Retention of triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine compared to combination methotrexate and leflunomide in rheumatoid arthritis.

OBJECTIVE: There are various combination conventional synthetic disease-modifying-antirheumatic drug (csDMARD) treatment strategies used in rheumatoid arthritis (RA). A commonly used csDMARD combination is triple therapy with methotrexate (MTX), sulfasalazine (SSZ) and hydroxychloroquine (HCQ). Another approach is double therapy with MTX and leflunomide (LEF). We compared the real-world retention of these two treatment combinations. METHODS: Patients with RA from the Ontario Best Practices Research Initiative (OBRI) who received triple or double therapy on or after OBRI enrolment were included. Retention rates were compared between these two groups. We also analyzed which medication in the combination was discontinued and the reasons for treatment discontinuation. Disease activity was assessed at baseline, 6 and 12 months after treatment initiation as well as at time of discontinuation. Risk factors for treatment discontinuation were also examined. RESULTS: Six hundred and ninety-two patients were included (258 triple and 434 double therapy). There were 175 (67.8%) discontinuations in the triple therapy group and 287 (66.1%) discontinuations in patients on double therapy. The median survival for triple therapy was longer (15.1 months; 95% CI: 11.2-21.2) compared to double therapy (9.6 months; 95%CI: 7.03-12.2). However, this was not statistically significant. Disease activity at 6 and 12 months, measured by 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR) was lower with triple therapy (mean DAS28 at 6 months 3.4 vs. 3.9, P<0.0001 and at 12 months 3.2 vs. 3.5, P=0.0005). CONCLUSION: Patients on triple therapy remained on treatment longer than patients on double therapy. However, this difference was not statistically significant.

Overlapping systemic lupus erythematosus, seropositive erosive rheumatoid arthritis, and ANCA-associated vasculitis: A case report and literature review.

The overlap of rheumatoid arthritis and systemic lupus erythematosus is well described, with a syndrome known as 'rhupus'. ANCA-associated vasculitis, however, is uncommonly associated with other autoimmune conditions. Here, we present a case of lupus, rheumatoid arthritis, and ANCA-associated vasculitis, with significant time elapsed between presentations, resulting in an accumulation of the three diagnoses over the course of 35 years. The patient was diagnosed with lupus at age 45, presenting with inflammatory polyarthritis, thrombocytopenia, leukopenia, positive ANA, positive anti-DNA, and hypocomplementemia. She was maintained on hydroxychloroquine therapy with minimal disease activity. Approximately 20 years later, she had a flare of polyarthritis with bilateral wrist erosive arthropathy and a positive rheumatoid factor, diagnosed as rheumatoid arthritis. Anti-TNFα therapy was initiated, and she was stable for a further 10 years. At age 79, she developed ANCA-associated vasculitis AAV with pulmonary and renal manifestations, treated with rituximab induction therapy and steroids. She recovered and her MPO-ANCA titre normalised. One year later, off the anti-TNFα, she again experienced an acute kidney injury with a repeat rise in MPO-ANCA. She was re-induced and maintained on steroids and rituximab. This novel case highlights the range of possible overlap syndromes, as well as how multiple autoimmune diagnoses can evolve over decades in previously stable disease. There is growing work around polyautoimmunity with ANCA-associated vasculitis and other systemic autoimmune diseases, which has potential to identify common aetiologies and pathogenesis. Knowledge of these overlap syndromes can help to recognise and manage these conditions in a timely manner.

Severe Intracranial Involvement in Giant Cell Arteritis: 5 Cases and Literature Review.

OBJECTIVE: Involvement of intracranial arteries in giant cell arteritis (GCA) is rare. We describe the neurologic complications of intracranial GCA (IC GCA) and available treatment options. METHODS: We describe 5 IC GCA cases from 3 Canadian vasculitis centers and review the literature. We searched English-language publications reporting similar patients meeting American College of Rheumatology (ACR) criteria for GCA and having intracranial artery involvement diagnosed by autopsy, magnetic resonance angiography, computed tomography angiography, or conventional angiography. RESULTS: All 5 cases of IC GCA met ACR criteria for GCA; 4 cases had a temporal artery biopsy that was consistent with GCA. All cases experienced cerebrovascular accident(s). Arteritis involved the following vessels: intracranial internal carotid (n = 1), vertebrobasilar arteries (n = 1), or both (n = 3). All cases received aspirin and oral prednisone (preceded by intravenous methylprednisone in 3 cases), combined with an immunosuppressant in 4 cases. All patients survived; 2 had complete neurological recovery, 3 had residual neurologic sequelae. The literature review included 42 cases from 28 publications. The clinical features of the reported cases were similar to those of our 5 cases. However, mortality was 100% in untreated cases (n = 2), 58% in those treated with corticosteroid alone (n = 31), and 40% in those treated with corticosteroid and an immunosuppressant (n = 10). CONCLUSION: IC GCA appears to be associated with neurologic complications and mortality. In some cases corticosteroid alone was not sufficient to prevent neurologic complications. The role of additional immunosuppressive agents needs further investigation.

