Myositis-Specific Antibodies and Myositis-Associated Antibodies in Patients With Idiopathic Inflammatory Myopathies From the PANLAR Myositis Study Group.

BACKGROUND: Dermatomyositis (DM) and polymyositis (PM) are forms of idiopathic inflammatory myopathies (IIMs), which are associated with the production of autoantibodies that are useful in the diagnosis and prognosis of the disease. OBJECTIVE: The aim of this study was to determine the frequency of antinuclear autoantibodies (ANAs), myositis-specific autoantibodies (MSAs), and myositis-associated autoantibodies (MAAs) in 6 Latin American countries. METHODS: Two hundred ten patients with IIM were included in this cross-sectional study from 2014 to 2017: 112 from Mexico, 46 from Colombia, 20 from Peru, 16 from the Dominican Republic, 10 from Argentina, and 6 from Guatemala. Antinuclear autoantibodies were detected by indirect immunofluorescence on HEp-2 cells. MSAs and MAAs were tested by a line immunoassay method. Mann-Whitney U and χ2 tests were used for statistical analysis. RESULTS: Of the 210 IIM patients, 139 (66.2%) had DM, 59 (28%) PM, and 12 (5.7%) juvenile DM. The mean age was 43.5 (6-79 years); 158 (75.2%) were female, and 52 (24.8%) were male. The overall frequency of ANA was 60%. The most frequent patterns were fine speckled (AC-4) (78.3%) and cytoplasmic (AC-19) (6.45%). The most frequent MSA were anti-Mi-2 (38.5%) and anti-Jo-1 (11.9%). Anti-Mi-2 was more frequent in patients from Colombia (40.1%). The MAA more frequent were anti-Ro-52/TRIM21 (17.6%) and anti-PM-Scl75 (7.5%). CONCLUSIONS: This is the first study of ANA, MSA, and MAA in patients from 6 countries from the Panamerican League against Rheumatism myositis study group. We observed a general prevalence of 60% of ANA. In relation to MSA and MAA, anti-Mi-2 was the more frequent (38.5%).

Patient Perspectives in OMERACT Provide an Anchor for Future Metric Development and Improved Approaches to Healthcare Delivery in Connective Tissue Disease Related Interstitial Lung Disease (CTD-ILD).

OBJECTIVE: The impact and natural history of connective tissue disease related interstitial lung disease (CTD-ILD) are poorly understood; and have not been previously described from the patient's perspective. This investigation sought insight into CTD-ILD from the patients' perspective to add to our knowledge of CTD-ILD, identify disease-specific areas of unmet need and gather potentially meaningful information towards development of disease-specific patient-reported outcome measures (PROMs). METHODS: A mixed methods design incorporating patient focus groups (FGs) querying disease progression and life impact followed by questionnaires with items of importance generated by >250 ILD specialists were implemented among CTD-ILD patients with rheumatoid arthritis, idiopathic inflammatory myopathies, systemic sclerosis, and other CTD subtypes. FG data were analyzed through inductive analysis with five independent analysts, including a patient research partner. Questionnaires were analyzed through Fisher's Exact tests and hierarchal cluster analysis. RESULTS: Six multicenter FGs included 45 patients. Biophysiologic themes were cough and dyspnea, both pervasively impacting health related quality of life (HRQoL). Language indicating dyspnea was unexpected, unique and contextual. Psycho-social themes were Living with Uncertainty, Struggle over Self-Identity, and Self-Efficacy - with education and clinician communication strongly emphasised. All questionnaire items were rated 'moderately' to 'extremely' important with 10 items of highest importance identified by cluster analysis. CONCLUSION: Patients with CTD-ILD informed our understanding of symptoms and impact on HRQoL. Cough and dyspnea are central to the CTD-ILD experience. Initial FGs have provided disease-specific content, context and language essential for reliable PROM development with questionnaires adding value in recognition of patients' concerns.

Antinuclear antibody (ANA) testing in patients treated with biological DMARDs: is it useful?

