Methylprednisolone Pulses and Prolonged Remission in Systemic Lupus Erythematosus: A Propensity Score Analysis of the Longitudinal Lupus-Cruces-Bordeaux Inception Cohort.

OBJECTIVE: The objective of this study was to analyze the effect of methylprednisolone pulses (MP), given during the first year after the diagnosis of systemic lupus erythematosus (SLE), in achieving prolonged remission according to the degree of lupus activity at presentation. METHODS: We conducted an observational study of routine clinical care data from the Lupus-Cruces-Bordeaux cohort. The end point was prolonged remission (ie, during five consecutive yearly visits). The effect of MP on remission during the first year was analyzed in the whole cohort and according to the baseline Systemic Lupus Erythematosus Disease Activity Index 2000 score: <6, 6 to 12, and >12, reflecting mild, moderate, and severe activity, respectively. For adjustment, logistic regression with propensity score (PS) and other therapeutic covariates was performed. RESULTS: Two hundred thirty-three patients were included. Prolonged remission was achieved by 132 patients (57%). MP were associated with prolonged remission (PS-adjusted odds ratio [OR] 2.50, 95% confidence interval [CI] 1.04-623, P = 0.042). A strong clinical effect was seen among patients with moderate (adjusted OR 5.28, 95% CI 1.27-21.97, P = 0.022) and moderate-severe SLE activity (adjusted OR 4.07, 95% CI 1.11-14.82, P = 0.033). The administration of MP resulted in reduced average dosages of prednisone during the first year among patient with moderate (mean 6.6 vs 10.2 mg/day, P = 0.017) and severe activity (mean 14 vs 28 mg/day, P = 0.015). The odds of prolonged remission were increased by longer-term use of hydroxychloroquine (HCQ) and decreased by higher initial doses of prednisone. CONCLUSION: This study supports the use of MP to induce prolonged remission in patients with SLE, particularly in those with moderate and severe activity. The extended use of HCQ also contributes to achieve prolonged remission.

Ocular involvement in adult and paediatric patients with monogenic autoinflammatory diseases: a Spanish multicentre retrospective study.

OBJECTIVES: Ophthalmologic involvement in monogenic autoinflammatory diseases has been explored mainly in paediatric patients. The aim of this study is to characterise ophthalmologic manifestations, therapeutic management and visual outcomes in a Spanish (UVESAI) cohort of adult/paediatric patients with monogenic autoinflammatory diseases. METHODS: Multicentre and retrospective study of patients with monogenic autoinflammatory diseases and ocular involvement. Eye manifestations, structural complications, treatments used and visual outcomes were analysed, and compared with previous studies. RESULTS: Forty-six patients (44/2 adults/children; 21/25 adult/paediatric-onset) with monogenic autoinflammatory diseases [cryopyrin associated periodic syndromes (n=13/28.3%), mainly Muckle-Wells syndrome (MWS) (n=11/24%); familial Mediterranean fever (FMF) (n=12/26%); TNF receptor-associated periodic syndrome (TRAPS); (n=9/20%); Blau syndrome (n=8/17%); hyperimmunoglobulin D syndrome (HIDS) (n=2/4.3%), deficiency of adenosine deaminase-2 and NLRC4-Autoinflammatory disease] (one each) were included. Conjunctivitis (n=26/56.5%) and uveitis (n=23/50%) were the most frequent ocular manifestations. Twelve (26.1%) patients developed structural complications, being cataracts (n=11/24%) and posterior synechiae (n=10/22%) the most frequent. Conjunctivitis predominated in TRAPS, FMF, MWS and HIDS (mainly in adults), and uveitis, in Blau syndrome. Seven (8%) eyes (all with uveitis) presented with impaired visual acuity. Local and systemic treatment led to good visual outcomes in most patients. Compared with previous studies mainly including paediatric patients, less severe ocular involvement was observed in our adult/paediatric cohort. CONCLUSIONS: Conjunctivitis was the most common ocular manifestation in our TRAPS, FMF, MWS and HIDS patients, and uveitis predominated in Blau syndrome. Severe eye complications and poor visual prognosis were associated with uveitis. Adults with monogenic autoinflammatory diseases seem to exhibit a less severe ophthalmologic presentation than paediatric patients.

