AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Willan and Heberden appeared to have first noted Henoch-Schoenlein (or Henoch-Schönlein) purpura (HSP) in the early 1800s. However, Schönlein first described the combination of acute purpura and arthritis in children in 1837, and Henoch reported the manifestations of abdominal pain and nephritis in 1874.¹

HSP is an acute immunoglobulin A (IgA)–mediated leukocytoclastic vasculitis that primarily affects children. The dominant clinical features of HSP include cutaneous purpura, arthritis, abdominal pain, GI bleeding, orchitis, and nephritis.

The prevalence of HSP peaks in children aged 3-10 years. In the Northern hemisphere, the disease occurs mostly from November to January. The male-to-female ratio is 1.5-2:1. In one half to two thirds of children, an upper respiratory tract infection precedes the clinical onset of HSP by 1-3 weeks. In general, patients with HSP appear mildly ill. They often have a fever, with a temperature usually not higher than 38°C (100.4°F). HSP is typically an acute, self-limited illness; however, one third of patients have one or more recurrences.

Pathophysiology

Etiology of Henoch-Schoenlein purpura

The etiology of HSP remains unknown. However, IgA clearly plays a critical role in the immunopathogenesis of HSP, as evidenced by increased serum IgA concentrations, IgA-containing circulating immune complexes, and IgA deposition in vessel walls and renal mesangium. HSP is almost exclusively associated with abnormalities involving IgA1, rather than IgA2.

The predominance of IgA1 in HSP may be a consequence of abnormal glycosylation of O-linked oligosaccharides unique to the hinge region of IgA1 molecules. Although several lines of evidence suggest a genetic susceptibility to HSP, the fundamental basis for this abnormality remains unclear.

IgA aggregates or IgA complexes with complement deposited in target organs, resulting in elaboration of inflammatory mediators, including vascular prostaglandins such as prostacyclin, may play a central role in the pathogenesis of HSP vasculitis.

A subpopulation of human lymphocytes bears surface Fc and/or C3 receptors (complement receptor lymphocytes), which can bind circulating immune complexes or C3 generated by activation of the alternative complement pathway. Such immune complexes appear in HSP and may be part of the pathogenetic mechanism.

Some have speculated that an antigen stimulates the production of IgA, which, in turn, causes the vasculitis. Allergens, such as foods, horse serum, insect bites, exposure to cold, and drugs (eg, ampicillin, erythromycin, penicillin, quinidine, quinine), may precipitate the illness. Infectious causes include bacteria (eg, Haemophilus, Parainfluenzae, Mycoplasma, Legionella, Yersinia, Shigella, or Salmonella species) and viruses (eg, adenoviruses, Epstein-Barr virus [EBV], parvoviruses, varicella). Vaccines such as those against cholera, measles, paratyphoid A and B, typhoid, and yellow fever have also been implicated. Evidence supporting a direct role of herpesvirus, retrovirus, or parvovirus infection in HSP is lacking.

Alterations in the production of interleukins (ILs) and growth factors may also have a role in the pathogenesis of HSP. Tumor necrosis factor (TNF), IL-1, and IL-6 may mediate the inflammatory process present in HSP. Transforming growth factor–beta (TGF-beta), is a recognized stimulant of IgA production. The elevated levels of hepatocyte growth factor present during the acute phase of HSP may reflect endothelial-cell damage or dysfunction. Increased levels of vascular endothelial growth factor may at least partly induce these changes. Cytokines have been implicated in the pathogenesis of HSP, and endothelins (ETs), which are vasoconstrictor hormones produced by endothelial cells, may also have a role. Levels of ET-1 are substantially higher during the acute phase of the disease than during remission or in a control group of children. However, ET-1 levels do not appear to be correlated with morbidity, severity of disease, or acute-phase reactant response.

A functional correlation of the IL1RN-2 allele and IL-1ra production in patients with IgA nephropathy and HSP nephritis (HSPN) has been described. Therefore, gene polymorphism may contribute to the diversity of clinical responses to inflammatory stimulation.

Emerging data

Results support a role of human leukocyte antigen (HLA)–B35 in the susceptibility to nephritis in unselected patients with HSP.

Researchers are currently investigating the importance of nitric oxide (NO) production in disease activity. Inducible NO synthase polymorphism is associated with susceptibility to HSP in northwestern Spain.

The prevalence of the human parvovirus B19 component NS1 gene in patients with HSP and hypersensitivity vasculitis is increased.

HSP that is likely due to montelukast has been noted in patients who present with subacute intestinal obstruction.

Other factors

Yilmaz et al (2005) examined 28 children with HSP and 79 healthy children to evaluate activities of protein C, free-protein S, and antithrombin; resistance to activated protein C; and levels of fibrinogen.² D-dimer, thrombin-antithrombin (TAT) complex, prothrombin fragments (PFs) 1 and 2, and von Willebrand factor antigen (vWAg) and its activity (RiCof) were also investigated.

Frequency

United States

In the United States, the prevalence is approximately 14-15 cases per 100,000 population.

International

In the United Kingdom, the estimated annual incidence of HSP is 20.4 cases per 100,000 population.⁴ In a Norwegian community hospital, the prevalence of HSP was 3.3 cases per 100,000 inhabitants.⁵

In a study that examined the renal biopsy results of 65 children younger than 18 years obtained by the Clinical Hospital in the Croatian region of Dalmatia over a 10-year period (1995-2005), 10.8% of glomerulonephritis cases were due to HSP.⁶ 

Nong et al (2007) reviewed the records of 107 Taiwanese pediatric patients diagnosed with HSP between 1991 and 2005 who had a mean age of 6.2 ± 2.5 years (range, 2-13 y); the male-to-female ratio was 1:0.7.⁷ The primary symptoms included the following:

• Skin rashes (95.3%)
• GI symptoms (72.0%)
• Joint involvement (46.7%)
• Kidney involvement (28.0%)

The most common first manifestations were as follows:

• Skin rashes (56.1%)
• GI symptoms (35.5%)
• Joint involvement (12.1%)

From January 1983 to June 2004, Suehiro et al (2007) followed 4,502 patients at the Pediatric Rheumatology clinic in Brazil.⁸ A diagnosis of HSP was made in 203 cases (4.5%); 5 patients (0.1%) had AHEI. All patients with AHEI were male, and the mean age at onset was 18 months (range, 8-21 mo). 

