Necrotizing autoimmune myositis following coronavirus disease 2019 infection: a case report.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 may be associated with late-onset necrotizing myositis, mimicking autoimmune inflammatory myositis; however, the exact underlying pathogenesis of severe acute respiratory syndrome coronavirus 2-induced myositis is still unclear. CASE PRESENTATION: Herein, we report a rare case of necrotizing autoimmune myositis in a 67-year-old middle eastern male following coronavirus disease 2019 infection, who presented with muscle weakness. The patient had positive anti-NXP2. The diagnosis of necrotizing autoimmune myositis was made according to muscle weakness, increased liver enzymes, electromyography and nerve conduction velocity results, and muscle biopsy. The patient underwent a full malignancy evaluation, which was unremarkable, and was discharged in relatively well condition with a daily dose of 1 mg/kg prednisolone and azathioprine 150 mg (2 mg/kg). CONCLUSION: Our report highlights the already known possible protracted sequence of coronavirus disease 2019 infection and the potential for delayed-onset necrotizing myositis.

Immune-mediated inflammatory diseases after anti-SARS-CoV-2 vaccines: new diagnoses and disease flares.

OBJECTIVE: New-onset immune-mediated inflammatory diseases (IMIDs) and flares of pre-existing IMIDs have been reported following anti- SARS-CoV2 vaccination. Our study aimed at describing a retrospective cohort of patients developing new-onset IMIDs or flares of known IMIDs within 30 days after any anti-SARS-CoV2 vaccine dose. METHODS: We evaluated clinical records of all inpatients and outpatients referring to our institution between February 2021 and February 2022 with any clinical manifestations. We then selected those having received any anti-SARS-CoV2 vaccine dose within the prior 30 days and classified them as having or not a previous IMID according to predefined criteria. We recorded new-onset IMIDs or flares of known IMIDs and investigated any relationship with demographic, clinical and serological variables. RESULTS: 153 patients that received any anti-SARS-CoV2 vaccine dose within the previous 30 days were included of which 45 (29%) already had a diagnosis of IMID while 108 (71%) had no previously diagnosed IMID. 33 (30%) of the 108 patients, were diagnosed with a new-onset IMID. Pericarditis, polymyalgia rheumatica and vasculitis were the most frequent conditions. Among the 45 patients that already had an IMID, disease flare was the reason for referral in 69% of patients. Patients with an IMID flare had a lower number of comorbidities and tended to be younger compared with those who developed other conditions after anti-SARS-CoV2 vaccination. CONCLUSION: We provided a retrospective overview of a cohort of patients who developed new-onset IMIDs or flares of known IMIDs within 30 days after any dose of anti-SARS-CoV2 vaccine. While vaccination campaigns proceed, postvaccination surveillance programmes are ongoing and hopefully will soon clarify whether a causal relationship between vaccines and new-onset/flares of IMIDs exists.

SARS-CoV-2 infection in patients with systemic autoimmune diseases.

Systemic autoimmune diseases (SAD) are a heterogeneous group of diseases with a common aetiopathogenic basis affecting all ages characterised by a systemic phenotypic expression with a wide range of severity and outcomes that often require immunosuppressive therapies, leaving patients at high risk of infection. Knowledge of the impact of COVID-19 in patients with SAD is limited because most are included in studies carried out in patients with autoimmune and rheumatic diseases (mainly inflammatory arthritis). Most studies supported an increased risk of SARS-Cov-2 infection in patients with AD and SAD. Although case-control studies reported no significant differences in the rate of poor outcomes between patients with and without AD, large population-based studies analysing baseline risk factors reported a 2-3 times higher rate of poor outcomes in patients with AD, especially in those with SAD. Individual risk factors associated with poor outcomes included gender male, older age, and underlying comorbidities and therapies (glucocorticoids, sulfasalazine, immunosuppressants and rituximab). Patients with SAD had less favourable COVID-19 outcomes than those with inflammatory arthritis, possibly due to a differentiated underlying therapeutic approach (glucocorticoids, immunosuppressants and B-cell depleting agents for most SAD, anti-cytokine therapies and JAK inhibitors for inflammatory arthritis). Despite the limited evidence, most studies suggest that patients with SAD have an increased risk of a worse evolution of SARS-CoV-2 infection, including a greater risk of hospitalisation/ICU admission and worse survival rates and, therefore, should be considered a high-risk group for COVID-19.

