History
IgA vasculitis (IgAV; Henoch-Schönlein purpura) typically has a prodrome, which includes the following:
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Headache
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Anorexia
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Fever
After the prodrome, a number of symptoms develop, of which the following are the most common:
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Rash (95-100% of cases), especially involving the legs
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Abdominal pain and vomiting (35-85%)
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Joint pain (60-84%), especially involving the knees and ankles
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Subcutaneous edema (20-50%)
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Scrotal edema (2-35%)
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Bloody stools
The hallmark of the disease is the characteristic rash (see the image below), which appears in nearly all patients (though in as many as 50% of children, it may not be the presenting feature). The rash typically appears in crops, with new crops appearing in waves. Eruptions usually last an average of 3 weeks.
Lesions tend to occur on the buttocks and upper thighs in younger children and on the feet, ankles, and lower legs in older children and adults. The primary differences between children and adults appear to be the chronicity and severity of the eruption in the latter population; bullae and ulcers are more common in adults, and cutaneous exacerbations may be seen for 6 months or longer. [75] Chan et al noted a case of IgAV presenting as painful bullae on both legs. [76]
Gastrointestinal (GI) symptoms typically develop about a week after the appearance of the characteristic rash, but may precede or accompany the onset of skin lesions in IgAV or occur weeks or months later. [77] The most common such symptom is colicky abdominal pain. In addition to abdominal pain, GI findings may include the following:
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Nausea
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Vomiting
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Diarrhea with gross or occult blood
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Hematemesis
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Intussusception - This occurs in 2-3% of patients, and the lead point can be a submucosal hematoma
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Bowel infarction, with or without perforation
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Ileal stricture
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Ileus with massive GI hemorrhage
Arthralgias occur in 60-84% of patients with IgAV and are the presenting complaint in approximately 25% of children. The large joints (eg, the knees and ankles) are the ones most commonly involved, with pain and edema being the only symptoms; the wrists and fingers are less commonly involved. True arthritis does not occur, and joint effusions are rare. Generally, the arthritis resolves completely over several days without permanent articular damage.
Acute hemorrhagic edema of infancy (AHEI) usually occurs in infants aged 4-24 months, often after drug ingestion or infection. Onset is dramatic, with acute palpable purpura, ecchymoses, and tender edema of the limbs and face. Fever, if present, remains mild. Infants remain hemodynamically stable. Dermatologic findings are notable for a cockadelike rosette-shaped pattern of macular-papular-hemorrhagic lesions on the face, auricles, and extremities, which usually appear in successive crops and display varying stages of evolution at any given time.
Subcutaneous edema is most common in infants. Urticaria, petechiae, and ear lobe necrosis are additional rare skin manifestations of AHEI. Visceral involvement is rare.
Scrotal involvement is not uncommon in IgAV and may mimic testicular torsion, which must be excluded. Male patients may have associated inflammation and hemorrhage of the testes, appendix testes, spermatic cord, epididymis, or scrotal wall. True torsion is rare. Ha and Lee reported that neurologic symptoms, localized edema, and high serum C3 levels were significantly related to scrotal involvement in male patients with IgAV. [80]
In women with IgAV, gynecologic symptoms can include painful menstruation.
IgAV can be accompanied by neurologic manifestations, particularly headaches. Ozkaya et al reported cerebral vasculitis in a child with IgAV and familial Mediterranean fever. [81] In rare cases, IgAV can be associated with seizures, paresis, or coma.
Other neurologic manifestations of IgAV include the following:
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Altered mental status
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Apathy
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Hyperactivity
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Irritability
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Mood lability
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Somnolence
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Seizures (partial, complex partial, generalized, or status epilepticus)
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Focal deficits (eg, aphasia, ataxia, chorea, cortical blindness, hemiparesis, paraparesis, or quadriparesis)
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Polyradiculoneuropathies (eg, brachial plexus neuropathy or Guillain-Barré syndrome)
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Mononeuropathies (eg, of the facial nerve, femoral nerve, peroneal nerve, sciatic nerve, or ulnar nerve)
The liver and gallbladder can be involved in IgAV. [82] Hepatomegaly, hydrops of the gallbladder, and cholecystitis may ensue. These may contribute to a patient’s abdominal pain. Acute appendicitis has been noted in patients with IgAV.
