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We report two cases of long-term juvenile idiopathic arthritis which developed recurrent subglottic stenosis secondary to localized Wegener's granulomatosis. In both cases, the biopsies taken from the affected region shown granulomatous vasculitis with multinucleated giant cells. Both patients presented positive serology for antineutrophil cytoplasmic antibodies by immunofluorescence (c-ANCA) and ELISA (PR3). The involvement or other organs was ruled out at the time of Wegener's granulomatosis diagnosis and during follow-up. To our knowledge, this is the first report of the association between juvenile idiopathic arthritis and a localized form of Wegener's granulomatosis. [ABSTRACT FROM AUTHOR]

Objective: To develop updated guidelines for the pharmacological management of rheumatoid arthritis (RA)., Methods: A group of experts representative of different geographical regions and various medical services catering to the Mexican population with RA was formed. Questions based on Population, Intervention, Comparison, and Outcome (PICO) were developed, deemed clinically relevant. These questions were answered based on the results of a recent systematic literature review (SLR), and the evidence's validity was assessed using the GRADE system, considered a standard for these purposes. Subsequently, the expert group reached consensus on the direction and strength of recommendations through a multi-stage voting process., Results: The updated guidelines for RA treatment stratify various therapeutic options, including different classes of DMARDs (conventional, biologicals, and JAK inhibitors), as well as NSAIDs, glucocorticoids, and analgesics. By consensus, it establishes the use of these in different subpopulations of interest among RA patients and addresses aspects related to vaccination, COVID-19, surgery, pregnancy and lactation, and others., Conclusions: This update of the Mexican guidelines for the pharmacological treatment of RA provides reference points for evidence-based decision-making, recommending patient participation in joint decision-making to achieve the greatest benefit for our patients. It also establishes recommendations for managing a variety of relevant conditions affecting our patients., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Rationale: Diffuse alveolar hemorrhage (DAH) is a life-threatening manifestation of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). The PEXIVAS (Plasma Exchange and Glucocorticoids in Severe Antineutrophil Cytoplasmic Antibody-Associated Vasculitis) (NCT00987389) trial was the largest in AAV and the first to enroll participants with DAH requiring mechanical ventilation. Objectives: Evaluate characteristics, treatment effects, and outcomes for patients with AAV with and without DAH. Methods: PEXIVAS randomized 704 participants to plasma exchange (PLEX) or no-PLEX and reduced or standard-dose glucocorticoids (GC). DAH status was defined at enrollment as no-DAH, nonsevere, or severe (room air oxygen saturation of ⩽ 85% as measured by pulse oximetry, or use of mechanical ventilation). Measurements and Main Results: At enrollment, 191 (27.1%) participants had DAH (61 severe, including 29 ventilated) and were younger, more frequently relapsing, PR3 (proteinase 3)-ANCA positive, and had lower serum creatinine but were more frequently dialyzed than participants without DAH ( n  = 513; 72.9%). Among those with DAH, 8/95 (8.4%) receiving PLEX died within 1 year versus 15/96 (15.6%) with no-PLEX (hazard ratio, 0.52; confidence interval [CI], 0.21-1.24), whereas 13/96 (13.5%) receiving reduced GC died versus 10/95 (10.5%) with standard GC (hazard ratio, 1.33; CI, 0.57-3.13). When ventilated, ventilator-free days were similar with PLEX versus no-PLEX (medians, 25; interquartile range [IQR], 22-26 vs. 22-27) and fewer with reduced GC (median, 23; IQR, 20-25) versus standard GC (median, 26; IQR, 25-28). Treatment effects on mortality did not vary by presence or severity of DAH. Overall, 23/191 (12.0%) with DAH died within 1 year versus 34/513 (6.6%) without DAH. End-stage kidney disease and serious infections did not differ by DAH status or treatments. Conclusions: Patients with AAV and DAH differ from those without DAH in multiple ways. Further data are required to confirm or refute a benefit of PLEX or GC dosing on mortality. Original clinical trial registered with www.clinicaltrials.gov (NCT00987389).

