Multidimensional tracking of phenotypes and organ involvement in a complete nationwide systemic sclerosis cohort.

OBJECTIVE: SSc is a severe, heterogeneous multi-organ disease where population-based estimates on phenotypic spectrum, overall disease burden and societal impact are largely missing. Here the objective was to provide the first-ever complete national-level data on phenotype and major organ afflictions in SSc. METHODS: A stepwise strategy was applied to find and characterize every SSc patient resident in Norway from 2000 to 2012. First we identified every case in the country registered with an International Classification of Diseases, Tenth Revision code for SSc (M34). Next we manually reviewed all cases coded as M34 to determine whether they met the 1980 ACR and/or 2013 ACR/EULAR classification criteria for SSc and could be included in the Norwegian SSc cohort (Nor-SSc). Finally, all disease features from SSc onset to study end were reviewed. RESULTS: The Nor-SSc cohort included 815 SSc patients. The mean age at diagnosis was 53 years, with 84% females and 77% limited cutaneous SSc. The estimated incidence increased from 4 per million in 2000 to 13 per million in 2012. We identified high cumulative frequencies of internal organ involvement, coexistence of multiple organ afflictions across disease subsets and autoantibody status and stable frequencies of pulmonary arterial hypertension across haemodynamic definitions, but indications of referral-related differences in pulmonary hypertension detection rates across the study area. CONCLUSION: This nationwide cohort study provides new, unbiased evidence for a high disease burden in SSc patients of Caucasian descent and indicates the existence of hurdles preventing equality of assessment across the SSc population.

Tracking Impact of Interstitial Lung Disease in Systemic Sclerosis in a Complete Nationwide Cohort.

Rationale: Interstitial lung disease (ILD) represents a major challenge in systemic sclerosis (SSc), but there are no precise, population-based data on its overall impact, limiting opportunities for screening and management strategies.Objectives: Evaluate impact of ILD in a unique, nationwide, population-based SSc cohort.Methods: ILD was assessed prospectively in the Norwegian SSc (Nor-SSc) cohort, including all 815 patients with SSc resident in the country from 2000 to 2012. Lung high-resolution computed tomography (HRCT) scans were available for fibrosis quantification at baseline (n = 650, 80%) and follow-up. Pulmonary function tests were assessed at baseline (n = 703, 86%) and follow-up. Vital status and standardized mortality ratios (SMRs) were estimated at study end (2018) in the 630 incident Nor-SSc cases and 15 individually matched control subjects. Cumulative survival rates were computed.Measurements and Main Results: At baseline, 50% of the subjects with SSc (n = 324) had ILD by HRCT and 46% displayed pulmonary function declines consistent with ILD progression. Mortality correlated with extent of lung fibrosis as SMR increased from 2.2 with no fibrosis to 8.0 with greater than 25% fibrosis. SMR was inversely related to baseline FVC% and increased at all FVC levels below 100%. In patients with normal-range baseline FVC (80-100%), the 5- and 10-year survival rates correlated with presence or absence of lung fibrosis, being 83% and 80%, respectively, with no fibrosis and 69% and 56%, respectively, with lung fibrosis (P = 0.03).Conclusions: The mere presence of ILD at baseline appears to affect outcome in SSc, suggesting that all patients with SSc should undergo a baseline pulmonary function test and lung HRCT screening to diagnose ILD early and tailor further management.

Live Birth Pregnancy Outcome after First In Vitro Fertilization Treatment in a Patient with Systemic Lupus Erythematosus and Isolated High Positive IgA Anti-ß2glycoprotein I Antibodies: A Case Report.

IgA anti-ß2glycoprotein I antibodies (IgA-anti-ß2GPI) seems to be the most prevalent isotype in patients with Systemic Lupus Erythematosus (SLE) with a significant association to thrombotic events. Both SLE and antiphospholipid syndrome (APS) can be associated with implantation failure, fetal loss and obstetric complications. Recent reports highlight the clinical value of IgA-anti-ß2GPI determination in supporting in vitro fertilization (IVF) treatment and IVF pregnancy outcomes. We report a 36-year-old female diagnosed with SLE, endometriosis and unexplained infertility. Conventional APS markers were consistently negative: anti-cardiolipin (aCL) and anti-ß2GPI: IgG/IgM. She was then tested with reports of repeatedly high IgA-anti-ß2GPI and tested positive from 2014 after IgA (aCL; anti-ß2GPI) were established in our APS diagnostic panel. She underwent successful first IVF procedure with a 30 week live birth pregnancy outcome. During the follow up no lupus flare, thrombosis or ovarian hyperstimulation syndrome were registered. Serum IgA anti-ß2GPI and anti-dsDNA levels declined statistically significant during the second and third trimester. Titres of IgA-anti-ß2GPI remained lower postpartum as well. This case highlights the clinical importance of IgA-anti-ß2GPI testing for family planning, assisted reproduction and pregnancy in women with SLE and/or APS.

[Diagnostic challenges in a man with subarachnoidal haemorrhage]. / Diagnostiske utfordringer hos en mann med subaraknoidalblødning.

A 39-year-old man with multiple sclerosis was admitted to the Neurological department because of sudden and intense headache, photophobia, nausea and vomiting. A subarachnoidal haemorrhage was suspected and cerebral CT scanning showed small amounts of subarachnoidal blood distributed symmetrically over both cerebral hemispheres - an unusual location for aneurismal bleeding. Liquor analysis revealed erythrocytes, positive bilirubin and slightly elevated protein. Subsequent cerebral MRI showed no signs of aneurysm, vascular malformation, venous sinus thrombosis or infarction. An intraarterial cerebral angiography was then performed and showed bilateral widespread segmental vasoconstriction in the anterior, middle and posterior cerebral arteries. A diagnostic workup on systemic vasculitis was negative. The patient's good general condition in spite of extensive angiographic findings rendered the diagnosis cerebral vasculitis unlikely. A state of reversible cerebral segmental vasoconstriction was suspected and the patient was treated with the calcium antagonist nifedipine and observed for four weeks. Cerebral angiography was then repeated and found to be normal. This case report highlights a less recognized and probably underdiagnosed cause of subarachnoidal bleeding.