Henoch Schonlein Purpura (2)

Henoch-Schonlein Henoch-Schonlein PurpuraPurpura

Jeremy Gitomer MD

Division of Pediatric Nephrology

Jeremy Gitomer MD

Division of Pediatric Nephrology

IntroductionIntroduction

• Heberden in 1801 described a 5 yo with edema, Heberden in 1801 described a 5 yo with edema, abdominal pain, bloody stools, hematuria and abdominal pain, bloody stools, hematuria and “bloody points” all over his body.“bloody points” all over his body.

• Schonlein in 1837 named the association of joint Schonlein in 1837 named the association of joint pain and purpura as “purpura rheumatica”pain and purpura as “purpura rheumatica”

• Henoch in 1874 described patients with purpura, Henoch in 1874 described patients with purpura, severe abdominal colic, melena and large joint severe abdominal colic, melena and large joint arthritisarthritis

IntroductionIntroduction

• HSP is the most common vasculitic HSP is the most common vasculitic disease of childhooddisease of childhood

• HSP is considered to be a form of HSP is considered to be a form of IgA Nephropathy with extrarenal IgA Nephropathy with extrarenal manifestations.manifestations.

EpidemiologyEpidemiology

• Incidence is 13.5-18/100000Incidence is 13.5-18/100000

• Male to female 1.5:1Male to female 1.5:1

• Can occur from 6 months- adulthoodCan occur from 6 months- adulthood

– 50% of cases are under 5 years of age50% of cases are under 5 years of age

• Wide geographical distributionWide geographical distribution

• More common in winter and springMore common in winter and spring

• Genetics play a small role Genetics play a small role

IgA Immune SystemIgA Immune System

• The most abundant immunoglobulin The most abundant immunoglobulin in the bodyin the body

• IgA is compartmentalizedIgA is compartmentalized– SecretorySecretory

– CirculatingCirculating

Immunoglobulin AImmunoglobulin A

Secretory Component is derived from epithelial surface IgA receptors J Chain produced in the plasma cell

PathogenesisPathogenesis

• Abnormalities in IgAAbnormalities in IgA::

– ProductionProduction

– ClearanceClearance

– GlycosylationGlycosylation

IgA GlycosylationIgA Glycosylation

Characteristics of Characteristics of Mesangial IgAMesangial IgA

• Predominantly IgAPredominantly IgA11

• Predominantly polymericPredominantly polymeric

• Contains J chainContains J chain

• Does not contain SC proteinDoes not contain SC protein

Origin of Deposited IgAOrigin of Deposited IgA

• Enhanced tonsillar production of pIgAEnhanced tonsillar production of pIgA11 has been has been reportedreported

• Assessment for pIgAAssessment for pIgA11 production by production by in situin situ hybridization for J chain mRNA in IgA plasma hybridization for J chain mRNA in IgA plasma cells shows downregulation in the mucosa and cells shows downregulation in the mucosa and upregulation in the bone marrowupregulation in the bone marrow

• If the marrow is the source of pIgAIf the marrow is the source of pIgA11 then the link then the link between mucosal infection and hematuria between mucosal infection and hematuria remains unexplainedremains unexplained

Clinical PresentationClinical Presentation

• Effects predominantly young children, but Effects predominantly young children, but adults are also affectedadults are also affected

• Peak incidence is 4-5 years of agePeak incidence is 4-5 years of age

• There is a slight male predominanceThere is a slight male predominance

• The condition is more prevalent in the winter The condition is more prevalent in the winter and early springand early spring

• The onset of illness is usually sudden and is The onset of illness is usually sudden and is preceded by a URI in at least 1/3 of casespreceded by a URI in at least 1/3 of cases

Clinical PresentationClinical Presentation

• Classic Triad of symptoms is the most Classic Triad of symptoms is the most common presentationcommon presentation– PurpuraPurpura

– Colicky abdominal painColicky abdominal pain

– arthritisarthritis

• 50% of children may present with 50% of children may present with symptoms other than purpurasymptoms other than purpura

Clinical Manifestations of Clinical Manifestations of HSPHSP

% at Onset % During Course

Purpura 50 100Arthritis 25 60-85Edema 10-20 20-50Gastrointestinal 30 85Renal ? 40-60Genitourinary ? 2-35

Szer IS. J Rheumatology 1996:23;1661-1665

Influence of Age on Influence of Age on Clinical ManifestationsClinical Manifestations

