*
* APRIL 1991
THE WESTERN JOURNAL OF MEDICINE
154 * 4
New Uses of Intravenous Immune Globulin Therapy ALTHOUGH THE MAIN INDICATION for intravenous immune globulin (IGIV) is the treatment of primary immunodeficiencies, recent studies have shown a role for IGIV in treating selected secondary immunodeficiencies and autoimmune diseases. Secondary immunodeficiency occurs in previously immunocompetent persons as a result of another disorder. Such disorders include prematurity, thermal and blunt trauma, leukemia, bone marrow transplantation, and human immunodeficiency virus (HIV) infection. Data from several recent studies indicate a decreased risk of group B streptococcal infections in premature infants treated prophylactically with IGIV. Further studies are being done to help better define guidelines for the use of IGIV in these infants. Bone marrow transplant recipients treated with IGIV have reduced rates of septicemia and a decreased incidence of graft-versus-host disease compared with untreated controls. Intravenous immune globulin is also effective in decreasing serious bacterial infections in patients with chronic lymphocytic leukemia and hypogammaglobulinemia. Severe head trauma is associated with diminished antibody responses, and, because of this, the usefulness of IGIV in pediatric head trauma is currently under study. Initial uncontrolled studies suggest a role for IGIV in patients with the acquired immunodeficiency syndrome, especially in young children who are antibody deficient and lack memory B cells. Until the results of controlled trials are available, the use of IGIV in patients with HIV infection remains controversial. The treatment of both acute and chronic immune thrombocytopenic purpura with IGIV is now well established. This success has led to the investigation of its use in other autoim-
461
mune disorders. High doses of IGIV given within ten days of the start of Kawasaki's disease have been shown to decrease the incidence of coronary aneurysms and to reduce fever and acute inflammation. Recent studies have shown that a single large dose of IGIV, 2 grams per kilogram, is as effective as the previously recommended smaller daily dose given over four days. Other autoimmune diseases treated with IGIV include autoimmune hemolytic anemia, autoimmune neutropenia, myasthenia gravis, lupus erythematosus, rheumatoid arthritis, bullous pemphigoid, and diabetes mellitus. Most of the reports to date are anecdotal or are of preliminary uncontrolled trials. The mechanism of IGIV action in autoimmune disease remains unknown. There is evidence in immune thrombocytopenic purpura that one mechanism may be Fc-receptor blockade. In Kawasaki's disease, the use of IGIV suppresses polyclonal immunoglobulin synthesis and T-cell activation. Another possible mechanism is immune network modulation by anti-idiotype antibodies present in IGIV. Elucidating the mechanism of this agent in these disorders will provide insight into the primary disorder itself that perhaps will lead to more specific and less costly therapies. NEVIN W. WILSON, MD La Jolla, California JOHN F. BASTIAN, MD San Diego, California
REFERENCES Berkman SA, Lee ML, Gale RP: Clinical uses of intravenous immunoglobulins. Ann Intern Med 1990; 112:278-292 Gonzalez LA, Hill HR: The current status of intravenous gammaglobulin use in neonates. Pediatr Infect Dis 1989; 8:315-322 Schwartz SA: Intravenous immunoglobulin (IVIG) for the therapy of autoimmune disorders. J Clin Immunol 1990; 10:81-89 Sullivan KM, Kopecky K1, Jocom J, et al: Immunomodulatory and antimicrobial efficacy of intravenous immunoglobulin in bone marrow transplantation. N EngI J Med 1990; 323:705-712 Wilson NW, Ochs HD, Hamburger RN, Peterson B, Bastian JF: Abnormal primary antibody response in pediatric trauma patients. J Pediatr 1989; 115:424-429
ADVISORY PANEL TO THE SECTION ON ALLERGY AND IMMUNOLOGY RICHARD O'CONNOR,
MD
Advisory Panel Chair Section Chair CMA Scientific Board Representative San Diego
PATRICK TELLEZ,
ABBA I. TERR,
MD
MICHAEL J. WELCH,
MD
Stanford University
CMA Section Secretary Sacramento
RICHARD B. MOSS, MD
MD
Stanford University
CMA Section Assistant Secretary Section Coeditor San Diego
STEPHEN M. NAGY, JR,
ALLEN L. SCHWANDT,
University of California, Irvine
Loma Linda University
EVA F. FANOUS,
MD
Loma Linda University
MD
MD
University of California, Davis
HAROLD NOVEY, GILDON BEALL,
MD MD
University of California, Los Angeles
DOUGLAS HEINER, MD Section Coeditor University of California, Los Angeles ROBERT N. HAMBURGER, MD University of California, San Diego STEPHEN WASSERMAN, MD University of California, San Diego OSCAR L. FRICK, MD, PhD University of California, San Francisco
EDWARD J. GOETZL, MD University of California, San Francisco ZACK HADDAD, MD University of Southern California NATHAN D. SCHULTZ, MD Walnut Creek
DEV M. DESAI Medical Student University of California, San Francisco
