Late skin fibrosis in systemic sclerosis: a study from the EUSTAR cohort.

OBJECTIVES: The early trajectory of skin fibrosis provides insights into the disease course of systemic sclerosis (SSc) including mortality; however, little is known about late skin fibrosis. The aims of our study were to ascertain the prevalence and characteristics of late skin fibrosis in SSc. METHODS: We developed and tested three conceptual scenarios of late (>5 years after first non-RP feature) skin fibrosis including new worsening of skin disease, and failure to improve after worsening within 5-year window. We defined skin worsening as change in modified Rodnan skin score (mRSS) ≥5 units or ≥25%. Using strict inclusion criteria including complete mRSS, we identified 1,043 (out of 19 115) patients within the EUSTAR database for our analysis. We further restricted analysis within 887 (out of 1043) patients who had lcSSc or dcSSc at baseline. RESULTS: One-fifth of patients among the whole cohort (n = 208/1043, 19.9%) experienced mRSS worsening, including in patients with lcSSc or dcSSc at baseline (n = 193/887, 21.8%). This was largely due to new skin worsening after the 5-year window or failure to improve with worsening within the 5-year window. Patients with lower baseline mRSS and lcSSc were more likely to develop late skin fibrosis. Anti-Scl-70 was associated with progression from baseline lcSSc to dcSSc, and anticentromere was protective. CONCLUSIONS: Late skin fibrosis is not uncommon in SSc. We have identified different patterns relevant to clinical practice and trial design. Late skin fibrosis is a neglected manifestation of SSc and warrants further investigation including to determine clinical outcomes and optimal therapeutic strategy.

Trends in incidence, mortality, and causes of death associated with systemic sclerosis in Denmark between 1995 and 2015: a nationwide cohort study.

BACKGROUND: To investigate the incidence and the mortality-rates of systemic sclerosis (SSc), its primary causes of death, and the temporal trends in events in Denmark during the last decades. METHODS: Using the Danish National Patient Registry, we identified all persons aged ≥18 years with a first-time diagnosis of SSc (ICD-10 code M34, excluding M34.2) between 1995 and 2015. RESULTS: A total of 2778 incident SSc cases were identified. The mean age at time of SSc diagnosis was 56 (standard deviation 15) years and 76% were women. The overall incidence rate (per 1,000,000 person-years) of diagnosed SSc was 24.4 (95% confidence interval 23.6-25.4), with a slight increase over the study period, age- and sex-adjusted incidence rate ratio 1.02 (95% confidence interval 1.01-1.02) per 1-year increase. The 1-year all-cause mortality rate per 100 person-years decreased from 6.1 (3.1-12.2) in 1995 to 5.3 (2.5-11.1) in 2015, sex- and age-adjusted hazard ratio 0.96 (95% CI 0.94-0.98) per 1-year increase. Over the period, the average age at SSc diagnosis increased and the proportion of women decreased, whereas the burden of comorbidities increased. One fifth of all deaths were attributable to cardiovascular causes, a fourth to pulmonary diseases, and 15% were due to cancer. CONCLUSIONS: Within the last few decades, the incidence of SSc has increased and the 1-year mortality rate has decreased slightly in Denmark. Almost half of all deaths were attributable to cardiopulmonary causes.

Mycobacterium intracellulare Infection Mimicking Progression of Scleroderma.

This case report describes a patient with scleroderma who developed Mycobacterium intracellulare infection, which for more than a year mimicked worsening of her connective tissue disorder. The patient was diagnosed with scleroderma based on puffy fingers that developed into sclerodactyly, abnormal nail fold capillaries, interstitial lung disease, Raynaud's phenomenon, esophageal dysmotility, and positivity for rheumatoid factor and anti-SSA antibodies. She developed massive inflammatory changes of the cutis, the subcutis, and the muscle fasciae of the right leg, that after several failed attempts of immunosuppressive treatments were found to be caused by Mycobacterium intracellulare. While she was receiving high-dose prednisolone, as worsening of her connective tissue disease was suspected to be the cause of the inflammatory changes, she had Listeria monocytogenes meningitis and was hospitalized for several weeks, but she recovered from this without sequelae. After Mycobacterium intracellulare infection was diagnosed, she was treated with clarithromycin and rifampicin. Her skin manifestations, arthralgias, and fatigue improved considerably, and the wounds of the right leg healed, unfortunately with significant scarring. Immunodeficiency testing was unremarkable. In summary, an infection with Mycobacterium intracellulare was mistaken for an unusually severe progression of scleroderma.

A comparison of anti-nuclear antibody quantification using automated enzyme immunoassays and immunofluorescence assays.

Anti-nuclear antibodies (ANA) have traditionally been evaluated using indirect fluorescence assays (IFA) with HEp-2 cells. Quantitative immunoassays (EIA) have replaced the use of HEp-2 cells in some laboratories. Here, we evaluated ANA in 400 consecutive and unselected routinely referred patients using IFA and automated EIA techniques. The IFA results generated by two independent laboratories were compared with the EIA results from antibodies against double-stranded DNA (dsDNA), from ANA screening, and from tests of the seven included subantigens. The final IFA and EIA results for 386 unique patients were compared. The majority of the results were the same between the two methods (n = 325, 84%); however, 8% (n = 30) yielded equivocal results (equivocal-negative and equivocal-positive) and 8% (n = 31) yielded divergent results (positive-negative). The results showed fairly good agreement, with Cohen's kappa value of 0.30 (95% confidence interval (CI) = 0.14-0.46), which decreased to 0.23 (95% CI = 0.06-0.40) when the results for dsDNA were omitted. The EIA method was less reliable for assessing nuclear and speckled reactivity patterns, whereas the IFA method presented difficulties detecting dsDNA and Ro activity. The automated EIA method was performed in a similar way to the conventional IFA method using HEp-2 cells; thus, automated EIA may be used as a screening test.