Mortality/Morbidity

• HSP is only fatal in the rarest of cases.
• Initial attacks of HSP can last several months, and relapses are possible. Kidney damage related to HSP is the primary cause of morbidity and mortality.
• Overall, an estimated 2% of cases of HSP progress to renal failure; as many as 20% of children who have HSP and are treated in specialized centers require hemodialysis. The renal prognosis appears to be worse in adults than in children.

Race

• Whites are affected more often than blacks.
• In one study in Thailand, the most common age at presentation was 3-5 years.⁹ The frequency peaked from December to February. Organs involved included the skin (100%), GI tract (74.5%), and kidneys (46.8%). Joints were also affected (42.6%). Renal involvement was detected within the first 2 months in 16 patients (72.7%); however, it was delayed until 6 months after diagnosis in 6 patients. No risk factors for renal involvement could be identified. Mean follow-up was 2.6 years (range, 1-5 y). Residual renal disease occurred in 6 (38%) of 16 patients, but none were had end-stage disease.
• In a study in China, a male predominance was observed in children but not in adults.¹⁰ Preceding infection was noted in 40.5% of children and 31.6% of adults; 8.3% of children and 13.2% of adults were receiving medication at the onset of the disease. Abdominal pain was more common in children than adults (70.2% vs 28.9%), but renal involvement was more common and severe in adults than in children; this involvement manifested as frequent hypertension and heavy proteinuria. During acute attacks, leukocytosis, thrombocytosis, and elevated serum C-reactive protein levels were most frequently observed in children, whereas elevated serum IgA and cryoglobulin levels were most common in adults.

Sex

HSP occurs more often in boys than in girls; the male-to-female ratio is 1.5-2:1.

Age

• In the United States, the prevalence peaks in children aged 5 years.
• Approximately 75% of cases occur in children aged 2-11 years.
• HSP is rare in infants and young children.
• A related milder condition called acute hemorrhagic edema of infancy (AHEI) occurs in infants younger than 2 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Prais et al studied 267 children (56.7% males) who were hospitalized secondary to Henoch-Schoenlein purpura (HSP); 7 of the children (2.7%) had HSP that resulted in hospitalization 2 or more times.¹¹ No specific risk factor for recurrence was determined. The mean age for the first recurrence in that subgroup was 3 years and 8 months (range, 10 mo to 7.4 y), and the mean age for the second recurrence was 5.03 years (2.2-10 y), with a mean lag time of 13.5 months ± 2.8 months (range, 2-26 mo). The duration of the recurrent clinical symptoms was 9-30 days. Resolution took more than 2 weeks in 72% of patients.
• Associated conditions that precede HSP include those listed in Causes.
• Scrotal involvement is not uncommon in HSP 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 (2007) reported that neurologic symptoms, localized edema, and high serum C3 levels have a significant relationship with scrotal involvement in male patients with HSP.¹²
• GI symptoms can accompany the onset of HSP or may develop later in the course of disease. Abdominal pain occurs in 35-85% of patients and is the third most common presenting symptom in HSP. GI problems usually follow the onset of rash and joint pain. Multiple and recurrent intestinal perforations are an unusual complication of HSP. In addition to abdominal pain, GI findings can include the following:
• • Nausea
  • Vomiting
  • Diarrhea with gross or occult blood
  • Hematemesis
  • Intussusception: This occurs in 2-3% of patients, and the lead point can be a submucosal hematoma.
  • Bowel infarction with or without perforation
  • Ileal stricture
  • Ileus with massive GI bleed
• Arthralgias occur in 60-84% of patients with HSP and most commonly affect the knees, ankles, and, less frequently, the wrists and fingers. True arthritis does not occur, and joint effusions are rare. HSP leaves no permanent joint deformities.
• In women, gynecologic symptoms can include painful menstruation.
• HSP can be accompanied by neurologic manifestations, particularly headaches. Ozkaya et al reported cerebral vasculitis in a child with HSP and familial Mediterranean fever.¹³
• • In rare cases, HSP can be associated with seizures, paresis, or coma.
  • Other manifestations include altered mental status, apathy, hyperactivity, irritability, mood lability, somnolence, seizures (partial, complex partial, generalized, status epilepticus), and focal deficits (eg, aphasia, ataxia, chorea, cortical blindness, hemiparesis, paraparesis, quadriparesis).
  • Polyradiculoneuropathies (eg, brachial plexus neuropathy, Guillain-Barré syndrome) and mononeuropathies (eg, facial nerve, femoral nerve, peroneal nerve, sciatic nerve, ulnar nerve) may also occur.
• The liver and gallbladder can be involved in HSP.
• • 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 HSP.
• Skin involvement is usually purpura. Chan et al (2007) noted a case of HSP presented as painful bullae on both legs.¹⁴
• Acute hemorrhagic edema of infancy (AHEI) usually occurs in infants aged 4-24 months.
• • AHEI often occurs after drug ingestion or infection. The onset of AHEI 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 cockade (medallionlike), rosette-shaped pattern of macular-papular-hemorrhagic lesions on the face, auricles, and extremities. The lesions usually appear in successive crops. The cockades display variable 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.
• Renal pathology is the most important cause of morbidity and mortality in patients with HSP.
• • Renal involvement may precede skin manifestations (1-4% of patients) but is usually evident during the acute phase of the disease.
  • In most cases, the severity of nephritis is not related to the extent of other HSP manifestations.
  • Hematuria, usually microscopic, can be accompanied by mild-to-moderate proteinuria (<2 g/d). Oliguria, hypertension, and azotemia are rarely present. Nephrotic syndrome (urinary protein excretion >40 mg/m²/h) 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 renal involvement is the focus in these patients.
  • Patients who present with hematuria and persistent proteinuria have an approximate 15% risk of developing renal failure. The risk may increase to 50% in patients with a nephrotic-nephritic syndrome.
• Urinary complications include bladder-wall hematoma, calcified ureter, hydronephrosis, and urethritis.
• Hemoptysis and hemarthroses can develop in patients who have bleeding abnormalities such as coagulopathy, factor VIII deficiency, vitamin K deficiency, or hypoprothrombinemia. They also probably include factor V Leiden, protein C deficiency, and protein S deficiency, but this has not been documented.

