Performance of clinical and histological prognostic scores for kidney survival in ANCA-associated vasculitis.

OBJECTIVES: Integrating clinical and histological parameters into prognostic scores may enhance the prediction of progression to kidney failure in anti-neutrophil cytoplasm antibodies-associated vasculitis (AAV). This study aimed to evaluate the prognostic performance of histological classifications and scoring systems for kidney survival in AAV. METHODS: This retrospective cohort study included 101 AAV patients with kidney involvement diagnosed by biopsy and followed for ≥12 months. The main outcome was the time to kidney failure. The prognostic performance of each histological and prognostic score was evaluated using Harrell's C statistic and Akaike's Information Criteria. RESULTS: Among the 101 patients, 37 progressed to kidney failure over a median follow-up of 75 months (IQR 39-123). The Harrell's C statistic was 0.702 (0.620-0.784), 0.606 (0.473-0.738), 0.801 (0.736-0.867), 0.782 (0.706-0.858), and 0.817 (0.749-0.885) for the EUVAS/Berden classification, Mayo Clinic Chronicity Score, Percentage of ANCA Crescentic Score (PACS), ANCA renal risk score (ARRS), and the improved ANCA kidney risk score (AKRiS), respectively. The AKRiS best discriminated the risk of kidney failure progression among subgroups. The AKRiS performance decreased with longer follow-up intervals. Adding the peak estimated glomerular filtration rate attained post-therapy improved the AKRiS performance at all follow-up intervals. Kidney relapses precipitated kidney failure in 71% of cases that progressed after the first year of follow-up. CONCLUSION: The novel AKRiS enhances the prediction of kidney failure in AAV with kidney involvement. As the prognostic yield of AKRiS decreases over time, a second calculation of AKRiS, including post-therapy kidney function, may improve its long-term performance.

Distinct features of ANCA-associated hypertrophic pachymeningitis compared to other etiologies: findings from a study of 74 patients.

OBJECTIVES: We aimed to characterize the clinical and radiological features, and outcomes, of a large cohort of hypertrophic pachymeningitis (HP) patients from a single center. METHODS: We conducted a retrospective study at a tertiary referral center, encompassing patients diagnosed with HP between 2003 and 2022. The diagnosis of HP relied on the identification of thickening of the dura mater via magnetic resonance imaging (MRI) of the brain or spine. RESULTS: We included 74 patients with a mean age of 43.6 ± 14.2 years, of whom 37 (50%) were male. Among them, 32 (43.2%) had an immune-mediated origin, including 21 with granulomatosis with polyangiitis (GPA) (predominantly PR3-ANCA positive), four with systemic lupus erythematosus, three with IgG4-related disease, three with idiopathic HP, and one with rheumatoid arthritis. Non-immune-mediated HP accounted for 45 cases (56.8%). Within this category, 21 (28.4%) were infectious cases, with 14 being Mycobacterium tuberculosis infection (TB-HP), and 21 (28.4%) were malignancy-associated HP. Clinical and MRI characteristics exhibited variations among the four etiological groups. Hypoglycorrhachia was primarily observed in infectious and malignancy-associated HP. Immune-mediated HP was associated with a peripheral pattern of contrast enhancement and the Eiffel-by-night sign. MRI features strongly indicative of TB-HP included leptomeningeal involvement, brain parenchymal lesions, and arterial stroke. MPO-ANCA GPA was associated with a higher prevalence of spinal HP. CONCLUSIONS: Within our cohort, GPA and Mycobacterium tuberculosis emerged as the predominant causes of HP. We identified significant disparities in clinical and radiological features among different etiologies, which could have implications for diagnosis.

Orbital/ocular inflammatory involvement in VEXAS syndrome: Data from the international AIDA network VEXAS registry.

