Version May 2024
INTRODUCTION — Immunoglobulin A vasculitis (IgAV), formerly called Henoch-Schönlein purpura (HSP) [1], is the most common systemic vasculitis of childhood. Ninety percent of cases occur in the pediatric age group. In contrast to other forms of systemic vasculitis, IgAV is usually self-limited and is characterized by a tetrad of clinical manifestations that vary in their presence and order of presentation:
●Palpable purpura in patients with neither thrombocytopenia nor coagulopathy
●Arthralgia and/or arthritis
●Abdominal pain
●Kidney disease
Management of IgAV includes supportive care, symptomatic therapy, and targeted treatment to decrease the risk of complications. The management and prognosis of IgAV are presented here. The pathogenesis, clinical manifestations, diagnosis, and differential diagnosis of IgAV are discussed separately. (See "IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis".)
MANAGEMENT — The vast majority of patients with IgAV recover spontaneously and can be cared for in the ambulatory setting. Therapy is primarily supportive and includes adequate hydration, rest, and symptomatic relief of pain (algorithm 1). Edema found in gravity-dependent areas, including the lower extremities, buttocks, and genital area, can be improved with bed rest and/or elevating the affected area.
Treatment of pain — Symptomatic treatment for abdominal and joint pain in patients with IgAV is reviewed in the algorithm (algorithm 1) and includes the use of acetaminophen or nonsteroidal antiinflammatory drugs (NSAIDs). Clinical experience and observational data suggest that the antiinflammatory effects of glucocorticoids can relieve many of the manifestations of IgAV, including the rash, arthritis/arthralgias, scrotal pain/orchitis, and gastrointestinal pain [2]. However, glucocorticoids are not usually indicated for these manifestations, unless symptoms are severe, given the limited data and the potential short- and long-term side effects of glucocorticoid therapy. Patients with IgAV who have gastrointestinal involvement, including bowel wall edema, may have disrupted absorption of enteral medications. Thus, failure of NSAIDs or oral glucocorticoids to benefit certain patients may be due to poor absorption. (See "Major adverse effects of systemic glucocorticoids".)
Mild-to-moderate pain — Though there are no randomized, controlled studies of the use of NSAIDs for symptomatic pain relief in patients with IgAV, they are commonly used in clinical practice. We typically prescribe NSAIDs to control pain, including joint and abdominal symptoms in patients with IgAV. Of note, there is no evidence to suggest that the risk of gastrointestinal hemorrhage in a child with bowel vasculitis is increased by the use of cyclooxygenase inhibitors. However, NSAIDs may be contraindicated in patients with active gastrointestinal bleeding or glomerulonephritis because of their effects on platelets and kidney perfusion.
For symptomatic relief of pain in patients with IgAV, we typically prescribe naproxen, 10 to 20 mg/kg divided into two doses per day, for its ease of dosing. In adolescents and adults, a maximum total daily dose of 1500 mg may be used for a few days, but a maximum dose of 1000 mg per day is suggested for longer-term use. Ibuprofen and other NSAIDs may be similarly effective and may be better tolerated in some patients, although ibuprofen requires more frequent dosing.
Severe pain — Most studies show that glucocorticoid therapy shortens the duration of abdominal pain in patients with IgAV [3-7]. However, glucocorticoids do not appear to otherwise impact the clinical course [8,9]. Thus, we suggest using prednisone (1 to 2 mg/kg per day, maximum dose of 60 to 80 mg per day) for patients with symptoms significant enough to substantially limit their oral intake; interfere with their ability to ambulate and perform activities of daily living; have severe, life-threatening IgAV; and/or require hospitalization. In patients who cannot tolerate oral medications, we administer equivalent doses of parenteral methylprednisolone (0.8 to 1.6 mg/kg per day, typical maximum dose of 64 mg per day). Intravenous methylprednisolone may be more beneficial early in the disease course, when patients have active gastrointestinal disease, due to submucosal edema and hemorrhage altering absorption of oral medications. (See 'Prevention of complications' below and 'Hospitalization' below.)
When glucocorticoids are used for treating IgAV, it is important to remember that, although the inflammation may be ameliorated, the acute pathophysiology of the disease does not appear to be altered. Accordingly, we advise lowering the glucocorticoid dose slowly, typically over three to four weeks or more, to minimize the chance of disease rebound from rapid medication tapering. In addition, patients who are treated with glucocorticoids for severe abdominal pain require particular vigilance since these glucocorticoids can obscure the signs and symptoms of abdominal catastrophes associated with IgAV. Published data as well as a practical guideline based upon expert opinion in the European initiative, Single Hub and Access Point for Paediatric Rheumatology in Europe (SHARE), do not support the use of glucocorticoids to prevent kidney disease [10,11]. (See "IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis", section on 'Gastrointestinal symptoms' and 'Prevention of complications' below.)
