Rochella A. Ostrowski

Ocular Toxicity of Hydroxychloroquine

This review summarizes the current literature regarding the ocular complications of hydroxychloroquine. Hydroxychloroquine has been used since the 1950s for the treatment of various rheumatic and dermatologic diseases. Hydroxychloroquine can cause ocular toxicity, with the most serious being an irreversible retinopathy. At the present time, no “gold standard” exists for identification of the ocular toxicity prior to its development. This has led to controversy regarding the recommendations for ophthalmologic examinations for screening patients on hydroxychloroquine.

Antiphospholipid antibody syndrome and autoimmune diseases.

The arbitrary division between antiphospholipid antibody syndrome and secondary antiphospholipid antibody syndrome has not proven useful. Antiphospholipid antibodies in the absence of antiphospholipid antibody syndrome often occur as epiphenomena in many autoimmune diseases. They are very common in systemic lupus erythematosus. Antiphospholipid antibody syndrome is a significant comorbidity in lupus but is uncommon in Sjögrens syndrome, rheumatoid arthritis, scleroderma, and systemic vasculitis. Evidence is growing that antiphospholipid antibodies may have a pathogenic role in pulmonary hypertension and accelerated atherosclerosis of autoimmune diseases.

Association of normal nailfold end row loop numbers with a shorter duration of untreated disease in children with juvenile dermatomyositis.

OBJECTIVE To determine the association of normal numbers of end row loops (ERLs) in nailfold capillaries at the time of diagnosis of juvenile dermatomyositis (DM) with clinical findings in untreated children with the disease and to identify predictors of the development of decreased numbers of ERLs. METHODS Clinical and laboratory data from 80 untreated children with juvenile DM were collected. ERL numbers were recorded at the time of diagnosis and at 24 months and 36 months thereafter. The 12 children who had normal ERLs at diagnosis were compared with the remaining 68 children. Outcomes included the duration of untreated disease, the duration of treatment with immunosuppressive medications, family medical history, Disease Activity Score (DAS) for juvenile DM, creatinine phosphokinase level, aldolase level, absolute number of CD3-CD56+/16+ natural killer cells, and von Willebrand factor antigen level. Cross-sectional and longitudinal analyses were performed. RESULTS At diagnosis, children with normal ERLs had a shorter duration of untreated disease (P = 0.03) and a lower skin DAS (P = 0.045). Over time, an increased likelihood of having decreased numbers of ERLs was associated with a longer duration of untreated disease and with a higher skin DAS. CONCLUSION The presence of a normal number of ERLs in juvenile DM appears to be associated with a shorter duration of symptoms and may be a useful indicator of disease chronicity in the newly diagnosed child. Normal ERLs is also associated with a lower skin DAS. The lack of association between normal ERLs and other variables indicates that normal findings on nailfold capillaroscopy should not be used as justification to delay immunosuppressive therapy in children with typical symptoms of juvenile DM.

Refractory adult-onset still disease successfully treated with abatacept.

Adult-onset Still disease (AOSD) is an inflammatory condition of unknown etiology that responds to glucocorticosteroids and disease-modifying antirheumatic drugs, particularly methotrexate. However, disease refractory to conventional treatment has led to the reported use of biologic therapy including tumor necrosis factor α inhibitors (infliximab, etanercept, and adalimumab), anakinra, rituximab, and tocilizumab. We report the successful use of abatacept in the treatment of a patient with AOSD manifested by polyarthritis, rash, fevers, elevated liver function tests, and ferritin levels refractory to treatment with methotrexate and hydroxychloroquine. Remission has been maintained for 35 months with the addition of abatacept administered once monthly. There is evidence that T-cell activity plays an important role in the autoimmune activity of AOSD, and modulation of CD28 costimulation of T cells by abatacept has specific immunosuppressive actions that make it an appealing alternative therapeutic option for refractory AOSD.

Survival and extrapulmonary course of connective tissue disease after lung transplantation.