The appearance of biologic agents for the treatment of diverse autoimmune diseases in particular rheumatoid arthritis at the end of the 1990s changed the treatment of these patients. With the introduction of new agents in the treatment of rheumatic diseases, we started to notice the presence of new and sometimes unexpected adverse events. It is well recognized that infections are the main concern with these types of treatments; however, the occurrence of autoimmune abnormalities is also seen and its gaining perhaps more attention as the use of these agents is increasing. The first clinical trials of anti-tumor necrosis factor-α (anti-TNFα) inhibitors showed an increase of antinuclear and anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies in patients treated with these agents. In this paper, we review the frequency of these autoantibodies in patients treated with biologic agents, particularly anti-TNF-α inhibitors, and its correlation with autoimmune processes as well as the clinical relevance of such findings.

Are anti-CCP antibodies in psoriatic arthritis patients a biomarker of erosive disease?

To determine the frequency of anticyclic citrullinated peptide (CCP) antibodies in a cohort of psoriatic arthritis (PsA) patients and to compare clinical, serological and radiological characteristics between PsA patients with and without anti-CCP antibodies. Patients with PsA, according to classification criteria for PsA, were consecutively recruited from an outpatient rheumatology clinic. Demographic and clinical data were collected in all cases. Serum samples from all patients were analyzed for rheumatoid factor and anti-CCP antibodies. Radiographs of hands and feet were obtained and the presence of erosions was recorded. The study included 81 patients; 43 (53 %) were men, with a median age of 45.7 years (interquartile range (IQR) 39-72) and median disease duration of 9.4 years (IQR 2-14). Anti-CCP antibodies were found in 11 patients (13.5 %), median titer 174.9 U/ml. Polyarticular involvement (72.7 vs. 17.1 %), frequency of erosive disease (72.7 vs. 37.1 %) and use of tumor necrosis factor-α inhibitors (54.5 vs. 28.5 %) were significantly higher in PsA patients with anti-CCP positivity. Anti-CCP negative PsA patients had predominantly more oligoarticular (62.8 vs. 27.2 %) and nail (81.4 vs. 36.3 %) involvement. Presence of enthesitis, dactylitis and Psoriasis Area Severity Index scores were similar in both groups. Anti-CCP antibodies were found in a subset of PsA patients, and their presence was associated with more severe disease phenotype. Further studies in a larger population are needed to define the role of anti-CCP as a biomarker of erosive disease in PsA.

Of bugs and joints: the relationship between infection and joints.

The association between microbes and joints has existed since antiquity, and remains complex. Diagnosis is often times difficult to determine despite highly suspicious clinical characteristics for the presence of an underlying infection. Over the several past decades, considerable advances have occurred in diagnostic methodologies and therapy. However, the morbidity and mortality of septic arthritis remains high. Great advances have occurred in the diagnosis, pathogenesis, and therapeutic management of reactive arthritis, and there is evidence that when the responsible microorganism is Chlamydia trachomathis, complete remission and cure is possible. Emergent infections, especially viral, has been recognized, i.e. HIV, hepatitis C, and most recently Chikengunya virus, and in the case of HIV associated articular manifestations, the introduction of HAART has resulted in a decrease in the incidence and development of newer complications such as the immune reconstitution syndrome. The infectious etiology of rheumatoid arthritis is being strongly considered once again, and the exciting association with periodontal disease is at the forefront of intense research. The gut microbiota is also being investigated and new and most interesting data is being gathered of the potential role of commensal gut organisms and the pathogenesis of rheumatoid arthritis.

Steps in the management of psoriatic arthritis: a guide for clinicians.

Psoriatic arthritis is a common systemic inflammatory disorder, which in addition to skin and nail involvement may be associated with peripheral and axial joint involvement, enthesitis, dactylitis, and important comorbidities - especially cardiovascular morbidity. Better insights into the involved pathogenic mechanisms have resulted in an improved therapeutic armamentarium, which targets key pathways in its pathogenesis. This has resulted in significant clinical responses to newer therapeutic agents, especially those directed at inhibition of tumor necrosis factor α. Biological therapy leads to significant levels of remission, improved quality of life, and retards or improves structural radiological damage.

Vasculopathy, hematological, and immune abnormalities associated with levamisole-contaminated cocaine use.

