Multifocal Oral Epstein–Barr Virus-Positive Mucocutaneous Ulcers Associated with Dual Methotrexate and Leflunomide Therapy: A Case Report

Epstein–Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is a unique clinicopathologic entity of lymphoproliferative disorder, occurring in immunosuppressed patients. Due to its rarity, EBVMCU may be under-recognized by clinicians as well as pathologists. In addition, its clinical and histopathologic features overlap with other benign and malignant conditions, making a diagnosis challenging. This report presents an unusual case of multifocal oral EBVMCUs in a 52-year-old female patient with rheumatoid arthritis, receiving the combination of methotrexate and leflunomide for 5 years. The patient presented with persistent multiple large painful ulcers involving her palate and gingiva for 6 months. The histopathologic examination revealed extensive ulceration with diffuse polymorphic inflammatory infiltrate admixed with scattered atypical lymphoid cells showing occasional Hodgkin and Reed/Sternberg-like cell features. These atypical cells showed immunoreactivity for CD20, CD30 and MUM1/IRF4. EBV-encoded small RNA in situ hybridization was positive, validating the presence of EBV-infected cells. Two months after discontinuation of both immunosuppressive medications, oral lesions gradually regressed. At 9-month follow-up, no evidence of relapsing oral EBVMCU has been observed. The multifocal presentation of EBVMCU is rare and could be resulted from the overwhelming immune suppression by long-term use of dual immunosuppressants. Its diagnosis requires comprehensive correlation of patient history, clinical findings, histopathologic, and immunophenotypic features. The ability of EBVMCU to regress following removal of immunosuppressive causes is in drastic contrast to a variety of its potential clinical and histopathologic mimics. Therefore, accurate diagnosis is crucial to avoid unnecessary patient management and achieve optimal patient outcomes.

Delayed Diagnosis: Tuberculous Arthritis of Right Knee Joint in a Patient with Rheumatoid Arthritis

Background. Though skeletal tuberculosis (TB) accounts about 3% of all TB cases, it occupies 10–35% of extrapulmonary TB cases. Common osteoarticular sites involved include the spine (40%), hip (25%), and knee (8%). Co-occurrence of rheumatoid arthritis (RA) and tuberculous arthritis involving peripheral joint is rarely reported in the literature. Case Presentation. We present a case of 42-year-old Sri Lankan-Sinhalese male with right knee joint pain and swelling for one-year duration. This patient had a history of long-standing RA with interstitial lung disease for which he was on multiple immunosuppressive medications including methotrexate, sulfasalazine, leflunomide, mycophenolate mofetil, and prednisolone. His knee joint aspiration fluid was positive for both acid fast bacilli (AFB) and polymerase chain reaction for TB (TB-PCR). He was started on anti-tuberculous chemotherapy. Conclusion. TB should be considered as an important differential diagnosis for chronic mono-arthritis of knee joint with a high degree of suspicion, particularly where TB is endemic.

Immunogenicity, safety and reactogenicity of a heterogeneous booster following the CoronaVac inactivated SARS-CoV-2 vaccine in patients with SLE: a case series

Since the COVID-19 pandemic, CoronaVac, an inactivated SARS-CoV-2 vaccine, has been widely deployed in several countries for emergency use. However, the immunogenicity of the inactivated vaccine was relatively lower when compared to other vaccine types and was even more attenuated in autoimmune patients with rheumatic disease. A third-dose SARS-CoV-2 vaccination in immunosuppressed population is recommended in order to improve immune response. However, the data were limited to those initially received mRNA or viral vector SARS-CoV-2 vaccine. Thus, we aimed to describe the safety, reactogenicity and immunogenicity of patients with systemic lupus erythematosus (SLE) who received a heterogenous booster SARS-CoV-2 vaccine following the initial CoronaVac inactivated vaccine series. Our findings support that the third booster dose of mRNA or viral vector vaccine following the inactivated vaccine is well tolerated and elicited a substantial humoral and cellular immune response in inactive patients with SLE having maintenance immunosuppressive therapy without interruption of immunosuppressive medications.

