Approach

Most patients with IgAV only require adequate analgesia and supportive treatment. IgAV commonly resolves spontaneously over weeks to a few months; complete recovery occurs in 94% of children.[35] The primary goal is therefore to provide symptomatic treatment. 

Corticosteroids and/or immunosuppressants may be indicated for renal involvement, cerebral vasculitis, pulmonary haemorrhage, other life-threatening manifestations of vasculitis, and orchitis. Moderate to severe gastrointestinal (GI) or skin involvement may require corticosteroid therapy. Prescribing a corticosteroid to prevent subsequent renal inflammation is not recommended.​[36][37]​​​ [ Cochrane Clinical Answers logo ]

This section focuses on the management of children only. Discussion of the management of adults is beyond the scope of this topic.

Management of nephritis

Corticosteroids are usually indicated for children with biopsy-proven IgAV nephritis.[29] Immunosuppressants can be used as corticosteroid-sparing agents, or as a second-line therapy. There is no evidence to support the use of one particular immunosuppressant; azathioprine, mycophenolate, cyclophosphamide, or a calcineurin inhibitor (e.g., ciclosporin, tacrolimus) are all in clinical use.[33][36]​​​​[38]​ In the presence of persistent proteinuria, an ACE inhibitor or angiotensin-II receptor antagonist can prevent or limit secondary glomerular injury.[7][29]​ 

Specific management strategies depend on the severity of nephritis. Patients should be referred to a nephrologist when starting treatment for IgAV nephritis.

Mild nephritis: normal GFR and mild or moderate proteinuria

In mild nephritis that has been biopsy proven, for most clinicians the first-line treatment is oral prednisolone. Supporting evidence is, however, of low quality.[29]

Azathioprine or mycophenolate may be considered as corticosteroid-sparing agents or as second-line treatment.[29] Pulsed-dose intravenous methylprednisolone is rarely required for mild IgAV nephritis.

Mild cases associated with persistent proteinuria may be managed with an ACE inhibitor or angiotensin-II receptor antagonist, either in combination with immunosuppression or in isolation.[7]​​[29][33] While these agents are typically used in combination with immunosuppressive therapy, UK guidance suggests that they may be considered as a first-line treatment without immunosuppressive therapy in mild cases associated with persistent proteinuria, even if they have not met the threshold for a kidney biopsy.[33]​​​​

Moderate nephritis: <50% crescents on renal biopsy and impaired GFR or severe persistent proteinuria

Pulsed-dose intravenous methylprednisolone and/or oral prednisolone should be used as first-line treatment in patients with moderate IgAV nephritis.[29] Pulsed-dose intravenous methylprednisolone is indicated for severe organ or life-threatening manifestations of IgAV.[29]

Azathioprine, mycophenolate, a calcineurin inhibitor, or intravenous cyclophosphamide may be used as part of first-line treatment as a corticosteroid-sparing agent or as a second-line treatment, subject to clinical features and histopathological findings of renal biopsy.​[29][33]​​ Intravenous cyclophosphamide is usually reserved for more severe cases.

An ACE inhibitor or angiotensin-II receptor antagonist should be added in cases of persistent proteinuria.[7][29][33]​​​​

Severe nephritis: >50% crescents on renal biopsy and impaired GFR or severe persistent proteinuria

Severe IgAV nephritis is managed in a similar manner to severe systemic small vessel vasculitides, such as ANCA-associated vasculitis. An immunosuppressant in combination with an intravenous and/or oral corticosteroid is recommended to induce remission.[29]

Evidence from uncontrolled observational studies suggests that pulsed-dose intravenous methylprednisolone may improve outcomes.[39][40]

There is a lack of evidence to support a preferred immunosuppressant.[33][36][38] The SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) guideline recommends cyclophosphamide first line for remission induction.[29] Azathioprine, a calcineurin inhibitor, or mycophenolate may be used as second-line options.[29][33]​​​​

Once remission is achieved with induction therapy, maintenance therapy is recommended. Azathioprine, a calcineurin inhibitor, or mycophenolate may be used in combination with an low-dose oral corticosteroid for maintenance treatment.[29][33]

There is a lack of evidence regarding duration of induction and maintenance phases, weaning of treatment, and monitoring treatment response. Expert supervision is required.

