IgA nephropathy (primary)<\/strong> IgA vasculitis nephritis (Henoch\u2013Sch\u00f6nlein)<\/strong> IgA-dominant infection-related GN<\/strong> Lupus nephritis (as mimic)<\/strong> Secondary (“hepatic”) mesangial IgA<\/strong> Dermatitis herpetiformis<\/strong> Linear IgA bullous dermatosis<\/strong> IgA pemphigus<\/strong> Cutaneous IgA vasculitis<\/strong> Selective IgA deficiency<\/strong> The renal group IgA nephropathy (primary) The commonest primary glomerulonephritis worldwide, with a marked predilection for East Asian and, to a lesser extent, European populations, and a peak in the second and third decades. The clinical signature is synpharyngitic visible haematuria \u2014 gross haematuria within a day or two of a mucosal (usually upper respiratory) […]<\/p>\n","protected":false},"author":1119,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-183","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"yoast_head":"\n
\nThe commonest primary glomerulonephritis worldwide, with a marked predilection for East Asian and, to a lesser extent, European populations, and a peak in the second and third decades. The clinical signature is synpharyngitic<\/em> visible haematuria \u2014 gross haematuria within a day or two of a mucosal (usually upper respiratory) infection \u2014 which contrasts usefully with the one-to-two-week latency of post-streptococcal GN. The rest present with asymptomatic microscopic haematuria and variable proteinuria picked up on screening. Pathogenesis is the four-hit model: circulating galactose-deficient IgA1 (hit one), glycan-specific autoantibodies against it (hit two, often IgG), immune-complex formation (hit three), and mesangial deposition with alternative- and lectin-pathway complement activation (hit four). Light microscopy shows mesangial hypercellularity and matrix expansion, with variable endocapillary proliferation, crescents and segmental sclerosis; the Oxford MEST-C score formalises the prognostically relevant lesions. IF gives dominant\/codominant mesangial IgA with C3, frequently IgG\/IgM, and \u2014 the point that keeps recurring \u2014 no C1q. EM confirms paramesangial dense deposits. Course is heterogeneous, with a substantial minority reaching ESRD over two decades.<\/p>\n
\nBest understood as the systemic expression of the same galactose-deficient-IgA1 biology, so the renal lesion is histologically and immunopathologically indistinguishable<\/em> from primary IgAN \u2014 the biopsy alone cannot separate them. What separates them is the clinical tetrad: palpable purpura over the buttocks and lower limbs, arthralgia\/arthritis, abdominal pain (with the risk of intussusception and GI haemorrhage), and nephritis. It is the commonest vasculitis of childhood, tends to be self-limiting in children, and behaves worse renally in adults. Crescents dominate the prognosis, and the paediatric lesion is graded by the ISKDC crescent-based scheme rather than MEST-C. Skin DIF shows perivascular IgA, tying it to the cutaneous vasculitis below.<\/p>\n
\nThe classic trap on this panel: IgA dominance or codominance in a GN that is emphatically not<\/em> IgAN. It is typically staphylococcal (MRSA or MSSA), disproportionately in older and diabetic patients, and \u2014 unlike post-streptococcal disease \u2014 the infection is often ongoing rather than resolved (deep-seated soft-tissue, skin, endocarditis or visceral). Histology is an acute diffuse endocapillary and exudative proliferative GN with neutrophils, sometimes crescents, and subepithelial “humps” on EM. IF shows IgA with characteristically strong<\/em> C3. The disambiguators from IgAN are therefore threefold: the clinical setting (active infection, diabetic\/elderly), the exudative proliferative morphology with humps, and the disproportionate C3. Prognosis is guarded, especially in diabetics.<\/p>\n
\nIncluded only because its “full-house” IF (IgG, IgA, IgM, C3 and<\/em> C1q) contains IgA, so isolated attention to the IgA channel is misleading. C1q positivity is the swing marker that pulls the case towards lupus and away from IgAN. Corroborating features \u2014 tubuloreticular inclusions on EM, wire-loop deposits, extraglomerular deposits along the TBM and vessels \u2014 and the ISN\/RPS class then take over. IgA here is a passenger, never dominant in the IgAN sense.<\/p>\n