New Onset of Autoimmune Diseases Following COVID-19 Diagnosis.

There is growing evidence that coronavirus disease 2019 (COVID-19) can lead to a dysregulation of the immune system with the development of autoimmune phenomena. The consequence of this immune dysregulation ranges from the production of autoantibodies to the onset of rheumatic autoimmune disease. In this context, we conducted a systematic review to analyze the current data regarding the new-onset systemic and rheumatic autoimmune diseases in COVID-19 patients. A literature search in PubMed and Scopus databases from December 2019 to September 2021 identified 99 patients that fulfilled the specific diagnostic/classification criteria and/or nomenclature for each rheumatic autoimmune disease. The main diseases reported were vasculitis and arthritis. Idiopathic inflammatory myopathies, systemic lupus erythematosus, and sarcoidosis were also reported in a limited number of patients, as well as isolated cases of systemic sclerosis and adult-onset Still's disease. These findings highlight the potential spectrum of systemic and rheumatic autoimmune diseases that could be precipitated by SARS-CoV-2 infection. Complementary studies are needed to discern the link between the SARS-CoV-2 and new onset-rheumatic diseases so that this knowledge can be used in early diagnosis and the most suitable management.

Differential diagnosis of necrotizing myopathy.

PURPOSE OF REVIEW: Necrotizing myopathy is a broad term. It includes patients with the recently described immune-mediated necrotizing myopathies (IMNM) who have specific antibodies, such as anti-hydroxy-3-methylglutaryl-CoA reductase or anti-signal recognition particle, seronegative phenotypes that can be associated with cancer, and other types of myositis and connective tissue diseases involving necrotic muscle fibers as a characteristic pathologic feature. Necrotizing myopathies that are not immune-mediated, such as those caused by drugs, dystrophies, infections, or even hypothyroidism are also included. The purpose of this review is to address the differential diagnosis of these disorders. RECENT FINDINGS: New IMNM have been described over the last few years, some of them related with checkpoint inhibitors, drugs that are being increasingly used in cancer treatment. Necrotizing myopathy has also been reported in association with specific phenotypes and autoantibodies (e.g. anti-Mi2 dermatomyositis, antisynthetase syndrome, and myositis associated with antimitochondrial antibodies). Rarer cases associated with graft-versus-host disease and severe acute respiratory syndrome coronavirus 2 infection are also emerging. SUMMARY: Differentiation between patients with IMNM and those without the superimposed autoimmune phenomena helps clinicians determine the best individualized approach to use and the appropriate immunosuppressive therapy, whenever needed.

Incidence and predictors of COVID-19 and flares in patients with rare autoimmune diseases: a systematic survey and serological study at a national reference center in France.

BACKGROUND: The risk of severe COVID-19 and its determinants remain largely unknown in patients with autoimmune and inflammatory rheumatic diseases. The objective of this study was to assess the prevalence of COVID-19 infection in patients followed for rare autoimmune diseases as well as the predictors of COVID-19 and disease flare-ups. METHODS: Cross-sectional phone survey from April 9, 2020, to July 2, 2020, during which patients with autoimmune diseases followed at the National Reference Center for Rare Autoimmune diseases of Strasbourg were systematically contacted by phone and sent a prescription for a SARS-CoV-2 serology. RESULTS: One thousand two hundred thirty-two patients were contacted. One thousand fifty-five patients with a confirmed diagnosis of systemic autoimmune disease were included (4 unreachable, 4 moves abroad, 5 deaths before pandemic, 50 without consent, and 114 without autoimmune disease). Among them, 469 (44.5%) patients were tested for SARS-CoV-2 serology. Thirty-nine patients (7.9%) had SARS-CoV-2 infection (either through chest CT-scan [n = 5], RT-PCR on nasopharyngeal swab [n = 14], or serology [n = 31]) among the 496 who underwent at least one of those 3 diagnosis modalities. Of the 39 proven cases, 33 had clinical manifestations (6 asymptomatic patients were diagnosed through systematic serology testing), 31 were managed by home care, 3 were hospitalized due to a need for oxygenation, two required admission to an intensive care unit, and one died. Among patients with confirmed SARS-CoV-2 infection, reported flares were more frequent than in uninfected patients (26.3% [10/38] vs. 7.0% [32/457], p < 0.0001). Preventive sick leave had no significant impact on the prevalence of SARS-CoV-2 infection (5.8% [3/53]) compared to work continuation (7.6% [30/397], p = 0.64). Overall, the seroprevalence of SARS-CoV-2 was 6.6% (31/469) which was numerically lower to the Grand-Est general population estimated to be 9.0%. CONCLUSIONS: This systematic survey of more than 1000 patients with rare systemic autoimmune diseases reports a low prevalence of proven SARS-CoV-2 infection and very rare severe infections, probably related to good compliance with prophylactic measures in these patients.

