Primary Sjögren syndrome‐related peripheral neuropathy: a systematic review and meta‐analysis

Background and purpose Primary Sjögren syndrome (pSS) is a chronic, systemic, autoimmune disorder characterized by lymphocytic infiltrates of the exocrine organs, leading to sicca symptoms and parotid enlargement. pSS has been linked to various neurological manifestations, including peripheral neuropathy (PN). We aimed to provide a comprehensive analysis of the currently available evidence regarding pSS-related PN. Methods A literature search in the PubMed database was performed, and 49 papers were eligible to be included in this systematic review and meta-analysis. Results The pooled prevalence of PN in pSS is estimated to be 15.0% (95% confidence interval = 10.7%–20.7%). The mean age of pSS patients at PN diagnosis is 59 years. Among the patients with pSS and PN, 83% are females. Neuropathic symptoms usually precede or lead to the pSS diagnosis at a 2:1 ratio in patients with pSS-related PN. The commonest type of pSS-related PN is distal axonal polyneuropathy (80% of patients with pSS-related PN), followed by sensory ganglionopathy. Peripheral and cranial mononeuropathies—particularly trigeminal—are also frequent. Risk factors for developing PN include increasing age and presence of vasculitis. Immune-mediated pathogenetic mechanisms are discussed. Glucocorticoids are the most commonly used treatment option for managing pSS-related PN, when associated with vasculitis, followed by the use of intravenous immunoglobulin. Conclusions PN is very common in pSS patients. Evidence on long-term prognosis of PN in pSS is limited, and further research is needed. Research into the use of immunosuppressive medication in nonvasculitic neuropathies in the context of pSS merits further consideration

Core domain set for chronic and/or recurrent manifestations of calcium pyrophosphate deposition disease: OMERACT delphi survey to establish consensus.

To agree on important domains for the Outcome Measures in Rheumatology (OMERACT) core domain set for chronic and/or recurrent manifestations of calcium pyrophosphate deposition (CPPD) disease. Patient research partners (PRPs) and other participants (mainly clinicians and researchers) contributed to three rounds of a consensus survey using Delphi methodology. Consensus was defined if ≥70% of both patients and other participants scored the domain as 'critically important domain to include'. In a subsequent ranking exercise, all participants were asked to select and rank up to 10 of the domains reaching consensus. Fifteen domains reached consensus as critically important. Within the Pathophysiological Manifestations area, these were joint pain, joint tenderness, joint swelling, acute CPP crystal arthritis flare, joint damage on imaging tests, joint calcification on imaging tests, and crystals in joint fluid. Within the Life Impact area, these were overall function, ability to complete daily tasks, ability to work, health related quality of life, patient global assessment response to treatment, patient global assessment of disease activity, physician global assessment of disease activity, and patient satisfaction with treatment. No domains within the Societal/Resource Use area reached consensus as critically important. In the ranking exercise, joint pain, joint tenderness, joint swelling, acute CPP crystal arthritis flare and overall function were most highly ranked. This work has identified potential domains for the OMERACT core domain set for chronic and/or recurrent manifestations of CPPD disease. There was strong support for joint pain, joint tenderness, joint swelling, acute CPP crystal arthritis flare, overall function, and global assessments of disease activity as core domains

Core domain set for studies of acute calcium pyrophosphate crystal arthritis: OMERACT delphi survey to establish consensus.

To identify potential domains for the Outcome Measures in Rheumatology (OMERACT) core domain set for studies of an individual flare of acute calcium pyrophosphate (CPP) crystal arthritis. Patient research partners (PRPs) and other participants (mainly clinicians and researchers) completed three rounds of survey using Delphi methodology. Consensus was defined as ≥ 70 % of both PRP and other participants groups rated the domain as a 'critically important domain to include'. In a subsequent ranking exercise, all participants were asked to rank and comment on up to 10 domains to include as core domains. Fourteen domains reached consensus as critically important in the Delphi survey. In the Pathophysiological Manifestations area, the domains were joint pain, joint tenderness, joint swelling, joint inflammation on imaging tests and duration of acute CPP crystal arthritis flare. In the Life Impact area, the domains were overall function, ability to complete daily tasks, ability to work, health related quality of life, patient global assessment response to treatment, patient and physician global assessments of disease activity, and patient satisfaction with treatment. In the Societal/Resource Use area, use of rescue medications reached consensus. In the ranking exercise, joint pain, joint tenderness, joint swelling, overall function and ability to complete daily tasks ranked highest. Joint pain, joint swelling, joint tenderness, duration of acute CPP crystal arthritis flare, overall function, ability to complete daily tasks, and patient global assessment of disease activity received the strongest support to be included in the OMERACT core domain set for studies of acute CPP crystal arthritis

