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.

Ocular involvement in adult and paediatric patients with monogenic autoinflammatory diseases: a Spanish multicentre retrospective study.

OBJECTIVES: Ophthalmologic involvement in monogenic autoinflammatory diseases has been explored mainly in paediatric patients. The aim of this study is to characterise ophthalmologic manifestations, therapeutic management and visual outcomes in a Spanish (UVESAI) cohort of adult/paediatric patients with monogenic autoinflammatory diseases. METHODS: Multicentre and retrospective study of patients with monogenic autoinflammatory diseases and ocular involvement. Eye manifestations, structural complications, treatments used and visual outcomes were analysed, and compared with previous studies. RESULTS: Forty-six patients (44/2 adults/children; 21/25 adult/paediatric-onset) with monogenic autoinflammatory diseases [cryopyrin associated periodic syndromes (n=13/28.3%), mainly Muckle-Wells syndrome (MWS) (n=11/24%); familial Mediterranean fever (FMF) (n=12/26%); TNF receptor-associated periodic syndrome (TRAPS); (n=9/20%); Blau syndrome (n=8/17%); hyperimmunoglobulin D syndrome (HIDS) (n=2/4.3%), deficiency of adenosine deaminase-2 and NLRC4-Autoinflammatory disease] (one each) were included. Conjunctivitis (n=26/56.5%) and uveitis (n=23/50%) were the most frequent ocular manifestations. Twelve (26.1%) patients developed structural complications, being cataracts (n=11/24%) and posterior synechiae (n=10/22%) the most frequent. Conjunctivitis predominated in TRAPS, FMF, MWS and HIDS (mainly in adults), and uveitis, in Blau syndrome. Seven (8%) eyes (all with uveitis) presented with impaired visual acuity. Local and systemic treatment led to good visual outcomes in most patients. Compared with previous studies mainly including paediatric patients, less severe ocular involvement was observed in our adult/paediatric cohort. CONCLUSIONS: Conjunctivitis was the most common ocular manifestation in our TRAPS, FMF, MWS and HIDS patients, and uveitis predominated in Blau syndrome. Severe eye complications and poor visual prognosis were associated with uveitis. Adults with monogenic autoinflammatory diseases seem to exhibit a less severe ophthalmologic presentation than paediatric patients.

ANCA-associated pulmonary-renal syndrome treated with cyclophosphamide, rituximab, repeated methyl-prednisolone pulses and a reduced oral glucocorticoid regime: an observational study.

OBJECTIVES: To describe the clinical outcome of patients with pulmonary-renal syndrome (PRS) due to ANCA-associated vasculitis (AAV) from a single centre. METHODS: Observational study of routine clinical care data of patients diagnosed with PRS due to AAV from 2010 to 2020 at the Autoimmune Diseases Unit, Hospital Universitario Cruces. Mortality due to any cause within 24 months was defined as the primary outcome. Secondary outcomes included end-stage kidney disease and the need for oxygen therapy at 24 months. RESULTS: Fourteen patients were identified with a mean age at diagnosis of 62.71 years. At diagnosis, the median serum creatinine was 2.46 mg/dl and the median Birmingham Vasculitis Activity Score (BVAS) was 24. All patients were treated with repeated methyl-prednisolone pulses, 13 patients received iv cyclophosphamide 500 mg every two weeks and 12 patients received rituximab. The mean (SD) initial dose of oral prednisone was 25 (7) mg/d. A rapid tapering of oral prednisone was achieved in all patients as per protocol, with a mean (SD) dose of 10.6 (1.9) mg/d received within the first three months. No cases of death, end-stage kidney disease or with need for long-term oxygen therapy were seen. Three patients suffered a relapse and five patients had major infections, none of them opportunistic. The median creatinine and BVAS at 24 months were 1.30 mg/dl and 0, respectively. CONCLUSIONS: Combination therapy with iv cyclophosphamide and rituximab, with repeated methyl-prednisolone pulses and a rapid prednisone taper, results in early disease control, with low mortality, chronic organ damage and infections.