Objective: To develop the first evidence-based Pan American League of Associations for Rheumatology (PANLAR) guidelines for the treatment of Takayasu arteritis (TAK)., Methods: A panel of vasculitis experts developed a series of clinically meaningful questions addressing the treatment of TAK patients in the PICO (population/intervention/comparator/outcome) format. A systematic literature review was performed by a team of methodologists. The evidence quality was assessed according to the GRADE (Grading of Recommendations/Assessment/Development/Evaluation) methodology. The panel of vasculitis experts voted each PICO question and made recommendations, which required ≥70% agreement among the voting members., Results: Eleven recommendations were developed. Oral glucocorticoids are conditionally recommended for newly diagnosed and relapsing TAK patients. The addition of nontargeted synthetic immunosuppressants (e.g., methotrexate, leflunomide, azathioprine, or mycophenolate mofetil) is recommended for patients with newly diagnosed or relapsing disease that is not organ- or life-threatening. For organ- or life-threatening disease, we conditionally recommend tumor necrosis factor inhibitors (e.g., infliximab or adalimumab) or tocilizumab with consideration for short courses of cyclophosphamide as an alternative in case of restricted access to biologics. For patients relapsing despite nontargeted synthetic immunosuppressants, we conditionally recommend to switch from one nontargeted synthetic immunosuppressant to another or to add tumor necrosis factor inhibitors or tocilizumab. We conditionally recommend low-dose aspirin for patients with involvement of cranial or coronary arteries to prevent ischemic complications. We strongly recommend performing surgical vascular interventions during periods of remission whenever possible., Conclusion: The first PANLAR treatment guidelines for TAK provide evidence-based guidance for the treatment of TAK patients in Latin American countries., Competing Interests: D.G.F.-Á. is consultant to Abbvie, Bristol Myers-Squibb, Eli Lilly, Fresenius Kabi, Janssen, Novartis, and Pfizer. M.V.S. is a speaker for and consultant to and receives research support from Abbvie, Bristol Myers-Squibb, GlaxoSmithKline, Janssen, Eli Lilly, Pfizer, Roche, and AstraZeneca. S.J.M. is a speaker for and consultant to and receives research support from Abbvie, Boehringer Ingelheim, GlaxoSmithKline, and Janssen. M.F.U.-G. receives research support and consulting fee from and is a speaker for Janssen, Pfizer, AztraZeneca, and GlaxoSmithKline. L.F.F.-S. is a speaker for Nippon Boehringer Ingelheim Co Ltd, Roche México, and Werfen Mexico. L.M.S.-R. is a speaker for and consultant to the advisory board of Novartis, Pfizer, Janssen, Bristol-Myers Squibb, Sanofi-Genzyme, Biopas, Amgen, Boehringer, Roche, and Eli Lilly. A.B. is a speaker and consultant to Abbvie, GlaxoSmithKline, Janssen, Pfizer, Boehringer Ingelheim, and Bristol-Myers Squibb. E.R.S.G. is a speaker for and consultant to and receives research support from Abbvie, Amgen, Bristol Myers-Squibb, Janssen, Eli Lilly, Novartis, Pfizer, Roche, Sandoz, and UCB. S.U. is a consultant to and receives research support from Kiniksa, Janssen, and Genentech. The other authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Considerable variability exists in the way health-care providers treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in Latin America. The most frequently used treatments for ANCA-associated vasculitis are cyclophosphamide and prolonged glucocorticoid tapers; however, randomised controlled trials conducted over the past 30 years have led to the development of several evidence-based treatment alternatives for these patients. Latin America faces socioeconomic challenges that affect access to care, and the use of certain costly medications with proven efficacy ANCA-associated vasculitis is often restricted. For these reasons, the Pan American League of Associations for Rheumatology developed the first ANCA-associated vasculitis treatment guidelines tailored for Latin America. A panel of local vasculitis experts generated clinically meaningful questions related to the treatment of ANCA-associated vasculitis using the Population, Intervention, Comparator, and Outcome (PICO) format. Following the Grading of Recommendations Assessment, Development, and Evaluation methodology, a team of methodologists conducted a systematic literature review. The panel of vasculitis experts voted on each PICO question and made recommendations, which required at least 70% agreement among the voting members. 21 recommendations and two expert opinion statements for the treatment of ANCA-associated vasculitis were developed, considering the current evidence and the socioeconomic characteristics of the region. These recommendations include guidance for the use of glucocorticoids, non-glucocorticoid immunosuppressants, and plasma exchange., Competing Interests: Declaration of interests Several authors of these guidelines, including voting members, have interacted with the pharmaceutical industry including the manufacturers of some of the drugs mentioned in these recommendations. However, none of the authors received any support or fee directly or indirectly related to or influencing the development of these guidelines. SJM reports being a speaker for, consulting for, and receiving research support from Roche, Pfizer, AbbVie, Janssen, Sandoz, and GlaxoSmithKline. MFU-G reports being a speaker for and receiving research support and consulting fees from Janssen, AstraZeneca, GlaxoSmithKline, AbbVie, and Pfizer. LFF-S reports being a speaker for and doing medical writing for the American College of Rheumatology, Sociedad Española de Reumatología, Editorial Médica Panamericana, and Elsevier. DGF-Á reports being a speaker for Amgen, Janssen, Novartis, Eli Lilly, and Pfizer; and receiving support for attending meetings from Janssen. MS reports being a speaker for, consulting for, and receiving research support from AbbVie, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Eli Lilly, Pfizer, Roche, and AstraZeneca. EIS reports consulting for Janssen. AWSdS reports being on the advisory board of Vifor Pharma. LMS-R reports being a speaker for, consulting for, and being on the advisory board of Novartis, Pfizer, Janssen, Roche, and Eli Lilly. AMB reports being a speaker for and consulting for AbbVie, GlaxoSmithKline, Janssen, Pfizer, Boehringer-Ingelheim, and Bristol-Myers Squibb. ERSG reports being a speaker for, consulting for, and receiving research support from AbbVie, Amgen, Janssen, Eli Lilly, Novartis, Pfizer, and Sandoz. SU reports consulting for and receiving research support from Kiniksa, Janssen, Genentech, GlaxoSmithKline, and Sanofi. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