Age < 2 yrs.% Involved

Age > 2 yrs.% Involved

Renal 23 43

Gastrointestinal 29 75

Arthritis 56 73

Scalp Edema 59 19

Other Edema 71 51

Allen et al. Am J Dis Child 1960;99:147-168

DermatologicDermatologic

• Begins as erythematous maculesBegins as erythematous macules

• Some of which develop raised urticarial papules Some of which develop raised urticarial papules which soon become purpuric or petechialwhich soon become purpuric or petechial

• The eruption is symmetric effecting the The eruption is symmetric effecting the extensor surfaces of the lower legs, forearms, extensor surfaces of the lower legs, forearms, buttocks and sparing the trunk.buttocks and sparing the trunk.

• Purpura occasionally affect earlobes, nose and Purpura occasionally affect earlobes, nose and external genitalia.external genitalia.

DermatologicDermatologic

• Younger children may only have urticariaYounger children may only have urticaria

• Also younger children may present with edema Also younger children may present with edema of the feet, dorsum of the hands, face and scalp.of the feet, dorsum of the hands, face and scalp.

• As primary lesions fade new crops can present As primary lesions fade new crops can present for up to three months from the onset of the for up to three months from the onset of the disease (and sometimes much longer)disease (and sometimes much longer)

• Erythema nodosum can occurErythema nodosum can occur

• Blistering lesions can occurBlistering lesions can occur

ArthralgiaArthralgia

• 60-84% of children exhibit transient 60-84% of children exhibit transient arthralgia and periarticular edema.arthralgia and periarticular edema.

– The knees, ankles, elbows and wrists are The knees, ankles, elbows and wrists are most commonly affectedmost commonly affected

– Erythema, tenderness or joint effusions may Erythema, tenderness or joint effusions may or may not be present in painful jointsor may not be present in painful joints

• Arthritis precedes the onset of skin Arthritis precedes the onset of skin findings in 25% of casesfindings in 25% of cases

Gastrointestinal Gastrointestinal ManifestationsManifestations

• Gastrointestinal manifestations occur in 50-Gastrointestinal manifestations occur in 50-70% of patients70% of patients

• The incidence is 90% in those patients with The incidence is 90% in those patients with renal involvementrenal involvement

• The most common symptom is abdominal The most common symptom is abdominal coliccolic

• Abdominal pain precedes rash in 14% of Abdominal pain precedes rash in 14% of casescases

GI ManifestationsGI Manifestations

• Melena occurs in 50% of patientsMelena occurs in 50% of patients

• Hematemesis occurs in up to 30% of Hematemesis occurs in up to 30% of patientspatients

• Massive GI bleeding occurs in 2%-Massive GI bleeding occurs in 2%-10% of patients10% of patients

Radiographic Findings in 22 Radiographic Findings in 22 Patients with HSP and Abdominal Patients with HSP and Abdominal ComplaintsComplaints

Findings/Location No. PtsSmall bowel fold thickening Duodenum and jejunum 6 Jejunum 5 Jejunum and ileum 3 Terminal ileum 3

Colonic Wall Edema Terminal ileum and cecum 1 Cecum and sigmoid 1

Intussusception Ileocolic 1 Ileoileal 1 Jejunojejunal 1

Glasier et al. AJR: 1981;136:1081-1085

GI ManifestationsGI Manifestations

Glasier et al. AJR: 1981;136:1081-1085

GI ManifestationsGI Manifestations

Glasier et al. AJR: 1981;136:1081-1085

GI ManifestationsGI Manifestations

Glasier et al. AJR: 1981;136:1081-1085

Intussusception and HSPIntussusception and HSP

• The incidence of intussusception in HSP is The incidence of intussusception in HSP is between 1-2% of all patients with HSP and between 1-2% of all patients with HSP and abdominal pain.abdominal pain.

