[A woman in her thirties with frequent mucosal ulcers]. / En kvinne i 30-årene med hyppige sår på slimhinner.

BACKGROUND: Haploinsuffiency A20 (HA20) was first described in 2016 and is caused by a mutation in TNFAIP3/A20. Non-related families living on different continents were examined with whole exome sequencing (WES). All had symptoms of Behçet's disease. An autosomal dominant mutation was found. CASE PRESENTATION: When in her early teens, the patient had presented with a painful labial ulcer. She also had recurrent mouth ulcers, sometimes accompanied by fever and elevated CRP, and on occasion by abdominal pain. The ulcers were biopsied, and she was diagnosed with likely Behçet's disease. Some family members were later admitted with similar symptoms, and a genetic cause was suspected. Twenty years later a new genetic test was performed, and a revised diagnosis of HA20 was correctly made. INTERPRETATION: HA20 is a newly identified autoinflammatory disease due to an inherited mutation. This leads to increased production of pro-inflammatory cytokines such as IL-1, IL-6 and TNF α. The disease-causing process in this monogenic, inherited disease is very similar to the immune process in the acquired, multifactorial Behçet's disease. Fever, young age, abdominal involvement and global occurrence are factors that could lead to suspicion of HA20.

Cardiac Involvement in Systemic and Local Vasculitides: The Value of Noninvasive Multimodality Imaging.

Despite significant advances in managing systemic vasculitides, cardiovascular morbidity, and mortality are still of primary concern. Advances in noninvasive imaging have broadened our understanding of the clinical heterogeneity of cardiac involvement in vasculitides. Common cardiovascular complications in primary or secondary vasculitides are; coronary artery aneurysms, acute coronary syndromes, myocarditis, pericarditis, endocarditis, and valvular dysfunction. Echocardiography, cardiac magnetic resonance , positron emission tomography, and computed tomography angiography are essential in identifying cardiac involvement and guiding treatment. Here, we present our experiences of cardiac involvement in systemic vasculitides, covering most aspects of common cardiac complications based on a multi-modality approach to challenging (real-world) cases. As many cardiac manifestations are clinically silent, heart function should be systemically assessed by a multimodality imaging-based approach, including ECG, serial echocardiograms with strain imaging and 3D, and cardiac magnetic resonance to detect early signs of cardiac manifestations. This enables timely intervention and optimal medical treatment, which is essential for a better prognosis. There is a need for better and closer collaboration in clinical practice and research fields between cardiologists and rheumatologists.

Cardiac dysfunction in mixed connective tissue disease: a nationwide observational study.

We aimed to identify cardiac function in patients with established mixed connective tissue disease (MCTD). This was a cross-sectional case-control study of well-characterised MCTD patients who had previously been included in a nationwide cohort. Assessments comprised protocol transthoracic echocardiography, electrocardiogram and blood samples. In patients only, we evaluated the findings of high-resolution pulmonary computed tomography and disease activity. We assessed 77 MCTD patients (mean age 50.5 ± 12.3 years) with a mean disease duration of 16.4 years, and 59 age- and sex-matched healthy controls (49.9 ± 11.7 years). By echocardiography, measures of left ventricular function, i.e. fractional shortening (38.1 ± 6.4% vs. 42.3 ± 6.6%, p < 0.001), mitral annulus plane systolic excursion (MAPSE) (13.7 ± 2.1 mm vs. 15.3 ± 2.3 mm, p < 0.001) and early diastolic velocity of the mitral annulus (e') (0.09 ± 0.02 m/s vs. 0.11 ± 0.03 m/s, p = 0.002) were subclinical and lower in patients than controls. Right ventricular dysfunction was found in patients assessed by tricuspid annular plane systolic excursion (TAPSE) (22.7 ± 4.0 mm vs. 25.5 ± 4.0 mm, p < 0.001). While cardiac dysfunction was not associated with pulmonary disease, e' and TAPSE were found to correlate with disease activity at baseline. In this cohort of MCTD patients, echocardiographic examinations demonstrated a higher frequency of cardiac dysfunction than in matched controls. Cardiac dysfunction was associated with disease activity at baseline, but was independent of cardiovascular risk factors and pulmonary disease. Our study indicates that cardiac dysfunction is part of the multi-organ affliction seen in MCTD.

