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.

Azathioprine vs methotrexate in eosinophilic granulomatosis with polyangiitis: a monocentric retrospective study.

OBJECTIVES: To analyse the effectiveness, safety and steroid-sparing effect of AZA and MTX as induction of remission and maintenance treatment in eosinophilic granulomatosis with polyangiitis. METHODS: We retrospectively collected data from 57 patients divided into four groups according to treatment: MTX/AZA as first-line agents (MTX1/AZA1) in non-severe disease or as second-line maintenance therapy (MTX2/AZA2) in severe disease previously treated with CYC/rituximab. During the first 5 years of treatment with AZA/MTX we compared the groups according to: remission rate [defined as R1: BVAS = 0; R2: BVAS = 0 with prednisone ≤5 mg/day; R3 (MIRRA definition): BVAS = 0 with prednisone ≤3.75 mg/day], persistence on therapy, cumulative glucocorticoid (GC) dose, relapse and adverse events (AEs). RESULTS: There were no significant differences in remission rates (R1) in each group (63% in MTX1 vs 75% in AZA1, P = 0.53; 91% in MTX2 vs 71% in AZA2, P = 0.23). MTX1 allowed R2 more frequently in the first 6 months compared with AZA1 (54% vs 12%, P = 0.04); no patients receiving AZA1 achieved R3 up to the first 18 months (vs 35% in MTX1, P = 0.07). The cumulative GC dose was lower for MTX2 vs AZA2 (6 g vs 10.7 g at 5 years, P = 0.03). MTX caused more AEs compared with AZA (66% vs 30%, P = 0.004), without affecting the suspension rate. No differences emerged in time-to-first relapse, although fewer patients treated with AZA2 had asthma/ENT relapses (23% vs 64%, P = 0.04). CONCLUSION: A significant proportion of patients achieved remission with both MTX and AZA. MTX1 had an earlier remission on a lower GC dose but MTX2 had a better steroid-sparing effect.

Unfolding dermatologic spectrum of Behçet's disease in Italy: real-life data from the International AIDA Network Behçet's disease Registry.

Behçet's disease (BD) is a heterogeneous multifactorial autoinflammatory disease characterized by a plethora of clinical manifestations. Cutaneous lesions are considered hallmarks of the disease. However, their evolution over time and a thorough description are scarcely reported in non-endemic regions. The aim of this study was to detail BD skin manifestations and their evolution over time in Italy, as well as the dermatological prognostic impact of specific cutaneous features in long-standing disease. Data were collected in a double fashion, both retrospectively and prospectively, from the AutoInflammatory Disease Alliance (AIDA) international registry dedicated to BD, between January 2022 and December 2022. A total of 458 Italian patients were included. When assessing skin manifestations course, the constant or sporadic presence or absence of cutaneous involvement between onset and follow-up was considered. Oral ulcers (OU) (88.4%) and genital ulcers (GU) (52.6%), followed by skin involvement (53.7%) represented the most common presenting mucocutaneous manifestations at disease onset. Up to the time of enrolment into the AIDA registry, 411 (93.8%) patients had suffered from OU and 252 (57.9%) from GU; pseudofolliculitis (PF) accounted for the most common skin manifestation (170 patients, 37.1%), followed by erythema nodosum (EN) (102 patients, 22.3%), skin ulcers (9 patients, 2%) and pyoderma gangrenosum (4 patients, 0.9%). A prospective follow-up visit was reported in 261/458 patients; 24/148 (16.2%) subjects with skin involvement as early as BD onset maintained cutaneous lesions for the entire period of observation, while 120 (44.1%) patients suffered from sporadic skin involvement. Conversely, 94/113 (83.2%) with no skin involvement at disease onset did not develop skin lesions thereafter. At follow-up visits, cutaneous involvement was observed in 52 (20%) patients, with a statistically significant association between PF and constant skin involvement (p = 0.031). BD in Italy is characterized by a wide spectrum of clinical presentations and skin manifestations in line with what is described in endemic countries. Patients with skin disease at the onset are likely to present persistent cutaneous involvement thereafter; mucocutaneous lesions observed at the onset, especially PF, could represent a warning sign for future persistent skin involvement requiring closer dermatological care.

Cytomegalovirus colitis unmasking human immunodeficiency virus infection as a cause of IgA vasculitis.

