Hypersensitivity - Different Types

Type I Anaphylactic

• antigen reacts with IgE bound to mast cells
• anaphylaxis, atopy (e.g. asthma, eczema and hayfever)

Type II Cell bound

• IgG or IgM binds to antigen on cell surface
• autoimmune haemolytic anaemia, ITP, Goodpasture's, pernicious anemia, acute hemolytic transfusion reactions, rheumatic fever, bullous pemphigoid, pemphigus vulgaris.

Type III Immune complex

• free antigen and antibody (IgG, IgA) combine
• serum sickness, systemic lupus erythematosus, poststreptococcal glomerulonephritis, extrinsic allergic alveolitis (especially acute phase)

Summary of Idiopathic Thrombocytopenic Purpura

Idiopathic thrombocytopenic purpura (ITP), thrombocytopenia that results from immunologic platelet destruction, may be acute (postviral thrombocytopenia) or chronic (Werlhof’s disease, purpura hemorrhagica, essential thrombocytopenia, autoimmune thrombocytopenia). Acute ITP usually affects children between ages 2 and 6; chronic ITP mainly affects adults younger than age 50, especially women between ages 20 and 40.

Causes
ITP may be an autoimmune disorder because antibodies that reduce the life span of platelets have been found in nearly all patients. The spleen probably helps to remove platelets modified by the antibody. Acute ITP usually follows a viral infection, such as rubella and chickenpox, and can follow immunization with a live virus vaccine. Chronic ITP seldom follows infection and is commonly linked to immunologic disorders, such as systemic lupus erythematosus or human immunodeficiency virus infection. It’s also linked to drug reactions.

Clinical Features
Signs and symptoms of ITP common to all forms of thrombocytopenia include petechiae, ecchymoses, and mucosal bleeding from the mouth, nose, and GI tract. Generally, hemorrhage is a rare physical finding. Purpuric lesions may occur in vital organs, such as the lungs, kidneys, or brain, and may prove fatal.
With acute ITP, which is common in children, onset is usually sudden and without warning, causing easy bruising, epistaxis, and bleeding gums. Onset of chronic ITP is insidious.

Understanding Bone marrow Transplantation

In bone marrow transplantation, usually 500 to 700 ml of marrow is aspirated from the pelvic bones of a human leukocyte antigen (HLA)–compatible donor (allogeneic) or of the recipient himself during periods of complete remission (autologous). The aspirated marrow is filtered and then infused into the recipient in an attempt to repopulate the patient’s marrow with normal cells.
This procedure has effected long-term, healthy survivals in about half of the patients with severe aplastic anemia. Bone marrow transplantation may also be effective in treating patients with acute leukemia, certain immunodeficiency diseases, and solid-tumor cancers.
Because bone marrow transplantation carries serious risks, it requires strict adherence to infection protection techniques and strict aseptic technique. It also requires that a primary caregiver provide consistent care and continuous monitoring of the patient’s status.

Before bone marrow infusion

• Explain to the patient that the success rate depends on the stage of the disease and on finding an HLA-identical sibling match.
• After bone marrow aspiration is completed under local anesthetic, apply pressure dressings to the donor’s aspiration sites. Observe the sites for bleeding. Relieve pain with an analgesic and ice packs as needed.
• Assess the patient’s understanding of bone marrow transplantation. If necessary, correct any misconceptions about the procedure and provide additional information. Prepare the patient to expect an extended facility stay. Explain that chemotherapy and, possibly, radiation therapy are necessary to remove cells that may cause the body to reject the transplant.
• Various treatment protocols are used. For example, I.V. cyclophosphamide may be used with additional chemotherapeutic agents or total body irradiation to suppress the patient’s immune system and requires aggressive hydration to prevent hemorrhagic cystitis. Control nausea and vomiting with an antiemetic (such as ondansetron, prochlorperazine, or metoclopramide) as needed. Give allopurinol, as prescribed, to prevent hyperuricemia resulting from tumor breakdown products. Because alopecia is a common adverse effect of high-dose cyclophosphamide therapy, encourage the patient to choose a wig or scarf before treatment begins.
• Total body irradiation (in one dose or several daily doses) follows chemotherapy, inducing total marrow aplasia. Warn the patient that cataracts, GI disturbances, and sterility are possible adverse effects.

