Efek Obat Imunosupresan Pada Pasien Autoimun dengan COVID-19 (A Scoping Review of The Clinical Evidence)

The main modality in autoimmune disease is a long-term immunosuppressant treatment aiming to control disease progression and increase patient life expectancy. This scoping review aims to evaluate the effect of immunosuppressant treatment in autoimmune patients with COVID-19 on clinical outcomes and disease progression. This scoping review was conducted following the PRISMA extension for scoping review (PRISMA-ScR) guidelines. The Pubmed and Science Direct databases are used to find articles that match the study objectives. Thirteen articles met the inclusion criteria, and all of them were classified as observational studies. Most immunosuppressant treatments are the disease-modifying anti-rheumatic drugs (DMARD) and glucocorticoids. The highest number of autoimmune patients with rheumatoid arthritis (RA) was 43.4%, systemic lupus erythematosus (SLE) 13.6%, and others was 43%. Autoimmune patients with COVID-19 taking immunosuppressant medications, particularly glucocorticoids, significantly increased the risk of hospitalization and the use of ventilators. However, there was no mention of the dosage and duration of immunosuppressant therapy in most of the studies. In general, the use of immunosuppressant drugs was not associated with an increased risk of COVID-19 infection and mortality compared with the general population. Increasing age and comorbidities were associated with poor clinical outcomes. In conclusion, autoimmune patients with COVID-19 who are taking immunosuppressant therapy particularly glucocorticoid exacerbate clinical outcomes. Periodic clinical monitoring and appropriate pharmacological interventions are required in autoimmune patients with COVID-19 to improve clinical outcomes and prevent death.Keywords: Autoimmune, COVID-19, Immunosuppressant, Clinical outcome.

Clarification of Eosinophilic Esophagitis Treatment in the DoD Retention Standards

ABSTRACT The DoD Instruction 6130.03, Volume 2, outlines the retention standards for the U.S. Military, providing guidance on medical conditions and treatments that are disqualifying for all branches of the military. This document states that patients with conditions requiring immunomodulating or immunosuppressant medications do not meet retention standards. Eosinophilic esophagitis is a common, chronic inflammatory disease of the esophagus that typically presents with dysphagia. Although proton pump inhibitors are effective at treating this disease in some cases, swallowed topical steroids are the most frequently used therapy within the DoD. These medications act locally in the esophagus and do not cause systemic side effects typical of oral steroid therapy, including immunosuppression. They are effective at inducing and maintaining disease remission and are generally well tolerated, with minimal side effects. We propose a brief amendment to this document to clarify the language used and avoid inappropriate Medical Evaluation Board referrals.

The use of elexacaftor/tezacaftor/ivacaftor in patients with cystic fibrosis post-liver transplant: a case series

Introduction Cystic fibrosis (CF) related liver disease (CFLD) manifests as a wide spectrum of hepatobiliary disease and can progress to need liver transplantation. Elexacaftor/tezacaftor/ivacaftor (elx/tez/iva) is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator which has superior efficacy compared to previously approved modulators. Use of elx/tez/iva, should be approached with caution in individuals with CFLD or following liver transplantation due to possible increases in LFTs and drug-drug interactions with several immunosuppressant medications. Objective The purpose of this case series was to explore if the use of elx/tez/iva is safe and tolerable in patients with CF post-liver transplantation. Methods A retrospective case series including patients prescribed elx/tez/iva following liver transplantation and an immunosuppressive regimen consisting of drug therapy metabolized by P-glycoprotein was completed. Results Ten patients at six CF centers with a median age of 22.1 years (range 14-43.4 years) and median time from transplant of 6.9 years (range 0.6-22 years) were included. Most patients (8, 80%) received a reduced or full dose of elx/tez/iva for a mean duration of 10.4 months (range 7-12 months). Fluctuations in LFTs occurred in all patients (10, 100%) and led to therapy discontinuation in two patients (20%). Elx/tez/iva initiation resulted in elevations in tacrolimus trough concentration in 7 patients (70%). Most patients who tolerated elx/tez/iva had symptomatic and quality of life improvement, increased body-mass-index, and maintained or improved lung function. Conclusion Initiation of elx/tez/iva in patients with CF who received a liver transplantation may be safe with clinical benefits.