ANCA-associated vasculitides (AAV) comprise three diseases: granulomatosis with polyangiitis, microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis. They are characterised by small vessel inflammation and have a broad range of clinical manifestations and multiorgan involvement which endanger the patient's life. An increasingly recognised complication of AAV, especially in MPA is lung fibrosis, for which no clearcut therapy in this context is available. The release of neutrophil extracellular traps (NETs) in these diseases has been related to the development of fibrosis, but the precise mechanisms are not fully unravelled. This review provides an overview of some of the important proteins known to compose NETs, and proposes some mechanisms by which these remarkable components may exert an impact on the different fibroblastic phenotypes leading to lung fibrosis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Lung involvement is one of the most common clinical features in ANCA-associated vasculitides (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). In this review, we detail the five main presentations of pulmonary involvement in AAV: necrotizing granulomatous inflammation, tracheobronchial inflammation, pulmonary capillaritis, interstitial lung disease (ILD) and asthma with their clinical, radiological and therapeutic characteristics. The prevalence of these manifestations is variable according to the subtype of AAV, necrotizing granulomatous inflammation and tracheobronchial inflammation being defining features of GPA whereas ILD is primarily seen in patients with MPA, especially in association with ANCA directed against myeloperoxydase (MPO-ANCA), and asthma is characteristic of EGPA. Despite recent progresses in the diagnosis and management of these conditions, several questions remain and are discussed here, including local treatments for subglottic stenosis, the uncertain efficacy of plasma exchanges for alveolar hemorrhage, the potential role of antifibrotic agents in ILD associated with MPA, and the use of novel anti-IL-5 strategies in EGPA., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

This document follows up on a 2017 revised international consensus on anti-neutrophil cytoplasm antibodies (ANCA) testing in granulomatosis with polyangiitis and microscopic polyangiitis and focuses on the clinical and diagnostic value of ANCA detection in patients with connective tissue diseases, idiopathic interstitial pneumonia, autoimmune liver diseases, inflammatory bowel diseases, anti-glomerular basement membrane (GBM) disease, infections, malignancy, and during drug treatment. Current evidence suggests that in certain settings beyond systemic vasculitis, ANCA may have clinical, pathogenic and/or diagnostic relevance. Antigen-specific ANCA targeting proteinase-3 and myeloperoxidase should be tested by solid phase immunoassays in any patient with clinical features suggesting ANCA-associated vasculitis and in all patients with anti-GBM disease, idiopathic interstitial pneumonia, and infective endocarditis associated with nephritis, whereas in patients with other aforementioned disorders routine ANCA testing is not recommended. Among patients with autoimmune liver diseases or inflammatory bowel diseases, ANCA testing may be justified in patients with suspected autoimmune hepatitis type 1 who do not have conventional autoantibodies or in case of diagnostic uncertainty to discriminate ulcerative colitis from Crohn's disease. In these cases, ANCA should be tested by indirect immunofluorescence as the target antigens are not yet well characterized. Many questions concerning the optimal use of ANCA testing in patients without ANCA-associated vasculitis remain to be answered., (Copyright © 2020 Elsevier B.V. All rights reserved.)

An international consensus on anti-neutrophil cytoplasm antibodies (ANCA) testing in eosinophilic granulomatosis with polyangiitis (EGPA) is presented. ANCA, specific for myeloperoxidase (MPO), can be detected in 30-35% of EGPA patients. MPO-ANCA should be tested with antigen-specific immunoassays in any patient with eosinophilic asthma and clinical features suggesting EGPA, including constitutional symptoms, purpura, polyneuropathy, unexplained heart, gastrointestinal or kidney disease, and/or pulmonary infiltrates or hemorrhage. A positive MPO-ANCA result contributes to the diagnostic work‑up for EGPA. Patients with MPO-ANCA associated EGPA have more frequently vasculitis features, such as glomerulonephritis, neuropathy, and skin manifestations than patients with ANCA negative EGPA. However, the presence of MPO-ANCA is neither sensitive nor specific enough to identify whether a patient should be subclassified as having "vasculitic" or "eosinophilic" EGPA. At present, ANCA status cannot guide treatment decisions, that is, whether cyclophosphamide, rituximab or mepolizumab should be added to conventional glucocorticoid treatment. In EGPA, monitoring of ANCA is only useful when MPO-ANCA was tested positive at disease onset.

