Acute aortoiliac thrombosis and mitral valve regurgitation as acute onset of eosinophilic granulomatosis with polyangiitis in a 26-year-old patient.

We present a rare case of eosinophilic granulomatosis with polyangiitis (EGPA), involving a 26-year-old woman with a history of asthma and nasal polyps. The patient presented with acute aortoiliac thrombosis and mitral insufficiency, which was successfully treated with thrombolysis, aortic thromboendarterectomy, and valve replacement. Peripheral hypereosinophilia with eosinophilic infiltration of the heart led to the diagnosis of antineutrophilic cytoplasmic antibody-negative EGPA. Treatment with prednisone and mepolizumab was started, resulting in a positive outcome. This case showcases an unusual manifestation of EGPA with large size vessel involvement and requiring surgical and pharmacological treatment. It also highlights the importance of early detection for timely intervention and an improved prognosis.

Novel insights into the management of rheumatoid arthritis: one year in review 2024.

New evidence from 2023 has slightly shifted some perspectives on rheumatoid arthritis (RA) management. Glucocorticoids have reaffirmed their role as bridging therapy, while novel studies on JAK inhibitors have examined efficacy, mechanism of action, and their potential in high-risk populations, bolstering our understanding with real-world data.Additionally, among treatment strategies, achieving low disease activity has emerged as comparable to achieving remission in the long term, and new insights have been gained regarding tapering both biological and conventional synthetic DMARDs. Furthermore, novel approaches have been proposed for managing difficult-to-treat RA and pre-RA. In this paper, the reviewers aim to present the most relevant studies published during the last year in the field of RA management.

Prevalence and clinical significance of ANCA positivity in lupus nephritis: a case series of 116 patients and literature review.

The prevalence and clinical significance of anti-neutrophil cytoplasmic antibodies [ANCAs] in patients with lupus nephritis [LN] is not fully elucidated. Our aim was to determine whether LN patients with ANCA positivity had different clinicopathological features and outcomes compared to ANCA-negative patients. METHODS: Among our LN patients we retrospectively selected those who underwent ANCA testing the day of the kidney biopsy and before the start of induction treatment. Clinical/histopathological features at kidney biopsy and renal outcome of ANCA-positive patients were compared with those of ANCA-negative subjects. RESULTS: We included 116 Caucasian LN patients in the study; 16 patients [13.8%] were ANCA-positive. At kidney biopsy, ANCA-positive patients presented more frequently with an acute nephritic syndrome than ANCA-negative ones; the difference however does not reach statistical significance [44 vs. 25%, p = 0.13]. At histological evaluation, proliferative classes [100% vs 73%; p = 0.02], class IV [68.8% vs 33%; p < 0.01] and necrotizing tuft lesions [27 vs 7%, p = 0.04] were more frequent, and the activity index was higher [10 vs 7; p = 0.03] in ANCA-positive than in ANCA-negative patients. Despite worse histological features, after a 10-year observation period, there were no significant differences in the number of patients with chronic kidney function impairment (defined as eGFR < 60 mL/min per 1.73 m2) between the ANCA-positive and negative groups [24.2 vs 26.6%, p = 0.9]. This could be the result of the more aggressive therapy, with rituximab plus cyclophosphamide, that ANCA-positive patients received more frequently than ANCA-negative ones [25 vs. 1.3%, p < 0.01]. CONCLUSIONS: ANCA-positive LN patients frequently have histological markers of severe activity (proliferative classes and high activity index) that require timely diagnosis and aggressive therapy to limit the development of irreversible chronic kidney damage.

Late skin fibrosis in systemic sclerosis: a study from the EUSTAR cohort.

