Management of Henoch Schonlein Purpura: the roles of family physicians

Keith K Lau 劉廣洪， Cheryl D Lau 劉舒懷， Chun-bong Chow 周鎮邦

HK Pract 2015;37:71-75

Summary

Henoch-Schonlein Purpura (HSP) is the commonest form of vasculitis in children. Most recover without any long term morbidity. However, those who develop renal complications may have grave outcomes. Care providers should monitor their patients and refer nephritic patients to nephrologists promptly.

摘要

過敏性紫癜（HSP）是兒童血管炎最常見的形式。大多數病兒康復後不會留下長期併發症，但是一旦出現腎臟併發症後果可能很嚴重。醫生應對患者進行監測，並將發生腎病的患者及時轉介至腎病專科醫生

Case scenario

Introduction

Henoch-Schonlein Purpura (HSP) is the commonest form of vasculitis in children.¹ Related symptoms include a low-severity purpuric rash, abdominal pain and arthritis. Renal involvement is observed in roughly half of the patients and is rarely severe. However, some patients will have an aggressive clinical course, which can lead to chronic renal impairment and progression to end-stage renal disease. HSP is characterised by the presence of immunoglobulin A1 (IgA1) immune deposits in the small vessels. The renal histological and immunofluorescence microscopic findings in HSP nephritis are indistinguishable from those seen in patients with IgA nephropathy (IgAN).^2,3 Both diseases are thought to be in the same spectrum of conditions as they share many clinical similarities.

HSP may also occur in adults, but its natural history and clinical outcomes in adults are much less known since most observations are conducted among children. However, available information from literature suggests that clinical presentations differ between adults and children, with less intercurrent infections and arthritis but more necrotic purpura, transient liver dysfunctions and cholestasis, as well as higher serum IgA levels among adults.^4,5 Despite the general impression that adults with HSP nephritis have poorer outcomes when compared to children, it should be stressed that existing literature are mostly retrospective and comprise only of a small numbers of patients.⁵

Epidemiology of HSP

The incidence of HSP in children is approximately 10 cases per 100,000 children per year in Europe.^6,7 Although similar data is unavailable in Hong Kong, a recent Taiwanese study reported a similar annual incidence of 12.9 per 100,000 among children aged below eighteen.⁸ In the cohort from Taiwan, HSP was seen throughout the year, but occurrence was higher in autumn and winter. The male to female ratio was 1.11 to 1.

Aetiology

HSP is distinguished from other systemic diseases by the deposition of IgA1 in the blood vessel walls of affected organs and of renal glomerular mesangium.⁹ Although galactose deficient IgA1 has been implicated in the pathogenesis of HSP, its levels have only been seen to be elevated in patients with nephritic complications.² It has also been suggested that elevated serum levels of galactose deficient IgA1 do not appear sufficient in themselves to cause nephritis, so it is likely that subsequent “hits”, including the formation of large circulating immune complex, are required before this glycosylation defect translate into clinical disease.^10,11

Although the aetiology of HSP is still unknown, triggering factors such as viral and bacterial infections have been reported.^12,13 Rare cases of post-streptococcal acute glomerulonephritis may mimic HSP.^14,15

Roles of family physicians

(1) Detection and confirmation of the diagnosis

The classical triad of HSP includes non-thrombocytopenic palpable purpuric rash, arthritis/ arthralgia, and abdominal pain. Among 261 children from Taiwan, purpuric rashes, abdominal pain, and arthritis occurred in 100%, 57.9% and 42.9%, respectively, of the children at presentation.¹⁶ Most of the time, HSP remains a clinical diagnosis and only minimal laboratory investigations are needed. Table 1 depicts the most current classification for HSP proposed by the Pediatric Rheumatology International Trials Organisation (PRINTO).¹⁷ According to the criteria, a patient can be classified to have HSP in the presence of purpuric rashes with typical distribution, in addition to one of the four other features (abdominal pain, leucocytoclastic vasculitis on skin biopsy or mesangial proliferation with predominant mesangial IgA deposition on renal biopsy, arthritis/arthralgias, and renal involvement).

(a) Skin rash

This usually starts as erythematous papules over the lower limbs and buttocks, but the upper limbs, face, and torso may also be involved. Within one to two days the rashes usually coalesce into the classical cutaneous appearance of palpable purpuric rashes. The diagnosis is usually obvious in children with the typical cutaneous rashes. However, it becomes a challenge when other features precede the rashes, including gastrointestinal symptoms such as severe abdominal pain. Abdominal pain may mimic an acute abdomen, and some reports the onset of pain up to 3 months before the appearance of the rash.^16,18,19

(b) Arthritis/arthralgia

Joint involvements are commonly seen with other features at presentation, usually involving the lower limbs and may be associated with prominent swelling and pain. However, the inflammation is often transient with no long term sequelae.