Background: More effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis., Methods: We conducted a randomized trial with a 2-by-2 factorial design to evaluate the use of plasma exchange and two regimens of oral glucocorticoids in patients with severe ANCA-associated vasculitis (defined by an estimated glomerular filtration rate of <50 ml per minute per 1.73 m 2 of body-surface area or diffuse pulmonary hemorrhage). Patients were randomly assigned to undergo plasma exchange (seven plasma exchanges within 14 days after randomization) or no plasma exchange (control group). Patients were also randomly assigned to follow either a standard-dose regimen or a reduced-dose regimen of oral glucocorticoids. Patients were followed for up to 7 years for the primary composite outcome of death from any cause or end-stage kidney disease (ESKD)., Results: Death from any cause or ESKD occurred in 100 of 352 patients (28.4%) in the plasma-exchange group and in 109 of 352 patients (31.0%) in the control group (hazard ratio, 0.86; 95% confidence interval [CI], 0.65 to 1.13; P = 0.27). The results were similar in subgroup analyses and in analyses of secondary outcomes. We also assessed the noninferiority of a reduced-dose regimen of glucocorticoids to a standard-dose regimen, using a noninferiority margin of 11 percentage points. Death from any cause or ESKD occurred in 92 of 330 patients (27.9%) in the reduced-dose group and in 83 of 325 patients (25.5%) in the standard-dose group (absolute risk difference, 2.3 percentage points; 90% CI, -3.4 to 8.0), which met the criterion for noninferiority. Serious infections at 1 year were less common in the reduced-dose group than in the standard-dose group (incidence rate ratio, 0.69; 95% CI, 0.52 to 0.93), but other secondary outcomes were similar in the two groups., Conclusions: Among patients with severe ANCA-associated vasculitis, the use of plasma exchange did not reduce the incidence of death or ESKD. A reduced-dose regimen of glucocorticoids was noninferior to a standard-dose regimen with respect to death or ESKD. (Funded by the U.K. National Institute for Health Research and others; PEXIVAS Current Controlled Trials number, ISRCTN07757494; ClinicalTrials.gov number, NCT00987389.)., (Copyright © 2020 Massachusetts Medical Society.)

Objectives: The aim of this study was to review the histologic diagnostic yield of airway biopsies with a suspected granulomatosis with polyangiitis (GPA) diagnosis at a single center devoted to respiratory diseases using previously published criteria. A secondary aim was to apply the algorithm proposed by the European Medicines Agency to determine whether more biopsies were confidently identified as having GPA diagnoses., Methods: From a total of 132 airway biopsies (2005-2015), 50 were randomly selected for second review by an expert pathologist, and previously published criteria were applied. Thereafter, antineutrophil cytoplasm autoantibody testing results and the European Medicines Agency algorithm were applied., Results: Repeat review and application of the published criteria resulted in an increase from 16 to 25 diagnoses of GPA. This increased to 35 of 50 when antineutrophil cytoplasm autoantibody results and the European Medicines Agency algorithm were applied. Interobserver correlation was 57.5% among pathologists (κ = 0.19), which was likely due to missing clinical information and inadequate tissue samples. Patients with generalized disease were 2.6 times more likely to obtain diagnostic GPA airway biopsy results than those with limited disease (airway only)., Conclusions: An increase in the diagnostic yield of this malady could be attained by following an algorithm that incorporates carefully retrieved clinical, endoscopic, and serologic data, coupled with systematic histopathologic sample review.

Objectives: Granulomatosis with polyangiitis-a primary systemic vasculitis-most frequent manifestations are respiratory. Airway disease can present with stenosis, and although subglottic stenosis (SGS) is well described, narrowing distal to the glottis has been more recently the focus of reporting. Our objectives, therefore, are to describe the frequency, characteristics, and treatment of tracheobronchial stenoses (TBS) in granulomatosis with polyangiitis (GPA) at our institution, a national referral center for respiratory diseases. Also, to identify factors associated with TBS development in GPA., Methods: We undertook a retrospective study of all identified TBS cases (n-29) in whom their demographics, clinical and paraclinical features, and treatment were analyzed with descriptive statistics. Comparisons between those who developed and did not develop TBS (n-79) were established with the χ 2 test with Yates correction or two-tailed exact Fisher test for comparisons among groups with or without this complication., Results: Females were predominantly affected by TBS (76%). Most patients had limited GPA (n-20, 69%). TBS appeared at a mean of 29 months after diagnosis of GPA. Main symptoms were dysphonia, stridor, and dyspnea. All TBS patients had tracheal involvement and 12 (41%) additional bronchial stenoses. Other accompanying manifestations by organ/system were rhinosinusal (n-26, 87%), musculoskeletal (n-16, 55%), ocular (n-13, 45%), pulmonary (n-12, 41%), renal (n-8, 27%), mucocutaneous (n-5, 17%), neurological (n-4, 13%). At TBS diagnosis, 17 patients were PR3-ANCA and/or C-ANCA positive, while 9 were MPO-ANCA and/or P-ANCA positive; results on the remaining were either negative or ANCA were not performed at that time. Seventeen patients had simultaneous medical (8 with glucocorticoid therapy, 9 with immunosuppressants) and surgical therapy, while the rest only the latter at the time of TBS diagnosis. Relapses were frequent (one in 18 patients; two in 11, three in 9 and 2 individuals had ≥4 relapses). Factors positively associated with TBS were the presence of general and musculoskeletal symptoms and rhinosinusal disease, while those negatively associated were prednisone oral daily dose >10mgqd and azathioprine intake. The extent of disease, either generalized or limited was not associated with TBS development, nor were ANCA levels., Conclusions: TBS are serious complications of GPA which can arise at any stage of the disease. Timely diagnosis plus optimal treatment and follow-up remain unmet needs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To present the results of an endoscopic and histopathologic evaluation of suspected nasal active granulomatosis with polyangiits (GPA) lesions, describe them as seen by the ENT specialist, and propose a guide for tissue sampling of the nasal cavity to improve the yield of confirmatory histology., Methods: Randomly selected patients seen from December 1997-October 2007 had a thorough endoscopic nasal evaluation, preceded by careful cleansing of the nasal cavity. Endoscopic lesions were described; sensitivities, specificities, and predictive values of the composites of endoscopic and histological activity were determined., Results: Six lesions, some not previously described in detail, were observed: white submucosal nodules, mucosal swelling, polypoid nodules, vascular submucosal dilatations, bloody submucosal patches, and ulcers. Of these, polypoid nodules (PPV 100%), persistent white submucosal nodules (PPV 81%), and bloody submucosal patches (PPV 93%) had the better diagnostic performance with confirmed histological diagnosis., Conclusions: Careful nasal cavity preparation, observation, and description of the nasal mucosa can guide tissue sampling documenting active GPA. This can lead to a better histological yield when definitive proof of the disease is needed.

