Immunoglobulin A Vasculitis (IgAV)

 Genetic and Ethnic Susceptibility

• Genome-wide association studies have implicated several HLA loci in IgAV, including the HLA-DQA1 and DQB1 intergenic regions, HLA-DRB1*01:11, HLA-B1*13, and the haplotype DQA101:01/DQB105:01/DRB1*01:01.
• Genes involved in vascular response and autoimmunity, such as endothelial nitric oxide synthase (eNOS) and the angiotensin-converting enzyme (ACE) gene, have been associated with increased susceptibility.
• There is a strong geographic and ethnic variation, with a higher incidence in East Asian populations, particularly Japan and China.

Infectious Triggers

• Over 75% of patients report a recent infection, most commonly of the upper respiratory tract.
• Group A Streptococcus is one of the most frequently implicated pathogens, particularly in cases involving renal involvement.
• Other bacterial and viral triggers include:
  • Bacterial: Mycoplasma, Helicobacter pylori, Yersinia, Shigella, Salmonella, Brucella, Legionella, Campylobacter, Subacute bacterial endocarditis.
  • Viral: Coxsackie virus, Hepatitis A/B, Parvovirus B19, Infectious mononucleosis (EBV), Varicella zoster virus, Adenovirus, Influenza, Parainfluenza, RSV, Rotavirus, Cytomegalovirus (CMV), COVID-19.
• COVID-19 infection and immunisation have more recently been reported as triggers, likely through endothelial damage and immune dysregulation.

Vaccination

• Various vaccines have been temporally associated with the onset of IgAV:
  • Measles, mumps, rubella (MMR)
  • Hepatitis B
  • Influenza
  • COVID-19
  • Yellow fever
  • Cholera
  • Typhoid and paratyphoid A/B

Drug-Related IgAV

• Certain medications have been implicated as potential triggers, especially in adults. These include:
  • Penicillin
  • Ampicillin
  • Cefaclor
  • Minocycline
  • Erythromycin
  • Hydralazine
  • Losartan
  • Cytarabine
  • Phenytoin
  • Quinine
  • Adalimumab
  • Infliximab

Environmental and Other Triggers

• IgAV may be triggered by:
  • Cold temperatures
  • Insect bites
  • Foods (allergic triggers)
  • Horse serum
• Rare associations include glomerulocystic kidney disease and systemic conditions such as cirrhosis, coeliac disease, and sarcoidosis, where secondary immune dysregulation may predispose to IgAV.

 Immune Complex Formation and Vascular Deposition

• The central pathological process involves the formation of IgA1-containing immune complexes, particularly those deficient in galactose. These complexes circulate and deposit in small vessels—particularly postcapillary venules—and in the mesangial regions of the kidneys.
• Immune complex deposition activates the alternative complement pathway, particularly component C3, along with fibrin deposition. This results in leukocytoclastic vasculitis marked by neutrophil and monocyte infiltration and perivascular necrosis.
• Skin biopsies reveal small-vessel vasculitis with IgA, C3, and fibrin seen on immunofluorescence microscopy.

Galactose-Deficient IgA1 and Autoimmune Complexes

• IgAV is characterised by elevated levels of circulating galactose-deficient IgA1, which exposes novel epitopes in the IgA hinge region.
• These neo-epitopes are recognised by IgG autoantibodies, forming pathogenic IgA1-IgG immune complexes. These complexes are implicated in both systemic and renal involvement.
• The reduced galactosylation is believed to result from diminished β1,3-galactosyltransferase activity in peripheral B cells.

Cytokine and Complement Activation

• Inflammatory cytokines such as IL-1, IL-6, TNF-α, and TGF-β are elevated and contribute to IgA production, endothelial injury, and recruitment of immune cells.
• Endothelin-1 and hepatocyte growth factor levels increase during the acute phase, reflecting endothelial activation.
• Matrix metalloproteinase-9 (MMP-9), thrombin-antithrombin complex, D-dimer, and von Willebrand factor are elevated during flares, indicating systemic inflammation and hypercoagulability.

Genetic and Environmental Contributions

• Genetic susceptibility is supported by associations with HLA-B35, HLA-DRB1, and MEFV gene mutations. Variants in genes regulating cytokine production, O-glycosylation, and endothelial responses (e.g., IL-18, eNOS, ACE) may modulate disease severity.
• Triggers include a variety of infections (e.g., group A streptococcus, Mycoplasma, Helicobacter pylori), environmental factors, and some medications. While vaccination (particularly with MMR) has been weakly associated in rare instances, it is not considered a significant risk factor, and routine vaccination should continue.

