Pulmonary manifestations, treatments and outcomes of IgG4-related disease-a systematic literature review.

Immunoglobulin G4-related disease (IgG4-RD) is a multisystem fibroinflammatory condition. A consistent feature of many cases is pulmonary infiltrates, or respiratory failure. This systematic literature review aims to summarise the pulmonary manifestations of IgG4-RD, including clinical outcomes and treatment. This review was registered on PROSPERO (CRD42023416410). Medline, Embase and Cochrane databases were searched for articles discussing IgG4-RD syndrome. Information was extracted on demographics, type and prevalence of pulmonary manifestations, treatment and clinical outcomes. Initially, after deduplication, 3123 articles were retrieved with 18 ultimately included. A pooled total of 724 patients with IgG4-RD were included, 68.6% male, mean age 59.4 years (SD 5.8) at disease onset. The most frequently described pulmonary manifestation was mediastinal lymphadenopathy (n = 186, 48.8%), followed by pulmonary nodules (n = 151, 39.6%) and broncho-vascular thickening (n = 85, 22.3%). Where treatment was reported, the majority of patients received glucocorticoids (n = 211, 93.4%). Other immunosuppressive therapy included cyclophosphamide (n = 31), azathioprine (n = 18), with mycophenolate mofetil (n = 6), rituximab (n = 6), methotrexate (n = 5) and other unspecified immunomodulators (50). Clinical outcomes were reported in 263 patients, where 196 patients had remission of their disease, 20 had relapse, 35 had stable disease, four had progression and eight patients died from complications of IgG4-RD. This systematic review summarises pulmonary manifestations, treatments and outcomes in patients with IgG4-RD. Pulmonary involvement in IgG4-RD is relatively common, leading to high levels of morbidity and mortality. Glucocorticoids remain the mainstay of treatment, but further work is required to explore the management of patients with pulmonary manifestations in association with IgG4-RD.

Incidence, management and prognosis of new-onset sarcoidosis post COVID-19 infection.

BACKGROUND AND AIM: SARS-CoV-2 infection has been linked to hyperinflammation in multiple organs with a potential mechanistic link with resulting autoimmunity. There have been reports of many inflammatory complications following COVID-19, including sarcoidosis. A literature review on new-onset sarcoidosis following COVID-19 is lacking. We evaluated potential associations between COVID-19 and development of new-onset sarcoidosis. METHODS: Articles discussing biopsy-proven sarcoidosis after confirmed COVID-19 infection, published 1956 until April 2023, were included. All article types were deemed eligible except opinion and review articles. RESULTS: A pooled total of 15 patients with new-onset diagnosis of sarcoidosis after COVID-19 infection were included, 45.5% female, mean age 46.1 years (standard deviation 14.7) at onset of sarcoidosis. Patients were from: Europe (n=11); North America (n=2); South America (n=1); Asia (n=1). The mean time between COVID-19 infection and diagnosis of sarcoidosis was 56.3 days, although this ranged from 10 to 140 days. Organ systems predominantly affected by sarcoidosis were: pulmonary (n=11); cutaneous (n=3); cardiac (n=2); ocular (n=1); systemic (n=1) (with overlapping features in certain patients). Sarcoidosis was treated as follows: glucocorticoids (n=8); azathioprine (n=1); cardiac re-synchronisation therapy (n=1); heart transplant (n=1). All patients were reported to have survived, with one requiring intensive care admission. CONCLUSIONS: Our result suggests there is a potential link between COVID-19 and new-onset sarcoidosis. The potential mechanism for this is through cytokine mediated immune modulation in COVID-19 infection. Obtaining a tissue sample remains key in confirming the diagnosis of sarcoidosis and this may be delayed during active COVID-19 infection.

Clinical characteristics, disease trajectories and management of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: a systematic review.

