Carlo Palazzi

Hepatitis C virus and arthritis

Arthritis is one of the several autoimmune disorders induced by HCV infection. There is not a specific clinical pattern of HCV-related arthritis, but two nonerosive subsets have more frequently been described: a RA-like polyarthritis and a less common mono-oligoarthritis involving medium-sized and large joints, often showing an intermittent course. This latter form is associated with the presence of serum cryoglobulins. Because of its variable characteristics, HCV-related arthritis must be considered in the differential diagnosis of many patients having inflammatory joint involvement. Antikeratin antibodies and possibly IgA RF can be useful in distinguishing between RA and HCV-related RA-like polyarthritis. In fact, these tests are highly specific in RA patients. In any case, the search for HCV antibodies should be more widely performed in the diagnostic approach to rheumatic diseases. An association between PsA and HCV infection has been described in the literature, but the authors were unable to confirm these data. Nonsteroidal anti-inflammatory drugs, hydroxychloroquine, and low doses of corticosteroids are the cornerstones of the treatment of HCV-related arthritis. An etiologic therapy with alpha-interferon and ribavirin is useful when required by hepatic or systemic involvement; such therapy could also be considered in selected cases of isolated arthritis that are unresponsive to other drugs. Few case reports described the onset of polyarthritis after the administration of alpha-interferon for HCV-related chronic hepatitis. This topic should be more accurately studied in the future to exclude a spurious association between the two events.

Pharmacological management of SAPHO syndrome

The SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome (SaS) includes different skeletal manifestations such as recurrent multifocal osteomyelitis, osteitis and arthritis, which are frequently associated with different forms of skin pustulosis (palmoplantar pustulosis, pustular psoriasis and severe acne). This syndrome is strictly related to the spondyloarthopathies (particularly to psoriatic arthritis) and many SaS cases fulfil the classification criteria for the spondyloarthopathies. Because SaS is an uncommon disease, current knowledge regarding its therapy is based on limited experiences gained by treating mainly small groups of patients. As a consequence, its treatment is still empiric. Several drugs (including NSAIDs, corticosteroids, sulfasalazine, methotrexate, ciclosporin, leflunomide, calcitonin and so on) have been administered and obtained conflicting results. The use of antibiotics, due to the isolation of Propionibacterium acnes from the bone biopsies of several subjects with SaS, has not represented a turning point in therapy, although some patients are responsive to this treatment. Initial reports concerning the administration of bisphosphonates (pamidronate and zoledronic acid) and of an anti-TNF-α agent (infliximab) are very promising for the future. In any case, larger, multi-centre, controlled, double-blind studies are required to emerge from the present pioneering phase.

Management issues with elderly-onset rheumatoid arthritis: an update.

Elderly-onset rheumatoid arthritis (EORA) is defined as rheumatoid arthritis (RA) starting at >60 years of age. EORA is characterised by a lower female/male ratio compared with RA in younger patients and it more frequently has an acute onset accompanied by constitutional symptoms. Two incompletely overlapping subsets of RA have been recognised: one exhibits the classical RA clinical picture while the other has a polymyalgia rheumatica-like appearance, characterised by shoulder involvement, absence of rheumatoid factor and, usually, by a nonerosive course. Identification of anti-cyclic citrullinated peptide antibodies is useful for distinguishing the latter subset from true polymyalgia rheumatica. Elderly-onset spondyloarthritis, crystal-related arthritis, remitting seronegative symmetrical synovitis with pitting oedema syndrome and hepatitis C virus-related arthritis must also be considered in the differential diagnosis. EORA treatment requires prudence because of the increase in age-related risks pertaining principally to the renal, cardiovascular and gastrointestinal systems. No groups of molecules usually employed for RA therapy in younger subjects (analgesics, NSAIDs, corticosteroids, disease-modifying antirheumatic drugs, anticytokine drugs) can be excluded a priori from the treatment of EORA patients. Nevertheless, the risk/benefit ratio relating to their use must be accurately evaluated for every single patient. Recently marketed compounds such as leflunomide and tumour necrosis factor-α antagonists have also increased the therapeutic opportunities for aged RA patients.

