Performance of the 2016 ACR/EULAR SS classification criteria in patients with secondary Sjögren's syndrome.

OBJECTIVES: To evaluate the performance of the 2016 ACR-EULAR classification Sjögren's syndrome (SS) criteria for classifying patients with secondary SS. METHODS: We randomly selected 300 patients with systemic lupus erythematosus, rheumatoid arthritis and scleroderma, as well as 50 with primary SS. SS diagnosis was established by two independent rheumatologists and was based on the combination of symptoms, signs, diagnostic tests and medical chart review. We evaluated the fulfillment of the 2002 AECG, 2012 ACR and 2016 ACR/EULAR criteria, and their performance using as the gold standard the clinical diagnosis. RESULTS: We identified 154 patients with a clinical (definitive/probable) SS diagnosis, 95 patients (61.7%) fulfilled the AECG, 96 patients (62.3%) the ACR and 90 (58.4%) the 2016 ACR/EULAR criteria. Among the subset with definitive SS clinical diagnosis (n=99), 83 patients (83.8%) fulfilled the AECG, 77 (77.7%) the ACR and 79 (79.7%) the 2016 ACR/EULAR criteria. The concordance rate between the clinical diagnosis (definitive/probable) and the AECG, ACR and 2016 ACR/ EULAR criteria was κ=0.58, κ=0.55 and κ=0.60, respectively. The 2016 ACR/EULAR criteria showed the best AUCs results (0.87 definitive/probable diagnosis, 0.90 definitive diagnosis), followed by the AECG (0.82 definitive/probable diagnosis, 0.85 definitive diagnosis) and ACR (0.80 definitive/probable diagnosis, 0.79 definitive diagnosis) criteria. As a sensitivity analysis, the results were similar when excluding patients with primary SS. CONCLUSIONS: Our study provides further evidence that the 2016 ACR/EULAR criteria are applicable in the setting of secondary SS.

Clinical significance of ocular manifestations in granulomatosis with polyangiitis: association with sinonasal involvement and damage.

Ocular involvement is present in 50-60% of granulomatosis with polyangiitis (GPA) patients and can affect any part of the ocular globe. The present study describes ophthalmologic manifestations, association with systemic symptoms, disease activity and damage in GPA. A cross-sectional study was conducted including patients with GPA who underwent rheumatologic and ophthalmologic evaluation. Demographics, comorbidities, ophthalmologic symptoms, serologic markers, radiographic studies, disease activity and damage were assessed. Descriptive statistics, correlation, univariable logistic regression analyses, Student's t, Mann-Whitney U, Chi-square and Fisher's exact tests were performed. Fifty patients were included, 60% female, the median age was 56 years, disease duration 72.5 months. Nineteen (38%) patients had ocular manifestations at GPA diagnosis, scleritis being the most frequent; 27 (54%) patients presented ocular involvement during follow-up, repeated scleritis and dacryocystitis being the most common manifestations. Concomitant ophthalmic and sinonasal involvement was present in 12 (24%). Ocular and ENT damage occurred in 58% and 70%, respectively. Epiphora and blurred vision were the most frequent symptoms; scleromalacia and conjunctival hyperemia (27%) the most frequent clinical abnormalities. Ocular involvement at diagnosis was associated with concomitant ocular and sinonasal involvement at follow-up (OR 4.72, 95% CI 1.17-19.01, p = 0.01). Ocular involvement at follow-up was associated with age at GPA diagnosis (OR 0.94, 95% CI 0.90-0.99, p = 0.03), VDI (OR 1.29, 95% CI 1.03-1.61, p = 0.02), and ENT damage (OR 5.27, 95% CI 1.37-20.13, p = 0.01). In GPA, ocular involvement is frequent, therefore, non-ophthalmologist clinicians should be aware of this manifestation to reduce the risk of visual morbidity and organ damage.

Utility of the American-European Consensus Group and American College of Rheumatology Classification Criteria for Sjögren's syndrome in patients with systemic autoimmune diseases in the clinical setting.