BACKGROUND: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly discovered autoinflammatory condition characterised by somatic mutation of the UBA1 gene. The syndrome leads to multi-system inflammation affecting predominantly the skin, lungs and bone marrow. METHODS: We undertook a systematic review of the multisystem features and genotypes observed in VEXAS syndrome. Articles discussing VEXAS syndrome were included. Medline, Embase and Cochrane databases were searched. Information was extracted on: demographics, type and prevalence of clinical manifestations, genetic mutations and treatment. Meta-analysis using a random effects model was used to determine pooled estimates of serum markers. RESULTS: From 303 articles, 90 were included, comprising 394 patients with VEXAS. 99.2% were male, with a mean age of 67.1 years (SD 8.5) at disease onset. The most frequent diagnoses made prior to VEXAS were: relapsing polychondritis (n = 59); Sweet's syndrome (n = 24); polyarteritis nodosa (n = 11); and myelodysplastic syndrome (n = 10). Fever was reported in 270 cases (68.5%) and weight loss in 79 (20.1%). Most patients had haematological (n = 342; 86.8%), dermatological (n = 321; 81.5%), pulmonary (n = 297; 75.4%%) and musculoskeletal (n = 172; 43.7%) involvement, although other organ manifestations of varying prevalence were also recorded. The most commonly reported mutations were "c.122T > C pMET41Thr" (n = 124), "c.121A > G pMET41Val" (n = 62) and "c.121A > C pMet41Leu" (n = 52). Most patients received glucocorticoids (n = 240; 60.9%) followed by methotrexate (n = 82; 20.8%) and IL-6 inhibitors (n = 61, 15.4%). One patient underwent splenectomy; 24 received bone marrow transplants. CONCLUSION: VEXAS syndrome is a rare disorder affecting predominantly middle-aged men. This is the first systematic review to capture clinical manifestations, genetics and treatment of reported cases. Further studies are needed to optimise treatment and subsequently reduce morbidity and mortality.

Improving outcomes in single chamber leadless pacemakers: strategies for minimizing vascular complications.

BACKGROUND: Leadless pacemaker therapy is associated with a significant reduction in lead-related complication rate compared to conventional transvenous single chamber pacemaker therapy. However, a significant complication rate of 1.2% was observed in vascular access due to the use of large delivery femoral sheath (27Fr). The aim of this study was to evaluate the effectiveness of real-time ultrasound guidance and Z suture technique in reducing total and major vascular complications in leadless pacemaker therapy. METHOD: In this study, we performed a retrospective and prospective analysis of all adverse events associated with leadless pacemaker (Micra) implantation by two operators at a single tertiary center from December 2016 to December 2018. To mitigate the risk of vascular complications, all patients underwent real-time ultrasound-guided venipuncture for vascular access, as well as the application of a Z-suture technique for hemostasis at the end of the procedure. Data were collected on implant indications, implant procedure details, complications, and follow-up information. RESULTS: In this study, 45 patients with an age range of 24 to 94 years (mean 76 ± 14 years) were recruited, with 21 (46.6%) being female. The pacing indications for the patients included atrial fibrillation (24, 53.3%), vascular (7, 15.5%), infection (9, 20%), cognitive/frailty (3, 6.6%), and occupational (2, 4.4%). The implant procedures were performed under general anesthesia in 6 (13.3%) of the cases, and under local anesthesia and sedation in 39 (86.6%) of the cases. A single deployment was achieved in 43 (95.5%) of the patients, while 2 deployments were required in 2 (4.4%) of the patients. Notably, no vascular or major complications were reported in our cohort of patients. CONCLUSIONS: The results of this observational study indicate that incorporating real-time ultrasound guidance during venipuncture and the use of a Z-suture technique significantly reduce the occurrence of both total and major vascular complications associated with the implantation of leadless pacemaker. However, more robust and larger studies are required in order to confirm these results and implications for clinical practice.

Incidence, clinical features, management and outcomes of ANCA-associated vasculitis in pregnancy- a systematic literature review.