A man in his sixties with chondritis and bone marrow failure. / En mann i 60-årene med kondritt og benmargssvikt.

BACKGROUND: VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic syndrome) first described in 2020, is caused by a limited repertoire of somatic mutations in UBA1, a gene involved in the initiation of ubiquitination. Ubiquitination, adding an ubiquitin protein to a substrate protein, can have various effects on the substrate. Disruption of UBA1 function results in diverse clinical manifestations, mimicking a variety of disorders. CASE PRESENTATION: A man in his sixties presented with fever, chest pain, fatigue, pulmonary infiltrates and elevated acute phase reactants. Initially he was thought to have extra-cranial giant cell arteritis. When he developed ear and nose chondritis, a revised diagnosis of relapsing polychondritis was made. Subsequently he developed macrocytic anaemia and thrombocytopenia. His condition remained resistant to medical therapy and he died eight years after disease onset. Analysis of stored DNA revealed a somatic mutation in UBA1 confirming the diagnosis of VEXAS syndrome. INTERPRETATION: VEXAS syndrome is a newly identified inflammatory disorder due to an acquired mutation in haematopoietic bone marrow cells in older men. The syndrome may be misdiagnosed as treatment-refractory relapsing polychondritis, polyarteritis nodosa, Sweet syndrome or giant cell arteritis. We describe the first individual with molecularly confirmed VEXAS syndrome in Norway.

Mortality and causes of death across the systemic connective tissue diseases and the primary systemic vasculitides.

Objectives: Studies assessing relative mortality risks across the spectrum of systemic inflammatory rheumatic diseases are largely missing. In this study, we wanted to estimate standard mortality ratios (SMRs) and causes of death in an ethnically homogeneous cohort covering all major CTDs and primary systemic vasculitides (PSVs). Methods: We prospectively followed all incident CTD and PSV cases included in the Norwegian CTD and vasculitis registry (NOSVAR) between 1999 and 2015. Fifteen controls for each patient matched for sex and age were randomly drawn from the Norwegian National Population Registry. Causes of death were obtained from the National Cause of Death Register, death certificates and hospital charts. Results: The cohort included 2140 patients (1534 with CTD, 606 with PSV). During a mean follow-up time of 9 years, 279 of the patients (13%) died, compared with 2864 of 32 086 (9%) controls (P < 0.001). Ten years after diagnosis, the lowest survival was 60% in dcSSc, 73% in anti-synthetase syndrome (ASS) and 75% in lcSSc. In the CTD group, the highest SMRs were observed in dcSSc (SMR 5.8) and ASS (SMR 4.1). In the PSV group, Takayasu arteritis (SMR 2.5) and ANCA-associated vasculitis (SMR 1.5) had the highest SMRs. Major causes of death were cardiovascular disease (CTD 27%, PSV 28%), neoplasms (CTD 25%, PSV 27%), chronic respiratory disease (CTD 20%, PSV10%) and infections (CTD 9%, PSV 16%). Conclusion: We observed premature deaths across the spectrum of CTDs and PSVs, with highest SMRs in dcSSc and ASS. The overall mortality was highest in the CTD group.

Progression and mortality of interstitial lung disease in mixed connective tissue disease: a long-term observational nationwide cohort study.