OBJECTIVES: To report 4 cases of cocaine-related purpura and to review previously reported cases of levamisole, levamisole-contaminated cocaine, and cocaine-induced vasculopathy. METHODS: We describe 4 patients suspected of vasculopathy associated with levamisole-tainted cocaine use. A retrospective review of the literature was performed using the PubMed, PubJet, MD consult, and Cochrane review databases. RESULTS: Four cases (2 females and 2 males), 46 to 55 years of age, presented with cocaine-related purpura, mainly affecting the ears, neutropenia, and autoantibodies. Skin biopsies revealed a mixed pattern of leukocytoclastic vasculitis and microvascular thrombosis in 2 cases, and pure thrombosis in the third case. The mixed vasculopathic pattern in association with neutropenia, both known adverse effects of levamisole, and levamisole positivity in 2 cases point to this compound as the true etiologic agent in our patients. Eleven cases of levamisole-contaminated cocaine-induced vasculopathy have been described in the English literature. Among these, 10 were females. Age range was 22 to 57 years. Urine levamisole positivity was tested and confirmed in 3 of the 11 cases. The clinical characteristics, laboratory features, histology, treatment, and recovery rates were compared for the published cases of levamisole, levamisole-contaminated cocaine, and cocaine-induced vasculopathy. CONCLUSIONS: Adulterated cocaine abuse is an increasingly recognized phenomenon in North America. Levamisole is among the many contaminants that have been detected in seized cocaine throughout North America and Europe. Recent reports described an association between levamisole-tainted cocaine and purpuric skin rash, neutropenia, and the presence of autoantibodies.

Methotrexate-induced pulmonary toxicity in psoriatic arthritis (PsA): case presentation and literature review.

A 45-year-old female with a 4-week history of psoriatic arthritis developed cough, fever, and progressive shortness of breath 2 weeks following initiation of methotrexate therapy. High resolution CT of chest revealed bilateral basal interstitial involvement and diffuse ground glass opacities. Patient, though, died despite immediate discontinuation of methotrexate and initiation of treatment with IV methylprednisolone and cyclophosphamide. Post-mortem examination showed diffuse interstitial pulmonary fibrosis. Methotrexate-induced pulmonary toxicity is a serious event, unpredictable, and unusual, especially in patients with psoriatic arthritis, and although reversible, it may be fatal.

Comparative assessment of biologics in treatment of psoriasis: drug design and clinical effectiveness of ustekinumab.

The development of psoriasis and psoriatic arthritis is a multistep process that leads to chronic or recurrent inflammation. Recent studies have suggested the importance of T helper (TH)1 and TH17 cells, accessory cells, and proinflammatory cytokines in the pathogenesis of the enthesis, synovium, and skin involvement in psoriasis in the presence of susceptibility genes that remain quiescent until triggered. Biologics, such as soluble CTLA-4 immunoglobulin, tumor necrosis factor (TNF) inhibitors, and ustekinumab, inhibit T cell activation which eventually leads to further stimulation of the interleukin 12, 17, and 23 axis, TNF-α, and lymphotoxin-α. Treatment with TNF-α blockers has been effective in refractory psoriasis and psoriatic arthritis, but there is still a subgroup of patients who do not respond to TNF inhibitors and, paradoxically, when treated, may develop TNF-induced psoriasis. Ustekinumab, because of its different mechanism of action at the level of the interleukin 12, 17, and 23 pathways, is an alternative treatment for this group of patients.

Efficacy and safety of febuxostat in patients with hyperuricemia and gout.

The past decade has witnessed an exponential increase of novel therapeutic modalities for a variety of rheumatic disorders, including gout. During the past few years two novel therapeutic agents have been approved by the US Food and Drug Administration for the treatment of hyperuricemia in patients with gout, one of them being febuxostat, a nonpurine selective inhibitor of xanthine oxidase. Review of its pharmacokinetics and pharmacodynamics, efficacy and safety profile, and use in gout patients with comorbid conditions reveals that age and gender have no clinically significant effect and dose adjustments based on age or gender are not required. In addition, febuxostat can be used in patients with mild-to-moderate renal or hepatic involvement. Its overall efficacy and safety profile is comparable and, in certain subsets such as gout patients with mild and moderate renal insufficiency, is superior to allopurinol.