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Antiphospholipid syndrome and systemic lupus erythematosus: are they separate entities or just clinical presentations on the same scale?

Curr Opin Rheumatol. 2009 Sep;21(5):495-500

Authors: Shoenfeld Y, Meroni PL, Toubi E

PURPOSE OF REVIEW: Although originally described in the context of systemic lupus erythematosus, antiphospholipid syndrome was then recognized as a primary antiphospholipid syndrome without any underlying autoimmune disease in almost half of the cases. However, cases of primary antiphospholipid syndrome were reported to evolve into systemic lupus erythematosus over time suggesting that these apparently different diseases are somehow related. RECENT FINDINGS: Peculiar biological systemic lupus erythematosus markers such as an autoantibody response against chromatin antigens and complement activation have been also described in patients with primary antiphospholipid syndrome. Distinct polymorphisms of common genetic factors have been associated with systemic lupus erythematosus and primary antiphospholipid syndrome supporting the notion that these entities are indeed variants within a continuum of the same disease. SUMMARY: A multiorgan involvement that cannot be explained by the thrombophilic state per se and similar to the well known clinical manifestations in lupus is reported in patients with primary antiphospholipid syndrome. Further studies, mainly genetic, will better underline the proximity between primary antiphospholipid syndrome and systemic lupus erythematosus.

PMID: 19593144 [PubMed - indexed for MEDLINE]

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An update on methotrexate.

Curr Opin Rheumatol. 2009 May;21(3):216-23

Authors: Braun J, Rau R

PURPOSE OF REVIEW: Methotrexate (MTX) has been used for the treatment of rheumatoid arthritis (RA) for about three decades now. MTX is one of the most effective and commonly used medicines to treat various forms of arthritis and other rheumatic conditions. MTX was shown to improve signs and symptoms of RA, disease activity and function, to a similar degree as the tumor necrosis factor blockers, and it inhibits radiographic progression to a smaller degree than the antitumor necrosis factor agents. MTX is considered as the anchor drug among the disease-modifying antirheumatic agents, and it is internationally accepted as the first choice in the management of RA. This review was performed on the basis of a PubMed literature search looking at all publications on MTX and arthritis in 2008. RECENT FINDINGS: MTX seems to even prolong the life span of patients who tolerate the drug and have clinical benefit from this therapy; this may partly be explained by beneficial effects on cardiovascular mortality. The reason for this may well be the suppression of inflammation, but direct atheroprotective effects of MTX may also play a role. MTX is used as monotherapy and in combination with other disease-modifying antirheumatic agents or biologic agents such as the antitumor necrosis factor agents. The ‘early’ use of MTX within 5 years after disease onset is clearly associated with improved outcomes. The management of RA should include an early strong suppression of inflammation and continuously a tight control strategy. The pharmacodynamics and kinetics of MTX are still incompletely understood. SUMMARY: In this review, we especially cover the following themes: new clinical studies on the use of MTX in RA, the use of MTX in other rheumatic conditions, prediction of response to MTX, optimal dosage, MTX use in the elderly, the mechanism of action, the pharmacokinetics and the pharmacogenetics of MTX, the prevention of side effects, and the overall long-term safety.

PMID: 19373092 [PubMed - indexed for MEDLINE]

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Use of imaging to evaluate gout and other crystal deposition disorders.

Curr Opin Rheumatol. 2009 Mar;21(2):124-31

Authors: Dalbeth N, McQueen FM

PURPOSE OF REVIEW: This review summarizes recent advances in plain radiography and advanced imaging for gout, calcium pyrophosphate dihydrate crystal arthropathy and basic calcium phosphate crystal arthropathy. RECENT FINDINGS: Plain radiography has diagnostic utility in the crystal-induced arthropathies. A gout radiographic damage index has been recently validated. High-resolution ultrasonography may improve noninvasive diagnosis of the crystal-induced arthropathies, and allow monitoring of intra-articular tophi in clinical trials. Computed tomography provides excellent definition of tophi and bone erosion, and three-dimensional computed tomography assessment of tophus volume is a promising outcome measure in gout. Magnetic resonance imaging is also a reliable method for assessment of tophus size in gout, and has an important role in detection of complications of disease in clinical practice. Emerging imaging techniques include three-dimensional ultrasonography and dual-energy computed tomography. Advanced imaging modalities also offer new insights into the mechanisms of cartilage and bone damage in the crystal-induced arthropathies. SUMMARY: Plain radiography and advanced imaging techniques may assist with diagnosis, assessment of disease complications and monitoring of crystal-induced arthropathies. Further study of these techniques will provide significant improvement in patient care and further aid in the understanding of disease pathogenesis.

PMID: 19339922 [PubMed - indexed for MEDLINE]

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Advances in understanding calcium-containing crystal disease.

Curr Opin Rheumatol. 2009 Mar;21(2):150-7

Authors: Ea HK, Lioté F

PURPOSE OF REVIEW: Calcium pyrophosphate dihydrate and basic calcium phosphate crystals are the two most common calcium-containing crystals involved in rheumatic diseases. Recent literature concerning their role in the pathogenesis of osteoarthritis is reviewed. RECENT FINDINGS: In some instances, these calcium crystals might worsen osteoarthritis cartilage destruction. Laboratory investigations have identified determinants of cartilage calcification, especially a better characterization of matrix vesicle content and a better understanding of the regulation of inorganic pyrophosphate and phosphate concentration. In-vitro studies have highlighted new pathogenic mechanisms of calcium crystal-induced cell activation. Several intracellular signalling pathways are activated by calcium crystals. Recent studies suggested the implication of the inflammasome complex and a pivotal role for IL-1 in pseudogout attacks and chondrocyte apoptosis in basic calcium phosphate crystal-related arthropathies. SUMMARY: Animal models of osteoarthritis and in-vitro studies using calcium pyrophosphate dihydrate and basic calcium phosphate crystals will improve our knowledge of these common crystals and could suggest new targets for drugs, as these common diseases are ‘orphan’ with respect to therapy.

