In the present study, we assessed the frequency and characteristics of the main causes of morbidity and mortality in systemic lupus erythematosus (SLE) during a 10-year period and compared the frequency of early manifestations with those that appeared later in the evolution of the disease. In 1990, we started a multicenter study of 1,000 patients from 7 European countries. All had medical histories documented and underwent medical interview and routine general physical examination when entered in the study, and all were followed prospectively by the same physicians during the ensuing 10 years (1990–2000). A total of 481 (48.1%) patients presented 1 or more episodes of arthritis at any time during the 10 years, 311 (31.1%) patients had malar rash, 279 (27.9%) active nephropathy, 194 (19.4%) neurologic involvement, 166 (16.6%) fever, 163 (16.3%) Raynaud phenomenon, 160 (16.0%) serositis (pleuritis and/or pericarditis), 134 (13.4%) thrombocytopenia, and 92 (9.2%) thrombosis. When the prevalences of the clinical manifestations during the initial 5 years of follow-up (1990–1995) were compared with those during the ensuing 5 years (1995–2000), most manifestations were found to be more frequent during the initial 5 years. Of the 1,000 patients, 360 (36%) presented infections, 169 (16.9%) hypertension, 121 (12.1%) osteoporosis, and 81 (8.1%) cytopenia due to immunosuppressive agents. Twenty-three (2.3%) patients developed malignancies; the most frequent primary localizations were the uterus and the breast. Sixty-eight (6.8%) patients died, and the most frequent causes of death were similarly divided between active SLE (26.5%), thromboses (26.5%), and infections (25%). A survival probability of 92% at 10 years was found. A lower survival probability was detected in those patients who presented at the beginning of the study with nephropathy (88% versus 94% in patients without nephropathy, p = 0.045). When the causes of death during the initial 5 years of follow-up (1990–1995) were compared with those during the ensuing 5 years (1995–2000), active SLE and infections (28.9% each) appeared to be the most common causes during the initial 5 years, while thromboses (26.1%) became the most common cause of death during the last 5 years. In conclusion, most of the SLE inflammatory manifestations appear to be less common after a long-term evolution of the disease, probably reflecting the effect of therapy as well as the progressive remission of the disease in many patients. Meanwhile, a more prominent role of thrombotic events is becoming evident, affecting both morbidity and mortality in SLE.

Antimalarial drugs (AMs), chloroquine (CQ) and hydroxychloroquine (HCQ), are frequently withdrawn in patients with lupus with either severe or remitting disease. However, additional effects beyond immunomodulation have been recently described. The aim of the present work was to analyse all the published evidence of the beneficial and adverse effects of AM therapy in systemic lupus erythematosus (SLE). A systematic review of the English literature between 1982 and 2007 was conducted using the MEDLINE and EMBASE databases. Randomised controlled trials (RCTs) and observational studies were selected. Case reports were excluded except for toxicity reports. The GRADE system was used to analyse the quality of the evidence. A total of 95 articles were included in the systematic review. High levels of evidence were found that AMs prevent lupus flares and increase long-term survival of patients with SLE; moderate evidence of protection against irreversible organ damage, thrombosis and bone mass loss. Toxicity related to AMs is infrequent, mild and usually reversible, with HCQ having a safer profile. In pregnant women, high levels of evidence were found that AMs, particularly HCQ, decrease lupus activity without harming the baby. By contrast, evidence supporting an effect on severe lupus activity, lipid levels and subclinical atherosclerosis was weak. Individual papers suggest effects in preventing the evolution from SLE-like to full-blown SLE, influencing vitamin D levels and protecting patients with lupus against cancer. Given the broad spectrum of beneficial effects and the safety profile, HCQ should be given to most patients with SLE during the whole course of the disease, irrespective of its severity, and be continued during pregnancy.

