Summary Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey.

Chronic recurrent multifocal osteomyelitis (CRMO) is a clinical entity which occurs mainly in children and adolescents with recurrent episodes of pain occurring over several years. Cause and physiopathology of disease is still uncertain. We aim to assess clinical characteristics and treatment options, need and response to anti-inflammatory therapies in children diagnosed chronic recurrent multifocal osteomyelitis Demographic data and clinical features of seventeen children diagnosed with CRMO in 2 pediatric rheumatology centers in Turkey were reviewed retrospectively. The diagnosis was based on clinical findings, radiological images and histopathological and microbiological studies. A total of 17 patients were included in the study. The median age of diagnosis was 9.6±4.2 years. The mean follow-up time was 31.6 months (range 6-35 months). Most patients (n: 10) had a recurrent multifocal disease course (>6 months), 6 patients had a persistent course and a patient had only one episode of CRMO. MEFV gene mutations were detected in 4 patients whose clinical features reduced with colchicine therapy. All patients had received nonsteroidal anti-inflammatory drugs but only one had complete response. Thirteen children with NSAID failure subsequently received corticosteroids, sulfasalazine, methotrexate, Anti TNF α drugs, or a combination of these drugs. This study is the largest cohort of pediatric CRMO patients in our country. Clinical evolution and imaging investigations should be closely done to avoid delays in diagnosis. Ethnic differences create changes in the presentation of the disease and response to treatment

Biologic therapies, such as tumor necrosis factor-alpha (TNF-α) blockers, are commonly used to treat rheumatological diseases in childhood. Screening patients for tuberculosis (TB) is highly recommended before starting therapy with TNF-α blockers. Despite appropriate screening, TB still remains a problem in patients receiving anti-TNF therapy in countries where TB is not endemic. TB in anti-TNF-treated patients is often diagnosed late due to altered presentation, and this delay results in high morbidity and mortality with a high proportion of extrapulmonary and disseminated disease. The aim of this study is to show the course of TB disease in children who are on biologic therapy, in an era where many of the children are BCG-vaccinated and TB is intermediately endemic. We recruited 71 patients with several types of inflammatory diseases. Six of them had a positive test result during TB screening and began taking isoniazid (INH) prophylactically. During the 3 years of follow-up, none of these patients developed TB disease. Biologic agents can be safely used in a BCG-vaccinated pediatric population, as long as patients are closely monitored to ensure that any cases of TB will be detected early.

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An increased incidence of cardiovascular disease has been found in rheumatic disorders. Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. Prolonged immunological inflammatory process leads these patients to an early onset of atherosclerosis. We aimed to assess the presence of early vascular dysfunction in patients with systemic onset juvenile idiopathic arthritis (sJIA) and investigate the role of therapy sJIA in vascular health. Thirty-three patients (22 males, 11 females) diagnosed with sJIA according to the International League of Associations for Rheumatology criteria were compared to 72 age- and sex-matched controls. None of the participants was overweight, obese, or had a history of hypertension, dyslipidemia, diabetes mellitus, or cardiovascular disease. Arterial stiffness (As) was evaluated by measurement of carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx) with a Vicorder. The mean age of patients in this study was 9.96 ± 3.71 years (range 4-16 years) and the mean age of controls was 10.9 ± 3.52 years (range 4-19 years). These two groups were well matched for age, sex, and BMI. The mean age of patients at the onset of disease was 7.06 ± 3.9 years (range 3-15 years). The mean duration of disease and active disease was 79 ± 45 months (range 6-162 months) and 58 ± 49 months (range 1-101 months), respectively. The highest levels of PWV and AIx were found in the patient group. Seven patients had had macrophage activation syndrome at presentation. In these patients, vascular changes were higher than other patients (6.30 ± 0.42 m/s vs 5.17 ± 0.55 m/s, p = 0.01, respectively). The corticosteroid therapy was found associated with higher PWV, (p < 0.05), while there was no difference between vascular parameters and use of non-steroid therapies (methotrexate (MTX), anti-TNF alfa agents). We also find statistically significant correlation between PWV and disease duration (p = 0.003, r = 0.45). Vascular function is impaired in patients with sJIA at a very young age. Vascular dysfunction may be partly attributed to the effects of disease-related characteristics (inflammation, disease activity, and medications).