OBJECTIVES: The early trajectory of skin fibrosis provides insights into the disease course of systemic sclerosis (SSc) including mortality; however, little is known about late skin fibrosis. The aims of our study were to ascertain the prevalence and characteristics of late skin fibrosis in SSc. METHODS: We developed and tested three conceptual scenarios of late (>5 years after first non-RP feature) skin fibrosis including new worsening of skin disease, and failure to improve after worsening within 5-year window. We defined skin worsening as change in modified Rodnan skin score (mRSS) ≥5 units or ≥25%. Using strict inclusion criteria including complete mRSS, we identified 1,043 (out of 19 115) patients within the EUSTAR database for our analysis. We further restricted analysis within 887 (out of 1043) patients who had lcSSc or dcSSc at baseline. RESULTS: One-fifth of patients among the whole cohort (n = 208/1043, 19.9%) experienced mRSS worsening, including in patients with lcSSc or dcSSc at baseline (n = 193/887, 21.8%). This was largely due to new skin worsening after the 5-year window or failure to improve with worsening within the 5-year window. Patients with lower baseline mRSS and lcSSc were more likely to develop late skin fibrosis. Anti-Scl-70 was associated with progression from baseline lcSSc to dcSSc, and anticentromere was protective. CONCLUSIONS: Late skin fibrosis is not uncommon in SSc. We have identified different patterns relevant to clinical practice and trial design. Late skin fibrosis is a neglected manifestation of SSc and warrants further investigation including to determine clinical outcomes and optimal therapeutic strategy.

Long-term kidney outcome of patients with rheumatological diseases and antineutrophil cytoplasmic antibody-glomerulonephritis: comparison with a primitive ANCA-glomerulonephritis cohort.

OBJECTIVES: Antineutrophil cytoplasmic antibody (ANCA) may appear in the course of rheumatic diseases (RD) but the kidney involvement is very rare and the prognosis poorly defined. METHODS: We retrospectively identified patients with RD among 153 patients with ANCA glomerulonephritis (ANCA-GN). Their clinical/histological presentation and outcome were compared with that of primitive ANCA-GN patients (1:4) matched for sex, age, ANCA type and follow-up. RESULTS: Nine patients (5.9%) were included: three had rheumatoid arthritis, two systemic sclerosis, two psoriatic arthritis, one ankylosing spondylitis and one seronegative spondylarthritis. Seven patients were MPO positive, two PR3 positive. ANCA-GN developed 74 months after RD with microscopic haematuria and acute kidney dysfunction in all but two patients. After 68-month follow-up, four patients (44.4%) achieved response to therapy defined as eGFR >60/min/1,73 m2 or stable, no microscopic haematuria and negative ANCA. At ANCA-GN diagnosis, serum creatinine and C-reactive protein were significantly lower in RD-ANCA-GN (2.38 vs. 3.34mg/dl, p=0.05 and 2.3mg/dl vs. 7.2mg/dl; p=0.05, respectively) while haemoglobin was higher (12.3g/dl vs. 9.3g/dl p<0.01) than in the 36 primitive ANCA-GN patients of control group. At kidney biopsy, focal forms were more frequent in RD patients (44.45% vs. 18.75%, p=0.11). The treatment between the two groups was not significantly different. At last observation, the percentage of patients with ESKD was lower in RD than in controls (11.1%vs. 30.5%; p=0.23). CONCLUSIONS: Patients with RD seem to develop ANCA-GN with less severe clinical/histological kidney involvement, and better long-term kidney survival than primitive ANCA-GN. This is probably due to the strict monitoring of RD patients that allows a prompter ANCA-GN diagnosis and treatment.

Sex influence on outcomes of patients with systemic sclerosis-associated interstitial lung disease: a EUSTAR database analysis.