• 50% of intussusceptions in HSP are ileoilial50% of intussusceptions in HSP are ileoilial

– In contrast, in children without HSP, ileocolic In contrast, in children without HSP, ileocolic intussusceptions are found in 90-95% of casesintussusceptions are found in 90-95% of cases

• High resolution ultrasound is the diagnostic study High resolution ultrasound is the diagnostic study of choice (ileoilial intussusception may not be of choice (ileoilial intussusception may not be detected by barium enema)detected by barium enema)

GI ManifestationsGI Manifestations

IntussusceptionReduced Intussusception

Obstructed proximal ileum

Glasier et al. AJR: 1981;136:1081-1085

Other GI ManifestationsOther GI Manifestations

• PancreatitisPancreatitis

• Biliary necrosisBiliary necrosis

• Biliary hydropsBiliary hydrops

• Hemorrhagic ascitesHemorrhagic ascites

• Bowel necrosisBowel necrosis

• DuodenitisDuodenitis

• Hemorrhagic duodenitisHemorrhagic duodenitis

GU ManifestationsGU Manifestations

• Acute scrotal swelling secondary to Acute scrotal swelling secondary to inflammation and hemorrhage of the inflammation and hemorrhage of the scrotal vessels occurs in 10-30% of scrotal vessels occurs in 10-30% of males with HSPmales with HSP

• Scrotal edema is commonScrotal edema is common

• Purpuric lesions on the scrotum are Purpuric lesions on the scrotum are commoncommon

GU ManifestationsGU Manifestations

Pulmonary ManifestationsPulmonary Manifestations

• Pulmonary hemorrhage is a rare but Pulmonary hemorrhage is a rare but often fatal complication of HSPoften fatal complication of HSP

• Acute interstitial lung disease, as Acute interstitial lung disease, as demonstrated by a decrease in TLCO demonstrated by a decrease in TLCO (56% of predicted), was noted in 28/29 (56% of predicted), was noted in 28/29 patients with HSP without pulmonary patients with HSP without pulmonary symptoms.symptoms.– Chaussain et al. J Ped 1992;121:12-16.Chaussain et al. J Ped 1992;121:12-16.

CNS ManifestationsCNS Manifestations

• CerebritisCerebritis

• ComaComa

• ParesisParesis

• Subacute Subacute encephalopathyencephalopathy

• Subdural Subdural hematomahematoma

• Cortical Cortical hemorrhagehemorrhage

• Cerebral Cerebral infarctioninfarction

• Peripheral Peripheral neuropathyneuropathy

Renal ManifestationsRenal Manifestations

• The incidence has been reported to be The incidence has been reported to be between 20-100%. between 20-100%.

• Two large studies in which routine urine Two large studies in which routine urine analysis was performed upon admission analysis was performed upon admission demonstrated an incidence of 41 and 61%demonstrated an incidence of 41 and 61%

• Patients with abdominal involvement are Patients with abdominal involvement are more likely to have renal involvementmore likely to have renal involvement– Relative Risk is 7.5Relative Risk is 7.5

Renal ManifestationsRenal Manifestations

• Microscopic hematuria and minimal Microscopic hematuria and minimal proteinuriaproteinuria

• Hematuria and heavy proteinuriaHematuria and heavy proteinuria

• Nephrotic syndromeNephrotic syndrome

• Nephritic syndromeNephritic syndrome

• Nephrotic-Nephritic syndromeNephrotic-Nephritic syndrome

Criteria for Diagnosis of Criteria for Diagnosis of HSPHSP• ACR established criteria in 1990ACR established criteria in 1990

• Children must have palpable purpura without Children must have palpable purpura without thrombocytopeniathrombocytopenia

• Adults must have 2 of the following:Adults must have 2 of the following:– Age <20 years at onsetAge <20 years at onset

– Palpable purpuraPalpable purpura

– Bowel anginaBowel angina

– Biopsy evidence of granulocytes in the walls of Biopsy evidence of granulocytes in the walls of arterioles or venulesarterioles or venules

Differential DiagnosisDifferential Diagnosis

• Systemic lupus erythematosusSystemic lupus erythematosus

• Polyarteritis nodosaPolyarteritis nodosa

• Wegener’s granulomatosisWegener’s granulomatosis

• Testicular torsionTesticular torsion

• Acute surgical abdomenAcute surgical abdomen

• Hypersensitivity vasculitisHypersensitivity vasculitis

• Sepsis with purpuraSepsis with purpura

Laboratory InvestigationLaboratory Investigation

• Urine analysisUrine analysis

• Urine for protein and creatinineUrine for protein and creatinine

• Occult blood should be checked in the stoolOccult blood should be checked in the stool

• Serum total protein and albuminSerum total protein and albumin

• Serum creatinineSerum creatinine

• ANCA in patients with appropriate historiesANCA in patients with appropriate histories