\nReduced hepatic clearance of IgA and IgA-containing immune complexes in chronic liver disease \u2014 most consistently alcohol-related cirrhosis with portal hypertension \u2014 produces mesangial IgA deposition that is usually clinically silent and lacks the proliferative lesion of primary IgAN. The same incidental deposition is described, less consistently, in coeliac disease, IBD, HIV, dermatitis herpetiformis and the seronegative spondyloarthropathies. The practical error to avoid is reading incidental mesangial IgA as primary IgAN without the clinicopathological context.<\/p>\nThe cutaneous group<\/h3>\n
\nThe cutaneous face of coeliac disease: intensely pruritic grouped papulovesicles over extensor surfaces \u2014 elbows, knees, buttocks, scalp \u2014 usually excoriated by the time they present. Histology is a subepidermal blister with neutrophilic microabscesses at the tips of the dermal papillae. DIF on perilesional or clinically normal skin shows granular<\/em> IgA at the papillary tips (with variable BMZ granularity). The autoantigen is epidermal transglutaminase (TG3), the cousin of the tissue transglutaminase (TG2) targeted in gut coeliac disease, and the HLA association is DQ2\/DQ8. It responds to a gluten-free diet and to dapsone. The clinically useful cross-link for your GI work: a confirmed DH diagnosis is effectively a coeliac diagnosis, and these patients carry the associated enteropathy and lymphoma risk even when gut symptoms are absent.<\/p>\n
\nA subepidermal blistering disease defined by homogeneous linear<\/em> IgA along the basement membrane zone \u2014 the pattern, not the immunoglobulin class alone, is what distinguishes it from DH. It has an adult idiopathic form and a childhood form (chronic bullous disease of childhood) with the characteristic annular “cluster of jewels”\/string-of-pearls arrangement of peripheral blisters. The drug-induced variant is classically vancomycin-associated (also captopril, NSAIDs and others). The target antigens are cleavage products of BP180\/collagen XVII (LAD-1, LABD97). Routine histology \u2014 a subepidermal blister with neutrophils \u2014 overlaps with both DH and bullous pemphigoid, so DIF is the arbiter: linear rather than granular, IgA rather than IgG.<\/p>\n
\nIntraepidermal acantholysis with intercellular<\/em> (“chicken-wire”) IgA on DIF \u2014 the same cell-surface pattern as classical pemphigus but with IgA replacing IgG, and generally a more pustular, less erosive clinical picture (flaccid pustules, sometimes sunflower-like annular lesions with central crust). Two subtypes: the subcorneal pustular dermatosis (SPD) type, with subcorneal pustules and desmocollin 1 as the target antigen, and the intraepidermal neutrophilic (IEN) type, with pustules deeper in the epidermis and a less consistently defined antigen. The contrast to hold in mind is that pemphigus vulgaris and foliaceus are IgG-mediated intercellular disease; IgA pemphigus is their IgA counterpart, generally milder and steroid\/dapsone-responsive.<\/p>\n
\nA leukocytoclastic vasculitis of superficial dermal small vessels with perivascular IgA on DIF \u2014 the skin lesion (palpable purpura) that, when accompanied by the systemic tetrad, marks IgA vasculitis, and which links directly back to the renal lesion above. The presence of IgA in the vessel walls is what elevates a non-specific leukocytoclastic vasculitis into this specific, systemically significant category.<\/p>\nThe immunodeficiency<\/h3>\n
\nThe commonest primary immunodeficiency in populations of European descent (roughly 1 in 300\u2013700), defined by very low or absent serum IgA with preserved IgG and IgM. Most are asymptomatic; a minority have recurrent sinopulmonary and GI infection, atopy, or autoimmune disease. In tissue it shows as reduced or absent IgA plasma cells in the lamina propria, and it associates with nodular lymphoid hyperplasia and giardiasis. Two practical consequences deserve flagging on any sheet: it invalidates IgA-based coeliac serology (the IgA-tTG will be falsely negative, so total IgA must be checked and IgG-based tests used instead), and it carries a risk of anaphylactic transfusion reactions to IgA-containing blood products in patients who have formed anti-IgA antibodies.<\/p>\n","protected":false},"excerpt":{"rendered":"