IgG4 related disease as a mimicker of metastatic pancreatic cancer.

A previously healthy 62-year-old female was referred to our hospital for epigastric discomfort in the previous month. Routine laboratory tests showed lipase and pancreatic isoamylase elevation. CT scan revealed an homogeneous mass arising from the pancreatic head-uncinate process in addition to multiple bilateral hypoattenuating lesions in the renal cortex and pulmonary nodules. US-guided biopsy of one of the kidney lesions was performed under the suspicion of pancreatic metastatic disease.

Anti-phospholipid antibodies do not predict damage in SLE patients in the 21st century-an observational study from the Lupus-Cruces cohort.

OBJECTIVE: To compare the influence of aPLs on global and cardiovascular damage in patients with SLE diagnosed before and after the year 2000. METHODS: Two hundred and eighty-six patients from the Lupus-Cruces cohort with a minimum follow-up of 5 years were divided into two subcohorts according to the date of diagnosis, before 2000 (less than 2000) and from 2000 on (2000 or more). We compared the mean Systemic Lupus Erythematosus International Collaborating Clinics-American College of Rheumatology (SLICC-ACR) Damage Index score and global and cardiovascular damage-free survival rates in the presence or absence of aPL in both subcohorts. Variables potentially modulating damage among aPL-positive patients were analysed. RESULTS: The subcohorts were comparable for demographic and lupus-related variables except for treatment variables: the 2000 or more subcohort received lower doses of prednisone and more HCQ, low-dose aspirin, statins, immunosuppressive agents and vitamin D. aPL-positive patients in the less than 2000, but not in the 2000 or more subcohort, accrued more damage compared with aPL-negative patients. In the less than 2000 subcohort, the adjusted hazard ratios (HRs) for global and cardiovascular damage in aPL-positive vs aPL-negative patients were 1.98 (95% CI 1.24, 3.14) and 9.3 (95% CI 3.24, 26.92), respectively. No differences in damage were seen between aPL-positive and aPL-negative patients in the 2000 or more subcohort. Hypertension (HR = 4.64, 95% CI 1.33, 16.19), LA (HR = 3.85, 95% CI 1.1, 13.41) and the number of months on HCQ (HR = 0.97, 95% CI 0.95, 0.99) were independent predictors of vascular damage in the combined analysis of all aPL-positive patients. CONCLUSION: The effects of aPL on damage accrual in SLE patients have been reduced over recent years. The widespread use of HCQ and a better thromboprophylaxis are likely causing this change.

Update on antimalarials and systemic lupus erythematosus.

PURPOSE OF REVIEW: The purpose of this review is highlighting the most recent evidence on the clinical efficacy and toxicity of antimalarials in systemic lupus erythematosus (SLE). RECENT FINDINGS: New data confirm the effects of antimalarials in preventing SLE activity, damage and infections and in decreasing mortality. An important reduction in use of health resources is related to continued antimalarial use. Hydroxychloroquine (HCQ) may prevent preeclampsia in pregnant women with SLE. HCQ ocular toxicity is infrequent and could be associated with blood levels. Gastrointestinal and skin toxicity are underrecognized and could influence adherence. Prolongation of QT interval is extremely unusual with HCQ. Doses of HCQ of 200 mg/day seem to offer a good efficacy/toxicity balance. HCQ protection against herpes zoster and Pneumocystis jirovecii infection has been shown. On the contrary, HCQ prescription by doctors and adherence by patients are both under recommended standards. The recent coronavirus disease 2019 pandemic has resulted in a significant shortage of HCQ in many countries with possible consequences in the correct treatment of lupus patients. SUMMARY: Recent evidence reinforces the central role of HCQ in SLE therapy. The reduction in activity, damage accrual and mortality is consistent across studies, countries and ethnical groups. On the contrary, and despite the well established beneficial effects of prolonged regular HCQ therapy, many SLE patients do never take this drug or it is eventually stopped in the setting of severe flares, pregnancy or presumed toxicity. Every effort must be made to assure the correct prescription of HCQ and not to withdraw the drug unless unequivocal signs of toxicity are present.