ANCA-associated pulmonary-renal syndrome treated with cyclophosphamide, rituximab, repeated methyl-prednisolone pulses and a reduced oral glucocorticoid regime: an observational study.

OBJECTIVES: To describe the clinical outcome of patients with pulmonary-renal syndrome (PRS) due to ANCA-associated vasculitis (AAV) from a single centre. METHODS: Observational study of routine clinical care data of patients diagnosed with PRS due to AAV from 2010 to 2020 at the Autoimmune Diseases Unit, Hospital Universitario Cruces. Mortality due to any cause within 24 months was defined as the primary outcome. Secondary outcomes included end-stage kidney disease and the need for oxygen therapy at 24 months. RESULTS: Fourteen patients were identified with a mean age at diagnosis of 62.71 years. At diagnosis, the median serum creatinine was 2.46 mg/dl and the median Birmingham Vasculitis Activity Score (BVAS) was 24. All patients were treated with repeated methyl-prednisolone pulses, 13 patients received iv cyclophosphamide 500 mg every two weeks and 12 patients received rituximab. The mean (SD) initial dose of oral prednisone was 25 (7) mg/d. A rapid tapering of oral prednisone was achieved in all patients as per protocol, with a mean (SD) dose of 10.6 (1.9) mg/d received within the first three months. No cases of death, end-stage kidney disease or with need for long-term oxygen therapy were seen. Three patients suffered a relapse and five patients had major infections, none of them opportunistic. The median creatinine and BVAS at 24 months were 1.30 mg/dl and 0, respectively. CONCLUSIONS: Combination therapy with iv cyclophosphamide and rituximab, with repeated methyl-prednisolone pulses and a rapid prednisone taper, results in early disease control, with low mortality, chronic organ damage and infections.

Anti-phospholipid antibodies do not predict damage in SLE patients in the 21st century-an observational study from the Lupus-Cruces cohort.

OBJECTIVE: To compare the influence of aPLs on global and cardiovascular damage in patients with SLE diagnosed before and after the year 2000. METHODS: Two hundred and eighty-six patients from the Lupus-Cruces cohort with a minimum follow-up of 5 years were divided into two subcohorts according to the date of diagnosis, before 2000 (less than 2000) and from 2000 on (2000 or more). We compared the mean Systemic Lupus Erythematosus International Collaborating Clinics-American College of Rheumatology (SLICC-ACR) Damage Index score and global and cardiovascular damage-free survival rates in the presence or absence of aPL in both subcohorts. Variables potentially modulating damage among aPL-positive patients were analysed. RESULTS: The subcohorts were comparable for demographic and lupus-related variables except for treatment variables: the 2000 or more subcohort received lower doses of prednisone and more HCQ, low-dose aspirin, statins, immunosuppressive agents and vitamin D. aPL-positive patients in the less than 2000, but not in the 2000 or more subcohort, accrued more damage compared with aPL-negative patients. In the less than 2000 subcohort, the adjusted hazard ratios (HRs) for global and cardiovascular damage in aPL-positive vs aPL-negative patients were 1.98 (95% CI 1.24, 3.14) and 9.3 (95% CI 3.24, 26.92), respectively. No differences in damage were seen between aPL-positive and aPL-negative patients in the 2000 or more subcohort. Hypertension (HR = 4.64, 95% CI 1.33, 16.19), LA (HR = 3.85, 95% CI 1.1, 13.41) and the number of months on HCQ (HR = 0.97, 95% CI 0.95, 0.99) were independent predictors of vascular damage in the combined analysis of all aPL-positive patients. CONCLUSION: The effects of aPL on damage accrual in SLE patients have been reduced over recent years. The widespread use of HCQ and a better thromboprophylaxis are likely causing this change.

