SARS-CoV-2 Infection and Active, Multiorgan, Severe cGVHD After HSCT for Adolescent ALL: More Luck Than Understanding? A Case Report

Graft-vs. -host disease (GvHD) is a serious and complex immunological complication of haematopoietic stem cell transplantation (HSCT) and is associated with prolonged immunodeficiency and non-relapse mortality. Standard treatment of chronic GvHD comprises steroids in combination with other immunosuppressive agents. Extracorporeal photopheresis (ECP), with its immunomodulatory mechanism, is applied as part of steroid-sparing regimens for chronic GvHD. Immunocompromised, chronically ill patients are at particular risk of severe disease courses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. T-cell immunity in SARS-CoV-2 infection is well-described but the role of the humoral immune responses is not fully understood. This case report describes a moderate course of SARS-CoV-2 infection in a patient <9 months after HSCT who was suffering from active, severe, chronic GvHD treated with prednisone and ECP. Following HSCT from a matched unrelated donor to cure acute lymphoblastic leukaemia, the 25-year-old male patient experienced multiple infectious complications associated with cytopenia, B-cell dyshomeostasis and autoantibody production followed by development of severe chronic GvHD thereafter at day +212. The steroid-sparing treatment plan consisted of supportive care, topical treatment, prednisone and ECP. He was diagnosed with SARS-CoV-2 infection at day +252, experiencing loss of smell and taste as well as a cough. The patient's oxygen saturation was between 94 and 97% on room air, and computed tomography images showed evolution of typical of SARS-CoV-2 infiltrates. In addition to cytopenia and immune dyshomeostasis, laboratory tests confirmed macrophage activating syndrome, transaminitis and Epstein-Barr virus viraemia. At that time, anti-SARS-CoV-2 monoclonal antibodies were not available in Austria and remdesivir seemed contraindicated. Surprisingly, despite severe lymphopenia the patient developed SARS-CoV-2-specific antibodies within 15 days, which was followed by clearance of SARS-CoV-2 and EBV with resolution of symptoms. Thereafter, parameters of immune dysregulation such as lymphopenia and B-cell dyshomeostasis, the latter characterised by elevated CD21low B cells and autoantibody expression, normalised. Moreover, we observed complete response of active chronic GvHD to treatment.

Pneumocystis jirovecii Pneumonia in Patients with Rheumatic Diseases: Risk Assessment and Prophylaxis

Pneumocystis jirovecii pneumonia (PJP) is an uncommon opportunistic infection in patients with rheumatic diseases with high mortality. Unlike other non-HIV conditions, international guideline for PJP prophylaxis in rheumatic diseases is currently lacking. Recent evidence regarding the risk of PJP and effectiveness of prophylaxis has been accumulating. This Review provides an update on the information about risk factors associated with PJP in patients with rheumatic diseases based on rheumatic diagnoses, use of immunosuppressive agents and other disease-related factors. The second part of the article summarizes evidence regarding the effectiveness of PJP prophylaxis by considering both disease-related and therapy-related factors. Finally, the Review outlined the currently available disease-specific recommendations and local guidelines, and appreciate the factors that influence physicians’ decision.

The Efficacy of Baricitinib in Real-World Patients with Refractory or Severe Juvenile Dermatomyositis:A Monocentric Retrospective Study