Treatment of kidney disease — Treatment of active kidney disease in IgAV and kidney transplantation for end-stage kidney disease are discussed in detail separately. (See "IgA vasculitis (Henoch-Schönlein purpura): Kidney manifestations", section on 'Management of IgAV nephritis'.)
Hospitalization — The rate of hospitalization and length of stay for IgAV is approximately 2.4 per 100, 000 children in the United States and has remained stable over the past decade [12]. Hospitalization is warranted for the following indications in patients with IgAV:
●Inability to maintain adequate hydration with oral intake
●Severe abdominal pain
●Significant gastrointestinal bleeding
●Changes in mental or respiratory status
●Severe pain or joint involvement limiting ambulation and/or self-care
●Kidney insufficiency (elevated creatinine), hypertension, and/or nephrotic syndrome
Intravenous hydration is provided in the hospital setting if the patient cannot maintain adequate oral intake of fluids. In addition, parenteral nutrition may be required in patients who have a severe and prolonged course of abdominal symptoms that precludes enteral nutrition.
Hospitalized patients also are monitored for potential complications from their disease. Frequent assessment of vital signs, urine output, and hematocrit, as well as serial abdominal examinations and stool examination for blood, may be required. (See "IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis", section on 'Laboratory findings' and "IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis", section on 'Additional evaluation'.)
●Patients with significant anemia may require red blood cell transfusion, as indicated by tachycardia and hypotension in a patient with a low hematocrit level. Blood loss from hemorrhage into organs such as the skin, lungs, gastrointestinal tract, or kidneys rarely depresses red blood cell levels enough to necessitate a transfusion, although superimposed decreased production due to inflammation may result in symptomatic anemia. (See "Red blood cell transfusion in infants and children: Indications".)
●Patients with an abdominal examination consistent with either signs of obstruction or peritonitis ("surgical abdomen") require prompt evaluation, including surgical consultation and/or intervention for possible intussusception, bowel infarction, or perforation. Bowel vasculitis often cannot be diagnosed by examination alone. In such cases, diagnostic imaging is necessary. Abdominal ultrasonography is typically used because it can detect changes in bowel wall thickness, hematomas, peritoneal fluid, and intussusception [13-15]. Contrast enema studies are not useful, because they may not detect small bowel intussusception (ileo-ileal), which are more commonly seen in patients with IgAV [14,15]. (See "IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis", section on 'Imaging studies'.)
●Patients with acute changes in behavior or mental status require evaluation for a potential intracranial complication, such as hemorrhage. These are rare events in IgAV. Most central nervous system findings are transient but may require additional investigation and treatment. (See "IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis", section on 'Other organ involvement'.)
●Patients with kidney disease may be hypertensive and require antihypertensive therapy. Close monitoring of fluid and electrolyte management is imperative in patients with decreased kidney function. Patients who present with nephrotic syndrome, hypertension, or kidney insufficiency are at increased risk for long-term kidney morbidity. (See "Prevention and management of acute kidney injury (acute renal failure) in children" and "IgA vasculitis (Henoch-Schönlein purpura): Kidney manifestations", section on 'Prognosis'.)
●Patients with severe arthritis usually improve with the use of NSAIDs. The risk of gastrointestinal hemorrhage resulting from bowel vasculitis has not been shown to increase when inhibitors of cyclooxygenase are used, and, therefore, these agents are not contraindicated in IgAV. When these medications fail, administration of oral or parenteral glucocorticoids will generally result in a rapid resolution of the arthritis. Rarely, a brief hospitalization may be required to address the pain of arthritis. (See 'Treatment of pain' above.)
Prevention of complications — The use of glucocorticoids in patients with IgAV is controversial. Although there may be more rapid symptomatic improvement in patients who receive glucocorticoids, it is questionable as to whether such treatment alters long-term clinical outcomes based upon available published studies [16]. In addition to the common side effects of glucocorticoid therapy (eg, hyperglycemia, hypertension, weight gain, acne, immunosuppression), there are potential side effects of glucocorticoid therapy more specific to IgAV, including the risk of obscuring the signs of compromised bowel viability if treatment is started after an intussusception has occurred, as well as masking signs of fever and pain. As a result, we do not recommend routine empiric glucocorticoid therapy for all patients with IgAV to treat mild symptoms or prevent kidney or gastrointestinal complications. (See 'Treatment of pain' above.)