Seventy years after Hench's Nobel prize: revisiting the use of glucocorticoids in systemic lupus erythematosus.

In 1950, Hench, Kendall and Reichstein were awarded with the Nobel Prize in Physiology and Medicine for the isolation and first therapeutic use of glucocorticoids. Since then, they have become one of the main agents in the treatment of systemic lupus erythematosus (SLE). The use of high-dose oral glucocorticoids (usually 1 mg/kg/day of prednisone equivalent) have become the rule for treating moderate to severe lupus activity. In addition, tapering schemes have not been well defined, all this leading to prolonged exposures to potentially damaging amounts of glucocorticoids. Several studies have shown that glucocorticoids are a major cause of toxicity in SLE in a dose-dependent manner, with prolonged doses greater than 7.5 mg/day being associated with damage accrual. Thus, there is an urgent need for different therapeutic schedules that can achieve a rapid and durable control of lupus activity while reducing the many unwanted effects of glucocorticoids. Recent data show that pulses of methyl-prednisolone are an effective first-line therapy to treat lupus flares (not only severe ones) without major short or long-term toxicity and allowing a reduction in oral prednisone doses. Universal use of hydroxychloroquine - always recommended, infrequently accomplished - and early therapy with immunosuppressive drugs also help control SLE and reduce prednisone load. Results from observational studies confirm the more rapid achievement of remission and the reduction of long-term damage using these combination schedules with reduced prednisone doses. Seventy years after their first therapeutic use, we are learning to use glucocorticoids in a more efficient and safe manner.

Ankle-brachial index and arterial vascular events in systemic lupus erythematosus patients: a 5-year prospective cohort.

OBJECTIVES: To determine the potential predictive value in patients with systemic lupus erythematous of the ankle-brachial index (ABI) for the occurrence of arterial vascular events. METHODS: 216 lupus patients from a prospective clinical cohort were evaluated using the ABI at the start of the study and then followed up for 5 years. Abnormal ABI was defined as an index ≤0.9 or >1.4. Several potential vascular risk factors were also evaluated. Arterial vascular events (AVE): coronary events, cerebrovascular events, peripheral arterial disease and death related to vascular disease. Survival analysis was performed using a competitive risk regression approach, considering non-vascular death as a competitive event. RESULTS: 18 arterial events and 14 deaths were identified. In the competitive risk regression analysis, independent predictors of higher risk were identified: family history of early AVE [subdistribution hazard ratio (SHR) 5.44, 95% confidence interval (CI) 1.69-17.50, p=0.004)], cumulative prednisone (grams) (SHR 1.01, 95% CI 1.01-1.03, p=0.007) and a personal history of arterial thrombosis (SHR 5.44, 95% CI 1.45-14.59, p=0.004). Female gender was a protective factor (SHR 0.22, 95% CI 0.07-0.77, p=0.017). A statistical trend was detected with abnormal ABI (SHR 2.65, 95% CI 0.86-8.14, p=0.089). CONCLUSIONS: Male gender, exposure to high cumulative doses of prednisone, family history of early arterial vascular disease and occurrence of previous arterial thrombosis are independent risk predictors of arterial vascular events in patients with systemic lupus erythematosus. Abnormal ABI may be related to high risk for arterial vascular events.

Prolonged remission in SLE is possible by using reduced doses of prednisone: An observational study from the Lupus-Cruces and Lupus-Bordeaux inception cohorts.

