Relapse of cryoglobulinemic vasculitis with new-onset severe renal involvement in two patients following mRNA COVID-19 vaccination: A case report.

RATIONALE: Since mass-scale severe acute respiratory syndrome coronavirus 2 vaccination, there have been case reports of several immune-mediated reactions, including new-onset and flares of glomerular disorders following immunization with mRNA coronavirus disease 2019 vaccines. Here, we report two cases, the first to our knowledge, of relapsing cryoglobulinemic vasculitis with new-onset severe renal involvement following mRNA coronavirus disease 2019 vaccination. PATIENT CONCERNS: The relapse of the cutaneous and the new onset of severe renal involvement of cryoglobulinemic vasculitis occurred three weeks after the second dose of the mRNA Moderna coronavirus disease 2019 vaccination and two days after the first dose of mRNA Pfizer coronavirus disease 2019 vaccination in the first and second patient, respectively. DIAGNOSIS: Kidney biopsies were performed. The first pacient's kidney biopsy showed a membranoproliferative pattern of glomerular injury with extensive mesangial and endocapillary hypercellularity, while severe endothelial swelling, loss of fenestrations and widening of subendothelial space were identified by electron-microscopy. The second patient's kidney biopsy was consistent with cryoglobulin associated membrano-proliferative pattern of glomerular injury. INTERVENTIONS: Our patients were managed with a combination of immunosuppressants consisting of corticosteroids, Cyclophosphamide and Rituximab with a favourable outcome at the end of the induction period. OUTCOMES: Clinical and immunological response was achieved in both patients after four months of follow-up. LESSONS: The temporal association of the relapse of the cryoglobulinemic vasculitis to mRNA coronavirus disease 2019 vaccination suggest that the vaccine might have been a trigger for the reactivation of the disease in our cases. This possible association should be acknowledged by physicians in order to provide optimal monitoring and treatment in case of reactivation of the disease post-immunization.

Upper Gastrointestinal Tract Associated Lesions in Patients with Newly Diagnosed Celiac Disease

(1) Background: Currently available guidelines require upper gastrointestinal (GI) endoscopy with biopsy sampling for adult celiac disease (CD) diagnosis. Based on the pediatric experience, there has been a growing interest if serology-based diagnosis would be possible for adult CD also. Our aim was to analyze the associated upper GI tract lesions in newly diagnosed CD patients, to see if significant associated pathology is detected during index endoscopy, which might impact patient management not related to CD. (2) Methods: We performed a retrospective analysis of newly diagnosed CD cases diagnosed over a period of 7 years (2014–2020). Demographic, clinical, laboratory, endoscopy and histopathology data were collected from the patients’ charts. Diagnosis was set according to ACG Guideline 2013. (3) Results: Altogether 79 patients were recruited for this study purpose, 75.9% female, median age 39 years. All patients had positive CD-specific serology and atrophic mucosal injury in duodenal biopsy samples. Besides villous atrophy, associated endoscopic findings were detected in 42/79 (53.16%) of patients. Most of the gastric lesions were minor endoscopic findings—small sliding hiatal hernias, non-specific chronic gastritis, but we also found two cases of peptic ulcers, one case of metaplastic gastritis, six cases of atrophic gastritis and one subepithelial lesion. Only one patient had changes in the duodenum except CD-related findings—an inflammatory polyp in the duodenal bulb. No malignancies were found. (4) Conclusions: In our cohort, there was a significant number of newly diagnosed CD patients who had associated lesions during the index upper GI endoscopy, but most of them were minor endoscopic findings.

Hydroxychloroquine in systemic lupus erythematosus: overview of current knowledge.

The antimalarial hydroxychloroquine (HCQ) has demonstrated several crucial properties for the treatment of systemic lupus erythematosus (SLE). Herein, we reviewed the main HCQ pharmacologic features, detailed its mechanism of action, and summarized the existing guidelines and recommendations for HCQ use in rheumatology with a systematic literature search for the randomized controlled trials focused on lupus. HCQ has been shown to decrease SLE activity, especially in mild and moderate disease, to prevent disease flare and to lower the long-term glucocorticoid need. The numerous benefits of HCQ are extended to pregnancy and breastfeeding period. Based on cohort studies, antithrombotic and metabolic HCQ's effects were shown, including lipid-lowering properties, which might contribute to an improved cardiovascular risk. Moreover, early HCQ use in antinuclear antibodies positive individuals might delay the progression to SLE. Finally, HCQ has a significant favorable impact on long-term outcomes such as damage accrual and mortality in SLE. Based on these multiple benefits, HCQ is now the mainstay long-term treatment in SLE, recommended by current guidelines in all patients unless contraindications or side effects. The daily dose associated with the best compromise between efficacy and safety is matter of debate. The concern regarding retinal toxicity rather than proper efficacy data is the one that dictated the daily dosage of ⩽5 mg/kg/day actual body weight currently agreed upon.

Physicians' Experience with COVID-19 Vaccination: A Survey Study.