Urticaria And Angioedema

Urticaria, commonly known as hives, is an episodic, usually self-limited skin reaction characterized by local dermal wheals surrounded by an erythematous flare. 

Angioedema, which can present either subcutaneously or dermally, produces deeper, larger wheals (usually on the hands, feet, lips, genitals, and eyelids) and a more diffuse swelling of loose subcutaneous tissue. Urticaria and angioedema can occur simultaneously, but angioedema may last longer.

Pathophysiology
Urticaria and angioedema are common allergic reactions. Causes include allergy to drugs, foods, insect stings and, occasionally, inhalants, such as animal dander and cosmetics, that provoke an immunoglobulin (Ig) E-mediated response to protein allergens. However, certain drugs may cause urticaria without an IgE response.
When urticaria and angioedema are part of an anaphylactic reaction, they almost always persist long after the systemic response has subsided. This occurs because circulation to the skin is inhibited after an allergic reaction, which results in slow histamine reabsorption at the reaction site. Nonallergic urticaria and angioedema are probably also related to histamine release.
External physical stimuli, such as cold (usually in young adults), heat, water, or sunlight, may provoke urticaria and angioedema. Dermographism urticaria develops with varying pressure, usually under tight clothing, and is aggravated by scratching.
Several different mechanisms and underlying disorders may provoke urticaria and angioedema. These include IgE-induced release of mediators from cutaneous mast cells; binding of IgG or IgM, resulting in complement activation; localized or secondary infections such as respiratory infection; neoplastic diseases such as Hodgkin’s disease; connective tissue diseases such as systemic lupus erythematosus; collagen vascular diseases; and psychogenic diseases.

Signs and symptoms
The characteristic features of urticaria are distinct, raised, evanescent dermal wheals surrounded by an erythematous flare. These lesions may vary in size. In cholinergic urticaria, the wheals may be tiny and blanched, surrounded by erythematous flares.

Angioedema characteristically produces nonpitted swelling of deep subcutaneous tissue, usually on the eyelids, lips, genitalia, and mucous membranes. These swellings don’t usually itch but may burn and tingle.

Severe Combined Immunodeficiency Disease

Both cell-mediated (T-cell) and humoral (B-cell) immunity are deficient or absent in severe combined immunodeficiency disease (SCID). This results in susceptibility to infection from all classes of microorganisms during infancy.

At least three types of SCID exist: 

1. reticular dysgenesis, the most severe type, in which the hematopoietic stem cell fails to differentiate into lymphocytes and granulocytes; 
2. Swiss-type agammaglobulinemia, in which the hematopoietic stem cell fails to differentiate into lymphocytes alone; and 
3. enzyme deficiency, such as adenosine deaminase (ADA) deficiency, in which  the buildup of toxic products in the lymphoid tissue causes damage and subsequent dysfunction.

SCID affects more males than females; its estimated incidence is 1 in every 100,000 to 500,000 births. Most untreated patients die from infection within 1 year of birth.

Causes
SCID is usually transmitted as an autosomal recessive trait, although it may be X-linked. In most cases, the genetic defect seems associated with failure of the stem cell to differentiate into T and B lymphocytes.
Many molecular defects, such as mutation of the kinase ZAP-70, can cause SCID. X-linked SCID results from a mutation of a subunit of the interleukin-2 (IL-2), IL-4, and IL-7 receptors. Less commonly, it results from an enzyme deficiency.

Signs and symptoms
An extreme susceptibility to infection becomes obvious in the infant with SCID in the first months of life. The infant fails to thrive and develops chronic otitis, sepsis, watery diarrhea (associated with Salmonella or Escherichia coli), recurrent pulmonary infections (usually caused by Pseudomonas, cytomegalo-virus, or Pneumocystis carinii), persistent oral candidiasis (sometimes with esophageal erosions), and possibly fatal viral infections (such as chickenpox).
P. carinii pneumonia usually strikes a severely immunodeficient infant in the first 3 to 5 weeks of life. Onset is typically insidious, with gradually worsening cough, low-grade fever, tachypnea, and respiratory distress. A chest X-ray characteristically shows bilateral pulmonary infiltrates.