Manish Butte

Immune Reconstitution in Pediatric Patients Following Hematopoietic Cell Transplant for Non-malignant Disorders.

Front Immunol. 2020;11:1988

Authors: Bhatt ST, Bednarski JJ

Abstract
Allogeneic hematopoietic cell transplant (HCT) is curative for pediatric patients with non-malignant hematopoietic disorders, including hemoglobinopathies, bone marrow failure syndromes, and primary immunodeficiencies. Early establishment of donor-derived innate and adaptive immunity following HCT is associated with improved overall survival, lower risk of infections and decreased incidence of graft failure. Immune reconstitution (IR) is impacted by numerous clinical variables including primary disease, donor characteristics, conditioning regimen, and graft versus host disease (GVHD). Recent advancements in HCT have been directed at reducing toxicity of conditioning therapy, expanding donor availability through use of alternative donor sources, and addressing morbidity from GVHD with novel graft manipulation. These novel transplant approaches impact the kinetics of immune recovery, which influence post-transplant outcomes. Here we review immune reconstitution in pediatric patients undergoing HCT for non-malignant disorders. We explore the transplant-associated factors that influence immunologic recovery and the disease-specific associations between IR and transplant outcomes.

PMID: 33013851 [PubMed – in process]

Powered by WPeMatico

Chronic rhinitis in South Africa – more than just allergy!

S Afr Med J. 2020 Jul 07;110(7):594-598

Authors: Green RJ, Hockman M, Friedman R, Van Niekerk A, Feldman C, Vardas E, Quitter C, Els C, Van Bruwaene L, Nanan A, Peter J, Seedat RY, Levin M, Bateman On Behalf Of The South African Allergic Rhinitis Working Group Saarwg C

Abstract
Chronic rhinitis is a troublesome condition for sufferers. It is tempting to label all patients with chronic nasal symptoms as having allergic rhinitis (AR), but many such patients have other causes of chronic rhinitis that need a specific diagnosis and management strategy. Even when the patient fully fits the definition of AR, their condition will be best served by combining medication with ongoing patient education.

PMID: 32880327 [PubMed – indexed for MEDLINE]

Powered by WPeMatico

Genetic susceptibility to fungal infection in children.

Curr Opin Pediatr. 2020 Sep 29;:

Authors: Ochoa S, Constantine GM, Lionakis MS

Abstract
PURPOSE OF REVIEW: Fungal infections have steadily increased in incidence, emerging as a significant cause of morbidity and mortality in patients with iatrogenic immunosuppression. Simultaneously, we have witnessed a growing population of newly described inherited immune disorders that have enhanced our understanding of the human immune response against fungi. In the present review, we provide an overview and diagnostic roadmap to inherited disorders which confer susceptibility to superficial and invasive fungal infections.
RECENT FINDINGS: Inborn errors of fungal immunity encompass a heterogeneous group of disorders, some of which confer fungal infection-specific susceptibility, whereas others also feature broader infection vulnerability and/or noninfectious manifestations. Infections by Candida, Aspergillus, endemic dimorphic fungi, Pneumocystis, and dermatophytes along with their organ-specific presentations provide clinicians with important clues in the assessment of patients with suspected immune defects.
SUMMARY: The absence of iatrogenic risk factors should raise suspicion for inborn errors of immunity in children and young adults with recurrent or severe fungal diseases. Expeditious diagnosis and prompt initiation of antifungal therapy and management of complications are paramount to achieve remission of fungal disease in the setting of primary immunodeficiency disorders.

PMID: 33009121 [PubMed – as supplied by publisher]

Powered by WPeMatico

Epstein-Barr virus-related hemophagocytic lymphohistiocytosis complicated with coronary artery dilation and acute renal injury in a boy with a novel X-linked inhibitor of apoptosis protein (XIAP) variant: a case report.