Relationship to IgA Nephropathy

• IgAV and IgA nephropathy share core pathological features such as galactose-deficient IgA1 and mesangial IgA deposition. However, they differ in clinical presentation and disease course.
• IgA nephropathy predominantly affects the kidneys and is more common in adults, while IgAV usually affects children and presents with systemic features.
• Patients with IgAV-associated nephritis may later develop IgA nephropathy, and familial clustering of both conditions has been reported.
• Despite overlaps, renal histopathology shows distinctions: IgAV tends to have more endothelial proliferation and less global sclerosis compared to IgA nephropathy.

Organ-Specific Manifestations

• The skin, joints, gastrointestinal tract, and kidneys are most commonly affected. Immune complex deposition leads to purpura, arthralgia, abdominal pain, and nephritis.
• Galactose-deficient IgA1 appears to localise to affected organs and correlates with disease activity, particularly in nephritis.
• The mesangial deposits in kidneys may co-localise with C3, IgG, and occasionally IgM, reflecting a mixed immune response.

 Age Distribution and Incidence

• IgAV predominantly affects children, particularly those aged between 2 and 10 years. The peak incidence occurs between the ages of 4 and 7 years.
• Approximately 90% of cases occur in children under 10, with markedly fewer cases in adolescents and adults.
• In children, the annual incidence ranges from 10 to 27 per 100,000 population, depending on geographic location and method of data collection.
• In the United Kingdom, a large primary care database analysis reported a childhood incidence of 27.22 per 100,000 person-years.
• In North America, reported rates are slightly lower, with approximately 13.5 cases per 100,000 children annually.

Sex and Ethnic Distribution

• Males are slightly more frequently affected than females, with male-to-female ratios as high as 2:1 in some cohorts.
• Ethnic disparities are observed, with the highest incidence seen among white and Asian children, and the lowest among black populations.

Seasonal Trends

• IgAV shows a pronounced seasonal variation, with the majority of cases presenting during the autumn, winter, and early spring months.
• This seasonal trend aligns with peaks in upper respiratory tract infections, which are a common preceding trigger in IgAV.

Age-Related Clinical Variability

• Younger children are more likely to present with the classical tetrad of IgAV: palpable purpura, arthralgia or arthritis, abdominal pain, and renal involvement.
• As age at onset increases during childhood, the incidence of joint and gastrointestinal symptoms tends to decrease, while the risk of renal complications increases.
• Adults with IgAV are more likely to have a severe and potentially progressive renal disease course compared to children.

 Prodromal Phase

• Patients often experience non-specific symptoms such as:
  • Headache
  • Anorexia
  • Fatigue
  • Low-grade fever
• These symptoms may precede the more recognisable clinical features by several days.

Skin Symptoms

• Palpable purpura is nearly universal and typically appears on the buttocks, lower limbs, and extensor surfaces.
• The rash may initially resemble macules or urticarial lesions, evolving into non-blanching purpura and petechiae, often occurring in crops.
• Lesions vary in colour (red to purple to rust) and resolve over approximately ten days.
• In some cases, particularly in adults, lesions may become bullous, necrotic, or persist in a chronic relapsing course.
• A skin-limited variant—Acute haemorrhagic oedema of infancy (AHEI)—presents with striking purpura and swelling, particularly in infants aged 4–24 months.

Joint Symptoms

• Arthralgia or arthritis occurs in 60–84% of patients and may be the presenting complaint in up to 25% of children.
• Symptoms typically affect the knees, ankles, and less frequently, the hands and wrists.
• Joint symptoms are usually migratory, transient, and non-destructive, often without warmth or significant swelling.
• Young children may refuse to walk due to lower extremity discomfort.
• Joint involvement may precede skin findings by one to two days.

Gastrointestinal Symptoms

• Present in approximately 50% of patients, GI symptoms can be initial or concurrent with other signs.
• Common complaints include:
  • Colicky abdominal pain
  • Nausea and vomiting
  • Diarrhoea, with or without gross or occult blood
  • Haematemesis
• Severe complications may include:
  • Intussusception (2–3% of cases)
  • Bowel infarction or perforation
  • Appendicitis
• Gastrointestinal manifestations may precede skin signs in up to 35% of cases, complicating early diagnosis.

