Faculty Bibliography

PURPOSE/OBJECTIVE:Corneal melting with perforation is a severe ophthalmic complication of autoimmune disorders such as rheumatoid arthritis. It requires urgent medical management in order to maintain the integrity of the globe and preserve vision. Treating this complication by penetrating keratoplasty is problematic due to the high rate of recurrence of corneal melting as well as other complications. We describe the use of a tectonic fresh-tissue corneolimbal covering graft. METHODS:An interventional case series including three patients that presented to our tertiary center between 2000 and 2015 with corneal melting and perforation, secondary to rheumatoid arthritis. Emergency surgery included suturing of a 13.00- to 13.50-mm full-thickness fresh-tissue corneolimbal covering graft to the patient's posterior limbal zone. RESULTS:The corneolimbal graft maintained the integrity of the cornea in all cases, by sealing the perforation and promoting the creation of a fibrovascular scar at the area of corneal melting. There were no complications, recurrences of host corneal melting, or perforation during the follow-up period. CONCLUSION/CONCLUSIONS:Fresh-tissue full-thickness corneolimbal grafts may be used to cover emergency corneal melting and perforations secondary to rheumatoid arthritis.

BACKGROUND:Chronic fatigue is common among patients with rheumatoid arthritis (RA), affecting quality of life. Osteoporosis is a prevalent co-morbidity in RA patients. OBJECTIVES/OBJECTIVE:To assess the effect of long-term treatment with tocilizumab on fatigue and bone mineral density (BMD) in RA patients with inadequate response to synthetic or biologic disease-modifying anti-rheumatic drugs. METHODS:In this multicenter, open-label, non-controlled, single-arm study, patients ≥ 18 years of age received intravenous tocilizumab 8 mg/kg every 4 weeks for 96 weeks. The primary outcome was the change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to weeks 24, 48, 72, and 96. BMD was assessed before and 96 weeks after treatment. RESULTS:The study comprised 145 patients (mean age 53.4 ± 13.4 years, 83.4% women). Of these, 88 (60.7%) completed the 2 year treatment period. The mean FACIT-Fatigue score improved consistently starting from week 4 and showed a statistically significant increase of 5.0 ± 9.7, 6.8 ± 10.5, 7.3 ± 10.9, and 7.3 ± 10.4 from baseline to weeks 24, 48, 72, and 96, respectively (P < 0.0001). Mean BMD of femoral neck and total spine remained stable. Disease activity, acute phase reactants, and composite efficacy measures decreased during the study, while hemoglobin levels increased. Adverse events and serious adverse events were as expected for the known and previously described data. CONCLUSIONS:Tocilizumab therapy for 2 years significantly and clinically decreased fatigue. BMD remained stable and no new safety issue was reported.

INTRODUCTION/BACKGROUND:IgG4-related disease is a syndrome of unknown etiology, which can affect any organ. It is characterized by lymphoplasmacytic infiltration of the affected organs that is rich in IgG4-positive plasma cells, fibrosis, and sometimes increased blood levels of IgG4. Treatment is determined according to the organs involved and the severity of involvement. Corticosteroids are considered to be the first line of treatment. In steroid-resistant or recurrent disease, immunosuppressive drugs or rituximab are used, although their efficacy has not been proven in clinical trials. This review describes the current understanding of the pathogenesis, clinical features, diagnosis and treatment of IgG4-related disease.

BACKGROUND:Tumor necrosis factor-alpha (TNFα) inhibitors are indicated for patients with psoriatic arthritis (PsA) in whom conventional disease-modifying anti-rheumatic drugs (DMARDs) are insufficient to achieve disease remission. OBJECTIVES/OBJECTIVE:To determine the value of acute-phase reactant levels at diagnosis of psoriatic arthritis in predicting the need for biologic treatment with TNFα inhibitors. METHODS:We conducted a longitudinal observational study of an inception cohort of 71 consecutive patients diagnosed with psoriatic arthritis. C-reactive protein (CRP) was assayed for all patients at their first visit. RESULTS:All patients were treated with one or more DMARDs, mainly methotrexate (81.6%). Thirty-seven patients (52.11%) had an inadequate response and received at least one TNF inhibitor. CRP level at diagnosis was positively correlated with need for a TNF inhibitor (P = 0.009, HR 1.8, 95% CI 1.27-1.85). Patients with CRP > 0.9 mg/dl at diagnosis started biologic treatment significantly earlier than patients with a lower level (P = 0.003, HR 2.62, 95% CI 0.393-2.5). CONCLUSIONS:In patients with psoriatic arthritis, CRP ≥ 0.9 mg/dl at diagnosis significantly predicts an earlier need for a TNF inhibitor to achieve disease control.