Objectives: To assess the prevalence, extent, progression, functional impact and mortality of interstitial lung disease (ILD) in a nationwide unselected MCTD cohort. Methods: The study cohort included patients with high-resolution CT lung scans available at baseline (n = 135) and at follow-up (n = 119). The extent of disease was expressed as percentage of total lung volume (TLV). Results: ILD was present in 41% of MCTD patients at follow-up. Median (interquartile) extent (% of TLV) was 5 (8) at baseline and 7 (17) at follow-up, mean length 6.4 years later. The lung disease progressed in 19% of patients across the observation period. Predictors of ILD progression were elevated anti-RNP titre [hazard ratio (HR) 1.5, 95% CI: 1.1, 2.0; P = 0.008], presence of anti-ro52 antibodies (HR = 3.5, 95% CI: 1.2, 10.2; P = 0.023), absence of arthritis (HR = 0.2, 95% CI: 0.1, 0.6; P = 0.004) and male gender (HR = 4.0, 95% CI: 1.4, 11.5; P = 0.011) after age and baseline disease adjustments. The risk of death increased by 2.9 (95% CI: 1.1, 7.9; P = 0.038) in patients where disease involved ⩾5% of TLV. Conclusion: Lung disease extent and progression in MCTD are modest. Yet, the extension continues several years after MCTD diagnosis causing lung function decline and increasing the risk of mortality. The study identified male gender, elevated anti-RNP titre, presence of anti-ro52 antibodies and absence of arthritis as the strongest predictors of ILD progression.

Frequencies of borderline pulmonary hypertension before and after the DETECT algorithm: results from a prospective systemic sclerosis cohort.

Objective: The DETECT algorithm was developed for screening patients with SSc at high risk of pulmonary arterial hypertension (PAH). We evaluated the impact of this algorithm in a SSc population. Methods: Patients from the unselected, prospective Oslo University Hospital SSc study were divided into the Early and DETECT cohorts, respectively, depending on whether an incident right heart catheterization (RHC) was performed before (2009-13) or after (2014-17) the DETECT algorithm was instituted. A PAH diagnosis and patient risk stratification (low, intermediate and high risk) were performed according to 2015 European Society of Cardiology guidelines. Results: At the time of the incident RHC, PAH frequency was similar between the DETECT (15/84 with PAH; 18%) and Early (16/77; 21%) cohorts, but more patients had borderline pulmonary hypertension (PH) in the DETECT (31%) than in the Early (17%) cohort. PAH risk levels were distributed differently. In the DETECT cohort, 27% and 27% were at low and high risk, respectively, at the time of PAH diagnosis. In the Early cohort, 19 and 44% were at low and high risk, respectively. A follow-up RHC, performed after [mean (SD)] 2.4 (1.8) years, showed that 39% of patients with borderline PH in the Early cohort had developed PAH. Conclusion: The DETECT algorithm did not alter PAH incidence in this unselected SSc population. However, it appeared to affect the risk distribution at the time of PAH diagnosis and increased the frequency of borderline PH cases. These findings may translate into novel opportunities for earlier PAH treatment and, possibly, prevention.

Disease evolution in mixed connective tissue disease: results from a long-term nationwide prospective cohort study.

BACKGROUND: The phenotypic stability of mixed connective tissue disease (MCTD) is not clear, and knowledge about disease activity and remission is scarce. We aimed to establish the occurrence of evolution from MCTD to another defined rheumatic condition, and the prevalence and durability of remission after long-term observation. METHODS: In this large population-based prospective observational MCTD cohort study (N = 118), disease conversion was defined by the development of new auto-antibodies and clinical features compliant with another well-defined rheumatic condition. Remission was defined by a combination of systemic lupus erythematosus disease activity index 2000 (SLEDAI-2 K) of 0 and European League Against Rheumatism scleroderma trials and research (EUSTAR) activity index <2.5. Predictors of phenotypic stability and disease remission were assessed by logistic regression. RESULTS: Among 118 patients, 14 (12%) developed another well-defined rheumatic condition other than MCTD after mean disease duration of 17 (SD 9) years. Puffy hands predicted a stable MCTD phenotype in univariable regression analysis (OR 7, CI 2-27, P = .010). Disease activity defined by SLEDAI-2 K, decreased gradually across the observation period and > 90% of patients had EUSTAR activity index <2.5. There were 13% patients in remission throughout the whole mean observation period of 7 (SD 2) years. The strongest predictor of remission was percentage of predicted higher forced vital capacity. CONCLUSIONS: Our results strengthen the view of MCTD as a relatively stable disease entity. Long-term remission in MCTD is not frequent; however, the low SLEDAI-2 K and EUSTAR scores during the observation period suggests that the disease runs a milder course than systemic lupus erythematosus and systemic sclerosis.

