Jurnal Purpura Haenox Scholen pada Anak

REVIEW ARTICLE

HenochSchnlein purpura in childrenPeter Trnka

Queensland Child and Adolescent Renal Service, Royal Childrens Hospital, Herston, Queensland, Australia

Abstract: HenochSchnlein purpura is the most common systemic vasculitis of childhood. In the majority of children, the outcome ofHenochSchnlein purpura is excellent with spontaneous resolution of symptoms and signs. However, a small subset of patients will developlong-term sequelae in the form of chronic kidney disease. While the clinical presentation and diagnosis of HenochSchnlein purpura isstraightforward, treatment of HenochSchnlein purpura nephritis and long-term renal outcomes of more severely affected children are lesscertain. This review article gives a general overview of HenochSchnlein purpura with emphasis on recently published information, includingthe new classication of childhood vasculitis, insights into pathogenesis of HenochSchnlein purpura and a summary of various treatments ofestablished HenochSchnlein purpura nephritis.

Key words: chronic kidney disease; immunoglobulin A; nephritis; purpura; vasculitis.

History

The first clinical description of HenochSchnlein purpura(HSP) comes from English physician William Heberden, who

described two boys with clinical findings suggestive of HSPincluding purpuric rash, arthralgia and abdominal pain.1 HSPcarries the names of two 19th century German physicians,Johann Schnlein and his student Eduard Henoch. Schnleindescribed the association of non-thrombocytopaenic purpuraand joint pain in 1837, which he called purpura rheumatica.2

Henoch added gastrointestinal and renal involvement in 1874.3

Purpura is a latin word for purple, which has its origin in Greekword porphyra, a name of the Tyrian purple dye secreted by seasnails Murex trunculus and Murex brandaris, used for centuries asan imperial dye. Anaphylactoid purpura, another commonlyused name for HSP, is incorrect and should not be used becauseanaphylaxis does not play a significant role in the pathogenesisof this vasculitis.

Denition and Classication

HSP is a systemic vasculitis characterised by the deposition ofimmunoglobulin A (IgA)-containing immune complexes in thewalls of small vessels (arterioles, capillaries andvenules).Accordingto the recently endorsed European League Against Rheumatism,Paediatric Rheumatology European Society and PaediatricRheumatology International Trials Organisation classificationof childhood vasculitis, HSP belongs to the group of non-granulomatous, predominantly small vessel vasculitides (Table 1).4

Epidemiology

HSP is the most common childhood vasculitis with a reportedannual incidence that varies between 10 and 30 cases per100 000 children < 17 years based on hospital and overall popu-lation estimates.5,6 These reports are likely to underestimate thetrue prevalence of HSP given the voluntary nature of reportingto these surveys. The mean age of presentation is 6 years withmost cases in children < 10 years of age,7 and recent studies

Key Points

1 HenochSchnlein purpura is the most common systemic vas-culitis of childhood presenting with a tetrad of purpura, arthri-tis or arthralgia, abdominal pain and renal disease. While thepresence of purpura is a compulsory criterion for the diagno-sis of HenochSchnlein purpura, other signs and symptomsare more variably present.

2 Abnormal glycosylation of immunoglobulin A1 moleculespredisposes patients with HenochSchnlein purpura toformation of large immune complexes. Clearance of theselarge molecules is impaired, they deposit in small vessel wallsof the affected organs and trigger immune response leadingto inammatory reaction presenting as clinical signs andsymptoms.

3 The long-term morbidity of HenochSchnlein purpura isrelated to nephritis. Based on the current evidence, earlyimmunosuppressive treatment of children with HenochSchnlein purpura should be reserved for those presentingwith severe kidney involvement (rapidly progressive glomeru-lonephritis, nephrotic syndrome). There might be a role forimmunosuppression in patients with ongoing nephritis(persistent/increasing proteinuria), but this approach willhave to be tested in large prospective studies before it canbe widely accepted in clinical practice.

Correspondence: Dr. Peter Trnka, Queensland Child and AdolescentRenal Service, Royal Childrens Hospital, Woolworths Building, 5th Floor,Herston Road, Herston, QLD, 4029, Australia. Fax: (07) 3636 5505; email:[email protected]

Conict of interest: None.

Accepted for publication 21 July 2013.

doi:10.1111/jpc.12403

bs_bs_banner

Journal of Paediatrics and Child Health 49 (2013) 9951003 2013 The AuthorJournal of Paediatrics and Child Health 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians)

995

suggesting an equal incidence in males and females.8 HSP occurspredominantly in cold months of the year and has beenreported worldwide.