Cardiac transplant recipient with COVID-19 induced acute hypoxic respiratory failure: a case report

Background Heart transplant recipients represent a particularly vulnerable patient population to the novel coronavirus disease 2019 (COVID-19) due to chronic immunosuppression and high rates of comorbidities. Currently, data are limited and evidence to guide management of heart transplant recipients with COVID-19 is sparse. In this case report, we provide a summary of the current literature as well as an in-depth analysis of our clinical decision-making. Case summary A 67-year-old female who underwent cardiac transplantation 1 year prior was found to have acute hypoxic respiratory failure due to COVID-19. Her immunosuppressant medications were modulated with discontinuation of mycophenolate and titration of tacrolimus troughs with a goal of 6–10 ng/dL. She was administered supportive treatment including convalescent plasma, remdesivir, and dexamethasone, in addition to antibiotic treatment that resulted in resolution of her symptoms within a matter of days despite her precarious disposition. Discussion This case demonstrates that it can be safe and efficacious to modulate immunosuppressant medications in cardiac transplant recipients in accordance with recommendations made by the International Society of Heart and Lung Transplantation. This case additionally demonstrates that aspects of the current literature regarding the management of COVID-19 can be safely extrapolated to cardiac transplant recipients. Providing supportive care with dexamethasone, remdesivir, and convalescent plasma as indicated can be beneficial in cardiac transplant recipients; although, the current literature regarding convalescent plasma and remdesivir is conflicting.

Post-Transplant Pregnancy and Contraception

Placed in a historic context, this overview focuses on post-transpant pregnancy, fatherhood, and contraception in women and men. The critical importance of early reproductive counseling because of improved sexual function and the early return of ovulation and menses post-transplant is emphasized. We explain the decision making regarding contraception choices. The available data on the safety of immunosuppressive drugs in pregnancy, and for men desiring fatherhood, are detailed. The risk of maternal ingestion of mycophenolate products on the in utero fetus is considered and contrasted with the lack of concern for their use by men fathering children. Pregnancy risks to the allograft, baby, and mother are discussed. An infant’s exposure to specific immunosuppressant medications through breastfeeding is reviewed. The ethics and realities of post-transplant parenthood are explored.

Challenges in Treating Statin-Associated Necrotizing Myopathy

Myalgia and mild elevation in muscle enzymes are common side effects of statin therapy. While these symptoms are generally self-limited, in rare cases, statin use is associated with an immune-mediated necrotizing myopathy caused by development of autoantibodies against HMG-CoA reductase. The primary presenting symptom of this condition is progressive symmetric proximal weakness that does not abate or worsens even after cessation of statin therapy and is associated with markedly elevated creatine kinase (CK) levels. To date, no randomized controlled trials have been conducted to identify the most effective treatment for statin-associated autoimmune myopathy. Treatment recommendations involve a combination of steroids and immunosuppressive drugs. This single-center case series highlights the clinicopathologic features diagnostic for statin-associated autoimmune myopathy as well as treatment challenges for the patient population. The series highlights a range of potential presentations, from mildly symptomatic despite highly elevated CK, to severe muscle weakness including dysphagia. Multiple patients required several immunosuppressant medications as well as intravenous immunoglobulin (IVIG) to achieve disease control. In this case series, marked improvement was noted in several diabetic patients with IVIG.

A case of Henoch‐Schonlein purpura presenting with pulmonary involvement

Pulmonary involvement in Henoch‐Schonlein purpura (HSP) although rare is an important treatable cause of hospital admission in patients. Its diagnosis is difficult due to the vague symptoms and non-specific radiographic findings. We present one such case of a known case of HSP presenting with pulmonary involvement and treated successfully with steroids and immunosuppressant medications after ruling out all other causes. This particular case could also have an additional component of methotrexate induced lung involvement. Overall it is an interesting case with some much needed learning points.

Patient on Immunomodulatory Therapy Experiencing Joint Pain and Skin Lesions: A Case Report

A woman in her late fifties was admitted to the Family Medicine Inpatient Service directly from Rheumatology clinic for polyarticular pain and erythema with concern for infection. She was taking immunosuppressant medications for a history of multiple autoimmune diseases. Examination showed increasing erythema and tenderness on the upper and lower extremity joints. Histologic evaluation, surgical evaluation, and cultures were consistent with mycobacterium haemophilum infection. Mycobacterium haemophilum is an uncommon opportunistic infection that usually affects immunocompromised patients. The patient was treated with a multi-drug antibiotic regimen for several months due to drug resistance. Although this opportunistic infection is not common it should be considered in the differential of immunocompromised patients with skin and articular symptoms. Treatment outcomes are usually favorable if it caught earlier in the course.

