Pediatric Annals

A Pediatrician's View

Milton I Levine, MD

Abstract

At times when I read articles on advances in modern medicine, I feel that I am peering into the future. So often we seem to be on the brink of some great scientific discovery- perhaps regarding susceptibility to some disease or disorder, or some newer method of diagnosis or treatment. The first article in this issue of Pediatrie Annals (the second of two issues discussing autoimmune diseases) is titled "Genetic Predisposition to Autoimmune Disorders." Dr. Walter L. Henley, Guest Editor of this symposium, is the author of this paper, and presents the most recent knowledge of genetics that may be a key to understanding the now-obscure etiologies of many conditions. Dr. Henley gives us the impression that we are just beginning to understand the underlying causes of such disorders as celiac disease, insulin-dependent diabetes, rheumatoid arthritis, rheumatic fever, multiple sclerosis, and lupus erythematosus, to mention just a few.

This article primarily discusses the HLA (histocompatible leukocyte antigen) types, which are specific for each human being and appear on all nucleated cells. These antigens can be readily detected in the blood serum. Dr. Henley points out that these HLAs are controlled by genes located on the short arm of chromosome number 6. He lists the more than 90 alleles presently identified as HLA types. This knowledge and identification is of inestimable value in selecting compatible tissue to avoid rejection in organ transplants.

Then follows an exciting concept - that certain HLA types are associated with susceptibility to various diseases and autoimmune disorders. A large list of autoimmune disorders and their respective HLA types are presented in a fascinating table. But what is the correlation between the specific antigen and the disease or disorder related to it? Dr. Henley notes that, although presently these associations are theoretical, they are ". . . certain to be of practical importance in the future."

Some knowledge, however, already gives us clues to some possible causes of many of the HLA-mediated disorders. Take, for example, the role of viruses in the etiology of insulin-dependent diabetes mellitus. It is known that there is a close association between this disorder and HLA types HLA-B8; HLADw3/Dr3; HLA-B15; and HLADw4/Dr4. It is felt that people with these genes are genetically susceptible and that, very possibly, a viral infection is the catalyst that triggers the onset of this disease. A similar relationship between viruses or toxins and many of the HLA-mediated disorders may also exist. I would refer the reader seeking further information to the article, "Insulin-dependent Diabetes Mellitus," by Dr. Fredda Ginsberg-Fellner, Pediatrie Annals 9(4): 142, 1980.

The second article in this issue of Pediatrie Annals continues the discussion of autoimmune diseases presented in the March issue of the journal. Last month, disorders discussed were: Acquired immune thrombocytopenic purpura; acquired immune hemolytic anemia; autoimmune endocrine diseases; and acquired autoimmune diseases of the liver and gastrointestinal tract. The subject now presented is "Juvenile Rheumatoid Arthritis," written by Dr. Jane Schaller, Head of Rheumatic Disease Division, Children's Orthopedic Hospital and Medical Center, Seattle, Washington. This is an excellent review of the entire subject. The various forms of the disease are discussed, with their diagnostic features and the most effective forms of therapy. Dr. Schaller emphasizes that, although rheumatoid arthritis is a chronic disease, every effort should be made to prevent these children from feeling like invalids. Activities should be restricted as little as possible, and bed rest is contraindicated unless absolutely necessary.

The next article is titled "Rheumatic Fever: A Streptococcal-Induced Autoimmune Disease?" and has been contributed by Dr. John Zabriskie, Associate Professor at The Rockefeller University in New York City. This…

At times when I read articles on advances in modern medicine, I feel that I am peering into the future. So often we seem to be on the brink of some great scientific discovery- perhaps regarding susceptibility to some disease or disorder, or some newer method of diagnosis or treatment. The first article in this issue of Pediatrie Annals (the second of two issues discussing autoimmune diseases) is titled "Genetic Predisposition to Autoimmune Disorders." Dr. Walter L. Henley, Guest Editor of this symposium, is the author of this paper, and presents the most recent knowledge of genetics that may be a key to understanding the now-obscure etiologies of many conditions. Dr. Henley gives us the impression that we are just beginning to understand the underlying causes of such disorders as celiac disease, insulin-dependent diabetes, rheumatoid arthritis, rheumatic fever, multiple sclerosis, and lupus erythematosus, to mention just a few.

This article primarily discusses the HLA (histocompatible leukocyte antigen) types, which are specific for each human being and appear on all nucleated cells. These antigens can be readily detected in the blood serum. Dr. Henley points out that these HLAs are controlled by genes located on the short arm of chromosome number 6. He lists the more than 90 alleles presently identified as HLA types. This knowledge and identification is of inestimable value in selecting compatible tissue to avoid rejection in organ transplants.

