- Henoch-Schönlein Purpura (Anaphylctoid purpura)

Henoch-Schönlein Purpura (Anaphylctoid purpura)

Immune complex mediated disease contain IgA within capillaries of skin, GI and renal involvement.
Incidence:

• HSP is the commonest generalized vasculitis of childhood.
• HSP is the commonest cause of non-thrombocytopenic purpura in children.
• Can occur at any age but peaking at 3–10 years of age.
• Male : female = 2:1
• Peaks during the winter months.

Etiology: the cause is unknown.
- It is postulated that genetic predisposition and antigen exposure increase circulating IgA levels and disrupt IgG synthesis.
-The IgA and IgG interact to produce complexes that activate complement and are deposited in affected organs, precipitating an inflammatory response with vasculitis.
- Antigen may be:

• Infections (e.g. Group A ß hemolytic streptococci or ohers)
•  Insect bites
• Drugs or food allergy.

Pathology and pathogenesis:

• IgA-mediated vasculitis of small blood vessels with IgA deposits seen in these vessels, primarily those of the skin and intestine.
• Deposition of polymeric immunoglobulin A (IgA) in glomeruli. 
• IgA deposits are present by immunofluorescence,
•  Broad spectrum of glomerular lesions that can range from mild proliferation to necrotic and crescentic changes can be seen

- Alport Syndrome (Hereditary nephritis).

Alport Syndrome (Hereditary nephritis)

AS, or hereditary nephritis, is a genetically heterogeneous disease caused by mutations in the genes coding for type IV collagen, a major component of basement membranes which is present in kidney, ear, and ocular lens.

GENETICS

• The most common form of hereditary nephritis.
• Approximately 85% of patients have X-linked inheritance caused by a mutation in the COL4A5 gene encoding the α5 chain of type IV collagen.
• Autosomal recessive forms of AS (10%)are caused by mutations in the COL4A3 and COL4A4 genes on chromosome 2 encoding the α3 and α4 chains, respectively, of type IV collagen.
• An autosomal dominant form of AS linked to the COL4A3-COL4A4 gene locus occurs in 5% of cases.

PATHOLOGY
- Light microscopy:

• Kidney biopsy specimens during the 1st decade of life show few changes
• Later, the glomeruli may develop mesangial proliferation and capillary wall thickening, leading to progressive glomerular sclerosis. Tubular atrophy, interstitial inflammation and fibrosis, and lipid-containing tubular or interstitial cells, called foam cells, develop as the disease progresses.

- Thin basement membrane disease (TBMD).

Thin Basement Membrane Disease

 Thin basement membrane disease (TBMD) is defined by the presence of persistent microscopic hematuria and isolated thinning of the GBM (and, occasionally, tubular basement membranes) on electron microscopy.
Etiology:
TBMD may be sporadic or transmitted as an autosomal dominant trait.
Heterozygous mutations in the COL4A3 and COL4A4 genes, which encode the α3 and α4 chains of type IV collagen present in the GBM, result in TBMD.
Homozygous mutations in these same genes result in autosomal recessive AS. Therefore, in these rare cases, the absence of a positive family history for renal insufficiency or deafness would not necessarily predict a benign outcome. 
Clinical Features:

• Microscopic hematuria is often initially observed during childhood and may be intermittent.
• Episodic gross hematuria can also be present, particularly after a respiratory illness.
• Isolated hematuria in multiple family members without renal dysfunction is referred to as benign familial hematuria.

Routine immunofluorescence studies are normal

- IgA nephropathy (Berger nephropathy).

IgA nephropathy (Berger nephropathy)

Glomerular disease characterized by renal IgA deposits mostly in the mesangial area.

Etiology
Mucosal infection has been found to be associated with development of IgAN. Upper respiratory tract pathogen, like Hemophilus para influenzae, Coxsackie B4, Staphylococcus aureus, CMV, EBV, Enterovirus, have been found to cause IgAN.

PATHOLOGY

• Focal and segmental mesangial proliferation and increased mesangial matrix are seen in the glomerulus with few crescents.
• IgA nephropathy is an immune complex disease initiated by excessive amounts of poorly galactosylated IgA1 in the serum causing the production of IgG and IgA autoantibodies.

Clinical Features

• More often in male than in female patients.
• peak incidence between 10-30 years of age.
• Hematuria:

- There may be persistent hematuria or recurrent episodes of gross hematuria which typically resolves within days.
- Asymptomatic microscopic hematuria with or without proteinuria

• Gross hematuria often occurs within 1-2 days of onset of an upper respiratory or gastrointestinal infection
• Proteinuria is often <1000 mg/24 hr in patients with asymptomatic microscopic hematuria.
• Mild to moderate hypertension is most often seen in patients with nephritic or nephrotic syndrome, but is rarely severe enough to result in hypertensive emergencies.
• Normal serum levels of C3 in IgA nephropathy help to distinguish this disorder from poststreptococcal glomerulonephritis.
• Normal renal function
• Serum IgA levels have no diagnostic value because they are elevated in only 15% of pediatric patients.
• Flank or loin pain
• Fever may be present
• Not associated with systemic manifestations.

- Indications Renal biopsy in cases of APSGN.

Indications Renal biopsy in cases of acute post streptococcal glomerulonephritis:

• Renal insufficiency, especially if the glomerular filtration rate remains less than 30 mL/min/1.73 m 2 for more than 1 week,
• Prescence of signs of chronic renal failure
• Family history of nephritis
• Past history of renal disease.
• Presence of nephrotic syndrome,
• absence of evidence of streptococcal infection,
• normal C3 complement levels (most important),
• Hematuria, proteinuria, ↓ renal function, and/or a low C3 level persist > 2 months after onset.

- Difference between APSGN and nephrotic syndrome.

Difference between APSGN and nephrotic syndrome.

	APSGN	N.S
clinical
Strept infection	+ve	-ve
Edema	minimal	massive
HTN	++	Rare,transient
Oliguria	marked	During edema
Hematuria	++	Rare , transient
Laboratory
S.albumin	Normal	low
S.cholsterol	normal	high
C3	low	normal
ASO	Usually +ve	-ve
Proteinuria	minimal	heavy
Casts	Red & granular	hyaline
Renal function	Impaired	Usually normal