VEXAS syndrome is a recently described monogenic autoinflammatory disease capable of manifesting itself with a wide array of organs and tissues involvement. Orbital/ocular inflammatory manifestations are frequently described in VEXAS patients. The objective of this study is to further describe orbital/ocular conditions in VEXAS syndrome while investigating potential associations with other disease manifestations. In the present study, twenty-seven out of 59 (45.8 %) VEXAS patients showed an inflammatory orbital/ocular involvement during their clinical history. The most frequent orbital/ocular affections were represented by periorbital edema in 8 (13.6 %) cases, episcleritis in 5 (8.5 %) patients, scleritis in 5 (8.5 %) cases, uveitis in 4 (6.8 %) cases, conjunctivitis in 4 (6.8 %) cases, blepharitis in 3 (5.1 %) cases, orbital myositis in 2 (3.4 %) cases. A diagnosis of systemic immune-mediated disease was observed in 15 (55.6 %) cases, with relapsing polychondritis diagnosed in 12 patients. A significant association was observed between relapsing polychondritis and orbital/ocular involvement in VEXAS syndrome (Relative Risk: 2.37, 95 % C.I. 1.03-5.46, p = 0.048). Six deaths were observed in the whole cohort of patients after a median disease duration of 1.2 (IQR=5.35) years, 5 (83.3 %) of which showed orbital/ocular inflammatory involvement. In conclusion, this study confirms that orbital/ocular inflammatory involvement is a common finding in VEXAS patients, especially when relapsing polychondritis is diagnosed. This makes ophthalmologists a key figure in the diagnostic process of VEXAS syndrome. The high frequency of deaths observed in this study seems to suggest that patients with orbital/ocular involvement may require increased attention and more careful follow-up.

Clinical Characteristics and Outcomes of Polyarteritis Nodosa: An International Study.

OBJECTIVE: We describe the demographics, clinical features, disease course, and survival of polyarteritis nodosa (PAN) through an international collaboration (GLOBAL-PAN). METHODS: Patients with PAN were recruited between 1990 and 2020 from observational cohorts of nine countries across Europe, Japan, and North America. Eligibility was retrospectively defined using the European Medicines Agency classification algorithm. Patients with PAN related to hepatitis B virus (n = 12) and two monogenic diseases mimicking PAN, deficiency of adenosine deaminase 2 enzyme (n = 16) or familial Mediterranean fever (n = 11), were excluded. Data regarding organ involvement, relapse, disease-related damage, and survival were analyzed. RESULTS: Three hundred fifty-eight patients (female:male ratio 174:184), including those with systemic PAN (sPAN, n = 282) and cutaneous PAN (n = 76), were included. Twenty-five were pediatric onset. Mean ± SD age at diagnosis was 44.3 ± 18.1 years. Constitutional symptoms (71.5%), cutaneous involvement (70.5%), musculoskeletal findings (69.1%), and neurologic features (48.0%) were common manifestations. Among patients with sPAN, gastrointestinal involvement and proteinuria over 400 mg/day were reported in 52.2% and 11.2%, respectively. During a median (interquartile range) 59.6 (99.5) months of follow-up, relapse occurred in 48.5% of patients. One, 5- and 10-year survival rates for sPAN were 97.1%, 94.0%, and 89.0%, respectively. Predictors of death for sPAN included age ≥65 years at diagnosis, serum creatinine at diagnosis >140 µmol/L, gastrointestinal manifestations, and central nervous system (CNS) involvement. CONCLUSION: The spectrum of PAN remains a complex, multifaceted disease. Relapse is common. Age ≥65 years and serum creatinine >140 µmol/L at diagnosis, as well as gastrointestinal and CNS involvement, are independent predictors of death in sPAN.

VEXAS syndrome: Clinical manifestations, diagnosis, and treatment.

VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an adult-onset autoinflammatory syndrome characterized by somatic mutations in the UBA1 gene and is considered the prototype of hematoinflammatory diseases. Patients with VEXAS syndrome exhibit inflammatory and hematological manifestations that can lead to clinical diagnoses such as relapsing polychondritis, polyarteritis nodosa, Sweet syndrome, and myelodysplastic syndrome. Diagnosis requires bone marrow evaluation to identify cytoplasmic vacuoles in myeloid and erythroid precursors. However, genetic confirmation of mutations in UBA1 is necessary. Treatment is challenging and often involves glucocorticoids and immunosuppressants with variable responses. Hypomethylating agents and allogenic haemopoietic stem cell transplant are considered promising therapies. Prognosis is influenced by genetic and clinical factors. The aim of this review is to provide an overview of the pathogenesis, clinical presentation, treatment, and prognosis of VEXAS syndrome for the Latin American medical community.

