A Case of X-Linked Moesin-Associated Immune Deficiency in a Pediatric Patient

Background: X-Linked Moesin-Associated Immune Deficiency (X-MAID) is a rare severe combined immunodeficiency (SCID) subtype that can present at any age due to its variability. Depending on severity, patients demonstrate failure to thrive, recurrent bacterial and viral infections, and increased susceptibility to varicella zoster. It has been characterized by marked lymphopenia with hypogammaglobulinemia and impaired T-cell migration and proliferation. Case Presentation: This is a report of a Cuban 7-year-old male with poor weight gain and facial dysmorphia. He had a history of recurrent bacterial gastrointestinal infections and pneumonia beginning at 4 months of age. He additionally had 4-6 upper respiratory tract and ear infections annually. While still living in Cuba, he was admitted for a profound EBV infection in the setting of significant leukopenia. A bone marrow biopsy confirmed no malignancy. After he moved to the United States, his laboratory work-up revealed marked leukopenia with low absolute neutrophil and lymphocyte count with low T and B cells, very low immunoglobulin levels IgG, IgA, and IgM, and poor vaccination responses to streptococcus pneumonia, varicella zoster, and SARS-CoV-2. Genetic testing revealed a missense pathogenic variant c.511C>T (p.Arg171Trp) in the moesin (MSN) gene associated with X-MAID. He was managed with Bactrim and acyclovir prophylaxis, and immunoglobulin replacement therapy, and considered for hematopoietic stem cell transplantation. Discussion(s): Diagnosis of X-MAID should be considered in patients with recurrent infections and profound lymphopenia. As with SCID, early diagnosis and intervention is of utmost importance to prevent morbidity and mortality. This case demonstrates the importance of genetic testing in identifying this disease as it may prompt an immunologist to consider HSCT if conservative management is suboptimal. In the current literature, HSCT appears promising, but the long-term outcomes have yet to be described.Copyright © 2023 Elsevier Inc.

Fulminant varicella infection complicated by disseminated intravascular coagulation following influenza-A case report

Objectives: Varicella is common infectious disease mainly in childhood, usually is a mild, self-limited illness and complications are usually rare. The incubation period for this disease is generally 14- 16 days but may vary from 7 to 21 days. Varicella in the adults with comorbidities or immunosuppressed children may be severe and prolonged with complications. Method(s): A case report of a 6-year-old girl hospitalized for new-onset manifestations of disseminated vesicular exanthema, the manifestations of which occurred mainly on the chest, back, capillitium, oral cavity, and genital area. The child was suffering from abdominal, knee and lumbosacral pain at that time. The patient's history revealed that 10 days prior to the cutaneous manifestations, she had influenza with bronchopneumonia requiring oxygen therapy, steroids and antibiotics. Result(s): The condition progressed within 48 h, complicated by the development of multi-organ failure, coagulopathy with the development of disseminated intravascular coagulopathy over the course of antiviral, antibiotic and antifungal therapy. Laboratory parameters included high elevation of C-reactive protein, il-6, leukocytosis, neutrophilia and highly elevated liver enzymes. Varicella infection was confirmed by detection of herpes zoster virus - polymerase chain reaction (PCR) from vesicles. The patient received intravenous immunoglobulin therapy at a dose of 2 g/L and fresh frozen plasma, thrombocyte concentrate. The girl was intubated with analogization. Laboratory parameters subsequently revealed high anti CoV-2 positivity, high CoV-2 IgG positivity and negative CoV-2 IgM. The patient's condition did not preclude the course of multisystem inflammatory syndrome in children (MIS-C) corticosteroids were added to the treatment at a dose of 1 mg/kg weight. Patient's condition stabilized after 1 month. Discussion(s): Our case report presents an example of fulminant complicated life-threatening course of varicella. Even in common respiratory infections, we must think about the risk and consequences of coinfections and post-infectious complications such as in our case especially influenza and COVID-19.

Correlation between levels of anti-cytokine antibodies, recombination activity of the mutant RAG proteins and clinical phenotype in patients with RAG deficiency