Aetiology and Pathogenesis

The majority of HSP cases are preceded by an upper respiratorytract infection suggesting a potential infectious trigger. Strepto-coccus, staphylococcus and parainfluenza are most commonlyimplicated but there are multiple case reports describing theassociation between virtually all respiratory pathogens andHSP.9 Anecdotal reports also describe HSP cases after vaccina-tion, with multiple vaccines implicated, including the recentlydeveloped pandemic influenza A (H1N1) vaccine.10 An associa-tion between drugs and HSP has also been reported, althoughthe role of these medications in pathogenesis of HSP is uncertaingiven that most were being used at the time of onset of thedisease for treatment of concurrent infection.

The characteristic pathological feature of HSP vasculitis is adeposition of IgA-containing immune complexes in vessel wallsof affected organs and in the kidney mesangium. Histologically,the appearance of HSP nephritis is identical to IgA nephropathyand recent studies in patients with HSP and IgA nephropathyhave detailed a potential role of IgA1 in the pathogenesis of bothof these conditions.11,12

IgA is found in serum and mucosal secretions and is a majorclass of immunoglobulin that plays an important role in mucosalimmunity. In man, more IgA is produced than all other immu-noglobulin classes combined because of the high mucosal

synthesis and short half-life of IgA of 56 days. Of two IgAsubclasses, IgA1 is phylogenetically younger and differs fromIgA2 by insertion of a 1317 amino acid sequence in the hingeregion of the IgA1 molecule.13 The hinge region of IgA1 is heavilyglycosylated in normal individuals. N-acetylgalactosamine(GalNAc) is O-linked to serine residues (O-glycosylation) andelongation of the glycan chains is achieved by further additionof galactose (Gal) and N-acetylneuraminic acid (NeuNAc)(galactosylation and sialylation) to GalNAc (Fig. 1).14 Glycosy-lation of IgA1 seems to play important role in facilitating clear-ance of IgA1 molecules. Normally glycosylated IgA1 moleculesinteract with the asialoglycoprotein receptor (ASGP-R)expressed on the hepatocytes, followed by internalisation anddegradation of these molecules. Patients with HSP and IgAnephropathy express inherited Gal deficient glycosylation ofIgA1 molecules.11 While the absence of Gal exposes GalNAc as aterminal glycan, the stimulus for the formation of antibodiesagainst GalNAc is unknown. However, many microorganismsexpress GalNAc-containing sugars on their surface. Duringinfection by these microorganisms, antibodies to GalNAc onbacteria or viruses could potentially cross-react with GalNAc onIgA1 molecule with subsequent formation of large IgA1-IgGimmune complexes that cannot reach ASGP-R in the space ofDisse in the liver but are able to cross endothelial fenestrae inthe glomerulus and deposit in the mesangium (Fig. 2).15 Depos-ited immune complexes activate the alternative complementpathway (with deposition of C3) and recruit inflammatory cells

Table 1 New EULAR/PRINTO/PRES endorsed classication of childhoodvasculitis (with permission from reference 4)

I Predominantly large vessel vasculitisTakayasu arteritis

II Predominantly medium sized vessel vasculitisChildhood polyarteritis nodosa

Cutaneous polyarteritis

Kawasaki disease

III Predominantly small vessel vasculitis(A) GRANULOMATOUS

Wegeners granulomatosis

Churg-Strauss syndrome

(B) NON-GRANULOMATOUS

Microscopic polyangiitis

HenochSchnlein purpura

Isolated cutaneous leucocytoclastic vaculitis

Hypocomplementic urticarial vasculitis

IV Other vasculitidesBehet disease

Vasculitis secondary to infection (including hepatitis B associated

polyrateritis nodosa), malignancies, and drugs, including

hypersensitivity vasculitis

Vasculitis associated with connective tissue diseases

Isolated vasculitis of the central nervous system

Cogan syndrome

Unclassied

Fig. 1 Glycosylation of IgA1 molecule. (a) The hinge region of the IgA1molecule is O-glycosylated by the attachment of N-acetylgalactosamine

(GalNAc) to serine residues. (b) The glycan chains may be elongated with

further addition of galactose (Gal) to GalNAc, and a variable degree of

sialylation with N-acetylneuraminic acid (NeuNAc). (with permission from

reference 14).