Mixed connective tissue disease.

The concept of mixed connective tissue disease (MCTD) as a separate connective tissue disease (CTD) has persisted for more than four decades. High titers of antibodies targeting the U1 small nuclear ribonucleoprotein particle (U1 snRNP) in peripheral blood are a sine qua non for the diagnosis of MCTD, in addition to distinct clinical features including Raynaud's phenomenon (RP), "puffy hands," arthritis, myositis, pleuritis, pericarditis, interstitial lung disease (ILD), and pulmonary hypertension (PH). Recently, population-based epidemiology data from Norway estimated the point prevalence of adult-onset MCTD to be 3.8 per 100,000 and the mean annual incidence to be 2.1 per million per year, supporting the notion that MCTD is the least common CTD. Little is known about the etiology of MCTD, but recent genetic studies have confirmed that MCTD is a strongly HLA (​human leukocyte antigen)-linked disease, as the HLA profiles of MCTD differ distinctly from the corresponding profiles of ethnically matched healthy controls and other CTDs. In the first section of this review, we provide an update on the clinical, immunological, and genetic features of MCTD and discuss the relationship between MCTD and the other CTDs. Then we proceed to discuss the recent advances in therapy and our current understanding of prognosis and prognostic factors, especially those that are associated with the more serious pulmonary and cardiovascular complications of the disease. In the final section, we discuss some of the key, unresolved questions related to anti-RNP-associated diseases and indicate how these questions may be approached in future studies.

Associations between anti-Ro52 antibodies and lung fibrosis in mixed connective tissue disease.

OBJECTIVE: MCTD is a chronic, immune-mediated disorder defined by the combined presence of serum anti-RNP antibodies and distinct clinical features, including progressive lung fibrosis. The aim of the study was to evaluate the potential impact of anti-SSA (i.e. Ro52 and Ro60) and anti-SSB autoantibodies as markers for disease outcomes in MCTD. METHODS: Stored serum samples from 113 patients included in the cross-sectional, nationwide Norwegian MCTD cohort were screened for the presence of anti-Ro52, anti-Ro60 and anti-SSB by a commercial line immunoassay. Correlation analyses were carried out with clinical parameters, including quantitative lung fibrosis scores by high-resolution CT. Lung fibrosis was defined by reticular pattern changes according to the Fleischner Society CT criteria for interstitial lung disease. RESULTS: Anti-Ro52 antibodies were present in 29%, anti-Ro60 in 19% and anti-SSB in 6% of the MCTD sera. High-resolution CT scoring identified lung fibrosis in 38 of 113 (34%) MCTD patients. Anti-Ro52 antibodies were detected in 50% (19 of 38) of the MCTD patients with lung fibrosis and in 19% (14 of 75) without lung fibrosis (P < 0.001). The odds ratio for the presence of anti-Ro52 antibodies in lung fibrosis was 4.4 (95% CI 1.8, 10.3). Anti-Ro52 antibodies were equally frequent in patients with mild to moderate (eight of 17; 44%) and severe fibrosis (11 of 21; 52%). Anti-Ro52 was not associated with any of the other clinical parameters assessed, nor was anti-Ro60 or anti-SSB. CONCLUSION: Our cross-sectional data suggest that anti-Ro52 antibodies may serve as a potential marker for lung fibrosis in MCTD.

