A 7-year-old boy is brought to the clinic by his parents after he developed red urine earlier in the day. The patient has a history of atopic dermatitis. He had a skin infection one month ago that was treated with a short course of antibiotics. Blood pressure is 140/90 mm Hg. On physical examination, there is periorbital edema, as well as pitting edema on both feet. Laboratory results are as follows:
| Serum chemistry | |
| Blood urea nitrogen | 14 mg/dL |
| Creatinine | 1.4 mg/dL |
Which of the following is most likely responsible for this patient's renal injury?
Hypersensitivity reactions | |||
Humoral | Cellular | Examples | |
Type I |
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Type II |
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Type III |
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Type IV |
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NK = natural killer; PSGN = poststreptococcal glomerulonephritis. | |||
This patient with atopic dermatitis is predisposed to secondary skin infections (eg, impetigo, cellulitis). His antecedent skin infection, along with overt nephritic syndrome (eg, hypertension, generalized edema, gross hematuria [cola- or red-colored urine]) is suggestive of poststreptococcal glomerulonephritis (PSGN). This disease is the most common cause of acute nephritis in children and typically manifests 2-4 weeks after a skin infection.
During infection, IgG antibodies form against nephritogenic antigens expressed by certain strains of group A Streptococcus. These antibodies complex with streptococcal antigens to form immune complexes that are deposited along the glomerular basement membrane (type III hypersensitivity). Subsequent activation of the complement cascade leads to neutrophil recruitment and inflammatory damage to the glomeruli.
(Choices A and E) Cytotoxic CD8+ T lymphocytes and macrophages play a prominent role in type IV (delayed-type) hypersensitivity reactions. These cells are stimulated by T-helper cells, leading to localized inflammation, cellular destruction, and (often) granuloma formation. Although certain forms of acute interstitial nephritis are due to type IV hypersensitivity, gross hematuria is uncommon and affected patients classically present with fever, rash, and eosinophilia.
(Choice B) Histamine is released by mast cells and basophils during type I (immediate) hypersensitivity, which is seen with anaphylaxis and allergies, not PSGN. Mast cells and basophils are coated by IgE molecules, which cross-link on antigen exposure, triggering the release of histamine and other mediators.
(Choice C) Direct binding of autoantibodies to tissue is responsible for type II (cytotoxic) hypersensitivity reactions. This underlies Goodpasture syndrome (antibodies directed at type IV collagen), which can cause generalized edema (glomerulonephritis) and hemoptysis (diffuse alveolar hemorrhage). However, PSGN is a much more common cause of glomerulonephritis in children.
Educational objective:
Poststreptococcal glomerulonephritis is the most common cause of nephritic syndrome (eg, hematuria, edema, hypertension) in children, typically occurring 2-4 weeks after a streptococcal skin infection (eg, impetigo, cellulitis). It is caused by a type III (immune complex–mediated) hypersensitivity reaction.