Association studies between COVID-19 and SSc-ILD

Severe COVID-19 patients may develop pulmonary fibrosis, similar to SSc-ILD disease, suggesting a potential link between the two diseases. However, there are limited treatment options for SSc-ILD-type diseases. Therefore, investigating pathological markers of the two diseases can provide valuable insights for treating related conditions. RNA sequencing technology offers high throughput and precision. However, the bimodal nature of RNA-Seq data cannot be accurately captured by commonly used algorithms such as DESeq2. To address this issue, the Beta-Poisson model has been developed to identify differentially expressed genes. Unlike the classical DESeq2 algorithm, the Beta-Poisson model introduces a Beta distribution to construct a new hybrid distribution in place of the Gamma distribution of the Gamma-Poisson distribution, effectively characterizing the bimodal features of RNA-Seq data. The transcriptomes of SARS-CoV infection and SSc-ILD disease in the lung epithelial cell dataset were analyzed to identify common differentially expressed genes of SARS-CoV and SSc-ILD disease. Gene function and signaling pathway enrichment analysis and protein-protein interaction (PPI) network were used to identify common pathways and drug targets for SSc-ILD with COVID-19 infection. The results show that there are 50 differentially expressed genes in common between COVID-19 and SSC-ILD. The functions of these genes are mainly enriched in immune system response, interferon signaling pathway and other related signaling pathways, and enriched in biological processes such as cell defense response to virus and interferon regulation. Based on the detection of hub genes based on PPIs network, it is predicted that STAT1, ISG15, IRF7, MX1, EIF2AK2, DDX58, OAS1, OAS2, IFIT1 and IFIT3 are the key genes involved in the pathological phenotype of the two diseases. Based on the key genes, the interaction of transcription factor (TF) and miRNA with common differentially expressed genes is also identified. The possible pathological markers of the two diseases and related molecular regulatory mechanisms of disease treatment are revealed to provide theoretical basis for the treatment of the two diseases. © 2023 Editorial Office of Journal of Shenzhen University. All rights reserved.

Ethnic, racial and migrant inequalities in respiratory health

Disparities in the incidence, prevalence, and morbidity and mortality rates of many respiratory diseases are evident among ethnic groups. Biological, cultural and environmental factors related to ethnicity can all contribute to the differences in respiratory health observed among ethnic minority groups, but the inequalities observed are most commonly due to lower socioeconomic position. People who migrate within a country or across an international border may experience an improvement in respiratory health associated with improvements in socioeconomic position. However, migrants may also experience worse health outcomes in destination countries, as they are faced by barriers in language and culture, discrimination, exclusion and limited access to health services. While some high-quality studies investigating ethnicity and respiratory health are available, further research into ethnic differences is needed. Improving the recording of ethnicity in health records, addressing barriers to accessing respiratory healthcare and improving cultural literacy more generally are some of the ways that inequalities can be tackled.Copyright © ERS 2023.

Mild COVID-19 clinical course among paediatric patients with primary immunodeficiency

Background: The clinical course of coronavirus disease-2019 (COVID-19) varies from those who are asymptomatic, experience mild symptoms such as fever, cough, and dyspnea, to more severe outcomes including acute respiratory distress, pneumonia, renal failure, and death. Early reports suggested severe outcomes in patients with primary immunodeficiency (PID), particularly those with type 1 interferon signalling defects. This prompted a rigid approach to social distancing to protect this patient population, particularly children. To date, real-world data describing the course and outcome of COVID-19 in paediatric PID patients remains scarce. Method(s): In this retrospective case series, we describe the clinical course of 36 paediatric patients with underlying primary immunodeficiency (PID) followed by SickKids Hospital (Toronto, Canada) who were symptomatic and tested positive for SARS-CoV-2 infection between October 2020 to November 2022. Result(s): Our cohort consisted of patients with combined immunodeficiency (66.7%), antibody deficiency (22.2%), neutrophil dysfunction (8.3%), and immune dysregulation (2.8%). The median age was 7.5 years (range: 8 months - 17 years), with 21 male and 15 female patients. Three (8.3%) patients were post-hematopoietic stem cell transplant (HSCT) and 12 (33%) patients were on immunoglobulin replacement. Nine (25%) patients had underlying lung problems including bronchiectasis (1), interstitial lung disease on home oxygen therapy (1), and underlying asthma (7). Most patients had mild clinical course and were managed at home. The most common symptoms were fever (80%), cough (75%) and other upper respiratory tract symptoms (72%). Nineteen (52.7%) patients experienced other symptoms which included headache, lethargy, or gastrointestinal upset. At the time of the infection, 13 patients (36.1%) had received 2 doses of a SARS-CoV-2 vaccine, 5 patients (13.9%) had received 1 dose, and 18 (50%) were not vaccinated. None of the patients received antiviral or monoclonal antibody as prophylaxis or treatment. Only 1 patient required hospital admission out of precaution given the close proximity to HSCT. All patients recovered without complications. Conclusion(s): The paediatric patients with PID followed by our centre experienced mild to moderate COVID-19 symptoms and recovered fully without complications. These findings support the return of much needed social interactions among children, which were impacted severely during the COVID-19 pandemic.Copyright © 2023 Elsevier Inc.