Physical

Purpura of the skin is the most prominent physical finding in HSP, but renal, GI, and joint manifestations are commonly present. Other manifestations have also been reported.

HSP begins with a symmetrical erythematous macular rash on the lower extremities that quickly evolves into purpura. The rash may initially be confined to malleolar skin but usually extends to the dorsal surface of the legs, the buttocks, and the ulnar side of the arms. 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. Several cases of HSP have been observed after varicella infections.

In children younger than 2 years, the clinical picture may be dominated by edema of the scalp, periorbital area, hands, and feet. This presentation is termed 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. 

Overview of renal findings

The most serious complication of HSP is renal involvement, which occurs in 50% of older children but is serious in only approximately 10% of patients. In 80% of patients, renal involvement becomes apparent within the first 4 weeks of illness. Overall, 2-5% of patients progress to end-stage renal failure (ESRF). 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.¹⁵ Only glomerular necrotizing lesions and cellular crescents correlated with the renal survival rate and were associated with clinically significant proteinuria and development of hypertension.

The relationship of HSP and IgA nephropathy requires further definition. Whether they are the same or distinct entities remains unclear. Evidence of both their commonality and distinctiveness is presented herein.

Evidence that they are the same entity includes the following:

• The occurrence of extrarenal manifestations in IgA nephropathy is similar to those observed in HSP.
• IgA nephropathy has developed in patients with a history of HSP. HSP and IgA nephropathy have occurred in the same families.
• In a survey of 40 families in which 2 or more members had IgA nephropathy, 5 presented with HSP.¹⁶
• Patients with HSP who undergo renal transplantation develop IgA deposits in the graft.
• The prevalence of both conditions is high in certain geographic areas.
• Similar changes in the IgA system (ie, high IgA, IgA-1C, IgA1-IC, IgA-fibronectin aggregates, aberrantly glycosylated IgA in the circulation) occur in both diseases.^{17, 18, 19}

• Skin manifestations
• • Palpable purpura usually occurs first on the lower limbs and then spreads to the buttocks. Purpura is usually most prominent over the buttocks, the posterior aspects of the lower legs, and the elbows.
  • Palpable purpura can also be present on the forearms and pinna. Scalp edema can occur. Hemorrhagic vesicles and bullae are rare. In most patients, the skin lesions are the first sign of HSP.
  • 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.
  • HSP with hemorrhagic bullae in children has been noted.
  • In AHEI, dermatologic findings are notable for a cockade (medallionlike), rosette-shaped pattern on the face, auricles, and extremities. The lesions usually appear in successive crops. The cockades display variable stages of evolution at any given time and look different from the normal purpura of HSP.
  • 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.
• Renal manifestations
• • Possible renal manifestations include microscopic hematuria, proteinuria, nephrotic syndrome, progressive glomerulonephritis, ESRF (rarely), and intestinal perforation.
  • The relationship of HSP and IgA nephropathy requires further definition. Whether they are the same or distinct entities remains unclear. Evidence of both their commonality and distinctiveness is presented in Overview of renal findings above.
  • If serial urine samples are obtained in patients with HSP, microscopic hematuria is usually found and is probably present in 100% of the patients. However, frank nephritis appears in only 20-30% of unselected children. The entire clinical spectrum of glomerulonephritis may occur in HSP. The most common renal manifestations are hematuria with mild-to-moderate proteinuria.
• GI manifestations
• • 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 an adult with HSP.
  • Ileal vasculitis has also been reported.
• Joint manifestations
• • Arthritis and/or arthralgia affects 60-75% of patients and is the presenting feature in 25%.
  • Joints may be swollen, tender, and painful. 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.
• Cardiac manifestations: Vasculitis involving the myocardia can occur.
• Pulmonary manifestations: Vasculitis can involve the lungs, resulting in pulmonary hemorrhage or severe bilateral pulmonary hemorrhage.
• Urinary manifestations: Vasculitis may cause stenosing ureteritis, priapism, penile edema, or orchitis. Ha and Lee (2007) reported that neurologic symptoms, localized edema, and high serum C3 levels show a significant relation with scrotal involvement in male HSP patients.¹²
• CNS manifestations: Vasculitis involving the CNS and intracranial hemorrhage has been reported.
• Eye manifestations: Bilateral subperiosteal orbital hematomas have been noted.
• Adrenal manifestations: Adrenal hematomas have occurred.
• Pancreatic manifestations: In rare patients, acute pancreatitis is the sole presenting feature of HSP.