Aortitis and periaortitis in ankylosing spondylitis

Aortic involvement is a potential life-threatening complication of ankylosing spondylitis, usually occurring late in the course of this frequent disease. Inflammatory lesions evolving to fibrosis are primarily localized in the aortic root causing regurgitation, but this process can extend into the left atrium (subaortic bump) involving the mitral valve and the heart conduction system. First, second and third degree atrioventricular blocks are the most common conduction alterations described and they can be temporary. Chronic periaortitis has been described in ankylosing spondylitis patients. This disease is characterized by inflammation evolving to fibrosis and it is localized in the periaortic and peri-iliac retroperitoneum. It causes compressive effects on ureters and venous, arterial and lymphatic vessels. Its treatment employs endoscopic and/or surgical procedures and administration of corticosteroids, even in association with immunosuppressive agents. Both aortitis (with conduction system alterations) and periaortitis should be kept in mind by the physicians because they can significantly influence the prognosis of ankylosing spondylitis patients and they can need a rapid treatment.

Hepatitis C virus-related arthritis

Although asymptomatic joint involvement and arthralgias are frequent in patients with hepatitis C virus chronic infection (HCV), a true arthritis affects only up to 4% of the subjects. HCV-related arthritis (HCVrA) is usually distinguished in two clinical subsets: a more frequent symmetrical polyarthritis (SP), similar to rheumatoid arthritis but much less serious, and an intermittent mono-oligoarthritis (IMO) that involves medium and large sized joints, mainly the ankle. This latter subset is strictly related to the presence of HCV-induced mixed cryoglobulinemia and its cutaneous manifestations, in particular purpura. According to recent reports, anti-CCP antibodies are considered very useful in differentiating the SP subset from rheumatoid arthritis. The treatment of HCVrA is still largely empirical because few studies have analyzed this topic. However, COXIBs, NSAIDs, low doses of corticosteroids, hydroxychloroquine and less frequently methotrexate and penicillamine have been used with partial or complete control of symptoms. On the basis of recent studies, the administration of cyclosporine also seems to be sufficiently safe. The scarcely aggressive nature of HCVrA does not favour the use of anti-TNF agents. Specific anti-viral therapy (interferon-alpha+ribavirin) must be accurately evaluated because interferon-alpha can induce the development or the worsening of several autoimmune HCV-related disorders including arthritis.

Beyond Early Diagnosis: Occult Psoriatic Arthritis

Psoriatic arthritis (PsA) is a heterogeneous disease involving the skin and nails and different musculoskeletal structures including synovial joints, entheses, synovial sheaths of tendons, and the axial skeleton1. Therefore, its clinical spectrum is broad and each clinical rheumatological manifestation can occur for a long time in isolation2. PsA should be diagnosed early because the major goals of management, reduction of pain, improvement of function, and inhibition of joint damage, can best be achieved by early intervention3–6. For identification of PsA, in either rheumatological or dermatological settings, it seems obvious that the patient must have symptoms and signs of musculoskeletal involvement. A recent study from Germany that analyzed 2009 patients with psoriasis from 13 dermatological hospitals and 129 dermatological private practices showed that in developed countries there is still a significant number of undiagnosed persons with PsA7. However, many dermatologists have time restrictions that make it impossible to routinely search for musculoskeletal symptoms. Screening tools to be filled in by the patient in the waiting room or at home have been suggested for identification of these inflammatory manifestations8–11. Since the 1970s, it has been recognized that each inflammatory lesion (joint synovitis, tenosynovitis, dactylitis, enthesitis, sacroiliitis, and spondylitis) can develop without symptoms or signs that are recognizable by the patient and the physician. Such patients can be considered to have subclinical or “occult” PsA. Their identification represents a further challenge for rheumatology. The prevalence of psoriasis in the general population has been estimated to be between 2% and 3%. The estimated prevalence of manifest PsA among patients with psoriasis has varied widely from 6% to 42%. Studies from Sweden and Italy suggest that evident PsA occurs in about one-third of patients with psoriasis12,13. If … Address correspondence to Dr. I. Olivieri, Rheumatology Department of Lucania, Ospedale San Carlo, Contrada Macchia Romana, 85100 Potenza, Italy. E-mail: ignazioolivieri{at}tiscalinet.it