Evaluation of Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Levels in Coronavirus Disease Breakthrough Infection During Immunosuppressive Therapy in a Patient with Connective Tissue Disease-Related Interstitial Lung Disease.

Herein, we report the case of a 67-year-old man with severe coronavirus disease (COVID-19) pneumonia and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine breakthrough infection during immunosuppressive therapy for connective tissue disease-related interstitial lung disease (CTD-ILD). The patient received glucocorticoids combined with tacrolimus (TAC) as maintenance therapy. His serum anti-SARS-CoV-2-IgG antibody levels were extremely low at the onset of COVID-19 pneumonia, even after the second dose of SARS-CoV-2 mRNA vaccine (BNT162b2). After treatment for COVID-19 pneumonia, the levels of anti-SARS-CoV-2-IgG antibodies increased. These results indicated a lack of the ability to produce neutralizing antibodies from immune cells despite the booster vaccination. Therefore, we suggest that advanced age patients with CTD-ILD receiving immunosuppressive therapy with polypharmacy require consistent personal protection, vaccination of close caregivers, increased awareness, and booster vaccination. Moreover, we recommend that TAC should be withdrawn for a while after vaccination under controlled conditions.

COVID-19 and protection of vaccination in patients with systemic sclerosis-associated interstitial lung disease.

Objectives: Data on COVID-19 in patients with interstitial lung disease are scarce and whether SARS-CoV-2 may trigger interstitial lung disease progression remains unknown. We aimed to analyze outcomes of COVID-19 in patients with systemic sclerosis-associated interstitial lung disease, including possible thoracic radiographic progression. Patients and Methods: All 43 patients with systemic sclerosis-associated interstitial lung disease followed in our center (mean ± SD, 55.2 ± 11.6 years, 36 female) with confirmed SARS-CoV2 infection up to 1 September 2022 were analyzed. Individual interstitial lung disease extent on high resolution CT (HRCT) performed before (up to 3 months) and after COVID-19 (2-5 months) was compared. Results: At SARS-CoV-2 infection, 9/43 patients were unvaccinated, whereas 5, 26, and 3 had received 2, 3, or 4 doses of an mRNA vaccine, respectively. Thirty-one patients were either on monotherapy with immunosuppressives (mycophenolate, n = 7; cyclophosphamide, n = 2; methotrexate, n = 10; tocilizumab, n = 7; rituximab, n = 1; etanercept, n = 1), or their combinations (n = 3). Eight patients (20%), of whom four unvaccinated, required hospitalization for pneumonia and three (7%) died of acute respiratory failure (n = 2, both unvaccinated) or cardiac arrest. Lack of vaccination was the only independent predictor for hospitalization (OR = 7.98, 95% CI: 1.25-51.09) and marginally for death (OR = 32.7, 95% CI: 0.97-1110.98), regardless of the presence of diffuse systemic sclerosis, interstitial lung disease extent greater than 20% or immunosuppressive treatment. In 22 patients with available HRCT pairs (vaccinated = 20), the interstitial lung disease extent before COVID-19 (20.4%± 17.8%) remained unchanged (22.4% ± 18.5%) in all but one patient. Conclusion: SARS-CoV-2 vaccination is of outmost importance for every systemic sclerosis patient with interstitial lung disease. COVID-19 does not seem to promote progression of systemic sclerosis-associated interstitial lung disease in vaccinated patients, but further studies are warranted.