Initial reported benefits of glucocorticoid therapy in preventing complications from a systematic review that included 3 randomized trials and 12 retrospective studies included decreased risk of intussusception, kidney involvement, and recurrence of disease [3]. One subsequent retrospective cohort study using an administrative database reported a decreased risk of gastrointestinal procedures (endoscopy, imaging, and surgery) in children with IgAV, who were hospitalized and treated early with glucocorticoids [17]. However, a prospective study of 223 children in Finland published after the systematic review found no effect of prednisone on the timing of the appearance of nephritis [18] or on the clinical course during six months of follow-up [19]. A randomized trial of glucocorticoids in children with IgAV found that glucocorticoid treatment did not change the frequency of proteinuria at 12 months [8]. A subsequent meta-analysis incorporating the results of this trial reported no differences in the risk of persistent kidney disease at 6 months (three studies) and 12 months (three studies) in children given prednisone for 14 to 28 days at presentation compared with those who received placebo or supportive care [16]. This meta-analysis also found no benefit in using antiplatelet agents such as heparin to prevent persistent kidney disease. Failure to demonstrate benefit may be an artifact of the low prevalence rate of complications and the small number of patients studied [4,20].
Treatment of recalcitrant disease — Additional therapies for the treatment of recalcitrant disease are not well defined and seldom necessary. There are reports and case series that suggest benefits from additional immunomodulation with a range of therapies that include colchicine [21], dapsone [22,23], rituximab [24], intravenous immune globulin [25], mycophenolate mofetil [26], cyclophosphamide [27], and plasmapheresis [28,29], especially in cases of aggressive, recalcitrant disease, typically with kidney involvement [30]. Management of kidney disease in IgAV is discussed in detail separately. (See "IgA vasculitis (Henoch-Schönlein purpura): Kidney manifestations", section on 'Management of IgAV nephritis'.)
PROGNOSIS — The short- and long-term outcomes of children with IgAV are generally excellent. In the absence of significant kidney disease, the initial episode of IgAV typically resolves within one month.
In two-thirds of children, there are no recurrent episodes [2,31]. In the remaining one-third of patients, IgAV recurs at least once, typically within four months of the initial presentation [2,32,33]. Each subsequent episode has similar clinical manifestations but is generally milder and/or shorter in duration than the preceding one. In a single-center study involving 417 patients, approximately one-third of the patients had at least one relapse, with a median time to relapse of one month. Presence of an infectious trigger was associated with a lower likelihood of relapse, while the risk of relapse was higher when joint and gastrointestinal symptom were present [34]. Recurrences are more common in patients with nephritis, in those with evidence of acute inflammation (eg, elevated erythrocyte sedimentation rate [ESR]), and in patients who received treatment with glucocorticoids [32,35]. One study found that persistent hematuria was a predictive factor for relapse [36]. Another study found that development of nephritis was associated with persistent purpura and gastrointestinal bleed [37], and others have reported more refractory disease in older patients [38]. These findings suggest that patients who have a more severe course of IgAV are at increased risk of recurrence.
One retrospective review from Israel reported a longer mean interval time of 13.5 months between the first and second episode of IgAV than was reported previously [39]. In addition, there was no difference in clinical and laboratory findings between patients with recurrent disease and those without recurrence. The reasons for these differences between study results are unclear.
Morbidity in the initial phase of IgAV is primarily a result of gastrointestinal complications, including intussusception and, less commonly, bowel ischemia, bowel perforation, or pancreatitis. (See "IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis", section on 'Gastrointestinal symptoms'.)
There is a greater risk of long-term kidney disease in patients with IgAV, although the overall long-term prognosis appears favorable for patients with IgAV compared with controls according to an Australian observational cohort study for comorbidity development, with no differences in survival or other comorbidities including rheumatic diseases [40]. Similar finding were reported from a cohort of patients from the United Kingdom, which suggested that patients with IgAV were at higher risk for hypertension and chronic kidney disease but not increased mortality [41].
The long-term morbidity in patients with IgAV is a result of kidney disease. The risk of chronic kidney disease is increased in older patients and adults [42]. The severity of kidney involvement correlates with the severity of the initial kidney presentation and histologic changes seen on kidney biopsy. Risk factors for a worse kidney prognosis include nephrotic-range proteinuria, elevated serum creatinine, hypertension, and certain histologic findings. The supportive data are discussed elsewhere. (See "IgA vasculitis (Henoch-Schönlein purpura): Kidney manifestations", section on 'Prognosis'.)