BACKGROUND: Human immunodeficiency virus (HIV) has a protean clinical picture, in rare instances manifesting as systemic autoimmune disorders such as vasculitides. HIV-induced autoimmune diseases often do not respond well to systemic immunosuppressive therapy. Opportunistic infections may occur in patients with either acquired immunodeficiency syndrome (AIDS) or heavy immunosuppressive treatment, and can further complicate the clinical presentation. CASE PRESENTATION: A patient presenting with immunoglobulin A (IgA) vasculitis (IgAV) with treatment-refractory purpuric skin rash and suspect intestinal vasculitis was discovered to have AIDS. HIV was the trigger of IgAV, and cytomegalovirus (CMV) colitis mimicked intestinal vasculitis. Antiretroviral treatment improved both CMV colitis and the control of the autoimmune disease. CONCLUSIONS: An autoimmune disease relapsing despite adequate immunosuppressive treatment and/or the presence of recurrent severe opportunistic infections may be clues to an underlying HIV infection.

Age at diagnosis influences the clinical phenotype, treatment strategies and outcomes in patients with giant cell arteritis: results from the observational GCAGE study on a large cohort of 1004 patients.

BACKGROUND: Immune and vascular ageing are proposed risk factors for giant cell arteritis (GCA). Data on the impact of age at diagnosis of GCA on the clinical presentation and course of the disease are scarce. METHODS: Patients with GCA followed at referral centres within the Italian Society of Rheumatology Vasculitis Study Group were enrolled up to November 2021. Patients were grouped according to age at diagnosis: ≤64, 65-79 and ≥80 years old. RESULTS: The study included 1004 patients, mean age 72.1±8.4, female 70.82%. Median follow-up duration was 49 (IQR 23-91) months. Patients in the oldest group (≥80 years) had significantly more cranial symptoms, ischaemic complications and risk for blindness compared with the groups 65-79 and ≤64 years (blindness: 36.98% vs 18.21% vs 6.19%; p<0.0001). Large-vessel-GCA was more frequent in the youngest group (65% of patients). Relapses occurred in 47% of patients. Age did not influence the time to first relapse, nor the number of relapses. Older age was negatively associated with the number of adjunctive immunosuppressants. Patients >65 years old had 2-3 fold increased risk for aortic aneurysm/dissection up to 60 months follow-up. Serious infections, but not other treatment-related complications (hypertension, diabetes, osteoporotic fractures), were significantly associated with older age. Mortality occurred in 5.8% of the population with age >65, cranial and systemic symptoms as independent risk factors. CONCLUSIONS: The highest risk of ischaemic complications, aneurysm development, serious infections and the possible undertreatment make of GCA a very challenging disease in the oldest patients.

Reactogenicity, safety and disease flares following BNT162b2 mRNA COVID-19 vaccine in patients with chronic immune-inflammatory arthritis treated with biological and targeted synthetic disease-modifying anti-rheumatic drugs.

OBJECTIVES: The safety of COVID-19 vaccination in rheumatic patients treated with biological (b) and targeted synthetic (ts) disease-modifying anti-rheumatic drugs (DMARDs) remains poorly explored. METHODS: Reactogenicity, safety and disease flares following each of the two doses of the BNT162b2 mRNA vaccine was evaluated in 186 patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis treated with b/tsDMARDs, who discontinued anti-rheumatic treatments around vaccination. A group of 53 healthy controls was used for comparison. RESULTS: The frequency and severity of systemic events was similar to that reported in the general population, and no particular safety concerns emerged. The use of methotrexate reduced systemic reactogenicity (adjORs [95% CI] 0.49 [0.25-0.94] and 0.63 [0.32-0.99] after each vaccine dose), whilst no specific effects of different b/tsDMARDs were seen. Flares around vaccination were reported by 24.5% of the patients. Factors associated with flares were active disease (adjORs [95% CI] 2.8 [1.01-8.09] and 1.86 [0.99-6.03] after each vaccine dose) and use of JAKi (adjORs [95% CI] 3.96 [1.39-11.27] and 3.10 [0.99-7.85]). The percentage of cases requiring change or increase in DMARD therapy due to persistent worsening of disease activity at follow-up visits was low (3.2%). CONCLUSIONS: The safety of mRNA COVID-19 vaccination in arthritis patients on treatment with b/tsDMARDs is reassuring. In a regimen of peri-vaccine drug interruption, transient flares of the disease more commonly occur in association with active arthritis and use of shorter half-life drugs. Most flares do not require treatment escalation or change.

Factors influencing patient-reported outcomes in ANCA-associated vasculitis: correlates of the Patient Global Assessment.

