis of linearity across categories of PAM and self-rated health was estimated using analysis of covariance (ANCOVA). RESULTS: It was found that 76 patients had low activity, 185 had moderate while 336 patients had high activity as measured with PAM. Patients with the highest activity were younger, less depressed, had a lower body mass index and a higher level of physical activity than those with the lower activity. Correspondingly, good SRH was perceived by 29, 45 and 67% of the patients in these three PAM groups adjusted with sex, age, depressive symptoms (BDI) and number of diseases. There was a significant linear trend (adjusted with age, number of diseases and depressive symptoms) between SRH and PAM, p < 0.001. CONCLUSIONS: Activity in self-care had an independent, linear relationship with the self-rated health. The present findings suggest that Patient Activation Measurement has the potential to categorize the patients according to their perceived health and their needs related to their disease management and self-care. The present results warrant longitudinal studies on the impact of promoting patient activation levels. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02992431 . Registered 14 December 2016 https://clinicaltrials.gov/ct2/show/NCT02992431.

Association of rheumatoid arthritis disease activity and antibodies to periodontal bacteria with serum lipoprotein profile in drug naive patients.

Objective: We investigated lipid concentrations, particle sizes and antibodies binding to periodontal bacteria Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis and to malondialdehyde-acetaldehyde (MAA) modified low-density lipoprotein in immunoglobulin (Ig) class A, G and M among patients with newly diagnosed rheumatoid arthritis (RA) in a population-based cohort.Methods: Concentrations and sizes of lipoprotein particles analysed by proton nuclear magnetic resonance spectroscopy and antibody levels to MAA modified low-density lipoprotein were studied at baseline and after one-year of follow-up. Serum Ig A and G class antibodies to periodontal bacteria were determined at baseline.Results: Sixty-three patients were divided into tertiles according to disease activity by disease activity score with 28 joint count and erythrocyte sedimentation rate (ESR) (<3.9, 3.9-4.7, >4.7). Small low-density lipoprotein concentration was lowest in the tertile with the highest disease activity. In high-density lipoprotein, the concentrations of total, medium and small particles decreased with disease activity. The particle size in low-density lipoprotein associated with disease activity and the presence of antibodies to P. gingivalis. Ig G and M antibodies to MAA modified low-density lipoprotein correlated with disease activity. Inflammation associated changes faded by one year.Conclusions: Drug naive RA patients had proatherogenic changes in lipid profiles, but they were reversible, when inflammation diminished.Key messagesPatients with drug naive rheumatoid arthritis showed proatherogenic lipid profiles.Reversible changes in lipid profiles can be achieved as response to inflammation suppression.Active therapy aimed at remission is essential in all patients with rheumatoid arthritis.

The profiles of health care utilization among a non-depressed population and patients with depressive symptoms with and without clinical depression.

Objective: To examine health service (HS) utilization profiles among a non-depressive population and patients with depressive symptoms (DS) with and without clinical depression. Design, subjects and setting: The study population was based on primary care patients with DS scoring ≥10 in the 21-item Beck Depression Inventory (BDI) and who were at least 35 years old and had been referred to depression nurse case managers (n = 705). Their psychiatric diagnosis was confirmed with the Mini-International Neuropsychiatric Interview (M.I.N.I.). Of these patients, 447 had clinical depression. The number of patients with DS without clinical depression was 258. The control group consisted of a random sample of 414 residents with a BDI score < 10. Use of HS (visits and phone calls to a doctor and a nurse) was based on patient records. Main outcome measures: Number of visits and calls to physicians and nurses. Results: Patients with DS regardless of their depression diagnosis used primary health care (PHC) services three times more than the controls (p < 0.001). In the secondary care, the differences were smaller but significant. Of the controls, 70% had 0-4 HS contacts per year whereas a majority of the patients having DS had more than 5 contacts per year. The number of contacts correlated with the BDI from a score of 0 to 10 but not as clearly in the higher scores. Conclusion: Depressive symptoms, both with or without clinical depression, are associated with increased HS use, especially in PHC. This study suggests that even mild depressive symptoms are associated with an increased use of HS. KEY POINTS We analyzed the health service (HS) use among primary health care patients screened for depression and non-depressive population. Screen positive patients without clinical depression used as much HS as those having clinical depression. Regardless of depression diagnosis, screen positive patients visited a GP and nurse three times more often than the control population. In the screen negative control population, milder depressive symptoms were correlated with the use of HS. Primary health care was responsible for most of the HS use among patients having depressive symptoms.