The syndrome of stroke-like migraine attacks after radiation therapy associated with prolonged unresponsiveness in an adult patient.

INTRODUCTION: The syndrome of stroke-like migraine attacks after radiation therapy (SMART) is an extremely rare complication of cerebral irradiation. It is characterized by reversible episodic neurological dysfunction, commonly associated with headaches and occasionally with seizures, occurring years after cranial radiotherapy. Approximately a dozen cases have been reported in adult patients to date. CASE REPORT: In 1997, a 48-year-old man underwent resection of a right cerebellar metastasis from renal cell carcinoma, followed by whole-brain irradiation. Two years later he began experiencing recurrent episodes of headache associated with reversible left hemiparesis, dysphasia, visual field defects, and confusion. Over subsequent years these episodes increased in frequency, and in 2009 and 2010 the patient experienced 2 episodes associated with seizures and characterized by severe depression in level of consciousness (GCS 5); the latter of these was particularly prolonged, with neurological recovery requiring almost 6 months. Cortical and leptomeningeal gadolinium enhancement was demonstrated on magnetic resonance imaging during the second episode. Repeated electroencephalography studies did not demonstrate any epileptiform activity, and extensive workup including brain biopsy failed to identify any neoplastic, vascular, or infective pathology. The diagnosis of SMART syndrome was therefore made. CONCLUSIONS: Reduced level of consciousness of such severity and duration as observed here has not previously been described in SMART syndrome. This report, however, suggests that an excellent prognosis can be expected even in cases of prolonged unresponsiveness. The pathogenic mechanisms of SMART syndrome remain unclear, but may involve pathways common to both migraine and epilepsy.

Anti-RNA polymerase III antibodies in the diagnosis of scleroderma renal crisis in the absence of skin disease.

Scleroderma renal crisis (SRC) occurs in approximately 10% of patients with systemic sclerosis (SSc), particularly in those with diffuse skin disease. Scleroderma renal crisis has rarely been described to occur in patients with SSc without skin involvement. Scleroderma renal crisis without skin disease represents a major diagnostic challenge, particularly in patients without overt SSc involvement of other organ systems. It closely mimics the presentation of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, and treatment is therefore often directed at this entity. Anti-RNA polymerase III antibody testing has been previously reported to be used in 4 patients to diagnose SRC in the absence of sclerotic skin disease.We report 2 patients without skin disease or overt visceral involvement at presentation who presented with microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Both patients eventually developed diffuse and rapidly progressive skin thickening. Anti-RNA polymerase III antibodies were strongly positive, supporting that their renal presentations were secondary to SRC.

Keloid scarring, but not Dupuytren's contracture, is associated with unexplained carotid atherosclerosis.

BACKGROUND: Atherosclerosis, a response to injury, may be thought of as scarring in the artery wall. TGF-beta and associated signaling molecules have been implicated in the pathophysiology of keloid scarring, Dupuytren's Contracture and atherosclerotic plaques in independent studies. PURPOSE: To test the hypothesis that excess cutaneous scarring and Dupuytren's contractures predispose independently to carotid atherosclerosis . METHODS: Among 1,747 patients with plaque measurements and complete data for multivariable regression analysis, 57 Caucasian patients had Dupuytren's contractures and 12 had keloid scars. Carotid total plaque area (TPA) was measured by 2-Dimensional ultrasound. RESULTS: In linear multivariable regression analysis with coronary risk factors, keloid scars were associated with TPA (P= 0.018), but Dupuytren's contractures were not. Patients with keloid scarring were younger (P < 0.0001), and more likely to be diabetic (P < 0.0001) CONCLUSIONS: Keloid scarring is a clinical clue to excess atherosclerosis not explained by traditional risk factors. Such patients may benefit from therapy directed at targets related to signalling molecules common to both the process of keloid scarring and atherosclerosis. These findings suggest previously unexplored possibilities for the prevention and treatment of atherosclerosis. The differences between Dupuytren's and keloid scars that may identify such targets are discussed.