P TrnkaHSP in children

Journal of Paediatrics and Child Health 49 (2013) 9951003 2013 The Author

Journal of Paediatrics and Child Health 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians)

996

causing glomerulonephritis.12,15 Deposition of IgA1-containingimmune complexes in other sites (skin, gut, joints) leads toorgan-specific clinical manifestations of HSP.

Clinical Manifestations

HSP is a systemic vasculitis with multiorgan involvement. Theclassic tetrad of signs and symptoms includes: 1/ palpablepurpura, 2/ arthritis or arthralgia, 3/ abdominal pain, and 4/renal disease.

Purpura

Skin involvement is present in all children with HSP.8 Petechiaeand palpable purpura are the most common, but erythematous,macular, urticarial or even bullous rashes have also beenobserved. Purpura is characteristically distributed symmetricallyover the extensor surfaces of the lower limbs, buttocks andforearms (Fig. 3) with involvement of trunk and face describedoccasionally in younger children. Recurrence of purpura, whichmight be associated with more severe renal involvement, isobserved in 25% of children with HSP.

Arthritis/arthralgia

Arthritis/arthralgia is present in three quarters of children withHSP.16 Joint involvement is usually oligoarticular with largejoints of the lower extremities (knee, ankle, hip) most com-monly affected. There is usually prominent periarticular swell-ing, tenderness and pain; erythema and joint effusion are rare.Arthritis is non-deforming and heals without chronic damagewithin a few weeks.

Abdominal pain

Approximately two thirds of children with HSP developabdominal pain,17 usually diffuse, increasing after meals, andsometimes associated with nausea and vomiting. These symp-toms are caused by submucosal haemorrhage and oedema ofthe bowel wall, predominantly affecting the proximal smallbowel. The most severe gastrointestinal complication is intus-susception, affecting 34% patients with HSP. In 60% of thesecases, it is limited to small bowel. Clinical presentation of intus-susception is characterised by severe abdominal pain, oftencolicky in nature and vomiting. Other significant, though lesscommon gastrointestinal complications are gangrene of thebowel, bowel perforation and massive haemorrhage.

Renal disease

Renal involvement is reported in 2055% of children withHSP.18,19 The most common finding is isolated microscopic hae-maturia, usually developing within 4 weeks of the onset of thedisease. Proteinuria of variable degree might be present, andif severe can present as nephrotic syndrome. Hypertensionmight develop at the onset or during recovery. Renal functionis usually normal but the occasional patient might presentwith a progressive glomerulonephritis with significant renalimpairment.

Other less common clinical manifestations of HSP includecerebral vasculitis, scrotal or testicular haemorrhage, and inter-stitial pulmonary haemorrhage.2022 Distal ureteric vasculitisresulting in ureteric stenosis, presenting as renal colic has alsobeen described.23 Potential complications of HSP are summa-rised in Table 2.

Diagnosis

Diagnosis of HSP is based on the presence of purpura (palpable)or petechiae (without thrombocytopaenia) with lower limb pre-dominance (mandatory criterion) plus at least one of the flowingfour features: (1) abdominal pain; (2) arthritis or arthralgia; (3)leukocytoclastic vasculitis or proliferativeglomerulonephritiswith predominant deposition of IgA on histology; (4) renal

Fig. 2 Pathogenesis of IgA glomerulonephritis. In patients with IgA neph-ropathy (IgAN), galactose-decient IgA1 is recognized by anti-glycan IgG

antibodies. The formed immune complexes cannot enter the space of

Disse due to their size and interact with the asialoglycoprotein receptor

(ASGP-R) on hepatocytes, but are able to pass through the larger fenestrae

in the glomerular capillaries overlying the mesangium. These deposited

complexes induce glomerular injury by activation of the alternative com-

plement pathway and recruiting inammatory cells (with permission from

reference 15).

Fig. 3 Purpuric skin changes in a patient with HSP.

HSP in childrenP Trnka


997

involvement (haematuria, red blood cell casts or proteinuria).24

Laboratory tests are complementary in assessing renal involve-ment (urinalysis, urine microscopy, serum creatinine), andimaging studies are helpful in the evaluation of abdominalinvolvement and its potential complications (intussusception). Inchildren with incomplete or unusual presentation, biopsy of theaffected organ (skin, kidney) confirms the diagnosis.

Urinalysis

Every child with HSP should have urinalysis performed at diag-nosis and during follow-up. Dipstick assessment of urine forblood and protein is a good screening test for nephritis. Urinemicroscopy may reveal dysmorphic red cells and red-cell casts.Positive dipstick reading for protein requires quantification ofprotein excretion either by measuring protein/creatinine ratioon a first morning urine sample or protein excretion on a timedurine sample (24-hour collection).