BMC Pediatr. 2020 Oct 02;20(1):456

Authors: Chen RY, Li XZ, Lin Q, Zhu Y, Shen YY, Xu QY, Zhu XM, Bai ZJ, Li Y

Abstract
BACKGROUND: X-linked lymphoproliferative disease (XLP) is a rare inherited X-linked primary immunodeficiency diseases (PID). One such disease, X-linked inhibitor of apoptosis protein (XIAP) deficiency, is characterized by Epstein-Barr virus-related hemophagocytic lymphohistiocytosis (EBV-HLH). However, EBV-HLH with coronary artery dilation and acute renal injury (AKI) in children is unusual.
CASE PRESENTATION: We report the case of a young boy aged 17 months with a novel XIAP variant. He was initially diagnosed with EBV-HLH based on the HLH-2004 diagnostic criteria and the condition was accompanied by coronary artery dilation and acute renal injury. The comprehensive genetic analysis of peripheral blood-derived DNA revealed a hemizygous variant of the XIAP gene [c.116G > C(p.G39A)], which was inherited from his mother (heterozygous condition). After combined treatment with rituximab, intravenous immunoglobulin, corticosteroids, antiviral drugs, and mycophenolate mofetil (MMF) in addition to supportive therapy, his clinical manifestations and laboratory indexes were improved. The patient achieved complete remission with MMF treatment in the 8-month follow-up.
CONCLUSIONS: We report the [c.116G > C(p.G39A)] variant in the XIAP gene for the first time in a case of XLP-2 associated with EBV-HLH. For male patients with severe EBV-HLH, the possibility of XLP should be considered and molecular genetic testing should be used early in auxiliary diagnosis. Reports of EBV-HLH with coronary artery dilation and AKI in children are rare. In the patients with EBV-HLH, color Doppler echocardiography and urine tests should be monitored regularly. If necessary, renal biopsy can be performed to clarify the pathology. Treatment with rituximab, immunosuppressors and supportive therapy achieved a good effect, but long-term follow-up is required.

PMID: 33008347 [PubMed – as supplied by publisher]

Powered by WPeMatico

AA amyloidosis secondary to primary immune deficiency: about 40 cases including 2 new French cases and a systematic literature review.

J Allergy Clin Immunol Pract. 2020 Sep 29;:

Authors: Delplanque M, Galicier L, Oziol E, Ducharme-Bénard S, Oksenhendler E, Buob D, Grateau G, Boutboul D, Georgin-Lavialle S

Abstract
BACKGROUND: Primary immune deficiencies (PID) are a heterogeneous group of disorders resulting from defects in immune system. They lead to increased susceptibility to infections and immune dysregulation. The resulting chronic inflammation can induce long-term complications, including AA amyloidosis (AAA).
OBJECTIVES: To present the French cases of PID-related AAA and perform a systematic literature review to determine its main features and predisposing factors.
METHODS: A systematic literature review was performed by searching MEDLINE up until 2019. New French cases were identified with the help of the Reference Center for Auto-Inflammatory Diseases and AA Amyloidosis (CEREMAIA) and the Reference Center for Hereditary Immune Deficiencies (CEREDIH).
RESULTS: Forty patients were identified including 2 new French cases. PID were varied: immunoglobulin deficits (n=30), chronic granulomatous disease (n=3), Hyper IgM syndrome (n=3), hereditary complete C4 deficiency (n=1), Leucocyte Adhesion Deficiency Type-1 (n=1), Hyper IgE syndrome (n=1) and Chediak-Higashi syndrome (n=1). Mean age at PID diagnosis was 22.2 ± 16.02 years. Renal involvement was the most common manifestation of AAA (80%). Infections were extremely heterogenous; bacterial infection with pulmonary involvement was the most frequent. Bronchiectasis was particularly common (52,5%). The delay between the first symptoms of PID and AAA diagnosis was 16.18 ± 7 years. Thirteen concomitant diagnoses were made. Twenty patients died during follow-up.
CONCLUSION: AAA is a rare life-threatening complication of PID, especially in cases of long diagnostic and therapeutic delays. Bronchiectasis should be considered as a warning sign of chronic inflammation and increased risk of AAA.

PMID: 33007500 [PubMed – as supplied by publisher]

Powered by WPeMatico

Infections in Infants with SCID: Isolation, Infection Screening, and Prophylaxis in PIDTC Centers.

J Clin Immunol. 2020 Oct 02;:

Authors: Dorsey MJ, Wright NAM, Chaimowitz NS, Dávila Saldaña BJ, Miller H, Keller MD, Thakar MS, Shah AJ, Abu-Arja R, Andolina J, Aquino V, Barnum JL, Bednarski JJ, Bhatia M, Bonilla FA, Butte MJ, Bunin NJ, Chandra S, Chaudhury S, Chen K, Chong H, Cuvelier GDE, Dalal J, DeFelice ML, DeSantes KB, Forbes LR, Gillio A, Goldman F, Joshi AY, Kapoor N, Knutsen AP, Kobrynski L, Lieberman JA, Leiding JW, Oshrine B, Patel KP, Prockop S, Quigg TC, Quinones R, Schultz KR, Seroogy C, Shyr D, Siegel S, Smith AR, Torgerson TR, Vander Lugt MT, Yu LC, Cowan MJ, Buckley RH, Dvorak CC, Griffith LM, Haddad E, Kohn DB, Logan B, Notarangelo LD, Pai SY, Puck J, Pulsipher MA, Heimall J