Strategies to Improve Immune Suppression Post-Liver Transplantation: A Review

Since the first liver transplantation operation (LT) in 1967 by Thomas Starzl, efforts to increase survival and prevent rejection have taken place. The development of calcineurin inhibitors (CNIs) in the 1980s led to a surge in survival post-transplantation, and since then, strategies to prevent graft loss and preserve long-term graft function have been prioritized. Allograft rejection is mediated by the host immune response to donor antigens. Prevention of rejection can be achieved through either immunosuppression or induction of tolerance. This leads to a clinical dilemma, as the choice of an immunosuppressive agent is not an easy task, with considerable patient and graft-related morbidities. On the other hand, the induction of graft tolerance remains a challenge. Despite the fact that the liver exhibits less rejection than any other transplanted organs, spontaneous graft tolerance is rare. Most immunosuppressive medications have been incriminated in renal, cardiovascular, and neurological complications, relapse of viral hepatitis, and recurrence of HCC and other cancers. Efforts to minimize immunosuppression are directed toward decreasing medication side effects, increasing cost effectiveness, and decreasing economic burden without increasing the risk of rejection. In this article, we will discuss recent advances in strategies for improving immunosuppression following liver transplantation.

Tietze syndrome - a case report of 20 year old male patient with steroid induced tinea incognito

Tietze syndrome is a self-limiting, rare and benign condition that might be mistaken with potentially fatal chest diseases and misdiagnosed mostly as costochondritis. This disease is most often diagnosed in young individuals under the age of 40, with painful, localized inflammation.Tinea incognito is a ringworm infection that has been altered by corticosteroids and other immunosuppressive medications. Corticosteroids are administered for pre-existing illness or are used incorrectly for the treatment of tinea. We report a case of 20years old male patient admitted in emergency department with complaints of chest pain and SOB with normal ECG while neutrophils, ESR, CRP have found to be abnormal. Patient has been using steroids and itraconazole for maculopapular rashes in lower limb since 1year. Other diagnostic methods such as CT, MRI should be performed to avoid misdiagnosis. He was prescribed with NSAIDS, antifungals, antihistamines and other supportive measures which helped him to relieve from pain. Proper diagnostic criteria and early diagnosis remain challenging tasks, resulting in undue treatment costs for patients. Before confirming a diagnosis, other underlying diseases should be ruled out.

Surgical Solution for Total Carpectomy due to Destructive Wrist Pan-Osteomyelitis Using a Free Femoral Condyle Osteocutaneous Flap for Wrist Arthrodesis

Osteomyelitis of the hand is rare, even more so in the carpal bones. Patients with rheumatoid arthritis (RA) have a higher infection rate overall, and up to a 14-fold increase in the incidence of septic arthritis of the hand. The destruction of immunologic barriers, such as cartilage and joint capsules, as well as the use of immunosuppressive medications will have an impact on the higher incidence of articular infections and osteomyelitis in these patients. Infection in these cases is often overlooked because of the similarity of presentation to an acute event of RA. When osteomyelitis is present, rapid and aggressive treatment should be given. Surgical debridement, lavage, and excision of necrotic bone is the best choice, followed by cemented antibiotic impregnated spacer to resolve the acute scenario. Vascularized bone grafts (VBG) can then be used for a definitive solution, as these have great biologic properties that increase the possibility of a good outcome. We hereby present a report of a wrist arthrodesis, using a free medial femoral condyle VBG for the treatment of destructive osteomyelitis of the carpal bones in a female patient with RA.

