HENOCH-SCHÖNLEIN PURPURAHENOCH-SCHÖNLEIN PURPURA

Morning Report Morning Report

July 6, 2007July 6, 2007

Sima Patel, MDSima Patel, MD

DEFINITIONDEFINITION

Also called “anaphylactoid purpura”Also called “anaphylactoid purpura” HSP is a systemic vasculitic HSP is a systemic vasculitic

syndrome with:syndrome with:– Palpable purpuraPalpable purpura– ArthralgiasArthralgias– GI involvementGI involvement– GlomerulonephritisGlomerulonephritis

BACKGROUNDBACKGROUND

First described in 1801 by William First described in 1801 by William Heberden, a physician in London, who Heberden, a physician in London, who wrote about a case of a 5 year old wrote about a case of a 5 year old boy with hematuria, abdominal pain, boy with hematuria, abdominal pain, joint pains and a skin rash.joint pains and a skin rash.

In 1837, Johann Schönlein and later in In 1837, Johann Schönlein and later in 1874, Edouard Henoch described 1874, Edouard Henoch described multiple case reports of similar cases. multiple case reports of similar cases. They also showed an association of They also showed an association of an upper respiratory infection an upper respiratory infection preceding development of symptoms. preceding development of symptoms.

EPIDEMIOLOGYEPIDEMIOLOGY

90% of cases reported in children90% of cases reported in children– Peak in children aged 4-7Peak in children aged 4-7

Male:Female (1.5:1) Male:Female (1.5:1) 50% follow a URI50% follow a URI Renal disease is more severe in Renal disease is more severe in

adultsadults

PATHOGENESISPATHOGENESIS

Likely mechanism thought to be an Likely mechanism thought to be an immune-complex mediated disease immune-complex mediated disease with deposits in the glomerular with deposits in the glomerular capillaries, dermal capillaries and GI capillaries, dermal capillaries and GI tract.tract.

Mesangial deposits of IgA are the Mesangial deposits of IgA are the same as those seen in IgA same as those seen in IgA nephropathy nephropathy

PRECIPITATING ANTIGENSPRECIPITATING ANTIGENS

INFECTIONSINFECTIONS– URIURI– MeaslesMeasles– RubellaRubella– Parvovirus B19Parvovirus B19– MycoplasmaMycoplasma– Coxsackie Coxsackie

virusvirus– ToxocaraToxocara– AmebiasisAmebiasis– SalmonellaSalmonella

– C.difficileC.difficile– H.pyloriH.pylori– AdenovirusAdenovirus– LegionellaLegionella– TuberculosisTuberculosis– MumpsMumps– StreptococcusStreptococcus– Morganella Morganella

morganiimorganii

PRECIPITATING ANTIGENSPRECIPITATING ANTIGENS

DrugsDrugs– VancomycinVancomycin– StreptokinaseStreptokinase– RanitidineRanitidine– CefuroximeCefuroxime– DiclofenacDiclofenac– EnalaprilEnalapril– CaptoprilCaptopril

PRECIPITATING ANTIGENSPRECIPITATING ANTIGENS

Other:Other:– Food hypersensitivityFood hypersensitivity– Cold exposureCold exposure– Autosomal recessive Chronic Autosomal recessive Chronic

granulomatous diseasegranulomatous disease– Myelodysplastic syndromeMyelodysplastic syndrome– Small cell lung cancerSmall cell lung cancer– Breast cancerBreast cancer

PATHOLOGIC FEATURESPATHOLOGIC FEATURES

DERMATOLOGIC FINDINGS: DERMATOLOGIC FINDINGS: Leukocytoclastic vasculitis with IgA Leukocytoclastic vasculitis with IgA depositiondeposition

Direct Immunofluorescence of skin biopsy. Granular IgA and C3 staining of cutaneous vasculature.

http://www.medscape.com/viewarticle/459714

H & E stain of skin biopsy showing leukocytoclastic vasculitis with infiltration of neutrophils.

http://www.medscape.com/viewarticle/459714

Skin biopsy: Leukocytoclastic vasculitis with mononuclear and polymorphonuclear cell infiltrates in the perivascular space

www.kjronline.org/abstract/view_articletext.asp?year=2004&page=178www.kjronline.org/abstract/view_articletext.asp?year=2004&page=178

PATHOLOGIC FEATURESPATHOLOGIC FEATURES

RENAL FINDINGS: Granular deposits of RENAL FINDINGS: Granular deposits of IgA, mesangioproliferative IgA, mesangioproliferative glomerulonephritis and crescent glomerulonephritis and crescent formation formation

Renal biopsy: sclerosis and fibrous crescents in the glomerulus.

http://www.ndt-educational.org/nagycase.asp

http://www.ndt-educational.org/nagycase.asp

Immunofluorescence: Glomerular deposits of IgAImmunofluorescence: Glomerular deposits of IgA

CLINICAL FEATURESCLINICAL FEATURES

Tetrad of symptomsTetrad of symptoms– Abdominal painAbdominal pain– Renal diseaseRenal disease– Palpable purpuraPalpable purpura– Arthritis/arthralgias – more common in Arthritis/arthralgias – more common in

adults and most common in knees and adults and most common in knees and ankles. Generally self-limitingankles. Generally self-limiting