OBJECTIVE: The aim of this study was to evaluate the feasibility and performance of the American-European Consensus Group (AECG) and ACR Classification Criteria for SS in patients with systemic autoimmune diseases. METHODS: Three hundred and fifty patients with primary SS, SLE, RA or scleroderma were randomly selected from our patient registry. Each patient was clinically diagnosed as probable/definitive SS or non-SS following a standardized evaluation including clinical symptoms and manifestations, confirmatory tests, fluorescein staining test, autoantibodies, lip biopsy and medical chart review. Using the clinical diagnosis as the gold standard, the degree of agreement with each criteria set and between the criteria sets was estimated. RESULTS: One hundred fifty-four (44%) patients were diagnosed with SS. The AECG criteria were incomplete in 36 patients (10.3%) and the ACR criteria in 96 (27.4%; P < 0.001). Nevertheless, their ability to classify patients was almost identical, with a sensitivity of 61.6 vs 62.3 and a specificity of 94.3 vs 91.3, respectively. Either set of criteria was met by 123 patients (80%); 95 (61.7%) met the AECG criteria and 96 (62.3%) met the ACR criteria, but only 68 (44.2%) patients met both sets. The concordance rate between clinical diagnosis and AECG or ACR criteria was moderate (k statistic 0.58 and 0.55, respectively). Among 99 patients with definitive SS sensitivity was 83.3 vs 77.7 and specificity was 90.8 vs 85.6, respectively. A discrepancy between clinical diagnosis and criteria was seen in 59 patients (17%). CONCLUSION: The feasibility of the SS AECG criteria is superior to that of the ACR criteria, however, their performance was similar among patients with systemic autoimmune diseases. A subset of SS patients is still missed by both criteria sets.

Rituximab in the treatment of refractory scleritis in patients with granulomatosis with polyangiitis (Wegener's).

PURPOSE: The purpose of this descriptive study was to evaluate the clinical response to rituximab (RTX) in patients with scleritis due to granulomatosis with polyangiitis (GPA), in patients who had proved refractory to treatment with systemic glucocorticoids and immunosuppressive agents. METHODS: Retrospective analysis of interventional case series. Single referral center study. Eight patients (12 affected eyes) due to scleritis secondary to GPA, refractory to conventional treatment were included to receive RTX as therapy for remission induction. RTX was administered as a 1-g infusion every 2 weeks, for a total of 2 g. Patient follow-up included clinical evaluation (systemic and ophthalmologic), B-cell subset (CD19, CD20, CD22) counts, proteinase-3 anti-neutrophil cytoplasmic antibody (PR-3 ANCA), and Birmingham Vasculitis Activity Score for Wegener's granulomatosis (BVAS-WG). Outcomes were response to treatment and achievement of remission, as well as number of ocular relapses. RESULTS: The main indication for treatment was refractory necrotising anterior scleritis. Four weeks after completion of treatment with RTX, all patients showed clear clinical improvement, with no further progression. In all patients, an absolute depletion of B cells was confirmed in the first 6 weeks after treatment. Seven patients (87.5 %) achieved remission of inflammatory activity in 7 months or less. However, three patients experienced ocular relapse, which comprised reactivation of the anterior scleritis, uveitis, and posterior scleritis, and two patients required a second dose of RTX, with immediate improvement. CONCLUSIONS: RTX is useful in the treatment of refractory necrotising scleritis in patients with GPA. Of note, in those who relapse after remission, RTX can be successfully used for retreatment.

Lactic Acidosis Complicating Metformin and Non-Nucleoside Reverse Transcriptase Inhibitor Combination Therapy: A Smoldering Threat in the Post-HAART Era.

Dear Editor, The prevalence of type 2 diabetes (DM-2) in HIV-infected patients and the concomitant use of metformin (MTF) and non-nucleoside reverse transcriptase inhibitors (NRTI) is rising. Through inhibition of NADH dehydrogenase and DNA pol-γ, both drugs hinder oxidative phosphorylation that may lead to lactic acidosis (LA). Among NRTIs, abacavir and tenofovir have the lowest mitochondrial toxicity, with only a few LA cases reported2-4. We describe here a case of MTF-associated LA (MALA) secondary to the interaction with NRTI.

Predicting Sjögren's syndrome in patients with recent-onset SLE.

