Severe forms of immunodeficiency states are so incompatible with life that they are rarely seen in clinical practice. What are these specific disorders?
They can be classified as:
1. Combined immunodeficiency states,
2. Deficiency of humoral immunity
3. deficiency of cellular immunity
4. Deficiency of phagocytes
5. Deficiency of complement system, and
6. Secondary immunodeficiency states.
Combined immunodeficiency: There is deficiency of both cellular and humoral immunity. This is produced as a result of block of maturation of the stem cells which give rise to immunocytes. Severely affected children are incapable of limiting bacterial, viral and fungal infections and they die in childhood. Severeal subtypes have been described e.g, sex-linked recessive types (thymic type0 and autosomal recessive (Swiss ) types. Relatively benign types are the Wiskott-Aldrich syndrome (sex-linked) and ataxia telenglectasia (autosomal recessive). In both lymphoreticular malignancies are more common.
Humoral immune deficiency: This may be a selective primary deficiency affecting only one of the G, M or A classes of immunoglobulins. In IgG deficiency, the affected persons suffer from repeated pyogenic infections, especially by encapsulated organisms such as H. Influenza and Streptococcus pyogenes. In IgA deficiency, respiratory and atopic allergies are also common. IgA deficiency, also lowers the resistance to gut commensals leading to malabsorption syndrome. Congenital hypogammaglobulinemia may be sex linked (Bruton type) or autosomal dominant. In these cases, severe depletion of B cells and circulating immunoglobulins are noticed with consequent severe bacterial infections. Incidence of auto-immune diseases such as hemolytic anemia are high in primary agammaglobulinemia. Immunodeficiency with normal quantity of functionally deficient immunoglobulins (Job's syndrome) has been described.
Cellular Immune deficiency: Primary deficiency of T cells leads to sevee viral and monilial infections and affected children usually succumb within the first few years of Life. The lymphocytes of the patients are unable to respond to mitogens in vitro. The thymus may be almost absent (Nezelof's syndrome), or aplastic (Di George syndrome) or in some cases it may be normal, e.g, chronic mucocutaneous candidiasis.
Defect of phagocytosis: Chronic granulomatous disease is a sex linked inherited condition where hydrogen peroxidase is deficient inside the phagocytes, leading to decreased microbial activity. Recurrent suppurative granulomas due to catalase positive and perosxidase negative organisms (Staphylococcus aureus and proteus) are common in this condition. In myeloperoxidase deficiency, infections by peroxidase positive bacteria such as hemophilus are common. In Chediak-Higashi syndrome, the neutrophils show defective degranulation and sluggish motility with consequent pyogenic infections.
Deficiencies in the complement system: Hereditary angioneurotic edema is inherited as an autosomal dominant disease, and is characterized by the absence of the enzyme which normally inhibits the activity of CI esterase which activates the complement cascade reactions leading to liberation of kinins and vaso-active peptides. Recurrent attacks of Edema of skin and mucosa are very common and edema of glottis may sometimes be life threatening. Deficiency of C3 is inherited as an autosomal recessive character. Deficiencies of other complement components, though reported, are very rare. Generally, the clinical conditions mimic immunoglobulin deficiency states.
Secondary immunodeficiency: The transplacental transfer of immunoglobulins takes place mostly in the last few weeks of pregnancy. Premature infants therefore may suffer from mild hypoglobunemia. Secondary defects in lymphocyte functions are seen in many conditions such as burns, malnutrition, leukemias, lymphomas and uremia. In Multiple myeloma, though total immunoglobulins are increased, the biologically active ones are depressed, leading to functional deficiency. Treatment of immunodeficiency states as a whole is unsatisfactory. Immunoglobulin injection (0.25g/Kg/week) may abort recurrent pyogenic infections in hypogammaglobulinemia. Treatment of cell mediated immune deficiency states is still more difficult. Transplantation of thymus and bone marrow are gaining acceptance.
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