eMedicine Specialties > Pediatrics: General Medicine > Nephrology

Henoch-Schonlein Purpura

Noah S Scheinfeld, MD, JD, FAAD, Assistant Clinical Professor, Department of Dermatology, Columbia University; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Private Practice
Elena L Jones, MD, Clinical Assistant Professor of Dermatology, College of Physicians and Surgeons of Columbia University; Clinic Chief, Department of Dermatology, St Luke's-Roosevelt Hospital Center

Updated: Sep 28, 2009

Introduction

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

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

The prevalence of Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura by 1-3 weeks. In general, patients with Henoch-Schoenlein purpura appear mildly ill. They often have a fever, with a temperature usually not higher than 38°C (100.4°F). Henoch-Schoenlein purpura is typically an acute, self-limited illness; however, one third of patients have one or more recurrences.

Purpuric papules and plaques of the lower extremity characteristic of Henoch-Schönlein purpura.

Hemorrhagic macules, papules, and patches on the ankle and foot of a child with Henoch-Schönlein purpura.

Pathophysiology

Etiology of Henoch-Schoenlein purpura

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

The predominance of IgA1 in Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura, 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 Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura is lacking.

Alterations in the production of interleukins (ILs) and growth factors may also have a role in the pathogenesis of Henoch-Schoenlein purpura. Tumor necrosis factor (TNF), IL-1, and IL-6 may mediate the inflammatory process present in Henoch-Schoenlein purpura. 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 Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura, 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 Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura.

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

The prevalence of the human parvovirus B19 component NS1 gene in patients with Henoch-Schoenlein purpura and hypersensitivity vasculitis is increased.

Henoch-Schoenlein purpura that is likely due to montelukast has been noted in patients who present with subacute intestinal obstruction.

Other factors

Yilmaz et al examined 28 children with Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura is 20.4 cases per 100,000 population.⁴ In a Norwegian community hospital, the prevalence of Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura.⁶  

Nong et al reviewed the records of 107 Taiwanese pediatric patients diagnosed with Henoch-Schoenlein purpura 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 followed 4,502 patients at the Pediatric Rheumatology clinic in Brazil.⁸ A diagnosis of Henoch-Schoenlein purpura was made in 203 cases (4.5%); 5 patients (0.1%) had acute hemorrhagic edema of infancy (AHEI). All patients with AHEI were male, and the mean age at onset was 18 months (range, 8-21 mo).

Mortality/Morbidity

Henoch-Schoenlein purpura is only fatal in the rarest of cases. Initial attacks of Henoch-Schoenlein purpura can last several months, and relapses are possible. Kidney damage related to Henoch-Schoenlein purpura is the primary cause of morbidity and mortality. Overall, an estimated 2% of cases of Henoch-Schoenlein purpura progress to renal failure; as many as 20% of children who have Henoch-Schoenlein purpura 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

Henoch-Schoenlein purpura 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. Henoch-Schoenlein purpura is rare in infants and young children. A related milder condition called AHEI occurs in infants younger than 2 years.¹¹

Clinical

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 Henoch-Schoenlein purpura that resulted in hospitalization 2 or more times.¹² 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 Henoch-Schoenlein purpura include those listed in Causes.
• Scrotal involvement is not uncommon in Henoch-Schoenlein purpura 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 have a significant relationship with scrotal involvement in male patients with Henoch-Schoenlein purpura.¹³
• GI symptoms can accompany the onset of Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura. GI problems usually follow the onset of rash and joint pain. Multiple and recurrent intestinal perforations are an unusual complication of Henoch-Schoenlein purpura. 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 Henoch-Schoenlein purpura and most commonly affect the knees, ankles, and, less frequently, the wrists and fingers. True arthritis does not occur, and joint effusions are rare. Henoch-Schoenlein purpura leaves no permanent joint deformities.
• In women, gynecologic symptoms can include painful menstruation.
• Henoch-Schoenlein purpura can be accompanied by neurologic manifestations, particularly headaches. Ozkaya et al reported cerebral vasculitis in a child with Henoch-Schoenlein purpura and familial Mediterranean fever.¹⁴
  • In rare cases, Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura.
  • 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 Henoch-Schoenlein purpura.
• Skin involvement is usually purpura. Chan et al noted a case of Henoch-Schoenlein purpura presented as painful bullae on both legs.¹⁵
• 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 Henoch-Schoenlein purpura.
  • 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 Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura, but renal, GI, and joint manifestations are commonly present. Other manifestations have also been reported.

Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura 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.¹⁶ 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 Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura.
• IgA nephropathy has developed in patients with a history of Henoch-Schoenlein purpura. Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura.¹⁷
• Patients with Henoch-Schoenlein purpura 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.^18,19,20

• 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 Henoch-Schoenlein purpura.
  • 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.
  • Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura.
  • 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 Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura, 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 Henoch-Schoenlein purpura. 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 Henoch-Schoenlein purpura.²²
  • 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 reported that neurologic symptoms, localized edema, and high serum C3 levels show a significant relation with scrotal involvement in male patients with Henoch-Schoenlein purpura.¹³
• 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 Henoch-Schoenlein purpura.²³

Causes

The following conditions may precede Henoch-Schoenlein purpura:

• 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
  • Helicobacter pylori infection^24,25,26
  • Yersinia infection
  • Shigella infection
  • Salmonella infection
• Vaccinations
  • Typhoid
  • Measles
  • Cholera
  • Yellow fever
• Environmental exposure to allergens
  • Drugs (eg, ampicillin, erythromycin, penicillin, quinidine, quinine, cytarabine²⁷ )
  • Foods
  • Horse serum
  • Cold exposure
  • Insect bites
• Idiopathic illness - Glomerulocystic kidney disease

Differential Diagnoses

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

Laboratory 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 Henoch-Schoenlein purpura 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.²⁸ 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.^29,30

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 Henoch-Schoenlein purpura using sonography and radionuclear scanning in a child presenting with bilateral acute scrotum as the main symptom of Henoch-Schoenlein purpura has been reported.
  • In children with GI involvement of Henoch-Schoenlein purpura, dedifferentiated wall thickening demonstrated by ultrasound reveals a poor clinical prognosis.³¹
• 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 Henoch-Schoenlein purpura.
  • In one case, a 6-year-old boy with Henoch-Schoenlein purpura 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

• Henoch-Schoenlein purpura is a vasculitis that often involves the kidneys.
• Histopathologic features of the skin lesions in infantile Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura, in which C3 and IgM are most commonly found in the affected vessel walls.
• The histology of the kidney in Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura 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

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 Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura.

Activity

Activity can be performed as tolerated.

Medication

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

Shenoy et al reported in an uncontrolled study that children with severe Henoch-Schoenlein purpura and IgA nephropathy recover well if treated with plasmapheresis alone without the need for immunosuppressive therapy.³² Plasmapheresis therapy has also been useful in treating rapidly progressive Henoch-Schoenlein purpura nephritis.³³

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. Guidelines for prescribing azathioprine in dermatology have been established.³⁴

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

Only cyclophosphamide has been demonstrated as effective in a recent randomized controlled trial. Although some studies have reported success, cyclosporin does not have clinical data to back its use.³⁵ 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 Henoch-Schoenlein purpura.³⁶

Massive GI hemorrhage in isolated intestinal Henoch-Schoenlein purpura that is responsive to intravenous immunoglobulin infusion has been reported.³⁷

Faedda reported favorable results in patients with severe Henoch-Schoenlein purpura with the following protocols:³⁸

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 Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura nephritis with tonsillectomy and corticosteroid pulse therapy has been reported.

Iqbal and Evans reported the use of dapsone therapy for Henoch-Schoenlein purpura and found it effective.³⁹

Plasmapheresis therapy has been useful for treating rapidly progressive Henoch-Schoenlein purpura nephritis.

Immunosuppressive agents

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

Methylprednisolone (Solu-Medrol)

Decreases inflammation by suppressing PMN leukocyte migration and reversing increased capillary permeability.

Dosing

Adult

0.25 mg/kg/d IV (typically about 1 g/d) for 3-7 d

Pediatric

Severe HSP: 250-750 mg IV qd for 3-7 d (administer with cyclophosphamide)

Interactions

Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels; phenobarbital, phenytoin, and rifampin may decrease levels (adjust dose); monitor for hypokalemia with coadministration of diuretics; grapefruit juice increases concentrations; inhibits cyclosporine and vice versa, increasing plasma levels of both

Contraindications

Documented hypersensitivity; viral, fungal, or tubercular skin infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections possible complications of glucocorticoid use

Prednisone (Deltasone, Meticorten, Orasone, Sterapred)

Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and suppresses lymphocyte and antibody production.

Dosing

Adult

5-60 mg/d PO qd or divided bid/qid; taper over 2 wk, as symptoms resolve

Pediatric

Short-term treatment: 4-5 mg/m²/d PO or 0.05-2 mg/kg PO divided bid/qid; taper over 2 wk as symptoms resolve adjust dose accordingly if potent forms of cortisone used
Severe HSP: After induction with IV methylprednisolone, start maintenance therapy with prednisone 100-200 mg PO qod for 30-75 d (in addition to cyclophosphamide); then taper by 25 mg/mo for >6 mo; then begin final slow taper

Interactions

Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Contraindications

Documented hypersensitivity; viral, fungal, or tubercular skin lesions

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in hyperthyroidism, cirrhosis, nonspecific ulcerative colitis, osteoporosis, peptic ulcer, diabetes mellitus, and myasthenia gravis; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Cyclophosphamide (Cytoxan)

Chemically related to nitrogen mustards. As alkylating agent, mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells. Cyclic polypeptide that suppresses some humoral activity. Transformed in liver to active alkylating metabolites, which interfere with growth of rapidly proliferating cells. When used in autoimmune diseases, mechanism of action thought to involve immunosuppression because of destruction of immune cells by DNA cross-linking.