OBJECTIVE: Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in systemic sclerosis (SSc) patients. We aimed to investigate the impact of sex on SSc-ILD. METHODS: EUSTAR SSc patients with radiologically confirmed ILD and available percentage predicted forced vital capacity (%pFVC) were included. Demographics and disease features were recorded. A change in %pFVC over 12 months (s.d. 6) (cohort 1) was classified into stable (≤4%), mild (5-9%) and large progression (≥10%). In those with 2-year longitudinal %pFVC (cohort 2), the %pFVC change at each 12-month (s.d. 6) interval was calculated. Logistic regression analyses [odds ratio (OR) and 95% CI] and Cox proportional hazards models adjusted for age and %pFVC were applied. RESULTS: A total of 1136 male and 5253 female SSc-ILD patients were identified. Males were significantly younger, had a shorter disease duration, had a higher prevalence of CRP elevation and frequently had diffuse cutaneous involvement. In cohort 1 (1655 females and 390 males), a higher percentage of males had stable ILD (74.4% vs 69.4%, P = 0.056). In multivariable analysis, disease duration and %pFVC [OR 0.99 (95% CI 0.98, 0.99) and OR 0.97 (95% CI 0.95, 0.99), respectively] in males and age, %pFVC and anti-centromere [OR 1.02 (95% CI 1.00, 1.04), OR 0.97 (95% CI 0.96, 0.98) and OR 0.39 (95% CI 0.245, 0.63), respectively] in females were associated with large progression. The 1-year mortality rate was higher in males (5.1% vs 2.5%, P = 0.013). In cohort 2 (849 females and 209 males), a higher percentage of females showed periods of large progression (11.7% vs 7.7%, P = 0.023), the percentage of patients with none, one or two periods of worsening was not different. The overall death rate was 30.9% for males and 20.4% in females (P < 0.001). In the survival analysis, male sex was a predictor of mortality [OR 1.95 (95% CI 1.66, 2.28)]. CONCLUSIONS: Male SSc-ILD patients have a poorer prognosis and sex-specific predictors exist in SSc-ILD.

Efficacy and safety of baricitinib in 446 patients with rheumatoid arthritis: a real-life multicentre study.

OBJECTIVES: Baricitinib, an oral Janus kinase (JAK) 1-2 inhibitor, is currently used along biologic DMARDs (bDMARDs) after the failure of methotrexate (MTX) in rheumatoid arthritis (RA). We investigated the efficacy and safety of baricitinib in real life. METHODS: We prospectively enrolled 446 RA patients treated with baricitinib from 11 Italian centres. Patients were evaluated at baseline and after 3, 6, and 12 months. They were arrayed based on previous treatments as bDMARD-naïve and bDMARD-insufficient responders (IR) after the failure or intolerance to bDMARDs. A sub-analysis differentiated the effects of methotrexate (MTX) and the use of oral glucocorticoids (OGC). RESULTS: Our cohort included 150 (34%) bDMARD-naïve and 296 (66%) bDMARD-IR patients, with 217 (49%) using baricitinib as monotherapy. Considering DAS-28-CRP as the primary outcome, at 3 and 6 months, 114/314 (36%) and 149/289 (51.6%) patients achieved remission, while those in low disease activity (LDA) were 62/314 (20%) and 46/289 (15.9%), respectively; finally at 12 months 81/126 (64%) were in remission and 21/126 (17%) in LDA. At all-timepoints up to 12 months, bDMARDs-naïve patients demonstrated a better clinical response, independently of MTX. A significant reduction in the OGC dose was observed at 3 and 12 months in all groups. The serum positivity for both rheumatoid factors (RF) and anti-citrullinated protein antibodies (ACPA) conferred a lower risk of stopping baricitinib due to inefficacy. Fifty-eight (13%) patients discontinued baricitinib due to adverse events, including thrombotic events and herpes zoster reactivation. CONCLUSIONS: Real-life data confirm the efficacy and safety profiles of baricitinib in patients with RA and provide evidence that drug survival is higher in bDMARDs-naïve and seropositive patients.

Interstitial Pneumonia with Autoimmune Features: Why Rheumatologist-Pulmonologist Collaboration Is Essential.