Associations between circulating endostatin levels and vascular organ damage in systemic sclerosis and mixed connective tissue disease: an observational study.

INTRODUCTION: Systemic sclerosis (SSc) and mixed connective tissue disease (MCTD) are chronic immune-mediated disorders complicated by vascular organ damage. The aim of this study was to examine the serum levels of the markers of neoangiogenesis: endostatin and vascular endothelial growth factor (VEGF), in our unselected cohorts of SSc and MCTD. METHODS: Sera of SSc patients (N = 298) and MCTD patients (N = 162) from two longitudinal Norwegian cohorts were included. Blood donors were included as controls (N = 100). Circulating VEGF and endostatin were analyzed by enzyme immunoassay. RESULTS: Mean endostatin levels were increased in SSc patients 93.7 (37) ng/ml (P < .001) and MCTD patients 83.2 (25) ng/ml (P < .001) compared to controls 65.1 (12) ng/ml. Median VEGF levels were elevated in SSc patients 209.0 (202) pg/ml compared to MCTD patients 181.3 (175) pg/ml (P = .017) and controls 150.0 (145) pg/ml (P < .001). Multivariable analysis of SSc subsets showed that pulmonary arterial hypertension (coefficient 15.7, 95 % CI: 2.2-29.2, P = .023) and scleroderma renal crisis (coefficient 77.6, 95 % CI: 59.3-100.0, P < .001) were associated with elevated endostatin levels. Multivariable analyses of MCTD subsets showed that digital ulcers were associated with elevated endostatin levels (coefficient 10.5, 95 % CI: 3.2-17.8, P = .005). The risk of death increased by 1.6 per SD endostatin increase (95 % CI: 1.2-2.1, P = .001) in the SSc cohort and by 1.6 per SD endostatin increase (95 % CI: 1.0-2.4, P = .041) in the MCTD cohort after adjustments to known risk factors. CONCLUSIONS: Endostatin levels were elevated in patients with SSc and MCTD, particularly SSc patients with pulmonary arterial hypertension and scleroderma renal crisis, and MCTD patients with digital ulcers. Elevated endostatin levels were also associated with increased all-cause mortality during follow-up in both groups of patients. We propose that endostatin might indicate the degree of vascular injury in SSc and MCTD patients.

The HLA profiles of mixed connective tissue disease differ distinctly from the profiles of clinically related connective tissue diseases.

OBJECTIVE: The Norwegian nationwide MCTD cohort was established to obtain unbiased data on key disease issues, and thereby reappraise the concept of MCTD. In the current study, the aims were to obtain detailed HLA profile data on the large Norwegian MCTD cohort and compare these with the HLA profiles of ethnically matched healthy controls and related CTD controls. METHODS: HLA profiles, determined by sequence-based typing of HLA-B* and DRB1*, were compared between four control groups of Norwegian ancestry, SLE (n = 96), SSc (n = 95), PM/DM (n = 84), healthy individuals (n = 282), the complete MCTD cohort (n = 155) and MCTD subsets defined by key clinical parameters. RESULTS: HLA-B*08 [odds ratio (OR) 2.05, P = 1.31 × 10(-4)) and DRB1*04:01 (OR 2.82, P = 3.64 × 10(-8)) were identified as risk alleles for MCTD, while DRB1*04:04, DRB1*13:01 and DRB1*13:02 were protective. Risk alleles for SLE and PM/DM were B*08 and DRB1*03:01. SSc risk was associated with DRB1*08:01. Analyses of MCTD subsets identified B*18 [OR 3.32 (95% CI 1.38, 8.01)] and DRB1*03:01 [OR 1.83 (95% CI 1.03, 3.25)] as independent risk factors for lung fibrosis. CONCLUSION: Novel HLA alleles associated with MCTD and disease subsets were identified and DRB1*04:01 was confirmed as a major risk allele. Altogether, the data reinforce the notion of MCTD as a disease entity distinct from SLE, SSc and PM/DM.