Renal Symptoms

• Renal involvement is seen in 20–54% of children, typically developing 1–3 months after rash onset.
• Historical indicators include:
  • Tea- or cola-coloured urine (suggestive of haematuria)
  • Periorbital or lower limb swelling (due to proteinuria)
  • Reduced urine output
  • Hypertension-related symptoms, such as headache or visual disturbances
• Persistent haematuria and proteinuria are red flags for progressive nephritis.

Scrotal and Urogenital Symptoms

• Around 13–38% of boys may report scrotal pain or swelling, occasionally as the initial complaint.
• Symptoms are typically unilateral and may mimic testicular torsion.
• Pain may radiate and be associated with nausea or systemic discomfort.

Neurological Symptoms

• Rare but important historical features include:
  • Headaches
  • Seizures
  • Altered mental status
  • Ataxia
  • Focal neurological deficits
     These may suggest cerebral vasculitis or hypertensive encephalopathy and are more commonly documented in older children or adults.

Respiratory and Other Systemic Complaints

• Though uncommon, some patients may describe:
  • Shortness of breath
  • Cough with haemoptysis, potentially indicating pulmonary haemorrhage
• Female patients may report dysmenorrhoea or other menstrual disturbances in rare cases.

Potential Trigers and Risk Factors Identified in History

• Recent upper respiratory tract infection, especially streptococcal, is frequently reported.
• Seasonal clustering in autumn and winter months is typical.
• Medication use (e.g., penicillin, hydralazine, cefaclor) may be noted, especially in adult-onset cases.
• Family history of autoimmune or renal disease may be relevant in some contexts.

Skin Examination

• Palpable purpura is the hallmark finding and present in virtually all patients. These lesions are:
  • Non-blanching, raised, and symmetric.
  • Typically distributed over dependent areas such as the lower extremities, buttocks, and, in young children, the upper limbs and back.
  • Lesions evolve from erythematous macules or urticarial wheals to petechiae, and then to palpable purpura.
  • Lesions appear in crops, ranging from 2–10 mm, and may coalesce into ecchymoses or plaques.
  • Colour progression: red → purple → rust-brown before fading over ~10 days.
  • In younger children, subcutaneous oedema (especially periorbital, scalp, and dorsum of hands or feet) is common.
  • In some cases, haemorrhagic vesicles, bullae, or targetoid and erythema multiforme–like lesions may be present.
  • The “cockade” pattern in infants with acute haemorrhagic oedema of infancy (AHEI) may mimic IgAV but has minimal visceral involvement.

Musculoskeletal Examination

• Arthralgia or arthritis occurs in up to 84% of patients, often in the early stages:
  • Usually oligoarticular and transient.
  • Most frequently affects large joints of the lower limbs (knees, ankles) and occasionally the upper limbs (elbows, wrists).
  • Not associated with erythema, warmth, or effusion.
  • Joint swelling and tenderness are common, but deformity or chronic joint damage does not occur.
  • In young children, pain may lead to refusal to walk or bear weight.

Gastrointestinal Examination

• Tenderness, particularly in the periumbilical or lower quadrant areas.
• Signs suggestive of gastrointestinal bleeding (e.g., melena, occult blood in stool).
• Abdominal distension, rebound tenderness, or guarding may be seen in cases complicated by intussusception or perforation.
• Severe colicky pain may prompt consideration of surgical conditions, particularly if the rash is absent or delayed.

Renal Examination

• While often asymptomatic, physical signs may include:
  • Hypertension on blood pressure measurement.
  • In some cases, peripheral oedema may suggest nephrotic syndrome.
  • No specific findings on abdominal palpation unless renal failure leads to generalised fluid overload.

Genitourinary Examination

• In boys, scrotal involvement is seen in up to 14–38%:
  • Presenting with unilateral or bilateral pain, swelling, and erythema of the scrotum.
  • May mimic testicular torsion but shows preserved or increased blood flow on Doppler ultrasound.
  • May be associated with epididymitis or orchitis.