Dosing

Adult

10 mg/kg/d IV q2wk

Pediatric

Administer as in adults or 100-200 PO mg/d

Interactions

Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; toxicity may increase with chloramphenicol; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia; coadministration with succinylcholine may increase neuromuscular blockade by inhibiting cholinesterase activity

Contraindications

Documented hypersensitivity; severely depressed bone marrow function

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis; instruct patient to consume a large quantity of water each day while taking cyclophosphamide

Follow-up

Further Inpatient Care

• Management of Henoch-Schoenlein purpura (HSP) 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.

Inpatient & Outpatient Medications

• 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

Medicolegal Pitfalls

• Failure to diagnosis Henoch-Schoenlein purpura (HSP) and monitor patients appropriately
• Failure to adequately monitor patients with Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura onset should be carefully observed during and after pregnancy.
• In adults with Henoch-Schoenlein purpura, permanent renal involvement is not uncommon.
  • Hematuria at disease onset and persistence of renal manifestations during the occurrence of Henoch-Schoenlein purpura 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.
• Henoch-Schoenlein purpura 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 Henoch-Schoenlein purpura. Losartan therapy has been reported to induce Henoch-Schoenlein purpura.
• 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.

Multimedia

Media file 1: Purpuric papules and plaques of the lower extremity characteristic of Henoch-Schönlein purpura.

Media file 2: Hemorrhagic macules, papules, and patches on the ankle and foot of a child with Henoch-Schönlein purpura.

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Keywords

Henoch Schönlein purpura, Henoch-Schönlein purpura, Henoch Schonlein purpura, Henoch-Schonlein purpura, Henoch Schoenlein purpura, Henoch-Schoenlein purpura, HSP, allergic purpura, Henoch's purpura, Schönlein purpura, Schönlein's purpura, Schönlein disease, Schönlein's disease, Henoch-Schönlein purpura, Henoch-Schönlein syndrome, Schönlein-Henoch syndrome, vascular purpura, acute vascular purpura, anaphylactoid purpura, hemorrhagic exudative erythema, purpura nervosa, purpura rheumatica, rheumatocelis, purpura fulminans, purpura hemorrhagica, nonthrombocytopenic purpura, rheumatoid purpura, allergic purpura

hemorrhagic capillary toxicosis, nonthrombocytopenic idiopathic purpura, peliosis rheumatica, rheumatic purpura, acute hemorrhagic edema of infancy, AHEI, postinfectious cockade purpura, Finkelstein disease, Finkelstein's disease, Seidelmayer syndrome, Seidelmayer's syndrome, infantile postinfectious irislike purpura and edema, vasculitis, arthritis, cutaneous purpura, orchitis, nephritis, species, adenoviruses, Epstein-Barr virus, EBV, parvoviruses, varicella, hypertension, proteinuria, mononucleosis, group A streptococcal infection, hepatitis, varicella-zoster infection

Contributor Information and Disclosures

Author

Noah S Scheinfeld, MD, JD, FAAD, Assistant Clinical Professor, Department of Dermatology, Columbia University; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Private Practice
Noah S Scheinfeld, MD, JD, FAAD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Optigenex Consulting fee Independent contractor

Coauthor(s)

Elena L Jones, MD, Clinical Assistant Professor of Dermatology, College of Physicians and Surgeons of Columbia University; Clinic Chief, Department of Dermatology, St Luke's-Roosevelt Hospital Center
Disclosure: Nothing to disclose.

Medical Editor

Richard Neiberger, MD, PhD, Director of Pediatric Renal Stone Disease Clinic, Associate Professor, Department of Pediatrics, Division of Nephrology, University of Florida College of Medicine and Shands Hospital
Richard Neiberger, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Medical Association, American Society of Nephrology, American Society of Pediatric Nephrology, Christian Medical & Dental Society, Florida Medical Association, International Society for Peritoneal Dialysis, International Society of Nephrology, National Kidney Foundation, New York Academy of Sciences, Shock Society, Sigma Xi, Southern Medical Association, Southern Society for Pediatric Research, and Southwest Pediatric Nephrology Study Group
Disclosure: The Osler Institute Honoraria Speaking and teaching

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Adrian Spitzer, MD, Professor, Department of Pediatrics, Albert Einstein College of Medicine; Director of NIH Training Program, Children's Hospital at Montefiore Medical Center
Adrian Spitzer, MD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Pediatric Society, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Howard Trachtman, MD, Program Director, Pediatrics Research, Schneider Children's Hospital, Department of Pediatrics, Division of Nephrology, Professor, Albert Einstein College of Medicine
Howard Trachtman, MD is a member of the following medical societies: American Society of Hypertension, American Society of Nephrology, American Society of Pediatric Nephrology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Craig B Langman, MD, The Isaac A Abt, MD, Professor of Kidney Diseases, Feinberg School of Medicine, Northwestern University; Division Head of Kidney Diseases, Children's Memorial Hospital, Chicago
Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, and International Society of Nephrology
Disclosure: Amgen Grant/research funds None; Altus Pharmaceuticals Grant/research funds None; Genzyme Grant/research funds None; Merck Grant/research funds None; NIH Grant/research funds None

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