Performance of the 2013 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Systemic Sclerosis (SSc) in large, well-defined cohorts of SSc and mixed connective tissue disease.

OBJECTIVE: To assess the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Classification Criteria for Systemic Sclerosis (SSc) on defined subgroups of SSc and in mixed connective tissue disease (MCTD) as an SSc-related disease. METHODS: The 2013 ACR/EULAR criteria were assessed in 425 consecutive patients suspected to have SSc and seen at Oslo University Hospital, and in the nationwide Norwegian MCTD cohort (n = 178). In the SSc group, 239/425 patients had disease duration < 3 years (in 82 of these, duration was < 1 yr). Patients were subgrouped as limited SSc (n = 294), diffuse SSc (n = 97), SSc sine scleroderma (n = 10), and early SSc (prescleroderma; n = 24). Item data were complete, except nailfold capillaroscopy and telangiectasia results, missing in the MCTD cohort. RESULTS: The 2013 ACR/EULAR SSc criteria were met by 409/425 patients (96%) in the SSc group. For comparison, only 75% (293/391) met the 1980 ACR SSc classification criteria. All the novel items in the 2013 ACR/EULAR criteria were frequent in the SSc cohort. Considering that there were missing data on 2 items, 10% (18/178) of the MCTD cohort met the 2013 ACR/EULAR criteria, giving an estimated specificity of 90% toward this SSc-like disorder. CONCLUSION: In our large and representative group of consecutive patients with SSc, the 2013 ACR/EULAR SSc criteria were more sensitive than the ACR 1980 criteria. However, the new criteria did not completely segregate SSc from MCTD, making specificity a potential issue.

Hemophagocytic lymphohistiocytosis in leprosy.

A patient from Southeast Asia was diagnosed with systemic lupus erythematosus. One year later, she experienced exacerbation of skin lesions and was diagnosed with erythema nodosum leprosum. Upon treatment, the patient developed hemophagocytic lymphohistiocytosis with multi-organ failure and died from invasive fungal infection. Hemophagocytic lymphohistiocytosis has to our knowledge, not previously been reported in leprosy.

Prevalence of pulmonary hypertension in an unselected, mixed connective tissue disease cohort: results of a nationwide, Norwegian cross-sectional multicentre study and review of current literature.

OBJECTIVES: The aim of this study was to assess the overall prevalence of pulmonary hypertension (PH) in an unselected MCTD cohort and review the current knowledge with a systematic database search. METHODS: A nationwide multicentre cohort of 147 adult MCTD patients were initially screened for PH by echocardiography, high-resolution computed tomography (HRCT), pulmonary function tests and N-terminal pro-brain natriuretic peptide (NT-proBNP) and then followed up for a mean of 5.6 years. Right-sided heart catheterization was performed when estimated pulmonary artery systolic pressure was >40 mmHg on echocardiography. PH was diagnosed according to the 2009 European Society of Cardiology and European Respiratory Society guidelines. RESULTS: At inclusion, 2.0% (3/147) had established PH. Two additional PH patients were identified during follow-up, giving a total PH frequency in the cohort of 3.4% (5/147). All five had elevated serum NT-proBNP. Two had isolated pulmonary arterial hypertension (PAH) and three PH associated with interstitial lung disease (PH-ILD). Three PH patients died during follow-up. Nine other patients in the cohort also died, but none of them had echocardiographic signs of PH prior to death. CONCLUSION: The data from the current unselected MCTD cohort suggest that the prevalence of PH is much lower than expected from previous studies but confirm the seriousness of the disease complication.

Prevalence and severity of interstitial lung disease in mixed connective tissue disease: a nationwide, cross-sectional study.

