Approach Considerations
To date, no form of therapy has been found to shorten the duration of IgA vasculitis (IgAV; Henoch-Schönlein purpura) to any significant degree. Therefore, treatment remains primarily supportive in most cases. This is consonant with the understanding that IgAV is a self-limited disease. The majority of patients recover quickly (ie, within several weeks) without treatment. [104]
Management of IgAV includes adequate hydration; immediate discontinuation of any exposure to antigenic stimulants (eg, drugs); and follow-up each week for the first month, every other week for the second month, and monthly thereafter until abnormal urinary findings subside.
Hospital admission and monitoring for complications should be considered. Hospitalization should be strongly considered for IgAV patients with severe abdominal pain, significant gastrointestinal (GI) bleeding, or marked kidney insufficiency. Complications such as acute abdomen, acute scrotum, and acute kidney injury may be severe and may occur precipitously.
IgAV may mimic an abdominal emergency and, in its most severe form, result in small-bowel infarction, perforation, or both.
In adults with IgAV, permanent kidney involvement is not uncommon. All pregnant women with even mild kidney symptoms at the onset of IgAV should be carefully observed during and after pregnancy. Hematuria at disease onset and persistence of kidney manifestations during the course of IgAV are significant predictors of possible development of kidney sequelae. Other features associated with the development of kidney sequelae include the following:
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Onset in summer
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Anemia at disease onset
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Relapse
Nephropathy is treated supportively, with monitoring of fluid and electrolyte balance, restriction of salt intake, and administration of antihypertensives when needed. Various drugs (eg, corticosteroids, azathioprine, and cyclophosphamide) and plasmapheresis have been used to prevent progression of kidney disease, but the results have been inconsistent, and no data from controlled studies are available.
Dietary restrictions have no clear role in the management of IgAV. Activities can be performed as tolerated.
Supportive Management
Treatment of IgAV is primarily supportive and includes ensuring adequate hydration and monitoring for abdominal and kidney complications. For minor complaints of arthritis, edema, fever or malaise, symptomatic treatment is advised, including use of acetaminophen, elevation of swollen extremities, eating a bland diet, and adequate hydration. All unnecessary drugs should be discontinued if a drug-related etiology is suspected.
Most patients with self-limited cases can be safely discharged home with close follow-up by the primary physician. The decision for or against hospital admission depends on the physician’s customary practice and individual preference. Admission to the hospital is recommended for control of abdominal pain or vomiting, monitoring of kidney function, confirmation of a doubted diagnosis, and observation and monitoring. Patients with kidney involvement require close attention to their fluid balance, electrolyte status, and use of antihypertensives (if indicated).
A study examining prevention and treatment of kidney disease in patients with IgAV revealed no significant difference in the risk of persistent kidney disease at 6 months and 12 months in children given prednisone for 14-28 days upon presentation in comparison with placebo or supportive treatment. [105] Also, no significant difference was noted in the risk of persistent kidney disease in children given cyclophosphamide compared with supportive treatment and with cyclosporine compared with methylprednisolone.
Pharmacologic Therapy
Analgesics
Pain control is essential for quality patient care. Analgesia with nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen may reduce joint and soft tissue discomfort. Such agents are often effective and do not seem to worsen the purpura; however, they should be used cautiously in patients with renal insufficiency.
Corticosteroids
Clinicians often use corticosteroids to treat subcutaneous edema and nephritis in IgAV, as well as to ameliorate associated arthralgias and symptoms associated with GI dysfunction. However, high-quality, large, prospective studies regarding the treatment of IgAV are lacking, [105, 106, 107] and the evidence does not yet support the use of steroids to prevent or treat kidney disease. [36, 108] Some authors recommend steroids; others do not. Nevertheless, corticosteroids may be considered in the following situations:
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Persistent nephrotic syndrome
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Crescents in more than 50% of glomeruli
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Severe abdominal pain
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Substantial GI hemorrhage
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Severe soft tissue edema
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Severe scrotal edema
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Neurologic system involvement
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Intrapulmonary hemorrhage
Prednisone in a dosage of 1 mg/kg/day for 2 weeks and then tapered over 2 more weeks may shorten the duration of abdominal pain and joint symptoms, but this benefit must be weighed against the potential adverse effects of steroids. [109, 110]
A review of randomized clinical trials for any intervention used to improve renal disease in children with IgAV noted that data were very limited except for short-term prednisone; moreover, prednisone had no benefit in preventing serious long-term kidney disease. [108]
The long-term prognosis of IgAV directly depends on the severity of kidney involvement. Patients with IgAV-related kidney dysfunction may benefit from therapy. However, prophylaxis of kidney complications in IgAV, though interesting, is not currently recommended. Treatment of overt IgAV includes methylprednisolone pulse therapy and prednisone and other immunosuppressive medications. If prednisone is used, a regimen consisting of 1-2 mg/kg/day PO for 7 days is recommended. Antihypertensives may be indicated with kidney involvement.
