The heterogeneity of lung involvement in vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome: a case of hypersensitivity pneumonitis-like pattern.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a recently characterized disease associated with somatic mutations in the UBA1 gene, which cause dysregulation of ubiquitin-mediated processes. This case describes a 71-year-old male patient with VEXAS syndrome who presented with refractory lung inflammation with a pattern similar to computed tomography hypersensitivity pneumonitis, a novel finding in VEXAS syndrome. The presented clinical case highlights the protean involvement of the lung in VEXAS syndrome and emphasizes the importance of considering interstitial lung disease in the differential diagnosis.

Presenting features and outcomes of cranial-limited and large-vessel giant cell arteritis: a retrospective cohort study.

Objectives: To compare the presenting features and outcomes of patients with cranial-limited (C-) and large-vessel (LV-) giant cell arteritis (GCA).Methods: Data from our GCA cohort were collected retrospectively. Patients who underwent total-body large-vessel imaging within 10 days after commencing steroid therapy were included. Patients with LV involvement were classified as LV-GCA. Presenting features, treatments, and outcomes of LV-GCA and C-GCA patients were compared.Results: 161 patients were included (LV-GCA, n = 100). At baseline, LV-GCA patients were younger than those with C-GCA (73.2 ± 8.9 vs 76 ± 8.8 years, p = 0.018) and had a longer delay to diagnosis (3.5 ± 4.6 vs 2.3 ± 4.9 months, p = 0.001). C-GCA patients had a higher incidence of headache (p = 0.006) and ischaemic optic neuropathy (p < 0.001), whereas LV-GCA patients had more systemic symptoms (fever, p = 0.002; fatigue, p < 0.001; weight loss, p < 0.001; night sweats, p = 0.015) and dry cough (p = 0.031). Corrected cumulative prednisone dose, relapse-free survival, relapse-rate, and incidence of ascending aortic aneurysms were not significantly different between the two subgroups. A steroid-sparing agent was added in 73% of LV- and 55.7% of C-GCA patients (p = 0.027), but was introduced more frequently at baseline in LV-GCA patients (52% vs 23.5%, p = 0.006). LV-GCA patients initially treated with glucocorticoid monotherapy relapsed sooner (relapse-free survival, HR = 0.56, 95% CI 0.41-0.78, p < 0.001) and had a higher relapse rate (relapses per 10 person-years, 6.73 ± 11.50 vs 3.82 ± 10.83, p = 0.011).Conclusion: LV-GCA patients were younger at diagnosis and suffered a longer diagnostic delay. The outcomes of the two subgroups were similar. An earlier introduction of steroid-sparing agents in LV-GCA patients might have played a positive role.

Gender differences in clinical presentation and vascular pattern in patients with Takayasu arteritis.

Objective: To compare clinical characteristics and pattern of vascular involvement at disease onset according to gender specificity in patients with Takayasu arteritis (TA).Methods: Data from 117 TA patients (11 male, 106 female), diagnosed according to the American College of Rheumatology criteria, from our centre were retrospectively collected. Differences between men and women regarding demographic features, diagnostic delay, signs and symptoms attributed to TA, and arteries involved at diagnosis were compared. Data were obtained from three published articles describing gender differences in TA. A global analysis of these three cohorts plus ours (a total of 578 patients; 108 men, 470 women) was performed.Results: In our TA cohort, age at disease onset and age at diagnosis were not significantly different between genders. Diagnostic delay was higher in men. Male patients showed higher involvement of iliac arteries (right, p = 0.016; left, p = 0.021); females suffered more frequently from upper limb claudication (p = 0.026). In the overall analysis, men had higher prevalence of arterial hypertension (p = 0.007) and more frequent involvement of abdominal aorta (p = 0.026), renal arteries (right, p < 0.001; left, p < 0.001), and iliac arteries (right, p = 0.009; left, p = 0.002). Women more frequently exhibited upper limb claudication (p = 0.042) and involvement of left subclavian artery (p = 0.005), carotid arteries (right, p < 0.001; left, p < 0.001), and supradiaphragmatic aorta (ascending, p = 0.050; arch, p < 0.001; descending, p = 0.003). Inflammatory markers were more frequently raised in women (p = 0.005).Conclusions: In TA patients, gender has a strong influence on pattern of vascular involvement and consequently on clinical presentation. Specifically, women have a higher involvement of the supradiaphragmatic vessels, whereas in men the abdominal vessels are more frequently affected.