OBJECTIVE: The aim of this study is to compare the frequency of remission, according to DORIS definitions, of inception patients from two European SLE cohorts, with a special focus on the differences between the therapeutic schemes of both Units. METHODS: Inception patients enrolled after 2000 from the longitudinal Cruces Lupus Cohort (CC) and Bordeaux Lupus Cohort (BC) were included. The main endpoint was the achievement of clinical remission on treatment (ClinROnT). ClinROnT was assessed yearly from the 1st until the 5th year following the diagnosis of SLE. RESULTS: 173 patients, 92 CC and 81 BC, were studied. The clinical presentation of both cohorts was similar, with no significant differences in the mean SLEDAI score at diagnosis (6.6 vs. 8.1, p = 0.06). Patients from CC were treated more frequently with hydroxychloroquine (mean 57 vs. 43 months), methotrexate (24% vs. 11%) and pulse methyl-prednisolone (42% vs. 26%), and received lower doses of oral prednisone (average dose during the follow up 2.3 vs. 7.2 mg/d, p < 0.001). Patients in CC were more likely to achieve ClinROnT at year one, 84% vs. 43% (p < 0.001). Prolonged ClinROnT during the 5 years of follow up was more frequent in CC: 70% vs. 28%, p < 0.001. Patients in CC were also more likely to achieve ClinROnT after controlling for baseline SLEDAI (adjusted HR 1.69, 95%CI 1.21-2.35) and for the presenting clinical manifestations (adjusted HR 1.72, 95% CI 1.2-2.4). CONCLUSION: Prolonged ClinROnT was achievable by using a therapeutic regime consisting of lower doses of oral prednisone and maximizing the use of hydroxychloroquine, pulse methyl-prednisolone and methotrexate.

Behavior of hyperreflective foci in non-infectious uveitic macular edema, a 12-month follow-up prospective study.

BACKGROUND: Hyperreflective foci have been described in OCT imaging of patients with retinal vascular diseases. It has been suggested that they may play a role as a prognostic factor of visual outcomes in these diseases. The purpose of this study is to describe the presence of hyperreflective foci in patients with non-infectious uveitic macular edema and evaluate their behavior after treatment. METHODS: We conducted a multicenter, prospective, observational, 12-month follow-up study. Inclusion criteria were age > 18 years and a diagnosis of non-infectious uveitic macular edema, defined as central macular thickness of > 300 µm as measured by OCT and fluid in the macula. Collected data included best corrected visual acuity, central macular thickness and the presence, number and distribution (inner or outer retinal layers) of hyperreflective foci. Evaluations were performed at baseline, and at 1, 3, 6, and 12 months after starting treatment. RESULTS: We included 24 eyes of 24 patients. The frequency of patients with ≥11 hyperreflective foci was 58.4% at baseline, falling to 20.8% at 12 months. Further, hyperreflective foci were observed in the outer retinal layers in 50% of patients at baseline and just 28.6% at 12 months. Mean LogMAR visual acuity improved from 0.55 (95% CI 0.4-0.71) at baseline to 0.22 (95% CI 0.08-0.35) at 12 months (p < 0.001). Mean central macular thickness decreased from 453.83 µm (95% CI 396.6-511) at baseline to 269.32 µm (95% CI 227.7-310.9) at 12 months (P < 0.001). Central macular thickness was associated with number (p = 0.017) and distribution (p = 0.004) of hyperreflective foci. CONCLUSIONS: We have observed hyperreflective foci in most of our patients with non-infectious uveitic macular edema. During follow-up and after treatment, the number of foci diminished and they tended to be located in the inner layers of the retina.

Restrictive Use of Oral Glucocorticoids in Systemic Lupus Erythematosus and Prevention of Damage Without Worsening Long-Term Disease Control: An Observational Study.