Anti-synthetase syndrome masquerading as recurrent pneumonia.

Anti-synthetase syndrome (ASS) is a rare inflammatory myopathy with a wide variety of clinical presentations. ASS-related interstitial lung disease (ASS-ILD) presents with rapid onset and progression, which could often be confused with other more common acute processes such as pneumonia, especially when ILD can be the sole manifestation. A woman in her 50s presented with recurrent dyspnoea for 2 months requiring multiple hospital admissions, and each time, she was diagnosed with multifocal pneumonia and treated with antibiotics. On admission, the evaluation revealed a markedly elevated creatine kinase level at 3258 U/L and a CT scan of the chest revealed worsening scattered ground-glass opacities. Given the concern for ILD as the cause of antibiotic failure, she underwent bronchoscopy with bronchoalveolar lavage which revealed non-specific interstitial pneumonia. A subsequent myositis panel revealed a positive anti-Jo-1 antibody, and she was diagnosed with ASS-ILD. She completed a course of intravenous immunoglobulin and methylprednisolone and experienced significant clinical improvement with the resolution of hypoxaemia and improved polyarthralgia.ASS could often be misdiagnosed as other more common acute lung processes, as a clinically subtle course can escape detection given its rarity, as well as its non-specific and highly variable presentations. This case highlights the importance of early suspicion and consideration of performing specific autoantibody testing when evaluating patients with a suspicion of undifferentiated autoimmune condition.

Diagnostic Dilemma: A Patient With Pulmonary Fibrosis Who Presented for Severe Tracheal Stenosis After COVID-19 Pneumonia.

A 44-year-old man with pulmonary fibrosis presented to our pulmonary hypertension clinic with biphasic stridor and dyspnea. He was sent to the emergency department, where he was found to have 90% subglottic tracheal stenosis and was successfully treated with balloon dilation. Seven months prior to the presentation, he required intubation for coronavirus disease 2019 (COVID-19) pneumonia complicated by hemorrhagic stroke. He was discharged after percutaneous dilatational tracheostomy, which was decannulated after three months. Our patient possessed several risk factors for tracheal stenosis, including endotracheal intubation, tracheostomy, and airway infection. Furthermore, our case is of great importance given the developing literature on COVID-19 pneumonia and its subsequent complications. Additionally, his history of interstitial lung disease may have confounded his presentation. Therefore, it is important to understand stridor, as it is an important exam finding that clinically distinguishes upper and lower airway disease. Our patient's biphasic stridor is consistent with the diagnosis of severe tracheal stenosis.

Corrigendum: Post-COVID-19 interstitial lung disease: Insights from a machine learning radiographic model.

[This corrects the article DOI: 10.3389/fmed.2022.1083264.].

Incidental findings arising from targeted lung health checks: a GP practice perspective

Introduction: Newcastle Gateshead is a phase one Targeted Lung Health Checks site. Walker Medical Group GP practice serves a deprived population and is a designated Deep End practice. We report on the experience of Targeted Lung Health Checks at this practice. Method(s): Invitations were sent to eligible participants registered at the practice. Lung health checks were carried out by telephone according to Standard Protocol in the context of the COVID 19 pandemic. Those meeting criteria for Low Dose CT were invited to a mobile scanner located in the community near to the practice. Scans were reported according to the Standard Protocol. Result(s): Of 1481 eligible patients, 736 (50.44%) attended a telephone lung health check. 458 (63.6%) met criteria for a CT scan, of whom 33 declined a scan and 2 were unable to lie flat. 11 lung cancers (2.6%) and one other cancer were diagnosed. 71 (16.8%) had nodules requiring follow-up. These cases were managed by the TLHC programme and lung cancer MDT. Incidental findings had the greatest impact on general practice. 72.3% of scans showed coronary artery calcification. Of these, over 1 in 4 was not currently prescribed a Statin. New diagnoses of bronchiectasis (8 patients = 2%) and interstitial lung disease (7 patients = 1.6%) required GP action. 5 new cases of undiagnosed thoracic aortic aneurysm were identified, requiring referral for further action (1%). Conclusion(s): Incidental findings of Targeted Lung Health Checks CT scans require substantial input from a GP team. Coronary artery calcification is numerically most significant. Participants and practices should be supported by information and resources. Thoracic aortic aneurysm cases are also found in significant numbers and TLHC projects are advised to work with cardiology and cardiac surgery units when setting up. We plan to explore the reasons for participant refusal of CT scanning. Disclosure: No significant relationships.Copyright © 2023 Elsevier B.V.