IgG4-related disease in Italy: clinical features and outcomes of a large cohort of patients.

OBJECTIVES: To describe the clinical features, treatment response, and follow-up of a large cohort of Italian patients with immunoglobulin (Ig)G4-related disease (IgG4-RD) referred to a single tertiary care centre. METHOD: Clinical, laboratory, histological, and imaging features were retrospectively reviewed. IgG4-RD was classified as 'definite' or 'possible' according to international consensus guidelines and comprehensive diagnostic criteria for IgG4-RD. Disease activity was assessed by means of the IgG4-RD Responder Index (IgG4-RD RI). RESULTS: Forty-one patients (15 females, 26 males) were included in this study: 26 with 'definite' IgG4-RD and 15 with 'possible' IgG4-RD. The median age at diagnosis was 62 years. The median follow-up was 36 months (IQR 24-51). A history of atopy was present in 30% of patients. The pancreas, retroperitoneum, and major salivary glands were the most frequently involved organs. Serum IgG4 levels were elevated in 68% of cases. Thirty-six patients were initially treated with glucocorticoids (GCs) to induce remission. IgG4-RD RI decreased from a median of 7.8 at baseline to 2.9 after 1 month of therapy. Relapse occurred in 19/41 patients (46%) and required additional immunosuppressive drugs to maintain long-term remission. Multiple flares occurred in a minority of patients. A single case of orbital pseudotumour did not respond to medical therapy and underwent surgical debulking. CONCLUSIONS: IgG4-RD is an elusive inflammatory disease to be considered in the differential diagnosis of isolated or multiple tumefactive lesions. Long-term disease control can be achieved with corticosteroids and immunosuppressive drugs in the majority of cases.

Efficacy and safety of biological agents in adult-onset Still's disease.

OBJECTIVES: To describe the efficacy and safety of different biological agents in a large cohort of 20 patients with adult-onset Still's disease (AOSD). METHOD: We retrospectively evaluated 20 patients with severe or refractory AOSD treated with at least one biological agent (anakinra, etanercept, tocilizumab, and adalimumab), followed up for at least 12 months at our Institution. We collected and analysed data on the disease course, treatment outcome, and adverse effects, and compared our data with other published series. RESULTS: The median duration of follow-up was 5 years. In 12 patients a single biological drug induced a clinical response. In eight patients the biological agent that was first administered proved ineffective, and a switch to a different biologic was necessary. In three patients a third biologic was necessary to achieve disease control. The biologics eventually determined a clinical response in all patients. Patients with systemic disease showed better responses than patients with chronic articular disease (p < 0.05). Biological agents allowed either the withdrawal or the tapering of corticosteroid therapy (p < 0.0001) and of disease-modifying anti-rheumatic agents (DMARDs; p < 0.05). Three patients experienced herpes zoster reactivation. CONCLUSIONS: This is the longest follow-up of a cohort of AOSD patients treated with biological agents. Our data show that biologics are safe and generally effective in the long-term management of AOSD, particularly in cases with systemic disease, and suggest that a clinical response can be obtained in almost all AOSD patients, although a switch to drugs with a different mechanism of action may be necessary.

Drug development and novel therapeutics to ensure a personalized approach in the treatment of systemic sclerosis.

INTRODUCTION: Systemic sclerosis (SSc) is a systemic disease encompassing autoimmunity, vasculopathy, and fibrosis. SSc is still burdened by high mortality and morbidity rates. Recent advances in understanding the pathogenesis of SSc have identified novel potential therapeutic targets. Several clinical trials have been subsequently designed to evaluate the efficacy of a number of new drugs. The aim of this review is to provide clinicians with useful information about these novel molecules. AREA COVERED: In this narrative review, we summarize the available evidence regarding the most promising targeted therapies currently under investigation for the treatment of SSc. These medications include kinase inhibitors, B-cell depleting agents, and interleukin inhibitors. EXPERT OPINION: Over the next five years, several new, targeted drugs will be introduced in clinical practice for the treatment of SSc. Such pharmacological agents will expand the existing pharmacopoeia and enable a more personalized and effective approach to patients with SSc. Thus, it will not only possible to target a specific disease domain, but also different stages of the disease.