Objective To evaluate the efficacy and safety of low dose baricitinib in children with refractory or severe juvenile dermatomyositis (JDM) in a real-world setting. Methods A monocentric retrospective real-world study was conducted, in which fourteen refractory and one severe newly diagnosed JDM patients were included. These patients were all treated by low dose baricitinib (below the recommended dose) combined with corticosteroids and or immunosuppressive agents. Clinical data were collected at the baseline and 4, 12, 24 weeks after baricitinib implication. Treatment response (complete response (CR), Partial response (PR) and non-response (NR)) was evaluated using both the Paediatric Rheumatology International Trials Organization (PRINTO) remission criteria and skin Disease Activity Score (DAS). All the adverse events (AEs) were recorded. Results After baricitinib treatment, all 15 patients showed improvement of skin involvement, including 14 patients with recurrent skin rashes and one newly diagnosed JDM. Calcinosis stabilized in two patients (2/3) and partially regressed in one. Four patients (4/15) had interstitial lung disease (ILD), which normalized in one, improved in two and stabilized in one. One patient complicated with macrophage activation syndrome (MAS) achieved clinical remission. CR was achieved in 3/15 patients, ranging from 4 to 12 weeks after baricitinib initiation. Five patients (5/15) got PR 4 to 24 weeks after baricitinib use. Daily steroid dosage was decreased from 0.632 mg/kg to 0.357 mg/kg (P = 0.043) at 24 weeks in all responders. However, there was no statistically difference in muscle improvement. One patient was stopped using baricitinib because of varicella zoster virus infection, while no other serious side effect was observed in this study. Conclusion Low dose baricitinib had efficacy and was safe to applied in refractory or severe JDM patients, especially for recurrent skin rashes. Baricitinib may also be helpful for JDM complicated with ILD and MAS.

Idiopathic multifocal choroiditis (MFC): aggressive and prolonged therapy with multiple immunosuppressive agents is needed to halt the progression of active disease. An offbeat review and a case series

Background and purpose Idiopathic multifocal choroiditis (MFC) is part of the group of choriocapillaritis entities. The clinical definition of the disease has evolved with time. The aim of this article was to undertake a review on MFC, on its present-day appraisal and nomenclature and we also report a series of patients with emphasis on the clinical presentation and the importance of vigorous immunosuppressive management. Methods A review of the literature and a retrospective case series study which was performed in the Centre for Ophthalmic Specialised care (COS), Lausanne, Switzerland. Patients diagnosed from 1994 to 2020 with idiopathic multifocal choroiditis (MFC) treated with multiple immunosuppressants were included. Exclusion criteria were insufficient follow up and cases not treated with vigorous immunosuppressive therapy. Imaging analysis included spectral domain optical coherence tomography (SD-OCT) / enhanced depth imaging OCT (EDI-OCT), OCT angiography (OCT-A). Fluorescein and Indocyanine angiography (FA, ICGA) before and after the instauration of treatment. Best corrected visual acuity (BCVA), intraocular pressure (IOP), routine ocular examination, laser flare photometry (LFP) were performed at presentation and follow-up. Immunosuppression comprised at minimum two among the following agents: prednisone, cyclosporine, azathioprine, mycophenolic acid or infliximab. Mean duration of therapy was calculated. Results 26 (52 eyes) of 2102 new patients (1.24%) were diagnosed with MFC. 25 (96%) patients were female and 1 (4%) was male. 43/52 (82%) eyes were myopic with a mean dioptre of − 5.87 ± 2.94, six (12%) eyes were hypermetropic with mean dioptres 2.0 ± 2.68 and three (6%) were emmetropic. 14/52 (27%) eyes had at least 1 anti-VEGF injection because of choroidal neovascularisation (CNVs), 1 eye had a phototherapy laser and 37/52 (71%) had no complication of CNVs during the follow-up. 5/26 (19%) fulfilled the inclusion criteria for our study. Mean age was 26.4 ± 9.3 years. Snellen best corrected visual acuity (BCVA) at presentation was 0.955+/-0.26. Mean follow up was 84+/-55 months. LFP at presentation was 6.34 ± 2.94 ph/ms. None of four patients with prolonged treatment and prolonged follow-up showed disease activity. One patient still under therapy after 4 months’ follow-up still showed an active neovascular membrane. Conclusion Treatment with multiple immunosuppressive agents was shown to stop the progression of the disease.