Causes

The following conditions may precede HSP:

• Infections
• • Mononucleosis
  • Group A streptococcal infection (most common)
  • Hepatitis
  • Mycoplasma infection
  • EBV infection
  • Varicella-zoster viral infection
  • Parvovirus B19 infection
  • Campylobacter enteritis
  • Hepatitis C–related liver cirrhosis
  • Subacute bacterial endocarditis
  • Yersinia infection
  • Shigella infection
  • Salmonella infection
• Vaccinations
• • Typhoid
  • Measles
  • Cholera
  • Yellow fever
• Environmental exposure to allergens
• • Drugs (eg, ampicillin, erythromycin, penicillin, quinidine, quinine)
  • Foods
  • Horse serum
  • Cold exposure
  • Insect bites
• Idiopathic illness - Glomerulocystic kidney disease

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Acute poststreptococcal glomerulonephritis
Leukocytoclastic vasculitis
Primary antiphospholipid syndrome
Wegener granulomatosis
Hypersensitivity vasculitis
Elevated renal function test results (BUN, creatinine)
Global organ involvement
Acute abdomen
Rheumatoid arthritis
Idiopathic thrombocytopenic purpura
Drug reactions

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

No specific diagnostic laboratory test is available to assess for markers of Henoch-Schoenlein purpura (HSP). Coppo et al (2006) reported that in patients in whom severe proteinuria, hypertension, or crescents are present at onset, the risk for HSPN progression is greater in adults and females and appears linked with increasing mean proteinuria levels during follow-up, even more so than in patients with decreased renal function at onset.²¹ Factor XIII activity apparently correlates tightly with the severity of abdominal manifestations, and, thus, measuring factor XIII activity aids in identifying patients with severe GI manifestation who could benefit from substitution therapy.²²

General laboratory tests may reveal the following:

• Antinuclear antibody and rheumatoid factor are absent.
• The level of plasma coagulation factor XIII (F XIII) is reduced in about 50% of patients.
• Urinalysis reveals hematuria. Proteinuria may also be found.
• Antinuclear antibody and rheumatoid factor are absent.
• The CBC count can show leukocytosis with eosinophilia and a left shift. Thrombocytosis is present in 67% of patients.
• Platelet counts may be elevated. Low platelet levels suggest thrombocytopenic purpura. The erythrocyte sedimentation rate (ESR) is variably elevated. Some reports state that the ESR is mildly elevated in 75% of patients.
• A stool guaiac test may reveal occult blood. BUN and creatinine levels may be elevated, indicating decreased renal function.
• Plasma D-dimer concentrations can be substantially increased.
• Plasma concentrations of TAT complex, PF-1, and PF-2 can be abnormal.
• The prothrombin time (PT) and activated partial thromboplastin time (aPTT) can be reduced (eg, hypoprothrombinemia).
• Serum IgA levels are increased in about 50% of patients during the acute phase of illness. Circulating IgA immune complexes may be present in some patients, though data supporting the presence of classic antigen-antibody complexes have been questioned.
• Factor VIII levels are decreased in some patients.
• The antistreptolysin O (ASO) titer is elevated in 30% of patients.
• CH50 is decreased in 30% of patients.
• C3 and C4 levels are occasionally low.
• Immunocomplexes of IgG and IgA can be increased.

Imaging Studies

• Ultrasonography
• • Abdominal ultrasonography can be used if GI symptoms are present.
  • Diagnosis of HSP using sonography and radionuclear scanning in a child presenting with bilateral acute scrotum as the main symptom of HSP has been reported.
  • In children with GI involvement of HSP, dedifferentiated wall thickening demonstrated by ultrasound reveals a poor clinical prognosis.²³
• Radiography
• • Plain radiography of the abdomen may help in diagnosing intestinal obstruction, and a barium enema study may be used to confirm and treat intussusception.
  • Chest radiography may help in determining the presence and extent of pulmonary hemorrhage.
  • Testicular ultrasonography may help in assessing the testes for hemorrhage or torsion.
  • Contrast-enhanced radiography of the small intestine demonstrates thickened mucosal folds or small barium flecks. Endoscopy may reveal multiple irregular ulcers, mucosal redness, and petechiae in the duodenum. The second part of the duodenum is sometimes predominantly affected. Ulcerating lesions accompanied by hematomalike protrusions can be detected in patients with histopathologically proven leukocytoclastic vasculitis.
• MRI
• • Some suggest that MRI is useful to assess neurologic findings in HSP.
  • In one case, a 6-year-old boy with HSP presented with depression, generalized convulsions, and cortical blindness. Sequential MRI revealed bilateral cerebral ischemic lesions in the cortex and white matter of parieto-occipital lobes caused by vasculitis.
• Summary of radiologic findings
• • Radiologic GI findings mainly include bowel ischemia with thumbprinting and bowel-wall edema, which is sometimes visible on abdominal radiographs.
  • Bowel ultrasonographic findings include thickening of the bowel wall, free fluid, and intussusception.
  • Hydrops of the gallbladder is rarely seen.
  • Renal involvement may result in no ultrasonographic features. If nephritis or nephrotic syndrome occurs, renal enlargement with loss of corticomedullary differentiation due to edema is observed.
  • If barium studies are performed, typical findings of ischemic colitis may be found, including a narrow colon with thickened mucosa and thumbprinting.
  • Some believe that imaging studies are indicated only if the diagnosis is uncertain.

Procedures

• In some cases, renal biopsy may be useful.
• Renal biopsy should be performed when the nephrotic syndrome persists (although other manifestations may have subsided) and when renal function deteriorates.
• During the acute phase of the disease, renal biopsy may reveal glomerular crescents. The extent of the crescents is of prognostic importance.

Histologic Findings

HSP is a vasculitis that often involves the kidneys.

Histopathologic features of the skin lesions in infantile HSP can range from a typical leukocytoclastic vasculitis with or without fibrinoid necrosis to the less specific findings of a lymphohistiocytic perivascular infiltrate with extravasation of erythrocytes.

Direct immunofluorescence (DIF) testing is a useful adjunct to histopathology; the yield of a positive test result is substantially higher when the test is performed within 48 hours of presentation. Immunofluorescence studies reveal perivascular IgA deposition in almost all patients; this finding is rare in infantile HSP, in which C3 and IgM are most commonly found in the affected vessel walls.