* APRIL 1991
THE WESTERN JOURNAL OF MEDICINE
154 * 4
New Uses of Intravenous Immune Globulin Therapy ALTHOUGH THE MAIN INDICATION for intravenous immune globulin (IGIV) is the treatment of primary immunodeficiencies, recent studies have shown a role for IGIV in treating selected secondary immunodeficiencies and autoimmune diseases. Secondary immunodeficiency occurs in previously immunocompetent persons as a result of another disorder. Such disorders include prematurity, thermal and blunt trauma, leukemia, bone marrow transplantation, and human immunodeficiency virus (HIV) infection. Data from several recent studies indicate a decreased risk of group B streptococcal infections in premature infants treated prophylactically with IGIV. Further studies are being done to help better define guidelines for the use of IGIV in these infants. Bone marrow transplant recipients treated with IGIV have reduced rates of septicemia and a decreased incidence of graft-versus-host disease compared with untreated controls. Intravenous immune globulin is also effective in decreasing serious bacterial infections in patients with chronic lymphocytic leukemia and hypogammaglobulinemia. Severe head trauma is associated with diminished antibody responses, and, because of this, the usefulness of IGIV in pediatric head trauma is currently under study. Initial uncontrolled studies suggest a role for IGIV in patients with the acquired immunodeficiency syndrome, especially in young children who are antibody deficient and lack memory B cells. Until the results of controlled trials are available, the use of IGIV in patients with HIV infection remains controversial. The treatment of both acute and chronic immune thrombocytopenic purpura with IGIV is now well established. This success has led to the investigation of its use in other autoim-
461
mune disorders. High doses of IGIV given within ten days of the start of Kawasaki's disease have been shown to decrease the incidence of coronary aneurysms and to reduce fever and acute inflammation. Recent studies have shown that a single large dose of IGIV, 2 grams per kilogram, is as effective as the previously recommended smaller daily dose given over four days. Other autoimmune diseases treated with IGIV include autoimmune hemolytic anemia, autoimmune neutropenia, myasthenia gravis, lupus erythematosus, rheumatoid arthritis, bullous pemphigoid, and diabetes mellitus. Most of the reports to date are anecdotal or are of preliminary uncontrolled trials. The mechanism of IGIV action in autoimmune disease remains unknown. There is evidence in immune thrombocytopenic purpura that one mechanism may be Fc-receptor blockade. In Kawasaki's disease, the use of IGIV suppresses polyclonal immunoglobulin synthesis and T-cell activation. Another possible mechanism is immune network modulation by anti-idiotype antibodies present in IGIV. Elucidating the mechanism of this agent in these disorders will provide insight into the primary disorder itself that perhaps will lead to more specific and less costly therapies. NEVIN W. WILSON, MD La Jolla, California JOHN F. BASTIAN, MD San Diego, California
REFERENCES Berkman SA, Lee ML, Gale RP: Clinical uses of intravenous immunoglobulins. Ann Intern Med 1990; 112:278-292 Gonzalez LA, Hill HR: The current status of intravenous gammaglobulin use in neonates. Pediatr Infect Dis 1989; 8:315-322 Schwartz SA: Intravenous immunoglobulin (IVIG) for the therapy of autoimmune disorders. J Clin Immunol 1990; 10:81-89 Sullivan KM, Kopecky K1, Jocom J, et al: Immunomodulatory and antimicrobial efficacy of intravenous immunoglobulin in bone marrow transplantation. N EngI J Med 1990; 323:705-712 Wilson NW, Ochs HD, Hamburger RN, Peterson B, Bastian JF: Abnormal primary antibody response in pediatric trauma patients. J Pediatr 1989; 115:424-429
ADVISORY PANEL TO THE SECTION ON ALLERGY AND IMMUNOLOGY RICHARD O'CONNOR,
MD
Advisory Panel Chair Section Chair CMA Scientific Board Representative San Diego
PATRICK TELLEZ,
ABBA I. TERR,
MD
MICHAEL J. WELCH,
MD
Stanford University
CMA Section Secretary Sacramento
RICHARD B. MOSS, MD
MD
Stanford University
CMA Section Assistant Secretary Section Coeditor San Diego
STEPHEN M. NAGY, JR,
ALLEN L. SCHWANDT,
University of California, Irvine
Loma Linda University
EVA F. FANOUS,
MD
Loma Linda University
MD
MD
University of California, Davis
HAROLD NOVEY, GILDON BEALL,
MD MD
University of California, Los Angeles
DOUGLAS HEINER, MD Section Coeditor University of California, Los Angeles ROBERT N. HAMBURGER, MD University of California, San Diego STEPHEN WASSERMAN, MD University of California, San Diego OSCAR L. FRICK, MD, PhD University of California, San Francisco
EDWARD J. GOETZL, MD University of California, San Francisco ZACK HADDAD, MD University of Southern California NATHAN D. SCHULTZ, MD Walnut Creek
DEV M. DESAI Medical Student University of California, San Francisco