Abstract
PURPOSE: The Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children with severe combined immunodeficiency (SCID) in a prospective natural history study of hematopoietic stem cell transplant (HSCT) outcomes over the last decade. Despite newborn screening (NBS) for SCID, infections occurred prior to HSCT. This study’s objectives were to define the types and timing of infection prior to HSCT in patients diagnosed via NBS or by family history (FH) and to understand the breadth of strategies employed at PIDTC centers for infection prevention.
METHODS: We analyzed retrospective data on infections and pre-transplant management in patients with SCID diagnosed by NBS and/or FH and treated with HSCT between 2010 and 2014. PIDTC centers were surveyed in 2018 to understand their practices and protocols for pre-HSCT management.
RESULTS: Infections were more common in patients diagnosed via NBS (55%) versus those diagnosed via FH (19%) (p = 0.012). Outpatient versus inpatient management did not impact infections (47% vs 35%, respectively; p = 0.423). There was no consensus among PIDTC survey respondents as to the best setting (inpatient vs outpatient) for pre-HSCT management. While isolation practices varied, immunoglobulin replacement and antimicrobial prophylaxis were more uniformly implemented.
CONCLUSION: Infants with SCID diagnosed due to FH had lower rates of infection and proceeded to HSCT more quickly than did those diagnosed via NBS. Pre-HSCT management practices were highly variable between centers, although uses of prophylaxis and immunoglobulin support were more consistent. This study demonstrates a critical need for development of evidence-based guidelines for the pre-HSCT management of infants with SCID following an abnormal NBS.
TRIAL REGISTRATION: NCT01186913.

PMID: 33006109 [PubMed – as supplied by publisher]

Powered by WPeMatico

Update in Primary Immunodeficiencies.

Acta Biomed. 2020 Sep 15;91(11-S):e2020010

Authors: Leonardi L, Rivalta B, Cancrini C, Chiappini E, Cravidi C, Caffarelli C, Manti S, Calvani M, Martelli A, Miraglia Del Giudice M, Duse M, Marseglia GL, Cardinale F

Abstract
Primary immunodeficiencies (PIDs) are inherited disorders classically characterized by increased susceptibility to infections. Nevertheless, in the last two decades, genomic analysis (such as NGS) coupled with biochemical and cellular studies led to a more accurate definition for a growing number of novel genetic disorders associated with PIDs. This revealed new aspects of the immune system and its function and regulation within these diseases. In particular, it has been clarified that the clinical features of PIDs are much broader that originally thought and extend beyond an increased susceptibility to infections. More specifi- cally, immune dysregulation is very often described in novel characterized PIDs and can lead to multiple autoimmune diseases, lymphoproliferation and malignancies. If not promptly diagnosed, these could negatively impact patient’s prognosis. The aim of this review is to increase the awareness of recently discovered PIDs, characterized predominantly by immune dysregulation phenotypes. Findings highlighted in this review  suggest screening for immunodeficiency in patients with lymphoproliferation or early onset/multiple autoimmune diseases. Prompt diagnosis would potentially allow most successful treatment and clinical outcome for patients with PIDs.

PMID: 33004780 [PubMed – in process]

Powered by WPeMatico

Pediatric Recurrent Fever and Autoinflammation from the Perspective of an Allergist/Immunologist.

J Allergy Clin Immunol. 2020 Sep 28;:

Authors: Broderick L, Hoffman HM

Abstract
Autoinflammatory diseases are monogenic and polygenic disorders due to dysregulation of the innate immune system. The inherited conditions have been clustered with primary immunodeficiencies in the latest practice parameters, however, these diseases have unique clinical presentations, genetics and available therapies. Given the presentation of fevers, rashes and mucosal symptoms observed in many of these syndromes, patients are likely to present to an allergist/immunologist. While there has been attention in the literature to diagnosis and treatment of rare, genetically-defined autoinflammatory disorders, physicians are challenged by increasing numbers of patients with intermittent or periodic fevers who face unnecessary morbidities due to a lack of a diagnosis. The broad differential of diseases presenting with fever includes autoinflammatory syndromes, infections associated with immunodeficiency and/or allergies complicated by infection, and less commonly, autoimmune disorders or malignancy. To address this challenge, we review the history of the medical approach to fever, current diagnostic paradigms, and controversies in management. We describe the spectrum of disorders referred to a recurrent fever disorders clinic established in an Allergy/Immunology division at a tertiary pediatric care center. Finally, we provide practical recommendations including historical features and initial laboratory investigations that can help clinicians appropriately manage these patients.