BACKGROUND: Mixed connective tissue disease (MCTD) is an immune-mediated, systemic disorder of unknown cause. OBJECTIVE: To assess the prevalence, pattern and severity of interstitial lung disease (ILD) in a cross-sectional study of the nationwide, Norwegian MCTD cohort. METHODS: 126 patients with MCTD were systematically examined for ILD by high-resolution CT (HRCT), pulmonary function tests (PFT), 6 min walk test (6MWT) and by the New York Heart Association (NYHA) functional classification of dyspnoea. The extent and type of HRCT lung abnormalities were scored according to the CT criteria of ILD recommended by the Fleischner Society. RESULTS: All 126 patients were Caucasian, 75% women. At the time of the cross-sectional ILD study, the patients had a mean disease duration of 9.0 years. 52% of the patients had abnormal HRCT findings, most commonly reticular patterns consistent with lung fibrosis (35%). Lung fibrosis was quantified as minor in 7%, moderate in 9% and severe in 19% of the patients. Fibrosis was uniformly concentrated in the lower parts of the lungs and was not associated with smoking. Patients with severe lung fibrosis had lower PFT values, shorter 6MWT and a higher mean NYHA functional class. After a mean 4.2 years' follow-up, overall mortality was 7.9%. Mortality in patients with normal HRCT was 3.3%, as compared with 20.8% in patients with severe lung fibrosis (p<0.01). CONCLUSIONS: Severe lung fibrosis is common in MCTD, has an impact on pulmonary function and overall physical capacity and is associated with increased mortality.

The prevalence and incidence of mixed connective tissue disease: a national multicentre survey of Norwegian patients.

OBJECTIVES: Mixed connective tissue disease (MCTD) is an immune-mediated, systemic disorder of unknown aetiology. As the epidemiology of the disease is largely unknown, the authors performed a nationwide cross-sectional retrospective study to assess the prevalence and incidence of MCTD in Norway. METHODS: Every adult patient (≥ 18 years) with MCTD seen at one of the departments of rheumatology was reviewed for inclusion. Only patients who satisfied the following four criteria were included: clinical diagnosis of MCTD verified by a rheumatologist; positive serum anti-ribonucleoprotein antibody test; fulfilment of at least one of three of following criteria sets: the modified Sharp's criteria, the criteria of Alarcón-Segovia and Villareal and those of Kasukawa; and exclusion of other connective tissue diseases. RESULTS: The four inclusion criteria were fulfilled by 147 adult Caucasian patients. The female to male ratio was 3.3 and the mean age at diagnosis of adult-onset MCTD was 37.9 years (95% CI 35.3 to 40.4 years). At the end of 2008, the point prevalence of living adult MCTD patients in Norway was 3.8 (95% CI 3.2 to 4.4) per 100,000 adults. The incidence of adult-onset MCTD in Norway during the period from 1996 to 2005 was 2.1 (95% CI 1.7 to 2.5) per million per year. CONCLUSIONS: MCTD has a female predominance and the incidence and prevalence of MCTD is low, and lower than reported figures for polymyositis, dermatomyositis, systemic sclerosis and systemic lupus erythematosus. The prevalence estimates were similar across the three criteria sets of MCTD.

[A man with erythrodermia, muscle weakness and weight loss]. / En mann med erytrodermi, muskelsvakhet og vekttap.

A man in his late fifties was treated with acitretin for psoriasis. The treatment was discontinued when liver enzymes started to increase. He subsequently developed erythrodermia, weakness of proximal muscle groups, heliotrope rash, Gottron's papules and elevation of creatine kinase to more than 9000 U/L. However, histological examination of a muscle biopsy displayed neuropathic atrophy and only a few scattered necrotic fibers. Alpha 1 foetoprotein was substantially elevated (1600 kU/L) and computed tomography showed two hepatic tumors, lytic lesions in the spine and in the ninth rib. Although no chronic liver disease could be documented, the patient was found to have a hepatocellular carcinoma which presented as dermatomyositis and erythrodermia.