Blood tests

There are no blood tests specific for HSP and measurement ofserum levels of total IgA is not helpful in confirming the diag-nosis or providing prognostic information. Galactose-deficientIgA1 serum levels seem to distinguish patients with HSP nephri-tis from patients without nephritis, and might become an impor-tant commercially available biomarker in the future.14,25

Imaging

Not all patients with HSP require diagnostic imaging, which isgenerally reserved for children with abdominal pain in whomintussusception is suspected. Abdominal ultrasound is the tech-nique of choice with the accuracy in diagnosing intussusception

approaching 100% in experienced hands.26 Concentric rings oftissue representing components of bowel and mesenteric fatcreate a classic target sign (Fig. 4). The classic meniscus sign ofintussusception on contrast enema, where the apex of the intus-susception projects into the contrast material, is not present incases of intussusception limited to small bowel.

Histology

Biopsy of the affected skin reveals leukocytoclastic vasculitiswith deposition of IgA-containing immune complexes, pre-dominantly in small vessels in the papillary dermis (primarilyvenules). Neutrophils undergo destruction (leukocytoclasis)with destructive fragmentation of the nuclei of dying cells(karyorrhexis) during apoptosis or necrosis (Fig. 5). Deposits ofIgA and C3 in the dermal capillaries of purpuric lesions anduninvolved skin by immune-fluorescent staining are consideredvalid diagnostic criterion, with 100% specificity in combinationwith leukocytoclastic vasculitis.8

Kidney biopsy is usually performed in patients with uncer-tain diagnosis and in those with more severe kidney involve-ment (rapidly progressive nephritis, nephrotic syndrome). Ingeneral, there is a correlation between the severity of renalmanifestations and findings on kidney biopsy. Light microscopyfindings can range from mild mesangial proliferation to severecrescentic glomerulonephritis. Diffuse mesangial IgA depositsseen on immunofluorescence are the hallmark of HSP nephritis(Fig. 6) and co-deposition of C3 complement (75%) might alsobe present. The absence of the classical complement pathwaycomponents (C1q and C4) distinguishes HSP nephritis fromother forms of immune-mediated glomerulonephritis, such aslupus nephritis. Electron microscopy shows electron dense

Table 2 Possible complications of HenochSchnlein purpura

RenalGlomerulonephritis

Nephrotic syndrome

Renal failure

Ureteric obstruction

GastrointestinalIntussusception

Gangrene of the bowel

Bowel perforation

Gastrointestinal haemorrhage

Central nervous systemCerebral haemorrhage

Seizures

Paresis

Peripheral neuropathy

OtherPulmonary haemorrhage

Testicular haemorrhage

Scrotal haemorrhage

Myositis

Myocarditis

Fig. 4 Target sign on transverse ultrasound of an intussusception. Theconcentric mass represents the tissue layers in the bowel wall of the

intussusceptum and the intussuscipiens. The curved, echogenic (bright)

area is due to the trapped mesenteric fat (with permission from

reference 26).




998

deposits in the mesangial areas. The current classification ofHSP nephritis is based on the extent of proliferation and thepresence of crescents on light microscopy,27 but other histologi-cal findings, such as mesangial/subendothelial deposits, theextent of tubulointerstitial damage or glomerular sclerosismight be better predictors of the outcome.28,29

Management of HSP

Management of HSP includes supportive care, symptomatictherapy and, in some cases, immunosuppressive treatment.

The basic principles of supportive care consist of maintenanceof good hydration, symptomatic pain relief and monitoringfor the development of complications. If adequate hydrationcannot be maintained orally, intravenous fluids should be con-sidered. Parenteral nutrition is usually unnecessary, except incases with prolonged severe abdominal involvement precludingenteral feeding. Patients with severe abdominal pain needprompt evaluation and investigations to exclude intussuscep-tion. In cases with sudden change of mental status, intracranialhaemorrhage should be excluded with appropriate imaging.Arthritis/arthralgia usually responds well to non-steroidal anti-inflammatory drugs (NSAIDs), but occasionally requires opioidsfor adequate symptomatic relief.30 Treatment is usually welltolerated and is not associated with an increased risk of gastro-intestinal bleeding. Patients with compromised renal functiontaking NSAIDs need close monitoring of their fluid status, bloodpressure and renal function.