Patients with interstitial lung disease are high-risk of COVID-19 morbidity with implications on access to early oral anti-viral treatments

Introduction/Aim: Patients with interstitial lung disease (ILD) are at higher risk of COVID-19 infection associated morbidity and mortality, and hence may benefit from early anti-viral therapy. The access criteria for early oral anti-viral therapies for COVID-19 varied in early 2022 due to limited supplies nationally. We created a live clinical database of ILD patients in a tertiary hospital setting, stratifying them by measurable risk factors and therefore accessibility by state or national criteria to anti-viral therapy. Method(s): A list of active ILD clinic patients was generated from the WEBPAS clinic database. Data on patient demographics, co-morbidities and immunosuppressive medications relevant to access to anti-viral medications via the PBS criteria and state-based criteria was gathered by medical records review. Demographic information included age, BMI, ethnicity, residential care living and rurality. Co-morbidity risk factors included congestive cardiac failure, neurological disease, diabetes mellitus, chronic kidney disease, liver cirrhosis, chronic lung disease and immunodeficiencies. Medications of relevance included glucocorticoids, steroid-sparing immunomodulators and chemotherapy. Combinations of the above risk factors equate to eligibility to treatment. Result(s): Between the data capture dates of 1 February 2021 and 31 January 2022, 526 patients were identified. Of these 457 fit the inclusion criteria. Median age was 71.4 years (range 20-92), ratio of F:M was 1.09. 11% of patients were on long term oxygen therapy. Commonest conditions were idiopathic pulmonary fibrosis (26.3%), connective-tissue disease ILD (18%) and sarcoidosis (13.4%). 92 (20%) of patients fit into 'moderate or severely immunocompromised' criteria. 346 (75%) of patients fit criteria for early anti-virals by the first iteration of PBS criteria. Using the second iteration of PBS criteria, 374 (82%) of the ILD patients fit criteria for early anti-viral treatment. Notably, some patients qualify for anti-virals on multiple eligibility PBS criteria. Conclusion(s): A large proportion of our ILD cohort is deemed 'high risk' for COVID-19 morbidity and would qualify for early anti-viral therapies (regardless of vaccination status).

Histomorphological Spectrum of Lung Lesions at Autopsy-A Tertiary Care Centre Experience

Background and aims: A wide variety of pathological conditions involve the lungs. In autopsy, the lungs are examined for disease, injury and other findings suggesting cause of death or related changes.Aims & Objectives: The present study aimed to study the histomorphological spectrum of lung lesions at autopsy and to assess the frequency of different types of lesions;and to associate histomorphological changes with cause of death.Material and Methods: It was a one-year observational study conducted in the Department of Pathology, Govt. Medical College, Jammu. Lung tissue pieces from all medicolegal autopsies received were fixed, examined grossly, processed;paraffin embedded sections obtained were stained with Hematoxylin and Eosin stain and examined under microscope. Findings were recorded and tabulated. Result(s): Out of 264 cases, males were predominantly affected (84%);median age was 38 years. The various changes observed were congestion (68%), edema (45.4%), pneumonia (5%), granulomatous inflammation (3%), diffuse alveolar damage (1.5%), haemorrhage (14.4%), interstitial changes (60%), malaria (0.4%) and malignancy (0.4%). Natural deaths were the commonest cause (75, 28%) followed by asphyxial deaths (65, 24.6%). Conclusion(s): Histopathological examination of lung autopsies highlights many incidental findings, establishes underlying cause of death, serves as a learning tool and also holds scope for detection of newer diseases.Copyright © 2023 JK Science.

