Manish Butte

Differentiating characteristics and evaluating intravenous and subcutaneous immunoglobulin.

Am J Manag Care. 2019 Jun;25(6 Suppl):S98-S104

Authors: Ness S

Abstract
Clinicians have a range of options for treating patients with disease states that require the use of immunoglobulin (Ig). Traditionally, intravenous immunoglobulin (IVIG) administration has provided effective therapy for a variety of disease states. More recently, subcutaneous immunoglobulin (SCIG) administration has become available for patients with primary immunodeficiencies and chronic inflammatory demyelinating polyneuropathy (CIDP). Ig is used as replacement therapy in patients with primary or secondary immunodeficiencies and has been shown to reduce morbidity due to bacterial infections associated with antibody deficiency. The mechanism of action for use of Ig in the treatment of autoimmune disorders is complex and partially understood, but immunomodulatory effects have been suggested in CIDP and multifocal motor neuropathy. The available IVIG and SCIG products differ in their pharmaceutical properties (eg, pH, osmolality, IgA content, sodium content, and stabilizer), which can affect safety and tolerability in some patients. The pharmacokinetics of Ig also differ based on the route of administration. With IVIG administration every 3 or 4 weeks, peak concentrations are greater and trough concentrations are lower, which can increase the propensity of systemic adverse effects (AEs) and impact tolerability of therapy. SCIG infusions are typically administered more frequently (ie, biweekly, weekly, and even daily based on patient need), resulting in steady state concentrations with fewer fluctuations in Ig plasma levels. The route of administration plays a major role in the types of AEs seen in patients receiving Ig therapy, with systemic AEs associated with IV administration and local reactions more commonly seen with SC administration. By understanding the differences in IVIG and SCIG products, which are not interchangeable, and the patient characteristics that guide product selection, clinicians and managed care providers can better serve patients with immunodeficiency disorders and other disease states.

PMID: 31318515 [PubMed – in process]

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Portal Pressure in Non-Cirrhotic Portal Hypertension: To Measure or Not to Measure.

Hepatology. 2019 Jul 18;:

Authors: Da BL, Surana P, Kapuria D, Vittal A, Levy E, Kleiner DE, Koh C, Heller T

Abstract
Non-cirrhotic portal hypertension (NCPH) is a heterogenous group of liver disorders characterized by elevated portal pressures in the absence of cirrhosis. Nodular regenerative hyperplasia (NRH) is a common cause of NCPH and can be due to drugs, hematological, autoimmune, and neoplastic disorders.(1) Patients with NCPH appear clinically distinct from cirrhotic patients due to their age, lack of significant alcohol intake or metabolic syndrome, and often carry associated risk factors (i.e. primary immunodeficiency). Interestingly, NCPH, especially when due to NRH, often results in peri- or pre-sinusoidal portal hypertension and unlike cirrhotic disease, patients often have a normal or mildly elevated hepatic venous pressure gradient (HVPG) that does not accurately reflect their actual degree of portal hypertension. Thus, it is unclear if HVPG measurements are routinely needed in the evaluation of patients suspected to have NCPH. This article is protected by copyright. All rights reserved.

PMID: 31318454 [PubMed – as supplied by publisher]

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Corrigendum: Assessing the Functional Relevance of Variants in the IKAROS Family Zinc Finger Protein 1 (IKZF1) in a Cohort of Patients With Primary Immunodeficiency.

Front Immunol. 2019;10:1490

Authors: Eskandarian Z, Fliegauf M, Bulashevska A, Proietti M, Hague R, Smulski CR, Schubert D, Warnatz K, Grimbacher B

Abstract
[This corrects the article DOI: 10.3389/fimmu.2019.00568.].

PMID: 31316524 [PubMed – in process]

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Primary Cutaneous Clonal CD8+ T-Cell Lymphoproliferative Disorder Associated With Immunodeficiency due to RAG1 Mutation.

Am J Dermatopathol. 2019 Jul 12;:

Authors: Avitan-Hersh E, Stepensky P, Zaidman I, Nevet MJ, Hanna S, Bergman R

Abstract
The development of T-cell lymphomas, granulomatous reactions, and autoimmunity has been observed in immunodeficiency due to milder forms of recombination activating gene (RAG) deficiency. A few cases of cutaneous clonal papulonodular CD8 lymphocytic infiltrates and cutaneous CD8 granulomatous T-cell lymphoma have been described in association with common variable immunodeficiency, and with X-linked agammaglobulinemia. We describe a 15-year-old girl with several autoimmune disorders and recurrent infections that presented with several nodules on her cheek. Histopathological studies demonstrate histological, immunohistochemical, and molecular findings compatible with a primary cutaneous clonal CD8 T-cell lymphoproliferative disorder. Vacuolar interface changes were also seen in the involved skin, reminiscent of cutaneous lupus erythematosus. Molecular genetic analysis revealed a germline novel homozygous missense mutation in RAG1 (T1003>C). The parents were heterozygous carriers. The facial cutaneous lesions recurred despite local radiation therapy. Because of recurrent life-threatening systemic infections, allogeneic bone marrow transplantation was performed. The pathogenesis of this primary cutaneous clonal CD8 T-cell lymphoproliferative disorder may have been related to a chronic stimulation of autoreactive T cells in the involved skin paired with reduced RAG1 activity.