PMID: 33002514 [PubMed – as supplied by publisher]

Powered by WPeMatico

Prospective study of live attenuated vaccines for patients receiving immunosuppressive agents.

PLoS One. 2020;15(10):e0240217

Authors: Kamei K, Miyairi I, Ishikura K, Ogura M, Shoji K, Arai K, Ito R, Kawai T, Ito S

Abstract
Patients receiving immunosuppressive agents are at risk of life-threatening infections. However, live vaccines are generally contraindicated in them. We conducted a prospective study regarding live attenuated vaccines for them. Patients elder than one year of age with immunosuppressive agents who showed negative or borderline antibody titers (virus-specific IgG levels < 4.0) against one or more of measles, rubella, varicella, and mumps and fulfilled the criteria (CD4 cell counts ≥ 500/mm3, stimulation index of lymphocyte blast transformation by PHA ≥ 101.6, serum IgG level ≥ 300 mg/dl, no steroid use or prednisolone < 1 mg/kg/day or < 2 mg/kg/2 days, trough levels of tacrolimus or cyclosporine were < 10 ng/ml or < 100 ng/ml and under good control of primary disease) were enrolled. Sixty-four vaccinations were administered to 32 patients. The seroconversion rates for measles, rubella, varicella, and mumps were 80.0%, 100.0%, 59.1%, and 69.2%, respectively. No life-threatening adverse events were observed, although one patient suffered from vaccine-strain varicella who showed cellular and humoral immunodeficiency (CD4 cell counts = 511/mm3, stimulation index of lymphocyte blast transformation by PHA = 91.1, serum IgG level = 208 mg/dl). This girl was immunized before we established the criteria for vaccination. Immunization with live attenuated vaccines for patients receiving immunosuppressive agents might be effective and safe if their cellular and humoral immunological parameters are within normal levels. However, determining the criteria for vaccination by immunological parameters should be established to guarantee the safety of live vaccines in the future. Clinical Trial Registration: UMIN Clinical Trials Registry (UMIN-CTR) UMIN000007710. The date of registration: 2012/4/13.

PMID: 33002085 [PubMed – as supplied by publisher]

Powered by WPeMatico

Nontraumatic Chylothorax: Nonenhanced MR Lymphography.

Radiographics. 2020 Oct;40(6):1554-1573

Authors: Cholet C, Delalandre C, Monnier-Cholley L, Le Pimpec-Barthes F, El Mouhadi S, Arrivé L

Abstract
Chylothorax is a rare cause of pleural effusion, secondary to accumulation of lymph in the pleural space. Diagnosis is based on the triglyceride and cholesterol content of pleural fluid obtained with thoracentesis. Because the lymphatic system plays an essential role in fat absorption and immune response, lymphatic leak associated with chylothorax may cause life-threatening malnutrition and immunodeficiency. Chylothorax is usually described as traumatic or nontraumatic. The main cause of chylothorax is traumatic, typically postsurgical, secondary to iatrogenic direct puncture of the thoracic duct during thoracic surgery. Causes of nontraumatic chylothorax include a wide range of differential diagnoses. Lymphoma and thoracic malignancies are the most common causes and are responsible for chylothorax by extrinsic compression or invasion of the thoracic duct. Other rare causes include primary and secondary diffuse lymphatic diseases, responsible for chylothorax by lymphatic vessel wall dysfunction. Imaging the lymphatic system remains a challenge in the days of modern imaging. Nonenhanced MR lymphography is a noninvasive technique based on heavily T2-weighted sequences, thus enabling visualization of the lymphatic circulation. This technique allows diagnosis and differential diagnosis, evaluation of disease severity, and guidance of therapeutic management in nontraumatic chylothorax. Furthermore, it may offer radiologic classification of primary lymphatic diseases on the basis of morphologic features of lymphatic vessels. The authors describe the anatomy and physiology of the thoracic lymphatic system, present the technique of nonenhanced MR lymphography, and discuss pathophysiologic mechanisms and imaging features in different causes of nontraumatic chylothorax. ©RSNA, 2020.

PMID: 33001788 [PubMed – as supplied by publisher]

Powered by WPeMatico