• IgA levels are uselessIgA levels are useless

Laboratory InvestigationsLaboratory Investigations

• Testicular ultrasound when associated with Testicular ultrasound when associated with testicular paintesticular pain

• Abdominal series and abdominal ultrasound Abdominal series and abdominal ultrasound when severe abdominal cramping presentwhen severe abdominal cramping present

• CXRCXR

• Pulmonary function tests if the patients have Pulmonary function tests if the patients have symptomssymptoms

• ACA IgA isotypeACA IgA isotype

Kidney BiopsyKidney Biopsy

• Generally not performed for routine Generally not performed for routine casescases

• Indications are:Indications are:

– Severe nephritic syndromeSevere nephritic syndrome

– Persistent heavy proteinuriaPersistent heavy proteinuria

– Atypical presentationsAtypical presentations

Morphologic Classification of Morphologic Classification of HSP Glomerulonephritis HSP Glomerulonephritis ISKDCISKDC• I. Minimal glomerular abnormalitiesI. Minimal glomerular abnormalities

• II. Pure mesangial proliferationII. Pure mesangial proliferation

• III. Crescents/Segmental lesions <50%III. Crescents/Segmental lesions <50%

• IV. Crescents/Segmental lesions 50-75%IV. Crescents/Segmental lesions 50-75%

• V. Crescents/Segmental lesions >75%V. Crescents/Segmental lesions >75%

• VI. PseudomesangiocapillaryVI. Pseudomesangiocapillary

• II-VI also categorized as (a)focal or (b) diffuse II-VI also categorized as (a)focal or (b) diffuse mesangial proliferationmesangial proliferation

HSP LightHSP Light

Epithelial CrescentEpithelial Crescent

Epithelial CrescentsEpithelial Crescents

ImmunofluorescenceImmunofluorescence

Electron MicroscopyElectron Microscopy

Extrarenal PathologyExtrarenal Pathology

• Skin biopsies of affected areas demonstrate a Skin biopsies of affected areas demonstrate a leukocytoclastic vasculitis with perivascular leukocytoclastic vasculitis with perivascular infiltration of polymorphs and mononuclear cells.infiltration of polymorphs and mononuclear cells.

• Necrosis of small blood vessels may also be seenNecrosis of small blood vessels may also be seen

• Immunostaining reveals IgA in most purpuric Immunostaining reveals IgA in most purpuric skin lesions and also in unaffected areas.skin lesions and also in unaffected areas.

• Similar findings are present in the gut and lungs Similar findings are present in the gut and lungs of affected individualsof affected individuals

Natural History for HSP Natural History for HSP without Nephritiswithout Nephritis

• Generally HSP is a self limited Generally HSP is a self limited illness.illness.

• No treatment is required for the No treatment is required for the purpurapurpura

• NSAIDs are used to treat arthralgiasNSAIDs are used to treat arthralgias– Steroids are not beneficialSteroids are not beneficial

Natural History of GI Natural History of GI ManifestationsManifestations

Resolution of Abdominal Pain in Pts with HSP

0

20

40

60

80

100

1 2 3 4 5

Days before resolution

Pe

rce

nt

No Steroids

Treated withSteroids

Rosenblum et al. Ped 1987;79:1018-1021

Treatment GI Treatment GI ManifestationsManifestations

Author n Findings CitationAllen et al. 70 37 pts treated with

steroids Half withresolution of abdominalpain in 72 hours

Am J Dis Child1960;99:147-168

Glasier et al 22 No improvement inabdominal symptomswith steroids (20/22resolved)

AJR1981;136:1081-1085

Rosemblumand Winter

43 After 3 days ¾ oftreated and untreatedpts had resolution ofabdominal pain

Periatr1987;79:1018-1021

Natural History of Natural History of Pulmonary ManifestationsPulmonary Manifestations• 29 patients with TLCO measurements29 patients with TLCO measurements

– 28/29 patients with HSP had decreased 28/29 patients with HSP had decreased TLCOTLCO

• 10 Children had resolution of HSP in 3 10 Children had resolution of HSP in 3 monthsmonths– TLCO returned to normal for all patientsTLCO returned to normal for all patients

Natural History of Natural History of Pulmonary ManifestationsPulmonary Manifestations