CLINICAL FEATURESCLINICAL FEATURES

PALPABLE PURPURA: most commonly PALPABLE PURPURA: most commonly seen on lower extremities and seen on lower extremities and buttocks, however can also been buttocks, however can also been seen on the trunk and arms. seen on the trunk and arms. – Lesions begin as erythematous macules Lesions begin as erythematous macules

and progress to purpuric, non-blanching, and progress to purpuric, non-blanching, nonpruritic lesions that may become nonpruritic lesions that may become confluentconfluent

CLINICAL FINDINGSCLINICAL FINDINGS

GI INVOLVEMENT: more common in GI INVOLVEMENT: more common in children. Symptoms include children. Symptoms include abdominal pain, nausea, vomiting, abdominal pain, nausea, vomiting, diarrhea, constipation or bowel diarrhea, constipation or bowel intussusception. May present with GI intussusception. May present with GI bleeding. bleeding.

CLINICAL FEATURESCLINICAL FEATURES

RENAL INVOLVEMENT: RENAL INVOLVEMENT: – in up to 50% of patientsin up to 50% of patients– Usually more rapidly progressive in Usually more rapidly progressive in

adults. Rare in childrenadults. Rare in children– May present with hematuriaMay present with hematuria– Can have mild glomerulonephritis Can have mild glomerulonephritis

leading to microscopic hematuria and leading to microscopic hematuria and can lead to a rapidly progressive can lead to a rapidly progressive glomerulonephritis with RBC castsglomerulonephritis with RBC casts

– Usually resolve spontaneously. Usually resolve spontaneously.

DIAGNOSTIC EVALUATIONDIAGNOSTIC EVALUATION

May have mild leukocytosisMay have mild leukocytosis Normal platelet countNormal platelet count Normal serum complement levelsNormal serum complement levels Elevated IgA in 50%Elevated IgA in 50%

DIAGNOSISDIAGNOSIS

Generally a clinical diagnosisGenerally a clinical diagnosis Skin Biopsy: can be helpful and used Skin Biopsy: can be helpful and used

to confirm IgA and C3 deposits and to confirm IgA and C3 deposits and leukocytoclastic vasculitis. leukocytoclastic vasculitis.

Renal Biopsy: not usually needed for Renal Biopsy: not usually needed for diagnosis. Will show mesangial IgA diagnosis. Will show mesangial IgA deposits and segmental deposits and segmental glomerulonephritisglomerulonephritis

MANAGEMENTMANAGEMENT

Usually self-limiting (1-6 weeks)Usually self-limiting (1-6 weeks) Steroids: Steroids:

– may decrease tissue edema, may aid in may decrease tissue edema, may aid in arthralgias and some abdominal painarthralgias and some abdominal pain

– Has not been shown to be beneficial in Has not been shown to be beneficial in kidney disease or dermal manifestationskidney disease or dermal manifestations

– Does not lessen chance of recurrenceDoes not lessen chance of recurrence– Does not shorten duration of diseaseDoes not shorten duration of disease

MANAGEMENTMANAGEMENT

if rapidly progressive if rapidly progressive glomerulonephritisglomerulonephritis– Multidrug regimens with cytotoxic drugs Multidrug regimens with cytotoxic drugs

however not many reports with however not many reports with treatment in adults.treatment in adults.

– PlasmaphoresisPlasmaphoresis– IVIGIVIG

Symptomatic management of GI Symptomatic management of GI symptoms and surgical intervention symptoms and surgical intervention if warranted. if warranted.

PROGNOSISPROGNOSIS

Prognostic factors: Prognostic factors: – generally a milder course in children generally a milder course in children

with shorter duration and fewer with shorter duration and fewer recurrences recurrences

– Proteinuria >1gm/day with worse Proteinuria >1gm/day with worse prognosis if develop nephrotic syndromeprognosis if develop nephrotic syndrome

1-5% children progress to ESRD1-5% children progress to ESRD Recurrence in up to 40% of patientsRecurrence in up to 40% of patients

REFERENCESREFERENCES Kasper, Dennis, and Eugene Braunwald, 16th Kasper, Dennis, and Eugene Braunwald, 16th

edition, eds. Harrison’s Principles of Internal edition, eds. Harrison’s Principles of Internal Medicine. New York: McGraw-Hill, 2005.Medicine. New York: McGraw-Hill, 2005.

Tierney Jr, Lawrence, and Stephen McPhee, 45th Tierney Jr, Lawrence, and Stephen McPhee, 45th edition, eds. Current Medical Diagnosis and edition, eds. Current Medical Diagnosis and Treatment. New York: McGraw-Hill, 2006.Treatment. New York: McGraw-Hill, 2006.

Uptodate: Clinical manifestations and diagnosis Uptodate: Clinical manifestations and diagnosis of Henoch-Schonlein Purpuraof Henoch-Schonlein Purpura

Anup Rai, et al., Henoch-Schonlein Purpura Anup Rai, et al., Henoch-Schonlein Purpura Nephritis. American Society of Nephrology. Nephritis. American Society of Nephrology. Volume 10, pages 2637-2644, 1999Volume 10, pages 2637-2644, 1999

Espositio et al., Henoch-Schonlein Purpura in Espositio et al., Henoch-Schonlein Purpura in Chronic Hemodialys patients. Journal of Chronic Hemodialys patients. Journal of Nephrology. Volume 12: 197-200, 1999Nephrology. Volume 12: 197-200, 1999