POS0711 SUICIDAL BEHAVIOUR IN SLE PATIENTS: A SYSTEMATIC LITERATURE REVIEW

Background:Previous studies have demonstrated that SLE patients have a higher risk of suicidal behaviour, including suicidal ideation, attempt and complete suicide (1,2). Data describing the SLE patients’ clinical characteristics and risk factors of suicidal behaviour are lacking.Objectives:To determine the magnitude of suicidal behaviour among SLE patients and to examine predictors associated with suicidal behaviour.Methods:According to the PRISMA guidelines, we conducted a systematic literature review of the online databases, PubMed/Medline, EMBASE, and Web of Science, from inception to December 2020 (Figure 1). Full-text original articles that examined the relationship between SLE patients with suicidal behaviour were eligible for our review. Two reviewers independently review articles to assess eligibility using the Newcastle-Ottawa Scale and the Joanna Briggs Institute tools. Systematic reviews, metanalysis, narrative review, case reports, case series, including less than 10 patients and conference abstracts, were excluded.Results:Of the 64 articles identified, 22 were relevant to the study question; cross-sectional (n=8) and prospective cohorts (n=6) were the most frequently retrieved studies. Among the 27106 SLE patients with SLE, 802 had suicidal behaviour (2.9%), and of those, 87.9% were female. Suicide attempt occurred in 573/802 (71.4%) and complete suicide in 18/802 (2,3%). Major depressive disorder (MDD) was the most frequently reported coexisting psychiatric condition associated with suicidal behavior, followed by psychosis and social phobia. Several clinical manifestations were linked to suicidal behaviour, particularly neuropsychiatric lupus, mucocutaneous, renal involvement and serositis. Further, high scores in disease activity and damage indices were associated with suicidal behaviour.Conclusion:Suicidal behavior in SLE patients was associated with MDD, NPSLE, active disease and damage. Awareness of these findings can guide clinicians to recognize suicide behavior promptly and prevent suicide attempts.References:[1]Hajduk A, Nowicka-Sauer K, Smoleńska Ż, Czuszyńska Z, Zdrojewski Z. Prevalence and correlates of suicidal thoughts in patients with neuropsychiatric lupus. Lupus. 2016 Feb;25(2):185-92. doi: 10.1177/0961203315603136.[2]Buji RI, Abdul Murad NA, Chan LF, Maniam T, Mohd Shahrir MS, Rozita M, Shamsul AS, Mohamad Hussain R, Abdullah N, Jamal R, Nik Jaafar NR. Suicidal ideation in systemic lupus erythematosus: NR2A gene polymorphism, clinical and psychosocial factors. Lupus. 2018 Apr;27(5):744-752. doi: 10.1177/0961203317742711.Figure 1.A PRISMA chart describing the inclusion/exclusion processDisclosure of Interests:None declared</jats:sec

POS1154 OUTCOMES AND RESOURCE UTILIZATION AFTER TOTAL HIP ARTHROPLASTY IN PATIENTS WITH CALCIUM PYROPHOSPHATE DEPOSITION DISEASE