Emerging drugs for psoriatic arthritis

ABSTRACT Introduction: The majority of Psoriatic Arthritis patients experience a good clinical response to anti-Tumor Necrosis Factor (TNF)-α therapies. However, treatment failure with anti-TNF-α can represent a relevant clinical problem. Areas covered: We review the efficacy and safety profile of biological therapies that have been reported from randomized, controlled trials in phase II and phase III available in Pubmed Database for agents targeting IL-12/23p40 antibody (ustekinumab) and IL-17 (secukinumab), inhibitor of phosphodiesterase 4, (apremilast), and of JAK/STAT pathways (tofacitinib) and CTLA4 co-stimulation (abatacept) in Psoriatic Arthritis. Expert opinion: In Psoriatic Arthritis, main emerging drugs are represented by the fully human monoclonal IL-12/23p40 antibody, ustekinumab, the agent targeting IL-17, secukinumab, and the inhibitor of phosphodiesterase 4, apremilast. Results on T cell co-stimulation inhibition by abatacept are insufficient both in psoriasis and in PsA. In vitro investigations on JAK/STAT pathways in PsA suggest that tofacitinib could represent a further valuable therapeutic option. Emerging biological treatments other than anti-TNF agents, ustekinumab, secukinumab and apremilast appear promising for Psoriatic Arthritis and recent studies have showed a good efficacy and an acceptable safety profile; however, further and long-term studies are advocated.Importance of the field: The socioeconomic burden of psoriatic arthritis (PsA) is considerable and not different from that of rheumatoid arthritis. Current treatment options do not always allow reaching the therapeutic objectives consisting of the remission of symptoms and prevention of the appearance of damage in the early stage of PsA or the blocking of PsA progression in the established cases.Areas covered in this review: After reviewing the current treatment choices, we examine the new drugs in clinical Phase II and III trials for PsA up to January 2010. Information was mainly obtained from the network of international clinical trial registries.What the reader will gain: The current management of PsA includes NSAIDs, corticosteroids, disease-modifying antirheumatic drugs (DMARDs) and anti-TNF-α blocking agents. These last drugs are more effective than traditional DMARDs on symptoms/signs of inflammation, quality of life and function and can inhibit the progression of the structural joint damage. Recen...

Can we reduce the dosage of biologics in spondyloarthritis

TNF blockers have revolutionized the management of spondyloarthritis (SpA). To date, four anti-TNFα agents (etanercept, infliximab, adalimumab, golimumab) have been approved for the management of ankylosing spondylitis (AS) and psoriatic arthritis (PsA). The first objective in the management of AS and PsA with TNF inhibitors is to reduce disease activity to clinical remission or low disease activity. After remission has been achieved, this state should be maintained as long as possible. However, the financial burden associated with the cost of anti-TNF agents as well as concerns about their long-term safety suggest reducing the dosage of the drug or discontinuing the therapy in the hopes of drug-free remission. The aim of this review is to examine what has, till now, been published on this topic in axial SpA, which includes AS and non-radiographic axial SpA (nr-axSpA), peripheral SpA and PsA. Discontinuation of therapy in axial SpA is not possible in the majority of patients, while on the contrary, reducing the dosage often is. In some patients with peripheral SpA and PsA it is also possible to discontinue therapy and to achieve drug-free remission.

Treatment strategies for early psoriatic arthritis

Background: Until a few years ago, the early diagnosis of psoriatic arthritis (PsA) did not receive much attention, especially in view of the lack of drugs capable of altering the disease course. This changed with the introduction of the TNF-α-blocking agents, as a result of which the early diagnosis of PsA is now a topic of great interest. Objective: The aim of the study was to review the treatment for PsA in order to determine the optimal approach to managing early disease. Methods: The systematic review performed by members of GRAPPA (Group of Research and Assessment of Psoriasis and Psoriatic Arthritis) was integrated with data from more recent studies. Results/conclusion: After making the diagnosis of PsA, the next step is to stage of the disease with the aim of establishing the prevalent manifestation (peripheral arthritis, peripheral enthesitis, axial involvement and dactylitis) and degree of severity (mild, moderate or severe) of the disease. Each patient should be treated according to the defined disease status following the suggested treatment algorithms.

Management of hepatitis C virus-related arthritis

In recent years, hepatitis C virus-related arthritis (HCVrA) has been recognised as an autonomous rheumatic disorder. Two subsets of the disease have been identified: a polyarthritis involving small joints that resembles rheumatoid arthritis, but is usually milder, and a mono-oligoarthritis that shows an intermittent course and is frequently associated with the presence of cryo-globulins in serum. Few data about HCVrA treatment are reported in the literature. As a consequence, the therapeutic approach for this disorder is still largely empirical. Hydroxychloroquine, low doses of corticosteroids and NSAIDs are frequently administered to patients with HCVrA, but some authors describe an incomplete relief of symptoms, especially in the rheumatoid-like subset. Intake of low doses of corticosteroids and NSAIDs is more effective in subjects belonging to the mono-oligoarthritis group. Use of antiviral drugs (IFN plus ribavirin) shows good results, but IFN can induce or worsen autoimmune disorders. For this reason, in our opinion, this approach should be prescribed only when required by the coexistent liver disease. On the basis of the poor available data, the administration of anti-TNF-α agents seems safe in HCV patients, but the usually non-aggressive course of HCVrA does not justify their use as a current therapy.