OBJECTIVE: To analyze the influence of 2 different treatment strategies on general and specific damage accrual in patients with systemic lupus erythematosus (SLE). METHODS: Two cohorts were identified according to the responsible physicians: patients treated at the autoimmune diseases unit (ADU), and patients treated by other members of the internal medicine (IM) department. Members of the ADU worked with a protocol including the universal prescription of hydroxychloroquine (HCQ), the use of maximum oral prednisone dosages ≤30 mg/day and maintenance therapy with ≤5 mg/day, by using methylprednisolone pulses and/or early immunosuppressive (IS) drugs. We analyzed the influence of these 2 treatment strategies on damage accrual, both general and domain specific, attributed to glucocorticoids, cardiovascular (CV) disease, SLE, and unclassified, since the diagnosis of disease in patients with a followup ≥5 years. RESULTS: A total of 74 patients were included in the ADU group and 213 in the IM group. They were comparable for most demographic and lupus-related variables. ADU patients received prednisone later and at lower doses, more methylprednisolone pulses, earlier IS drugs and more HCQ (P < 0.05 for all comparisons). The Systemic Lupus Erythematosus Disease Activity Index score decreased similarly in both cohorts (P = 0.4). Patients in the ADU group were less likely to accrue any damage (P = 0.007). They accrued less glucocorticoid-related (adjusted hazard ratio [HR] 0.23 [95% confidence interval (95% CI) 0.07-0.80]), CV disease (adjusted HR 0.28 [95% CI 0.08-0.95]), and unclassified damage (adjusted HR 0.58 [95% CI 0.3-1.1]). Both groups accrued similar SLE-related damage (adjusted HR 0.84 [95% CI 0.40-1.75]). CONCLUSION: The use of reduced oral prednisone doses, which was possible by combining different therapies, reduced glucocorticoid-related damage and improved CV prognosis without increasing damage caused by SLE.

Predictors of peripheral arterial disease in SLE change with patient's age.

OBJECTIVE: To analyse the differential influence of risk factors of peripheral artery disease (PAD) according to age in patients with SLE. METHODS: 216 patients from the Lupus-Cruces cohort were divided in three age groups: ≤34 years, 35-49 years and ≥50 years. A low ankle-brachial index defined PAD. Significant variables were identified by univariant and multivariant analysis in each age group. RESULTS: Different factors were identified in different age groups: antiphospholipid antibodies/antiphospholipid syndrome and glucocorticoids in patients ≤34 years; in patients 35-49 years old, hypertension was the only statistically significant predictor, although a trend was observed for fibrinogen levels; a trend was observed for hypercholesterolaemia in those ≥50 years. CONCLUSIONS: Age may modulate the influence of risk factors for PAD in patients with SLE.

New insights into the genetic component of non-infectious uveitis through an Immunochip strategy.

BACKGROUND: Large-scale genetic studies have reported several loci associated with specific disorders involving uveitis. Our aim was to identify genetic risk factors that might predispose to uveitis per se, independent of the clinical diagnosis, by performing a dense genotyping of immune-related loci. METHODS: 613 cases and 3693 unaffected controls from three European case/control sets were genotyped using the Immunochip array. Only patients with non-infectious non-anterior uveitis and without systemic features were selected. To perform a more comprehensive analysis of the human leucocyte antigen (HLA) region, SNPs, classical alleles and polymorphic amino acid variants were obtained via imputation. A meta-analysis combining the three case/control sets was conducted by the inverse variance method. RESULTS: The highest peak belonged to the HLA region. A more detailed analysis of this signal evidenced a strong association between the classical allele HLA-A*2902 and birdshot chorioretinopathy (p=3.21E-35, OR=50.95). An omnibus test yielded HLA-A 62 and 63 as relevant amino acid positions for this disease. In patients with intermediate and posterior uveitis, the strongest associations belonged to the rs7197 polymorphism, within HLA-DRA (p=2.07E-11, OR=1.99), and the HLA-DR15 haplotype (DRB1*1501: p=1.16E-10, OR=2.08; DQA1*0102: p=4.37E-09, OR=1.77; DQB1*0602: p=7.26E-10, OR=2.02). Outside the HLA region, the MAP4K4/IL1R2 locus reached statistical significance (rs7608679: p=8.38E-07, OR=1.42). Suggestive associations were found at five other loci. CONCLUSIONS: We have further interrogated the association between the HLA region and non-infectious non-anterior uveitis. In addition, we have identified a new non-HLA susceptibility factor and proposed additional risk loci with putative roles in this complex condition.