Impact of early systemic lupus erythematosus on work disability-results from the Finnish nationwide register 2000-2007.

Objectives of this study were to examine work disability (WD) and its leading causes in incident SLE patients. Data were derived from the Finnish nationwide registries to identify all non-retired, 18 to 64-year-old incident SLE patients between 2000 and 2007. Sick benefits and WD pensions and the causes for them were monitored until the end of 2008. A total of 446 working-aged, incident SLE patients available for work force (mean age 42 ± 13 years, 89% females) were found. During the follow-up (median 5.3 years), WD pension was granted to 27 patients. The most common cause was SLE itself (14 patients, 52%), with cumulative incidence of 3.4% (95% CI 1.9 to 5.8) in 5 years and 5.0% (95% CI 3.0 to 8.5) in 8 years, followed by musculoskeletal and psychiatric causes. The age- and sex- adjusted incidence ratio for WD pension in SLE patients due to any cause was 5.4 (95% CI 3.7 to 7.9) compared to the Finnish population. The mean number of WD days was 32 (95% CI 28 to 35) per patient-year among all SLE patients during the follow-up. The study concludes that SLE patients have an increased risk for WD already in early course of the disease.

Automated immunoassays for the autoantibodies to carbamylated or citrullinated telopeptides of type I and II collagens.

BACKGROUND: The aim of the study was to describe automated immunoassays for autoantibodies to homocitrulline or citrulline containing telopeptides of type I and II collagen in various disease categories in an early arthritis series. METHODS: Serum samples were collected from 142 patients over 16 years of age with newly diagnosed inflammatory joint disease. All samples were analyzed with an automated inhibition chemiluminescence immunoassay (CLIA) using four different peptide pairs, each consisting of a biotinylated antigen and an inhibiting peptide. Assays were performed with an IDS-iSYS analyzer. Autoantibodies binding to homocitrulline and citrulline containing C-telopeptides of type I (HTELO-I, TELO-I) and type II collagens (HTELO-II, TELO-II) were analyzed. RESULTS: The mean ratio of HTELO-I inhibition in seropositive and seronegative rheumatoid arthritis (RA) was 3.07 (95% CI 1.41-11.60), p=0.003, and in seropositive and seronegative undifferentiated arthritis (UA) 4.90 (1.85-14.49), p<0.001. The respective mean ratios in seropositive and seronegative RA and UA were in TELO-I 8.72 (3.68-58.01), p<0.001 and 3.13 (1.49-6.16), p=0.008, in HTELO-II 7.57 (3.18-56.60), p<0.001 and 2.97 (1.23-6.69), p=0.037, and in TELO-II 3.01 (1.30-9.51), p=0.002 and 3.64 (1.86-7.65), p=0.008. In reactive arthritis, ankylosing spondylitis, psoriatic arthritis and unspecified spondyloarthritis the inhibition levels were similar to those observed in seronegative RA or UA. CONCLUSIONS: Autoantibodies binding to homocitrulline or citrulline containing telopeptides of type I and II collagen did not differ significantly. They were highest among patients with seropositive disease and they differentiated seropositive and seronegative arthritis.

Incidence of systemic lupus erythematosus in Finland, 2000-2007, a nationwide study.

OBJECTIVES: To determine the age- and sex-specific incidence rates of systemic lupus erythematosus (SLE) in Finland. METHODS: The incident cases were identified through diagnostic register searches for SLE on the nationwide database of the Social Insurance Institution. RESULTS: During the 8-year study period 599 incident cases occurred (518 females, 81 males). The mean annual incidence rate of SLE for adults was 1.69 per 100,000 (95% CI 1.56-1.84) and was highest among females aged 40-59 years. The gender incidence rate ratio was 6.43 (95% CI 5.06-8.26). The incidence for children was 0.39 (95% CI 0.27-0.55). CONCLUSIONS: The incidence of SLE was lower compared to the countries at the same latitudes. SLE in children remained a rarity.

[Adverse muscle effects of a podofyllotoxin-containing cytotoxic drug product with simvastatin]. / Podofyllotoksiinia sisältävän solunsalpaajavalmisteen ja simvastatiinin lihashaitat.

With the ageing population, drug interactions pose an increasing challenge to health professionals. We describe four patients, for whom concurrent administration of a podofyllotoxin-containing cytotoxic drug product and simvastatin caused severe adverse effects on muscles, including muscle pain, soreness or fatigue or weakness, and in some patients also disintegration of muscle tissue, i.e. rhabdomyolysis. The metabolism of both drugs proceeds via the common CYP3A4 enzyme pathway.