BACKGROUND:Despite the overall safety and efficacy of COVID-19 vaccinations, rare cases of systemic autoimmune diseases (SAIDs) have been reported post-vaccination. This study used a global survey to analyze SAIDs in susceptible individuals' post-vaccination. METHODS:A cross-sectional study was conducted among participants with self-reported new-onset SAIDs using the COVID-19 Vaccination in Autoimmune Diseases (COVAD) 2 study dataset-a validated, patient-reported e-survey-to analyze the long-term safety of COVID-19 vaccines. Baseline characteristics of patients with new-onset SAIDs and vaccinated healthy controls (HCs) were compared after propensity score matching based on age and sex in a 1:4 ratio. RESULTS:Of 16 750 individuals, 74 (median age 52 years, 79.9% females, and 76.7% Caucasians) had new-onset SAID post-vaccination, mainly idiopathic inflammatory myopathies (IIMs) (n = 23, 31.51%), arthritis (n = 15; 20.53%), and polymyalgia rheumatica (PMR) (n = 12, 16.40%). Higher odds of new-onset SAIDs were noted among Caucasians (OR = 5.3; 95% CI = 2.9-9.7; p < .001) and Moderna vaccine recipients (OR = 2.7; 95% CI = 1.3-5.3; p = .004). New-onset SAIDs were associated with AID multimorbidity (OR = 1.4; 95% CI = 1.1-1.7; p < .001), mental health disorders (OR = 1.6; 95% CI = 1.3-1.9; p < .001), and mixed race (OR = 2.2; 95% CI = 1.2-4.2; p = .010), where those aged >60 years (OR = 0.6; 95% CI = 0.4-0.8; p = .007) and from high/medium human development index (HDI) countries (compared to very high HDI) reported fewer events than HCs. CONCLUSION:This study reports a low occurrence of new-onset SAIDs following COVID-19 vaccination, primarily IIMs, PMR, and inflammatory arthritis. Identified risk factors included pre-existing AID multimorbidity, mental health diseases, and mixed race. Revaccination was well tolerated by most patients; therefore, we recommend continuing COVID-19 vaccination in the general population. However, long-term studies are needed to understand the autoimmune phenomena arising post-vaccination.

Rheumatoid arthritis has a well-established association with pulmonary manifestations, including pleural effusions. However, only 3-5% of pleural effusions are known to be symptomatic and are frequently unilateral.1 Herein, we present an atypical case of a patient with respiratory failure found to have bilateral pleural effusions as the initial presenting manifestation of rheumatoid arthritis.