RAG mutations cause various phenotypes: SCID, Omenn syndrome (OS), leaky SCID (LS) and combined immunodeficiency (CID). We had previously reported autoantibodies targeting IFN-alpha, IFN-omega in patients with RAG deficiency. However, how the presence of such antibodies correlated with the severity of the clinical phenotype and with the recombination activity of the mutant proteins was unknown. To address this, we have studied anti-cytokine antibodies in 118 patients with RAG defects (SCID, n = 28;OS, n = 29;LS, n = 29;CID, n = 32), and in 42 controls (protocols NCT03394053 and NCT03610802). RAG mutant proteins associated with CID and LS retained 35.6 +/- 4.3 (mean +/- SE) and 29.8 +/- 5.1% recombination activity respectively, compared to wildtype protein, which was significantly higher than the recombination activity of the mutant RAG proteins associated with OS (4.1 +/- 1.5%) and SCID (5.7 +/- 2.1%) (p < 0.0001). Among 32 CID patients, 24 tested positive for anti-IFN-alpha and 21 for anti-IFN-omega antibodies. Among 29 LS patients, 15 had high levels of anti-IFN-alpha and 13 of anti-IFN-omega antibodies. A minority of the CID and LS patients had also high levels of anti-IFN-beta and anti-IL-22 antibodies. By contrast, none of the OS patients tested positive for anti-cytokine antibodies. High levels of anti-IFN-alpha and anti-IFN-omega antibodies correlated with their neutralizing activity as demonstrated in vitro by analysis of STAT1 phosphorylation upon stimulation of healthy donor monocytes in the presence of the appropriate cytokine and patient's or control plasma. Severe viral infections were recorded in 26/41 patients with CID and LS who tested positive and in 7/20 who tested negative for anti-IFN-alpha and/or anti-IFN-omega antibodies (p <0.05). Among those with anti-IFN antibodies, EBV (n = 8), CMV (n = 6), HSV (n = 5), VZV (n = 4) and adenovirus (n = 4) infections were more common. Two patients had COVID-19, which was fatal in one. Presence of the rubella virus was documented in 5 patients with anti-type I IFN antibodies. These results demonstrate that high levels of neutralizing anti-IFN-alpha and anti-IFN-omega antibodies are common in patients with RAG mutations manifesting as CID and LS, but not in those with OS, and that their presence is associated with a high risk of serious viral infections.Copyright © 2023 Elsevier Inc.

SAFETY ANALYSIS OF JAKINIBS IN REAL CLINICAL PRACTICE IN A COHORT OF 116 PATIENTS

BackgroundJanus kinase inhibitors (JAKinibs) have demonstrated efficacy in the treatment of rheumatoid arthritis (RA) and spondyloarthritis (SpA), although their safety profile continues to be analysed due to the possible increase in adverse events (AEs) in relation to anti-TNFs (mild and severe infections, haematological alterations, thromboembolism, increase in neoplasms).ObjectivesTo evaluate in real clinical practice the AEs of JAKinibs in a cohort of patients with RA and SpA. In addition, adherence and reasons for discontinuation (1st or 2nd failure, AE) are analysed.MethodsObservational study of 116 patients diagnosed with RA or SpA who received treatment with JAKinibis (tofacitinib, baricitinib, upadacitinib) after failure of treatment with different classical synthetic (FAMEsc) or biological (FAMEb) disease-modifying drugs. The following data were analysed: demographic characteristics of the patients, years of disease progression, 1st or 2nd failures and AE.ResultsMean age was 52 years, with Baricitinib being older (60 years -SD 13.6), higher prevalence of females in all groups, and a disease progression time of about 10 years. Mean number of FAMEsc was 1.6 and mean number of FAMEb was 2,3 to Tofacitinib(Tofa), 2,76 to Baricitinib(Bari) and 4,4 to Upadacitinib(Upa). 71 (63%) patients had active corticosteroid therapy. The median treatment time with Tofa was 8.8 months, Bari 9.5 and Upa 2.4 months.Most frequent AEs with Tofa were urinary tract infections(UTI) (11.9%, 7 cases) and headaches (8.47%, 5 cases). There were 3 cases of herpes zoster (5.1%), one of which was recurrent, and 2 cases respectively of tachycardia and gastrointestinal intolerance (3.4%). With Baricitnib, 2(5%) cases of UTI and 2(5%) of influenza A were reported. Most frequent AEs related to Upadacitinb are gastrointestinal intolerance, labialis and facial herpes, anterior uveitis and recurrent UTI, with 1 case for each adverse event. There were 4 success with Baricitinib treatment: 2 due to severe COVID, 1 influenza A and 1 due to stroke. 17 patients had 1st failure to Tofa(28.81%), 8 to Bari20.0%) and 3 to Upa(18.75%);7(11.86%) and 2(5%) patients had 2nd failure to Tofa and Bari respectively, no with Upa.Mean CRP to Tofa-SD 18.9-was 17.19, 20-SD 22.7- to Bari and 24.2-SD 27.40- to Upa. Mean ESR-SD 15.3- was 25.4, -SD 26.4 and 44.3 -SD 32-, respectively. At 6 months, 36(62%) were continuing on Tofa, 22(56%) on Bari and 4(27%) on Upa. At 12 months, 27(46.6%) were still on Tofa and 12 on Bari(30.8%) and no patients were on upa.Table 1.TofaBariUpaMean age496047Male19%18%20%Female81%82%80%Time course of disease(years)81111Permanence 6 months62%56%27%Permanence 12 months46,6%31%0%Patients with corticotherapy62%64%60%Previous biological drugs2,3 SD 22,8 SD 2,34,4 SD 2,9Patients who discontinued the drug62%59%33%Mean CRP at the end of treatment172024Mean end-of-treatment ESR252644Repeated AEsUTI(7) Headache(5) Shingles(3) Nephritic colic(2) Gastrointestinal intolerance(2) Tachycardia(2)UTI(4) Headache(2)Serious AEsShingles (3)Varicella encephalopathy(1) Stroke(1) Shingles (1)1st failure28,8%20%18,7%2nd failure11,9%5%0%SuccessSARS-Cov2(2) Influenza(1) Stroke(1)Figure 1. Months stay pharmacoConclusionMost frequent adverse events with JAKinibs are mild infections, except gastrointestinal complaints with upadacitinib. Serious adverse events, including 3 deaths from viral infections, were observed, mostly in patients over 65 years. Most frequent cause of discontinuation was treatment failure. We believe that further observational studies are needed to stratify and profile the risk of infection with JAKinibs.References[1]Atzeni F, Popa CD, et al. Safety of JAK inhibitors: focus on cardiovascular and thromboembolic events. Expert Rev Clin Immunol. 2022 Mar;18(3):233-244. Doi: 10.1080/1744666X.2022.2039630 Epub 2022 Feb 17.PMID: 35129033[2]Alves C, Penedones A,et al. The Risk of Infections Associated With JAK Inhibitors in Rheumatoid Arthritis: A Systematic Review and Network Meta-analysis. J Clin Rheumatol. 2022 Mar 1;28(2):e407-e414 PMID:33902098Ackn wledgements:NIL.Disclosure of InterestsNone Declared.

