RESUMEN
Felty's syndrome was first described in 1924 by the US-American physician Augustus Roi Felty as a triad of rheumatoid arthritis, splenomegaly and leucopenia. Even nearly 100 years later, this rare syndrome is still paralleled by diagnostic and therapeutic challenges and its pathogenesis is incompletely understood. Neutropenia with potentially life-threatening infections is the main problem and several pathomechanisms like Fas-mediated apoptosis, anti-neutrophil antibodies, anti-G-CSF antibodies, neutrophil consumption in the context of NETosis and suppression of granulopoiesis by T-LGLs have been suggested. Felty's syndrome has various differential diagnoses as splenomegaly and cytopenia are common features of different infectious diseases, malignancies and autoimmune disorders. Additionally, benign clonal T-/NK-LGL lymphocytosis is increasingly noticed in Felty's syndrome, which further complicates diagnosis. Today's treatment options are still sparse and are largely based on case reports and small case series. Methotrexate is the mainstay of therapy, followed by rituximab, but there is less evidence for alternatives in the case of adverse reactions or failure of these drugs. This article gives an updated review about Felty's syndrome including its pathogenesis and treatment options.
RESUMEN
Childhood obesity is an increasing health care problem associated with insulin resistance and low-level systemic inflammation, which can ultimately lead to diabetes. Evidence for efficacy of therapeutic intervention programs on the early development of obesity associated sequelae is moderate. This paper investigates the effect of a multidisciplinary short-term intervention program on insulin resistance and metaflammation in childhood obesity. Two hundred and 36 overweight or obese children and adolescents between the ages of 10 and 14 were included in a prospective 5 months intervention study, which included sports, psychotherapy, and nutritional counseling. Primary endpoints were the effects on body mass index standard deviation score (BMI-SDS) and homeostatic model assessment of insulin resistance (HOMA-IR), key secondary endpoints were the levels of C-reactive protein (CRP), leptin, and adiponectin. At baseline, a substantial proportion of participants showed signs of insulin resistance (mean HOMA-IR 5.5 ± 3.4) despite not meeting the diagnostic criteria for diabetes, and low-level inflammation (mean CRP 3.9 mg/l ± 3.8 mg/l). One hundred and 95 participants (83%) completed the program resulting in a significant reduction in BMI-SDS, HOMA-IR, CRP, and leptin and a significant increase in adiponectin (mean change compared to baseline -0.14, -0.85, -1.0 mg/l, -2.8 ng/ml, and 0.5 µg/ml, respectively; p < 0.001 each). Effects on BMI-SDS, HOMA-IR, CRP, and adiponectin were largely independent whereas leptin was positively correlated with BMI-SDS and total fat mass before and after intervention (r = 0.56 and 0.61, p < 0.001 each). Short-term multidisciplinary intervention successfully improved body composition, insulin sensitivity, low-level systemic inflammation, and the adipokine profile in childhood obesity. Our findings highlight the immediate connection between obesity and the pathophysiology of its sequelae, and emphasize the importance of early intervention. Continued lifestyle modification is likely necessary to consolidate and augment the long-term effects.