IgG4-related disease: an atypical presentation of steroid-responsive renal mass.

IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory disease characterised by dense lymphoplasmacytic infiltration rich in IgG4-positive plasma cells, storiform fibrosis and obliterative phlebitis. Serum IgG4 levels are typically elevated but half of the patients had normal serum IgG4 levels. IgG4-RD represents a spectrum of diseases that involve various organs such as the pancreas, liver, kidneys, and salivary glands often manifesting as diffuse organ enlargement or a mass-like lesion mimicking cancer. An increased incidence of malignancy among patients with IgG4-RD has been reported. Thus, differentiating malignancy from IgG4-RD manifestation is important as the treatment differs. Glucocorticoids are considered first-line therapy and should be started early to prevent fibrosis. Patients usually have an excellent clinical response to steroids, and poor steroid response is indicative of an alternative diagnoses such as malignancy. This case report describes a case of IgG4-RD with renal mass in a young man that resolved with glucocorticoid therapy alone.

Gastric cancer, inflammatory bowel disease and polyautoimmunity in a 17-year-old boy: CTLA-4 deficiency successfully treated with Abatacept.

Gut involvement is frequent in immunologic disorders, especially with inflammatory manifestations but also with cancer. In the last years, advances in functional and genetic testing have improved the diagnostic and therapeutic approach to immune dysregulation syndromes. CTLA-4 deficiency is a rare disease with variable phenotype, ranging from absence of symptoms to severe multisystem manifestations and complications. We describe a rare case of CTLA-4 deficiency in a boy with gastric cancer, very early onset inflammatory bowel disease and polyautoimmunity, the second-ever reported in the literature with the same characteristics. A 17-year-old boy was referred to Bambino Gesù Children's Hospital of Rome, a tertiary care center, for a gastric mass and a long-term history of very early onset inflammatory bowel disease, diabetes mellitus type 1, polyarthritis and psoriasis. Histology of gastric biopsies revealed the presence of neoplastic signet ring cells. Imaging staging showed localized cancer; therefore, the patient underwent subtotal gastrectomy with termino-lateral gastro-jejunal anastomosis. Immunological work up and genetic testing by next-generation sequencing panels for primary immunodeficiencies led to the diagnosis of CTLA-4 deficiency. Good disease control was obtained with the administration of Abatacept. The patient experienced an asymptomatic SARS-CoV-2 infection without any concern. Eighteen months after treatment initiation, the patient is alive and well. Immunologic and genetic testing, such as next-generation sequencing, should always be part of the diagnostic approach to patients with complex immune dysregulation syndrome, severe clinical course, poor response to treatments or cancer. The early recognition of the monogenic disease is the key for disease management and targeted therapy.

Autoimmune and Rheumatic Manifestations Associated With COVID-19 in Adults: An Updated Systematic Review.