Efficacy and Safety of Adalimumab in Pediatric Non-infectious Non-anterior Uveitis: Real-life Experience From the International AIDA Network Uveitis Registry.

INTRODUCTION: Scientific evidence of the effectiveness of the tumor necrosis factor inhibitor adalimumab (ADA) in pediatric patients with non-infectious non-anterior uveitis is still limited. The aim of this study is to investigate the therapeutic role of ADA in a cohort of pediatric patients with non-anterior uveitis. METHODS: This is an international multicenter study analyzing real-life data referred to pediatric patients treated with ADA for intermediate uveitis/pars planitis, posterior uveitis and panuveitis. Data were drawn from the AutoInflammatory Disease Alliance (AIDA) registry for patients with uveitis. RESULTS: Twenty-one patients (36 affected eyes) were enrolled, and all patients benefited from ADA administration. In detail, 11 patients (19 affected eyes) did not experience further ocular inflammation after ADA introduction; 10 cases (17 affected eyes) showed a significant clinical improvement consisting of a decrease in severity and/or frequency of ocular relapses. The number of ocular flares dropped from 3.91 to 1.1 events/patient/year after ADA introduction (p = 0.0009); macular edema and retinal vasculitis were respectively observed in 18 eyes and 20 eyes at the start of ADA and in 4 eyes and 2 eyes at the last assessment. The mean daily glucocorticoid dosage significantly decreased from 26.8 ± 16.8 mg/day at the start of ADA to 6.25 ± 6.35 mg/day at the last assessment (p = 0.002). Intermediate uveitis/pars planitis (p = 0.01) and posterior uveitis (p = 0.03) were more frequently observed in patients with full response to ADA; panuveitis (p = 0.001) was significantly more frequent among patients continuing to experience uveitic flares. This could be related to a higher use of systemic glucocorticoids (p = 0.002) and conventional immunosuppressants (p = 0.007) at the start of ADA when treating intermediate uveitis/pars planitis. Regarding the safety profile, only one adverse event was reported during ADA treatment, consisting of the development of generalized adenopathy. CONCLUSIONS: ADA proved to have an effective therapeutic role in all pediatric patients with non-anterior uveitis enrolled in the study. An overall glucocorticoid-sparing effect was observed despite the severity of cases enrolled. A more aggressive treatment of panuveitis and posterior uveitis at start of ADA could increase the likelihood of full response to therapy.

Patient-reported outcomes in ANCA-associated vasculitis: a cross-sectional study to explore the interactions between patients' and physicians' perspectives.

To evaluate associations between the domains of the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) instrument and clinical variables. Patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), or renal-limited vasculitis (RLV) were recruited from a tertiary care center in Mexico City. Demographic, clinical, serological, and treatment-related data were retrieved. Disease activity, damage, patient and physician global assessments (PtGA and PhGA) were evaluated. All patients completed the AAV-PRO questionnaire, male patients also completed the International Index of Erectile Function (IIEF-5) questionnaire. Seventy patients (44 women and 26 men) were included, with a median age of 53.5 years (43-61), and a disease duration of 82 months (34-135). Moderate correlations were identified between the PtGA and the AAV-PRO domains: social and emotional impact, treatment side effects, organ-specific symptoms, and physical function. The PhGA correlated with the PtGA and prednisone doses. Subanalyses of the AAV-PRO domains according to sex, age, and disease duration showed significant differences in the treatment side effects domain, with higher scores in women, in patients < 50 years, and in patients with disease duration < 5 years. The domain of concerns about the future showed a higher score in patients with disease duration < 5 years. A total of 17/24 (70.8%) of men who completed the IIEF-5 questionnaire were classified as having some degree of erectile dysfunction. The domains of AAV-PRO correlated with other outcome measures, while differences were found between some of the domains according to sex, age, and disease duration.

Cachexia measured by bioelectrical impedance vector analysis and risk of infection in women with rheumatoid arthritis.

