Sara Tenti

May spa therapy be a valid opportunity to treat hand osteoarthritis? A review of clinical trials and mechanisms of action

Osteoarthritis (OA) is the most common form of arthritis and its current treatment includes non-pharmacological and pharmacological modalities. Spa therapy represents a popular treatment for many rheumatic diseases. The aim of this review was to summarize the currently available information on clinical effects and mechanisms of action of spa therapy in OA of the hand. We conducted a search of the literature to extract articles describing randomized clinical trials (RCTs) in hand OA published in the period 1952–2015. We identified three assessable articles reporting RCTs on spa therapy in hand OA. Data from these clinical trials support a beneficial effect of spa therapy on pain, function and quality of life in hand OA. Spa therapy seems to have a role in the treatment of hand OA. However, additional RCTs are necessary to clarify the mechanisms of action and the effects of the application of thermal treatments.

Intravenous immunoglobulins and antiphospholipid syndrome: How, when and why? A review of the literature

The antiphospholipid syndrome (APS) is defined by the occurrence of venous and arterial thromboses and recurrent fetal losses, frequently accompanied by a moderate thrombocytopenia, in the presence of antiphospholipid antibodies (aPL), namely lupus anticoagulant (LA), anticardiolipin antibodies (aCL), or anti-β2 glycoprotein-I (β2GPI) antibodies. The current mainstay of treatment for thrombotic APS is heparin followed by long-term anticoagulation, while in obstetric APS, the accepted first-line treatment consists in low-dose aspirin (LDA) plus prophylactic unfractionated or low-molecular-weight heparin (LMWH). Recently, new emerging treatment modalities, including intravenous immunoglobulins (IVIG), have been implemented to manage APS refractory to conventional therapy. The objective of this review is to summarize the currently available information on the IVIG therapy in APS, focusing on the use of IVIG in the obstetric form, CAPS and on primary or secondary thromboprophylaxis. We analyzed 35 studies, reporting the effects of IVIG in APS patients, and we discussed their results. IVIG in obstetric APS seem to be very useful in selected situations (patients not responsive to the conventional treatment, concomitant autoimmune manifestations or infections or patients in whom anticoagulation is contraindicated). IVIG treatment represents an important component of the combination therapy of CAPS and they could be useful, in addition to the standard therapy, to prevent recurrent thrombosis in APS patients refractory to conventional anticoagulant treatment. Anyway, in some cases we also found controversial results that claim the need of further well-designed studies to definitely state the efficacy and tolerability of IVIG in CAPS, obstetric and non-APS.

Granulomatosis with polyangiitis and intravenous immunoglobulins: A case series and review of the literature

Granulomatosis with polyangiitis, formerly known as Wegeners granulomatosis or disease, is a systemic, necrotizing small-vessel vasculitis, belonging to the group of anti-neutrophil cytoplasm antibody vasculitis. The therapeutic strategy includes, in most cases, corticosteroids associated, at least in severe forms of the disease, with immunosuppressive agents: cyclophosphamide and rituximab to induce remission, methotrexate, azathioprine and mycophenolate mofetil to prevent relapses. Intravenous immunoglobulins represent an alternative adjuvant therapy. We described 5 cases of patients with granulomatosis with polyangiitis treated with monthly high-dose intravenous immunoglobulins (500mg/kg/daily for 3 consecutive days for 9months). No patients experienced adverse reactions, and 4 patients (80%) achieved a complete remission after 9 courses of this therapy, which was maintained also 3months later, although we are unable to determine whether improvement in outcomes was a direct result of the IVIG. We also discussed the beneficial effects of intravenous immunoglobulins in patients suffering from granulomatosis with polyangiitis, reporting the previously published data.

Fibromyalgia syndrome and spa therapy: myth or reality?