In 2015 the European Respiratory Society (ERS) and the American Thoracic Society (ATS) "Task Force on Undifferentiated Forms of Connective Tissue Disease-associated Interstitial Lung Disease" proposed classification criteria for a new research category defined as "Interstitial Pneumonia with Autoimmune Features" (IPAF), to uniformly define patients with interstitial lung disease (ILD) and features of autoimmunity, without a definite connective tissue disease. These classification criteria were based on a variable combination of features obtained from three domains: a clinical domain consisting of extra-thoracic features, a serologic domain with specific autoantibodies, and a morphologic domain with imaging patterns, histopathological findings, or multicompartment involvement. Features suggesting a systemic vasculitis were excluded. Since publication of ERS/ATS IPAF research criteria, various retrospective studies have been published focusing on prevalence; clinical, morphological, and serological features; and prognosis of these patients showing a broad heterogeneity in the results. Recently, two prospective, cohort studies were performed, confirming the existence of some peculiarities for this clinical entity and the possible progression of IPAF to a defined connective tissue disease (CTD) in about 15% of cases. Moreover, a non-specific interstitial pneumonia pattern, an anti-nuclear antibody positivity, and a Raynaud phenomenon were the most common findings. In comparison with idiopathic pulmonary fibrosis (IPF), IPAF patients showed a better performance in pulmonary function tests and less necessity of oxygen delivery. However, at this stage of our knowledge, we believe that further prospective studies, possibly derived from multicenter cohorts and through randomized control trials, to further validate the proposed classification criteria are needed.

Functional Progression in Patients with Interstitial Lung Disease Resulted Positive to Antisynthetase Antibodies: A Multicenter, Retrospective Analysis.

Antisynthetase syndrome (ASSD) is a rare autoimmune disease characterized by serologic positivity for antisynthetase antibodies. Anti-Jo1 is the most frequent, followed by anti PL-7, anti PL-12, anti EJ, and anti OJ antibodies. The lung is the most frequently affected organ, usually manifesting with an interstitial lung disease (ILD), which is considered the main determinant of prognosis. Some evidences suggest that non-anti-Jo-1 antibodies may be associated with more severe lung involvement and possibly with poorer outcomes, while other authors do not highlight differences between anti-Jo1 and other antisynthetase antibodies. In a multicenter, retrospective, "real life" study, we compared lung function tests (LFTs) progression in patients with ILD associated with anti-Jo1 and non-anti-Jo1 anti-synthetase antibodies to assess differences in lung function decline between these two groups. Therefore, we analyzed a population of 57 patients (56% anti-Jo1 positive), referred to the outpatient Clinic of four referral Centers in Italy (Modena, Monza, Siena, and Trieste) from 2008 to 2019, with a median follow-up of 36 months. At diagnosis, patients showed a mild ventilatory impairment and experienced an improvement of respiratory function during treatment. We did not observe statistically significant differences in LFTs at baseline or during follow-up between the two groups. Moreover, there were no differences in demographic data, respiratory symptoms onset (acute vs. chronic), extrapulmonary involvement, treatment (steroid and/or another immunosuppressant), or oxygen supplementation. Our study highlights the absence of differences in pulmonary functional progression between patients positive to anti-Jo-1 vs. non anti-Jo-1 antibodies, suggesting that the type of autoantibody detected in the framework of ASSD does not affect lung function decline.

Belimumab may decrease flare rate and allow glucocorticoid withdrawal in lupus nephritis (including dialysis and transplanted patient).

BACKGROUND: Belimumab (Benlysta) is currently approved for the treatment of active Lupus despite standard therapy. Few data are available on the efficacy of this drug in lupus nephritis (LN). METHODS: 17 LN female followed in two Nephrology Italian Unit received belimumab for a median period of 36 months (range 6-42 months). The indications were: arthralgia in 3 patients, cutaneous manifestations in 2, residual proteinuria in 8, and the need to reduce steroids for severe side effects in 4. Of interest, 1 patient started therapy during Peritoneal Dialysis and continued after kidney transplantation due to non-responsive arthralgias. RESULTS: Arthralgia and skin manifestations resolved in all patients. Proteinuria normalized in three patients and stabilized in all but one of the others. Steroids were indefinitely stopped in six patients (35%) and reduced to around 40% of the basal dosage in the other patients. During belimumab therapy, three extrarenal and one renal SLE flares were diagnosed accounting for a rate of renal flares of 0.02/patient/year. No major adverse events leading to therapy withdrawal occurred. CLINICAL CASE: Arthralgia resolved, immunological parameters improved and prednisone could be reduced within few months in the patient who started belimumab during peritoneal dialysis. After kidney transplantation belimumab was stopped but due to arthralgias unresponsive to standard immunosuppressive therapy it was restarted with success. CONCLUSIONS: Belimumab allows the achievement of complete response together with the withdrawal or the reduction of corticosteroids in almost all our patients. Of interest its satisfactory use in a patient in peritoneal dialysis and after kidney transplantation.

