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Objectives Autoantibody seroconversion has been extensively studied in the context of COVID-19 infection but data regarding post-vaccination autoantibody production is lacking. Here we aimed to determine the incidence of common autoantibody formation following mRNA COVID-19 vaccines in patients with inflammatory arthritis (IA) and in healthy controls. Methods Autoantibody seroconversion was measured by serum ELISA in a longitudinal cohort of IA participants and healthy controls before and after COVID-19 mRNA-based immunization. Results Overall, there was a significantly lower incidence of ANA seroconversion in participants who did not contract COVID-19 prior to vaccination compared with those who been previously infected (7.4% vs 24.1%, P = 0.014). Incidence of de novo anti-CCP seroconversion in all participants was low at 4.9%. Autoantibody levels were typically of low titre, transient, and not associated with increase in IA flares. Conclusions In both health and inflammatory arthritis, the risk of autoantibody seroconversion is lower following mRNA-based immunization than following natural SARS-CoV-2 infection. Importantly, seroconversion does not correlate with self-reported IA disease flare risk, further supporting the encouragement of mRNA-based COVID-19 immunization in the IA population.

Dermatomyositis (DM) and alopecia areata are two diseases characterised by aberrant interferon signalling. While patchy alopecia of the scalp is a known feature of DM, alopecia universalis, which involves hair loss over the entire body, has rarely been reported in conjunction with DM. Herein, we report the case of a 30-year-old female with DM who developed refractory cutaneous disease and alopecia universalis that were successfully treated with tofacitinib. This could suggest that concomitant severe alopecia and refractory cutaneous DM may reflect a strong baseline interferon gene signature that may predict responsiveness to janus kinase inhibitors.

Summary Background Patients with systemic lupus erythematosus (SLE) are at risk of developing COVID-19 due to underlying immune abnormalities and regular use of immunosuppressant medications. We aimed to evaluate the presence of SARS-CoV-2 IgG antibodies in patients with SLE with or without previous COVID-19-related symptoms or RT-PCR-confirmed SARS-CoV-2 infection. Methods For this analysis, we included patients with SLE from two cohorts based in New York City: the Web-based Assessment of Autoimmune, Immune-Mediated and Rheumatic Patients during the COVID-19 pandemic (WARCOV) study; and the NYU Lupus Cohort (a prospective registry of patients at NYU Langone Health and NYC Health + Hospitals/Bellevue). Patients in both cohorts were tested for SARS-CoV-2 IgG antibodies via commercially available immunoassays, processed through hospital or outpatient laboratories. Patients recruited from the NYU Lupus Cohort, referred from affiliated providers, or admitted to hospital with COVID-19 were tested for SARS-CoV-2 IgG antibodies as part of routine surveillance during follow-up clinical visits. Findings 329 patients with SLE were included in this analysis, 146 from the WARCOV study and 183 from the NYU Lupus Cohort, and were tested for SARS-CoV-2 antibodies between April 29, 2020, and Feb 9, 2021. 309 (94%) were women and 91 (28%) were of Hispanic ethnicity. 51 (16%) of 329 patients had a positive SARS-CoV-2 IgG antibody test. Seropositive patients were more likely than seronegative patients to be Hispanic (24 [47%] of 51 vsz 67 [24%] of 278). Other demographic variables, SLE-specific factors, and immunosuppressant use were not associated with SARS-CoV-2 positivity. Of the 29 patients with COVID-19 previously confirmed by RT-PCR, 18 (62%) were on immunosuppressants; 24 (83%) of 29 patients tested positive for SARS-CoV-2 IgG antibodies. Of 17 patients who had symptoms of COVID-19 but negative concurrent RT-PCR testing, one (6%) developed an antibody response. Of 26 patients who had COVID-19-related symptoms but did not undergo RT-PCR testing, six (23%) developed an antibody response. Of 83 patients who had no symptoms of COVID-19 and no RT-PCR testing, four (5%) developed an antibody response. Among 36 patients who were initially SARS-CoV-2 IgG positive, the majority maintained reactivity serially (88% up to 10 weeks, 83% up to 20 weeks, and 80% up to 30 weeks). Seven (70%) of ten patients with confirmed COVID-19 had antibody positivity beyond 30 weeks from disease onset. Interpretation Most patients with SLE and confirmed COVID-19 were able to produce and maintain a serological response despite the use of a variety of immunosuppressants, providing reassurance about the efficacy and durability of humoral immunity and possible protection against re-infection with SARS-CoV-2. Funding National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, and Bloomberg Philanthropies COVID-19 Response Initiative Grant.

Aberrant epidermal differentiation is a hallmark of inflammatory skin diseases, including psoriasis and atopic dermatitis. If and how differentiated epidermal cells contribute to inflammatory pathology is unclear. In their new article in the Journal of Investigative Dermatology, Shao et al. (2021) report that IRAK2 signaling downstream of IL-1 and IL-36 links epidermal differentiation and skin inflammation.