FOLLOW-UP — Ninety percent of children who develop kidney involvement do so within two months of onset, and 97 percent within six months [43]. Adults are at higher risk for kidney disease both early in the course of disease and longer term [44-46]. Accordingly, all patients with IgAV should be followed with urinalysis and blood pressure monitoring weekly or biweekly for the first one to two months after presentation. Results from one study suggested that home urine dipstick testing was adequate for detecting development of nephritis [18]. Once the disease appears to be inactive, additional follow-up for urine and blood pressure monitoring should be scheduled monthly at first, then every other month until one year after the initial presentation. To identify patients who may develop late kidney disease, continued screening (eg, urinalysis and blood pressure measurements) should be performed by the primary care provider during annual well-child visits. In the previously discussed study, an increasing percentage of children showed some degree of kidney involvement over a 15-year follow-up period, although none developed severe kidney disease [18]. (See "IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis", section on 'Kidney studies'.)
A serum creatinine should be obtained to assess kidney function in any patient with significant or persistent urinary abnormalities or elevated blood pressure.
Patients with persistent proteinuria, hypertension, or kidney insufficiency should be referred to a pediatric nephrologist for further evaluation and treatment. In addition, pregnant women with a history of IgAV should be monitored closely as they have a higher risk of hypertension [47].
Close observation and frequent abdominal exams are recommended, in addition to follow-up imaging, for patients who presented with abdominal pain and required treatment with glucocorticoids, especially if the patient has hematochezia, persistent abdominal pain, guarding, or other significant change in the physical exam.
IgAV does not appear to impact fertility, but pregnancy outcomes appear to be worse in those with a history of IgAV, with higher rates of spontaneous abortions, preterm delivery, and pregnancy-induced hypertension [48].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Vasculitis".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: IgA vasculitis (Henoch-Schönlein purpura) (The Basics)")
●Beyond the Basics topic (see "Patient education: Vasculitis (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●General management – Most patients with immunoglobulin A vasculitis (IgAV), formerly called Henoch-Schönlein purpura (HSP), may be cared for in the ambulatory setting with therapy directed toward adequate oral hydration, bed rest, and symptomatic relief of joint and abdominal pain (algorithm 1).
●Treatment of joint and/or abdominal pain – In patients with joint and/or abdominal pain, we suggest the use of a nonsteroidal antiinflammatory agent (Grade 2C). We typically use naproxen (10 to 20 mg/kg divided into two doses per day). A maximum dose of naproxen of 1500 mg per day may be used for a few days provided that adequate hydration is maintained. If more than a week of nonsteroidal antiinflammatory drug (NSAID) treatment is necessary, the dose of naproxen should not exceed 1000 mg per day. (See 'Mild-to-moderate pain' above.)
●Treatment of severe, refractory abdominal pain – In patients with severe abdominal pain that interferes with their oral intake and who fail to respond to a nonsteroidal antiinflammatory agent, we suggest the use of systemic glucocorticoids (Grade 2C). We use oral prednisone (1 to 2 mg/kg per day) for children or adults, with a maximum dose of 60 to 80 mg per day, or equivalent doses of intravenous methylprednisolone (0.8 to 1.6 mg/kg per day, maximum dose of 64 mg per day). Patients who are treated with glucocorticoids for severe abdominal pain require particular vigilance since these medications can obscure the signs and symptoms of abdominal catastrophes associated with IgAV. Glucocorticoids should be tapered slowly, by no more than 25 percent per week, lest symptoms relapse. (See 'Severe pain' above.)
●Indications for hospitalization – Hospitalization is indicated in patients who fail to maintain oral hydration and require the administration of intravenous fluids. Inpatient management may also be necessary to manage patients who have significant gastrointestinal bleeding, severe abdominal pain, changes in mental status, severe joint involvement limiting ambulation and/or self-care, or evidence of significant kidney disease (elevated creatinine, hypertension, or proteinuria). (See 'Hospitalization' above.)
●Empiric prophylaxis with glucocorticoids not recommended – We do not recommend empiric glucocorticoid administration to prevent kidney or gastrointestinal complications (Grade 1B). (See 'Prevention of complications' above.)
●Prognosis and complications – Although prognosis is excellent in children with IgAV, a small minority of patients (<1 percent) develop long-term complications, primarily kidney disease. In adults, the risk of significant kidney disease is increased. At present, there is no known therapeutic regimen to forestall development of kidney involvement. Therapy for optimal control of IgAV-related nephritis or nephrosis is discussed elsewhere. (See 'Prognosis' above and "IgA vasculitis (Henoch-Schönlein purpura): Kidney manifestations", section on 'Management of IgAV nephritis'.)
●Monitoring for kidney involvement – Patients who have developed IgAV should be seen in follow-up with testing for urinary abnormalities and elevated blood pressure to identify patients with significant and potentially progressive kidney involvement. (See 'Follow-up' above.)
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