Background: Numerous cases of the coronavirus disease 2019 (COVID-19) with autoimmune and rheumatic manifestations have been reported. Despite the available reviews that summarized its autoimmune/rheumatic manifestations, a systematic approach is still lacking. Therefore, we conducted a comprehensive systematic review in order to give an overview upon these rare but clinically significant manifestations. Methods: We performed a literature search of PubMed and EMBASE as of October 9, 2020. All articles relevant to either systemic or organ-specific autoimmune and rheumatic manifestations potentially associated with COVID-19 were collected. The reviewed literature were limited to adults ≥18 years. Results: Although most of the existing evidence was based on case reports or case series without a long-term follow-up, a variety of autoimmune/rheumatic manifestations were associated with COVID-19. The manifestations that have a consistent association with COVID-19 include autoimmune cytopenia, cutaneous vasculitis, encephalitis, and Guillain-Barre syndrome. Such association is conflicting as regards to antiphospholipid syndrome, hemophagocytic lymphohistiocytosis, and myasthenia gravis. Conclusion: Our systematic review indicated the potential of the COVID-19 virus to trigger a myriad of autoimmune and rheumatic manifestations, which should be considered amid global efforts to combat COVID-19.

[Immunoendocrinology - issues and challenges of today].

The World Health Organization has declared this century to be the century of autoimmune diseases. These include a whole spectrum of endocrine disorders, with type 1 diabetes mellitus, thyropathies, autoimmune polyglandular syndromes (APS), adrenal insufficiency and others, are among the most severe chronic non-infectious diseases in humans. Both the etiology and pathogenesis of autoimmune endocrinopathies are being actively studied, the concepts of the manifestation and progression of these diseases have already been formed, data on the genetic predisposition to one or another autoimmune damage to the endocrine system organs have been obtained, prenatal diagnosis of APD is being actively developed and introduced, attempts are being made to edit the genome in order to prevent their development. Despite this, there are still enough «white spots¼ in understanding the processes of induction and implementation of the mechanisms of autoimmunity in a particular person. The close connection of the immune and endocrine systems is obvious. The key question is: what is still primary, a genetic predisposition to «breakdown¼ of the immune system, leading to the development of an autoimmune endocrine disease, or some external influence that can cause direct damage to the endocrine organ (up to its destruction), leading in the end to the breakdown of immune tolerance and the launch of a cascade of autoimmune processes that aggravate an endocrine disorder? Modern advances not only in endocrinology, but also in immunology, molecular genetics, cell biology, etc. are absolutely necessary to clarify the relationship of immuno-inflammatory, hormonal and metabolic disorders in the pathogenesis of endocrine diseases at the cellular and molecular level and to develop new methods of prevention, early diagnosis, predicting the course and effectiveness of therapy for autoimmune endocrinopathies.

Risk of death among people with rare autoimmune diseases compared with the general population in England during the 2020 COVID-19 pandemic.

OBJECTIVES: To quantify the risk of death among people with rare autoimmune rheumatic diseases (RAIRD) during the UK 2020 COVID-19 pandemic compared with the general population, and compared with their pre-COVID risk. METHODS: We conducted a cohort study in Hospital Episode Statistics for England from 2003 onwards, and linked data from the NHS Personal Demographics Service. We used ONS published data for general population mortality rates. RESULTS: We included 168 691 people with a recorded diagnosis of RAIRD alive on 1 March 2020. Their median age was 61.7 (IQR 41.5-75.4) years, and 118 379 (70.2%) were female. Our case ascertainment methods had a positive predictive value of 85%. A total of 1815 (1.1%) participants died during March and April 2020. The age-standardized mortality rate (ASMR) among people with RAIRD (3669.3; 95% CI: 3500.4, 3838.1 per 100 000 person-years) was 1.44 (95% CI: 1.42, 1.45) times higher than the average ASMR during the same months of the previous 5 years, whereas in the general population of England it was 1.38 times higher. Age-specific mortality rates in people with RAIRD compared with the pre-COVID rates were higher from the age of 35 upwards, whereas in the general population the increased risk began from age 55 upwards. Women had a greater increase in mortality rates during COVID-19 compared with men. CONCLUSION: The risk of all-cause death is more prominently raised during COVID-19 among people with RAIRD than among the general population. We urgently need to quantify how much risk is due to COVID-19 infection and how much is due to disruption to health-care services.

Systemic diseases and the cornea.