Multifocal EBV-associated smooth muscle tumors in a patient with cytomegalovirus infection after liver transplantation: a case report from Shiraz, Iran

Introduction Immunodeficient patients, including the recipients of solid organs, exhibit an increase in the incidence of neoplasms. Post-transplant smooth muscle tumor (PTSMT) is a distinct and infrequent entity of these groups of neoplasms. Epstein–Barr virus (EBV) is considered to be involved in the etiology of this neoplasm. Case report A 28-year-old man who underwent liver transplantation presented with abdominal pain and diarrhea for several months. He had a history of resistant systemic cytomegalovirus (CMV) infection after transplantation. Radiologic evaluation and colonoscopy revealed multiple liver, spleen, lung, and colon lesions. Microscopic assessment of colon and liver lesions using IHC study were in favor of spindle cell proliferation with mild atypia and a mild increase in mitotic rate without any necrosis, with features of smooth muscle tumor. Considering the transplantation history, EBER chromogenic in situ hybridization (CISH) study on paraffin blocks was requested, which demonstrated EBV RNA in tumor cell nuclei, suggesting EBV-associated smooth muscle tumor. In addition, PCR for CMV on paraffin blocks was positive. PCR for EBV and CMV viremia were negative. The dosage of immunosuppressive agents was reduced, and currently, he is being followed, with slow expansion in the size of the lesions. Conclusion Although the incidence of post-transplant smooth muscle tumors (PTSMTs) is low, it should be remained in the differential diagnosis in post-transplantation patients, especially dealing with multifocal tumors. As strong stimulant for smooth muscle tumors, close follow-up and screening for EBV and CMV infection and early treatment at the time of diagnosis are recommended to avoid these virus-induced tumors.

Humoral response to SARS-CoV-2 infection among liver transplant recipients

ObjectiveImmunosuppressive agents are known to interfere with T and/or B lymphocytes, which are required to mount an adequate serologic response. Therefore, we aim to investigate the antibody response to SARS-CoV-2 in liver transplant (LT) recipients after COVID-19.DesignProspective multicentre case–control study, analysing antibodies against the nucleocapsid protein, spike (S) protein of SARS-CoV-2 and their neutralising activity in LT recipients with confirmed SARS-CoV-2 infection (COVID-19-LT) compared with immunocompetent patients (COVID-19-immunocompetent) and LT recipients without COVID-19 symptoms (non-COVID-19-LT).ResultsOverall, 35 LT recipients were included in the COVID-19-LT cohort. 35 and 70 subjects fulfilling the matching criteria were assigned to the COVID-19-immunocompetent and non-COVID-19-LT cohorts, respectively. We showed that LT recipients, despite immunosuppression and less symptoms, mounted a detectable antinucleocapsid antibody titre in 80% of the cases, although significantly lower compared with the COVID-19-immunocompetent cohort (3.73 vs 7.36 index level, p<0.001). When analysing anti-S antibody response, no difference in positivity rate was found between the COVID-19-LT and COVID-19-immunocompetent cohorts (97.1% vs 100%, p=0.314). Functional antibody testing showed neutralising activity in 82.9% of LT recipients (vs 100% in COVID-19-immunocompetent cohort, p=0.024).ConclusionsOur findings suggest that the humoral response of LT recipients is only slightly lower than expected, compared with COVID-19 immunocompetent controls. Testing for anti-S antibodies alone can lead to an overestimation of the neutralising ability in LT recipients. Altogether, routine antibody testing against separate SARS-CoV-2 antigens and functional testing show that the far majority of LT patients are capable of mounting an adequate antibody response with neutralising ability.

Transplantation of IPSC-Derived Cardiomyocyte Patches for Ischemic Cardiomyopathy

Background: Despite major therapeutic advances, heart failure remains a life-threatening disorder, with 26 million patients worldwide, causing more deaths than cancer as a non-communicable disease. Therefore, novel strategies for the treatment of heart failure continue to be an important clinical need. Based on preclinical studies, allogenic human-induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) patches have been proposed as a potential therapeutic candidate for heart failure. We report the implantation of allogeneic hiPSC-CM patches in a patient with ischemic cardiomyopathy (ClinicalTrials.gov, #jRCT2053190081). Methods: The patches were produced under clinical-grade conditions and displayed cardiogenic phenotypes and safety in vivo (severe immunodeficient mice) without any genetic mutations in cancer-related genes. The patches were then implanted via thoracotomy into the left ventricle epicardium of the patient under immunosuppressive agents. Results: Positron emission tomography and computed tomography confirmed the possible efficacy and did not detect tumorigenesis in either the heart or other organs; the clinical symptoms improved 6 months after surgery, without any major adverse events, suggesting that the patches were well-tolerated. Furthermore, changes in the wall motion in the transplanted site were recovered, suggesting a favorable prognosis and the potential tolerance to exercise. Conclusions: This study is the first report of a successful transplant of hiPSC-CMs for severe ischemic cardiomyopathy.