Faedda reported favorable results from the following protocols in patients with severe IgAV [111] :
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Induction with 250-750 mg of intravenous (IV) methylprednisolone daily for 3-7 days plus oral (PO) cyclophosphamide 100-200 mg/d
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Maintenance with prednisone 100-200 mg PO every other day plus cyclophosphamide 100-200 mg/day PO for 30-75 days
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Tapering of prednisone by approximately 25 mg/month (with the cyclophosphamide dose remaining constant)
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Discontinuation of treatment after at least 6 months by abruptly stopping cyclophosphamide and tapering prednisone completely
Other agents
Other treatment regimens have included IV or oral steroids with or without any of the following:
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Azathioprine
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Cyclophosphamide
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Cyclosporine
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Dipyridamole
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High-dose IV immunoglobulin G (IVIg)
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Angiotensin-converting enzyme inhibitors (ACEIs)
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Angiotensin receptor blockers (ARBs)
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Danazol
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Fish oil
Of those, only cyclophosphamide has been shown to be effective in a randomized controlled trial. Although some studies have reported success, cyclosporine does not have sufficient clinical data to establish its utility in this setting. [112]
Azathioprine, mycophenolate mofetil, and urokinase must be tested before their use is consistently advocated. Guidelines for prescribing azathioprine in dermatology have been established. [113] No convincing studies have yet been conducted regarding the use of IVIg, factor XIII administration, antioxidant vitamin E, and fish oil to treat IgAV. [114]
A randomized clinical trial comparing cyclosporine with methylprednisolone pulses in IgAV with nephritis found that cyclosporine had superior efficacy and many fewer complications. [115] A study of 12 patients with severe IgAV nephritis indicated that patients did well with methylprednisolone at 30 mg/kg/day for 3 days followed by oral corticosteroids at 2 mg/kg/day for 2 months, cyclophosphamide at 2 mg/kg/day for 2 months, and dipyridamole at 5 mg/kg/day for 6 months. [116]
Some have noted that parvovirus B19–associated IgAV must be recognized in adults because the treatment of choice is IV gamma globulin combined with tumor necrosis factor (TNF)–α inhibitor therapy. Immunosuppressive therapy may lead to a persistent or worsening disease course in these patients.
Massive GI hemorrhage in isolated intestinal IgAV that is responsive to IVIg infusion has been reported. [117] IVIg was used in a complex case of IgAV with brain hemorrhage, but more work must be done to validate the use of this treatment. [118]
Dapsone has been used to treat associated purpuras and arthralgias. Iqbal and Evans found it to be effective for IgAV. [119]
Rituximab has been noted to be a successful treatment for severe refractory chronic IgAV. [120]
Factor VIII concentrate has been used to relieve abdominal pain when corticosteroids are contraindicated. Recombinant factor VIIa has been used in patients with very pronounced factor XIII deficiency and compartment syndrome.
Treatment of complicated IgAV with mycophenolate mofetil has been reported in a series of patients. [121, 122]
Beneficial effects of methylprednisolone pulses with oral prednisone was reported in a prospective case series and also suggested in patients receiving combinations of multiple immunosuppressive drugs. [123, 124, 125, 126, 127]
Kidney Disease Improving Global Outcomes (KDIGO) 2021 guidelines note there are no data to support the use of glucocorticoids in the prevention of nephritis in children with mild IgAV or absent evidence of kidney involvement. Key recommendations for the management of IgAVN in children include the following [128] :
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Urinary monitoring for nephritis is necessary for 6-12 months from initial presentation of systemic disease.
