On- and off-label use of rituximab in rheumatic diseases

Steadily growing knowledge about pathogenetic mechanisms in autoimmune rheumatic diseases (RDs) has paved the way to different therapeutic approaches. In particular, the availability of biologics on the market has dramatically modified the natural history of rheumatic chronic inflammatory diseases with a meaningful impact on patients’ quality of life. Among the wide spectrum of available biological treatments, rituximab (RTX), initially used in the treatment of non- Hodgkin’s lymphoma, was later approved for rheumatoid arthritis and anti-neutrophil cytoplasmic antibodies-associated vasculitis. Currently, in rheumatology, RTX is also used with off-label indications in patients with systemic sclerosis, Sjögren’s syndrome and systemic lupus erythematosus. RTX is a monoclonal antibody targeted to CD20 molecules expressed on the surface of pre-B and mature B lymphocytes. It acts by causing apoptosis of these cells with antibody- and complement-dependent cytotoxicity. As inflammatory responses to cell-associated immune complexes are key elements in the pathogenesis of several autoimmune RDs, such an approach might be effective in these patients. In fact, RTX promotes a rapid and long-term depletion of circulating and lymphoid tissue-associated B cells, thus leading to a lower recruitment of these effector cells at sites of immune complex deposition, therefore reducing inflammation and tissue damage. RTX is extremely interesting for rheumatologists, as it represents an important additional therapeutic approach. Therefore, the advent in clinical practice of approved RTX biosimilars, such as CT-P10, may help in improving treatment access as well as reducing cost

Epstein-Barr Virus Reactivation after Infliximab in Rheumatoid Arthritis: A Case Report

TNF-alpha blockers represent one of the most important therapeutic strategies for rheumatoid arthritis, but their use has raised the question about their safety profile, particularly in respect to viral infections/reactivations. We describe the case of a patient who developed a symptomatic EBV reactivation 11 days after the first infusion of infliximab

EULAR guidelines on ANCA-associated vasculitis in the real life

Anti-neutrophil cytoplasmic antibodies-associated vasculitides (AAVs) are a heterogenous group of inflammatory diseases which primarily involve small vessels and include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). They present heterogeneous clinical manifestations, while their diagnosis and management still remain a challenge for clinicians. Nowadays, the treatment is based on two different regimens: the remission-induction treatment and the remission-maintenance treatment. The therapeutic armamentarium has grown over the years, with the aim to lessen adverse effects, improve quality of life of patients and maintain the disease under control. Biological treatments are the future: they act on different pathogenic pathways and may offer in the future a personalized management approach tailored to actual clinical manifestations. The latest guidelines were published in 2015 by the European League Against Rheumatism (EULAR) and still represent the vade mecum for the management of AAVs. In this review, we will focus on the principal strategies to treatAAVs. We discuss the remission-induction therapy and the remission-maintenance therapy; we have also distinguished the management of GPA and MPA from that of EGPA, because of their different clinical picture

The management of large vessel vasculitides

Giant cell arteritis (GCA) and Takayasu arteritis (TAK) represent the most common large vessel vasculitides (LVV). An early recognition of these conditions is crucial in order to start a prompt treatment to prevent severe ischemic complications, such as irreversible visual loss in GCA and cardiovascular or cerebrovascular accidents in TAK. Isolated glucocorticoids (GCs) still remain the cornerstone of GCA therapy. However, long-term treatment with GCs is burdened by an important toxicity. Furthermore, relapses are frequent during the follow-up period and relapsing patients have to cope with a longer duration of the GC therapy and a higher cumulative GC dose. On the other hand, TAK treatment usually relies on immunosuppressors in addition to GCs from the beginning. Also, since TAK patients are in general young women with a progressive disease, it is essential to treat this vasculitis with steroidsparing drugs in order to avoid excessive GC exposure. For this reason, efforts have been made to discover new therapeutic options able to reduce the cumulative GC dose that is strictly related to GC-toxicity. In recent years, new advances in the management of LVV have become available and have changed the therapeutic approach to these diseases. The aim of this review is to report new evidence of treatment efficacy and safety in LVV