Case of mixed viral infection caused by Varicella Zoster and COVID-19 in adolescents.

We report two cases of mixed infection caused by Varicella Zoster and COVID-19 in sibling adolescents. We describe the disease course and provide the results of laboratory examination. High prevalence of these infections necessitates timely verification of the diagnosis and causal therapy. Particular attention should be paid to people with a high risk of pneumonia. Timely vaccination of children against Varicella Zoster and COVID-19 is increasingly important now. The aim of this article is to draw attention to the problem of this coinfection. It allows us to accumulate the data on such cases, identify the risk factors, as well as risk factors for complications.Copyright © 2022, Dynasty Publishing House. All rights reserved.

New definition of RIME: Mucocutaneous eruptions, bullous lesions and multi-mucosal involvement

Objectives: A 14-year-old female patient presents with marked haemorrhagic, adherent crusting of the upper and lower lip and enoral vesicles and erosions. Two weeks before, she had suffered from a respiratory tract infection. She did not take antibiotics but ibuprofen. One week later, she described a swelling and crusting of the upper and lower lips. Urogenital mucosa was also erosive. There was no ocular involvement. Another week later, cocard-like single lesions with partly central blister formation developed. A flaccid blister of 15 mm in diameter was detected in the left ear helix. In total, there was a limited cutaneous involvement of <10% BSA. The girl was admitted to the paediatric clinic. Method(s): Due to mucocutaneous eruptions, bullous lesions and multimucosal involvement, we assumed a Steven-Johnson syndrome or reactive infectious mucocutaneous eruption (RIME). Intravenous rehydration and prophylactic administration of cefotaxime and aciclovir were given. She was balanced and given analgesia with novalgin. The recent increased intake of ibuprofen was discontinued. Local therapy included mometasone cream and serasept dressings. During the inpatient stay, the general condition stabilised and the skin efflorescence's showed a clear regression. Result(s): The microbiological smears for COVID-19, HSV, VZV, mycoplasma, and chlamydia were negative. Discussion(s): As adult classifications for blistering severe cutaneous adverse reactions are limited applicable in children, Ramien et al. proposed revised paediatric-focused clinical criteria 2021. They leave traditional definitions of EEM, SJS and TEN. But they distinguish erythema multiforme (EM) for classic targets with/without mucosal involvement, RIME for cases with mucosal predominance and a respiratory infection trigger, and drug-induced epidermal necrolysis (DEN) for cases caused by medications. (Ramien BJD 2021) There are no current guidelines for RIME therapy. A reasonable management approach includes symptomatic therapy, treatment of identifiable infectious triggers (if possible), consulting urologists, ophthalmologists and gynaecologists (if necessary), immunosuppression, and psychological support. (Ramien ClinExpDermatol 2021).