OBJECTIVE: To determine the prevalence of SS in a cohort of recent-onset SLE patients and evaluate the clinical and immunological variables that may identify SLE patients prone to develop SS. METHODS: A total of 103 patients participating in a prospective cohort of recent-onset SLE were assessed for fulfilment of the American European Consensus Group criteria for SS using a three-phase approach: screening (European questionnaire, Schirmer-I test and wafer test), confirmation (fluorescein staining test, non-stimulated whole-salivary flow and anti-Ro/La antibodies) and lip biopsy. Anti-Ro/SSA and anti-La/SSB antibodies and RF were measured at entry into the cohort and at SS assessment. RESULTS: Ninety-three females and 10 males were included. Mean age at lupus diagnosis was 25.9 ± 8.9 years, and lupus duration at SS assessment was 30.9 ± 9.1 years. SS was diagnosed in 19 (18.5%) patients, all female, and the patients were older at SLE diagnosis than patients without SS (30.8 ± 9.3 vs 24 ± 8.8 years, P = 0.004). Anti-Ro/SSA antibody was more common in SLE-SS patients (84% vs 55%, P = 0.02, LR + 1.53, 95% CI 1.14, 2.04). In the multivariate analysis, age ≥25 years and anti-Ro/SSA antibodies at SLE diagnosis were identified as predictors of SLE-SS, while the absence of anti-Ro/SSA, anti-La/SSB and RF seems to be protective (LR- 0.14, 95% CI 0.02, 0.95). CONCLUSION: The overlap of SLE and SS occurs in almost one-fifth of SLE patients and presents early during its evolution. SLE onset at age ≥25 years plus the presence of anti-Ro/SSA antibody at diagnosis are useful predictors, while the absence of anti-Ro/SSA, anti-La/SSB and RF identifies patients at lowest risk.

Usefulness of IgA Anti-α-fodrin Antibodies in Combination with Rheumatoid Factor and/or Antinuclear Antibodies as Substitute Immunological Criterion in Sjögren Syndrome with Negative Anti-SSA/SSB Antibodies.

OBJECTIVE: We aimed to evaluate the usefulness of anti-α-fodrin antibodies (AFA) in combination with rheumatoid factor (RF) and/or antinuclear antibodies (ANA) as an alternative immunological criterion for Sjögren syndrome (SS) among patients with negative anti-Ro/La serology. METHODS: The study included 350 patients (100 with rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, and 50 with primary SS) randomly selected and assessed for SS. All patients were tested for ANA, RF, anti-SSA/SSB, and AFA antibodies. SS diagnosis was made on a clinical basis by 2 rheumatologists based on the 6-item screening questionnaire, Schirmer-I test, nonstimulated whole salivary flow rate, fluorescein staining test, autoantibodies, lip biopsy, and medical chart review. Non-SS was defined as lack of clinical diagnosis and not fulfilling the American-European Consensus Group classification criteria and the American College of Rheumatology (ACR) criteria. The ACR criteria were applied substituting the immunological criteria as follows: (1) RF plus ANA > 1:320, (2) RF plus AFA, (3) ANA > 1:320 plus AFA, (4) RF alone, and (5) 2 positive tests out of RF, ANA > 1:320, or AFA. We estimated the sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio positivity with 95% CI for each criterion. RESULTS: There were 236 patients (67%) who tested negative for anti-SSA/SSB antibodies, of whom 65 (27.5%) were clinically diagnosed as SS, and 149 (63%) with non-SS. RF + AFA and ANA + AFA performed similarly to RF + ANA > 1:320. The model 2 out of 3 of RF, ANA, or AFA improved the sensitivity from 56.9% to 70.7%, although the specificity decreased. CONCLUSION: The combination AFA + RF, AFA + ANA > 1:320, or at least 2 out of 3, performed well as a proxy immunological test for patients with SS and negative Ro/La serology.

Extensive dynamics in location, shape, and size of aneurysms in a patient with idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome. Idiopathic retinal vasculitis, aneurysms, and neuroretinitis.

PURPOSE: To describe an unusual case of idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome with rapid dynamics in the number and appearance of the aneurysms. DESIGN: Observational case report. METHODS: Clinical and angiographic data of the patient were reviewed. RESULTS: In the course of only 6 months, preexisting retinal aneurysms resolved while new ones appeared. Changes were observed in the shape and size of preexisting lesions. The resolution of lesions in eyes previously untreated by laser is reported for the first time. CONCLUSIONS: Vascular lesions in IRVAN syndrome may show an unusually rapid turnover. The resolution of aneurysms is a part of the natural course of the disease and may occur without previous retinal laser photocoagulation.

Pars planitis in the Mexican Mestizo population: ocular findings, treatment, and visual outcome.