(c) Gastro-intestinal symptoms

These include colicky abdominal pain, nausea and vomiting. Symptoms may be present before or after the appearance of the skin rashes. Rare but significant complications such as paralytic ileus, haemorrhage, intussusception, bowel necrosis, and perforation have also been reported in children.¹⁶ As intussusception associated with HSP is usually ileoileal, abdominal ultrasonography has been promoted as the preferred screening test. ²⁰ Rare and fatal gastrointestinal complication have also been reported before.²¹

(d) Renal involvement

Among all of the presenting features of HSP, kidney involvement has the most significant long term implication. Approximately 40% of children with HSP develop nephritis within four to six weeks after their initial presentation.^3,22 Microscopic haematuria with various degree of proteinuria is most common, but gross haematuria may also be seen in 25% of patients.^16,23 Nephrotic syndrome and end-stage renal diseases at presentation are rare and are associated with poor long term prognosis.^24,25

The diagnosis of HSP is usually quite obvious in children presenting with the classical triad, but is more difficult when skin rash is absent at presentation when other differential diagnosis should be considered, such as acute surgical abdomen and rheumatologic diseases.

Although laboratory investigations are sometimes helpful in detecting complications, the diagnosis of HSP mostly depends on the clinical findings. Complete blood count may show normal or elevated white cells and platelet counts. Electrolytes are usually within normal limits in the absence of gastro-intestinal or renal complications. A rise in urea and creatinine indicates the possibility of rapidly progressive glomerulonephritis and deserve an immediate referral to paediatric nephrologists. Complement 3 and 4 levels are typically normal. However, microscopic haematuria and guaiac positive stool are fairly common at presentation. Elevated serum IgA levels are present in over half of patients but are neither sensitive nor specific.

(2) Provide acute phase management

The disease is usually self-limited and without any long term complications. However, up to half of the patients may have recurrence of the clinical features within the first few months. The mainstay of treatment is supportive with special care to ensure sufficient hydration, adequate control of pain, and close monitoring for acute complications. Skin rashes do not require any therapy, while most of the arthritic symptoms can be alleviated by non-steroidal anti-inflammatory drugs. Most of the symptoms subside within a few weeks, but due to the risks of renal complications (see below), children with HSP should be followed up for development of proteinuria for at least 6 months.

Most children with HSP can be managed as outpatients. Those with severe symptoms or unresponsive to treatment, should be admitted for further management. Most children do not require parenteral fluid, unless they have prolonged severe abdominal pain and other gastro-intestinal complications such as intussusception. Corticosteroids are commonly prescribed for controlling abdominal pain especially among those unresponsive to supportive treatment, but few clinical evidence supports this practice. Although rare, any children with changes in conscious levels should have intracranial bleeding excluded.26 Other rare complications include pulmonary haemorrhage and uveitis.^27,28

(3) Monitor for long term consequences

Nephritis typically occurs four to six weeks after the appearance of the rashes, but may have a delayed onset of up to six months after the appearance of rashes. It is therefore essential to monitor for proteinuria. Ideally, families should be educated to perform home urine dipstick weekly for the occurrence of proteinuria.²⁹ Otherwise, children should be followed up every monthly for 6 months to monitor blood pressure, perform urinalysis and check for symptoms recurrence. Despite the fact that some investigators have suggested that corticosteroids had preventive effects on development of nephritis³⁰, a recent Cochrane study does not support this.³¹ Hence, the current available information from literature does not support the initiation of corticosteroids for the purpose of prevention of nephritis.

(4) Decision on when to refer to specialists

Although most nephritic children with minimal proteinuria have excellent prognosis, some are at risk of suffering from chronic kidney diseases and so should be referred to nephrologists for follow up. Depending on the severity, medical management ranges from just monitoring to administering drug therapies. Commonly used medications include ACE inhibitors, ARB, corticosteroids, and other immunosuppressive drugs such as mycophenolate mofetil and cyclophsphamide. The majority of patients achieve remissions after therapies, but a long term study from Mayo clinic showed that renal impairment may recur even after long term remission.32 Hence, patients should be followed up for regular surveillance for an extensive period of time. Patients present with hypertension, acute nephritic/ nephritic syndrome with or without renal dysfunctions should also be referred to nephrologists for further management.

Clinical course of the patient

The patient was sent home with a prescription of ibuprofen 100mg three times daily. His ankle pain subsided after 3 days of medications. His mother called the office 2 days later due to worsening of abdominal pain, but the pain abated after a week without any intervention. His skin rashes disappeared after 2 weeks and his urinalysis upon following up at 4 weeks after the onset of the rashes showed no proteinuria. Several urinalyses afterwards were also negative for protein. He was discharged from the clinic after 6 months and was reminded to have urine checked every time he attended for his physical check-up.

Conclusion

HSP is a common and self-limiting illness where most patients require only supportive care. Although most of these patients should be followed up by their family physicians, caregivers should monitor the patients vigilantly for development of nephritis. While many patients do not suffer from long-term complications, a minority of patients may develop chronic kidney diseases, and referrals to paediatric nephrologists are necessary in such circumstances.