Severe combined immunodeficiency disease (SCID) is characterized by absence of both humoral and cell-mediated immunity.
The terms "swiss type lymphopenic agamma-globulinemia", an autosomal-recessive form of disease, and "x-linked lymphopenic agamma-globulinemia" have been used to describe this disorder, which, as the names imply can follow either mode of inheritance.
Pathophysiology The exact cause of SCID is unknown.
The theories include 1.
a defective stem cell that is incapable of differentiating into B- or T-cells 2.
defective organs responsible for the differentiating process, primarily the thymus and lymphoid complex, or 3.
an enzymatic defect that suppresses lymphocytic cell function.
The consequence of the immunodeficiency is an overwhelming susceptibility to infection and to the graft-vs-host reaction.
The latter occurs when any histo-incompatible tissue from an immuno-competent donor is infused into the immunodeficient recipient.
Due to its immunodeficiency, the body is unable to reject the foreign incompatible tissue.
Therefore, the antigenic donor cells attack the host's tissues.
The graft-vs-host reaction is a serious complication in the only known treatment for SCID, bone marrow transplant.
Clinical manifestations Obviously the most common manifestation is susceptibility to infection early in life, most often by 3 months of age when maternal immunity is low.
Specifically, the disorder in children is characterized by chronic infection, failure to completely recover from an infection, frequent reinfection, and infection with unusual agents.
In addition, the history reveals no logical source of infection.
Failure to thrive is a consequence of the persistent illnesses.
If the child should receive a foreign tissue, such as blood supplements, signs of graft-vs-host reaction, such as fever, skin rash, alopecia, hepatsplenomegaly, and diarrhea are expected.
Since the reaction requires 7 to 20 days for tissue damage to become evident, the symptoms may be mistaken for an infection.
However, the presence of a graft-vs-host reaction increases the child's susceptibility to overwhelming infection and therefore, is a grave complication.
Diagnostic evaluation Diagnosis is usually based on a history of recurrent, severe infections from early infancy, a familial history of recurrent, severe infections from early infancy, a familial history of the disorder, and specific laboratory findings, which include lymphopenia, lack of lymphocyte response to antigens, and absence of plasma cells in the bone marrow.
Documentation of immunoglobulin deficiency is difficult during infancy because of the normally delayed response of the infant to produce its own immunogobulins and maternal transfer of immunoglobulin G.
Therapeutic management The only definitive treatment is a histo-compatible bone marrow transplant, the perfect donor is an identical twin because the human lymphocyte antigens (HLA) are exactly the same.
The second best choice is a sibling.
The procedure consists of aspirating several samples of bone marrow from the donor and infusing the marrow intravenously into the host.
However, bone marrow transplants are usually done at medical centers where measures to control post-transplantation infection, such as sterile environment, and other specialized facilities are available.
Since the host's immunologic system is incompetent, graft rejection is not a problem.
However, a graft-vs-host reaction is always a possibility in a non-identical twin graft, and once it occurs, little can be done to reverse the process.
Other approaches to SCID are providing passive immunity with immune globulin and maintaining the child in a sterile environment.
The latter is effective if instituted before the existence of any infectious process in the infant.
Other investigations involving transplant procedures include non-identical HLA bone marrow grafts and fetal liver or thymus transplants.
However, the results are still uncertain, although they provide potential hope for future children hone with the disorder.
The terms "swiss type lymphopenic agamma-globulinemia", an autosomal-recessive form of disease, and "x-linked lymphopenic agamma-globulinemia" have been used to describe this disorder, which, as the names imply can follow either mode of inheritance.
Pathophysiology The exact cause of SCID is unknown.
The theories include 1.
a defective stem cell that is incapable of differentiating into B- or T-cells 2.
defective organs responsible for the differentiating process, primarily the thymus and lymphoid complex, or 3.
an enzymatic defect that suppresses lymphocytic cell function.
The consequence of the immunodeficiency is an overwhelming susceptibility to infection and to the graft-vs-host reaction.
The latter occurs when any histo-incompatible tissue from an immuno-competent donor is infused into the immunodeficient recipient.
Due to its immunodeficiency, the body is unable to reject the foreign incompatible tissue.
Therefore, the antigenic donor cells attack the host's tissues.
The graft-vs-host reaction is a serious complication in the only known treatment for SCID, bone marrow transplant.
Clinical manifestations Obviously the most common manifestation is susceptibility to infection early in life, most often by 3 months of age when maternal immunity is low.
Specifically, the disorder in children is characterized by chronic infection, failure to completely recover from an infection, frequent reinfection, and infection with unusual agents.
In addition, the history reveals no logical source of infection.
Failure to thrive is a consequence of the persistent illnesses.
If the child should receive a foreign tissue, such as blood supplements, signs of graft-vs-host reaction, such as fever, skin rash, alopecia, hepatsplenomegaly, and diarrhea are expected.
Since the reaction requires 7 to 20 days for tissue damage to become evident, the symptoms may be mistaken for an infection.
However, the presence of a graft-vs-host reaction increases the child's susceptibility to overwhelming infection and therefore, is a grave complication.
Diagnostic evaluation Diagnosis is usually based on a history of recurrent, severe infections from early infancy, a familial history of recurrent, severe infections from early infancy, a familial history of the disorder, and specific laboratory findings, which include lymphopenia, lack of lymphocyte response to antigens, and absence of plasma cells in the bone marrow.
Documentation of immunoglobulin deficiency is difficult during infancy because of the normally delayed response of the infant to produce its own immunogobulins and maternal transfer of immunoglobulin G.
Therapeutic management The only definitive treatment is a histo-compatible bone marrow transplant, the perfect donor is an identical twin because the human lymphocyte antigens (HLA) are exactly the same.
The second best choice is a sibling.
The procedure consists of aspirating several samples of bone marrow from the donor and infusing the marrow intravenously into the host.
However, bone marrow transplants are usually done at medical centers where measures to control post-transplantation infection, such as sterile environment, and other specialized facilities are available.
Since the host's immunologic system is incompetent, graft rejection is not a problem.
However, a graft-vs-host reaction is always a possibility in a non-identical twin graft, and once it occurs, little can be done to reverse the process.
Other approaches to SCID are providing passive immunity with immune globulin and maintaining the child in a sterile environment.
The latter is effective if instituted before the existence of any infectious process in the infant.
Other investigations involving transplant procedures include non-identical HLA bone marrow grafts and fetal liver or thymus transplants.
However, the results are still uncertain, although they provide potential hope for future children hone with the disorder.