Neurological Examination

• Neurological signs are rare but include:
  • Headache, seizures, ataxia, or altered mental status if central nervous system involvement occurs.
  • Focal deficits may suggest stroke or vasculitis-related haemorrhage.
  • Peripheral neuropathies and mononeuritis multiplex have also been reported, particularly in adults.

Pulmonary Examination

• Lung auscultation is typically normal in children, although rare cases may reveal:
  • Reduced breath sounds or crackles in cases of pulmonary haemorrhage.
  • Signs of respiratory compromise (e.g., tachypnoea or hypoxaemia) in severe adult cases with alveolar haemorrhage.

Initial Laboratory Investigations

 Serum IgA levels

• Elevated in approximately 50–70% of patients. Higher levels correlate with renal involvement but are not diagnostic.

Complete blood count (CBC)

• May reveal normochromic anaemia secondary to occult or overt gastrointestinal bleeding.
• Leucocytosis and elevated erythrocyte sedimentation rate (ESR) are more common when IgAV follows a bacterial infection.
• In contrast, IgAV post-viral infection often lacks acute phase reactant elevation.

Inflammatory markers

• Non-specific; ESR and C-reactive protein (CRP) are not consistently elevated and their presence may suggest an alternative diagnosis.

Coagulation profile

• Prothrombin time (PT), partial thromboplastin time (PTT), bleeding time, and platelet count are typically normal.
• Important to confirm when purpura may be due to thrombocytopenia or coagulopathy rather than IgAV.

Complement levels

• Hypocomplementemia is observed in a subset of children, particularly those with evidence of recent streptococcal infection.
• Complement levels usually normalise within 3 months.

Urinalysis

• Often normal at presentation but may later reveal haematuria, proteinuria, or red blood cell casts, signalling renal involvement.
• Early morning samples are preferred and regular monitoring is advised for at least 6 months.

Serum creatinine and electrolytes

• Used to assess renal function. Elevations indicate impaired glomerular filtration and may necessitate further renal evaluation.

Predictive Laboratory Parameters for Disease Severity

 Neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume (MPV)

• May help predict the severity of gastrointestinal involvement.
• Require further validation in larger cohort studies.

Diagnostic Confirmation

 Skin biopsy

• Indicated in patients with atypical rash or absence of rash.
• Optimal diagnostic yield from lesions less than 24 hours old.
• Histology reveals leukocytoclastic vasculitis in postcapillary venules.
• Direct immunofluorescence shows IgA (and sometimes C3 and fibrin) deposition in vessel walls.

Renal biopsy

• Indicated in cases of:
  • Severe proteinuria (>250 mg/mmol),
  • Persistent moderate proteinuria,
  • Declining renal function or acute kidney injury,
  • Nephrotic or nephritic presentation.
• Histology typically demonstrates mesangial IgA deposition, often indistinguishable from IgA nephropathy.
• Classification may follow the International Study of Kidney Disease in Children (ISKDC) criteria, supplemented by chronicity and activity indices.

Imaging Studies

 Abdominal ultrasound

• Indicated for severe abdominal pain to exclude complications such as intussusception or bowel perforation.

Scrotal ultrasound

• Performed in males presenting with testicular pain or swelling to evaluate for epididymo-orchitis or torsion.

Endoscopic studies

• In patients with isolated abdominal symptoms and diagnostic uncertainty, oesophagogastroduodenoscopy or video capsule endoscopy may reveal petechiae, erythema, or ulcerations consistent with vasculitic involvement.

Diagnostic Criteria

• Diagnosis is primarily clinical and based on:
  • Palpable purpura without thrombocytopenia or coagulopathy.
  • Plus two of: arthritis/arthralgia, abdominal pain, and renal involvement.
• The absence of purpura at initial presentation may necessitate biopsy to confirm diagnosis.

Conditions Presenting with Purpura

• Immune thrombocytopenia (ITP), leukaemia, disseminated intravascular coagulation (DIC), and thrombotic microangiopathies (e.g., haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura) may present with petechiae and purpura. These are typically associated with thrombocytopenia or coagulopathy—distinguished by abnormal platelet counts and coagulation studies, unlike IgAV where these are usually normal.
• Acute haemorrhagic oedema of infancy (AHEI) presents similarly with purpura and oedema in infants, but kidney and gastrointestinal involvement are rare. Histology may reveal leukocytoclastic vasculitis with occasional IgA deposition, leading to overlap with IgAV.
• Hypersensitivity vasculitis, often triggered by infections or drugs, shares histological features with IgAV but lacks IgA deposition. Systemic features such as urticaria and lymphadenopathy are more prominent.
• Small vessel vasculitides such as granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) may present with purpura, renal involvement, or neuropathy, though these are rare in children. IgA deposition is absent in these conditions, and autoimmune serologies (e.g., ANCA) may be positive.