Immune checkpoint inhibitors (ICIs) are a class of medications targeting mostly the PD-1/PD-L1 and CTLA-4 immune pathways in the treatment of many cancers. Despite the encouraging success of ICIs, they are associated with immune-related adverse events as well as exacerbation of underlying autoimmune conditions. The treatment of these conditions often involves discontinuation of ICI in addition to the utilization of immunomodulatory agents. In this report, we discuss a case in which a patient with metastatic renal cell carcinoma experienced exacerbation of underlying paraneoplastic dermatomyositis after treatment with ICI. He was successfully continued on ICI with the use of intravenous immunoglobulin. The patient experienced adequate control of his myositis but also experienced deepening of his antitumor response.

OBJECTIVE: To characterize the hospitalization and death rates among patients with inflammatory arthritis (IA) affected by coronavirus disease 2019 (COVID-19) and to analyze the associations of comorbidities and immunomodulatory medications with infection outcomes. METHODS: Data on clinical and demographic features, maintenance treatment, disease course, and outcomes in individuals with IA (rheumatoid arthritis and spondyloarthritis) with symptomatic COVID-19 infection were prospectively assessed via web-based questionnaire followed by individual phone calls and electronic medical record review. Baseline characteristics and medication use were summarized for hospitalized and ambulatory patients, and outcomes with the different medication classes were compared using multivariable logistic regression. RESULTS: A total of 103 patients with IA were included in the study (80 with confirmed COVID-19 and 23 with high suspicion of COVID-19). Hospitalization was required in 26% of the participants, and 4% died. Patients who were hospitalized were significantly more likely to be older (P < 0.001) and have comorbid hypertension (P = 0.001) and chronic obstructive pulmonary disease (P = 0.02). IA patients taking oral glucocorticoids had an increased likelihood of being admitted for COVID-19 (P < 0.001), while those receiving maintenance anticytokine biologic therapies did not. CONCLUSION: Among patients with underlying IA, COVID-19 outcomes were worse in those receiving glucocorticoids but not in patients receiving maintenance anticytokine therapy. Further work is needed to understand whether immunomodulatory therapies affect COVID-19 incidence.

Covid-19 in Immune-Mediated Inflammatory Diseases The authors describe patients in New York City with known immune-mediated inflammatory disease in whom Covid-19 developed while they were receiving...

IntroductionPsoriatic arthritis (PsA) is a complex, immune-mediated disease associated with skin psoriasis that, if left untreated, can lead to joint destruction. Up to 30% of patients with psoriasis progress to PsA. In most cases, psoriasis precedes synovio-entheseal inflammation by an average of 5–7 years, providing a unique opportunity for early and potentially preventive intervention in a susceptible and identifiable population. Guselkumab is an effective IL-23p19 inhibitor Food and Drug Administration (FDA)-approved for treatment of moderate-to-severe psoriasis and PsA. The Preventing Arthritis in a Multicentre Psoriasis At-Risk cohort (PAMPA) study aims to evaluate the efficacy of guselkumab in preventing PsA and decreasing musculoskeletal power Doppler ultrasound (PDUS) abnormalities in a population of patients with psoriasis who are at-increased risk for PsA progression.Methods and analysisThe PAMPA study is a multicentre, randomised, double-blind, placebo-controlled, interventional, preventive trial comparing PDUS involvement and conversion to PsA in patients with psoriasis at-increased risk for progression treated with guselkumab compared with non-biological standard of care. The study includes a screening period, a double-blind treatment period (24 weeks) and an open-label follow-up period (72 weeks). At baseline, 200 subjects will be randomised (1:1) to receive either guselkumab 100 mg (arm 1) or placebo switching to guselkumab 100 mg starting at week 24 (arm 2). Arm 3 will follow 150 at-risk psoriasis patients who decline biological therapy and randomisation. Changes from baseline in the PDUS score at week 24 and the difference in proportion of patients transitioning to PsA at 96 weeks will be examined as the coprimary endpoints.Ethics and disseminationEthics approval for this study was granted by the coordinating centre’s (NYU School of Medicine) Institutional Review Board (IRB). Each participating site received approval through their own IRBs. The findings will be shared in peer-reviewed articles and scientific conference presentations.Trial registration numberNCT05004727.

1206 Figure 1SARS-CoV-2 IgG in SLE[Figure omitted. See PDF]ConclusionsMost patients with SLE and confirmed COVID-19 were able to produce a serologic response despite use of a variety of immunosuppressants. These findings provide reassurances regarding the efficacy of humoral immunity and possible reinfection protection in patients with SLE.AcknowledgmentsData presented on behalf of the NYU WARCOV investigators. We thank Leora Horwitz for her assistance with the ICD-10 query at NYU. We also acknowledge Tania Moin and Ranit Shriky for assistance in navigating regulatory matters.