The histology of the kidney in HSP widely varies. In some cases, most glomeruli appear unaffected when assessed using light microscopy; only a few show mesangial proliferation. In instances of moderate renal involvement, focal and segmental intracapillary and extracapillary proliferation may be present with adhesions and small crescents. Severe cases are characterized by a diffuse proliferation with infiltration of neutrophils and circumferential crescents in most of the glomeruli. Tubular atrophy and interstitial infiltration with mononuclear cells may also be present.

Deposits of IgA in the mesangium and the walls of cutaneous capillaries are detected in most patients. The IgA deposited in the mesangium is mainly of the IgA1 subclass, although deposits of IgA2 are rarely noted. In addition to IgA, the deposits in mesangium and cutaneous capillaries frequently contain C3, IgG, and fibrin. The deposits of C3 are often accompanied by properdin, whereas C1Q and C4 are usually not present. This observation suggests that the complement components have been activated by means of the alternative pathway.

The specific renal pathology of HSP includes the following:

• Diffuse hypercellularity
• Focal and segmental proliferation
• Mesangial proliferation
• Minimal change to severe crescentic glomerulonephritis
• Segmental sclerosis fibrosis
• Mononuclear cell infiltration
• Mesangial, subendothelial, and subepithelial deposits
• Diffuse glomerular deposits of IgA, C3, fibrin, IgG, properdin, and IgM
• IgA deposits in the mesangium

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Patients with Henoch-Schonlein purpura (HSP) are often admitted to the hospital and monitored for abdominal and renal complications.

Nephropathy is treated supportively. Patients' fluid and electrolyte balance should be monitored, their salt intake should be restricted, and antihypertensives should be prescribed when needed. Various drugs (steroids, azathioprine, cyclophosphamide) and plasmapheresis have been used to prevent renal disease from progressing. The results have been inconsistent. No data from controlled studies are available.

Consultations

Because HSP is a multisystem disease, consultations with the following specialists can be helpful in diagnosis and treatment.

• Dermatologist
• Gastroenterologist
• Nephrologist
• Rheumatologist

Diet

Dietary restrictions have no clear role in HSP.

Activity

Activity can be performed as tolerated.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

To date, no form of therapy appreciably shortens the duration of HSP. Therefore, treatment for most patients remains primarily supportive. This is consonant with the understanding that HSP is a self-limited disease.  

Shenoy et al (2007) reported in an uncontrolled study that children with severe HSP and IgA nephropathy recover well if treated with plasmapheresis alone without the need for immunosuppressive therapy.²⁴ Plasmapheresis therapy has also been useful in treating rapidly progressive HSP nephritis.

Corticosteroids can ameliorate associated arthralgias and the symptoms associated with GI dysfunction. No definitive evidence shows that corticosteroids affect the outcome of renal disease; nevertheless, corticosteroids may be considered in the following serious situations:

• Persistent nephrotic syndrome
• Crescents in more than 50% of glomeruli
• Severe abdominal pain
• Substantial GI hemorrhage
• Severe soft tissue edema
• Severe scrotal edema
• Neurologic system involvement
• Intrapulmonary hemorrhage

No controlled clinical trials have been performed with immunosuppressive drugs, although some claim beneficial results with azathioprine or cyclophosphamide.

The long-term prognosis of HSP directly depends on the severity of renal involvement. The renal dysfunction that HSP causes can benefit from therapy. However, the prophylactic treatment of renal complications in HSP patients, although interesting, is not mandated because study has yielded conflicting results and is ultimately unproven. The treatment of overt HSPN includes methylprednisolone pulse therapy and prednisone and other immunosuppressive medications. 

Only cyclophosphamide has been demonstrated as effective in a recent randomized controlled trial. Cyclosporine does not have clinical data to back its use. ACE-I, azathioprine, mycophenolate mofetil, and urokinase need to be tested before their use is consistently advocated. Plasmapheresis has shown effectiveness in delaying the progression of kidney disease. However, no convincing studies have yet been conducted regarding the use of intravenous immunoglobulin, factor XIII administration, antioxidant vitamin E, and fish oil to treat HSPN.²⁵

Massive GI hemorrhage in isolated intestinal HSP that is responsive to intravenous immunoglobulin infusion has been reported.²⁶

Faedda reported favorable results in patients with severe HSP with the following protocols:²⁷  

1. Induction with 250-750 mg of intravenous (IV) methylprednisolone daily for 3-7 days plus cyclophosphamide 100-200 mg/d administered orally (PO)
2. Maintenance with prednisone 100-200 mg PO every other day plus cyclophosphamide 100-200 mg/d PO 30-75 days
3. Tapering of prednisone by approximately 25 mg/mo (The cyclophosphamide dose remains constant.)
4. Discontinuation of treatment after at least 6 mo by abruptly discontinuing cyclophosphamide and complete prednisone taper

Some have noted that parvovirus B19–associated HSP must be recognized in adults because the treatment of choice is IV gamma globulin combined with anti–TNF-alfa therapy. In contrast, immunosuppressive therapy may lead to a persistent and/or worsening disease course in these patients.

Successful treatment of progressive HSP nephritis with tonsillectomy and corticosteroid pulse therapy has been reported.

Iqbal and Evans (2005) reported the use of dapsone therapy for HSP and found it effective.²⁸

Plasmapheresis therapy has been useful for treating rapidly progressive HSP nephritis.

Drug Category: Immunosuppressive agents

These agents decrease inflammation by suppressing migration of polymorphonuclear (PMN) leukocytes and reversing increased capillary permeability.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Management includes adequate hydration; immediate discontinuation of any exposure to antigenic stimulants (ie, 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.

Further Outpatient Care

• Monitor kidney function in patients who initially had kidney involvement.

In/Out Patient Meds

• Once the initial course of prednisone is administered, additional prednisone appears to have no role.
• Nonsteroidal anti-inflammatory drugs (NSAIDs) can be administered for joint problems. Because of Reye syndrome, the use of NSAIDs should be discussed with the patient's physician.