COVID-19 and Alimentary Tract: Current Evidence and Recent Recommendations

The pandemic of coronavirus disease 2019 (COVID-19), first reported in China, in December 2019 and since then the digestive tract involvement of COVID-19 has been progressively described. In this review, I summed recent studies, which have addressed the pathophysiology of COVID-19-induced gastrointestinal symptoms, their prevalence, and bowel pathological and radiological findings of infected patients. The effects of gut microbiota on SARS-CoV-2 and the challenges of nutritional therapy of the infected patients are depicted. Moreover, I provide a concise summary of the recommendations on the management of inflammatory bowel disease, colorectal cancer, and performing endoscopy in the COVID era. Finally, the COVID pancreatic relation was explored. Conclusions: digestive symptoms in COVID-19 patients can be the only manifestation and they may be correlated with worse clinical outcomes. The likelihood of fecal-oral transmission of COVID-19 has significant consequences and requires further research. A clear link may exist between the gut microbiome and COVID-19 progression and it may have a therapeutic and prognostic value. No evidence for an increased frequency of covid-19 cases in IBD and stopping immunosuppressive medications is not advised. Triage and risk assessment of patients with suspected or confirmed COVID-19 before endoscopy is essential; deferral of elective endoscopies should be considered.

Trends in actual medication use for child-onset systemic lupus erythematosus using the Japanese health insurance database 2009–18

ABSTRACT Objectives Immunosuppressive therapy is the mainstay of treatment for child-onset systemic lupus erythematosus (cSLE). Since epidemiological data on Japanese cSLE patients are not available, we evaluated the trends in how treatment choices have changed over time in Japan. Methods Using the Japanese health insurance database provided by Medical Data Vision Co., Ltd, we identified cSLE patients and evaluated changes in the use of corticosteroids and immunosuppressive medications and maximum daily doses of prednisolone from 2009 to 2018. Results Of 182 cSLE patients, 86% were female, and the median age was 14 years. Oral prednisolone was used in more than 97% of cSLE patients during the study period, and the median of the maximum daily dose in each patient decreased over time. Intravenous cyclophosphamide was used less frequently after 2016, while mycophenolate mofetil and hydroxychloroquine were used frequently after 2016. The use of mizoribine reduced after 2014, whereas the other immunosuppressive medications showed no significant change over time; the use of biological agents was very limited. Conclusions Oral prednisolone was the mainstay of treatment for cSLE, and the maximum daily dose has reduced over the past decade. The most frequently prescribed immunosuppressive therapy has shifted to mycophenolate mofetil over time.

Persistent viremia in an immunocompetent patient with inherited chromosomally integrated HHV-6B

Human herpesvirus-6 (HHV-6), the virus which causes roseola, has traditionally been associated with benign and self-limited childhood illness. However, HHV-6 establishes lifelong latency and can reactivate in immunocompromised adult patients. In about 1% of cases, it integrates into the human genome as inherited chromosomally integrated HHV-6 (iciHHV-6). We report the case of a 70-year-old man presenting with altered mental status and agitation. His infectious workup revealed a cerebrospinal fluid sample positive for HHV-6 with virus detectable in the blood as well. He was subsequently treated with ganciclovir. HHV-6 viremia (DNAemia) persisted, and the antiviral medications were switched to foscarnet under the assumption of treatment failure due to drug resistance. After several admissions to the hospital for the same complaint, and after noticing that DNAemia persisted despite adequate treatment for HHV-6, infectious disease specialists ordered testing for chromosomally integrated virus. Test results confirmed the presence of iciHHV-6, explaining his consistently elevated serum viral load. Primary HHV-6 infection in adults causes a transient increase in viral load with resolution and clearance after a few weeks while iciHHV-6 is characterized by persistent detection of viral DNA at a high copy number. Individuals with iciHHV-6 can develop HHV-6 disease and are at increased risk for active viral replication when treated with immunosuppressive medications, but only mRNA testing, which is not widely available can differentiate between latent and active infection. This makes the decision to treat challenging in this patient population. When faced with a positive HHV-6 DNA result in the setting of equivocal symptoms, clinicians should consider the possibility of chromosomally integrated virus rather than drug-resistant virus in order to reduce exposure to potentially toxic antiviral medications.