Observational study on the QUality of life of Italian Axial SpondyloARthritis patients (QUASAR): baseline data.

OBJECTIVES: To describe the baseline characteristics of the patients enrolled in the QUality of life in patients with Axial SpondyloARthritis (QUASAR) study in terms of quality of life (QoL), disease activity, therapy adherence, and work ability in a real-world setting. METHODS: QUASAR is an Italian multicentre, prospective 12-month observational study, including consecutive adult patients classified as axial spondyloarthritis (axSpA) according to the Assessment of SpondyloArthritis international Society criteria for axSpA. RESULTS: Of 512 patients enrolled in 23 rheumatology centres, 80.7% had ankylosing spondylitis (AS) and 19.3% had non-radiographic axSpA (nr-axSpA). Mean ages were 34.1±13.3 years at axSpA symptoms onset and 39.5±13.0 years at diagnosis. Of the patients, 51.4% presented with ≥1 extra articular manifestation (EAM); the most common were psoriasis (17.8%) and uveitis (16.4%). Patients with nr-axSpA and AS had similar EAM rates, disease activity, and QoL. Biologic disease-modifying anti-rheumatic drugs (bDMARDs; 83.2%) were the most commonly received medication, followed by conventional synthetic DMARDs (22.9%) and non-steroidal anti-inflammatory drugs (NSAIDs; 16.6%). At baseline, higher treatment satisfaction was reported with bDMARDs which, together with NSAIDs, were associated with the best overall scores for disease activity, function, and QoL in the overall population and AS subgroup. CONCLUSIONS: QUASAR is the first Italian prospective study that comprehensively evaluated a large axSpA patient sample in a real-world setting. This interim analysis at baseline confirmed that i) patients with AS and nr-axSpA have similar QoL and disease burden, ii) nearly all axSpA patients receive treatment, and iii) bDMARDs and NSAIDs, overall, yield better disease activity and QoL.

Non-specific interstitial pneumonia and features of connective tissue disease: What are the consequences of a different point of view?

Patients with Interstitial Lung Disease (ILD) without a definitive diagnosis of connective tissue diseases (CTD) were historically described as Undifferentiated Connective Tissue Disease (UCTD-ILD). Recently a new classification, Interstitial Pneumonia with Autoimmune Features (IPAF), has been proposed. Aim of this study was to describe the prevalence, clinical characteristics and prognostic factors of UCTD and IPAF subjects in a cohort of Non-Specific Interstitial Pneumonia (NSIP) patients. This retrospective, observational study enrolled 102 adult patients characterized by NSIP pattern on High Resolution Computed Tomography, without a specific diagnosis of CTD. Three groups were identified according to patients' characteristics: IPAF, UCTD or idiopathic NSIP (iNSIP). Forty percent, 27% and 55% of patients showed diagnostic criteria for IPAF, UCTD and iNSIP, respectively. No significant differences in age, gender, smoking habit, pulmonary function tests and three-year survival rate were observed among study groups. IPAF patients with antisynthetase antibodies positivity, in comparison to IPAF without antisynthetase antibodies positivity, showed more frequently an acute onset (44% vs 9%, p<0.012). The presence of autoimmune features seems not to be associated with better outcomes in NSIP patients. IPAF criteria seem to be more representative than UCTD criteria in identifying patients with autoimmune features. Further studies are needed to verify if IPAF should include patients with positive antisynthetase serology.