Rheumatoid arthritis (RA) patients have a higher frequency of infections than the healthy population. The reason has yet to be explained but involves several factors, of which body composition and rheumatoid cachexia are often overlooked. This study aimed to evaluate whether patients with cachexia, measured by bioelectrical impedance vector analysis, are at an increased risk of developing infections compared with patients without cachexia. A secondary analysis of 186 women with RA enrolled in a randomized trial (ClinicalTrials.gov ID: NCT02900898, September 14, 2016) was completed. Medical records and phone calls were used to record infectious events diagnosed and treated during follow-up. Hazard ratios were calculated using Cox proportional hazard regression analysis, and a predictive model of infection was created. After 36 months of follow-up, 62 patients (26.7% non-cachectic and 44.3% cachectic, p < 0.01) developed at least one infectious event. The most common site of was the urinary tract, followed by the lungs and respiratory tract. The presence of cachexia (HR 1.90, 95% CI 1.15-3.13) and the use of glucocorticoids (HR 1.77, 95% CI 1.01-3.09) were associated with infection in univariate and multivariate models. Body mass index (BMI), smoking, and methotrexate use were not associated with a higher frequency of infections. The presence of cachexia and the use of glucocorticoids were identified as predictors of infections in a cohort of female RA patients. More extensive measurements of body composition should be performed beyond BMI in RA patients to better understand its impact and to prevent additional comorbidities and complications. Key Points • The presence of cachexia measured by bioelectrical impedance vector analysis was associated with infectious events in women with rheumatoid arthritis, whereas body mass index did not show an association. • Glucocorticoids were the only drug associated with a higher frequency of infection. None of the disease-modifying antirheumatic drugs, including methotrexate, showed an association.

Rituximab treatment in ANCA-associated vasculitis patients: outcomes of a real-life experience from an observational cohort.

Rituximab is a first-line therapy in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Among previous studies evaluating its efficacy, the Hispanic/Latino population has been underrepresented. This study aimed to assess the outcomes of AAV patients treated with rituximab in a tertiary care center in Mexico. This is a retrospective cohort study including patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), or renal-limited vasculitis (RLV), who received at least one dose of rituximab (induction or maintenance therapy) from January 2014 to October 2020. Demographic, clinical, serological, histopathological, and treatment-related variables were retrieved. Outcomes were the rate of remission at 6 months during induction and the rate of relapses during maintenance. Damage, serious infections, and death were assessed. Differences between patients with and without remission were analyzed. Forty-two patients received rituximab, 34 of them as induction to remission. Twenty-two patients (65%) achieved remission after 6 months. Patients who achieved remission were younger than those who did not (50 vs. 60 years, p = 0.03). During induction, severe infections, most frequently pneumonia, occurred in 9 (26%), and one patient died. Twenty-four patients received rituximab as maintenance; of them, 23 (96%) achieved complete response, and 8 (33%) experienced relapses (median follow-up time 19 months). During maintenance, severe infections (pneumonia) occurred in 5 patients (21%), and 3 of them (13%) died. In this observational cohort study, the outcomes were similar to the ones reported in other populations, whereas severe infections were frequent and associated with mortality. Key Points • In this study, the outcomes of 42 Mexican patients with ANCA-associated vasculitis treated with rituximab were assessed in a real-life setting. • At 6 months, 65% of the patients achieved remission with rituximab, especially those younger than 50 years of age. • During maintenance therapy with rituximab, 96% of the patients achieved complete response, and 33% experienced relapses. • Severe infections, mostly pneumonia, occurred in 26% of patients during induction and 21% of patients during maintenance therapy with rituximab.

ANCA-associated vasculitis and IgG4-related disease overlap syndrome: a case report and literature review.

