A 7-year-old boy is brought to the emergency department by his parents for arthralgias. He had a cough and runny nose last week but otherwise has been in good health. Temperature is 37 C (98.6 F), blood pressure is 95/65 mm Hg, pulse is 92/min, and respirations are 20/min. Physical examination shows raised, red-purple papules, some of which have coalesced, over the patient's buttocks and thighs. Auscultation of the lungs and heart is normal. The abdomen is soft with normal bowel sounds. The knees are tender but do not appear warm or swollen. Urinalysis results are as follows: Which of the following mechanisms is the most likely underlying cause of this patient's renal findings?

Question

A 7-year-old boy is brought to the emergency department by his parents for arthralgias.  He had a cough and runny nose last week but otherwise has been in good health.  Temperature is 37 C (98.6 F), blood pressure is 95/65 mm Hg, pulse is 92/min, and respirations are 20/min.  Physical examination shows raised, red-purple papules, some of which have coalesced, over the patient's buttocks and thighs.  Auscultation of the lungs and heart is normal.  The abdomen is soft with normal bowel sounds.  The knees are tender but do not appear warm or swollen.  Urinalysis results are as follows:  Which of the following mechanisms is the most likely underlying cause of this patient's renal findings?

Quizplus · Accepted Answer

11ec160b_37e1_3556_9249_3155c313bac0_MD0001_00 This patient has findings consistent with Henoch-Schönlein purpura (HSP) (ie, IgA vasculitis), a leukocytoclastic vasculitis most common in school-aged children and characterized by lower extremity palpable purpura, arthralgia/arthritis, abdominal pain, and/or renal abnormalities. HSP is caused by the deposition of IgA immune complexes in small-vessel walls and may be precipitated by an upper respiratory tract infection, as seen in this patient. HSP renal disease is an immune-mediated glomerulonephritis with microscopic features identical to IgA nephropathy: Mesangial deposition of IgA immune complexes triggers mesangial cell proliferation and extracellular matrix deposition, primarily via enhanced expression of platelet-derived growth factor and transforming growth factor beta. IgA Immune complexes also trigger complement activation via the alternative and lectin pathways; hydrolyzed complement proteins (eg, c5a) act as chemokines that attract neutrophils, which produce oxidants and release proteases (eg, elastase) that are damaging to glomerular capillaries. Macrophages may also be recruited to the glomerulus, where they cause further damage to glomerular capillaries, promote fibrin deposition, and contribute to crescent formation in severe cases. Most children with HSP-related renal disease have mild nephritis characterized by hematuria, red blood cell (RBC) casts, non-nephrotic range proteinuria, and a normal creatinine. However, severe complications (eg, nephrotic syndrome, acute kidney injury) can occur. (Choice A) IgG autoantibodies to phospholipase A₂ receptor on podocytes can lead to subepithelial immune deposition and membranous nephropathy. Patients have nephrotic syndrome (eg, edema, marked proteinuria [usually ≥3+]), not hematuria. (Choice B) Anti-glomerular basement membrane disease is caused by an autoantibody to the alpha 3 chain of type IV collagen and is often associated with pulmonary hemorrhage. Although patients have nephritic syndrome with hematuria and RBC casts, arthralgias and purpura are not seen. (Choice D) Prothrombotic conditions (eg, antiphospholipid syndrome) can cause thrombosis of the glomerular capillaries, and urinalysis may show hematuria and/or proteinuria. Although purpura may occur due to consumptive thrombocytopenia, the lesions would be diffuse, not localized to the lower extremities (immune complex vasculitis tends to affect dependent areas of the skin). In addition, his recent upper respiratory tract infection is more characteristic of HSP. (Choice E) In rapidly progressive glomerulonephritis, activated T lymphocytes secrete cytokines that stimulate macrophage activity, a process that contributes to crescent formation. However, T lymphocyte-mediated cytotoxicity is not a mechanism of glomerular injury in HSP. Educational objective: Henoch-Schönlein purpura is an IgA-mediated, leukocytoclastic vasculitis that presents with palpable purpura, arthralgia/arthritis, abdominal pain, and/or hematuria. Renal involvement is due to mesangial deposition of IgA immune complexes with subsequent mesangial cell proliferation, neutrophilic infiltration, and glomerular damage. __________ References: Henoch-Schönlein purpura nephritis. (http://www.ncbi.nlm.nih.gov/pubmed/24733586)

A 7-Year-Old Boy Is Brought to the Emergency Department by His