Anti-neutrophil cytoplasmic antibodies (ANCAs) are valuable laboratory markers used for the diagnosis of well-defined types of small-vessel vasculitis, including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). According to the 1999 international consensus on ANCA testing, indirect immunofluorescence (IIF) should be used to screen for ANCAs, and samples containing ANCAs should then be tested by immunoassays for proteinase 3 (PR3)-ANCAs and myeloperoxidase (MPO)-ANCAs. The distinction between PR3-ANCAs and MPO-ANCAs has important clinical and pathogenic implications. As dependable immunoassays for PR3-ANCAs and MPO-ANCAs have become broadly available, there is increasing international agreement that high-quality immunoassays are the preferred screening method for the diagnosis of ANCA-associated vasculitis. The present Consensus Statement proposes that high-quality immunoassays can be used as the primary screening method for patients suspected of having the ANCA-associated vaculitides GPA and MPA without the categorical need for IIF, and presents and discusses evidence to support this recommendation.

Purpose of Review: The purpose of this study is to describe the most relevant advances concerning lung involvement in the ANCA-associated vasculitides (excluding eosinophilic granulomatosis with polyangiitis which may have different disease mechanisms). Focus is on pathophysiology, recent important imagenological procedures, treatment, and outcome., Recent Findings: Emerging information exists on potential newly investigated diagnostic procedures (v.g. transbronchial cryobiopsies), detailed tomographic abnormalities, the potential favorable role of rituximab and the still uncertain one of plasma exchange in the treatment, and the increasing description of interstitial lung disease. Survival is reduced in case of both, diffuse alveolar hemorrhage and diffuse parenchymal disease. There is the need to expand the knowledge concerning better long-term treatment options with specific regimes, and to incorporate other measures regarding integral treatment in patients afflicted with lung involvement these maladies, as the outcome seems adverse in this scenario.

Anti-neutrophil cytoplasmic antibodies (ANCA) vasculitides are immune-mediated disorders that primarily affect small blood vessels of the airway and kidneys. Lung involvement, one of the hallmarks of microscopic polyangiitis and granulomatosis with polyangiitis, is associated with increased mortality and morbidity. In recent years, several retrospective series and case reports have described the association of interstitial lung disease (ILD) and ANCA vasculitis, particularly those positive for ANCA specific for myeloperoxidase. In the majority of these patients pulmonary fibrosis occurs concurrently or predates the diagnosis of ANCA vasculitis. More importantly, these studies have shown that ILD has an adverse impact on the long-term prognosis of ANCA vasculitis. This review focuses on the main clinical and radiologic features of pulmonary fibrosis associated with anti-neutrophil cytoplasmic antibodies. Major histopathology features, prognosis and therapeutic options are summarized., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Sclerodermatomyositis is an overlap syndrome of myositis and scleroderma, with dermatological, muscular and joint involvement, but may also present with ocular manifestations., Clinical Case: A 57 year-old woman presented with ophthalmological manifestations, including scleral thinning 360°, and the presence of cells in the anterior and posterior chamber. Oriented physical examination and laboratory studies led to the diagnosis, with the need for systemic treatment., Conclusion: Sclerodermatomyositis is a rare disease. Its diagnosis needs thorough clinical and laboratory studies, and its management should be multidisciplinary when inflammatory ocular manifestations may be present., (Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.)