The use of glucocorticosteroids (GCS) in HSP has been sourceof controversy for many years. While the suggested benefits ofearly GCS treatment have included shortened duration ofabdominal pain, decreased risk of intussusception and decreasedrisk of surgical intervention,3133 the quality of evidence is gen-erally poor, having come from mostly from small studies or casereports. In clinical practice, short courses of GCS are being usedin patients with severe abdominal pain, usually with rapidsymptomatic improvement.30 This treatment cannot be recom-mended in all patients with HSP since the majority will improvespontaneously. While some reports have suggested that earlytreatment with GCS might prevent development of nephritisand chronic kidney disease,32 a recent Cochrane review con-cluded that there is no evidence from randomised controlledtrials that the use of GCS prevents kidney disease in childrenwith HSP.34

Immunosuppressive treatment of HSP nephritis is used inpatients with severe kidney involvement (nephrotic range pro-teinuria and/or progressive renal impairment). In these cases,renal biopsy should be considered before treatment. Mild renalinvolvement (microscopic haematuria or mild proteinuria) doesnot require biopsy or immunosuppressive treatment, but thesechildren need close follow-up.

In patients with rapidly progressive glomerulonephritis ornephrotic syndrome (usually accompanied by crescents onkidney biopsy), pulse intravenous methylprednisolone followedby 3 to 6-month course of oral steroids is most commonlyused.35 A current KDIGO guideline suggests adding cyclophos-phamide to steroid treatment for crescentic glomerulonephri-tis36 even though the quality of evidence is low with a lack ofdemonstrated improvement in renal outcome.37,38 Plasmapher-esis has also been used in children with rapidly progressiveglomerulonephritis, but it is difficult to assess its efficacy due toselection bias (used in the most severe cases) and concurrentadministration of other immunosuppressive treatments.39

Recent studies in children with HSP nephritis and nephroticsyndrome suggest a potential benefit of cyclosporine A (CsA) inachieving remission of proteinuria and histological improve-ment of nephritis on follow-up kidney biopsies.40,41 Other treat-ments used with some success in small studies includeintravenous immunoglobulin, combined therapy of immuno-suppression and anti-clotting therapy (warfarin, dipyridamol

Fig. 5 Leukocytoclastic vasculitis of the skin in a child with HenochSchnlein purpura. Supercial dermal vessels showing inammatory inl-

trate consisting predominantly of neutrophils and eosinophils (arrows)

[haematoxyillin/eosin; magnication 200]. (Courtesy of Dr Leo Francis,Pathology Queensland, Royal Brisbane and Womens Hospital, Brisbane).

Fig. 6 Deposition of IgA immunoglobulin in HenochSchnlein purpuranephritis. Immunohistological staining demonstrates granular deposition

of IgA immunoglobulin in the mesangium of the affected glomerulus [mag-

nication 200]. (Courtesy of Dr Leo Francis, Pathology Queensland, RoyalBrisbane and Womens Hospital, Brisbane).



999

and acetylsalicylic acid), tonsillectomy, and B-cell depletionwith rituximab and mycophenolate mofetil.4246 The efficacy ofthese treatments is yet to be tested in prospective clinical trials.

Use of angiotensin-converting enzyme inhibitors (ACEIs) orangiotensin receptor blockers (ARBs) has become an acceptedtreatment of HSP nephritis with persistent proteinuria, withbeneficial effects not only on reduction of proteinuria but alsoon inhibition of renal fibrosis. Although there are no availablestudies on the efficacy of ACEIs or ARBs in HSP nephritis,long-term data showing their beneficial effect on renal survivaland improvement of proteinuria in patients with IgA nephropa-thy, a disease with the same pathophysiology, are encouraging.47

Prognosis of HSP

In the majority of children, the outcome of HSP is excellent withspontaneous resolution of symptoms and signs. HSP recurs inapproximately one third of patients, typically within 4 monthsof the initial presentation. Recurrent purpura can be occasion-ally associated with joint complaints and episodes of gross hae-maturia although each subsequent episode is generally milderand shorter. The long-term morbidity of HSP is related to thedegree of HSP nephritis.