Fibromyalgia syndrome (FS) is a common musculoskeletal disorder characterized by otherwise unexplained chronic widespread pain, a lowered pain threshold, high tender point counts, sleep disturbances, fatigue, headache, irritable bowel syndrome, morning stiffness, paraesthesias in the extremities, often psychological distress and depressed mood. Consequently, FS has a negative impact on working capacity, family life, social functioning and quality of life. Because of unknown etiology and not clearly understood pathogenesis, there is no standard therapy regime for FS. A variety of medical treatments, including antidepressants, opioids, analgesic or non-steroidal anti-inflammatory drugs, sedatives, muscle relaxants and antiepileptics, have been used to treat FS. Currently, no pharmacological treatment for FS is consistently successful. According to recent guidelines, the optimal treatment of FS requires a multidisciplinary approach with a combination of non-pharmacological and pharmacological treatment modalities. Spa therapy is a popular treatment for FS in many European countries, as well as in Japan and Israel. However, despite their long history and popularity spa treatments are still the subject of debate and their role in modern medicine is still not clear. The objective of this review is to summarize the currently available information on clinical effects and mechanism of action of spa therapy in FS. We also provide some suggestions for further development in this area.

What about strontium ranelate in osteoarthritis? Doubts and securities.

Abstract Osteoarthritis (OA) is the most common disabling joint disease worldwide and its treatment is based on a combination of non-pharmacological and pharmacological modalities. Commonly prescribed OA medications include symptomatic drugs (non-steroidal anti-inflammatory drugs, analgesics, locally administered corticosteroids, viscosupplementation) and new compounds that are potentially able to reduce or stop the disease progression, called “Disease Modifying Osteoarthritis Drugs (DMOADs)”. Strontium ranelate (SR) is an anti-osteoporotic treatment that increases bone formation, while decreasing bone resorption and it potentially acts as a new DMOAD. The objective of this review is to summarize the currently available information on clinical effects and mechanism of action of SR in OA. We have examined two post hoc analysis conducted on the large, randomized Treatment of Peripheral Osteoporosis study and the double-blind, randomized, controlled trial about SR in knee OA. Furthermore, we analyzed three studies in animal models and two in vitro experiments to better understand the mechanism of action of SR in OA. The available data demonstrate that SR could be considered a new promising symptomatic and disease-modifying agent in the treatment of OA and was safe and well tolerated. Additionally, there is a need for further investigations to establish the optimal dosage and to better clarify the mechanism of action of SR in OA.

Effect of Additional Treatments Combined with Conventional Therapies in Pregnant Patients with High-Risk Antiphospholipid Syndrome: A Multicentre Study

The effect of additional treatments combined with conventional therapy on pregnancy outcomes was examined in high-risk primary antiphospholipid syndrome (PAPS) patients to identify the most effective treatment strategy. The studys inclusion criteria were (1) positivity to lupus anticoagulant alone or associated with anticardiolipin and/or anti-β2 glycoprotein I antibodies; (2) a history of severe maternal-foetal complications (Group I) or a history of one or more pregnancies refractory to conventional therapy leading to unexplained foetal deaths not associated with severe maternal-foetal complications (Group II). Two different additional treatments were considered: oral-low-dose steroids (10-20 mg prednisone daily) and/or 200 to 400 mg daily doses of hydroxychloroquine and parenteral-intravenous immunoglobulins at 2 g/kg per month and/or plasma exchange. The studys primary outcomes were live birth rates and pregnancy complications. A total of 194 pregnant PAPS patients attending 20 tertiary centres were retrospectively enrolled. Hydroxychloroquine was found to be linked to a significantly higher live birth rate with respect to the other oral treatments in the Group II patients. The high (400 mg) versus low (200 mg) doses of hydroxychloroquine (p = 0.036) and its administration before versus during pregnancy (p = 0.021) were associated with a significantly higher live birth rate. Hydroxychloroquine therapy appeared particularly efficacious in the PAPS patients without previous thrombosis. Parenteral treatments were associated with a significantly higher live birth rate with respect to the oral ones (p = 0.037), particularly in the Group I patients. In conclusion, some additional treatments were found to be safe and efficacious in high-risk PAPS pregnant women.