Dexamethasone intravitreal implants in the management of tubercular multifocal serpiginoid choroiditis.

BACKGROUND: Continuous progression of lesions despite an adequate treatment has been described in tubercular multifocal serpiginoid choroiditis. Reported treatments for this paradoxical response include systemic steroids, immunosuppressive drugs, and intravitreal methotrexate. We describe the use of dexamethasone intravitreal implants in a patient presenting with this condition. FINDINGS: A 46-year-old woman sought medical attention for scotomas in her left eye. Tests suggested multifocal serpiginoid choroiditis associated with latent tuberculosis infection, and hence, she was started on anti-tuberculosis drugs in combination with corticosteroids. Given that lesions progressed despite this treatment, we began treatment with dexamethasone intravitreal implants. After injection of the second implant, we succeeded in inactivating the inflammatory process. CONCLUSIONS: Dexamethasone intravitreal implants may be a suitable alternative to systemic steroids or immunosuppressive therapy in the management of continuous progression of lesions in tubercular multifocal serpiginoid choroiditis.

SAFETY AND EFFICACY OF INTRAVITREAL DEXAMETHASONE IMPLANTS IN THE MANAGEMENT OF MACULAR EDEMA SECONDARY TO INFECTIOUS UVEITIS.

PURPOSE: To assess the safety and efficacy of intravitreal dexamethasone implants in the treatment of macular edema secondary to infectious uveitis. METHODS: We retrospectively reviewed clinical records from three uveitis referral units in Spain. The main outcome measures were rate of reactivation of infection, improvements in visual acuity and resolution of macular edema, as measured by optical coherence tomography. RESULTS: We included eight eyes from seven patients with a median age of 64 years (30-75). Etiologies of the infections were Herpes simplex virus-type 1, Varicela-Zoster virus, Treponema pallidum, Brucella mellitensis, Borrelia burgdorferi, Toxoplasma gondii, and cytomegalovirus. Median visual acuity was 20/160 (20/30-20/400) at baseline and 20/70 (20/25-20/200) at the last follow-up visit. Mean macular thickness was 516 µm (115) at baseline and 266.3 µm (40) at the last follow-up visit. Visual acuity improved in 100% of the eyes and none of the eyes showed macular edema at the last follow-up visit. Five patients required reinjections of the implant. Only one patient required antiglaucoma drops for a temporary increase in ocular pressure. There were no cases of reactivation of the infectious ocular disease. Median follow-up time was 18 months. CONCLUSION: In this small case series of eyes with macular edema secondary to infectious uveitis, treatment with dexamethasone intravitreal implants was not associated with reactivation of the infectious ocular disease. Furthermore, significant improvements in visual acuity and macular thickness were observed in our patients.

Comparison of high versus low-medium prednisone doses for the treatment of systemic lupus erythematosus patients with high activity at diagnosis.

OBJECTIVE: To compare the efficacy and safety of high vs. low-moderate oral doses of prednisone to treat patients with highly active lupus at diagnosis. PATIENTS AND METHODS: Patients from the Lupus-Cruces cohort with an SLEDAI score ≥6 at diagnosis and treated with regimes containing low-medium prednisone doses (≤30 mg/day) were identified (group M). They were matched by sex and SLEDAI score with historical patients treated with high doses (>30 mg/day) at diagnosis (group H). Patients with proliferative nephritis were excluded. The difference in SLEDAI scores between baseline (SLEDAI-0) and year one (SLEDAI-1) was the efficacy variable. Damage at 5 years was calculated using the SLICC damage index (SDI) and regarded as the safety variable. Glucocorticoid related damage was considered in the presence of cataracts, osteonecrosis, osteoporotic fractures and/or diabetes mellitus. RESULTS: 30 patients were included in each group. Patients in group H received 5-fold higher doses of prednisone, less hydroxychloroquine and less methyl-prednisolone pulses. SLEDAI improvement was similar in both groups. Patients in group H were more likely to accrue new damage (adjusted HR 3.85 (95% CI 1.03-14.2)). No patients in group M suffered glucocorticoid-related damage, vs. 5 patients in group H (p=0.02). The average daily prednisone dose during the first year predicted accrual of new damage (adjusted HR 1.03, 95% CI 1.0-1.07, p=0.056) and accrual of glucocorticoid-related damage (adjusted HR 1.06, 95% CI 1.01-1.13, p=0.03). Likewise, average doses of prednisone >7.5mg/day were an independent predictor of new damage (adjusted HR 4.8, 95% CI 1.2-19.1). CONCLUSION: Prednisone doses ≤30 mg/day are similarly effective and safer than higher doses for treating active lupus.