Impact of Provider Nudges on Herpes Zoster Vaccine Series Completion during the COVID-19 Pandemic in the United States

Objectives: To determine the impact of a pharmacy-based, clinical decision support (CDS) tool on herpes zoster (HZ) vaccine series completion during the initial months of the COVID-19 pandemic across the US. Method(s): In partnership with Kroger Health, a pharmacy CDS tool alerted staff of patients due for their second HZ vaccine dose, which had been accompanied previously by a timed text message. Once operations changed due to COVID-19, the system limited outreach to only patients visiting the pharmacy. Primary outcomes included the proportion of patients receiving both doses within a Kroger-owned pharmacy (n=2,293) and the number of days between doses, both within and across two 32-week periods before and after the pandemic hit the US. Generalized estimating equation-based (GEE) logistic and linear regression models determined differences in completion rates and time to completion. Result(s): During the observation period, 38,937 adults received at least one HZ vaccine dose, with 77.2% receiving both doses. Patients engaged by the CDS tool achieved 80.5% dose completion, versus 65.4% of those not intervened (p<0.0001), which was lower than in the period immediately before the pandemic (85.8%, p<0.0001). The dosing window averaged 119.4 days (SD: 26.91), which was the longest timeframe between doses since the HZ vaccine was launched and nearly one month longer than before the pandemic (93.0 days [SD: 28.02], p<0.0001). The odds of dose completion increased in areas of higher health literacy (OR: 1.01;95% CI: 1.007-1.014), but decreased in areas of higher poverty (OR: 0.992;95% CI: 0.988-0.995). Time to completion was slightly shorter (B=-0.04, p<0.05) in areas of higher health literacy. Conclusion(s): Despite changes in clinical processes, a nationwide community pharmacy was successful in completing HZ vaccine dose series for adults during the pandemic, suggesting that processes in community pharmacies can protect staff while remaining committed to providing preventive health services during public health crises.Copyright © 2023

Retrospective review of vaccination status in patients with newly diagnosed chronic lymphocytic leukaemia

Introduction: Patients with chronic lymphocytic leukaemia (CLL) are at increased risk of infection. CLL is associated with a secondary immunodeficiency and impaired response to vaccination. Recent British Society of Haematology guidelines recommend that patients with CLL should receive vaccination against pneumococcal infection at diagnosis, an annual influenza vaccine and COVID-19 vaccination. Patients aged 70-79 years should also receive the Shingrix vaccine. Patients with CLL should not receive live vaccines. In response to this guideline, a letter detailing vaccination requirements was created for patients to give to their general practitioner (GP). The local process for vaccination referral has since changed. Previously, vaccination requirements were communicated to the GP via letter. There is now a dedicated Vaccination Hub to which clinicians can directly refer patients for appropriate vaccinations. Aim(s): The aim of this project was to assess vaccination referral and vaccination status in patients with newly diagnosed CLL. Method(s): All new diagnoses of CLL from 2021 to 2022 were identified by review of the Haematology Multi-Disciplinary Team meeting electronic registration forms. Electronic patient records were reviewed to determine vaccination referral completion and vaccination status. Result(s): A total of 29 patients were identified as new diagnoses of CLL. Seventeen patients were diagnosed in 2021 and 12 in 2022. Sixty-nine percent of the patients were male and the average age was 70.9 years. Vaccination was discussed with 11 patients (38%) and 10 patients (34%) were referred for vaccination. Eleven patients (38%) had never received a pneumococcal vaccine. Nine patients (31%) had previously received the vaccine but not within the past 5 years. Five patients (17%) patients had received one dose of Pneumovax 23 following referral. No patients had received the initial Prevenar 13 vaccine. Twelve patients (41%) had not received an influenza vaccine. Of those who had received the vaccine, the majority (70%) had received this routinely. Similarly, 71% of patients had received the COVID-19 vaccine routinely as opposed to three patients who received this postreferral. Of those who were eligible, 50% had received the Shingrix vaccine. Conclusion/Discussion: Local rates of vaccination in patients with CLL are low. Numbers were too small to allow for comparison between the methods of referral. Of those referred, not all received the appropriate vaccinations. Further work is therefore required to improve both the number and completion of the referrals. Future steps will include local teaching on vaccinations in CLL and the referral pathway.

Can the COVID-19 Vaccine Cause Recrudescence of Herpes Zoster Virus While Taking Antiviral Medication?

Coronavirus disease 2019 (COVID-19) represents a multisystem disease that has caused a devastating global pandemic. The COVID-19 vaccine produced in response to the pandemic has been effective but can have side effects. One well-established condition is the reactivation of herpes zoster (HZ). Various risk factors increase the risk of HZ reactivation such as age, infections, and immunosuppressed states. HZ can have severe complications, including herpes zoster ophthalmicus and postherpetic neuralgia. Here, we present a unique case where a patient experienced HZ reactivation after both primary doses of the COVID-19 vaccine despite receiving early antiviral treatment.