• 3 children had recurrent skin lesions and 3 children had recurrent skin lesions and urinary abnormalities the first 3 months but urinary abnormalities the first 3 months but had clinically recovered by 6 monthshad clinically recovered by 6 months– TLCO was 45.7% initially, 58% at three months and TLCO was 45.7% initially, 58% at three months and

97.5% of predicted at 6 months97.5% of predicted at 6 months

• 5 patients never clinically resolved during the 5 patients never clinically resolved during the study periodstudy period– 3 of the 5 significant TLCO decreases from 3 of the 5 significant TLCO decreases from

predicted at the time of study closurepredicted at the time of study closure

Treatment of Pulmonary Treatment of Pulmonary ManifestationsManifestations

• No studies have been performed to No studies have been performed to see if steroids or other treatments see if steroids or other treatments for HSP improvefor HSP improve

• Aggressive immunomodulating Aggressive immunomodulating therapy should be used in patients therapy should be used in patients with severe pulmonary hemorrhage with severe pulmonary hemorrhage since it is often life threatening since it is often life threatening

Treatment for Neurologic Treatment for Neurologic ManifestationsManifestations• 3 patients with severe cerebritis 3 patients with severe cerebritis

were treated with plasma exchange were treated with plasma exchange and had complete resolution of and had complete resolution of symptomssymptoms– Gianviti et al. Arch Dis Child Gianviti et al. Arch Dis Child

1996;75:186-1901996;75:186-190

Long Term Renal Long Term Renal Outcome of HSNOutcome of HSN

• HSP is the diagnosis for 5-15% of HSP is the diagnosis for 5-15% of patients diagnosed end stage renal patients diagnosed end stage renal diseasedisease

• Stewart followed 270 patients with HSP Stewart followed 270 patients with HSP for 13 yearsfor 13 years– 1% renal morbidity1% renal morbidity

– <1% mortality<1% mortality• Eur J Pediatr 1988;147:113-115Eur J Pediatr 1988;147:113-115

Clinicopathologic Clinicopathologic CorrelationCorrelation

Clinical Presentation BiopsyGrade

Risk of RenalFailure

Hematuria/ proteinuriaminimal or absent

1,2, rarely 3 <5%

Hematuria andpersistent heavyproteinuria

1-4 15%

Acute NephriticSyndrome

2-4 15%

Nephrotic Syndrome 2-4, rarely 1or 5

40%

Nephritic-NephroticSyndrome

2-5, mostly 5 >50%

Long Term Renal Long Term Renal Outcome for HSNephritisOutcome for HSNephritis

Authors No.Pts

YearsFU

Citation

Coppoet al

57 4.8 Nephrol DialTransplant 1997;12:2277-2283

Levy etal

100 >1 year Adv Nephrol1978;8;183-227

Niaudetet al

151 >1 year Adv Nephrol1993;23:121-141

Long Term Renal Long Term Renal Outcome of HSNephritis Outcome of HSNephritis

Study AnyProblem

Remission Minimal Persistent ESRD

Niaudet etal

102 (65) 55 (35) 61 (39) 27 (17) 14 (9)

Levy et al 55 (65) 29 (34) 15 (18) 11 (13) 19 (22)

Coppo etal

39 (69) 18 (31) 24 (42) 10 (17) 4 (7)

Actual Number of patients

(Percent of total)

Long Term Renal Long Term Renal Outcome of HSNephritisOutcome of HSNephritis

Oral Steroids to Prevent Oral Steroids to Prevent Nephritis in HSNephritisNephritis in HSNephritis

Author Pts Design Findings CitationBuchanec etal

33 Retro 23 pts treated with 2 mg/kg/day.Of the treated pts 1 developednephritis while 5 developednephritis in the untreated group

Int JNephrol1988;20:409-412

Mollica et al 168 Open,prosp

84 pts treated with 1 mg/kg/daysteroids for 2 weeks. No patientstreated with steroids developednephropathy. 12 control patientsdeveloped nephropathy

Eur JPediatr1992;151:140-144

Saulsbury 50 Retro 20 pts treated with a mean doseof 1.7 mg/kg/day for 5-10 days.Nephritis developed in 20% oftreated patients and 20% ofuntreated patients

PediatrNephrol1993;7:69-71

Pulse Steroids for HSNPulse Steroids for HSN

• Niaudet and Habib reported 38 patients Niaudet and Habib reported 38 patients with severe nephritis treated with pulse with severe nephritis treated with pulse solumedrol.solumedrol.– 1-16 years of followup was obtained1-16 years of followup was obtained