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides are infrequent autoimmune diseases characterized by inflammation of the walls of small vessels leading to tissue and endothelial damage. On the other hand, IgG4-related disease is a fibroinflammatory disease characterized histologically by lymphoplasmacytic infiltrates with IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis that may affect nearly every organ of the body. There are similarities in clinical, serological, radiological, and histopathological features between both diseases, and hence, they usually mimic each other complicating the differential diagnosis. Furthermore, reports of patients with the coexistence of both conditions (overlap syndrome) have been reported. We herein report a patient with an unequivocal diagnosis of ANCA-associated vasculitis, specifically granulomatosis with polyangiitis (posterior uveitis, polyneuropathy, pauci-immune glomerulonephritis with crescent formation and granulomas, and MPO-ANCA positivity) and IgG4-related disease (thoracic aortitis, tubulointerstitial nephritis with prominent IgG4+ plasma cell infiltration, fibrosis, and obliterative arteritis, high levels of serum IgG4, and eosinophilia) overlap syndrome.

From Head to Toe: Granulomatosis with Polyangiitis.

Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody-associated vasculitis. It is an uncommon multisystem disease involving predominantly small vessels and is characterized by granulomatous inflammation, pauci-immune necrotizing glomerulonephritis, and vasculitis. GPA can involve virtually any organ. Clinical manifestations are heterogeneous and can be classified as granulomatous (eg, ear, nose, and throat disease; lung nodules or masses; retro-orbital tumors; pachymeningitis) or vasculitic (eg, glomerulonephritis, alveolar hemorrhage, mononeuritis multiplex, scleritis). The diagnosis of GPA relies on a combination of clinical findings, imaging study results, laboratory test results, serologic markers, and histopathologic results. Radiology has a crucial role in the diagnosis and follow-up of patients with GPA. CT and MRI are the primary imaging modalities used to evaluate GPA manifestations, allowing the differentiation of GPA from other diseases that could simulate GPA. The authors review the main clinical, histopathologic, and imaging features of GPA to address the differential diagnosis in the affected organs and provide a panoramic picture of the protean manifestations of this infrequent disease. The heterogeneous manifestations of GPA pose a significant challenge in the diagnosis of this rare condition. By recognizing the common and unusual imaging findings, radiologists play an important role in the diagnosis and follow-up of patients with GPA and aid clinicians in the differentiation of disease activity versus disease-induced damage, which ultimately affects therapeutic decisions. Online supplemental material is available for this article. ©RSNA, 2021.

Classification of ANCA-associated vasculitis: differences based on ANCA specificity and clinicopathologic phenotype.

The classification of vasculitis according to a schema with universal acceptance is challenging, given the heterogeneous and protean nature of these diseases. Formal nomenclature and classification criteria for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have suffered several changes since their first description; none provides comprehensive diagnostic and classification criteria. Different factors account for the difficulties in the classification of vasculitis, including the incomplete understanding of the pathogenesis, the multisystemic nature of the disease, the non-specific patterns of vascular involvement, the overlap between entities, and the presence of various classification systems. The present article reviews the classification of AAV considering different points of view, including clinical, serologic, pathogenetic, organ predilection, therapeutic, and prognostic factors, and provides perspectives on future challenges in the understanding of AAV. There is an unmet need for a unifying view of the disease spectrum that considers the constantly evolving paradigms.

Takayasu's Arteritis from the Patients' Perspectives: Measuring the Pulse to the Patient-Reported Outcomes.

BACKGROUND: Patients with Takayasu's arteritis (TA) experience important changes in lifestyle, quality of life, and functional status due to ischemic symptoms or treatment toxicity. PURPOSE: To describe the clinical characteristics and the patient-reported outcomes (PROs), such as quality of life, disability, fatigue, and perception/impact of the disease in Mexican patients with TA. METHODS: Cross-sectional study including patients with established diagnosis of TA recruited at a tertiary care center. Demographics, comorbidities, clinical characteristics, laboratory, imaging, and treatment were retrieved. Disease activity (the Indian Takayasu Clinical Activity Score (ITAS) 2010), damage (Vasculitis Damage Index (VDI)), quality of life (Short Form 36 (SF-36)), disability (Health Assessment Questionnaire Disability Index (HAQ-DI)), fatigue (Multidimensional Fatigue Inventory-20), and patient's disease perceptions were assessed. RESULTS: Fifteen women were included, with a median age of 41 years (interquartile range (IQR) 30-45) and disease duration of 108 months (IQR 55-197). Median ITAS 2010 and VDI scores were 0 (IQR 0-2) and 3 points (IQR 2-6), respectively. Mean SF-36 score was 71.38 ± 13.39, with mean physical and mental component summaries of 66.52 ± 13.37 and 76.24 ± 14.89, respectively. HAQ-DI mean score was 0.48 ± 0.62, being grip the most affected domain. Among fatigue subscales, the higher scores were present in the physical fatigue (16.3 ± 5.8). Correlations between the HAQ-DI and the VDI score (r = 0.64, P = 0.03); between the general fatigue, score, and disease duration (r = -0.71, P = 0.01); and between the SF-36 total score and the HAQ-DI (r = -0.87, P = 0.0004) were found. CONCLUSIONS: It is important to identify disease-specific outcomes of interest to the patients to develop tools that assess them with a holistic approach.