BackgroundTotal hip arthroplasty (THA) is a safe and effective treatment option in patients with advanced degenerative joint disease who have failed conservative management. Calcium pyrophosphate deposition disease (CPPD) is a common crystal-induced arthritis in older adults characterized by the deposition of calcium pyrophosphate crystals in the articular and periarticular tissues1. CPPD might manifested with acute and chronic arthritis that can lead to joint damage and the need for joint replacement. To our knowledge, no previous studies investigated the outcomes of CPPD patients who underwent THA.ObjectivesWe aim to examine the mortality, in-hospital complications, and resource utilization following THA in patients with and without CPPD.MethodsWe queried the US National Inpatient Sample (NIS) database to identify patients who underwent THA between 2006 and 2014. The ICD-9 code 81.51 was used to identify the patients who underwent THA and of those, we classified 2 groups of patients: (i) those with ICD-9 codes defining CPPD (275.49 and 712.1–712.39) and (ii) those without any CPPD code. Data collection included patient demographics and comorbidities. Outcomes post-THA were in-hospital mortality, hospital length of stay, hospital charges, and discharge disposition. Associations between CPPD and specific morbidity were evaluated with chi-square tests. T tests were used for continuous variables.ResultsAmong the 4,111,808 (adjusted for sampling weight) patients who underwent THA between 2006 and 2014, 6198 (0.15%) had CPPD, with a mean age of 77 years and 65.2% were females (Table 1). CPPD patients were more likely to be older (mean age 77 vs 72.7; p&lt;0.001) than non-CPPD patients. Comorbidities more frequently observed among CPPD patients included chronic kidney disease, osteoarthritis, rheumatoid arthritis, gout, hyperparathyroidism and hypomagnesemia. Further, Charlson Comorbidity Index scores ≥ 2 was more frequent seen in CPPD (96.1% vs 89.1%, p &lt;0.001). The in-hospital mortality post-THA was lower in the CPPD patients (0.76% vs 1.72%, p &lt;0.001). THA in CPPD patients was associated with a longer mean length of stay than those without CPPD (6 vs 5.1 days; p &lt;0.001) while mean total charges were not statistically different between the 2 groups (p=0.344). CPPD patients were more likely to be discharged to rehabilitation or other nursing facilities (p&lt;0.001).Table 1.Demographics, clinical characteristics, outcomes and resource utilization of patients with and without CPPD who underwent hip arthroplasty between 2006-2014.No CPDD, n (%) (N=4105610)CPPD, n (%) (N=6198)P-value*Age in years at admission, median (mean ± SD)75 (72.7 ± 31.5)80 (77.0 ± 24.2)&lt;0.001†Female2507971 (61.1)3979 (64.2)&lt;0.001Chronic kidney disease516688 (12.5)1154 (18.6)&lt;0.001Osteoarthritis684171 (16.6)1280(20.6)&lt; 0.001Gout139648 (3.4)330 (5.3)&lt;0.001Rheumatoid arthritis199175 (4.8)478(7.7)&lt;0.001Hyperparathyroidism7959 (0.1)24(0.3)&lt;0.001Hypomagnesemia100390 (2.45)239 (3.86)&lt;0.001Charlson Comorbidity Index score ≥ 23659906 (89.1)5961(96.1)&lt;0.001Outcomes/Resource utilizationLength of stay, (mean ± SD)5.15 ± 11.726.04 ± 13.91&lt;0.001†Total hospital charges, (mean ± SD)$41284 ± 108238($ 42757 ± 124894)0.344†Death during hospitalization70706 (1.7)47 (0.7)&lt;0.001†Discharge DispositionHome (including home health care)2653860 (64.7)3558 (57.4)&lt;0.001All others§1447312 (35.3)2635 (42.5)&lt;0.001*Chi-square P except †t-test§All others include transfer to nursing or rehabilitation facility.ConclusionCPPD patients who underwent THA were more likely to be older, with a higher comorbidity burden, longer length of stay, and discharged to a non-home setting, than non-CPPD patients.References[1]Rosenthal AK, Ryan LM. Calcium Pyrophosphate Deposition Disease. N Engl J Med. 2016;d 374(26):2575-84.Disclosure of InterestsNone declared</jats:sec

Workup and Clinical Assessment for Allergen Immunotherapy Candidates

Allergen Immunotherapy (AIT) is a well-established, efficient, and safe way to treat respi-ratory and insect-venom allergies. After determining the diagnosis of the clinically relevant culprit allergen, AIT can be prescribed. However, not all patients are eligible for AIT, since some dis-eases/conditions represent contraindications to AIT use, as described in several guidelines. Allergists are often preoccupied on whether an extensive workup should be ordered in apparently healthy AIT candidates in order to detect contra-indicated diseases and conditions. These preoccupations often arise from clinical, ethical and legal issues. The aim of this article is to suggest an approach to the workup and assessment of the presence of any underlying diseases/conditions in patients with no case history before the start of AIT. Notably, there is a lack of published studies on the appropriate evaluation of AIT candidates, with no globally accepted guidelines. It appears that Allergists are mostly deciding based on their AIT training, as well as their clinical experience. Guidance is based mainly on experts’ opinions; the suggested preliminary workup can be divided into mandatory and optional testing. The evaluation for possible underlying neoplastic, autoimmune, and cardiovascular diseases, primary and acquired immunodeficiencies and pregnancy, might be helpful but only in subjects for whom the history and clinical examination raise suspicion of these conditions. A workup without any reasonable correlation with potential contraindications is useless. In conclusion, the evaluation of each individual candidate for possible medical conditions should be determined on a case-by-case basis. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