Real-World Single-Centre Experience of Jak Inhibitor Use in Ra

Background/Aims The use of Janus Kinase Inhibitors (JAKi) has been gradually increasing overtime in the management of rheumatoid arthritis (RA) and other inflammatory arthritis and these appeal to patients. being oral agents. Nevertheless, rheumatologists have become cautious about their use since recent trials have shown safety concerns about VTEs, MACE and malignancies. Methods We decided to study use of JAKi at our centre in Princess of Wales Hospital Bridgend. The aim was to assess whether appropriate patients were selected (considering cautions about MACE, VTEs and malignancies). We also wanted to see whether all patients had required pretreatment safety testing and post-treatment monitoring performed. Results These were 70 patients;59 were females and 11 were males. All of them were diagnosed as RA. Average age was 61.1 years (20-85), average duration of disease 129.9 months (16-340) and average duration of treatment was 58.1 weeks. The most common JAKi being used was baricitinib (84%) followed by tofacitinib (12%) and upadacitinib (4%). 50% patient were on concomitant csDMARDs among whom two-thirds were on methotrexate. Looking at previous biologic use, 9 patients were biologic naive, 22 had one biologic, 15 had two biologics used in the past. All patients were appropriately selected (severe RA and no significant risk factors for MACE, VTEs and malignancies). All patients had pre-treatment Hepatitis B, Hepatitis C, latent TB, FBC and LFTs checked. All patients had FBC and LFTs monitored post treatment. No patient developed VTE, MACE or cancer on treatment. 84.2% patients had lipids tested before starting JAKi. 22.8% patients had abnormal lipids before Rx initiation and 62.5% of these were on lipid lowering Rx. All patients had lipids tested post treatment, but the timing was quite variable and only 62.5% of patients had lipids tested on the recommended time. There were 2 deaths recorded in this cohort. One of those was an 80-year-old RA patient on baricitinib 2mg OD, who died due to chest infection on the background of ILD. He was not on steroids or csDMARDs. The second patient was 63 years' old (on baricitinib 4mg OD), and died due to respiratory sepsis, and was also on azathioprine. She had RA with advanced ILD. The reasons for discontinuing JAKi were inefficacy (46%), side effects (39%) and both inefficacy and side effects (15%). 41.4%of patient experienced side effects due to JAKi. These included infection 28%, deranged lipids 17%, cytopenia 14%, deranged LFTs 14%, GI side effects 10%, skin rash 7% and varicella zoster 3%. Conclusion There has been steady increase in the use of tsDMARDs for RA and other rheumatic conditions. Due to short half-life, these drugs became a popular choice during COVID-19 pandemic but on the other hand safety monitoring became extremely challenging during this time.

Knowledge About Preventive Health Guidelines for Inflammatory Bowel Diseases in Patients: A Quality Improvement Project

Introduction: Preventive care guidelines for patients with Inflammatory Bowel Disease (IBD) emphasize the need for a patient-centered interdisciplinary approach, with assessment and management of the patient's physical and mental health as well as the IBD. There is no data about compliance with current IBD preventive care guidelines in Puerto Rico. This study aims to evaluate current IBD preventive care in the clinic, and knowledge among patients and gastroenterologists about the preventive care guidelines. The 3-phase study includes retrospective medical record review, an anonymous online survey of gastroenterologists, and an anonymous survey of patients. We report the results of the patient survey. Method(s): Adult patients with an established diagnosis of at least 6 months of ulcerative colitis (UC), Crohn's disease (CD) or indeterminate colitis (IC), were recruited from the IBD Clinics and through IBDrelated social media. Questionnaires were filled in the clinic and online using Google forms. Statistical analysis was performed using descriptive statistics. Comparisons of proportions and means between groups was based on Fisher's exact and chi square tests. The study was approved by the MSC IRB. Result(s): 83 patients completed the survey, 42 from the clinics and 41 through social media. 60% had CD, 47.4% were diagnosed more than 10 years ago, 57.9% were younger than 38 years old and 68% were on immunosuppressants/biologics. 83.13% and 60.24% of patients knew that COVID and Influenza vaccines were indicated, respectively. However only 42.17%, 36.14%, 32.53% and 31.33% of patients knew about indications for HPV, pneumococcal, varicella and zoster vaccines, respectively. There was a significant difference about knowledge regarding screening for latent TB (p=0.019), anxiety and depression (p= 0.03) and smoking status (p=0.033) between CD and UC/IC patients, as shown in Table. Conclusion(s): Our study showed a significant lack of knowledge about IBD preventive care in patients. Strategies to improve patient education are needed. The results of the review of records from the clinic as well as the knowledge of gastroenterologists will point out other deficiencies in the healthcare system and help design methods to improve patient care. Another aspect that needs to be explored is access to preventive measures such as vaccines. (Table Presented).