Conditions Presenting with Arthralgia or Arthritis

• Joint symptoms in IgAV may precede rash in up to 15% of cases. Before the appearance of cutaneous signs, consider:
  • Juvenile idiopathic arthritis (JIA) – chronic, oligoarticular arthritis.
  • Systemic lupus erythematosus (SLE) – often with other systemic features and positive ANA or anti-dsDNA.
  • Acute rheumatic fever – post-streptococcal, migratory arthritis, with evidence of recent infection (e.g., positive ASO titre).
  • Septic arthritis – monoarticular, erythematous, warm joint with fever; diagnosis may require aspiration.
  • Reactive arthritis – post-infectious arthritis (e.g., following genitourinary or gastrointestinal infection), generally without purpura.
  • Transient synovitis (toxic synovitis) – a self-limited condition affecting the hip in children.

Conditions Presenting with Abdominal Pain

• Appendicitis and other acute abdominal emergencies must be considered, especially in the absence of rash. Serial abdominal examinations and imaging (e.g., ultrasound) are essential.
• IgAV gastrointestinal symptoms may mimic intussusception, bowel perforation, or infarction, and imaging is often necessary.

Conditions Presenting with Renal Involvement

• IgA nephropathy is histologically identical to the renal lesion in IgAV, with IgA deposition in the mesangium. Unlike IgAV, it lacks systemic features such as purpura or gastrointestinal symptoms.
• Other causes of glomerulonephritis such as post-infectious glomerulonephritis, lupus nephritis, and ANCA-associated vasculitis can mimic the renal manifestations of IgAV but have distinct serologic and histopathologic profiles.

Laboratory and Histopathological Clues

• Normal platelet count and coagulation parameters help rule out thrombocytopenic and coagulopathic conditions.
• Negative autoimmune serologies (ANA, dsDNA, ANCA) favour IgAV over other autoimmune vasculitides.
• Complement levels are typically normal in IgAV but may be reduced in SLE and post-streptococcal glomerulonephritis.
• Skin or renal biopsy confirming leukocytoclastic vasculitis with predominant IgA deposition distinguishes IgAV from most mimics.

General Principles

• Most children with IgA vasculitis (IgAV) recover spontaneously with supportive care including hydration, rest, and pain relief. Hospitalisation is reserved for complications such as severe abdominal pain, GI bleeding, or renal involvement.
• Analgesia with paracetamol is first-line; NSAIDs can be used cautiously for joint and abdominal pain, though they should be avoided in patients with renal impairment or gastrointestinal bleeding.
• Corticosteroids are not routinely indicated for mild disease, and evidence does not support their use for the prevention of renal involvement. However, they are useful for severe manifestations such as significant gastrointestinal symptoms, orchitis, cerebral vasculitis, and pulmonary haemorrhage.

Renal Involvement (IgAV Nephritis)

Referral & Evaluation

• All cases with renal involvement should be referred to a nephrologist.
• Management depends on biopsy findings and degree of proteinuria or renal dysfunction.

Mild Nephritis

• Normal glomerular filtration rate (GFR) with mild to moderate proteinuria.
• First-line treatment is typically oral corticosteroids (e.g., prednisolone).
• ACE inhibitors or ARBs may be initiated in patients with persistent proteinuria even without immunosuppression.

Moderate Nephritis

• Renal biopsy showing <50% crescents with impaired GFR or persistent severe proteinuria.
• Managed with pulsed IV methylprednisolone and/or oral corticosteroids.
• Corticosteroid-sparing agents include azathioprine, mycophenolate, or calcineurin inhibitors. Cyclophosphamide is reserved for more severe disease.

Severe Nephritis

• 50% crescents on biopsy or significant renal dysfunction.
• Aggressive immunosuppression is required, typically cyclophosphamide plus corticosteroids for induction.
• Maintenance therapy may include azathioprine or mycophenolate with tapering corticosteroids.
• Plasmapheresis may be considered in rapidly progressive glomerulonephritis, though evidence is limited.