BACKGROUND: Patient-reported outcomes (PROs) are currently poorly integrated in the clinical evaluation of disease activity in patients with ANCA-associated vasculitis (AAV). OBJECTIVES: To assess the distribution of the Patient Global Assessment (PtGA) in patients with AAV in stable remission, and to identify correlates of PtGA; to assess the discordance between PtGA score and Physician Global Assessment (PhGA). METHODS: Patients with a diagnosis of AAV in stable remission (BVAS=0) and with a Physician Global Assessment (PhGA)=0 were included. The following PROs on a 0-100 visual analogue scale (VAS) were assessed: PtGA, fatigue, pain, general health, sleep quality, and chronic damage according to the patient's opinion. The Cragg Hurdle model was used to assess the predictors of PtGA. RESULTS: 65 patients were included, female 57%, mean age 61±12 years. Median disease duration 6 years (IQR 3-12). Vasculitis damage index (VDI) was 4.4±2.3. Despite having been classified as being in remission, PtGA was elevated in 37% of patients. The PtGA was not associated with older age, comorbidities, educational level, the type of AAV diagnosis, number of organ-systems involved, previous relapses, disease duration, nor higher VDI. Female sex was significantly associated with PtGA: 51% of female patients reported an elevated PtGA compared to 18% of males (p=0.009). PtGA significantly correlated with all the other assessed PROs. Pain and fatigue were the main determinants of an elevated PtGA. CONCLUSIONS: A significant proportion of patients with AAV considered to be in remission by the physician still declares to have persistent aspects of uncontrolled disease. PtGA is significantly influenced by pain and fatigue, which should receive more attention in the future assessment of patients with AAV.

Ultrasound halo sign as a potential monitoring tool for patients with giant cell arteritis: a prospective analysis.

OBJECTIVES: To assess the sensitivity to change of ultrasound halo features and their association with disease activity and glucocorticoid (GC) treatment in patients with newly diagnosed giant cell arteritis (GCA). METHODS: Prospective study of patients with ultrasound-confirmed GCA who underwent serial ultrasound assessments of the temporal artery (TA) and axillary artery (AX) at fixed time points. The number of segments with halo and maximum halo intima-media thickness (IMT) was recorded. Time points in which >80% of patients were assessed were considered for analysis. Halo features at disease presentation and first relapse were compared. RESULTS: 49 patients were assessed at 354 visits. Halo sensitivity to change was assessed at weeks 1, 3, 6, 12 and 24 and showed a significant standardised mean difference between all time points and baseline for the TA halo features but only after week 6 for the AX halo features. The number of TA segments with halo and sum and maximum TA halo IMT showed a significant correlation with erythrocyte sedimentation rate (0.41, 0.44 and 0.48), C reactive protein (0.34, 0.39 and 0.41), Birmingham Vasculitis Activity Score (0.29, 0.36 and 0.35) and GC cumulative dose (-0.34, -0.37 and -0.32); no significant correlation was found for the AX halo features. Halo sign was present in 94% of first disease relapses but with a lower mean number of segments with halo and sum of halo IMT compared with disease onset (2.93±1.59 mm vs 4.85±1.51 mm, p=0.0012; 2.01±1.13 mm vs 4.49±1.95 mm, p=0.0012). CONCLUSIONS: Ultrasound is a useful imaging tool to assess disease activity and response to treatment in patients with GCA.

Novel Therapies for ANCA-associated Vasculitis.

PURPOSE OF REVIEW: The purpose of this review is to discuss the most recent evidence on the treatment innovations and future prospective in the management of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs). RECENT FINDINGS: In AAV, a growing body of research is available on novel treatment options for remission induction and to clarify some uncertainties concerning the optimal use of available drugs. Efforts are being made to reduce the toxicity associated with high-dose, prolonged glucocorticoids (GC) regimens. Despite major advances in the prognosis of AAV, relapses are still common and the intensity and duration of remission treatment constitute a great challenge in the management of these chronic conditions. A paradigm shift in practice in the management of AAV is being supported by recent evidence suggesting the comparable efficacy and improved safety profile of schemes with a reduced dose of GC for the induction and maintenance of remission in patients with severe granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Moreover, recent appraisal of pathogenetic mechanisms, including complement activation pathways, has introduced the revolutionary concept of an alternative to GC, such as avacopan. Plasma exchange failed to prevent end-stage renal disease and mortality in patients with severe renal involvement or pulmonary haemorrhage according to a large multicentre randomised trial. Intensified immunosuppressive strategies for patients with life-threatening manifestations, including the combination of rituximab (RTX) with cyclophosphamide (CYC) have revealed promising preliminary data. New evidence for the use of alternative immunosuppressive agents (e.g. mycophenolate mofetil or abatacept) for the induction of remission in patients with non-severe disease is emerging. Several studies have been recently published, or are ongoing, to assess the optimal strategy and duration of maintenance of remission with the available treatment options (GC, azathioprine, and RTX). Preliminary evidence supports the superiority of a more prolonged course of maintenance treatment. The management of refractory or relapsing eosinophilic granulomatosis with polyangiitis (EGPA) has been improved by the recent demonstration of efficacy and safety of an interleukin-5 inhibitor, mepolizumab. Ongoing randomised studies will clarify the role of RTX in patients with severe manifestations of EGPA.