BACKGROUND: COVID-19 vaccine hesitancy remains high in the general population and is the main determinant of low vaccination rates and of the fourth pandemic wave severity in Romania. Additional information is needed to raise awareness over vaccine efficiency and the safety profile. OBJECTIVE: To assess self-reported experience related to COVID-19 vaccination in Romanian physicians. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional, self-administered questionnaire-based survey, distributed online in the period 24 March to 24 May 2021. The survey included 30 cascade questions with skip logic filters. All physicians included filled in the questionnaire voluntarily and anonymously. Not all respondents filled in all questions. Main outcome and measure: Primary outcomes addressed were related to the COVID-19 vaccine safety profile. RESULTS: 407/467 (87.15%) of the respondents' physicians were fully vaccinated, mostly with the Pfizer-BioNTech (Comirnaty)-BNT162b2 vaccine, with the peak of immunization in January 2021, with almost four-fifths of the study participants. Regarding COVID-19, almost 20% physicians had the infection and one declared COVID-19 re-infection. A number of 48/420 (11.42%) and 47/419 (11.22%) of the vaccinated physicians did not report any side effects after the first or second vaccine dose. However, most of the side effects reported were minor. Only 50/360 (13.88%) physicians reported the vaccine side effects on the dedicated online national platform. Approximately 40% respondents checked the anti-spike SARS-CoV2 antibodies' titer after complete vaccination, of which two cases reported indeterminate levels. Lower anti-spike SARS-CoV2 antibodies' titer of 100-1000 times the laboratory limit was more frequent in naive physicians (36.95% versus 14.28%, p = 0.012), moderate titers were similar, while very high levels, more than 10,000 times laboratory limit, were more frequent in physicians with previous COVID-19 infection (2.17% versus 42.85%, p < 0.001). CONCLUSIONS AND RELEVANCE: In this cross-sectional survey study on the COVID-19 vaccination among Romanian physicians, we describe a safety vaccination profile among Romanian physicians.

The impact of the COVID-19 pandemic on patients with primary Sjögren syndrome.

The aim of this study was to investigate the perspective of Romanian patients with Sjögren syndrome (SS) on various aspects of the disease during the SARS-CoV-2 outbreak, including both the impact of COVID-19 on the disease itself as well as the effects of vaccination against SARS-CoV-2 in this group of patients. The study is an online questionnaire-based survey. We received responses from 137 SS patients. Regarding the general emotional status, 33 patients (24.0%) and 47 patients (34.3%) declared to have been sadder/depressive and more agitated/anxious during the SARS-CoV2 outbreak, respectively. During the lockdown, 49 (33.7%) patients strictly and 77 patients (56.2%) did their best to respect the home isolation measures. The income was unchanged for most of the patients (94 patients, 68.6%). Regarding access to healthcare providers, 27 patients (18.7%) postponed the consultation for fear of getting SARS-CoV2. In our study group, 31 patients (22.6%) responded that they have had COVID-19. Only one patient was completely asymptomatic, while the most frequently declared symptom was weakness (84.0%). In 17 patients among the respondents (68%) the symptoms lasted for at least 2 weeks; the most frequent long-lasting symptoms were fatigue (40.0%) and weakness (36.0%). Out of all the respondents, 53 patients (41.4%) were vaccinated against SARS-CoV2 with at least one dose. After the first dose, the most prevalent side effect was pain at the site of injection (89.2%), followed by weakness (25.0%) and myalgias (21.4%). This information will be useful for developing special programs dedicated to SARS-CoV2 infection and vaccination in patients with SS and other autoimmune diseases.

Hydroxychloroquine dans les maladies systémiques et auto-immunes : où en sommes-nous ?

Résumé L’hydroxychloroquine (HCQ), l’un des plus anciens médicaments utilisés en rhumatologie, a récemment été placée sur le devant de la scène comme l’une des thérapies testées dans le contexte de la maladie du syndrome respiratoire aigu sévère à coronavirus 2 (COVID-19). Utilisée dans un premier temps comme antipaludéen puis dans les maladies rhumatismales, l’HCQ a été employée dans diverses affections parmi lesquelles des maladies infectieuses, des troubles de l’immunité, le diabète, la dyslipidémie ou les néoplasies. Sur le plan des maladies systémiques, l’HCQ est le traitement de référence du lupus érythémateux systémique (LES) et les dernières directives européennes préconisent son utilisation chez tous les patients ne présentant pas de contre-indications ou d’effets indésirables. Les effets positifs de l’HCQ dans le LES ont été démontrés pour des critères robustes tels que l’accumulation de dommages, l’activité de la maladie et la survie. Des effets pléiomorphiques ont également été observés : moindre besoin de glucocorticoïdes, risque réduit de lupus néonatal, diminution de la glycémie à jeun et protection contre le diabète, le risque thrombotique, la dyslipidémie, les infections, etc. L’HCQ peut en outre être utilisée pendant la grossesse et l’allaitement. En dehors du LES, le rôle de l’HCQ dans le syndrome des antiphospholipides (SAPL) et le syndrome de Gougerot-Sjögren (SGS) est encore controversé. En revanche, de récentes études n’ont fait apparaître qu’un intérêt limité dans la polyarthrite rhumatoïde, en particulier parce que l’HCQ ne prévient pas les dommages structuraux. Il n’existe pas à ce jour de données solides en faveur de l’utilisation de l’HCQ dans d’autres maladies systémiques. Dans cette revue, nous résumons les données sur l’utilité et l’efficacité de l’HCQ dans différentes affections cliniques pertinentes pour la pratique rhumatologique.