BACKGROUND AND AIM: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare multi-system conditions, usually presenting in older age groups. However, younger individuals are also affected. The average increase of childbearing age and lack of studies in pregnancy necessitates this comprehensive review of data to guide the management of AAV in pregnancy. This systematic review (SR) aimed to summarise the incidence, clinical features, management and maternal and foetal outcomes in female patients with AAV. METHODS: The protocol was registered on PROSPERO (CRD42023437482). Articles published in Medline, Embase and Cochrane Databases from 1946 until June 2023 were included. Single case reports, reviews and conference abstracts were excluded. Articles meeting inclusion criteria were examined by two authors. Data on demographics, treatment, clinical features, flares during pregnancy and maternal and foetal outcomes were extracted. RESULTS: Eight studies were included, detailing 82 pregnancies in 64 women. The most common drugs used for remission induction pre-conception were cyclophosphamide, rituximab, prednisolone and azathioprine. Serious maternal complications in pregnancy included progressive tracheal/subglottic stenosis (n=5), renal disease (n=2), preeclampsia (n=10) and miscarriages (n=5). Foetal anomalies were rare (n=5). The mean birth weight was 3.37kgs and mean gestation age was 38.26 weeks. No maternal deaths or vasculitis in newborns were reported.  Conclusions: Patients can have positive maternal and foetal outcomes following strong induction therapy, vigorous monitoring and prompt treatment of flares during pregnancy. Serious complications and flares are not associated with worse outcomes for newborns.

Opportunistic optimization of inhaler technique in hospitalized adults with asthma: a two-phase educational study.

OBJECTIVE: To investigate effectiveness of two different educational methods to improve inhaler techniques in patients with prior diagnosis of asthma, hospitalized with a non-asthma-related diagnosis. METHODS: We undertook a real-world, opportunistic quality-improvement project. Inhaler technique in hospitalized patients with prior diagnosis of asthma was assessed in two cohorts over two 12-week cycles using a standardized device-specific proforma of seven-step inhaler technique, classed: "good" if 6/7 steps achieved; "fair" if 5/7 compliant; "poor" for others. Baseline data was collected in both cycles. Cycle one involved face-to-face education by a healthcare professional; cycle two involved additional use of an electronic device to show device-specific videos (asthma.org.uk). In both cycles, patients were reassessed within two days for improvements and the two methods compared for effectiveness. RESULTS: During cycle one 32/40 patients were reassessed within 48 h; eight lost to follow-up. During cycle two 38/40 patients were reassessed within 48 h; two lost to follow-up During cycle one, two and 12 had good/fair baseline technique respectively, and 26 poor. Most commonly missed steps were no expiry check/not rinsing mouth after steroid use. On reassessment 17% patients improved from poor to fair/good. During cycle two, initial technique assessment identified: 23 poor; 12 fair; five good. Post-videos, 35% of patients improved from poor to fair/good. Proportion of patients improving from poor to fair, or poor/fair to good increased in cycle two vs one (52.5% vs 33%). CONCLUSION: Visual instruction is associated with improved technique compared to verbal feedback. This is a user-friendly and cost-effective approach to patient education.

A systematic review of the incidence, management and prognosis of new-onset autoimmune connective tissue diseases after COVID-19.

A literature review on new-onset autoimmune connective tissue diseases (ACTDs) following COVID-19 is lacking. We evaluated potential associations between COVID-19 and the development of new-onset ACTDs. The "population" was adults with disease terms for ACTDs, including systemic lupus erythematosus (SLE), Sjogren's syndrome, systemic sclerosis (SSc), idiopathic inflammatory myositis (IIM), anti-synthetase syndrome, mixed CTD and undifferentiated CTD, and "intervention" as COVID-19 and related terms. Databases were searched for English-language articles published until September 2022. We identified 2236 articles with 28 ultimately included. Of the 28 included patients, 64.3% were female, with a mean age was 51.1 years. The USA reported the most cases (9/28). ACTD diagnoses comprised: 11 (39.3%) IIM (including four dermatomyositis); 7 (25%) SLE; four (14.3%) anti-synthetase syndrome; four (14.3%) SSc; two (7.1%) other ACTD (one lupus/MCTD overlap). Of eight, four (14.3%) patients (including that with lupus/MCTD) had lupus nephritis. The average time from COVID-19 to ACTD diagnosis was 23.7 days. A third of patients were admitted to critical care, one for treatment of haemophagocytic lymphohistiocytosis in SLE (14 sessions of plasmapheresis, rituximab and intravenous corticosteroids) and nine due to COVID-19. 80% of patients went into remission of ACTD following treatment, while three (10%) patients died-one due to macrophage activation syndrome with anti-synthetase syndrome and two from unreported causes. Our results suggest a potential association between COVID-19 and new-onset ACTDs, notably in young females, reflecting more comprehensive CTD epidemiology. The most common diagnosis in our cohort was IIM. The aetiology and mechanisms by which ACTDs emerge following COVID-19 remain unknown and require further research.