The objective of this study is to describe the characteristics of patients with pachymeningitis (PM) in granulomatosis with polyangiitis (GPA) from Latin America, including three young patients. This is a retrospective case series. Patients were classified according to the ACR criteria, the 2012 Chapel Hill Consensus Conference Nomenclature and the EMA algorithm. Demographic, clinical, serological, and neuroimaging characteristics are described. Thirteen patients (nine females, four males) were identified. Mean age ± SD of PM diagnosis was 35.5 ± 20.4 years (median 48, range 8-71 years). Mean time ± SD between GPA first symptom and PM diagnosis was 59.8 ± 70.1 months (median 48, range 2-252 months). An important difference between children and adults was the median time elapsed between first GPA symptoms and PM diagnosis (range 2-4 months vs 5-252 months, respectively). Chronic headache was present in all, followed by intracranial hypertension (n = 5), single cranial nerve palsy and orbital mass (n = 4), seizures (n = 3), cavernous sinus syndrome and multiple cranial nerve palsies (n = 2), and meningism and cerebellar syndrome (n = 1 each). At time of PM diagnosis, mean BVAS/WG (Birmingham Vasculitis Activity Score for Wegener's granulomatosis) was 4 ± 2.4 and mean VDI of 2 ± 1.6, mostly due to ENT damage. Gadolinium-enhanced brain MRI showed dural thickening in 12 patients and leptomeningeal enhancement in one. All received a combination of glucocorticoids plus immunosuppressants, rituximab being used favourably in one refractory case. Improvement was observed in 12 patients. Chronic headache should lead to suspect PM. PM predominates in localised GPA. Children may present it earlier in the disease course than adults. Treatment is non-standardised and remains difficult.

Case Description: A 16 year-old female who presented with initial ear, nose and throat manifestations who later progressed to severe renal disease, requiring hemodialysis after 11 months of unique laryngeal involvement., Clinical Findings: Unilateral vocal cord paralysis without other symptoms or signs, but with positive perinuclear anti-neutrophil cytoplasmic antibodies (ANCA) and anti-myeloperoxidase autoantibodies, followed an unfavorable course months later with rapidly progressive glomerulonephritis. Renal biopsy confirmed an ANCA-associated vasculitis. She was diagnosed with microscopic polyangiitis., Treatment and Outcome: High-dose glucocorticoids, intravenous cyclophosphamide, plasma exchange and finally, hemodialysis and renal transplantation., Clinical Relevance: In contrast to granulomatosis with polyangiitis (Wegener), ear, nose and throat manifestations in microscopic polyangiitis are uncommon, while involvement of the lungs and kidneys are usual. We present a case with an isolated rare involvement, which progressed to severe disease. This atypical case warns about laryngeal symptoms as initial manifestation of an anti-myeloperoxidase positive systemic vasculitides, and emphasizes the relevance of close observation when unexplained isolated conditions with accompanying evidence of autoimmunity, in this case high levels of specific autoantibodies, are present.

Background: Patients with systemic lupus erythematosus (SLE) have 3times the risk of death compared to the rest of the population, with cardiovascular events (CVD) being one of the main causes. Índices such as waist-height (W-Ht I), waist-hip (W-Hp I) and pulse-mass (PMI) predict CVD, though the behaviour is unknown in patients with SLE. The aim of this study was to determine the prognostic value of PMI in the development of CVD in premenopausal women with SLE., Methodology: Cohort study. Included were premenopausal women with SLE without prior CVD; excluded were those patients with antiphospholipid syndrome (APS), pregnancy, thyroid disease, recent liposuction, and chronic kidney disease. Exposure variables were: PMI, W-Ht I, W-Hp I and metabolic syndrome at onset of the cohort. Considered confounding variables were time of evolution, disease activity, cumulative damage and treatment. Through semi-annual appointments, accident and emergency admittance and hospitalisation records the CVD were screened. Analysis was performed with Cox for proportional hazards and survival with Kaplan Meier., Results: We included 238 women with a median age of 31 (18-52) years, with a follow-up of 8years. We identified 22 (9.6%) cases of CVD. In the Cox proportional hazards analysis, the prognostic variables were: PMI with HR=8.1 (95% CI: 1.1-65), metabolic syndrome with 2.4 (95% CI: 1-5.8), cumulative damage with HR=1.5 (95% CI: 1.1-2.2) and body fat percentage HR=2.8 (95% CI: 1.1-6.9) CONCLUSIONS: The PMI is a better predictor factor of CVD in women with SLE., (Copyright © 2016 Elsevier España, S.L.U. All rights reserved.)

Background: Transbronchial lung cryobiopsy (TLCB), performed with a flexible cryoprobe, is an interventional pulmonology procedure that has proved its diagnostic value for interstitial pulmonary disease. However, it has not been explored extensively as a diagnostic tool for patients with non-interstitial lung pathology, including infectious and malignant diseases., Objective: To evaluate the diagnostic yield and safety of an interventional pulmonology approach that integrates TLCB and bronchoalveolar lavage (BAL) for the diagnosis of non-interstitial pulmonary disease., Methods: TLCB and BAL were performed under general anesthesia through the same bronchoscopic access on 103 adult patients (including immunocompromised HIV+ individuals) with clinical/radiological evidence of non-interstitial lung disease admitted to the Interventional Pulmonology Service between May 2015 and April 2016. Samples obtained were sent to pathology and microbiology laboratories for standard diagnostic analysis., Results: Samples of TLCB allowed the diagnosis of 75.7% of patients, while 39.8% were diagnosed from BAL. The global diagnostic yield from the dual sampling was 92.2%. TLCB allowed the diagnosis of 94.7% of cancer cases and 60.0% of infectious cases, while BAL samples identified 77.5% of infectious cases and 21.2% of malignant lesions. The incidence of complications was 4.9% with full recovery in all cases., Conclusions: Simultaneous TLCB and BAL constitute a safe and useful diagnostic procedure for non-interstitial pulmonary disease, with a global diagnostic yield of 92.2%. Complementary advantages of samples obtained by each technique result in a robust diagnostic strategy for infectious and malignant disease in adults, including HIV+ individuals., (© 2017 S. Karger AG, Basel.)

