immunology allergic disorders
Approach to the Patient With Suspected Immunodeficiency
Treatment of Suspected Immunodeficiency
Avoidance of live vaccines and exposure to infection Antibiotics and sometimes surgery Replacement of missing immune components Treatment of immunodeficiency disorders generally involves preventing infection, managing acute infection, and replacing missing immune components when possible. type b (Hib) vaccines are the recommended risk-specific vaccines, but their effectiveness varies with the degree of immunodeficiency ( Treatment references ). Messenger RNA-based and adenovirus-based vaccines for prevention of COVID appear to be safe in patients with a primary immunodeficiency. but it is as yet unclear how much these vaccines will raise antibody titers and how long they will continue to be protective. It is likely that patients with humoral and B-cell deficiencies will have a decreased response. Prophylaxis for reactivation of hepatitis B or C in immunosuppressed patients with serologic evidence of exposure can be provided by antiviral drugs such aslamivudineorentecavir. Patients at risk of serious infections (eg, those with SCID, chronic granulomatous disease, Wiskott-Aldrich syndrome, or asplenia) or of specific infections (eg, withPneumocystis jiroveciiin patients with T-cell disorders) can be given prophylactic antibiotics (eg,trimethoprim/sulfamethoxazole 5 mg/kg orally twice a day). To prevent Graft-vs-host disease (GVHD) after transfusions, clinicians should use blood products from cytomegalovirus-negative donors; the products should be filtered to remove white blood cells and irradiated (15 to 30 Gy). After appropriate cultures are obtained, antibiotics that target likely causes should be given promptly. Sometimes surgery (eg, to drain abscesses) is needed. Viral infections that are usually self-limited may cause severe persistent disease in immunocompromised patients. Antivirals (eg,oseltamivir,peramivir, orzanamivirfor influenza;acyclovirfor herpes simplex and varicella-zoster infections;ribavirinfor respiratory syncytial virus or parainfluenza 3 infections) may be lifesaving. Such replacement helps prevent infection. Therapies used in more than one primary immunodeficiency disorder include the following: IV immune globulin(IVIG) is effective replacement therapy in most forms of antibody deficiency. The usual dose is 400 mg/kg once a month; treatment is begun at a low infusion rate. Some patients need higher or more frequent doses. IVIG 800 mg/kg once a month helps some antibody-deficient patients who do not respond well to conventional doses, particularly those with a chronic lung disorder. High-dose IVIG aims to keep IgG trough levels in the normal range (>600 mg/dL [> 6 g/L]). Subcutaneous immune globulin (SCIG)can be given instead of IVIG. SCIG can be given at home, usually by patients themselves. The usual dose is 100 to 150 mg/kg once a week. Because SCIG and IVIG differ in bioavailability, the dose of SCIG may need to be adjusted if patients are switched from IVIG. With SCIG, local site reactions are a risk, but SCIG seems to have fewer systemic adverse effects. Hematopoietic Stem Cell Transplantation None Gene therapyrefers to the introduction of an exogenous gene (transgene) into one or more cell type with the hopes of correcting for a missing or malfunctioning gene known to cause disease. Gene therapy using gamma-retroviral vectors has been used foradenosinedeaminase (ADA) deficiency (a type of SCID) and has resulted in vector insertion in oncogenes, with some cures; leukemias have not developed to date. In mouse models of chronic granulomatous disease, CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9) technology has been used to correct theCYBBmutation. cDNA under transcriptional regulation of its own human Artemis promoter has been used to correct severe combined immunodeficiency ( Primary immunodeficiency references ). Other gene therapies are being investigated for treatment of X-linked SCID, hyper IgM syndrome, chronic granulomatous disease, and X-linked agammaglobulinemia. T-cell gene therapy ( Modified T cells ) is also being studied to correct T cell–intrinsic defects in IPEX syndrome, hyper IgM syndrome, X-linked lymphoproliferative disease, Munc 13-4 deficiency, and perforin deficiency ( 1.Shearer WT, Fleisher TA, Sullivan K, et al: Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts. J Allergy Clin Immunol 133 (4): 961–966, 2014. 2.Marsh RA, Hebert KM, Keesler D, et al: Practice pattern changes and improvements in hematopoietic cell transplantation for primary immunodeficiencies.J Allergy Clin Immunol142(6): 2004–2007, 2018. 3.Punwani D, Kawahara M, Sanford U, et al: Lentivirus mediated correction of Artemis-deficient severe combined immunodeficiency.Hum Gene Ther28: 112–124, 2017. doi: 10.1089/hum.2016.064 4.Ferreira LMR, Muller YD, Bluestone JA, et al: Next-generation regulatory T cell therapy.Nat Rev Drug Discov18(10): 749–769, 2019. doi: 10.1038/s41573-019-0041-4 