Kidney pathology is the most important cause of morbidity and mortality in patients with IgAV. Kidney involvement may precede skin manifestations (1-4% of patients) but is usually evident during the acute phase of the disease, sometimes developing as long as 3 months after the initial presentation. [83] It may persist for as long as 6 months after the onset of the rash. In most cases, the severity of nephritis is not related to the extent of other IgAV manifestations.
Hemoptysis and hemarthroses can develop in patients who have bleeding abnormalities such as coagulopathy, factor VIII deficiency, vitamin K deficiency, or hypoprothrombinemia. Inherited thrombophilias (eg, factor V Leiden, protein C deficiency, and protein S deficiency) may contribute to necrotic cutaneous lesions in IgAV. [84]
Recurrence
Disease recurrence occurs throughout weeks to months in adults and children. In a large pediatric study by Allen et al, children older than 2 years had a recurrence rate of 50%, whereas those younger than 2 years had a recurrence rate of less than 25%. [85]
Prais et al studied 267 children (56.7% males) who were hospitalized secondary to IgAV of whom 7 (2.7%) had IgAV that resulted in hospitalization at least twice. [86] No specific risk factor for recurrence was determined. The mean age for the first recurrence in that subgroup was 3.67 years (range, 10 months to 7.4 years), and that for the second was 5.03 years (range, 2.2-10 years), with a mean lag time of 13.5 ± 2.8 months (range, 2-26 months). The duration of the recurrence was 9-30 days. Resolution took more than 2 weeks in 72% of patients.
Physical Examination
Because IgAV can affect all organ systems, a full physical examination is indicated. Purpura of the skin is the most prominent physical finding in IgAV, but kidney, GI, and joint manifestations are commonly present. Other manifestations have also been reported.
Skin findings
In most patients, skin lesions are the first sign of IgAV. The eruption commonly begins as erythematous macular or urticarial lesions, progressing to blanching papules and later to palpable purpura, usually 2-10 mm in diameter (see the image below). Various stages of eruption may be present simultaneously. Lesions usually occur in crops and may fade over several days.
Purpuric papules and plaques of the lower extremity characteristic of IgA vasculitis (Henoch-Schönlein purpura).
Lesions typically are symmetrical and tend to be distributed in dependent body areas, such as the ankles and lower legs in older children and adults (see the images below), and the back, buttocks, upper extremities, and upper thighs in young children (because these regions tend to be dependent in young children). The face, palms, soles, and mucous membranes usually are spared, except in infants, in whom facial involvement may not be uncommon.
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.
A 7-year-old girl with IgA vasculitis (Henoch-Schönlein purpura). Image courtesy of Pamela L Dyne, MD.
Hemorrhagic macules, papules, and patches on the ankle and foot of a child with IgA vasculitis (Henoch-Schönlein purpura).
Palpable purpura can also be present on the forearms and pinnae. Scalp edema can occur. Hemorrhagic vesicles and bullae are rare.
Within 12-24 hours, the macules evolve into purpuric lesions that are dusky red and have a diameter of 0.5-2 cm. The lesions may coalesce into larger plaques that resemble ecchymoses (see the image below). Color in the areas of purpura progresses from red to purple and then becomes rust-colored or brown before fading. Recurrences tend to take place in the same sites as previous lesions.
Older lesions of IgA vasculitis (Henoch-Schönlein purpura) demonstrating increased extravasation with ecchymoses on dorsal foot and ankle.
Hives, angioedema, and target lesions can also occur. Vesicular eruptions and swelling and tenderness of an entire limb have been noted. Erythema multiforme–like lesions can be present. IgAV with hemorrhagic bullae in children has been noted.
In children younger than 2 years, the clinical picture may be dominated by edema of the scalp, periorbital area, hands, and feet (AHEI). The severity of edema is correlated with the severity of the vasculitis and not with the degree of proteinuria. However, the edema has been attributed to the enteric loss of protein. The “cockades” characteristic of AHEI display variable stages of evolution at any given time and look different from the normal purpura of IgAV.
The subcutaneous edema of AHEI is more common in infants. Urticaria, petechiae, and necrosis of the ear lobe are additional rare skin manifestations of AHEI. AHEI is rarely associated with visceral involvement.
Kidney findings
The most serious complication of IgAV is kidney involvement, which occurs in 50% of older children but is serious in only approximately 10% of patients. In 80% of patients, kidney involvement becomes apparent within the first 4 weeks of illness. Overall, 2-5% of patients progress to end-stage kidney disease (ESKD).