Buerger's disease or thromboangiitis obliterans: description of two cases

Buerger's disease, or thromboangiitis obliterans (TAO), is a segmental non-atherosclerotic occlusive inflammatory condition of small arteries and veins of the upper and lower extremities, characterized by thrombosis and recanalization of the affected vessels. It is triggered by substantial exposure to tobacco, especially in males aged from 20 to 50. Currently, the most effective treatment, together with the suspension of the smoking habit, is represented by prostacyclin infusion (Iloprost). We described two cases of Buerger's disease recently presented to our observation, with some different clinical features and therapeutic pathways

Non-Hodgkin Lymphoma in Psoriatic Arthritis Treated with Sequential, Multiple Anti-TNF-α Agents: A Case Report

Data obtained by large observational studies and meta-analysis indicate the absence of an increased risk of lymphoma related to therapy with anti-TNF-α, but there is limited information in literature about the safety of sequential, multiple biological agents therapy for a time longer than three years. We hereby present a case of psoriatic arthritis developing non-Hodgkin lymphoma after a six-year history of poorly effective therapy with different anti-TNF-α

Sanitary costs of osteoarthritis

Muscoloskeletal disorders are the first cause of disability and the second cause of permanent disablement in Italy. Osteoarthritis is the most frequent rheumatic disease and affects about 4 million Italians. In spite of that, data concerning social costs are lacking. On account of this lack we measured sanitary costs of 314 patients suffering from osteoarthritis. A retrospective, prevalence-based multicentric study was performed using a bottom-up approach. The study period was 12 months and referred to 1999. Eight percent of patients didn't take any drug for the treatment of osteoarthritis; NSAIDs were prescribed to 86.9% of patients, analgesics to 29.9%, chondroprotective drugs to 7.6%, and gastroprotective drugs to 36.9%. Total sanitary costs came to 455 euro / patient / year: 122 euro were spent on diagnostics, 293 euro on therapy and 40 euro on management of drug-related gastropathy. Since the costs of anti-inflammatory drugs came to 30 euro we calculated iatrogenic cost factor of 2.3. Moreover, the study supplied interesting informations about prescriptive habits, which differ in Italy from international guidelines for the medical treatment of OA, about patient management, because of hospitalization, which by itself absorbs 1/3 of resources, and about physiotherapy, which costs twice as much as pharmacological therapy. At last, data analysis gave the cue for suggestions on changing patients' managemen

Early Occupational Therapy Intervention: Patients’ Occupational Needs

The occupational therapy management involves the assessment of the individual’s specific needs. This kind of assessment facilitates the therapeutic relationship and boosts the person’s motivation, as he or she feels valued and heard. Early-stage collection of information about meaningful activities for the individual helps them project themselves outside the context of illness. Collecting occupational need at an early stage, permits “Engagement”, which means participating in activities even without actually doing them. An occupational therapy model called “Personal Environment Occupation Model” suggests that already at an early stage we should make the environment and occupations meaningful to the person in order to maximise the patient’s performance. An observational study on stroke patients shows how people have personal occupational needs beyond simple self-care, including productive life and leisure time, already in the subacute phase. A further study is underway to demonstrate the effectiveness of early occupational therapy intervention, including complex patients regardless of diagnosis and taking into account their need for care and disability in order to promote their participation and maximise their autonomy

Endothelial Dysfunction in Acute Hepatic Porphyrias

Background Acute hepatic porphyrias (AHPs) are a group of rare diseases caused by dysfunctions in the pathway of heme biosynthesis. Although acute neurovisceral attacks are the most dramatic manifestations, patients are at risk of developing long-term complications, several of which are of a vascular nature. The accumulation of non-porphyrin heme precursors is deemed to cause most clinical symptoms. AimWe measured the serum levels of endothelin-1 (ET-1) and nitric oxide (NO) to assess the presence of endothelial dysfunction (ED) in patients with AHPs. Forty-six patients were classified, according to their clinical phenotype, as symptomatic (AP-SP), asymptomatic with biochemical alterations (AP-BA), and asymptomatic without biochemical alterations (AP-AC). Results Even excluding those under hemin treatment, AP-SP patients had the lowest NO and highest ET-1 levels, whereas no significant differences were found between AP-BA and AP-AC patients. AP-SP patients had significantly more often abnormal levels of ED markers. Patients with the highest heme precursor urinary levels had the greatest alterations in ED markers, although no significant correlation was detected. Conclusions ED is more closely related to the clinical phenotype of AHPs than to their classical biochemical alterations. Some still undefined disease modifiers may possibly determine the clinical picture of AHPs through an effect on endothelial functions