Distinct phenotypes of multisystem inflammatory syndrome in children: a cohort study

To characterize the clinical features and outcomes of childhood-onset primary Sjögren’s syndrome (pSS). Patients less than 18 years old who were diagnosed with pSS by paediatric rheumatologists were included, and all patients were applied the 2002 American-European Consensus Group (ACEG) criteria, the 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for pSS, or the 1999 proposed juvenile pSS criteria. The electronic medical records of patients with pSS from 2013 to 2020 were collected and analysed. Thirty-nine patients were included. Of them, 27 (69.2%), 38 (97.4%) and 35 (89.7%) patients fulfilled the AECG criteria, ACR/EULAR criteria and proposed juvenile pSS criteria, respectively. The female:male ratio was 3.9:1. The median ages at first signs or symptoms and at diagnosis were 9.2 (4.7, 14.5) years and 10.9 (6.3, 15.0) years, respectively. The main clinical manifestations were rash or purpura (20, 51.3%), followed by fever (12, 30.8%), glandular enlargement/recurrent parotitis (10, 25.6%), and dry mouth and/or dry eyes (9, 23.1%). Twenty-eight (56.4%) patients had systemic damage, the most common of which was haematological involvement (14, 35.9%), followed by hepatic (13, 33.3%) and renal involvement (8, 20.5%). Thirty-eight (97.4%) patients underwent labial minor salivary gland biopsy, and all exhibited focal lymphocytic sialadenitis. All patients had a global ESSDAI score ≥ 1 at diagnosis, and the median total score at diagnosis was 8 (2, 31). Thirty-six (92.3%) patients were followed up for a median time of 23.6 (7.9, 79.5) months, and three patients developed systemic lupus erythematosus (SLE) at follow-up times of 13.3, 38.8 and 63.8 months. The presentation of childhood-onset pSS is atypical, and extraglandular manifestations and systemic involvement are more common than in adult-onset pSS. Labial salivary gland biopsy is vital for patients with probable pSS. Some patients may develop SLE over time.     

Response times follow lognormal or gamma distribution in arthritis patients

ObjectiveThis study evaluated the statistical distribution of time to treatment response in patients with rheumatic diseases.Study Design and SettingThe study used a secondary data analysis design. Data from the trial of etanercept and methotrexate with radiographic patient outcomes were used to model the response times for etanercept (ETN), methotrexate (MTX), and combined ETN + MTX in patients with rheumatoid arthritis. The German etanercept registry was used to evaluate the response time distributions in patients with juvenile idiopathic arthritis.ResultsFor MTX, the lognormal distribution was considered to be the best model for the outcome American College of Rheumatology (ACR20), lognormal, generalized gamma, and log-logistic distributions for ACR50, and lognormal and generalized gamma for ACR70. For ETN, the lognormal model was best for ACR20, the generalized gamma for ACR50, and both lognormal and generalized gamma distributions for ACR70. For combined treatment, the best model was the log-logistic distribution for ACR20, generalized gamma for ACR50, and both lognormal and generalized gamma distributions for ACR70. For the German etanercept registry, the lognormal distribution was the best model for all three outcomes of pediatric ACR30, ACR50, and ACR70 without interval censoring.ConclusionStudy designs might be more efficient if the response distributions are taken into consideration during planning.     

Influence of methylenetetrahydrofolate reductase polymorphisms on efficacy and toxicity of methotrexate in patients with juvenile idiopathic arthritis

OBJECTIVE: To study the relationship of C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene to toxicity and efficacy of methotrexate (MTX) in patients with juvenile idiopathic arthritis (JIA). METHODS: Single nucleotide polymorphisms of the MTHFR gene were investigated by polymerase chain reaction and restriction enzyme analysis of DNA extracted from peripheral blood cells. The fasting plasma homocysteine concentration was analyzed by enzyme immunoassay. Clinical data of 58 patients with JIA treated with MTX were analyzed retrospectively. RESULTS: The 1298A/A genotype was present in 31 patients, 1298C/C in 4 patients, and 21 patients were heterozygous. The 677C/C genotype was present in 29 patients, 677 T/T in 3 patients, and 26 patients were heterozygous. In patients who presented the C allele of the A1298C polymorphism, improvement with respect to the number of swollen joints, the number of tender joints, and a decrease in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels occurred more frequently than in 1298 A/A homozygous patients (p < 0.05 for ESR, p < 0.01 for CRP, chi-square test). There was no relationship between the C677T polymorphism and the efficacy of MTX treatment. Forty-two adverse events were noted in 26 patients; gastrointestinal symptoms were most common (n = 20), followed by elevated serum levels of transaminases (n = 19) and hair loss (n = 3). There was no cytopenia. Patients with the heterozygous genotype 677C/T exhibited adverse events more frequently than patients with the homozygous C/C genotype (65% vs 31%; p < 0.05, chi-square test). The A1298C polymorphism, however, was not associated with occurrence of adverse events. Plasma homocysteine was elevated in 6 patients with up to 16.9 mmol/l. No association was found to a specific genotype or to adverse events. CONCLUSION: These preliminary data suggest an association of the MTHFR 677C/C polymorphism to a higher tolerability of MTX, and of the 1298A/A to lower clinical efficacy of MTX therapy in JIA.     

Elderly patients diagnosed with idiopathic pulmonary arterial hypertension: Results from the COMPERA registry

Background

Originally reported to occur predominantly in younger women, idiopathic pulmonary arterial hypertension (IPAH) is increasingly diagnosed in elderly patients. We aimed to describe the characteristics of such patients and their survival under clinical practice conditions.

Methods

Prospective registry in 28 centers in 6 European countries. Demographics, clinical characteristics, hemodynamics, treatment patterns and outcomes of younger (18–65 years) and elderly (> 65 years) patients with newly diagnosed IPAH (incident cases only) were compared.

Results

A total of 587 patients were eligible for analysis. The median (interquartile, [IQR]) age at diagnosis was 71 (16) years. Younger patients (n = 209; median age, 54 [16] years) showed a female-to-male ratio of 2.3:1 whereas the gender ratio in elderly patients (n = 378; median age, 75 [8] years) was almost even (1.2:1). Combinations of PAH drugs were widely used in both populations, albeit less frequently in older patients. Elderly patients were less likely to reach current treatment targets (6 min walking distance > 400 m, functional class I or II). The survival rates 1, 2, and 3 years after the diagnosis of IPAH were lower in elderly patients, even when adjusted for age- and gender-matched survival tables of the general population (p = 0.006 by log-rank analysis).

Conclusions

In countries with an aging population, IPAH is now frequently diagnosed in elderly patients. Compared to younger patients, elderly patients present with a balanced gender ratio and different clinical features, respond less well to medical therapy and have a higher age-adjusted mortality. Further characterization of these patients is required.Clinical trials registration: NCT01347216.     

Prader-Labhart-Willi syndrome in infants

We report an infant with severe hypotonia, feeding problems and failure to thrive in the neonatal period, followed by developmental delay. In addition, pale skin, eyelid and pedal edema, cryptorchidism and micrognathia were present. The tentative diagnosis of Prader-Labhart-Willi syndrome was made and confirmed by specific molecular testing at the age of 5 months.The Prader-Labhart-Willi syndrome is usually diagnosed in older infants when the main clinical features such as obesity, short stature, hypogonadism and developmental delay become obvious, in most of the patients typical clinical features are present already in the neonatal period. In conclusion, in neonates and young infants presenting with hypotonia and feeding problems, the Prader-Labhart-Willi syndrome should be considered.