Lung ultrasound scoring system vs ROX index as a predictor for progression to the invasive mechanical ventilation in COVID-19 patients

Background: During the outbreak of the highly contagious Coronavirus disease 19 (COVID19), rapid and simple prognostic tools were needed to support clinical decisions and predict the need of invasive mechanical ventilation. the ROX index, and the lung ultrasound score (LUSS) were proposed to objectively predict patient prognosis in addition to the subjective clinical assessment Aim: This study aimed to compare lung ultrasound score with ROX index in predicting the need of invasive ventilation in COVID-19 patients requiring advanced oxygen therapy. Patients and Methods: We studied 50 patients with severe COVID-19 pneumonia in the intensive care unit in the isolated area at Kasr Al-Ainy hospital. Complete Medical history, physical examination and laboratory investigations were obtained on admission. All patients underwent bedside lung ultrasonography scan and LUSS was calculated at the 2nd and the 12th hours, also ROX index was calculated at the 2nd, 6th and 12th hours from initiating the advanced oxygen therapy. Result(s): From a total of fifty patients with COVID-19, 56.0% were males, with mean age of 65.98 + 11.68 years, and mortality rate was 68%. The optimal cut off value of the ROX index at (2, 6, 12 hour) is (2.495, 2.675, 3.06) respectively, (p <0.001) with sensitivity 90.9% and specificity 76.5% at the 12 hour. Also the optimal cut off point of LUSS is 25.50 (p <0.001) with sensitivity 93.9% and specificity 88.2% for prediction of the invasive mechanical ventilation. Conclusion and recommendations: The study concluded that LUSS is more sensitive in predicting the need of invasive mechanical ventilation than ROX index.Copyright © 2023, Codon Publications. All rights reserved.

42nd International Symposium on Intensive Care and Emergency Medicine

The proceedings contain 369 papers. The topics discussed include: effective FiO2 delivered by a new frugal CPAP system with low oxygen needs: from bench to clinical observations;effect of non invasive respiratory support on interstitial lung disease with acute respiratory failure: a systematic review and meta analysis;causes of mortality of severe COVID 19 patients receiving high flow oxygen therapy;patient ventilator interaction during noninvasive ventilation with helmet: a comparison between pressure support ventilation and the new neural pressure support (NPS) software;tidal volume measurement during non invasive respiratory support by helmet continuous flow CPAP is feasible and accurate in a bench model;delayed intubation with high flow nasal cannula in COVID: a comparison between a first and second pandemic wave;outcomes following application of high flow nasal cannula and non invasive ventilation during the second COVID 19 wave in Singapore;ventilator avoidance among critically ill COVID 19 patients with acute respiratory distress syndrome;and mortality rate, intensive care unit length of stay and time to orotracheal intubation of COVID 19 patients under different non invasive ventilatory therapies: retrospective cohort study.

Contemporary Concise Review 2022: Interstitial lung disease.

Novel genetic associations for idiopathic pulmonary fibrosis (IPF) risk have been identified. Common genetic variants associated with IPF are also associated with chronic hypersensitivity pneumonitis. The characterization of underlying mechanisms, such as pathways involved in myofibroblast differentiation, may reveal targets for future treatments. Newly identified circulating biomarkers are associated with disease progression and mortality. Deep learning and machine learning may increase accuracy in the interpretation of CT scans. Novel treatments have shown benefit in phase 2 clinical trials. Hospitalization with COVID-19 is associated with residual lung abnormalities in a substantial number of patients. Inequalities exist in delivering and accessing interstitial lung disease specialist care.

Pulmonary lymphomatoid granulomatosis in a patient with long-term use of a tumour necrosis factor-α inhibitor.

A man in his 60s presented with intermittent constitutional symptoms along with waxing and waning chest radiographic abnormalities, eventually leading to a diagnosis of lymphomatoid granulomatosis (LYG). LYG is a rare, progressive Epstein-Barr virus (EBV)-driven lymphoproliferative disease associated with immune dysregulation most commonly involving the lungs. The diagnosis requires tissue biopsy; thus, the decision to pursue tissue sampling with histopathology examination in a timely manner is essential. Currently, there are no established guidelines regarding the treatment of LYG, which varies from cessation of immunosuppressants to immunochemotherapy and usually requires multidisciplinary team discussion.