Acute Respiratory Distress Syndrome after Rotavirus Infection in a C1q Nephropathy Patient: A Case Report

C1q nephropathy is a rare glomerulopathy that typically presents with nephrotic syndrome in children. Treatment with immunosuppressive agents renders patients vulnerable to infection and its complications. Gastroenteritis is common in children, and rotavirus is a leading cause. Extraintestinal manifestations of rotavirus have recently been reported; however, there is a paucity of cases exploring the involvement of a rotavirus on the respiratory system. Acute respiratory distress syndrome (ARDS) is a rapid onset respiratory failure characterized by noncardiogenic pulmonary edema and hypoxemia. Causes of ARDS include sepsis, pneumonia, pancreatitis, aspiration, and trauma. In this paper, we report a case of ARDS after rotavirus infection in a child with C1q nephropathy who had been treated with immunosuppressive agents.

Rituximab in Remission Induction and Maintenance Therapy for Microscopic Polyangiitis Associated with Gastric Cancer: A Case Report

We herein report a case of a patient with gastric cancer-associated microscopic polyangiitis (MPA) who was treated with combination glucocorticoids and rituximab (RTX) for remission induction and maintenance, and finally to discontinue glucocorticoids without recurrence of gastric cancer or MPA in a year. A 69-year-old man was suspected of having MPA because of fever, high C-reactive protein levels, neuritis, and a high titer of myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA). Upper gastrointestinal endoscopy indicated early-stage gastric cancer, for which he underwent surgery preceded by immunosuppressive therapy for vasculitis. Histopathological images showed vasculitis in the vicinity of the cancerous tissue, suggesting an association between gastric cancer and vasculitis. Postoperatively, fever and inflammatory response improved, but MPO-ANCA increased further and the patient developed alveolar hemorrhage. He resulted in remission with high-dose glucocorticoids and RTX, and he received maintenance therapy with RTX without additional immunosuppressive agents. After 1 year of treatment, he was able to discontinue glucocorticoids without recurrence of gastric cancer or vasculitis. There is no established treatment for malignancy-associated vasculitis other than glucocorticoids. Although more cases need to be accumulated in the future, RTX is expected to be useful in malignancy-associated vasculitis.

Nocardiosis in Japan: a multicentric retrospective cohort study

Background Nocardia species cause a broad spectrum of infections, especially in immunocompromised patients. Given its relative rarity, data on the prognosis and distribution of nocardiosis from a large cohort are scarce. The present study aimed to scrutinize the clinical features and outcomes of nocardiosis in Japan, including one-year mortality and microbiological data. Methods The present, multicentric, retrospective cohort study enrolled patients aged ≥ 18 years with nocardiosis diagnosed between January 2010 and December 2017 and recorded their clinical and microbiological characteristics. Factors associated with one-year mortality were also determined using Cox proportional hazard analysis. Results In total, 317 patients were identified at 89 hospitals. Almost half (155/317, 48.9%) were receiving immunosuppressive agents, and 51 had disseminated nocardiosis (51/317, 16.1%). The one-year, all-cause mortality rate was 29.4% (80/272; lost to follow-up, n = 45). The most frequently isolated species was Nocardia farcinica (79/317, 24.9%) followed by the N. nova complex (61/317, 19.2%). Selected antimicrobial agents were generally effective, with linezolid (100% susceptibility [S]) and amikacin (94% S) having the most activity against Nocardia species. In Cox proportional hazard analysis, factors independently associated with one-year mortality were a Charlson Comorbidity Index score ≥ 5 (adjusted hazard ratio [aHR], 3.61; 95% confidence interval [CI], 1.95-6.71, P < 0.001) and disseminated nocardiosis (aHR, 1.79; 95%CI, 1.01-3.18, P = 0.047). Conclusions The presence of advanced comorbidities and disseminated infection, rather than variations in antimicrobial therapy or Nocardia species, were independently associated with one-year mortality.