An ACE inhibitor or angiotensin-II receptor antagonist should be added in cases of persistent proteinuria.[7][29][33]​​

Renal transplant may be required in patients who progress to end-stage renal disease; the risk of relapse in the graft is low.[41]

Other organ involvement

The skin rash of IgAV can be managed conservatively in the majority of cases. A topical corticosteroid may be used for dermatological manifestations.

Joint pain can be treated with either paracetamol or a non-steroidal anti-inflammatory drug (NSAID) such as ibuprofen (considered equally efficacious); mild to moderate abdominal pain can be managed with paracetamol, rest, and supportive care.[31]​ Concerns about renal toxicity, cardiovascular events, and GI bleeding often limit the use of NSAIDs, and they should not be used first line for pain management in patients with IgAV. NSAIDs should be used at the lowest effective dose for the shortest duration possible.

Patients with severe rash (such as skin blistering or necrotic areas), moderate to severe GI involvement, or orchitis are likely to respond to a short course of corticosteroid treatment and/or immunosuppressant.[33][42][43][44]​​​​ In practice, immunosuppressants are rarely required for children without nephritis, and there is very little evidence to guide choice of treatment. Expert consultation is recommended.

Corticosteroids are not recommended for musculoskeletal involvement, because one study found that corticosteroid treatment did not reduce the duration of musculoskeletal symptoms.[31]

Severe vasculitis

There is some evidence to suggest that patients with severe IgAV nephritis have more severe extrarenal symptoms.[8]​ In any case of severe extrarenal symptoms such as organ or life-threatening vasculitis (including cerebral vasculitis, or pulmonary haemorrhage), hospital admission, intravenous corticosteroids, and immunosuppressants are recommended.[29]

In severe, immediately life-threatening disease, plasmapheresis may be considered; however, the lack of a causative antibody may make active monitoring more challenging than in other forms of vasculitis.​[37][45]​​​ Evidence on the use of plasmapheresis in patients with IgAV is limited. One systematic review assessed the use of plasmapheresis in patients with IgAV and rapidly progressive glomerulonephritis. In the included case reports and case series, 76.3% (29/38 patients) achieved remission and 23.6% (9/38 patients) progressed to end-stage kidney disease.[45]​ Case series also suggest plasmapheresis may be beneficial for patients with life- or organ-threatening extrarenal complications of IgAV.[37][46]​​ In cases of severe abdominal pain or rectal bleeding, complications such as intestinal intussusception must be excluded.[33]

Relapsed/refractory disease

Relapsing/refractory disease is rare, and there is limited evidence for management.[33]​ Consult a specialist for guidance on managing children with relapsing/refractory disease.

Adverse effects associated with immunosuppressant therapy

Corticosteroids and immunosuppressants are associated with numerous adverse effects, including some serious adverse effects. The risks and benefits of treatment should be assessed before starting treatment. Patients should be closely monitored during treatment.

Corticosteroids

  • Long-term corticosteroid therapy may be associated with serious adverse effects including growth retardation, adrenal suppression, Cushing syndrome, glaucoma, cataracts, increased risk of infection, osteoporosis, and osteonecrosis. Cardiovascular, GI, and neuropsychiatric adverse effects are also possible. Preventative measures should be taken where possible (e.g., gastroprotection, bone protection, Pneumocystis pneumonia prophylaxis). Monitor growth velocity in children.

Cyclophosphamide

  • Cyclophosphamide may be associated with bone marrow suppression, pulmonary toxicity, hepatotoxicity, haemorrhagic cystitis, and an increased risk of infections and malignancy. Doses should be taken in the morning with increased fluid intake to prevent haemorrhagic cystitis; mesna may be prescribed in some patients, if appropriate.

Azathioprine

  • Azathioprine may be associated with GI adverse effects, dose-related haematological toxicities, hepatotoxicity, pancreatitis, and an increased risk of infections or malignancy.

Mycophenolate

  • Mycophenolate may be associated with GI adverse effects, bone marrow suppression, haematological toxicities, and an increased risk of infections and malignancy.

Calcineurin inhibitors

  • Calcineurin inhibitors may be associated with nephrotoxicity, neurotoxicity, hepatotoxicity, gingival hyperplasia, hypertension, and an increased risk of infections and malignancy. Serum drug monitoring is recommended.

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