End-stage Renal Disease

• Renal transplantation may be required. Relapse in the transplanted kidney is uncommon.

Gastrointestinal Involvement

• Paracetamol is first-line for mild to moderate pain. NSAIDs are second-line but avoided in patients with renal or GI involvement.
• Severe abdominal pain, rectal bleeding, or signs of acute abdomen warrant urgent imaging to exclude complications such as intussusception or perforation.
• Corticosteroids are used in moderate to severe gastrointestinal disease unresponsive to conservative management.
• Parenteral corticosteroids are preferred if oral absorption is compromised due to bowel oedema.

Skin and Joint Involvement

• Skin lesions typically resolve spontaneously. Topical corticosteroids may be used if symptomatic.
• Arthralgia and arthritis are managed with paracetamol or NSAIDs.
• Corticosteroids are not routinely indicated for musculoskeletal symptoms, as they have not been shown to reduce symptom duration.
• Severe dermatological manifestations such as necrotic or blistering lesions may require systemic corticosteroids.

Severe Vasculitis and Multisystem Involvement

• Cerebral vasculitis and pulmonary haemorrhage necessitate hospitalisation, intravenous corticosteroids, and immunosuppressive therapy.
• Plasmapheresis may be used in selected cases with life-threatening complications.
• Close monitoring is essential due to the potential for corticosteroids to obscure signs of acute complications, especially in the GI tract.

Refractory or Relapsing Disease

• Rare and poorly characterised; managed in conjunction with specialist input.
• Case reports suggest potential benefit from alternative immunomodulators such as rituximab, IVIG, colchicine, dapsone, and mycophenolate in refractory cases.

Hospitalisation Criteria

• Inability to maintain oral hydration.
• Severe abdominal pain or GI bleeding.
• Altered mental or respiratory status.
• Significant joint pain impairing ambulation.
• Renal insufficiency, hypertension, or nephrotic syndrome.
• In-hospital care involves IV hydration, nutritional support, and close monitoring for signs of haemorrhage, obstruction, peritonitis, or CNS involvement.

Adverse Effects of Treatment

Corticosteroids

• Risks include growth suppression, adrenal insufficiency, infection, osteoporosis, hyperglycaemia, and psychological effects.
• Prophylactic strategies include gastroprotection and bone mineral density preservation.

Cyclophosphamide

• May cause bone marrow suppression, haemorrhagic cystitis, infertility, malignancy risk, and hepatotoxicity. Hydration and mesna are used to mitigate bladder toxicity.

Azathioprine and Mycophenolate

• GI intolerance, haematological toxicity, hepatotoxicity, and infection risks are common.

Calcineurin Inhibitors

• Associated with nephrotoxicity, neurotoxicity, hypertension, and gingival hyperplasia; require serum level monitoring.

 Typical Clinical Course and Resolution

• Most children with IgAV experience full recovery within eight weeks, with only a small proportion (fewer than 5%) developing chronic symptoms or complications.
• Younger children, particularly those under three years, tend to have milder disease and fewer relapses compared to older children and adults.
• The disease is fatal in only the rarest of cases.

Recurrence and Relapsing Course

• Approximately one-third of children experience at least one relapse, often within four to nine months after initial presentation. Each episode tends to be milder than the last.
• Relapses have been associated with the presence of joint and gastrointestinal involvement during the initial presentation.
• Although most relapses occur early, late recurrences—up to seven years after the initial event—have been reported.
• Persistent purpura, especially around the buttocks, and gastrointestinal bleeding are associated with a higher risk of renal complications and relapses.

Renal Involvement and Long-Term Outcomes

• Kidney involvement is the most significant predictor of long-term morbidity and the primary driver of mortality in IgAV.
• Up to 15% of patients with renal manifestations may develop chronic kidney disease (CKD); however, only about 1–2% progress to end-stage kidney disease (ESKD).
• Predictors of poor renal outcome include:
  • Persistent nephrotic-range proteinuria
  • Elevated serum creatinine
  • Hypertension
  • Histologic findings such as crescents on renal biopsy
• The degree of proteinuria at presentation and its persistence beyond three months are strong indicators of long-term renal outcome.
• A normal urinalysis at six months post-diagnosis in patients without initial renal involvement is associated with a negligible risk of future kidney disease.