Herein, we report a case of a 49-year-old Caucasian man with a medical history of gastroesophageal reflux disease, occasional premature ventricular contractions, and unvaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who presented with myalgias, fevers, and right-sided neck swelling approximately 26 days after he had tested positive for SARS-CoV-2 and 21 days after receiving the casirivimab–imdevimab (REGEN-COV) infusion. His initial workup showed leukocytosis and thrombocytopenia (platelets: 108 × 109/L, reference range [RR]: 150−328 × 109/L). The SARS-CoV-2 rapid antigen-detection test was negative. The patient was started on intravenous antibiotics for presumed lymphadenitis; however, his fevers persisted, with subsequent development of worsening thrombocytopenia at 91 × 109/L and increasing C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), with peak values at 13.4 mg/dL (RR: < 0.8 mg/dL) and 35 mm/1 h (RR: 0−10 mm/1 h), respectively. A few days later, he developed polymorphic ventricular tachycardia causing cardiac arrest. Return of spontaneous circulation was achieved after 5 min. The patient was subsequently admitted to the critical care unit for acute respiratory failure requiring mechanical ventilation, shock requiring multiple pressors, and acute renal failure requiring continuous renal replacement therapy (CRRT). Transthoracic echocardiogram showed severely reduced left ventricular ejection fraction (LVEF) of 20%–25% with multiple regional wall abnormalities. Coronary angiography of the left and right heart showed patent coronaries, increased left ventricular filling pressures, and moderate pulmonary hypertension. A physical exam showed a new erythematous, punctate rash on the right medial thigh (Figure 1A). An extensive infectious workup—including human immunodeficiency virus, syphilis, cytomegalovirus, toxoplasma, respiratory syncytial virus, influenza, hepatitis B virus, hepatitis C virus, typhus, Bartonella serologies, and Histoplasma—was negative. Given the high suspicion for multisystem inflammatory syndrome in adults (MIS-A), as the patient fulfilled the Centers for Disease Control and Prevention (CDC) case definition (unexplained fever unresponsive to antibiotics, neck lymphadenopathy, cardiac dysfunction, lymphopenia, worsening rash, high inflammatory markers 2–6 weeks after initial coronavirus disease 2019 (COVID-19), the patient was started on a 4-day course of intravenous immunoglobulin (IVIG) infusion and methylprednisone. After completion of the first round of IVIG, the patient improved clinically and his fractional inspired oxygen (FiO2) requirement decreased from 100% to 50%, pressors were weaned off, repeat echo showed recovered ejection fraction (EF) > 65%, urine output improved off CRRT, the rash started clearing up (Figure 1B), fever resolved, and inflammatory biomarkers including white blood cell count, CRP, procalcitonin, and interleukin (IL)-6 improved. However, he remained unresponsive off sedation. Head computed tomography (CT) showed diffuse edema suggestive of hypoxic-ischemic injury. Lumbar puncture was performed, and cerebrospinal fluid analysis was negative for central nervous system infection. As MIS-A with extrapulmonary multiorgan involvement is difficult to distinguish with acute biphasic COVID-19 and postacute sequelae of COVID-19 infection,1 repeat COVID-19 polymerase chain reaction was done to rule out biphasic SARS-CoV-2 infection, which was negative. The patient received the second round of IVIG with intravenous methylprednisone. On Day 21, he was started on anakinra (IL-1 inhibitor), with improvement in inflammatory markers, as ESR improved from 91 to 48 mm/1 h, CRP decreased from 1.7 to 1.1 mg/dL, and ferritin decreased from 4360 to 1500 ng/mL (RR: 18.0–464.0 ng/mL). Given worsening platelet counts, we discontinued anakinra after 5 days and it was unclear whether thrombocytopenia was secondary to anakinra or worsening of MIS-A. Clinically, the patient's prognosis remained guarded secondary to hypoxic brain injury and he continued to require intermittent pressor, mechanical ventilation, and CRRT support. The family opted for comfort care and the patient died on hospital Day 28, with presumed cause of death as multiorgan failure secondary to MIS-A. MIS-A is a rare and fatal complication of SARS-CoV-2 infection. The MIS-A is more complex and could be detrimental, as reported in case series by CDC where 37% (10/27) of patients required critical care during hospitalization.2 A systematic review including 221 patients with MIS-A reported 57% of patients (115 of 201) requiring admission to the intensive care unit and death in 7% (15/220) of patients.1 Although the pathophysiology of MIS-A is still poorly understood, it is proposed to be hyperinflammatory response attributed to disrupted immunity1 secondary to autoantibody formation, persistent viral antigen recognition, and viral super antigens.3 Most of the MIS-A cases are reported in unvaccinated patients. A PubMed search for “adult multisystem inflammatory disease, REGEN-COV” only yielded one report.4 There is not enough evidence to support the possibility of aggravation of systemic response in susceptible patients' status post-REGEN-COV infusion. Regardless, our case report reinforces that REGEN-COV infusion does not prevent patients from developing MIS-A in the post-COVID-19 condition. A systemic review concluded fever and rash as the most common presenting symptoms and cardiovascular, gastroenterology, and mucocutaneous as the most commonly involved systems.3 Our patient fulfilled the primary clinical criteria of CDC5 as he developed documented fever before and within his first 3 days of hospitalization, severe cardiac illness, new-onset reduced left ventricular dysfunction (LVEF < 50%), ventricular tachycardia causing cardiac arrest, and rash. He fulfilled the secondary clinical criteria, including diarrhea, thrombocytopenia, and shock, not secondary to medical therapy. Also, he fulfilled the laboratory criteria of a recent positive SARS-CoV-2 test and elevation of inflammatory markers including CRP, procalcitonin, and IL-6. Since no specific guidelines are available regarding definitive treatment of MIS-A, a variety of modalities are used including IVIG, steroids, antibiotics, immunomodulator therapies, aspirin, and anticoagulants as discussed in a systemic review.3 Although our patient showed objective evidence of improvement in symptoms and laboratory markers in response to MIS-A-specific therapies, including IVIG, steroids, and anakinra, his prognosis remained guarded as he was treated with MIS-A-specific therapies later during the disease course after he had cardiac arrest causing hypoxic brain injury. Our patient died on hospital Day 28, with presumed cause of death as multiorgan failure secondary to MIS-A. Mildly elevated D-dimer with normal levels of fibrinogen and prothrombin time (PT)—international normalized ratio (INR) did not meet the laboratory criteria of disseminated intravascular coagulation. In conclusion, this case emphasizes the necessity of keeping MIS-A in differentials during early assessment when evaluating patients with systemic symptoms after a recent SARS-CoV-2 infection despite treatment with monoclonal antibody infusions, so that diagnosis and treatment can be done in a timely manner. Sameen Zafar: Conceptualization; writing—original draft; writing—review and editing. Daniel Gonzalez: writing—original draft; writing—review and editing. Leonard Kuan-Pei Wang: writing—original draft; writing—review and editing. Alexandria Soybel: writing—original draft; writing—review and editing. Emilio B. Gonzalez: Writing—review and editing. Vijaya Murthy: Writing—review and editing. The authors have nothing to report. The authors declare no conflict of interest. All images are obtained with the permission of the patient and family. Written consent was obtained from the patient for participation in research and publication.