ANCA-associated vasculitides (AAV) are chronic autoimmune diseases characterized by inflammation and destruction of small vessels. Rituximab is now licensed for use as a remission-induction agent in the treatment of these disorders. During recent years, several non-controlled studies have suggested that rituximab may be of value in maintaining disease remission in AAV. In these series, 3 techniques have been tried: "watch-and-wait", repeated cycles in fixed intervals, or administration based on proposed biomarkers. More importantly, the results of the MAINRITSAN trial showed that this anti-CD20 agent is superior to azathioprine for preventing major relapses in AAV. This review summarizes current information regarding the effectiveness, timing, dosing, duration and safety of rituximab as a valid option for remission maintenance., (Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

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.

Background and Objective: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease of unknown etiology. In lupus patients there is an increased cardiovascular risk due to an accelerated atherogenesis. Furthermore, Metabolic Syndrome (MS) adds an independent risk for developing Cardiovascular Disease (CVD) in the population. Therefore, it is important to determine whether lupus patients have an increased risk of developing Cardiovascular Disease in the presence of MS. To estimate the prognostic value of MS in the incidence of cardiovascular events in a cohort of premenopausal patients with SLE., Methodology: Cohort study in 238 patients was carried out. Clinical, biochemical, dietetic and anthropometric evaluations were performed. Patients were classified according to the prevalence of MS in 2001. There was a patient follow-up from 2001 to 2008. In 2008, after studying the records, we obtained the "cases" (patients with CVD) and the "no cases" (patients without CVD)., Results: The basal prevalence of MS in the cohort was of 21.8% (ATPIII). The MS component with the highest prevalence in the population studied in 2001 was low HDL-Cholesterol (<50mg/dL) with a prevalence of 55.0%. The cumulative incidence of CVD in the group with MS was 17.3% and in the group without MS it was 7.0% with a Relative Risk (RR) of 2.48 (1.12-5.46) and p<0.05. In the multivariable analysis it was noted that MS is a predictive factor of CVD., Conclusions: We observed the prognostic value of MS for an increased risk of cardiovascular damage in premenopausal patients with lupus., (Copyright © 2014 Elsevier España, S.L.U. All rights reserved.)

It is now 25 years since the first European studies on vasculitis--the anti-neutrophil cytoplasmic antibody (ANCA) standardization project. Over that period of time, there have been major developments in the classification of the vasculitides, which has permitted the conduct of high-quality epidemiology studies. Studying the epidemiology of rare diseases such as the ANCA-associated vasculitides (AAV) poses considerable challenges to epidemiologists. The first is the need for a clear definition of a case with good differentiation from similar disorders. The second is case capture. The vasculitides are rare, and therefore, a large population is required to determine the incidence and prevalence, and this poses questions of feasibility. A large population increases the risk of incomplete case detection but permits a reasonable number of cases to be collected in a practicable time frame, whereas a smaller population requires a much longer time frame to collect the necessary cases, which may also not be feasible. Statistical methods of capture-recapture analysis enable estimates to be made of the number of missing cases. The third is case ascertainment. The AAV are virtually always managed in secondary care, and therefore, hospital-based case ascertainment may be appropriate. Fourthly, the rarity of the conditions makes prospective case-control studies investigating risk factors difficult to conduct because the population size required to achieve statistical confidence is in excess of that which is readily available. Thus, much of the data on risk factors are derived from retrospective studies with inherent potential bias., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Introduction: Respiratory manifestations in antineutrophil cytoplasmic antibody-associated vasculitis (AASV) are common, though their suspicion is lower than expected in respiratory devoted centers, with few descriptions coming from them., Objective: To describe the clinical, paraclinical and radiological manifestations, plus the prognosis of AASV patients seen in a respiratory referral center in Mexico City., Material and Methods: Retrospective review of patients with final diagnosis of AASV, based on the American College of Rheumatology criteria and the 1994 Chapel Hill Consensus Conference Nomenclature, from 1982 to 2010., Results: The characteristics of 74 granulomatosis with polyangiitis, 10 microscopic polyangiitis, and six eosinophilic granulomatosis with polyangiitis cases are described. Mean time elapsed from initial suspicion to definitive diagnosis was 30 months. As expected, respiratory findings dominated this cohort, but no significant differences were observed when compared to other series with AAS\1, except for a higher frequency of subglottic stenosis. After a mean follow-up of 22 months, 83% of patients were alive, with remission being achieved in 87% and response in 9%. Seven patients died, mostly from infectious complications., Conclusion: This study documents that airway manifestations in Mexican patients with AASV are similar to what has been previously described. However, time to diagnosis is long. Respiratory specialists should be more aware of the modes of presentation in AASV patients in order to facilitate their recognition.