PURPOSE: To describe the clinical manifestations of classic pars planitis (CPP) in Mexican patients. We report here the most frequent complications, medical and surgical treatment, and visual prognosis. MATERIAL AND METHODS: A retrospective, descriptive case series examined the clinical features, complications, and treatment (medical and surgical) of CPP patients seen at the Inflammatory Eye Disease Clinic from January 1990 to September 1999. RESULTS: One hundred and sixty patients met inclusion criteria for the study. Mean age at presentation was 10 years and males were more frequently affected. Both eyes were affected in 84.4% of the cases. The most frequent complaint was decreased visual acuity. Initial visual acuity (VA) ranged from no light perception to 20/20 (mean 20/50), and mean final VA was 20/30. The most frequent clinical manifestations were vitritis (99.7%), snowballs (99.3%), retinal vasculitis (89.2%), and snowbanks (63.1%). The most common complications were cystoid macular edema (63.4%) and cataract (47.5%). Periocular corticosteroids were used in 97.5% of cases, systemic corticosteroids in 68.1%, and other immunosuppressive drugs in 21.3%. CONCLUSIONS: CPP in the Mexican population is more frequent in males and usually presents in patients less than 14 years of age. It is typically bilateral, and the most common symptom is decreased visual acuity. The most important clinical findings are located in the vitreous and retina. Cataract and cystoid macular edema are the most frequent complications. Treatment comprises periocular and systemic corticosteroids or other immunosuppressive drugs.

Fuchs' heterochromic iridocyclitis: clinical manifestations in dark-eyed Mexican patients.

PURPOSE: To describe the clinical features of Fuch's heterochromic iridocyclitis (FHI) in dark-eyed Mexican patients. MATERIAL AND METHODS: A longitudinal, retrospective, and analytical study of the clinical features of FHI patients was performed. It reviewed the clinical charts of all patients with a diagnosis of FHI seen at the Inflammatory Eye Diseases Clinic of 'Dr. Luis Sánchez Bulnes' Hospital between April 1988 and September 1999. RESULTS: Data of 68 patients (136 eyes) were reviewed. One eye was affected in 89.71% of the cases (61 patients). Fifty patients had brown eyes and iris heterochromia was clinically evident in 25%. Mild stellate keratic precipitates were seen in 80% of the affected eyes. Blurring of the iris surface was found in 40 eyes; iris nodules (Koeppe and/or Busacca) were present in half the cases. A cataract was observed in 69% of the affected eyes, 57.7% of which underwent surgery. Ocular hypertension was present in 30.66% of the affected eyes, glaucoma in 4%. CONCLUSIONS: The more common clinical features in this group of patients were fine and stellate keratic precipitates, atrophy of the iris crypts, and iris nodules. Clinically evident iris heterochromia was present in only 25% of the affected eyes. FHI diagnosis in brown-eyed patients cannot rely on iris heterochromy only.

[Ocular manifestations of primary systemic vasculitis]. / Manifestaciones oculares de las vasculitis primarias sistémicas.

A variety of ophthalmic manifestations can occur in patients who have systemic vasculitides and may be the presenting feature. Ocular involvement is frequently found and can result in significant morbidity, even in blindness. Early diagnosis and treatment may improve visual outcome. The management is challenging and requires a multidisciplinary approach. Treatment of ocular manifestations and systemic disease usually follows the same path. The mainstay of treatment is the use of systemic corticosteroids, usually combined with steroid-sparing immunosuppressive drugs. New, promising, emerging therapies rely on the development of biologic agents, which seem useful in the ocular manifestations of systemic vasculitides.

Lupus relapse presented as frosted branch retinal angiitis: case report.

PURPOSE: To describe a systemic lupus erythematosus (SLE) relapse, which presented as frosted branch retinal angiitis. DESIGN: Clinical case report. METHODS: A 16-year-old female patient had an SLE relapse that appeared as frosted branch angiitis while being treated with deflazacort and azathioprine. RESULTS: Complete resolution of the vasculitis was achieved with a 3-day course of pulsed intravenous methylprednisolone and oral prednisone 3 weeks later. CONCLUSIONS: Even with proper immunosuppressive treatment, SLE can relapse. This case presented as frosted branch retinal angiitis, which is a clinical picture that is rarely described in SLE.

Similarities and differences between primary and secondary Sjögren's syndrome.