Complications

• Myocardial infarction
• Pulmonary hemorrhage
• Pleural effusion
• Intussusception
• GI bleeding
• Bowel infarction
• Renal failure
• Hematuria
• Proteinuria
• Seizures
• Mononeuropathies
• Recurrence of symptoms, specifically those of renal impairment (rare)

Prognosis

• The prognosis is excellent; however, complications arise in rare cases.
• The disease usually spontaneously resolves.
• Children younger than 3 years have a shorter, milder course than that of other patients and fewer recurrences than other patients.
• A clinical course with complete resolution of the disease usually occurs in patients with the following:
• • Mild kidney involvement
  • No neurologic complications
  • Disease that lasts less than 4-6 weeks initially
• Recurrences occur in 50% of patients within 6 weeks but can happen as late as 7 years after the initial disease. The higher the number of recurrences, the higher the likelihood of permanent renal damage.
• Persistent renal disease develops in 2-5% of patients (<1% develop ESRF). Age older than 6 years is a negative prognostic indicator.
• Predictors of serious nephropathy or ESRF include the following:
• • Bloody stools
  • Rash persistence
  • Signs of nephritis or nephrotic syndrome (progresses to ESRF within 10 years in 50% of patients)
  • Renal biopsy with extensive glomerular crescents

Patient Education

• Inform patients that the disease is most likely to resolve with few residual adverse effects but that relapses are possible. Explain that severe kidney involvement is rare, but if it does occur, they may require aggressive treatment.
• For excellent patient education resources, visit eMedicine's Kidneys and Urinary System Center. Also, see eMedicine's patient education article Blood in the Urine.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to diagnosis Henoch-Schoenlein purpura (HSP) and monitor patients appropriately
• Failure to adequately monitor patients with HSP and renal involvement for signs of renal dysfunction and failure
• Failure to deal with rare complications involving the kidneys, intestines, CNS, or joints

Special Concerns

• All pregnant women with even mild renal symptoms at HSP onset should be carefully observed during and after pregnancy.
• In adults with HSP, permanent renal involvement is not uncommon.
  