Then follows an exciting concept - that certain HLA types are associated with susceptibility to various diseases and autoimmune disorders. A large list of autoimmune disorders and their respective HLA types are presented in a fascinating table. But what is the correlation between the specific antigen and the disease or disorder related to it? Dr. Henley notes that, although presently these associations are theoretical, they are ". . . certain to be of practical importance in the future."

Some knowledge, however, already gives us clues to some possible causes of many of the HLA-mediated disorders. Take, for example, the role of viruses in the etiology of insulin-dependent diabetes mellitus. It is known that there is a close association between this disorder and HLA types HLA-B8; HLADw3/Dr3; HLA-B15; and HLADw4/Dr4. It is felt that people with these genes are genetically susceptible and that, very possibly, a viral infection is the catalyst that triggers the onset of this disease. A similar relationship between viruses or toxins and many of the HLA-mediated disorders may also exist. I would refer the reader seeking further information to the article, "Insulin-dependent Diabetes Mellitus," by Dr. Fredda Ginsberg-Fellner, Pediatrie Annals 9(4): 142, 1980.

The second article in this issue of Pediatrie Annals continues the discussion of autoimmune diseases presented in the March issue of the journal. Last month, disorders discussed were: Acquired immune thrombocytopenic purpura; acquired immune hemolytic anemia; autoimmune endocrine diseases; and acquired autoimmune diseases of the liver and gastrointestinal tract. The subject now presented is "Juvenile Rheumatoid Arthritis," written by Dr. Jane Schaller, Head of Rheumatic Disease Division, Children's Orthopedic Hospital and Medical Center, Seattle, Washington. This is an excellent review of the entire subject. The various forms of the disease are discussed, with their diagnostic features and the most effective forms of therapy. Dr. Schaller emphasizes that, although rheumatoid arthritis is a chronic disease, every effort should be made to prevent these children from feeling like invalids. Activities should be restricted as little as possible, and bed rest is contraindicated unless absolutely necessary.

The next article is titled "Rheumatic Fever: A Streptococcal-Induced Autoimmune Disease?" and has been contributed by Dr. John Zabriskie, Associate Professor at The Rockefeller University in New York City. This is a most interesting article about a most interesting and puzzling disease. We know that the disease is due to group A Streptococcus, that its numerous signs and symptoms occur weeks after the original acute Streptococcus infection, and that subsequent lesions occur in the heart, joints, kidneys, skin, and brain. In the scientific investigation of the pathogenesis of rheumatic fever, there are three theories: A persistent streptococcal infection; a toxic reaction; and an abnormal immune response to the initial streptococcal infection. These various theories are individually discussed, and the numerous investigators' results reported. Today, according to Dr. Zabriskie, the majority of investigators favor the "abnormal immune response" theory. The evidence for this view of the pathogenesis is carefully and clearly presented - almost like a mystery story where many ctues are being gathered and correlated to reach" a final solution. The full answer has not yet been found. Further studies are necessary to depict more clearly the role of genetic susceptibility and relative roles of cellular and humoral immunity.

The final contribution to this symposium on autoimmunity discusses systemic lupus erythematosus, and is authored by Dr. Naomi F. Rothfield, Professor of Medicine and Chief of the Division of Rheumatic Diseases at the University of Connecticut School of Medicine. Most practicing pediatricians view SLE as a very rare disease. However, as Dr. Rothfield points out, it occurs in about six per 100,000 white women (and is more prevalent in nonwhite women); 32 percent have their first symptoms before the age of 21 years. This means that in approximately one-third of all cases, the pediatrician, as the primary physician, is - or should be - the first to observe and diagnose the symptoms of the disease. It follows that the pediatrician should become familiar with SLE's early clinical manifestations. This article gives an excellent review of the early signs and symptoms, the laboratory abnormalities (specifying which tests are most sensitive), and the most effective methods of treatment.

Since, in recent years, the survival of children with SLE has markedly improved, contraception for these patients may now be a consideration. The use of birth control pills by girls with this disease is contraindicated; if necessary, other methods should be utilized.

The actual cause of systemic lupus erythematosus is not known, but, as pointed out by Dr. Henley in his article in this issue, SLE has specific antigens (HLA-Dw2 and HLA-Dw3). This probably means that a genetic disorder predisposes the individual to occurrence of this disease.

This symposium on autoimmune diseases is a good example of continuing pediatrie education and brings to the practicing pediatrician the most recent knowledge of certain diseases considered to be of obscure origin.

10.3928/0090-4481-19820401-06

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