An Emerging Role of Interferon Targeted Therapy in Mucocutaneous Sle: A Prospective Real-World Evaluation of Anifrolumab for Refractory Cutaneous Lupus

Background/Aims Advances in rational drug design and recent clinical trials are leading to emergence of a range of novel therapies for SLE and therapeutic options in clinical practice are expected to broaden rapidly. The optimal real-world place of emerging and established agents will be guided by understanding their differential efficacy on specific SLE manifestations as well as efficacy for more resistant disease. Anifrolumab, a type-I interferon receptor blocking monoclonal antibody, showed efficacy in SLE in phase III trials with a notable effect on mucocutaneous disease although specific lesion subtypes and chroncicity were not explored. Severe refractory mucocutaneous SLE such as scarring discoid lesions are an important and common clinical challenge in current practice. We therefore prospectively evaluated the real-world efficacy and quality of life impact of anifolumab for active mucocutaneous SLE, recalcitrant to multiple biologic and immunosuppressant therapies. Methods Seven patients commenced anifrolumab (300mg by monthly iv infusion) following application to the manufacturer's early access programme (NCT 04750057). Prior biologic therapies were discontinued at least 5 half-lives in advance. Mucocutaneous disease activity was captured by Cutaneous Lupus Disease Area and Severity Index (CLASI) activity score and medical photography. Patient reported health-related quality of life comprising the Dermatology Life Quality Index (DLQI);Lupus-QoL and EQ5D-5L were evaluated at baseline, three and six months. Results Seven female patients with active mucocutaneous SLE (Discoid LE n=5, chilblain LE n=1, subacute cutaneous LE n=1) and median disease duration of 17 years were evaluated. Median baseline CLASI activity score was 17 (range 10-26;higher scores indicating severe disease). Median number of previously failed therapies was 7 and included rituximab in 6/7, belimumab in 2/7 and thalidomide in 4/7. Rapid resolution of scale and erythema in DLE was established within 1 month of anifrolumab treatment. Improvements to chilblain lupus were evident by three months. CLASI activity score was improved >=75% in all patients at 3 months. Clinical responses were associated with significant improvements in DLQI (p<0.001) and EQ5D-VAS (p=0.002) by three months. Lupus-QoL trended toward improvement across all domains but most strongly for fatigue (p=0.01) and pain (p=0.002) by 6 months. One patient discontinued treatment after 4 months due to polydermatomal shingles complicated by sensorineural hearing loss. Infection coincided with background prednisolone dose >15mg daily, recent COVID-19 infection and new on-treatment hypogammaglobulinaemia (IgG <5g/L). Prolonged aciclovir treatment was required for lesion resolution. Conclusion We report rapid real-world efficacy and quality of life impact of anifrolumab on highly refractory mucocutaneous SLE, which exceeded that anticipated from existing clinical trial data. Findings suggest a unique role for emerging interferon targeting therapies in management of mucocutaneous SLE but emphasize need for enhanced VZV precautions among higher risk patients.

Hepatotoxicity From Marijuana Gummies

Introduction: We report a case of drug-induced liver injury (DILI) induced by cannabis gummies containing Corydalis Rhizome. Case Description/Methods: A 37-year-old female presented to her primary care clinic with recurrent fevers, night sweats, and myalgias for 7 weeks accompanied by eye redness, brain fog, headache, nausea, and abdominal pain. She denied rashes, tick-bites, cough, dyspnea, chest pain, joint swelling, or genitourinary symptoms. Past medical history was notable for IBS, migraines, and anxiety. She reported edible marijuana use four times a week, rare alcohol use, and denied tobacco use. She denied a family history of liver disease. Physical exam was notable for tachycardia to 110 and scleral injection with the remainder of vitals and exam unremarkable. Initial labs were notable for AST 61, ALT 44 and CRP of 12. CBC, BMP, urinalysis, ESR, blood cultures, blood smear for parasite screen, tests for Lyme disease, Babesia, Tularemia, Anaplasma, Ehrlichia, Rickettsia, EBV, HIV, RPR, ANA, CMV, parvovirus B19, and chest x-ray were all negative. The patient was referred to infectious disease with further testing for West Nile, Leptospira, lymphocytic choriomeningitis virus, and COVID-19 returning negative. Repeat LFTs showed worsening transaminitis with ALT 979 and AST 712, alkaline phosphatase 88, total bilirubin 0.7, and albumin 4.9. Hepatitis workup including hepatitis A, B, and C, HSV, EBV, VZV serologies, AMA, ASMA, antiLKM Ab, acetaminophen level, INR, iron panel, CPK, TSH, and abdominal ultrasound were all normal. It was later discovered that her marijuana gummies contained Corydalis rhizome extract known to be hepatotoxic. Cessation of this drug was strongly advised. She was discharged with hepatology follow-up and underwent a liver biopsy showing patchy periportal and lobular inflammation with extension across the limiting plate, hepatocyte injury and apoptosis, and increased lipofuscin for age compatible with mild to moderate hepatitis. She had complete recovery after cessation of Corydalis-containing gummies. (Figure) Discussion: Our patient consumed '1906 Midnight', an American cannabis brand containing Corydalis rhizopus 100 mg, advertised to improve sleep, pain, and have a liver protective effect. A Korean systematic review on herbal-induced liver injury reported that Corydalis was the 3rd most frequent causative herb, with 36 cases. Although there are several personal accounts on social networking sites and other websites, there are no American-based publications reported on DILI from Corydalis. (Table Presented).