There is a number of systemic diseases affecting the cornea. These include endocrine disorders (diabetes, Graves' disease, Addison's disease, hyperparathyroidism), infections with viruses (SARS-CoV-2, herpes simplex, varicella zoster, HTLV-1, Epstein-Barr virus) and bacteria (tuberculosis, syphilis and Pseudomonas aeruginosa), autoimmune and inflammatory diseases (rheumatoid arthritis, Sjögren's syndrome, lupus erythematosus, gout, atopic and vernal keratoconjunctivitis, multiple sclerosis, granulomatosis with polyangiitis, sarcoidosis, Cogan's syndrome, immunobullous diseases), corneal deposit disorders (Wilson's disease, cystinosis, Fabry disease, Meretoja's syndrome, mucopolysaccharidosis, hyperlipoproteinemia), and genetic disorders (aniridia, Ehlers-Danlos syndromes, Marfan syndrome). Corneal manifestations often provide an insight to underlying systemic diseases and can act as the first indicator of an undiagnosed systemic condition. Routine eye exams can bring attention to potentially life-threatening illnesses. In this review, we provide a fairly detailed overview of the pathologic changes in the cornea described in various systemic diseases and also discuss underlying molecular mechanisms, as well as current and emerging treatments.

The risk for severe COVID 19 in patients with autoimmune and/or inflammatory diseases: First wave lessons.

Data regarding the risk for severe COVID19 in patients with autoimmune or inflammatory diseases are scarce. To estimate the risk of those patients to develop a more severe COVID19 infection All active patients and those with dermatologic and/or rheumatologic autoimmune/inflammatory diseases were identified in a single tertiary center. The charts of those tested positive for COVID19 between 1 March 2020 and 31 May 2020 reviewed including demographics, co-morbidities, and medications. COVID19 outcome of those with dermatologic and/or rheumatologic autoimmune/inflammatory diseases were compared to COVID19 infected matched controls without an autoimmune/inflammatory background. Overall, 974 of 381 268 active patients were tested positive for COVID19, including 35 out of 13 225 with dermatologic and/or rheumatologic autoimmune/inflammatory diseases. No statistically significant difference in severity of COVID19 infection or mortality rate was found. The rate of asymptomatic, mild, moderate, severe/critical and fatal COVID19 infection was 11.4%, 37.1%, 22.8%, 11.4%, and 17.1%, respectively, for the patients with autoimmune diseases and 17.8%, 45.8%, 10.9%, 6.8%, and 18.4%, respectively for the controls . Patients with autoimmune/inflammatory diseases seem not to develop a more severe COVID19 infection than controls.

COVID-19 and Autoimmune Diseases: A Systematic Review of Reported Cases.

INTRODUCTION: Over 4.9 million cases of Coronavirus disease 2019 (COVID-19) have been confirmed since the worldwide pandemic began. Since the emergence of COVID-19, a number of confirmed cases reported autoimmune manifestations. Herein, we reviewed the reported COVID-19 cases with associated autoimmune manifestations. METHODS: We searched PubMed database using all available keywords for COVID-19. All related studies between January 1st, 2020 to May 22nd, 2020 were reviewed. Only studies published in English language were considered. Articles were screened based on titles and abstracts. All reports of confirmed COVID-19 patients who have associated clinical evidence of autoimmune disease were selected. RESULTS: Among the 10006 articles, searches yielded thirty-two relevant articles for full-text assessment. Twenty studies has met the eligibility criteria. The twenty eligible articles reported 33 cases of confirmed COVID-19 diagnosis who developed an autoimmune disease after the onset of covid-19 symptoms. Ages of patients varied from a 6 months old infant to 89 years old female (Mean=53.9 years of 28 cases); five cases had no information regarding their age. The time between symptoms of viral illness and onset of autoimmune symptoms ranged from 2 days to 33 days (Mean of the 33 cases=9.8 days). Autoimmune diseases were one case of subacute thyroiditis (3%), two cases of Kawasaki Disease (6.1%), three cases of coagulopathy and antiphospholipid syndrome (9.1%), three cases of immune thrombocytopenic purpura (9.1%), eight cases of autoimmune hemolytic anemia (24.2%), and sixteen cases of Guillain-Barré syndrome (48.5%). CONCLUSION: COVID-19 has been implicated in the development of a range of autoimmune diseases, which may shed light on the association between autoimmune diseases and infections.