  
  • Hematuria at disease onset and persistence of renal manifestations during the occurrence of HSP can be significant predictors of possible development of renal sequelae.
  • These manifestations plus other features, such as onset in summer, anemia at disease onset, or relapses of the disease, may predict the development of renal sequelae in most patients.
• HSP may mimic an abdominal emergency and, in its severest form, result in small-bowel infarction and/or perforation.
• 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.
• Medications can cause HSP. Losartan therapy has been reported to induce HSP.
• 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.
• When patients present with nephrotic syndrome, hypertension, and rapidly deteriorating renal function, biopsy frequently shows circumferential crescents in most of the glomeruli. Approximately 60% of patients develop renal failure, either in the acute phase of the disease or after an interval of several years.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Henoch EH. Uber ein eigenthe Form von Purpura. Berl Klin Wochenschr. 1974;11:641-3.
2. Yilmaz D, Kavakli K, Ozkayin N. The elevated markers of hypercoagulability in children with Henoch-Schonleinpurpura. Pediatr Hematol Oncol. Jan-Feb 2005;22(1):41-8. [Medline].
3. Aliyazicioglu Y, Ozkaya O, Yakut H, et al. Leptin levels in Henoch-Schonlein purpura. Clin Rheumatol. Mar 2007;26(3):371-5. [Medline].
4. Gardner-Medwin JM, Dolezalova P, Cummins C, Southwood TR. Incidence of Henoch-Schonlein purpura, Kawasaki disease, and rare vasculitides in children of different ethnic origins. Lancet. Oct 19 2002;360(9341):1197-202. [Medline].
5. Haugeberg G, Bie R, Bendvold A, et al. Primary vasculitis in a Norwegian community hospital: a retrospective study. Clin Rheumatol. 1998;17(5):364-8. [Medline].
6. Bazina M, Glavina-Durdov M, Scukanec-Spoljar M, et al. Epidemiology of renal disease in children in the region of Southern Croatia: A 10-year review of regional renal biopsy databases. Med Sci Monit. Mar 27 2007;13(4):CR172-176. [Medline].
7. Nong BR, Huang YF, Chuang CM, Liu CC, Hsieh KS. Fifteen-year experience of children with Henoch-Schonlein purpura in southern Taiwan, 1991-2005. J Microbiol Immunol Infect. Aug 2007;40(4):371-6. [Medline].
8. Suehiro RM, Soares BS, Eisencraft AP, Campos LM, Silva CA. Acute hemorrhagic edema of childhood. Turk J Pediatr. Apr-Jun 2007;49(2):189-92. [Medline].
9. Pabunruang W, Treepongkaruna S, Tangnararatchakit K, et al. Henoch-Schonlein purpura: clinical manifestations and long-term outcomes in Thai children. J Med Assoc Thai. Nov 2002;85 Suppl 4:S1213-8. [Medline].
10. Lin SJ, Huang JL. Henoch-Schonlein purpura in Chinese children and adults. Asian Pac J Allergy Immunol. Mar 1998;16(1):21-5. [Medline].
11. Prais D, Amir J, Nussinovitch M. Recurrent Henoch-Schonlein purpura in children. J Clin Rheumatol. Feb 2007;13(1):25-8. [Medline].
12. Ha TS, Lee JS. Scrotal involvement in childhood Henoch-Schonlein purpura. Acta Paediatr. Apr 2007;96(4):552-5. [Medline].
13. Ozkaya O, Bek K, Alaca N, et al. Cerebral vasculitis in a child with Henoch-Schonlein purpura and familial Mediterranean fever. Clin Rheumatol. Oct 2007;26(10):1729-32. [Medline].
14. Chan KH, Tang WY, Lo KK. Bullous lesions in Henoch-Schonlein purpura. Pediatr Dermatol. May-Jun 2007;24(3):325-6. [Medline].
15. Szeto CC, Choi PC, To KF, et al. Grading of acute and chronic renal lesions in Henoch-Schönlein purpura. Mod Pathol. Jul 2001;14(7):635-40. [Medline].
16. Levy M. Familial cases of Berger's disease and anaphylactoid purpura. Kidney Int. Oct 2001;60(4):1611-2. [Medline].
17. Coppo R, Basolo B, Piccoli G, et al. IgA1 and IgA2 immune complexes in primary IgA nephropathy and Henoch-Schonlein nephritis. Clin Exp Immunol. Sep 1984;57(3):583-90. [Medline].
18. Davin JC, Malaise M, Foidart J, Mahieu P. Anti-alpha-galactosyl antibodies and immune complexes in children with Henoch-Schonlein purpura or IgA nephropathy. Kidney Int. May 1987;31(5):1132-9. [Medline].
19. Jennette JC, Wieslander J, Tuttle R, Falk RJ. Serum IgA-fibronectin aggregates in patients with IgA nephropathy and Henoch-Schonlein purpura: diagnostic value and pathogenic implications. The Glomerular Disease Collaborative Network. Am J Kidney Dis. Oct 1991;18(4):466-71. [Medline].
20. Zhou JH, Huang AX, Liu TL. [A clinico-pathological study comparing Henoch-Schonlein purpura nephritis with IgA nephropathy in children]. Zhonghua Er Ke Za Zhi. Nov 2003;41(11):808-12. [Medline].
21. Coppo R, Andrulli S, Amore A, et al. Predictors of outcome in Henoch-Schonlein nephritis in children and adults. Am J Kidney Dis. Jun 2006;47(6):993-1003. [Medline].
22. Prenzel F, Pfaffle R, Thiele F, Schuster V. Decreased factor XIII activity during severe Henoch-Schoenlein purpura -- does it play a role?. Klin Padiatr. May-Jun 2006;218(3):174-6. [Medline].
23. Nchimi A, Khamis J, Paquot I, Bury F, Magotteaux P. Significance of bowel wall abnormalities at ultrasound in Henoch-Schonlein purpura. J Pediatr Gastroenterol Nutr. Jan 2008;46(1):48-53. [Medline].
24. Shenoy M, Ognjanovic MV, Coulthard MG. Treating severe Henoch-Schonlein and IgA nephritis with plasmapheresis alone. Pediatr Nephrol. Aug 2007;22(8):1167-71. [Medline].
25. Zaffanello M, Brugnara M, Franchini M. Therapy for children with henoch-schonlein purpura nephritis: a systematic review. ScientificWorldJournal. 2007;7:20-30. [Medline].
26. Fagbemi AA, Torrente F, Hilson AJ, Thomson MA, Heuschkel RB, Murch SH. Massive gastrointestinal haemorrhage in isolated intestinal Henoch-Schonlein purpura with response to intravenous immunoglobulin infusion. Eur J Pediatr. Sep 2007;166(9):915-9. [Medline].
27. Faedda R, Pirisi M, Satta A, et al. Regression of Henoch-Schonlein disease with intensive immunosuppressive treatment. Clin Pharmacol Ther. Nov 1996;60(5):576-81. [Medline].
28. Iqbal H, Evans A. Dapsone therapy for Henoch-Schonlein purpura: a case series. Arch Dis Child. Sep 2005;90(9):985-6. [Medline].
29. Abend NS, Licht DJ, Spencer CH. Lupus anticoagulant and thrombosis following Henoch-Schonlein purpura. Pediatr Neurol. May 2007;36(5):345-7. [Medline].
30. Amitai Y, Gillis D, Wasserman D, Kochman RH. Henoch-Schonlein purpura in infants. Pediatrics. Dec 1993;92(6):865-7. [Medline].