Overview on Mrna Vaccines Beyond Covid-19

COVID-19 mRNA vaccines: COVID-19 pandemic has made an extraordinary impact on global vaccine technology platform developments. Never in human history have there at least 6 vaccine platforms including: inactivated, protein subunit, VLP and other 3 new platforms i.e., mRNA, viral vector, and DNA, with more than 160 vaccine candidates being developed and tested in clinical trials. Nonetheless, among these several vaccine platforms, mRNA vaccine has been proven to be one of the most effective vaccines against COVID-19. There are two mRNA vaccines authorized for emergency use within a year and currently more than 20 mRNA vaccines are in clinical trials. The main advantages of mRNA vaccines are that they are speedily to design and develop, induce strong antibody and T-cell responses, manufacturing faster and at a lower cost. However, one of the major limitations is that it must be stored in cold temperatures. Currently more than billion doses of COVID-19 mRNA vaccines have been given globally. mRNA vaccines will be a key platform for next pandemics preparedness, it is therefore establishing this platform in various regions and LMICs is critical. Beyond COVID-19: A number of viral and cancer mRNA vaccines have been developing even before COVID-19. At least 12 mRNA vaccines against various infectious diseases are now in clinical evaluation, including Chikungunya virus, Cytomegalovirus, Epstein-Barr virus, Human metapneumovirus and parainfluenza virus type3, HIV, Influenza, Nipah, Rabies, Lasa, RSV, Zika, Varicella-zoster virus. Only few are entering phase 3 such as a CMV vaccine, RSV, seasonal influenza. Current mRNA cancer vaccines development, including brain, breast, melanoma, esophagus, lung, ovarian, prostate and solid tumors. Most are aimed for personalized therapy. By 2023, at least 1 viral mRNA vaccine may get approval, whereas a cancer vaccine might take much longer time. Nevertheless, the remaining challenge at the global level is how to truly overcome the vaccine inequity issues in a sustainable way.Copyright © 2023

An Immunocompetent Adult With Adenovirus Hepatitis

Introduction: In the US there has been a recent outbreak of adenovirus hepatitis in the pediatric population. However, to our knowledge, there has been only one reported case of adenovirus hepatitis in an immunocompetent adult. We have identified another such case. Case Description/Methods: A 25 year old female with no medical history presented with abdominal pain, nausea, vomiting, diarrhea, and subjective fevers for two weeks and was found to have transaminitis 25-30x the upper limit of normal, which were: AST 791, ALT 542, ALP 92, and total bilirubin of 2.9. The patient reported no prior history of liver disease. She denied alcohol, tobacco, illicit drugs, or herbal medications, but did report taking acetaminophen 1500 mg daily for two weeks. Serum acetaminophen levels were normal and serum and urine toxicology were negative. US with doppler was unremarkable, CT showed cholelithiasis, MRCP showed a normal common bile duct without obstructive calculus. Autoimmune causes of hepatitis, ceruloplasmin and alpha-1 antitrypsin were all unremarkable. HAV, HBV, HCV, HDV, HEV, CMV, HSV, VZV, EBV, HIV, and COVID19 were all negative. Ultimately, the serology for adenovirus was positive. After a week of supportive treatment, the patient's labs trended down and symptoms resolved. Discussion(s): Adenovirus is confirmed by a rise in antibody titer or by virus detection. Coagulative necrosis in histopathology is a finding in liver biopsies if they are pursued in unexplained cases of liver injury. Ultimately, adenovirus hepatitis can be diagnosed once all common causes of hepatitis have been excluded. In the current outbreak, only children have been getting adenovirus hepatitis. In adults, a high prevalence of neutralizing antibodies contributes to immunity, and therefore only in immunocompromised states, do adults get such an infection. Supportive care with IV fluids, electrolyte correction, and antiemetics usually is enough with eventual symptomatic and laboratory improvement as it was for our patient. Studies have shown that extensive disease can be treated with antiviral drugs, cidofovir, and ribavirin. Our patient's history of acetaminophen use is a confounder, however, her normal serum level and her symptoms suggestive of an infectious cause made acetaminophen less of a culprit. We hypothesize that our patient's use of acetaminophen when she was initially exposed to the virus is what made her susceptible to developing adenovirus hepatitis and we hope this case adds insight for clinicians dealing with future adult cases.