Specific association of IL17A genetic variants with panuveitis.

BACKGROUND/AIMS: A pathogenic role of Th17 cells in uveitis has become clear in recent years. Therefore, in the present study, we aimed to evaluate the possible influence of the IL17A locus on susceptibility to non-anterior uveitis and its main clinical subgroups. METHODS: Five IL17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909), selected by tagging, were genotyped using TaqMan assays in 353 Spanish patients with non-anterior uveitis and 1851 ethnically matched controls. RESULTS: The case/control analysis yielded a consistent association between two of the analysed genetic variants, rs8193036 and rs2275913, and the presence of panuveitis under a dominant model (pFDR=2.86E-03, OR=2.26, 95% CI 1.42 to 3.59 and pFDR=0.033, OR=1.83, 95% CI 1.13 to 2.97, respectively). Subsequently, a specific association of both polymorphisms with the diffuse form of the disease was evident in the subphenotype analysis when considering this same genetic model (panuveitis vs posterior and intermediate uveitis: rs8193036, p=0.020; rs2275913, p=0.038). Independent effects of rs8193036 and rs2275913 were observed by conditional regression analysis. CONCLUSIONS: Polymorphisms within the IL17A locus show a novel association with panuveitis. Our data agree with the elevated levels of this cytokine that are found in patients with uveitis, supporting a crucial role of Th17 cells in this pathology. SUBTITLE: Our results clearly evidenced the role of IL17A as a novel genetic risk factor for panuveitis, thus suggesting the implication of Th17 cells in the extensive inflammation of the uveal tract that occurs in this subtype of uveitis.

Minimal disease activity and anti-tumor necrosis factor therapy in psoriatic arthritis.

OBJECTIVE: A state of minimal disease activity (MDA) was defined and validated as target for treatment in psoriatic arthritis (PsA). We aimed to identify disease characteristics, outcome, and predictors of MDA in patients treated with tumor necrosis factor α (TNFα) blockers. METHODS: Patients fulfilling the Classification of Psoriatic Arthritis criteria treated with TNFα blockers were followed every 3-6 months. Patients were considered in MDA when they meet at least 5 of the 7 criteria. Sustained MDA was defined as an MDA state lasting ≥12 months. Patients achieving MDA were compared to non-MDA patients. A proportional odds discrete time survival analysis model was applied, adjusting for sex, age, PsA duration, abnormal erythrocyte sedimentation rate (ESR) and clinically damaged joint count at each visit to identify predictors for MDA. RESULTS: Of the 306 patients treated with TNFα blockers identified from our database, 23 patients were in an MDA state when treatment was commenced; 57 were taking TNFα blockers prior to enrollment. Therefore, 226 subjects were in a non-MDA state and constituted the study population. One hundred forty-five patients of 226 patients (64%) achieved MDA within a mean ± SD duration of 1.30 ± 1.68 years. The mean ± SD duration of MDA was 3.46 ± 2.25 years. At total of 17 patients withdrew from therapy and remained in an MDA state. Male sex (odds ratio [OR] 1.65, 95% confidence interval [95% CI] 1.08-2.53; P = 0.02) and normal ESR (OR 2.27, 95% CI 1.22-4.17; P = 0.009) increased the odds for achieving MDA. CONCLUSION: MDA is achieved in 64% of patients treated with TNFα blockers in a clinical setting. Male sex and normal ESR are predictors for MDA. On withdrawal or reduction in treatment, 11.6% of patients maintained MDA state.