The vasculities are complex diseases. Their cutaneous manifestations are very important and often mirror several pathologies. Cocaine use has been related to both, vasculitis and thrombotic vasculopathy and pseudovasculitis. A new syndrome has been described in association with its adulteration with levamisole. It can be very serious, leading patients to death. This is relevant as levamisole-adultered cocaine seems to be increasingly offered to consumers. Our goal is to report the first two cases in Mexico, which faces an important raise in cocaine use, emphasizing that a high suspicion based on certain characteristics allows for early recognition and adequate treatment.

Background: The pharmacologic management of rheumatoid arthritis has progressed substantially over the past years. It is therefore desirable that existing information be periodically updated. There are several published international guidelines for the treatment of rheumatoid arthritis that hardly adapt to the Mexican health system because of its limited healthcare resources. Hence, it is imperative to unify the existing recommendations and to incorporate them to a set of clinical, updated recommendations; the Mexican College of Rheumatology developed these recommendations in order to offer an integral management approach of rheumatoid arthritis according to the resources of the Mexican health system., Objective: To review, update and improve the available evidence within clinical practice guidelines on the pharmacological management of rheumatoid arthritis and produce a set of recommendations adapted to the Mexican health system, according to evidence available through December 2012., Methods: The working group was composed of 30 trained and experienced rheumatologists with a high quality of clinical knowledge and judgment. Recommendations were based on the highest quality evidence from the previously established treatment guidelines, meta-analysis and controlled clinical trials for the adult population with rheumatoid arthritis., Results: During the conformation of this document, each working group settled the existing evidence from the different topics according to their experience. Finally, all the evidence and decisions were unified into a single document, treatment algorithm and drug standardization tables., Conclusions: This update of the Mexican Guidelines for the Pharmacologic Treatment of Rheumatoid Arthritis provides the highest quality information available at the time the working group undertook this review and contextualizes its use for the complex Mexican health system., (Copyright © 2013 Elsevier España, S.L. All rights reserved.)

The vasculitides are a group of protean diseases, some of which are caused by conditions including infections, other autoimmune diseases, or neoplasias. They are a challenge to the clinician, in terms of both diagnosis and therapy. No diagnostic criteria exist, although a multinational effort to develop them is in progress. However, many classification criteria have been proposed, and these have served as diagnostic surrogates and have made it possible to discriminate between many, although not all, of the vasculitides, mainly for epidemiological and therapeutic trial design purposes. In this review we recognise the difficulties of defining such criteria, but at the same time attempt to provide a critical overview of efforts to do so. The increasing knowledge regarding many of these diseases makes us confident that the time will come when their aetiology, or at least their main pathogenic features, is known, rendering proposed classification criteria obsolete.

Microscopic polyangiitis (MPA) frequently involves the lungs. However, as opposed to granulomatosis with polyangiitis (Wegener's), limited forms are not recognised. In recent years, cases have been reported in which the lungs were affected without other organ manifestations. For years, many have been labelled as idiopathic pulmonary fibrosis (IPF). In this review, support for the existence of a limited form of MPA affecting the lungs as well as questions and discussions concerning the similarities and differences to IPF are offered.

Although primary systemic vasculitides (PSV) are infrequent diseases, basic and clinical research have increased the knowledge of these autoimmune conditions substantially. Some PSV seem to be more frequent in certain countries. Here we present a brief history of the modest, but important contributions made in Mexico in this area of research.

Granulomatosis with polyangiitis and microscopic polyangiitis are two autoimmune diseases characterised by necrotising small-vessel vasculitis and presence of antineutrophil cytoplasm autoantibodies (ANCA). Current immunosuppressive regimes that combine cyclophosphamide and glucocorticoids have dramatically improved the outcome for these patients. However, these treatments are associated with toxic effects and do not lead to permanent remission in the majority of cases. Newer approaches have been sought during the last 15 years, with improvement in medication protocols and inclusion of novel therapies. This review develops on seven clinical conundrums of evidence-based therapeutic strategies for ANCA-vasculitis, posed as questions on aspects such as the role of established drugs in both remission induction and maintenance: glucocorticoids (and its duration), oral cyclophosphamide, methotrexate, TNF-α blockers, plasma exchange, mycophenolate mofetil, plus one related to newer developments in treatment with agents blocking the complement system and the possible role of sequential or combined therapies, mainly directed against B cells.

The primary vasculitidies are complex diseases with varied clinical manifestations, which may be common to those present in multiple diseases. The antineutrophil cytoplasm autoantibodies (ANCA) led to a revolution in the diagnosis and research of these diseases, being the first and so far, the only biomarkers for three of these diseases, which affect small caliber vessels. From their description, much progress has been made, but there are still gray or misunderstood areas regarding their best use in the clinic. This can lead to errors as making a positive test synonym for vasculitis, or to overestimation of its importance. This review will address aspects such as nomenclature, employment in the diagnosis and monitoring of vasculitis, their presence in other diseases, their methods of detection, and finally, some comments on other potential biomarkers in vasculitis., (Copyright © 2012 Elsevier España, S.L. All rights reserved.)