Patient and Physician Assessments of Clinical Status: A Mixed-Methods Study of Interstitial Lung Disease

Background The SARS-CoV-2 pandemic necessitated novel health-care delivery for patients with interstitial lung disease (ILD), including reduced in-person appointments and physiologic testing to minimize transmission. Clinicians often have been required to rely on patients' subjective assessments of their clinical status during phone follow-up appointments. It is unknown how accurate a patient's self-assessment is compared with that of their physician during an in-person evaluation. Research Question Are patients' self-assessments of their clinical status in agreement with their physicians' assessments, and are telemedicine vs in-person visits acceptable? Study Design and Methods Patients were enrolled prospectively from the University of Calgary ILD clinic. Participants were asked by phone before the in-person appointment and after the appointment to rate their clinical status on a five-point Likert scale. Physicians then rated the patient's clinical status after the appointment on a similar five-point Likert scale, masked to patient responses. Patients and physicians were asked if an in-person appointment was necessary or if telemedicine would have sufficed. Clinical variables associated with physician assessments were assessed. Results Fifty patients with mean age of 67 ± 11.8 years participated. Mean time since last follow-up was 5.0 ± 3.0 months. No correlation was found between the preclinical patient self-assessment and postclinical physician assessment (P = .18;κ = 0.28). Correlation of postclinical assessment was statistically significant (P < .001), with moderate agreement (κ = 0.49). Physicians thought telephone visits were acceptable for 58% of appointments, whereas only 12% of patients preferred telephone visits. Physician's assessment of clinical status seemed to be driven by change in diffusion capacity of the lungs for carbon monoxide (P = .039). Interpretation Telemedicine may improve access to care for patients during pandemic management, in rural communities, and for those with impaired mobility. Despite these benefits, our data support that patients and physicians may not agree on determination of clinical status and that patients generally prefer in-person patient-physician interactions.

Hypogammaglobulinemia after Rituximab Treatment in an Italian Real-Life Cohort of Iim

Background. Rituximab (RTX) is a chimeric monoclonal antibody that binds the CD20 molecule on the surface of B cells and leads to B cell depletion. RTX is recommended by the European League Against Rheumatism (EULAR) as off-label in patients affected by idiopathic inflammatory myopathies (IIM). The real-world experience has shown that hypogammaglobulinemia occurring early after anti-CD20 treatment can be multifactorial (active disease, effect of other drugs) and usually transient, with a minimal increase in the risk of infections. The present study aimed to analyse the differences in the rate of RTX-associated hypogammaglobulinemia in a cohort of IIM patients in clinical practice, as well as the onset of major infections and its correlation with hypogammaglobulinemia. Methods. Patients followed at Rheumatology Unit of Siena University Hospital from January 2020 to September 2021 were retrospectively enrolled. Inclusion criteria were as follows: fulfilment of disease-specific classification criteria 2017 EULAR criteria and /or Peter and Bohan criteria for dermatomyositis (DM) and polymyositis (PM), positivity of anti-synthetase antibody and typical clinical features for anti-synthetase syndrome (ASS) and the measurement of serum Ig levels at the time of RTX administration (maximum 2 weeks before) (T0) and 6 (T1) to 12 (T2) months later, consistently with previous studies. Ig serum levels, measured by standard nephelometry (normal ranges: IgG 700-1600 mg/dL, IgM 40-240 mg/dL, IgA 70-400 mg/dL) were assessed as part of routine clinical care. Hypogammaglobulinemia was defined as moderate (serum IgG <600 mg/dL) and severe (IgG <400 mg/dL), as previously reported. Results. Seven patients (mean+/-SD, 57.3+/-19.7 years;7 female) were enrolled. Three of them had diagnosis of DM, three ASS and one PM. Two patients showed MDA5-positivity, two JO1-positivity, one TIF1-gamma-positivity, one PL7-positivity and the other one PM/Scl-positivity. All patients had at least two organs involved, and 4 out of 7 (57%) suffered from interstitial lung disease. Before starting RTX treatment, three and four patients underwent at least one and two synthetic immunosuppressants. All patients underwent low dosage of corticosteroids, and four patients underwent concomitant synthetic immunosuppressants (2 hydroxychloroquine and 2 MTX). IgG concentrations were statically lower at T2 compared to those at baseline (p=0.0391). None of them showed severe hypogammaglobulinemia. Similarly, IgM concentration significantly decreased at T2 compared to those at baseline (p=0.0078). Two patients showed major infections and two patients had paucisymptomatic COVID-19 (one of them had twice). Corticosteroids dosages were inversely correlated with IgG T2 concentrations (p=0.040, r=-0.919). Conclusion. Hypogammaglobulinemia following RTX is uncommon in IIM and is more likely in patients with high glucocorticoids, immunosuppressants and CYC exposure. IgG monitoring at least 6 months after RTX treatment may be useful in stratifying patients to identify those who require closer monitoring. These results shine a spotlight for increased awareness of the role of immunoglobulin measurement before maintenance doses of RTX.