Introduction::Multicentric reticulohistiocytosis (MRH) is a rare disease that is known to affect the skin and joints, primarily. It is considered a rare form of non‐Langerhans cell histiocytosis (Group C) that can cause destructive inflammatory arthritis involving both the small and large joints. Cutaneous eruptions of periungual, "coral beads" and nodules appearing over the distal fingers are considered pathognomonic clues for identifying this disorder. Histology evaluation of the cutaneous papules typically shows infiltrative histiocytes and multinucleated giant cells. Although no well‐established therapies exist to date, a variety of immunosuppressants have been used with varying degrees of success.Case Description::A 53‐year‐old Caucasian female patient with a family history of rheumatoid arthritis and a personal history of Sjogren's syndrome presented to the rheumatology clinic complaining of pain in her bilateral hands and fingers. There were several small, papulo‐nodular lesions ranging from 1 to 2 mm in size noted at the base of her nails. A 4 mm punch biopsy of one of the papules from the neck showed dermal infiltration of eosinophilic mononucleated and multinucleated giant cells with "ground glass" appearing cytoplasm consistent with MRH. X‐ray of her hands showed periarticular demineralization and erosions surrounding several bilateral proximal and distal interphalangeal joints, and thus tofacitinib in addition to methotrexate, hydroxychloroquine, and dexamethasone (dosed weekly) was started to help control any further articular damage.Conclusion::Our aim is to further support the relation of MRH with autoimmune diseases, including Sjogren's syndrome. Autoimmune diseases have been reported in association with MRH, although a clear association has yet to be made.

We report the case of a young Hispanic woman who was originally admitted to the emergency department following hypertensive urgency and right-sided blurry vision. The patient did not carry a diagnosis of scleroderma at the time of the visit. However, upon further evaluation, the patient was found to have a scleroderma renal crisis. An angiotensin-converting enzyme (ACE) inhibitor was initiated promptly with subsequent normalization of the blood pressure and creatinine level. Scleroderma renal crisis is a rare, highly feared complication of scleroderma that if left untreated can be life-threatening. Therefore, it is important to identify this condition early and initiate therapy without delay.

Anti-MDA5 (Melanoma differentiation-associated protein 5) myositis is a rare subtype of dermatomyositis (DM) characterized by distinct ulcerative, erythematous cutaneous lesions and a high risk of rapidly progressive interstitial lung disease (RP-ILD). It has been shown that SARS-CoV-2 (COVID-19) replicates rapidly in lung and skin epithelial cells, which is sensed by the cytosolic RNA-sensor MDA5. MDA5 then triggers type 1 interferon (IFN) production, and thus downstream inflammatory mediators (EMBO J 40(15):e107826, 2021); (J Virol, 2021, https://doi.org/10.1128/JVI.00862-21 ); (Cell Rep 34(2):108628, 2021); (Sci Rep 11(1):13638, 2021); (Trends Microbiol 27(1):75–85, 2019). It has also been shown that MDA5 is triggered by the mRNA COVID-19 vaccine with resultant activated dendritic cells (Nat Rev Immunol 21(4):195–197, 2021). Our literature review identified one reported case of MDA5-DM from the COVID-19 vaccine (Chest J, 2021, https://doi.org/10.1016/j.chest.2021.07.646 ). We present six additional cases of MDA5-DM that developed shortly after the administration of different kinds of COVID-19 vaccines. A review of other similar cases of myositis developing from the COVID-19 vaccine was also done. We aim to explore and discuss the evidence around recent speculations of a possible relation of MDA5-DM to COVID-19 infection and vaccine. The importance of vaccination during a worldwide pandemic should be maintained and our findings are not intended to discourage individuals from receiving the COVID-19 vaccine.

Chronic non-healing leg ulcers are often due to peripheral arterial disease, trauma, or neuropathy. In rare cases, it can be due to vasculitis. Here we present a case of a 28-year-old female with a history of rheumatoid arthritis with leg ulcers refractory to standard wound care.