PMID: 31313695 [PubMed – as supplied by publisher]

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WHIM Syndrome: from Pathogenesis Towards Personalized Medicine and Cure.

J Clin Immunol. 2019 Jul 16;:

Authors: Heusinkveld LE, Majumdar S, Gao JL, McDermott DH, Murphy PM

Abstract
WHIM syndrome is a rare combined primary immunodeficiency disease named by acronym for the diagnostic tetrad of warts, hypogammaglobulinemia, infections, and myelokathexis. Myelokathexis is a unique form of non-cyclic severe congenital neutropenia caused by accumulation of mature and degenerating neutrophils in the bone marrow; monocytopenia and lymphopenia, especially B lymphopenia, also commonly occur. WHIM syndrome is usually caused by autosomal dominant mutations in the G protein-coupled chemokine receptor CXCR4 that impair desensitization, resulting in enhanced and prolonged G protein- and β-arrestin-dependent responses. Accordingly, CXCR4 antagonists have shown promise as mechanism-based treatments in phase 1 clinical trials. This review is based on analysis of all 105 published cases of WHIM syndrome and covers current concepts, recent advances, unresolved enigmas and controversies, and promising future research directions.

PMID: 31313072 [PubMed – as supplied by publisher]

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The European Blood and Marrow Transplantation Textbook for Nurses: Under the Auspices of EBMT

Book. 2018

Authors: Kenyon M, Babic A

Abstract
The HSCT (haematopoietic stem cell transplant) is a particular treatment for many haematological and non-haematological diseases. Broadly, there are three different categories of transplantation, autologous, allogeneic and syngeneic, which can be applied to most disease scenarios. Haematopoietic stem cells can be derived from the bone marrow, peripheral blood and umbilical cord blood. HSCT treatment can be divided into separate phases that start with the harvest of the stem cells and passing through the conditioning, aplasia and engraftment until the recovery of the haematopoietic functions. HSCT is indicated in many diseases, and these indications depend on numerous factors such as the disease type, stage and response to previous treatment. Among non-malignant diseases, aplastic anaemia, sickle cell disease and, more recently, autoimmune diseases can also be effectively treated with HSCT. One third of the transplants in children are performed for rare indications such as severe combined immunodeficiencies. Allogeneic HSCT can also cure a number of non-malignant diseases in children, such as Wiskott-Aldrich syndrome and chronic granulomatous disease (CGD). This chapter will include transplant in primary immunodeficiency in children as well as inherited bone marrow failure and inborn errors of metabolism.

PMID: 31314315

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Intravenous immunoglobulin therapy: a snapshot for the internist.

Intern Emerg Med. 2019 Jul 15;:

Authors: Vitiello G, Emmi G, Silvestri E, Di Scala G, Palterer B, Parronchi P

Abstract
Intravenous immunoglobulins are the cornerstone for the treatment of primary humoral immunodeficiencies and may be used for a great number of other autoimmune, neurological and hematological conditions as well. Given their wide application, the possibility of running across a patient who needs this kind of therapy is becoming increasingly common. Generally, intravenous immunoglobulins are well tolerated. However, numerous adverse reactions ranging from mild to severe have been reported and linked to patient- and product-related factors. For all these reasons, we present herein a comprehensive review of the on- and off-label applications of intravenous immunoglobulins and provide a guide for the internist how to minimize the risk of adverse reactions and manage them.

PMID: 31309519 [PubMed – as supplied by publisher]

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Current concepts in pediatric inflammatory bowel disease; IL10/IL10R colitis as a model disease.

Int J Pediatr Adolesc Med. 2019 Mar;6(1):1-5

Authors: Almana Y, Mohammed R

Abstract
Inflammatory bowel disease (IBD) is a heterogeneous group of disorders composed mainly of ulcerative colitis (UC) and Crohn’s disease (CD) and undetermined IBD. The peak incidence of occurrence is mainly beyond the pediatric age group. Recent knowledge about genetic factors had been strongly linked to pediatric IBD (PIBD). Recent advances in genomic technologies have prompted the identification of genetic defects underlying rare, very early-onset IBD (VEO-IBD) as a disease subgroup noted especially in populations with higher consanguinity rates. A better understanding of key players in the complex homeostasis of the immune system in the gut and illustrating the relationships between intestinal microbiome, systemic immune dysregulation and primary immunodeficiency have received growing recognition over the years. In this article, we provide a review of the key players of the immunity of the gut, compare between adult and pediatric IBD as an interesting module to investigate the relationship between monogenic and multifactorial/polygenic diseases, list genetic mutations confirmed to be linked to VEO IBD and summarize the scientific work that led to the discovery of one of the monogenic mutations related to infantile colitis, namely IL10 and IL10 receptor defects.

PMID: 31304220 [PubMed]

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