In the course of investigating anti-DNA autoantibodies, we examined IgM and IgG antibodies to poly-G and other oligonucleotides in the sera of healthy persons and those diagnosed with Systemic Lupus Erythematosus (SLE), Scleroderma (SSc), or Pemphigus Vulgaris (PV); we used an antigen microarray and informatic analysis. We now report that all of the 135 humans studied, irrespective of health or autoimmune disease, manifested relatively high amounts of IgG antibodies binding to the 20-mer G oligonucleotide (G20); no subjects entirely lacked this reactivity. IgG antibodies to homo-nucleotides A20, C20 or T20 were present only in the sera of SLE patients who were positive for antibodies to dsDNA. The prevalence of anti-G20 antibodies led us to survey human, mouse and Drosophila melanogaster (Fruit fly) genomes for runs of T20 and G20 or more: runs of T20 appear more than 170,000 times compared to only 93 runs of G20 or more in the human genome; of these runs, 40 were close to brain-associated genes. Mouse and fruit fly genomes showed significantly lower T20/G20 ratios than did human genomes. Moreover, sera from both healthy and SLE mice contained relatively little or no anti-G20 antibodies; thus natural anti-G20 antibodies appear to be characteristic of humans. These unexpected observations invite investigation of the immune functions of anti-G20 antibodies in human health and disease and of runs of G20 in the human genome

OBJECTIVES: To assess serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) levels in disease-modifying anti-rheumatic drug (DMARD)-naive early rheumatoid arthritis (ERA), to investigate the association of sTREM-1 levels with Disease Activity Score in 28 joints (DAS28) and seropositivity for anti- cyclic citrullinated peptide (CCP) antibody, and to determine the predictive value of sTREM-1with respect to clinical response to DMARD therapy. METHODS: Twenty-two consecutive patients with DMARD-naive ERA were prospectively evaluated for serum sTREM-1 by means of ELISA at diagnosis and at the following clinic visit after prednisone and/or DMARD has been administered, and related to DAS28 and serum level of anti-CCP antibody. We compared the sTREM-1 level to that of 31 patients with established RA as well as to 24 controls. RESULTS: Serum sTREM-1 level was significantly higher in the DMARD-naive ERA group (2,122.9+/-388.9 rhog/ml) compared to established RA group (1,478.0+/-280.0 rhog/ml, p = 0.001) and normal control (34.4+/-7.4 rhog/ml, p < 0.001). In the ERA group, elevated basal sTREM-1 level correlated with higher DAS28-CRP score (p = 0.001, HR3.23, 95% CI 1.4 - 8.12), DAS28-ESR (p = 0.04, HR 2.34 95%CI 0.1-8.12), as well as predicted higher DAS28 score at the following encounter after DMARD treatment was administered (p = 0.001, HR 3.2 95% CI 1.1-7.2). Higher serum level of sTREM-1 correlated with higher titers of anti-CCP antibody (p < 0.001). CONCLUSIONS: Our results suggest that serum sTREM-1 may provide a novel biomarker for DMARD-naive ERA as well as for seropositivity for anti-CCP antibody and RA activity

Antiphospholipid syndrome (APLS) is an autoimmune hypercoagulable syndrome characterized by thrombotic and obstetric manifestations. We sought to determine the rate of APLS feature in patients tested positive for antiphospholipid antibodies (APLA) regardless of the serum level of anticardiolipin (ACL) and/or anti-beta2-glycoprotein I (beta2GPI) antibodies. An inception cohort of individuals who were tested positive for ACL and/or beta2GPI IgG/IgM antibody, and/or lupus anticoagulant (LAC) on two occasions of at least 12 weeks apart. A total of 243 patients were included; their mean age was 40.1 +/- 15.9 years. Thrombotic vascular events occurred in 118 patients (48.5%) of the entire cohort, of which 62 patients (25.5%) suffered from an arterial event and 56 patients (23%) from thrombotic venous events. Obstetrical morbidity occurred in 106 female patients (43.6%). In our cohort, we found no difference in the frequency of thrombotic or obstetric manifestations of APLS between patients with ACL IgG/IgM of low serum antibody level (<40 U) and medium-to-high level (>/=40 U) and/or anti-beta2GPI IgG, IgM higher than the 99th percentile vs. lower (>20 U). We suggest that in 'real life' the diagnosis of APLS should not be excluded because of low titer of APLA.