Severe infections in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis: a retrospective cohort study with a clinical phenotype approach.

Severe infections are common in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We aimed to describe the characteristics of patients with AAV and severe infections according to clinical phenotype. Retrospective cohort study including patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Baseline characteristics were compared between patients with and without at least one severe infection. Demographics, comorbidities, clinical characteristics, laboratory and treatment were retrieved at diagnosis and at every infectious event. One hundred and eight patients were included (57 with and 51 without infections). Patients with an infection had received more frequently methylprednisolone boluses at AAV diagnosis than patients without infections (OR 2.6, 95% CI 1.1-5.9, p = 0.01). There were a total of 108 severe infections in 57 patients (median follow-up 18 months). Thirty-two patients (56%) had an infectious complication within the first year of AAV diagnosis, 43 (75%) had pulmonary involvement during the first infection. The most frequent type of infection was pneumonia. Phenotypes were: Non-severe AAV (n = 11), severe PR3-AAV (n = 30), severe MPO-AAV (n = 9); the number of infectious events in each group was 11, 69, 18, respectively. Patients with severe MPO phenotype were older and required more frequently ICU stay compared to other phenotypes. Positive correlation was found between total of infections and pulmonary infiltrates due to vasculitis (ρ = 0.40, p = 0.003), endobronchial involvement (ρ = 0.40, p = 0.003), and alveolar hemorrhage (ρ = 0.34, p = 0.015). Severe infections, most commonly pneumonia, were frequent in this cohort, especially during the first year after diagnosis, in patients with pulmonary involvement and severe PR3 phenotype who received methylprednisolone boluses.

Validation of a renal risk score in a cohort of ANCA-associated vasculitis patients with severe kidney damage.

OBJECTIVE: To validate the renal risk score in a cohort of patients with advanced kidney damage. METHODS: A total of 72 patients with biopsy-proven ANCA glomerulonephritis with >12 months of follow-up were studied. The renal risk score was calculated and evaluated by survival analysis for time of renal survival. Cohort-specific clinical, histopathologic, and post-treatment factors associated with renal survival were determined by Cox regression analysis. RESULTS: Kidney biopsies were classified as focal, crescentic, mixed, and sclerotic classes in 6 (8%), 4 (6%), 25 (35%), and 37 (51%) patients, respectively. The 1-, 3-, and 5-year renal survival rates were 79%, 73%, and 68%, respectively. Patients were segregated by the risk score in low- (18%), medium- (47%), and high-risk (35%) groups. Patients in the low-risk group had 36-, 60-, and 84-month renal survival of 100%; those in the medium risk 85% (95% CI 72-92), 81% (95% CI 66-95), and 76% (95% CI 60-92), respectively; and those in the high risk 37% (95% CI 17-57), 26% (95% CI 7-45), and 18% (95% CI 1-36), respectively. Six (43%) of the 14 patients in the high-risk group recovered renal function after the initial episode, and 2 (14%) remained dialysis-free. Other parameters associated with renal survival included age, proteinuria, general symptoms, cellular crescents, glomerulosclerosis, tubulointerstitial lesions, best post-treatment eGFR, and renal relapses. CONCLUSIONS: We validated the renal risk score as a prognostic tool in a cohort with predominantly mixed and sclerotic histologic categories. Since patients in the high-risk group still benefited from immunosuppressive therapy, this score should be used in conjunction with other predictive parameters to aid therapeutic decisions.Key Points• The ANCA renal risk score is validated in a cohort with advanced kidney damage.• Patients in the high-risk group still benefited from immunosuppressive therapy.• Parameters not included in the risk score are associated with renal survival and may be useful.

