Update of the guidelines for the pharmacological treatment of rheumatoid arthritis by the Mexican College of Rheumatology 2023.

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.

Alveolar Hemorrhage in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Results of an International Randomized Controlled Trial (PEXIVAS).

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).

Pan American League of Associations for Rheumatology Guidelines for the Treatment of Takayasu Arteritis.

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.

Pan American League of Associations for Rheumatology Guidelines for the treatment of ANCA-associated vasculitis.

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.

2020 international consensus on ANCA testing beyond systemic vasculitis.

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.

Lung involvement in ANCA-associated vasculitis.

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.

International Consensus on ANCA Testing in Eosinophilic Granulomatosis with Polyangiitis.

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 work­up 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.

Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis.

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 m2 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.).

Airway Biopsy Results From Patients With Suspected Granulomatosis With Polyangiitis (2005-2015): Clinicopathological Correlation and Proposal of an Algorithm to Improve Diagnosis.

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.

Frequency, treatment, evolution, and factors associated with the presence of tracheobronchial stenoses in granulomatosis with polyangiitis. Retrospective analysis of a case series from a single respiratory referral center.

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 χ2 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.

Increased histopathological yield for granulomatosis with polyangiitis based on nasal endoscopy of suspected active lesions.

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.

Position paper: Revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis.

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.

Pulmonary Involvement in Systemic Vasculitis.

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.

Utility of Transbronchial Lung Cryobiopsy in Non-Interstitial Diseases.

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.

Severe microscopic polyangiitis with unilateral vocal cord paralysis as initial manifestation.

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.

DESCRIPCIÓN DEL CASO: Una mujer de 16 años se presentó inicialmente con manifestaciones otorrinolaringológicas y posteriormente progresó hacia enfermedad renal grave, requiriendo hemodiálisis después de 11 meses de tener exclusivamente afección laríngea. HALLAZGOS CLÍNICOS: parálisis de cuerda vocal unilateral sin otros síntomas ni signos, pero con autoanticuerpos anticitoplasma de neutrófilo (ANCA) con patrón perinuclear y especificidad contra mieloperoxidasa, siguiendo un curso desfavorable meses después con desarrollo de glomerulonefritis rápidamente progresiva. La biopsia renal confirmó una vasculitis asociada con ANCA (VAA). Se diagnosticó entonces como poliangitis microscópica. TRATAMIENTO Y DESENLACE: Glucocorticoides a dosis altas, ciclofosfamida endovenosa, recambio plasmático y finalmente, hemodiálisis y transplante renal. RELEVANCIA CLÍNICA: en contraste con la granulomatosis con poliangitis (Wegener), las manifestaciones otorrinolaringológicas en poliangitis microscópica son poco comunes, mientras que la afección pulmonar y renal es común. Presentamos un caso con afección inusual aislaea, que progresó a enfermedad grave. Este caso atípico enfatiza sobre los síntomas laríngeos como manifestación inicial de una vasculitis antimieloperoxidasa positiva, y subraya la relevancia de una estrecha observación cuando condiciones aisladas inexplicables, que como en este caso se acompañan de evidencia de autoinmunidad manifestado por presencia de niveles altos de autoanticuerpos, se presentan para su atención.

Interstital lung disease in ANCA vasculitis.

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.

Severe microscopic polyangiitis with unilateral vocal cord paralysis as initial manifestation / Parálisis unilateral de cuerda vocal como manifestación inicial de poliangitis microscópica grave

Abstract 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.

Resumen Descripción del caso: Una mujer de 16 años se presentó inicialmente con manifestaciones otorrinolaringológicas y posteriormente progresó hacia enfermedad renal grave, requiriendo hemodiálisis después de 11 meses de tener exclusivamente afección laríngea. Hallazgos clínicos: parálisis de cuerda vocal unilateral sin otros síntomas ni signos, pero con autoanticuerpos anticitoplasma de neutrófilo (ANCA) con patrón perinuclear y especificidad contra mieloperoxidasa, siguiendo un curso desfavorable meses después con desarrollo de glomerulonefritis rápidamente progresiva. La biopsia renal confirmó una vasculitis asociada con ANCA (VAA). Se diagnosticó entonces como poliangitis microscópica. Tratamiento y desenlace: Glucocorticoides a dosis altas, ciclofosfamida endovenosa, recambio plasmático y finalmente, hemodiálisis y transplante renal. Relevancia clínica: en contraste con la granulomatosis con poliangitis (Wegener), las manifestaciones otorrinolaringológicas en poliangitis microscópica son poco comunes, mientras que la afección pulmonar y renal es común. Presentamos un caso con afección inusual aislaea, que progresó a enfermedad grave. Este caso atípico enfatiza sobre los síntomas laríngeos como manifestación inicial de una vasculitis antimieloperoxidasa positiva, y subraya la relevancia de una estrecha observación cuando condiciones aisladas inexplicables, que como en este caso se acompañan de evidencia de autoinmunidad manifestado por presencia de niveles altos de autoanticuerpos, se presentan para su atención.