ObjectiveTo investigate the humoral and cellular immune response to mRNA COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment.MethodsEstablished patients at NYU Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunization. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analyzed for humoral response. Cellular immune response to SARS-CoV-2 was further analyzed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany were also analyzed for humoral immune response.ResultsAlthough healthy subjects (n=208) and IMID patients on biologic treatments (mostly on TNF blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, IMID patients do not demonstrate an increase in CD8+ T cell activation after vaccination.ConclusionsIn two independent cohorts of IMID patients, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunization efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines.KEY MESSAGESWhat is already known about this subject?The impact of COVID-19 has been felt across the globe and new hope has arisen with the approval of mRNA vaccines against the SARS-CoV-2. Studies have shown immunogenicity and efficacy rates of over 90% in the immunocompetent adult population. However, there is a lack of knowledge surrounding the response of patients with immune-mediated inflammatory diseases (IMIDs) who may also be on immunomodulatory medications.Patients with IMID have been shown to have attenuated immune responses to seasonal influenza vaccination.What does this study add?This study looks at the humoral and cellular immune response to two doses of BNT162b2 mRNA COVID-19 Vaccine in participants with IMID (on immunomodulators) compared with healthy controls.Individuals with IMID on methotrexate demonstrate up to a 62% reduced rate of adequate immunogenicity to the BNT162b2 mRNA vaccination. Those on anti-cytokine or non-methotrexate oral medications demonstrate similar levels of immunogenicity as healthy controls (greater than 90%).Similarly, vaccination did not induce an activated CD8+ T cell response in participants on background methotrexate, unlike healthy controls and patients with IMID not receiving methotrexate.How might this impact of clinical practice or future developments?These results suggest that patients on methotrexate may need alternate vaccination strategies such as additional doses of vaccine, dose modification of methotrexate, or even a temporary discontinuation of this drug. Further studies will be required to explore the effect of these approaches on mRNA vaccine immunogenicity.

Objective To characterize patients with systemic lupus erythematosus (SLE) affected by coronavirus disease 2019 (COVID-19) and to analyze associations of comorbidities and medications on infection outcomes. Methods Patients with SLE and reverse transcriptase-polymerase chain reaction-confirmed COVID-19 were identified through an established New York University lupus cohort, query of 2 hospital systems, and referrals from rheumatologists. Data were prospectively collected via a web-based questionnaire and review of medical records. Data on baseline characteristics were obtained for all patients with COVID-19 to analyze risk factors for hospitalization. Data were also collected on asymptomatic patients and those with COVID-19-like symptoms who tested negative or were not tested. Statistical analyses were limited to confirmed COVID-19-positive patients. Results A total of 226 SLE patients were included: 41 with confirmed COVID-19, 19 who tested negative for COVID-19, 42 with COVID-19-like symptoms who did not get tested, and 124 who remained asymptomatic without testing. Of the SLE patients with confirmed COVID-19, hospitalization was required in 24 (59%) and intensive care unit-level of care in 4, and 4 died. Hospitalized patients tended to be older, nonwhite, Hispanic, have higher body mas index (BMI), history of nephritis, and at least 1 comorbidity. An exploratory (due to limited sample size) logistic regression analysis identified race, presence of at least 1 comorbidity, and BMI as independent predictors of hospitalization. Conclusion In general, the variables predictive of hospitalization in our SLE patients were similar to those identified in the general population. Further studies are needed to understand additional risk factors for poor COVID-19 outcomes in patients with SLE.

While the success or failure of carpal tunnel release ultimately depends on the interplay of a wide array of factors, a broad understanding of the normal anatomy of the carpal tunnel accompanied by awareness of the possible variations of the individual structures that make up its contents is crucial to optimizing surgical outcomes. While anatomic variants such as extension of the flexor digitorum muscle bellies have been described as a cause of primary carpal tunnel syndrome (CTS), there have been no reports depicting its association with recurrent CTS following initially successful carpal tunnel release, a finding with potentially significant prognostic implications that can aid in operative planning. In such cases where muscle extension is identified preoperatively, careful debulking of the muscle belly may be beneficial in improving long-term surgical outcomes.

Purpose of Review In dermatomyositis (DM), antibodies have been shown to closely correlate with clinical phenotypes. The focus of this review is to describe the known clinical associations of the different antibodies related to DM. Recent Findings The DM-specific antibodies include anti-Mi-2, anti-NXP2, anti-TIF1-gamma, anti-MDA5, and anti-SAE. They present with varying levels of skin, muscle, and other target organ involvement. The anti-synthetase antibodies can present as DM, but define a distinct subset displaying other features known as the anti-synthetase syndrome. Anti-PM/Scl, anti-Ro, anti-RNP, and anti-Ku are myositis-associated antibodies that can present as DM as well as other overlap syndromes. Summary More homogenous subgroups are created by viewing DM through the filter of antibodies. The demonstration of one of these antibodies in a patient suspected of having DM is valuable for informing the diagnosis, prognosis, and treatment of the disease. As antibody testing becomes more widely available, we expect even better characterization of disease and treatment response based on antibody groups to emerge in the coming years.

Giant cell arteritis (GCA) is the most common form of primary vasculitis and it mainly involves large to medium sized vessels. It is also referred to as temporal arteritis as it primarily affects the temporal artery. Ocular involvement frequently occurs in GCA; if not promptly diagnosed, it can cause devastating ocular complications including complete vision loss and permanent blindness. In the majority of cases, it is unilateral; however, there are rare instances where bilateral ocular involvement is reported. In our report, we present the case of a patient presenting with bilateral sudden vision loss associated with GCA.