The Diagnosis and Treatment of Antisynthetase Syndrome.

Anti-synthetase syndrome is an autoimmune condition, characterized by antibodies directed against an aminoacycl transfer RNA synthetase along with clinical features that can include interstitial lung disease, myositis, Raynaud's phenomenon, and arthritis. There is a higher prevalence and increased severity of interstitial lung disease in patients with anti-synthetase syndrome, as compared to dermatomyositis and polymyositis, inflammatory myopathies with which it may overlap phenotypically. Diagnosis is made by a multidisciplinary approach, synthesizing rheumatology and pulmonary evaluations, along with serologic, radiographic, and occasionally muscle and/or lung biopsy results. Patients with anti-synthetase syndrome often require multi-modality immunosuppressive therapy in order to control the muscle and/or pulmonary manifestations of their disease. The long-term care of these patients mandates careful attention to the adverse effects and complications of chronic immunosuppressive therapy, as well as disease-related sequelae that can include progressive interstitial lung disease necessitating lung transplantation, pulmonary hypertension, malignancy and decreased survival. It is hoped that greater awareness of the clinical features of this syndrome will allow for earlier diagnosis and appropriate treatment to improve outcomes in patients with anti-synthetase syndrome.

Benefit of adjunctive tacrolimus in connective tissue disease-interstitial lung disease.

We evaluated the safety and effectiveness of adjunctive tacrolimus therapy with conventional immunosuppression in patients with severe connective tissue disease-related interstitial lung disease (CTD-ILD). We included patients from our interstitial lung disease (ILD) registry with CTD-ILD, in whom tacrolimus was added to corticosteroids and an additional immunosuppressive agent. Demographic data, clinical features, lung function, radiographic images, and pathologic findings were reviewed. Effectiveness was assessed by comparing pulmonary function tests (PFTs) closest to tacrolimus initiation to PFTs approximately 6-12 months later. Corticosteroid dose at these time points was also evaluated. We report adverse events attributed to tacrolimus. Seventeen patients with CTD-ILD were included in adverse event analysis; twelve were included in efficacy analysis. Length of tacrolimus therapy ranged from 6 to 110 months (mean 38.8 months ± 31.4). The mean improvement in percent predicted total lung capacity was 7.5% ± 11.7 (p = 0.02). Forced vital capacity mean improvement was 7.4% ± 12.5 (p = 0.06). The average decrease in corticosteroid dose at follow-up was 20.3 mg ± 25.2 (p = 0.02) with complete discontinuation in six patients. No patients experienced a life-threatening adverse event attributed to tacrolimus. Tacrolimus can be effective and is well tolerated as an adjunctive therapy and allows tapering of corticosteroids.

Nephrogenic systemic fibrosis associated with stromal and vascular calcification, report of two cases.

Nephrogenic systemic fibrosis (NSF) is a systemic fibrosing disorder characterized by the development of large indurated plaques on the skin, primarily in patients with end-stage renal disease (ESRD). Skin biopsy reveals an increased frequency of CD34(+) and Factor XIIa+ cells. Microscopic calcification has been reported in the skin biopsies of rare cases of NSF. The etiology and significance of this calcification is not clear. We present two cases of typical NSF, for which marked stromal and vascular calcification was identified on skin biopsy. In both cases, the calcification was within typical NSF lesions and was intimately associated with aggregates of CD34(+), Factor XIIIa+ spindle and stellate cells. This particular pattern of calcification strongly argues against either nonspecific dystrophic calcification or coincidental metastatic calcification. These findings suggest that calcification may be intrinsic to the pathophysiology of NSF, at least in a subset of NSF patients. In addition, the vascular calcification involving small arteries and arterioles in these two cases morphologically resembled calciphylaxis, which is another poorly understood complication of ESRD. This resemblance raises the possibility that NSF may predispose to or develop in the vicinity of indolent lesions of early-stage calciphylaxis. We propose that skin biopsies performed as part of a diagnostic workup for suspected NSF should preferably include the deep dermis and subcutis, in order to assess possible vascular calcification.

Infliximab-responsive uveitis and vasculitis in a patient with Takayasu arteritis.