In unselected cohorts of children, HSP nephritis is a milddisease, characterised by microscopic haematuria and minimalproteinuria, with

d. Contrast enema is an imaging test of choice for diagnosisof intussusception in children with HSP

e. Kidney biopsy is usually performed in children with HSPwho have haematuria or proteinuria on presentation

A2. Correct answer is a.Diagnosis of HSP is clinical and is based on presence of purpura orpetechiae plus one of the following: abdominal pain, arthritis orarthralgia, histological presence of leukocytoclastic vasculitis orproliferative glomerulonephritis, or renal involvement (haema-turia, red blood cell casts or proteinuria). There are no testsspecific for HSP. Serum level of total IgA is not clinically usefultest since it is elevated in 50%of patientswithHSP. Serum levelsof galactose-deficient IgA1 can distinguish patientswithHSP from

healthy controls, but this test is not widely available for clinicalpurposes. Contrast enema would miss intussusception limited tothe small bowel; abdominal ultrasound is the imaging test ofchoice. Kidney biopsy is usually done in patients with uncertaindiagnosis and in those with more severe kidney involvement(rapidly progressive nephritis, nephrotic syndrome).Q3. Which one of the following is the correct answer with

regard to management of HenochSchnlein purpura:a. All children with HSP should be admitted to hospital for

close monitoring and intravenous hydrationb. Treatment with non-steroidal anti-inflammatory drugs is

contraindicated in children with HSP because of thepotential adverse effects on the kidneys

Fig. 7 Suggested clinical pathway for detection and referral of patients with HSP nephritis. This pathway has been adapted from local guidelines developedby Dr D Hothi and Bristol Paediatric Nephrologists, and reprinted with permission from reference 50. Abbreviations: EMU early morning urinalysis; UP:PC

urine protein/creatinine ratio.



1001

c. Early treatment with glucocorticosteroids will preventdevelopment of HSP nephritis and chronic kidneydisease

d. Children with HSP who have persistent microscopichaematuria require kidney biopsy and immunosuppres-sive treatment

e. Treatment with angiotensin-converting enzyme inhibi-tors or angiotensin receptor blockers is an acceptedtreatment of HSP nephritis in children with persistentproteinuria

A3. Correct answer is e.Majority of children with HSP can be managed out of hospitalwith close monitoring in an outpatient setting. NSAIDs areuseful treatment for arthralgia/arthritis in children with HSP,but potential side effects on the kidney must be kept in mindand close monitoring of kidney function is important. There isno evidence from randomised controlled trials that early use ofglucocorticoids prevents kidney disease in children with HSP.Persistent microscopic haematuria is a common finding in chil-dren with mild HSP nephritis; most of these children continue tohave normal kidney function and will do well. In children withHSP nephritis and persistent proteinuria (especially those whoare also hypertensive), treatment with angiotensin-convertingenzyme inhibitors or angiotensin receptor blockers seems toslow down the progression of kidney disease. At what level ofproteinuria one should start this treatment is, however, unclear.

References

1 Rook A. William Heberdens cases of anaphylactoid purpura. Arch.Dis. Child. 1958; 33: 271.

2 Schnlein JL. Allgemeine und Specielle Pathologie und Therapie, Vol.2, 3rd edn. Wurzburg: Herisau, 1837; 48.

3 Henoch EH. ber eine eigenthmliche Form von Purpura. Berl. Klin.Wochenschr. 1874; 11: 6413.

4 Ozen S, Ruperto N, Dillon MJ et al. EULAR/PReS endorsed consensuscriteria for the classication of childhood vasculitides. Ann. Rheum.Dis. 2006; 65: 93641.

5 Dolezalov P, Telekesov P, Nemcov D et al. Incidence of vasculitis inchildren in the Czech Republic: 2-year prospective epidemiologysurvey. J. Rheumatol. 2004; 31: 22959.

6 Penny K, Fleming M, Kazmierczak D et al. An epidemiological study ofHenoch-Schnlein purpura. Pediatr. Nurs. 2010; 22: 305.

7 Saulsbury ST. Henoch-Schnlein purpura in children: report of 100children and review of the literature. Medicine 1999; 78: 395409.

8 Gonzlez LM, Janniger CK, Schwartz RA. Pediatric Henoch-Schnleinpurpura. Int. J. Dermatol. 2009; 48: 115765.

9 Weiss PF, Klink AJ, Luan X, Feudtner C. Temporal association ofStreptococcus, Staphylococcus, and parainuanza pediatrichospitalizations and hospitalized cases of Henoch-Schnlein purpura.J. Rheumatol. 2010; 37: 258794.

10 Watanabe T. Henoch-Schnlein purpura following inuenzavaccinations during the pandemic of inuenza A (H1N1). Pediatr.Nephrol. 2011; 25: 7958.

