To review the official international recommendations on the management of latent tuberculosis infection (LTBI) in patients with rheumatic diseases undergoing biologic therapy.
A systematic search of ...all clinical practice recommendations on the diagnosis and treatment of LTBI in rheumatic patients eligible for starting biologic drugs published between January 2002 and March 2013.
For the diagnosis of LTBI, based on positivity of tuberculin skin test (TST), interferon-γ release assay (IGRA) is also available. Most recommendations advise using both TST and IGRA, especially in case of Bacillus Calmette-Guérin vaccination, to screen patients before commencing biologic drugs. There is a general consensus that evaluation of the global risk of TB infection is a crucial point and that patients with LTBI must receive chemoprophylaxis prior to biologic therapy. However, recommendations on the need for rescreening for activation of LTBI or new TB infection while patients are being treated are inadequate. Nevertheless, the main concern is poor compliance with TB recommendations of rheumatologists in clinical practice, which seems to be the main cause of the occurrence of active TB in rheumatic patients receiving biologic therapy.
Notwithstanding some differences, mainly related to regional TB incidence, international recommendations strongly suggest careful screening for LTBI before starting biologic therapy. However, the critical point is implementing dissemination and awareness of the recommendations among rheumatologists to improve adherence in real life.
Obesity is one of the main risk factors for osteoarthritis (OA). For many years the association of obesity and OA has been simply attributed to the effects of overload on weight-bearing joints, and ...epidemiological surveys have shown a strict correlation between an increased body mass index and the severity of knee or hip OA, as well as some relief of pain and disability following weight loss. Instead, there is now a growing body of evidence that obesity is a complex syndrome in which an abnormal activation of neuroendocrine and pro-inflammatory pathways leads to an altered control of food intake, fat expansion and metabolic changes. Activated white adipose tissue increases the synthesis of pro-inflammatory cytokines, such as IL-6, IL-1, IL-8, TNFalpha, IL-18, while regulatory cytokines, such as IL-10, are decreased. Adipocytes also produce peculiar cytokines, namely adipokines, that exert multiple effects, being capable of promoting synovial inflammation, cartilage degrading enzymes, and bone matrix remodeling. Furthermore, pro-inflammatory cytokines stimulate adipocytes to synthesize neuropeptides, such as substance P and nerve growth factor, that have been shown to be critical in regulating both the appetite and cartilage homeostasis. In this scenario, where the influence of obesity on OA stems from a complex interaction of genetic, metabolic, neuroendocrine, and biomechanical factors, there may be various different potential targets for OA therapy.
Scleroderma renal crisis (SRC) occurs in 5–10% of SSc patients, who may present with an abrupt onset of hypertension, acute renal failure, headaches, fevers, malaise, hypertensive retinopathy, ...encephalopathy and pulmonary oedema. Patients at greatest risk of developing SRC are those with diffuse cutaneous or rapidly progressive forms of SSc, and treatment with a recently commenced high dose of corticosteroid. Laboratory tests may demonstrate hypercreatinaemia, microangiopathic haemolytic anaemia (MAHA), thrombocytopaenia and hyperreninaemia. Renal crisis is also linked to a positive ANA speckled pattern, antibodies to RNA polymerase I and II, and an absence of anti-centromere antibodies. Early, aggressive treatment with angiotensin-converting enzyme inhibitors has improved prognosis in SRC, although 40% of the patients may require dialysis, and mortality at 5 yrs is 30–40%. Median time to recovery is 1 yr, and typically occurs within 3 yrs. Prognosis is worse for males, but may not be related to corticosteroid use, presence of MAHA or severity of renal pathology. Modification of endothelin over-activity, which is implicated in the pathogenesis of SRC, may offer a future therapeutic approach.
To assess the long-term effectiveness and safety of tocilizumab, abatacept, and tumor necrosis factor-α inhibitors (TNFi), in the Italian real-world setting of rheumatoid arthritis (RA). The records ...of adult RA patients from the Italian biologics’ registry Gruppo Italiano Studio Early Arthritis (GISEA) were analyzed. Demographic and clinical data were obtained at entry. The disease remission rate (28-joint disease activity score calculated using the erythrocyte sedimentation rate DAS28-ESR ≤ 2.6) and frequency of adverse events (AEs) were evaluated at 2 years. From 1999 to 2014, 7539 patients were treated with biologics (61.3% in first- and 22.6% in second-line), 68% of cases received TNFi, 9.1% tocilizumab, and 8.6% abatacept. Treatment groups showed a similar DAS28 at entry. As first-line, tocilizumab induced a significantly higher remission rate than abatacept or TNFi at 6 (51 vs 23.3 and 26.2%, respectively;
p
< 0.0001) and 24 months (52.3 vs 33.3 and 34.4%, respectively;
p
< 0.01). A similar pattern was observed in later lines. The most common AEs reported were infections, reactions to biologics (more frequent among TNFi-treated patients), increased transaminase (more frequent among TCZ-treated patients), and cardiovascular events. In clinical practice, TCZ induced a rapid and long-lasting remission and in a higher percentage of patients compared to abatacept and TNFi, with a good safety profile.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Non-tuberculous mycobacteria (NTM) are generally free-living organism, widely distributed in the environment, with sporadic potential to infect. In recent years, there has been a ...significant increase in the global incidence of NTM-related disease, spanning across all continents and an increased mortality after the diagnosis has been reported. The decisions on whether to treat or not and which drugs to use are complex and require a multidisciplinary approach as well as patients’ involvement in the decision process.
Methods and Results
This review aims at describing the drugs used for treating NTM-associated diseases emphasizing the efficacy, tolerability, optimization strategies as well as possible drugs that might be used in case of intolerance or resistance. We also reviewed data on newer compounds highlighting the lack of randomised clinical trials for many drugs but also encouraging preliminary data for others. We also focused on non-pharmacological interventions that need to be adopted during care of individuals with NTM-associated diseases
Conclusions
Despite insufficient efficacy and poor tolerability this review emphasizes the improvement in patients’ care and the needs for future studies in the field of anti-NTM treatments.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objectives: Iloprost plays an important role in the treatment of Raynaud's phenomenon (RP), but has transient vasodilatory effects owing to its very short half-time. We aimed to evaluate short- and ...medium-term haemodynamic effects of iloprost by measuring dorsal finger microvessel blood flow using laser Doppler flowmetry (LDF), in patients with RP associated with systemic sclerosis (SSc).
Method: In 24 consecutive SSc patients with RP (disease duration 10.5 ± 1.3 years), LDF with heating probes was used to measure blood flow in four fingers by occlusive and heating tests, at baseline, after 3 consecutive days of iloprost infusion, and at 24 h and 7 days after last iloprost infusion. Nailfold videocapillaroscopy (NVC) patterns of microvascular damage were investigated. Sixteen healthy controls were studied to compare baseline flows.
Results: Compared to controls, SSc patients showed significantly impaired axon reflex vasoregulation and nitric oxide responses at baseline (p = 0.001 and p = 0.03, respectively). After iloprost, a prompt but transient significant improvement in endothelial-dependent vasodilation (occlusive test) was seen only in SSc patients with an 'active' NVC pattern (p ≤ 0.05). The iloprost effects vanished within 7 days after the last infusion. No significant differences were found, in the whole study, between patients with and without digital ulcers.
Conclusions: Microcirculatory blood flow increases following 3 days of iloprost infusion but fades shortly after treatment. Although iloprost is effective in reducing the severity of RP in SSc, the most suitable regimen and timing to obtain longer lasting vasodilatory benefits remain to be established.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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