Uveitis rarely occurs in patients with Takayasu arteritis (TA) and may be the presenting manifestation in some. We present the case of a 22-year-old black woman who presented with bilateral uveitis. She was subsequently diagnosed with TA and treated with high doses of corticosteroids and methotrexate. However, she experienced recurrent episodes of uveitis and arteritis on this regimen. Addition of infliximab resulted in resolution of both uveitis and arteritis, thereby permitting tapering of steroids and discontinuation of methotrexate over a period of 1 year. The case highlights the importance of keeping TA in the differential in patients with uveitis and considering infliximab in resistant uveitis and patients with TA.

Benign angiopathy of the central nervous system.

Apparent central nervous system vasculitis could have a benign course in a subset of patients and is referred to as benign angiopathy of the central nervous system (BACNS). This is mostly is seen in young women and presents with acute onset of neurologic symptoms, usually in the form of severe headache and/or a focal neurologic event. Cerebrospinal fluid analysis could be normal or nearly normal. Brain angiogram typically shows segmental narrowing, ectasia, or beading in multiple vascular territories on brain angiogram. Like in all cases of CNS vasculitis, exclusion of other systemic diseases or its mimickers associated with cerebral involvement is important.BACNS could respond favorably to treatment with corticosteroids alone or in combination with a calcium channel blocker, thereby avoiding unnecessary and prolonged treatment with other immunosuppressants like cyclophosphamide with their side effects. Little is published in the literature about BACNS, but is a rapidly emerging concept. It is thus important to recognize. We report a patient with classic presentation of BACNS to highlight the significance of distinguishing benign angiopathy from the more aggressive form of CNS vasculitis, because the treatment and response varies in these 2 entities.

Underuse of intra-articular and periarticular corticosteroid injections by primary care physicians: discomfort with the technique.

Musculoskeletal disorders account for 11% to 13% of office visits in ambulatory care clinics and 9% of all physician visits in the United States. Intra-articular or periarticular aspiration or injections are an integral part of the management of arthritis or periarthritis. Our aim was to determine the use and level of comfort of administering intra-articular and periarticular injections by primary care physicians (PCPs) practicing in a university setting.A self-administered questionnaire with 20 questions querying experience and training in local injection therapy was mailed to 82 physicians (junior residents, senior residents, and faculty) offering primary care at the University of Chicago. Comfort scores were measured with a scale of 1 to 10 (1 = minimum and 10 = maximum). The response rate to the questionnaire was 67% (36 residents and 19 faculty). Seventy-one percent of PCPs routinely suggested the procedure for severe arthritis and bursitis, but only 19% had (self-administered) performed it themselves. Eighty-nine percent of the PCPs referred their patients to specialty clinics. Forty-eight percent referred their patients to rheumatology, 11.5% to orthopedics, and 29% to both. Other PCPs were consulted for the procedure by 9.6%. Discomfort with the performance of the technique was the predominant reason for 83% of the referrals. The mean comfort score for intra-articular or periarticular injections was 3.10 +/- 2.14 in general and 4.45 +/- 2.92 for knee joint. The mean comfort score for other joints and bursae ranged from 1.20 to 2.15. Ninety-five percent of PCPs regarded themselves to be inadequately trained. Regarding the training, 41% had received a lecture during medical school and residency, while 40% had received demonstration of the techniques during residency. Of the faculty, 26% had never received any formal lecture, and 5.2% had never received formal demonstration of the techniques during their training. Joint injections observed ranged from 89% for knee to 59% for shoulder and 22% for wrist joints. Only 11% of faculty had performed more than 5 intra-articular injections during their training. A need for formal training in these techniques was identified by 95% of the subjects, of whom 65% thought the residency period was the best time to do so. Performing 5 to 10 intra-articular injections during residency was considered optimal training by 60%. On subanalysis, the mean comfort scores were higher in the residents in general (3.60 +/- 2.29 versus 2.18 +/- 1.47;P = 0.01) as compared with faculty. The residents' scores were also higher across different joints as compared with those of faculty but assumed statistical significance only for olecranon bursa injection (2.32 +/- 2.76 versus 1.27 +/- 0.67;P = 0.04) and subacromial bursa injection (2.08 +/- 2.27 versus 1.27+/- 0.75;P = 0.06). The mean comfort scores were lower by 1.74 (P = 0.007) for women physicians. There is underuse of self-administered intra-articular and periarticular injection techniques by PCPs in the management of arthritis or periarthritis. The reasons include inadequate training and low comfort in performing these procedures. Eighty-nine percent of PCPs would refer their patients to subspecialty clinics for these "routine" injections. There is a clear need for a training in these procedures during residency.