Could Oxidative Stress Regulate the Expression of MicroRNA-146a and MicroRNA-34a in Human Osteoarthritic Chondrocyte Cultures?

Oxidative stress and the overproduction of reactive oxygen species (ROS) play an important role in the pathogenesis of osteoarthritis (OA). Accumulating evidence has demonstrated the involvement of microRNAs (miRNAs) dysregulation in disease development and progression. In this study, we evaluated the effect of oxidative stress on miR-146a and miR-34a expression levels in human OA chondrocytes cultures stimulated by H2O2. Mitochondrial ROS production and cell apoptosis were detected by flow cytometry. The antioxidant enzymes SOD-2, CAT, GPx, the transcriptional factor NRF2 and the selected miRNAs were analyzed by qRT-PCR. The H2O2-induced oxidative stress was confirmed by a significant increase in superoxide anion production and of the apoptotic ratio. Furthermore, H2O2 significantly up-regulated the expression levels of SOD-2, CAT, GPx and NRF2, and modulated miR-146a and miR-34a gene expression. The same analyses were carried out after pre-treatment with taurine, a known antioxidant substance, which, in our experience, counteracted the H2O2-induced effect. In conclusion, the induction of oxidative stress affected cell apoptosis and the expression of the enzymes involved in the oxidant/antioxidant balance. Moreover, we demonstrated for the first time the modification of miR-146a and miR-34a in OA chondrocytes subjected to H2O2 stimulus and we confirmed the antioxidant effect of taurine.

Intravenous Immunoglobulins as a new opportunity to treat discoid lupus erythematosus: A case report and review of the literature

Discoid lupus erythematosus (DLE) is a chronic dermatological disease that can lead to scarring, alopecia and dyspigmentation, if not properly treated. Actually, no drugs are specifically approved for the treatment of CLE, although the first-line therapy usually consists of photoprotection associated to topical or oral steroids, topical calcineurin inhibitors and hydroxychloroquine (HCQ). In cases of DLE refractory to these medications, many other agents have been employed, such as dapsone, methotrexate, azathioprine, cyclophosphamide, biologic drugs and Intravenous Immunoglobulin (IVIG). We described the case of a DLE patient resistant to combination therapy with steroid and HCQ who was successfully treated with cyclical IVIG therapy. The treatment with IVIG resulted rapidly effective with persistent efficacy and low rates of relapses, although more cycles of IVIG are needed to achieve a stable clinical remission. We also discussed the beneficial and promising effects of IVIG in patients with Cutaneous Lupus reporting the previously published data.

The Emerging Role of Bradykinin in the Pathogenesis of Osteoarthritis and its Possible Clinical Implications

Osteoarthritis (OA) is a multifaceted disorder defined by the alteration of homeostasis and degradation in articular cartilage. Recently mounting evidence suggests that OA should be conceived as an inflammatory disease rather than a simple wear-and-tear problem. Bradykinin (BK) and B2 receptors play a role in the pathogenesis of OA. The aim of this paper is to analyze preclinical and clinical studies examining the potential role of BK and of B2 receptor blockade in OA pathogenesis. We analyzed the data about the effects of BK in synoviocytes, endothelial cells and chondrocytes cultures and described the action of B2 receptor antagonists (Icatibant and Fasitibant). In conclusion, the BK is an endogenous proinflammatory molecule that is involved in the pathophysiology of OA, and B2 receptor antagonists are believed to be considered as a potential symptomatic therapy for this disease. There is a need for further preclinical and clinical trials to better explain the mechanisms of action and the efficacy and tolerability of the B2 receptor antagonists in OA.

Phytothermotherapy in osteoarthritis: new evidence for an old therapy

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