Glucocorticoids and irreversible damage in patients with systemic lupus erythematosus.

OBJECTIVE: The aim of this study was to analyse the relationship between glucocorticoids and damage accrual in SLE. METHODS: We report an observational cohort study including 230 patients with SLE enrolled at diagnosis with 5 years of follow-up. Damage was calculated using the SLICC damage index. Glucocorticoid-related damage was defined as avascular osteonecrosis, osteoporotic fractures, diabetes mellitus or cataracts. Prednisone doses were calculated at the end of the fourth year of follow-up (prednisone-4). A categorical prednisone-4 variable was constructed: no prednisone, ≤7.5 mg/day (low dose), >7.5 mg/day (medium-high dose). The relationship between methylprednisolone pulses and damage was also tested. RESULTS: By the fifth year, 188 patients (82%) had been treated with prednisone. Eighty-seven patients (37.8%) had accrued damage at 5 years. Patients with damage at year 5 had received a higher mean daily prednisone-4 dose (10.4 vs 6 mg/day, P < 0.001). The mean daily prednisone-4 dose was higher in patients accruing glucocorticoid-attributable damage (11 vs 7 mg/day, P = 0.04). Patients taking medium-high doses of prednisone-4 had a higher risk of accruing damage than those taking no prednisone [adjusted odds ratio (OR) 5.39, 95% CI 1.59, 18.27]. Patients taking medium-high doses of prednisone-4 were more likely to develop glucocorticoid-related damage than those on no prednisone (adjusted OR 9.9, 95% CI 1.1, 84). No differences were seen between patients on low doses and those on no prednisone. The cumulative dose of i.v. methylprednisolone-4 was not associated with global or glucocorticoid-related damage. CONCLUSION: Prednisone causes damage in SLE. Doses <7.5 mg/day and methylprednisolone pulses are not associated with damage accrual.

Predictors of major infections in systemic lupus erythematosus.

INTRODUCTION: Infections commonly complicate the course of systemic lupus erythematosus (SLE). Our aim is to investigate the clinical predictors of major infections in patients with SLE. METHODS: A nested case-control study design was used within the prospective Lupus-Cruces cohort. The endpoints of the study were major infections. Cases were defined as patients with a major infection. Two controls (SLE patients without major infections), matched for time of follow-up until the event and age at diagnosis, were selected for each case. Univariate analysis and logistic regression models were used for the analysis of data. RESULTS: Two hundred and forty-nine patients (83 cases, 166 controls) were selected. Eighty-three episodes of major infections were analyzed; E. coli, S. aureus, M. tuberculosis and S. pneumoniae being the most frequent isolates. Univariate analysis identified several variables related with infection: lung and renal involvement, at or previous to the study point; leukopenia at the study point; antiphospholipid antibody-positivity and treatment with prednisone within 3 months previous to the study point, and the dose of prednisone received. Treatment with antimalarials, on the other hand, showed a strong inverse association with major infections. Logistic regression models identified treatment with antimalarials (odds ratio (OR) = 0.06, 95% confidence interval (CI) = 0.02 to 0.18), prednisone dose (OR = 1.12, 95% CI = 1.04 to 1.19) and lung involvement (OR = 4.41, 95% CI = 1.06 to 18.36) as significant and independent predictors of major infections. No significant interactions among these three variables were found. Further adjustment for potential confounders related with antimalarial treatment did not change the results. CONCLUSIONS: The risk of major infections in patients with SLE is mostly influenced by treatment. Prednisone treatment, even at moderate doses, increases the risk, whilst antimalarials have a protective effect.