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Children with IgAVN and persistent proteinuria for >3 months should be treated with an ACEi or ARB. A pediatric nephrologist should be consulted.
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A kidney biopsy should be performed in children with nephrotic-range proteinuria, impaired GFR, or persistent moderate (>1 g/d) proteinuria.
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Oral prednisone/prednisolone or pulsed intravenous methylprednisolone should be used in children with mild or moderate IgAVN.
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Children with IgAVN with nephrotic syndrome and/or rapidly deteriorating kidney function are treated in the same way as those with rapidly progressive IgAN
Plasmapheresis
Plasmapheresis may be effective in delaying the progression of kidney disease. A case series demonstrated good outcomes in adults with severe IgAV who were treated with plasma exchange in addition to steroids. [129] In an uncontrolled study, Shenoy et al reported that children with severe IgAV and IgA nephropathy recover well if treated with plasmapheresis alone, without the need for immunosuppressive therapy. [130] Plasmapheresis has been useful in treating rapidly progressive IgAV nephritis. [131]
Surgical Intervention
Surgery may be undertaken to treat severe bowel ischemia. Kidney transplantation may be indicated in patients with severe kidney disease that is resistant to medical therapy. Successful treatment of progressive IgAV nephritis with tonsillectomy and corticosteroid pulse therapy has been reported.
Consultations
Because IgAV is a multisystem disease, consultations with the following specialists can be helpful in diagnosis and treatment:
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Dermatologist
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Gastroenterologist
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Nephrologist (particularly for assistance in determining if dialysis is indicated)
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Rheumatologist
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Dermatopathologist [132] (the utility of the consultation is limited to untypical or incomplete manifestations of IgAV to buttress positive vascular IgA immunohistochemical evidence of the deposits)
Consultation is recommended for patients with kidney involvement before discharge from the emergency department and for all patients who appear acutely ill.
Long-Term Monitoring
In all patients, urinalysis and blood pressure monitoring to evaluate for renal involvement should be continued for up to 6 months after presentation, even if initial urinalysis results were normal. Once the initial course of prednisone is administered, additional prednisone appears to have no role.
When terminal renal failure develops, long-term hemodialysis should be instituted until a kidney is available for transplantation. Mesangial deposits of IgA are common in the graft, but they rarely lead to clinical manifestations of recurrent glomerulonephritis.
Children who have demonstrated renal manifestations in the acute phase and continue to have hematuria or proteinuria should be examined every 3-6 months because renal failure or hypertension can develop up to 10 years after disease onset.
NSAIDs may be administered to address joint problems. Because of the risk of Reye syndrome, the use of NSAIDs should be discussed with the patient’s physician.
Complications
In IgAV nephritis that has progressed to end-stage kidney disease, kidney transplantation is the treatment of choice. Recurrence of glomerular IgA deposits after kidney transplantation is very frequent in patients with IgAV nephritis, but does not significantly affect the rate of graft loss. In one study, the risk of graft loss at 10-year follow-up was 7.5%. [133]
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Purpuric papules and plaques of the lower extremity characteristic of IgA vasculitis (Henoch-Schönlein purpura).
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Hemorrhagic macules, papules, and patches on the ankle and foot of a child with IgA vasculitis (Henoch-Schönlein purpura).
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Typical rash distribution of IgA vasculitis (Henoch-Schönlein purpura).
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Characteristic rash of IgA vasculitis (Henoch-Schönlein purpura).
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Older lesions of IgA vasculitis (Henoch-Schönlein purpura) demonstrating increased extravasation with ecchymoses on dorsal foot and ankle.
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A 9-year-old boy with IgA vasculitis (Henoch-Schönlein purpura). Note confluence of purpura around the ankles. Image courtesy of Pamela L Dyne, MD.
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A 7-year-old girl with IgA vasculitis (Henoch-Schönlein purpura). Image courtesy of Pamela L Dyne, MD.