– 27 (71%) patients had completely recovered27 (71%) patients had completely recovered

– 3 (8%) had minor urinary abnormalities3 (8%) had minor urinary abnormalities

– 4 (11%) had persistent nephropathy4 (11%) had persistent nephropathy

– 4 (11%) developed ESRD4 (11%) developed ESRD

Pediatr Nephrol 1998;12:238-243

Combined Therapy for Combined Therapy for HSNHSN

• Oner described 12 patients with HSP and Oner described 12 patients with HSP and severe crescentic glomerulonephritis treated severe crescentic glomerulonephritis treated with methylprednisolone, oral with methylprednisolone, oral cyclophosphamide, dipyridamole and cyclophosphamide, dipyridamole and prednisolone. prednisolone. – 7 (58%) patients went into remission7 (58%) patients went into remission

– 8 (67%) patients had resolution of nephrosis8 (67%) patients had resolution of nephrosis

– 9 (75%) patients had resolution of hematuria9 (75%) patients had resolution of hematuria

– 1 (8%) patient developed ESRD1 (8%) patient developed ESRD

Pediatr Nephrol 1995;9:6-10.

Plasma Exchange for HSNPlasma Exchange for HSN

• Khono treated 9 patients with nephrotic Khono treated 9 patients with nephrotic syndrome and decreased GFR solely with syndrome and decreased GFR solely with plasmapheresis. plasmapheresis.

• AJKD 1999 Mar;33(3):427-33AJKD 1999 Mar;33(3):427-33

• Jardim treated 14 patients with severe renal Jardim treated 14 patients with severe renal disease with plasma exchange, dipyrimadole, disease with plasma exchange, dipyrimadole, steroids and imuran.steroids and imuran.– 9 patients responded to therapy with improvement in 9 patients responded to therapy with improvement in

renal functionrenal function• Pediatr Nephrol 1992;6:231-235Pediatr Nephrol 1992;6:231-235

Intravenous Gamma Intravenous Gamma Globulin for HSNGlobulin for HSN

• Rostoker et al treated 14 patients Rostoker et al treated 14 patients diagnosed with IgAN or HSP nephritis. diagnosed with IgAN or HSP nephritis. – All patients had normal GFRAll patients had normal GFR

– All patients had proteinuriaAll patients had proteinuria

• The average proteinuria decreased from The average proteinuria decreased from 766 mg/day to 171 mg/day during the 6 766 mg/day to 171 mg/day during the 6 months of the study.months of the study.– All but 1 patient responded to the IMIGAll but 1 patient responded to the IMIG

Nephron 1995;69:327-334

Treatment for Chronic Treatment for Chronic HSNHSN• SteroidsSteroids

• Fish oilFish oil

• Vitamin EVitamin E

• Gluten free dietGluten free diet

• TonsillectomyTonsillectomy

• IV/IM IGIV/IM IG

• Combination therapyCombination therapy

Recurrence in TransplantRecurrence in Transplant

• Meulders and coworkers reported the course Meulders and coworkers reported the course of renal transplantation in 78 patients with of renal transplantation in 78 patients with ESRD secondary to HSP in 1994ESRD secondary to HSP in 1994– Histologic recurrence occurred in 50% of patientsHistologic recurrence occurred in 50% of patients

– Clinical recurrence occurred in 20% of patientsClinical recurrence occurred in 20% of patients

– Graft failure (12%) and graft loss (9%) were Graft failure (12%) and graft loss (9%) were commoncommon

– Waiting for 6 months prior to transplant had no Waiting for 6 months prior to transplant had no effect on recurrenceeffect on recurrence

Transplantation 1994;58:1179-1186

ConclusionsConclusions

• HSP has a variable presentationHSP has a variable presentation

• Most patients will have complete recovery and Most patients will have complete recovery and their long term prognosis is goodtheir long term prognosis is good

• Patients with severe crescentic GN or cerebritis Patients with severe crescentic GN or cerebritis should receive aggressive immunomodulating should receive aggressive immunomodulating therapytherapy

• Patients need long term follow-up because of the Patients need long term follow-up because of the low, but significant, incidence of late renal low, but significant, incidence of late renal complications.complications.