11 Kiryluk K, Moldoveanu Z, Sanders JT et al. Aberrant glycosylation ofIgA1 is inherited in both pediatric IgA nephropathy andHenoch-Schnlein purpura nephritis. Kidney Int. 2011; 80: 7987.

12 Sanders JT, Wyatt RJ. IgA nephropathy and Henoch Schnlein purpuranephritis. Curr. Opin. Pediatr. 2008; 20: 16370.

13 Kerr MA. The structure and function of human IgA. Biochem. J. 1990;271: 28596.

14 Allen AC, Willis FR, Beattie TJ et al. Abnormal IgA glycosylation inHenoch-Schnlein purpura restricted to patients with clinicalnephritis. Nephrol. Dial. Transplant. 1998; 13: 9304.

15 Novak J, Julian BA, Tomana M et al. IgA glycosylation and IgA immunecomplexes in the pathogenesis of IgA nephropathy. Semin. Nephrol.2008; 28: 7887.

16 Trapani S, Micheli A, Grisolia F et al. Henoch Schonlein purpura inchildhood: epidemiological and clinical analysis of 150 cases over a5-year period and review of literature. Semin. Arthritis Rheum. 2005;35: 14353.

17 Choong CK, Beasley SW. Intra-abdominal manifestations ofHenoch-Schnlein purpura. J. Paediatr. Child Health 1998; 34: 4059.

18 Narchi H. Risk of long term renal impairment and duration of followup recommended for Henoch-Schonlein purpura with normal orminimal urinary ndings: a systematic review. Arch. Dis. Child. 2005;90: 91620.

19 Jauhola O, Ronkainen J, Koskimies O et al. Renal manifestations ofHenoch-Schnlein purpura in a 6-month prospective study of 223children. Arch. Dis. Child. 2010; 95: 87782.

20 Belman AL, Leicher CR, Mosh SL et al. Neurologic manifestations ofSchoenlein-Henoch purpura: report of three cases and review of theliterature. Pediatrics 1985; 75: 68792.

21 Ha TS, Lee JS. Scrotal involvement in childhood Henoch-Schnleinpurpura. Acta Paediatr. 2007; 96: 5525.

22 Vats KR, Vats A, Kim Y et al. Henoch-Schnlein purpura andpulmonary hemorrhage: a report and literature review. Pediatr.Nephrol. 1999; 13: 5304.

23 Robson WL, Leung AK, Mathers MS. Renal colic due toHenoch-Schnlein purpura. J. S. C. Med. Assoc. 1994; 90: 5925.

24 Ozen S, Pistorio A, Iusan SM et al. EULAR/PRINTO/PRES criteria forHenoch-Schnlein purpura, childhood polyarteritis nodosa, childhoodWegener granulomatosis and childhood Takayasu arteritis: Ankara2008. Part II.Final classicication criteria. Ann. Rheum. Dis. 2010; 69:798806.

25 Lau KK, Wyatt RJ, Moldoveanu Z et al. Serum levels ofgalactose-decient IgA in children with IgA nephropathy andHenoch-Schnlein purpura. Pediatr. Nephrol. 2007; 22: 206772.

26 Williams H. Imaging and intussusception. Arch. Dis. Child. Educ. Pract.Ed. 2008; 93: 306.

27 Haas M. IgA nephropathy and Henoch-Schnlein purpura nephritis. In:Jennette JC, Olson JL, Schwartz MM, Silva FG, eds. HeptinstallsPathology of the kidney, Vol. 1, 6th edn. Philadelphia: LippincottWilliams & Wilkins, 2007; 42386.

28 Edstrm Halling S, Sderberg MP, Berg UB. Predictors of outcome inHenoch-Schnlein nephritis. Pediatr. Nephrol. 2010; 25: 11018.

29 Davin JC. Henoch-Schonlein purpura nephritis: pathophysiology,treatment and future strategy. Clin. J. Am. Soc. Nephrol. 2011; 6:67989.

30 Szer IS. Gastrointestinal and renal involvement in vasculitis:management strategies in Henoch-Schnlein purpura. Cleve. Clin. J.Med. 1999; 66: 31217.

31 Ronkainen J, Koskimies O, Ala-Houhala M et al. Early prednisonetreatment in Henoch-Schnlein purpura: a randomized, double-blindplacebo-controlled trial. J. Pediatr. 2006; 149: 2417.

32 Weiss PF, Feinstein JA, Luan X et al. Effects of corticosteroid onHenoch-Schnlein purpura: a systematic review. Pediatrics 2007;120: 107987.