Perceptions of Romanian Physicians on Lockdowns for COVID-19 Prevention.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) was declared a pandemic in March 2020, triggering important changes for the entire society and healthcare systems, as well as significant lockdown measures aimed to limit the disease spread. We herein intended to catch the dynamic of Romanian physicians' perceptions of COVID-19 impact. For this purpose, after a literature review, a 30-item questionnaire was designed. The questionnaire was twice distributed online, about 1 month apart, during which partial relaxation measures were decreed in Romania. The questionnaire was voluntarily filled in by Romanian physicians who were willing to participate in the study. A total of 214 physicians answered the questionnaire upon its first release, and 199 respondents were registered upon its second release, most of whom (94.9%) were involved in clinical work, with one-third working in units dedicated to COVID-19 patients. In parallel with the relaxation of lockdown measures, along with increased confidence in the efficiency of protective measures (46.7% vs. 31.3%), separation from household members decreased from 36.9% to 22.1%. Nevertheless, the feeling of rejection felt by doctors remained similar (22.4% vs. 24.6%). Furthermore, answers regarding the clinical picture, diagnostic approach, and treatment options are discussed. Most of therapeutic options considered for SARS-CoV-2 treatment (e.g., lopinavir/ritonavir, oseltamivir, hydroxychloroquine, azithromycin, tocilizumab, and convalescent plasma) failed to confirm significant efficiency. On the contrary, vaccines for widescale use are already available despite the initial skepticism. In the beginning of the pandemic, 25.2% (18.2% vs. 32.2%) considered that there will not be an effective COVID-19 vaccine, while 41.6% (43.0% vs. 40.2%) thought that a vaccine would be available after at least 12 months. In conclusion, initially, following only a 1 month period, Romanian physicians' intention to consider treatments such as hydroxychloroquine or lopinavir/ritonavir for COVID-19 decreased significantly. Moreover, confidence in the efficiency of available protective measures increased, and the rates of separation from household members decreased.

Hydroxychloroquine in systemic and autoimmune diseases: Where are we now?

Hydroxychloroquine (HCQ), one of the oldest drugs used in rheumatology, came recently into attention as one of the potential therapies tested for the severe acute respiratory syndrome coronavirus-2 disease treatment. Used initially as an antimalarial, then translated to rheumatic diseases, HCQ has been used in a wide range of pathologies, including infectious diseases, immune disorders, diabetes, dyslipidemia, or neoplasia. Regarding systemic diseases, HCQ is the mainstay treatment for systemic lupus erythematosus (SLE), where, according to last European guidelines, it is proposed to all SLE patients unless contraindicated or with side effects. HCQ proved positive impact in SLE on robust outcomes, such as accrual damage, disease activity and survival, but also pleiomorphic effects, including decrease in the need for glucocorticoids, reduction in the risk of neonatal lupus, lower fasting glucose and protection against diabetes, thrombotic risk, dyslipidemia, infections, etc. Moreover, HCQ can be used during pregnancy and breast-feeding. Besides SLE, the role for HCQ in the anti-phospholipid syndrome and Sjögren's disease is still under debate. On the contrary, recent advances showed only limited interest for rheumatoid arthritis, especially due the lack of structural damage prevention. There are still no strong data to sustain the HCQ use in other systemic diseases. In this review, we summarised the utility and efficacy of HCQ in different clinical conditions relevant for rheumatology practice.

Physicians' Perspectives on COVID-19: An International Survey.

Coronavirus disease 2019 (COVID-19) has put a tremendous pressure over health care systems worldwide. Physicians were faced to fight this novel, emerging disease, without evidence-based recommendations. Our aim was to investigate physicians' point of view regarding the new coronavirus disease. We designed an on-line survey with 30 questions to assess physicians' perception of personal impact as well as epidemiology, clinical features, management, and outcome in COVID-19. A total of 194 physicians from 43 countries, of which 42.3% were male, 45.4% had more than 5 years' experience and 10.8% were heads of department/professors, filled-out the questionnaire. Although 47.4% of the physicians were currently treating patients, over 80% thought that they might get in contact with COVID-19 patients. A total of 36.6% physicians thought that they are not and 30.9% were not sure if they were being protected by the ongoing procedures. A total of 21.1% of the doctors felt that they are avoided by the persons with whom they usually interact in daily life and 24.7% were isolated from the household members they usually live with. A total of 72.7% of physicians considered that COVID-19-free patients are currently neglected. The results of the current survey raise awareness about the impact of COVID-19 on physicians' practice.