[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.

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.

Prevalence and clinical characteristics of adult polymyositis and dermatomyositis; data from a large and unselected Norwegian cohort.

OBJECTIVES: The occurrence of polymyositis (PM) and dermatomyositis (DM) in the general population is largely unknown and unbiased data on clinical and laboratory features in PM/DM are missing. Here, we aim to identify and characterise every PM/DM patient living in southeast Norway (denominator population 2.64 million), 2003-2012. METHOD: Due to the structure of the Norwegian health system, all patients with PM/DM are followed at public hospitals. Hence, all public hospital databases in southeast Norway were screened for patients having ICD-10 codes compatible with myositis. Manual chart review was then performed to identify all cases meeting the Peter & Bohan and/or Targoff classification criteria for PM/DM. RESULTS: The ICD-10 search identified 3160 potential myositis patients, but only 208/3160 patients met the Peter & Bohan criteria and 230 the Targoff criteria (100 PM, 130 DM). With 56 deaths during the observation period, point prevalence of PM/DM was calculated to 8.7/100 000. Estimated annual incidences ranged from 6 to 10 /1 000 000, with peak incidences at 50-59 (DM) and 60-69 years (PM). Myositis specific antibodies (Jo-1, PL-7, PL-12, signal recognition particle (SRP) and Mi-2) were present in 53% (109/204), while 137/163 (87%) had pathological muscle MRI. Frequent clinical features included myalgia (75%), arthritis (41%) dyspnoea (62%) and dysphagia (58%). Positive anti-Jo-1, present in 39% of DM and 22% of PM cases, was associated with dyspnoea, arthritis and mechanic hands. CONCLUSIONS: Our data indicate that the population prevalence of PM/DM in Caucasians is quite low, but underscores the complexity and severity of the disorders.