33 Weiss PF, Klink AJ, Localio R et al. Corticosteroids may improveclinical outcomes during hospitalization for Henoch-Schnleinpurpura. Pediatrics 2010; 126: 67481.

34 Chartapisak W, Opastirakul S, Hodson EM et al. Interventions forpreventing and treating kidney disease in Henoch-Schnleinpurpura (HSP). Cochrane Database Syst. Rev. 2009; (8):CD005128.




1002

35 Niaudet P, Habib R. Methylprednisolone pulse therapy in thetreatment of severe forms of Schnlein-Henoch purpura nephritis.Pediatr. Nephrol. 1998; 12: 23843.

36 Kidney Disease: Improving Global Outcomes (KDIGO)Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline forGlomerulonephritis. Kidney Int. 2012; 2: 139247. http://kdigo.org/home/glomerulonephritis-gm/ [accessed September 2013].

37 Tarshish P, Bernstein J, Edelmann CM Jr. Henoch-Schnlein purpuranephritis: course of disease and efcacy of cyclophosphamide.Pediatr. Nephrol. 2004; 19: 516.

38 Pillebout E, Alberti C, Guillevin L et al. Addition of cyclophosphamideto steroids provides no benet compared with steroids alone intreating adults patients with severe Henoch Schnlein Purpura.Kidney Int. 2010; 78: 495502.

39 Shenoy M, Ognjanovic MV, Coulthard MG. Treating severeHenoch-Schnlein and IgA nephritis with plasmapheresis alone.Pediatr. Nephrol. 2007; 22: 116771.

40 Park JM, Won SC, Shin JI et al. Cyclosporin A therapy forHenoch-Schnlein nephritis with nephrotic range proteinuria. Pediatr.Nephrol. 2011; 26: 41117.

41 Jauhola O, Ronkainen J, Autio-Harmainen H et al. Cyclosporine A vs.methylprednisolone for Henoch-Schnlein nephritis: a randomizedtrial. Pediatr. Nephrol. 2011; 26: 215966.

42 Heldrich FJ, Minkin S, Gatdula CL. Intravenous immunoglobulin inHenoch-Schnlein purpura: a case study. Md Med. J. 1993; 42:5779.

43 Iijima K, Ito-Kariya S, Nakamura H et al. Multiple combined therapy forsevere Henoch-Schnlein purpura nephritis in children. Pediatr.Nephrol. 1998; 12: 2448.

44 Kanai H, Sawanobori E, Kobayashi A et al. Early treatment withmethylprednisolone pulse therapy combined with tonsillectomy forheavy proteinuric henoch-schnlein purpura nephritis in children.Nephron Extra 2011; 1: 10111.

45 Donnithorne KJ, Atkinson TP, Hinze CH et al. Rituximab therapy forsevere refractory chronic Henoch-Schnlein purpura. J. Pediatr. 2009;155: 1369.

46 Du Y, Hou L, Zhao C et al. Treatment of children withHenoch-Schnlein purpura nephritis with mycophenolate mofetil.Pediatr. Nephrol. 2012; 27: 76571.

47 Coppo R, Peruzzi L, Amore A et al. IgACE: a placebo-controlled,randomized trial of angiotensin-converting enzyme inhibitors inchildren and young people with IgA nephropathy and moderateproteinuria. J. Am. Soc. Nephrol. 2007; 18: 18808.

48 Schrer K, Krmar R, Querfeld U et al. Clinical outcome ofSchnlein-Henoch purpura nephritis in children. Pediatr. Nephrol.1999; 13: 81623.

49 Butani L, Morgenstern BZ. Long-term outcome in children afterHenoch-Schnlein purpura nephritis. Clin. Pediatr. (Phila) 2007; 46:50511.

50 Tizard EJ, Hamilton-Ayres MJ. Henoch Schonlein purpura. Arch. Dis.Child. Educ. Pract. Ed. 2008; 93: 18.

51 Thervet E, Aouizerate J, Noel LH et al. Histologic recurrenceof Henoch-Schnlein Purpura nephropathy after renaltransplantation on routine allograft biopsy. Transplantation 2011;92: 90712.

52 Han SS, Sun HK, Lee JP et al. Outcome of renal allograft in patientswith Henoch-Schnlein nephritis: single-center experience andsystematic review. Transplantation 2010; 89: 7216.

8 Ways Aboriginal Perspective, by Ayla Cornall (12) from Operation Art 2012.



1003

Documents

Jurnal Purpura Haenox Scholen pada Anak