In one series, acute glomerular lesions, including mesangial hypercellularity, endocapillary proliferation, necrosis, cellular crescents, and leukocyte infiltration, were observed in 41%, 12%, 50%, 29%, and 32% of patients, respectively. [87] Only glomerular necrotizing lesions and cellular crescents correlated with the renal survival rate and were associated with clinically significant proteinuria and development of hypertension.
In a prospective study of 223 children with IgAV, Jauhola et al reported that 46% developed renal manifestations. [88] The authors recommended that children with kidney involvement be followed for more than 6 months. In addition, they noted that treatment with prednisone did not affect the renal manifestations.
Gastrointestinal findings
Abdominal pain and bloody diarrhea may precede the typical purpuric rash of IgAV, complicating the initial diagnosis and even resulting in unnecessary laparotomy. GI manifestations occur in about 50% of cases and usually consist of colicky abdominal pain, melena, or bloody diarrhea. Hematemesis occurs less frequently. Intussusception should be suspected in IgAV patients with abdominal pain or melena. Barium enema is frequently therapeutic.
The duodenum and small intestine are the most frequently involved segments of the GI tract. Duodenal ulcers also occur. Massive GI bleeding has been reported in IgAV. [89] Ileal vasculitis has also been reported.
Joint findings
Arthralgia is the presenting feature in as many as 25% of cases. Joints may be swollen, tender, and painful. Warmth, erythema, and effusions are not typically associated with IgAV. The knees and ankles are most commonly affected. On rare occasions, symptoms involve the fingers and wrists. Findings are transient but can occur again during active disease. The joints are not permanently deformed.
Other findings
Vasculitis involving the myocardium may occur. Vasculitis may also involve the lungs, resulting in pulmonary hemorrhage or severe bilateral pulmonary hemorrhage, and it may cause stenosing ureteritis, priapism, penile edema, or orchitis. Ha and Lee reported that neurologic symptoms, localized edema, and high serum C3 levels were significantly correlated with scrotal involvement in male patients with IgAV. [80] Vasculitis involving the CNS and intracranial hemorrhage have been reported.
Bilateral subperiosteal orbital hematomas have been noted. Adrenal hematomas have occurred. In rare patients, acute pancreatitis is the sole presenting feature of IgAV. [90, 91, 5] A case involving cystic changes of the ovaries and IgAV has been reported. [42]
Complications
IgAV can involve nearly every organ system. Reported complications include the following:
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Myocardial infarction
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Pulmonary hemorrhage
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Pleural effusion
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Intussusception
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GI bleeding
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Bowel infarction
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Protein-losing enteropathy [92]
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Chronic kidney failure
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Hematuria
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Proteinuria
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Seizures
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CNS bleeding
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Mononeuropathies
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Recurrence of symptoms, specifically those of kidney impairment (rare)
Hematuria, usually microscopic, can be accompanied by mild-to-moderate proteinuria (< 2 g/day). Oliguria, hypertension, and azotemia are rarely present. Nephrotic syndrome (urinary protein excretion > 40 mg/m2/hr or protein:creatinine ratio ≥200 mg/mmol in an early morning spot urine) can also occur. In most cases, histologic examination of the kidneys reveals mesangial proliferation that can be diffuse or focal and segmental. Resolution of the kidney involvement is the focus in these patients.
A study reported that even patients with mild forms of IgAV nephritis are at risk for significant long-term proteinuria. The study also added that very early introduction of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers may improve the long-term outcome independent of histological lesions. [93]
GI complications include hydrops of the gallbladder, pancreatitis, and GI bleeding. Surgical complications include intussusception, bowel infarction, and perforation.
Overall, 5% of patients develop ESKD. Urinary complications include bladder-wall hematoma, calcified ureter, hydronephrosis, and urethritis.
In a retrospective Korean study of 212 children with IgAV, Lee et al found palpable purpura spots 98.1% of subjects, GI symptoms in 75.0%, joint symptoms in 69.8%, renal involvement in 26.9%, and nephrotic syndrome in 4.7%. The study also found that patients with severe GI symptoms and children over age 7 years had a significantly greater incidence of kidney involvement and nephrotic syndrome. [94]
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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.