Pulmonary manifestations in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome: a systematic review.

BACKGROUND: VEXAS (vacuoles, E1 enzyme, X-linked, auto-inflammatory, somatic) syndrome is a newly described auto-inflammatory disease. Many cases feature pulmonary infiltrates or respiratory failure. This systematic review aimed to summarize respiratory manifestations in VEXAS syndrome described to date. METHODS: Databases were searched for articles discussing VEXAS syndrome until May 2022. The research question was: What are the pulmonary manifestations in patients with VEXAS syndrome? The search was restricted to English language and those discussing clinical presentation of disease. Information on basic demographics, type and prevalence of pulmonary manifestations, co-existing disease associations and author conclusions on pulmonary involvement were extracted. The protocol was registered on the PROSPERO register of systematic reviews. RESULTS: Initially, 219 articles were retrieved with 36 ultimately included (all case reports or series). A total of 269 patients with VEXAS were included, 98.6% male, mean age 66.8 years at disease onset. The most frequently described pulmonary manifestation was infiltrates (43.1%; n = 116), followed by pleural effusion (7.4%; n = 20) and idiopathic interstitial pneumonia (3.3%; n = 9). Other pulmonary manifestations were: nonspecific interstitial pneumonia (n = 1), bronchiolitis obliterans (n = 3), pulmonary vasculitis (n = 6), bronchiectasis (n = 1), alveolar haemorrhage (n = 1), pulmonary embolism (n = 4), bronchial stenosis (n = 1), and alveolitis (n = 1). Several patients had one or more co-existing autoimmune/inflammatory condition. It was not reported which patients had particular pulmonary manifestations. CONCLUSION: This is the first systematic review undertaken in VEXAS patients. Our results demonstrate that pulmonary involvement is common in this patient group. It is unclear if respiratory manifestations are part of the primary disease or a co-existing condition. Larger epidemiological analyses will aid further characterisation of pulmonary involvement and disease management.

Spontaneous adverse drug reaction reports for neonates and infants in the UK 2001-2010: content and utility analysis.

AIMS: The UK Medicines and Healthcare products Regulatory Agency (MHRA) runs a national spontaneous reporting system (Yellow Card [YC] Scheme) to collect 'suspected' adverse drug reaction (ADR) data. We aim to describe the content and utility of YC reports received for patients aged <2 years. METHODS: Data on all ADRs reported using YC in infants aged <2 years from the years 2001-10 were supplied by the MHRA. RESULTS: For infants age <2 years, 3496 suspected ADRs were reported using YC (paternal medication pre-conception n = 3, transplacental n = 246, transmammary n = 30, neonates n = 97, infant n = 477, and vaccinations n = 2673), averaging 0.96 YC per day. There was a male preponderance (male 49.1%, female 44.4%, unknown 6.5%), and only 34 (1.0%) of YC reports stated a gestational age. The medications most frequently reported were: transplacental and transmammary (fluoxetine, n = 21 and n = 4 respectively), neonate (swine flu vaccine, n = 8) infant (oseltamivir, n = 37) and vaccines (meningococcal vaccine, n = 693). Paternal, transmammary, neonatal and infant YC did not reflect clinical concerns raised by the UK regulator. Transplacental and vaccination reports did correlate with some of the changes in practice and clinical alerts received. CONCLUSIONS: The frequency of YC reports for those <2 years is low, neonates are poorly represented, and recording of gestational age is poor. With the exception of vaccinations, spontaneous reports alone are not currently generating the data required, and important safety messages from the regulator do not match reporting patterns. Additional reporting strategies are required to improve the quantity and quality of suspected ADR data in young children.