Second-Line Therapy for Immune Thrombocytopenia: Real-World Experience in Canada

BackgroundThe sequence of second-line therapy used for the treatment of immune thrombocytopenia (ITP) is variable. This study aimed to describe the types and sequences of second-line therapies for a large cohort of ITP patients in Canada. MethodsWe completed a retrospective cohort study of the McMaster ITP Registry. We included patients with primary or secondary ITP who had received one or more second-line therapies including any of the splenectomy, rituximab, danazol, dapsone, or thrombopoietin receptor agonists (TPO-RAs), or immunosuppressant medications. Immunosuppressant medications included azathioprine, cyclophosphamide, cyclosporine, or mycophenolate given alone or in combination. ResultsWe identified 204 ITP patients who had received one or more second-line therapies. The most common second-line therapies were immunosuppressant medications (n = 106; 52.0%), splenectomy (n = 106; 52.0%), TPO-RAs (n = 75; 36.8%), danazol (n = 73; 35.8%), and rituximab (n = 67; 32.8%). For patients who received only one second-line therapy (n = 88), the most common treatment was splenectomy (n = 28; 31.8%). For patients who received more than one second-line therapy (n = 116), the most common treatment sequence was splenectomy, followed by immunosuppressant medications (n = 7; 6.0%). Of the 154 evaluable patients at the end of follow-up, 69 (44.8%) achieved a complete platelet count response and 101 (65.5%) achieved a partial response. ConclusionImmunosuppressant medications and splenectomy are commonly used as second-line therapies for ITP in Canada. Treatment choices and the sequence of treatments were variable. RESUME Contexte La séquence de la thérapie de deuxième ligne utilisée pour le traitement de la thrombocytopénie immunitaire (PTI) est variable. Cette étude visait à décrire les types et les séquences des thérapies de deuxième ligne pour une large cohorte de patients atteints de PTI au Canada. MéthodesNous avons réalisé une étude de cohorte rétrospective du registre ITP de McMaster. Nous avons inclus des patients atteints de PTI primaire ou secondaire qui avaient reçu une ou plusieurs thérapies de deuxième ligne, y compris une splénectomie, du rituximab, du danazol, de la dapsone ou des agonistes des récepteurs de la thrombopoïétine (AR-TPO), ou des médicaments immunosuppresseurs. Les médicaments immunosuppresseurs comprennent l’azathioprine, le cyclophosphamide, la cyclosporine ou le mycophénolate, administrés seuls ou en combinaison. RésultatsNous avons identifié 204 patients atteints de PTI qui avaient reçu une ou plusieurs thérapies de seconde ligne. Les thérapies de deuxième ligne les plus courantes étaient les immunosuppresseurs (n = 106; 52.0%), la splénectomie (n = 106; 52.0%), les AR-TPO (n = 75; 36.8%), le danazol (n = 73; 35.8%) et le rituximab (n = 67; 32.8%). Pour les patients qui n’ont reçu qu’un seul traitement de deuxième intention (n = 88), le traitement le plus courant était la splénectomie (n = 28; 31.8%). Pour les patients qui ont reçu plus d’un traitement de deuxième ligne (n = 116), la séquence de traitement la plus courante était la splénectomie, suivie par les médicaments immunosuppresseurs (n = 7; 6.0%). Sur les 154 patients évaluables à la fin du suivi, 69 (44.8%) ont obtenu une réponse complète de la numération plaquettaire et 101 (65.5%) une réponse partielle. ConclusionLes médicaments immunosuppresseurs et la splénectomie sont couramment utilisés comme traitements de deuxième intention pour le PTI au Canada. Les choix de traitement et la séquence des traitements sont variables.

Effect of Revaccination with Recombinant Hepatitis B Virus Vaccine Containing Higher Antigen Concentration in Non-responder Children

BACKGROUND: Hepatitis B is a global health problem carrying significant morbidity and mortality. Vaccination against hepatitis B virus (HBV) has been implemented with good effectiveness, but a small proportion of children do not respond well after complete routine vaccination. They are called non-responders and are at higher risk for HBV infection. AIM: The objective of the study was to determine the effect of revaccination with recombinant HBV vaccine containing higher antigen concentration in non-responder children. METHODS: A prospective study was conducted from January 2018 until December 2019. Inclusion criteria were children aged 9–15 months and had three doses of recombinant HBV at 0, 1, and 6 months old. Exclusion criteria were the presence of acute or chronic hepatitis B and conditions which alter immune function and immunosuppressant medications consumption. Demographic and clinical characteristics were gathered from each subject along with serum HBsAb titer examination. Subjects with serum anti-hepatitis B surface antigen (HBsAb) titer of <10 IU/L were classified into non-responders and underwent revaccination with 3 doses of vaccine containing 20 μg HBsAg. The revaccination series was repeated until all subjects showed seroconversion. After each series, repeated serum HBsAb titer measurements were conducted. RESULTS: A total of 400 children were enrolled in this study with a mean age of 12.1 (SD 2.64) months. Subjects were dominated with females (54.0) and normal nutritional status (79.0). The rate of non-responsiveness was 9.0%. Of all non-responders, 88.9% experienced seroconversion after the first revaccination series. After the third revaccination series, all subjects had serum HBsAb titer at the protective level. CONCLUSION: Revaccination with recombinant HBV vaccine containing higher antigen concentration in non-responder children is effective.