AB0647 CATASTROPHIC ANTIPHOSPHOLIPID SYNDROME TRIGGERED BY CONCURRENT VZV AND HSV INFECTION. A CASE REPORT

Background:Catastrophic antiphospholipid syndrome (CAPS) is a severe autoimmune condition, characterized by multiorgan failure due to thromboses and/or hemorrhage. Concurrent HSV/VZV infection is an exceedingly rare event, occurring mostly in immunocompromised patients. Herein, we report the first case of CAPS triggered by concurrent HSV/VZV infection, manifesting with zosteriform rash and haemorrhages at multiple sites.Objectives:To describe a case of CAPS provoked by concurrent HSV/VZV infection, manifesting with zosteriform rash and haemorrhages at multiple sites.Methods:A 36-year-old male, with a history of antiphospholipid syndrome (APS) presented with a 5-day history of epigastric pain, associated with fever, hematuria, rash and swelling in bilateral ears. Past medical history was remarkable for APS, based on 4 episodes of DVT/PE and triple positive antiphospholipid antibodies, on chronic well-maintained warfarin anticoagulation. On examination, a purpuric rash was evident on the right side of the neck as well as on both ears, consistent with a C3 dermatomal distribution (Figure 1). Laboratory studies revealed anemia, thrombocytopenia and acute kidney injury.Figure 1.Results:A full-body CT scan demonstrated the presence of multifocal lymphadenopathy, alveolar infiltrates suggestive of diffuse alveolar haemorrhage, and haemorrhage in both kidneys and the left adrenal gland; anticoagulation was held, despite the INR being within the patient’s baseline therapeutic levels. He was admitted with a working diagnosis of CAPS and possible zoster infection. Appropriate immunologic workup was requested. He was prescribed intravenous acyclovir, antibiotics, pulse dose of glucocorticoids, and IVIG. Bronchoscopy with bronchoalveolar lavage revealed the presence of haemosiderin-laden macrophages. The rash regressed, and the patients’ condition improved. He was discharged with glucocorticoid tapering regimen, hydroxychloroquine, aspirin and warfarin.Antibody titers were taken prior to IVIG administration at presentation, and at 4 weeks. High VZV IgG titers found at presentation regressed over four times on follow-up. Furthermore, at 4 weeks the patient had developed IgM antibodies against both VZV and HSV. These findings confirmed a concurrent infection.Conclusion:This is the first report of coexisting HSV/VZV infection associated with CAPS. A literature review identified a total of 28 patients with coexisting HSV/VZV infection, whereas only one case of CAPS triggered by HSV was identified1. This case illustrates that concurrent infection can occur in the absence of immunosuppressive therapy in patients with APS, serving as a trigger for hemorrhagic CAPS. Simultaneous treatment with antiviral against herpesviruses, glucocorticoids and IVIG may mitigate the inflammatory cascade associated with CAPS.References:[1]Catoggio C, Alvarez-Uría A, Fernandez PL, Cervera R, Espinosa G. Catastrophic antiphospholipid syndrome triggered by fulminant disseminated herpes simplex infection in a patient with systemic lupus erythematosus. Lupus. 2012 Oct;21(12):1359-61.Disclosure of Interests:None declared.</jats:sec

Immunoglobulin Use for the Management of Painful Peripheral Neuropathy: A Systematic Review and Meta-Analysis

Background: Immunoglobulins (IG) are widely used for the treatment of a variety of immune-mediated diseases. The exact mechanism of action remains unknown, but IG modulate the expression and function of Fc receptors, interfere with complement activation and production of cytokines, neutralize pathogenic autoantibodies, and affect the activation and effector functions of B and T lymphocytes. Immunoglobulins are usually delivered intravenously, and are effective in ameliorating motor symptoms, and/or preventing disease progression in immune-mediated neuropathies, including Guillain–Barré syndrome and chronic inflammatory demyelinating polyneuropathy. Objective: The aim of this systematic review and meta-analysis was to study the potential of IG for the treatment of painful peripheral neuropathy (PPN). The outcome of interest was the percentage of patients with PPN who achieved pain relief following IG administration. Methods: We performed a systematic literature search on March 17, 2022, in the PubMed database without any publication date restrictions. We also looked for unpublished or ongoing trials in clinicaltrials.org. Pain reduction following IG treatment had to be within the aims (primary or secondary). Results: The aforementioned literature search strategy revealed five studies (two open-label, three randomized placebo-controlled) eligible to be included. The pooled estimate of the percentage of patients with PPN who received immunoglobulins and reported pain relief was found to be 65% (95% CI 58–71%). The likelihood of achieving pain relief with immunoglobulin treatment was 2.9 times higher (95% CI 1.6–5.2) compared to placebo (p = 0.0003). Conclusion: The use of IG for the treatment of pain due to peripheral neuropathy has a potential therapeutic benefit. Further studies across patients with different types of painful peripheral neuropathy are needed to better characterize this effect. Registration number on PROSPERO: CRD42022319614. © 2022, The Author(s)