Association Between Atrial, Ventricular and Vascular Morphofunctional Alterations in Rheumatoid Arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) represents a risk of non-fatal and cardiovascular events. The aim of the present study was to evaluate simultaneously left and right atrial and ventricular function, as well as arterial stiffness, in RA patients. METHODS: This cross-sectional study included 55 consecutive RA patients and 55 healthy age and gender-matched controls. Blood pressure and arterial stiffness were assessed in all participants, who also underwent a complete echocardiographic examination. RESULTS: RA patients were treated with steroid therapy (52.7%), methotrexate (66.6%) and biological therapy (54.5%). Disease activity score revealed low average RA activity. Augmentation index was significantly higher in RA patients (32.2 ± 8.6 vs. 28.4 ± 8.9%, P = 0.02). Left atrial volume was also higher among RA patients (23.1 ± 8.2 vs. 20.1 ± 7.1 ml/m2, P = 0.04), whereas mitral and tricuspid E/A ratios were significantly lower in RA individuals (0.90 ± 0.24 vs. 1.03 ± 0.35, P = 0.02; 1.07 ± 0.31 vs. 1.27 ± 0.35, P = 0.003, respectively). Tissue Doppler systolic and diastolic velocities were similar between the observed groups. Arterial stiffness index showed significant correlation with disease duration (r = 0.29; P = 0.03). Tissue Doppler-derived transmitral late diastolic velocity (A') showed significant correlation with index of disease activity in the RA patients. CONCLUSIONS: Our results showed that left and right ventricular diastolic function and arterial stiffness were significantly deteriorated in the RA patients comparing with controls. The assessment of left and right ventricular diastolic function, as well as vascular function, should be an essential part of clinical evaluation in the RA patients.

Interstitial pneumonia with autoimmune features: an additional risk factor for ARDS?

BACKGROUND: Interstitial pneumonia with autoimmune features (IPAF) identifies a recently recognized autoimmune syndrome characterized by interstitial lung disease and autoantibodies positivity, but absence of a specific connective tissue disease diagnosis or alternative etiology. We retrospectively reviewed the clinical presentation, diagnostic workup and management of seven critically ill patients who met diagnostic criteria for IPAF. We compared baseline characteristics and clinical outcome of IPAF patients with those of the population of ARDS patients admitted in the same period. RESULTS: Seven consecutive patients with IPAF admitted to intensive care unit for acute respiratory distress syndrome (ARDS) were compared with 78 patients with ARDS secondary to a known risk factor and with eight ARDS patients without recognized risk factors. Five IPAF patients (71%) survived and were discharged alive from ICU: Their survival rate was equal to that of patients with a known risk factor (71%), while the subgroup of patients without risk factors had a markedly lower survival (38%). According to the Berlin definition criteria, ARDS was severe in four IPAF patients and moderate in the remaining three. All had multiple organ dysfunction at presentation. The most frequent autoantibody detected was anti-SSA/Ro52. All patients required prolonged mechanical ventilation (median duration 49 days, range 10-88); four received extracorporeal membrane oxygenation and one received low-flow extracorporeal CO2 removal. All patients received immunosuppressive therapy. CONCLUSIONS: This is the first description of a cohort of critical patients meeting the diagnostic criteria for IPAF presenting with ARDS. This diagnosis should be considered in any critically ill patient with interstitial lung disease of unknown origin. While management is challenging and level of support high, survival appears to be good and comparable to that of patients with ARDS associated with a known clinical insult.

Granulomatosis with polyangiitis presenting with diffuse alveolar hemorrhage requiring extracorporeal membrane oxygenation with rapid multiorgan relapse: A case report.

RATIONALE: Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmatic antibodies (ANCA)-associated vasculitis affecting small- and medium-sized blood vessels, mostly involving lung and kidney. PATIENT CONCERNS: We report the case of a 33-year-old man that presented with acute respiratory distress syndrome caused by alveolar hemorrhage. DIAGNOSES: Aggressive GPA presenting with diffuse alveolar hemorrhage and multiorgan involvement. INTEVENTIONS: Immunosuppressive therapy, plasma exchange, extracorporeal membrane oxygenation (ECMO). OUTCOMES: Relapse occurred very early, despite immunosuppressive treatment, with a rare involvement of genital system (epididymitis) and rapidly progressive glomerulonephritis difficult to treat. LESSONS: GPA is a challenging, multifaceted disease that can require aggressive supportive therapy and is associated with a high rate of relapse that may present with uncommon site of involvement.