Background Connective tissue disease (CTD)–related lung dysfunction is a common cause of morbidity and mortality; however, few lung transplantations (LTs) are performed in this population secondary to uncertainty regarding the posttransplant survival, outcome, and management. Objectives The objectives were to evaluate the survival and the pulmonary and extrapulmonary courses of CTD after LT. Methods Survival outcomes of patients documented within the Organ Procurement and Transplantation Network who had undergone a LT for CTD were compared with those who underwent LT for chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). In addition, the pulmonary and extrapulmonary courses of the CTD were evaluated after LT. Results From 1991 to 2009, there were 284 documented LT in patients with CTD. Post-LT cumulative survival of patients with CTD was less than that for COPD through 5 years, with a difference that peaked at 1 year (72.7% vs. 83.1%, P < 0.001). When patients with CTD were compared with those with IPF, a difference was only noted at 1 year (72.7% vs. 77.7%, P = 0.049). There were no documented post-LT pulmonary recurrences of the CTD, and extrapulmonary flares of the CTD were rare (1 possible flare per 20.3 patient-years and 1 probable flare per 81.0 patient-years). Conclusions Cumulative survival of patients with CTD who underwent LT is similar to those with IPF and slightly less than those with COPD, with an increased risk of mortality that was most prominent at 6 months after transplant followed by subsequent narrowing of the survival differences over time. Lung transplantation may be a viable therapeutic option for patients with end-stage lung dysfunction resulting from a CTD.

Rheumatoid arthritis, spondyloarthropathies, and relapsing polychondritis.

The neurologic complications of rheumatic disease are highly variable and their manifestations are linked to the pathogenesis and clinical phenotype of the specific rheumatologic syndrome. In active rheumatoid arthritis (RA), the peripheral nervous system is most commonly involved and mononeuritis multiplex, nerve entrapment and vascultitic sensorimotor neuropathy are not uncommon. Central nervous system complications such as pachymeningitis and cerebral vasculitis are rare. TNF blockade therapy of RA is rarely associated with demyelinating syndromes. In the spondyloarthropathies, especially ankylosing spondylitis (AS), neurologic complications are more frequent in long-standing, advanced disease and include atlantoaxial subluxation, cauda equina syndrome, spinal stenosis, and acute vertebral fractures. Peripheral nervous system involvement in any of the spondyloarthropaties is rare. Relapsing polychondritis (RP) is characterized by recurring bouts of inflammation, destruction of cartilaginous structures, and systemic and rarely central nervous system vasculitis. Visual-oculo and auditory complications are common. Definitive treatment of the neurologic complications and prevention of subsequent ones is dependent upon effective treatment of RA, AS or RP.

Giant cell arteritis.

This review summarizes the diagnosis, clinical manifestations and management of giant cell arteritis. Giant cell arteritis is an immune-mediated vasculitis of medium to large sized arteries that affects individuals older than the age of 50. Patients typically present with signs of vascular insufficiency of the extracranial arteries of the head and systemic inflammation. Temporal artery biopsy remains the hallmark of diagnosis. Specific treatment regimens must be tailored to each individual, but steroids remain the backbone of therapy.

Giant Cell Arteritis: Oral Versus Intravenous Corticosteroids

This review summarizes the current literature on the use of oral versus intravenous steroids for giant cell arteritis. Giant cell arteritis is an immune-mediated vasculitis of medium to large sized arteries that affects individuals older than the age of fifty. Patients typically present with signs of vascular insufficiency of the extracranial arteries of the head and systemic inflammation. Steroids remain the backbone of therapy, but the dose, maintenance and route of administration remain debatable.

Rituximab in the Treatment of Thyroid Eye Disease: A Review

ABSTRACT Graves disease is an autoimmune thyroid disease classically characterised by a clinical triad consisting of hyperthyroidism, diffuse goitre, and thyroid eye disease. Thyroid eye disease is an immunologically mediated condition in which humoral immunity is thought to play a central role. Thyroid eye disease is traditionally treated with high-dose glucocorticosteroids and surgical orbital decompression. However, responses are inadequate and alternative treatment options are needed. Rituximab, an anti-CD20 monoclonal antibody, shows promise as a novel therapeutic option for thyroid eye disease. There are 43 cases of thyroid eye disease treated with rituximab in the medical literature, and larger studies are warranted to determine the long-term effectiveness of rituximab. Rituximab may represent an attractive new treatment option for thyroid eye disease, especially in the case of disease that is refractory to current treatment strategies.

Biologic Therapy for the Treatment of Giant Cell Arteritis

Abstract Giant cell arteritis (GCA), a vasculitis of the medium and large arteries, is traditionally managed with glucocorticoids. However, the side effects of chronic glucocorticoid use and the occurrence of refractory cases warrant the consideration of steroid-sparing agents, including biologic agents. Interleukin-6 (IL-6) inhibition shows the most promise as biologic therapy for refractory cases of GCA, but data to support the use of other existing biologic agents are currently lacking. A better understanding of the pathogenesis of GCA as well as clinical trials investigating both existing and emerging biologic agents is needed to expand therapeutic options for the treatment of GCA.