Gastrointestinal Complications

• While often self-limiting, gastrointestinal manifestations can lead to significant morbidity.
• Complications may include:
  • Intussusception (commonly ileo-ileal)
  • Bowel infarction or perforation
  • Massive gastrointestinal bleeding
  • Pancreatitis
  • Hydrops of the gallbladder

Prognosis by Renal Syndrome Subtype

• Nephrotic + nephritic syndrome: >50% progress to CKD
• Nephrotic syndrome alone: ~40% progress to CKD
• Nephritic syndrome alone: ~15% progress to CKD
• Heavy non-nephrotic proteinuria: ~15% progress to CKD
• Haematuria ± minimal proteinuria: <5% progress to CKD
• Nephrotic syndrome <3 months: Rarely progresses to ESKD
• Nephrotic syndrome >3 months: ~40% progress to ESKD

Prognosis in Adults

• Adults tend to have a more severe disease course and worse renal outcomes than children, particularly those diagnosed after age six.
• Persistent renal abnormalities and need for long-term immunosuppression are more common in this group.

Other Long-Term Considerations

• Women who had IgAV in childhood may be at increased risk for hypertension and proteinuria during pregnancy.
• Chronic kidney disease may manifest years after apparent clinical recovery, indicating the need for long-term follow-up in patients with nephritis.

Renal Complications

 Haematuria and Proteinuria

• These are the most common renal findings.
• Persistent haematuria with or without proteinuria may reflect ongoing glomerular inflammation.

Nephrotic Syndrome

• Occurs in more severe cases and is associated with increased risk of chronic kidney disease (CKD).

Rapidly Progressive Glomerulonephritis (RPGN)

• Severe IgAV nephritis characterised by crescents on biopsy may mimic RPGN.
• Leads to accelerated loss of renal function if untreated.

Chronic Kidney Disease and ESRD

• Approximately 1–15% of children with IgAV nephritis develop chronic renal failure.
• The progression to end-stage renal disease (ESRD) is rare but increases with the severity and duration of nephritis.
• Key predictors of long-term renal dysfunction include:
  • Persistent nephrotic syndrome >3 months
  • Elevated creatinine at presentation
  • Nephritic-nephrotic presentation
  • Histological features such as crescent formation on biopsy

Management

• Requires immunosuppressive therapy.
• Close follow-up with a nephrologist is essential.
• In some cases, renal transplantation may be needed.

Gastrointestinal Complications

 Intussusception

• A recognised complication in children, often ileoileal.
• Presents with colicky abdominal pain, vomiting, and bloody stools.
• Urgent imaging and potential surgical intervention are needed.

GI Haemorrhage

• Can range from occult bleeding to massive haemorrhage.
• May lead to anaemia or haemodynamic instability.

Bowel Infarction or Perforation

• Rare but life-threatening.
• Requires prompt surgical management.

Other GI Events

• Pancreatitis and hydrops of the gallbladder have been reported in isolated cases.

Management

• Supportive care is standard.
• Corticosteroids may be used for severe abdominal symptoms.
• Refractory or life-threatening symptoms necessitate hospitalisation and surgical consultation.

Pulmonary Complications

 Pulmonary Haemorrhage

• A rare but serious manifestation.
• Presents with haemoptysis, dyspnoea, and hypoxaemia.
• Associated with severe systemic vasculitis.

Pleural Effusion

• Reported in some cases, usually as part of systemic inflammation.

Management

• Requires high-dose corticosteroids and immunosuppressive agents.
• Plasmapheresis may be needed for severe or refractory pulmonary involvement.

Neurological Complications

 CNS Haemorrhage and Seizures

• Uncommon complications.
• May present with altered mental status, focal neurological signs, or seizures.

Peripheral Neuropathy

• Though rarely seen, can manifest as sensory or motor deficits.

Prognosis

• Generally favourable.
• Most symptoms resolve over time.
• Persistent or severe symptoms require neuroimaging and specialist evaluation.

Other Complications

 Testicular Involvement

• Orchitis and testicular torsion have been observed, particularly in boys.
• Scrotal pain and swelling should prompt ultrasonography to rule out torsion.

Ocular Manifestations

• Very rare.
• Occasional reports of keratitis or uveitis.

Cutaneous Necrosis

• Severe purpura may evolve into necrotic lesions or ulceration in rare cases.

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