PMID: 19339926 [PubMed - indexed for MEDLINE]

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Update on emerging urate-lowering therapies.

Curr Opin Rheumatol. 2009 Mar;21(2):143-9

Authors: Chohan S, Becker MA

PURPOSE OF REVIEW: To discuss currently available urate-lowering therapeutic options for gout in the United States and newer therapeutic initiatives in development. RECENT FINDINGS: Currently available urate-lowering drugs include allopurinol and probenecid. These drugs are effective but are often underdosed or underutilized, and caution must be taken in patients with multiple comorbidities. Newer therapeutic agents in development include febuxostat, a nonpurine analogue xanthine oxidase inhibitor, and pegloticase, a pegylated recombinant uricase. SUMMARY: There have been no new US Food and Drug Administration-approved urate-lowering drugs for gout in the past 40 years. Recent advances in therapeutics promise to provide the opportunity for much needed improvement in patient outcomes in this disorder.

PMID: 19339925 [PubMed - indexed for MEDLINE]

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Central nervous system vasculitis.

Curr Opin Rheumatol. 2009 Jan;21(1):10-8

Authors: Hajj-Ali RA, Calabrese LH

PURPOSE OF REVIEW: In the past decade, primary and secondary central nervous system (CNS) vasculitides have been more commonly diagnosed and recognized than previously. With the increasing awareness of these disorders, it is crucial for the treating physician to differentiate between causes of CNS vasculitis and to recognize their marked clinical and pathophysiological heterogeneity. This review focuses on the major forms of primary CNS vasculitis, as well as secondary CNS vasculitis with emphasis on their clinical findings, diagnoses, and treatment. RECENT FINDINGS: The proposal of reversible cerebral vasoconstriction syndromes (RCVS) as a unifying concept for a group of disorders which are characterized by acute-onset severe recurrent headaches, with or without additional neurologic signs and symptoms, and prolonged but reversible vasoconstriction of the cerebral arteries, has been a major breakthrough in this field over the past decade. Recognition of this common mimic (i.e. RCVS) has allowed optimal management of a sizable group of patients previously confused with pathologically documented CNS vasculitis. SUMMARY: Sound treatment decisions are based on accurate diagnosis. It is essential for the clinicians involved in the evaluation of patients with CNS vasculitis to be aware of its mimics especially RCVS. This article provides a comprehensive review of CNS vasculitis and its differential diagnosis. Furthermore, it touches upon workup and treatment of CNS vasculitis.

PMID: 19093322 [PubMed - indexed for MEDLINE]

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Spinal infections: evolving concepts.

Curr Opin Rheumatol. 2008 Jul;20(4):471-9

Authors: Kourbeti IS, Tsiodras S, Boumpas DT

PURPOSE OF REVIEW: Although rare, spinal infections are characterized by an indolent clinical course and delay in diagnosis. Physicians should be aware of current diagnostic and therapeutic developments. RECENT FINDINGS: The range of the pathogens causing spinal infections has expanded as a result of the increasing number of individuals at risk and enhanced diagnostics. The role of newer biological therapies in producing spinal infections has not been elucidated yet. Pyogenic bacteria still account for most of the cases; however, tuberculosis and brucellosis remain major causes in endemic countries and susceptible patients. Endoscopic techniques assist in sampling suspicious lesions and molecular microbiology has revolutionized diagnosis. Magnetic resonance imaging techniques remain the gold standard for diagnostic imaging; their role in follow-up is a matter of debate. Long-term antimicrobial treatment is currently the standard of care. The identification of individuals most likely to benefit from surgical intervention is crucial. Surgery may be required early to address any neurological deficits and later to treat infection refractory to conservative treatment. SUMMARY: Prompt diagnosis is essential in spinal infections. Early surgical intervention is required in patients with neurological deficits. Further research should clarify the appropriate duration of antimicrobial treatment and the overall role of surgery.

PMID: 18525363 [PubMed - indexed for MEDLINE]

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Septic arthritis: current diagnostic and therapeutic algorithm.

Curr Opin Rheumatol. 2008 Jul;20(4):457-62

Authors: Mathews CJ, Coakley G

PURPOSE OF REVIEW: To propose and discuss an evidence-based algorithm for the diagnosis and treatment of bacterial septic arthritis. Also, to review the recent literature on emerging management strategies and discuss the potential impact of these developments on clinical practice. RECENT FINDINGS: Evidence-based guidelines have recently been published to assist in the diagnosis and management of suspected and confirmed septic arthritis. All suspected septic joints should be aspirated and the synovial fluid examined by microscopy for the presence of crystals and microorganisms. There is controversy surrounding the diagnostic utility of quantifying the synovial fluid white cell count, with two recent systematic reviews reaching opposite conclusions. The emergence of multidrug resistant pathogens has led to a search for alternative antimicrobial agents such as linezolid. Studies in animals and children have suggested that corticosteroid therapy may be a useful adjunct to conventional antibiotic therapy. Research using experimental murine models of septic arthritis is also generating novel immunotherapeutic targets as potential adjuncts to antibiotic regimens. SUMMARY: There is a striking paucity of high-quality evidence upon which to base guidelines on the management of the hot-swollen joint. Ultimately, the diagnosis of septic arthritis rests on the opinion of a clinician experienced in the assessment of musculoskeletal disease. Future research may provide alternative investigative and treatment strategies to improve the accuracy of diagnosis as well as the outcome in this group of patients.

PMID: 18525361 [PubMed - indexed for MEDLINE]

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