OBJECTIVE: To define the clinical, serological, and histopathological characteristics of primary (pSS) and secondary Sjögren's syndrome (SS). METHODS: Fifty subjects with pSS and 300 with connective tissue diseases (CTD; systemic lupus erythematosus 100, rheumatoid arthritis 100, scleroderma 100) were selected randomly from our patient registry. Selected patients were assessed for fulfillment of the American-European Consensus Group criteria for SS using a 3-phase approach: screening (European questionnaire, Schirmer-I test, wafer test), confirmatory (fluorescein staining test, nonstimulated whole salivary flow, anti-Ro/La antibodies), and lip biopsy (H&E and immunohistochemical staining for anti-CD20 and anti-CD45RO scored by morphometry). RESULTS: All patients with pSS and 65 with CTD met criteria for SS. Oral symptoms (pSS = 92% and secondary SS = 84%; p = 0.02), parotid enlargement (pSS 56%, secondary SS 9.2%; p < 0.001), and higher prevalence (pSS 82%, secondary SS 41%; p < 0.001) and titers of anti-Ro/La antibodies were more common in pSS. Extraglandular manifestations were similar in both groups, except for Raynaud's phenomenon, which was more common in those with secondary SS (pSS 16% vs secondary SS 41%; p = 0.001). These results remained after 3 different sensitivity analyses. The prevalence of focal infiltration was also similar in both SS varieties; however, a higher B:T cell ratio and higher expression of CD20 cells (2922 vs 607.5 positive cells; p < 0.001) were observed in pSS. CONCLUSION: A higher frequency of oral symptoms and parotid enlargement and stronger B cell activity (autoantibody production and lymphocyte infiltration) were observed in pSS. Whether these results reflect a true difference between the 2 disease entities or derive from underlying variables remains uncertain.

Clasificación, frecuencia y distribución de las lesiones linfoides oculares y orbitarias en la A.P.E.C. (revisión de 30 años: 1959-1990) / Study of ocular and orbital lymphoid lesions in a 30 year period at the A.P.E.C

Se presenta un estudio retrospectivo de revisión de lesiones linfoides oculares y orbitarias en un periodo de 30 años en el Hospital de la A.P.E.C. En total se evaluaron 60 casos, de los cuales, el 41.66 por ciento correspondió a lesiones malignas, el 31.66 por ciento a lesiones benignas y el 21.66 por ciento a lesiones limítrofres constituídas por todos aquellos casos con diagnóstico histopatológico dudoso entre linfoma e hiperplasia linfoide. De las lesiones malignas, el 76 por ciento correspondió a linfoma con predominio del tipo linfocítico y el 94.74 por ciento de la patología benigna se debió a hiperplasi linfoide. Los linfomas se presentaron entre la 7a. y 8a. decádas de la vida; por lo contrario la hiperplasia prevaleció en pacientes con edades entre 20 y 40 años. Se encontró una mayor frecuencia de las lesiones conjuntivales y no se demostraron diferencias clínicas significativas que distingan a los procesos benignos de los malignos. Se realiza una revisión de los factores inmunogenéticos involucrados en las nuevas clasificaciones de lesiones linfoides y se concluye que es necesaria la utilización de inmunohistoquímica para la clasificaicón definitiva de las lesiones limítrofes y se propone un protocolo clínico para la adecuada evaluación de los pacientes con tumores linfoides.

Síndrome de Vogt Koyanagi Harada / Vogt-Koyanagi-Hada syndrome

El síndrome de Vogt Koyanagi Harada es una uveitis difusa, bilateral, aguda, granulomatosa, asociada a manifestaciones dermatológicas, auditivas y del sistema nervioso central. Es la panuveitis bilateral más frecuentemente encontrada en la población mestiza e indígena mexicana. Una respuesta autoinmune, regulada por factores genéticos y aparentemente dirigada contra los melanocitos parece ser la causa del proceso inflamatorio. El diagnóstico básicamente es clínico, aunque la florangiografía de retina y el estudio ecográfico pueden ayudar a sustentar el diagnóstico básicamente es clínico, aunque la florangiografía de retina y el estudio ecográfico pueden ayudar a sustentar el diagnóstico en algunos casos. En el presente artículo revisamos los conocimientos que en relación a fisiopatogenia, diagnóstico, pronóstico, tratamiento médico y quirúrgico se tienen actualmente