Dermatomyositis with Specific Autoantibodies Appearing after Sars-Cov-2 Infection or Mrna Vaccination: Hints at a Shared Pathogenetic Mechanism

Background. Environmental factors such as infections and vaccines are known to trigger dermatomyositis (DM), and during the recent SARS-CoV-2 pandemic this has become even clearer. SARS-CoV-2 infection may share features with anti-MDA5 DM, such as rapidly progressive lung involvement, cutaneous lesions and cytokine release syndrome. A few case reports of DM following SARSCoV-2 vaccination have been published, suggesting the onset of an aberrant immune response leading to DM with specific autoantibody signatures and severe organ impairment. Methods. Clinical and laboratory data of the 2 case reports were obtained from electronic clinical charts in Humanitas Research Hospital (Rozzano, Milan, Italy). Autoantibody analysis was performed by protein-immunoprecipitation for anti-MDA5 and immunoblot for anti-Ro52 and TIF1gamma antibodies as per protocol. Results. Case report 1 is a 71-year-old woman who developed fever, cough, and anosmia, which resolved spontaneously in two weeks, but did not undergo a nasopharyngeal swab, while her relatives were diagnosed with SARS-CoV-2 infection. When symptoms improved, she developed arthralgia and skin lesions on her face, chest, and hands for which she started topical treatment, with negative SARSCoV-2 nasopharyngeal swab and positive serum test for IgG against SARS-CoV-2 spike protein. For the persistence of the skin rash and arthralgia, she was admitted to our Department in March 2021. Blood tests showed mild elevation of C reactive protein (2.1 mg/L -normal value NV<5), aspartate (84 UI/L) and alanine aminotransferase (133 UI/L -NV<35), ferritin (595 ng/ml -NV<306), troponin I (19 ng/L -NV<14), and BNP (251 pg/ml -NV<100) with normal complete blood cell count, creatine kinase, C3 and C4. IgG antibodies for SARS-CoV-2 spike protein were confirmed to be elevated (96 AU/ml -NV<15). Autoantibodies associated with connective tissue diseases were tested and only anti-MDA5 antibodies were positive at immunoprecipitation. A punch biopsy of a Gottron-like lesion on the left hand showed leukocytoclastic vasculitis. We observed reduced capillary density with neoangiogenesis and ectasic capillaries at the nailfold capillaroscopy. EKG and ecocardiography were normal, while cardiac magnetic resonance detected abnormalities in the parametric sequences, consistent with signs of previous myocarditis. A lung CT scan revealed pulmonary emphysema while respiratory function tests demonstrated reduced volumes (FVC 82%, FEV1 64%, inadequate compliance CO diffusion test). Based on the biochemical and clinical findings, a diagnosis of anti-MDA5-associated DM with skin and heart involvement was made and treatment with low-dose methylprednisolone (0.25 mg/kg daily) and azathioprine 100 mg was started, then switched to mycophenolate because not effective on skin lesions. Case report 2 is an 84-year-old woman with history of colon cancer (surgical treatment) and oral lichen treated with low doses steroids in the last 2 years. After the 2nd dose of SARS-CoV-2 mRNA vaccination, in March 2021 she developed skin rash with V-sign, Gottron's papules, periungueal ulcers, muscle weakness and fatigue, thus she performed a rheumatologic evaluation. Blood tests showed mild elevation of creatine kinase (484 UI/L, NV <167), CK-MB (9.6ng/ml, NV <3.4), BNP (215 pg/ml -NV<100) with normal values of complete blood cell count, C3 and C4. Anti-Ro52kDa and TIF1gamma were positive at immunoblot, thus we confirmed a diagnosis of DM. The clinical evaluation also showed active scleroderma pattern at nailfold capillaroscopy, normal echocardiography, bronchiectasia but not interstitial lung disease at lung CT, and normal respiratory function tests (FVC 99%, FEV1 99%, DLCO 63%, DLCO/VA 81%). A PET-CT scan was performed to exclude paraneoplastic DM, and treatment with steroids and mycophenolate was started. Conclusions. SARS-CoV-2 may induce mechanisms for escaping the innate immunity surveillance and causing autoimmune diseases, but more clinical and functional studies are needed to demonstrate this possible association.