The therapeutic management of Sjögren syndrome (SjS) has not changed substantially in recent decades: treatment decisions remain challenging in clinical practice, without a specific therapeutic target beyond the relief of symptoms as the most important goal. In view of this scenario, the European League Against Rheumatism (EULAR) promoted and supported an international collaborative study (EULAR SS Task Force) aimed at developing the first EULAR evidence and consensus-based recommendations for the management of patients with SjS with topical and systemic medications. The aim was to develop a rational therapeutic approach to SjS patients useful for healthcare professionals, physicians undergoing specialist training, medical students, the pharmaceutical industry and drug regulatory organisations following the 2014 EULAR standardised operating procedures. The Task Force (TF) included specialists in rheumatology, internal medicine, oral health, ophthalmology, gynaecology, dermatology and epidemiology, statisticians, general practitioners, nurses and patient representatives from 30 countries of the 5 continents. Evidence was collected from studies including primary SjS patients fulfilling the 2002/2016 criteria; when no evidence was available, evidence from studies including associated SjS or patients fulfilling previous sets of criteria was considered and extrapolated. The TF endorsed the presentation of general principles for the management of patients with SjS as three overarching, general consensus-based recommendations and 12 specific recommendations that form a logical sequence, starting with the management of the central triplet of symptoms (dryness, fatigue and pain) followed by the management of systemic disease. The recommendations address the use of topical oral (saliva substitutes) and ocular (artificial tear drops, topical non-steroidal anti-inflammatory drugs, topical corticosteroids, topical CyA, serum tear drops) therapies, oral muscarinic agonists (pilocarpine, cevimeline), hydroxychloroquine, oral glucocorticoids, synthetic immunosuppressive agents (cyclophosphamide, azathioprine, methotrexate, leflunomide and mycophenolate), and biological therapies (rituximab, abatacept and belimumab). For each recommendation, levels of evidence (mostly modest) and TF agreement (mostly very high) are provided. The 2019 EULAR recommendations are based on the evidence collected in the last 16 years in the management of primary 2002 SjS patients and on discussions between a large and broadly international TF. The recommendations synthesise current thinking on SjS treatment in a set of overarching principles and recommendations. We hope that the current recommendations will be broadly applied in clinical practice and/or serve as a template for national societies to develop local recommendations.

Tumor necrosis factor (TNF)-targeted therapies are increasingly used for a rapidly expanding number of rheumatic and autoimmune diseases. With this use and longer follow-up periods of treatment, there are a growing number of reports of the development of autoimmune processes related to anti-TNF agents. We have analyzed the clinical characteristics, outcomes, and patterns of association with the different anti-TNF agents used in all reports of autoimmune diseases developing after TNF-targeted therapy found through a MEDLINE search of articles published between January 1990 and December 2006. We identified 233 cases of autoimmune diseases (vasculitis in 113, lupus in 92, interstitial lung diseases in 24, and other diseases in 4) secondary to TNF-targeted therapies in 226 patients. The anti-TNF agents were administered for rheumatoid arthritis (RA) in 187 (83%) patients, Crohn disease in 17, ankylosing spondylitis in 7, psoriatic arthritis in 6, juvenile RA in 5, and other diseases in 3. The anti-TNF agents administered were infliximab in 105 patients, etanercept in 96, adalimumab in 21, and other anti-TNF agents in 3. We found 92 reported cases of lupus following anti-TNF therapy (infliximab in 40 cases, etanercept in 37, and adalimumab in 15). Nearly half the cases fulfilled 4 or more classification criteria for systemic lupus erythematosus (SLE), which fell to one-third after discarding preexisting lupus-like features. One hundred thirteen patients developed vasculitis after receiving anti-TNF agents (etanercept in 59 cases, infliximab in 47, adalimumab in 5, and other agents in 2). Leukocytoclastic vasculitis was the most frequent type of vasculitis, and purpura was the most frequent cutaneous lesion. A significant finding was that one-quarter of patients with vasculitis related to anti-TNF agents had extracutaneous involvement. Twenty-four cases of interstitial lung disease associated with the use of anti-TNF agents were reported. In these patients, 2 specific characteristics should be highlighted: the poor prognosis in spite of cessation of anti-TNF therapy, and the possible adjuvant role of concomitant methotrexate. In conclusion, the use of anti-TNF agents has been associated with an increasing number of cases of autoimmune diseases, principally cutaneous vasculitis, lupus-like syndrome, SLE, and interstitial lung disease.