31. Ansell BM, Falcini F. Cutaneous vasculitis in children. Clin Dermatol. Sep-Oct 1999;17(5):577-80. [Medline].
32. Cioc AM, Sedmak DD, Nuovo GJ, et al. Parvovirus B19 associated adult Henoch Schonlein purpura. J Cutan Pathol. Nov 2002;29(10):602-7. [Medline].
33. Dubin BA, Bronson DM, Eng AM. Acute hemorrhagic edema of childhood: an unusual variant of leukocytoclastic vasculitis. J Am Acad Dermatol. Aug 1990;23(2 Pt 2):347-50. [Medline].
34. Dudley J, Afifi E, Gardner A, et al. Polymorphism of the ACE gene in Henoch-Schonlein purpura nephritis. Pediatr Nephrol. Mar 2000;14(3):218-20. [Medline].
35. Gandy A. Henoch-Schonlein purpura. Children's Intensive Caring Web site. Available at http://www.intensivecaring.com.
36. Garcia-Porrua C, Gonzalez-Louzao C, Llorca J, Gonzalez-Gay MA. Predictive factors for renal sequelae in adults with Henoch-Schonlein purpura. J Rheumatol. May 2001;28(5):1019-24. [Medline].
37. GE Medical Systems. Henoch-schonlein purpura. Medcyclopaedia. Available at http://www.medcyclopaedia.com.
38. Ha TS, Lee JS. Scrotal involvement in childhood Henoch-Schönlein purpura. Acta Paediatr. Apr 2007;96(4):552-5. [Medline].
39. Harada T, Machida H, Ito S, Aihara Y, Yokota S. Henoch-Schonlein purpura presenting duodenal involvement similar to superior mesenteric artery syndrome in a girl. Eur J Pediatr. May 2007;166(5):489-90. [Medline].
40. Kaku Y, Nohara K, Honda S. Renal involvement in Henoch-Schonlein purpura: a multivariate analysis of prognostic factors. Kidney Int. Jun 1998;53(6):1755-9. [Medline].
41. Kawasaki Y, Suyama K, Matsumoto A, et al. Efficacy of tonsillectomy plus methylprednisolone pulse therapy for a child with Henoch-Schoenlein purpura nephritis. Tohoku J Exp Med. Mar 2007;211(3):291-5. [Medline].
42. Kawasaki Y, Suzuki J, Murai M, et al. Plasmapheresis therapy for rapidly progressive Henoch-Schonlein nephritis. Pediatr Nephrol. Aug 2004;19(8):920-3. [Medline].
43. Kim CJ, Chung HY, Kim SY, et al. Acute appendicitis in Henoch-Schonlein purpura: a case report. J Korean Med Sci. Oct 2005;20(5):899-900. [Medline].
44. Korzets Z, Magen E, Tetro J, et al. [Crescentic glomerulonephritis and cerebral vasculitis in the course of Henoch-Schonlein purpura]. Harefuah. Nov 2002;141(11):960-3, 1010. [Medline].
45. Koskimies O, Mir S, Rapola J, Vilska J. Henoch-Schonlein nephritis: long-term prognosis of unselected patients. Arch Dis Child. Jun 1981;56(6):482-4. [Medline].
46. Kraft DM, Mckee D, Scott C. Henoch-Schonlein purpura: a review. Am Fam Physician. Aug 1998;58(2):405-8, 411. [Medline]. [Full Text].
47. Lau KK, Wyatt RJ, Moldoveanu Z, et al. Serum levels of galactose-deficient IgA in children with IgA nephropathy and Henoch-Schonlein purpura. Pediatr Nephrol. Dec 2007;22(12):2067-72. [Medline].
48. Legrain V, Lejean S, Taieb A, et al. Infantile acute hemorrhagic edema of the skin: study of ten cases. J Am Acad Dermatol. Jan 1991;24(1):17-22. [Medline].
49. Martinez Lopez MM, Rodriguez Arranz C, Pena Carrion A, Merino Munoz R, Garcia-Consuegra Molina J. [Henoch-Schonlein purpura. Study of factors associated with the development and course of the disease]. An Pediatr (Barc). May 2007;66(5):453-8. [Medline].
50. Millard T, Harris A, MacDonald D. Acute infantile hemorrhagic oedema. J Am Acad Dermatol. Nov 1999;41(5 Pt 2):837-9. [Medline].
51. Moses S. Henoch-Schonlein purpura. Family Practice Notebook Web site. Available at http://www.fpnotebook.com/HEM33.htm. Accessed 2003.
52. Nan DN, Fernandez-Ayala M, Garcia-Ibarbia C. Henoch-Schonlein purpura after intravesical administration of bacillus Calmette-Guerin. Scand J Infect Dis. 2005;37(8):613-615. [Medline].
53. Quercia O, Emiliani F, Foschi FG, Stefanini GF. Unusual reaction to hymenoptera sting: a case of Schonlein-Henoch purpura. Allergy. Mar 2007;62(3):333-4. [Medline].
54. Ronkainen J, Nuutinen M, Koskimies O. The adult kidney 24 years after childhood Henoch-Schonlein purpura: a retrospective cohort study. Lancet. Aug 31 2002;360(9334):666-70. [Medline].
55. Saraclar Y, Tinaztepe K, Adalioglu G, Tuncer A. Acute hemorrhagic edema of infancy (AHEI)--a variant of Henoch-Schonlein purpura or a distinct clinical entity?. J Allergy Clin Immunol. Oct 1990;86(4 Pt 1):473-83. [Medline].
56. Saulsbury FT. Henoch-Schonlein purpura in children. Report of 100 patients and review of the literature. Medicine (Baltimore). Nov 1999;78(6):395-409. [Medline].
57. Saulsbury FT. Henoch-Schonlein purpura. Pediatr Dermatol. Jan 1984;1(3):195-201. [Medline].
58. Shetty AK, Desselle BC, Ey JL, et al. Infantile Henoch-Schonlein purpura. Arch Fam Med. Jun 2000;9(6):553-6. [Medline].
59. Snow IM. Purpura, urticaria and angioneurotic edema of the hands and feet in a nursing baby. JAMA. 1913;61:18-9.
60. Soylemezoglu O, Ozkaya O, Erbas D, et al. Nitric oxide in Henoch-Schonlein purpura. Scand J Rheumatol. 2002;31(5):271-4. [Medline].
61. Sugiyama H, Watanabe N, Onoda T, et al. Successful treatment of progressive Henoch-Schonlein purpura nephritis withtonsillectomy and steroid pulse therapy. Intern Med. Jun 2005;44(6):611-5. [Medline].
62. Szer IS. Gastrointestinal and renal involvement in vasculitis: management strategies in Henoch-Schonlein purpura. Cleve Clin J Med. May 1999;66(5):312-7. [Medline].
63. Szer IS. Henoch-Schonlein purpura. Curr Opin Rheumatol. Jan 1994;6(1):25-31. [Medline].
64. Szer IS. Henoch-Schonlein purpura: when and how to treat. J Rheumatol. Sep 1996;23(9):1661-5. [Medline].
65. Tizard EJ. Henoch-Schonlein purpura. Arch Dis Child. Apr 1999;80(4):380-3. [Medline].
66. Vila Cots J, Gimenez Llort A, Camacho Diaz JA, Vila Santandreu A. [Nephropathy in Schonlein-Henoch purpura: a retrospective study of the last 25 years]. An Pediatr (Barc). Mar 2007;66(3):290-3. [Medline].
67. Watanabe T, Sato Y. Renal involvement and hypocomplementemia in a patient with acute hemorrhagic edema of infancy. Pediatr Nephrol. Nov 2007;22(11):1979-81. [Medline].
68. Zoch-Zwierz W, Biernacka A, Tomaszewska B, et al. [Vasculitis of cerebral vessels, probable cause of neurological complications in a child with Schonlein-Henoch purpura]. Pol Merkuriusz Lek. Apr 2002;12(70):306-8. [Medline].

Article Last Updated: May 28, 2008