Pituitary dysfunction in granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA) is a necrotizing granulomatous vasculitis of small vessels that affect the pituitary gland in less than 1% of cases being exceptionally rare. To describe the clinical, biochemical, radiological findings, treatment, and outcomes of 4 patients with GPA-related hypophysitis. A systematic review of published cases with the same diagnosis is presented as well. A cross-sectional case series of patients with hypophysitis due to GPA from 1981 to 2018 at a third level specialty center. Literature review was performed searching in seven different digital databases for terms "granulomatosis with polyangiitis" and "pituitary gland" or "hypophysitis," including in the analysis all published cases between 1950 and 2019 with a minimum follow-up of 6 months. We found 197 patients with GPA in our institution of whom 4 patients (2.0%) had pituitary involvement. Clinical characteristics and outcomes are described. We also reviewed 7 case series, and 36 case reports describing pituitary dysfunction related to GPA from 1953 to 2019, including the clinical picture of an additional 74 patients. Pituitary dysfunction due to GPA is rare. Treatment is targeted to control systemic manifestations; nevertheless, the outcome of the pituitary function is poor. Central diabetes insipidus, particularly in younger women with other systemic features, should raise suspicion of GPA.Key Points• Involvement of the pituitary gland is an uncommon manifestation in GPA patients. The presence of central diabetes insipidus in the setting of systemic symptoms should prompt its suspicion.• In patients with pituitary involvement due to GPA, affection of other endocrine glands is rare, neither concomitant nor in different times during the disease course. This may arise the hypothesis of a local or regional pathogenesis affection of the gland.• There is no consensus on the best therapy strategy for GPA hypophysitis. Although the use of glucocorticoids with CYC is the most common drug combination, no differences in the outcome of the pituitary function and GPA disease course are seen with other immunosuppressants.• Poor prognosis regarding pituitary function is expected due to possible permanent pituitary tissue damage that results in the need of permanent hormonal replacement.

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.

Prevalence of overlap of antineutrophil cytoplasmic antibody associated vasculitis with systemic autoimmune diseases: an unrecognized example of poliautoimmunity.

We aimed to estimate the frequency of overlap of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with systemic autoimmune diseases. Retrospective single-center study to identify patients with AAV diagnosis and concomitant autoimmune systemic diseases, simultaneously, before or after the diagnosis of AAV. Sociodemographic characteristics, such as comorbidities; follow-up time; type of AAV; disease duration; relapses; treatment and response; clinical, serological, and histological characteristics; disease activity and damage; prognosis; dialysis requirements, and death were assessed. Twenty-eight of two hundred and forty-seven patients (11.3%) with AAV had a concomitant diagnosis of autoimmune disease. The predominant AAV type was renal-limited vasculitis (39%), followed by granulomatosis with polyangiitis (29%), mycroscopic polyangiitis (25%), and eosinophilic granulomatosis with polyangiitis (7%). Mean age at AAV diagnosis was 50 ± 17 years and 24/28 were ANCA positive. The main clinical manifestations were renal (79%), otorhinolaryngologic (43%), and pulmonary and peripheral neuropathy (32%). Sixteen patients (57%) experienced partial or total remission at a median follow-up of 34 months, and four patients (14%) died. The most frequent autoimmune disease overlapped was rheumatoid arthritis (39%), followed by Sjögren's syndrome and systemic sclerosis (14%), mixed connective tissue disease (11%), systemic lupus erythematosus and juvenile idiopathic arthritis (7%), and ankylosing spondylitis and IgG4-related disease (4%). In nine patients (32%), both diagnoses were simultaneous; in the rest, median time elapsed between the autoimmune disease and AAV diagnosis was 173 months. The prevalence of overlap AAV with other autoimmune diseases was low. The most common AAV phenotype was renal-limited vasculitis, and the most frequent overlap disease was rheumatoid arthritis.