No Safety Concerns Observed When the Adjuvanted Recombinant Zoster Vaccine (Rzv) and the Covid-19 Mrna-1273 Booster Were Co-Administered in >=50-Year-Olds

Intro: The US CDC recommends that COVID-19 vaccines may be coadministered with other age-appropriate vaccines. There is limited data assessing outcomes, including reactogenicity, on such co-administration. For the first time, we present interim safety data of RZV administered concomitantly or sequentially with an mRNA-1273 booster vaccine. Method(s): In this phase 3, randomized, open-label, multi-center study (NCT05047770), adults aged >=50 years were randomized 1:1 to receive the first RZV dose with mRNA-1273 booster (50 mug) at day 1 and the second RZV dose at week (W)8 (Co-Administration group [Co-Ad]), or mRNA-1273 at day 1, the first RZV dose at W2 and the second RZV dose at W10 (Sequential group [Seq]). Descriptive analyses of solicited/unsolicited adverse events (AEs) with onset within 7/30 days post-mRNA-1273 or first RZV dose, and of serious AEs/potential immune-mediated diseases/AEs of special interest (SAEs/pIMDs/AESIs) reported until database freeze are reviewed. Finding(s): The exposed set comprised 267 (Co-Ad) and 272 (Seq) participants. In each group, most solicited AEs were mild/moderate in intensity and each with <=2.5 days median duration, the most frequent were injection site pain, myalgia, and fatigue. Unsolicited (vaccines-related) AEs were reported by 25.0% (2.9%) of participants post-mRNA-1273 in Seq, 25.2% (0.8%) post-RZV in Seq, and 37.1% (3.7%) in Co-Ad. SAEs/pIMDs/AESIs were reported for 6/1/2 participants in Co-Ad and 5/1/3 in Seq. In Seq, one SAE/AESI (pulmonary embolism) and one pIMD/AESI (cutaneous vasculitis) occurred 2 and 9 days postmRNA-1273 (before RZV administration), respectively, and were considered mRNA-1273-related by investigators. In Co-Ad, one AESI (chronic hepatitis) occurred 35 days post-second RZV dose, considered vaccines-related by Sponsor. No fatalities occurred. Conclusion(s): No safety concerns were identified. The frequency/severity/type of AEs were comparable between groups and consistent with the known safety profile of each vaccine, whether RZV and mRNA-1273 booster were administered concomitantly or sequentially. Co-administration may enhance vaccine coverage rates. Funding(s): GSKCopyright © 2023

Pole-to-pole involvement of varicella zoster virus reactivation following COVID-19 vaccination.

The aim of this study is to report the clinical features, imaging findings including confocal imaging, corneal nerve fiber analysis, and management outcomes in a series of three cases of varicella zoster virus (VZV) reactivation following one dose of coronavirus disease 2019 (COVID-19) vaccination. This was a retrospective and observational study. All the patients who developed uveitis post-vaccination were pooled together. Patients who had VZV reactivation were included. Two cases had polymerase chain reaction positive for VZV from aqueous humor. At the time of presentation, IgG and IgM spike protein antibodies for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were tested. Out of this pool, three patients with classical features to describe pole-to-pole manifestations were chosen. A 36-year-old lady with post-vaccination sclerokeratouveitis associated with reactivation of herpes zoster ophthalmicus, a 56-year-old lady with post-vaccination acute anterior uveitis associated with herpes zoster ophthalmicus, and a 43-year-old gentleman with post-vaccination acute retinal necrosis were included. We present a possible link between anti-SARS-CoV-2 virus vaccination and varicella zoster reactivation in these patients and also describe the clinical features, imaging findings including confocal imaging, corneal nerve fiber analysis, and management with detailed discussion.

Case of mixed viral infection caused by Varicella Zoster and COVID-19 in adolescents.

We report two cases of mixed infection caused by Varicella Zoster and COVID-19 in sibling adolescents. We describe the disease course and provide the results of laboratory examination. High prevalence of these infections necessitates timely verification of the diagnosis and causal therapy. Particular attention should be paid to people with a high risk of pneumonia. Timely vaccination of children against Varicella Zoster and COVID-19 is increasingly important now. The aim of this article is to draw attention to the problem of this coinfection. It allows us to accumulate the data on such cases, identify the risk factors, as well as risk factors for complications.Copyright © 2022, Dynasty Publishing House. All rights reserved.

Disseminated Herpes Zoster During COVID-19.

During the SARS-CoV-2 pandemic, a variety of dermatological conditions were reported by physicians. Given the context, these lesions have been labeled as secondary to SARS-CoV-2 infection. We report the case of a recurrence of herpes zoster in a patient hospitalized with an SARS-CoV-2 infection. The rash occurred on the 15th day of hospitalization while the patient was recovering from a severe form. Local swab showed the presence of varicella-zoster virus within the vesicles. Dermatological symptoms secondary to COVID-19 have been frequently described. This is the first case that demonstrates the recurrence of herpes zoster during a SARS-CoV-2 infection.

Herpes Zoster Ophthalmicus in an Immunocompetent Child With Concurrent COVID-19 Infection: A Case Report and Literature Review.

Herpes zoster ophthalmicus (HZO) is a rare complication of herpes zoster (HZ) that can occur in pediatric patients. It can have significant implications for affected individuals, with the potential for patients to experience ocular complications. Additionally, HZO can have a chronic disease course, requiring long-term treatment in some patients. Following the progression of the COVID-19 pandemic, reports worldwide have identified a potential association between HZO and COVID-19. This case report describes a rare case of a child presenting HZO during a COVID-19 infection.