 Summary  Epidemiology  Etiology and Pathogenesis  Clinical Manifestations  Diagnosis  Treatment

 Most common systemic vasculitis in children  90% of cases occur in the pediatric group  Etiology: Unknown  Pathogenesis: End organ IgA immune complex (IC) deposition  Complications: Renal

 Clinical Diagnosis:  Palpable purpura without thrombocytopenia  Abdominal pain  Renal disease  Arthritis  Treatment: Disease usually self limited and treatment is usually symptomatic

 Disease of early childhood ages 3-15  20 per 100,000 in UK children < 17 years-old  70 per 100,000 in UK children 4-6 years-old  No comparable data in adults, less common  Male : Female ratio : 1 Arthritis Rheum 1997 May;40(5):859-64

 Less common in African American children  More severe course in adults  More frequent and severe renal disease  requirement for more aggressive treatment  Seasonal variance occurs in the fall, winter and spring and is rare in summer

 Unknown etiology!  Precipitating antigen may be infectious  Many cases follow upper respiratory infection (URI)  Example: identical twins following adenovirus infection:  HSP in one, IgA nephropathy in other J Pediatr 1985 Jan;106(1):27-32.

 Immune-complex (IC) mediated disease associated with Immunoglobin A (IgA) deposition  Characteristic findings is leukocytoclastic vasculitis (LCV)of post capillary venules  Accompanied by IgA deposition within affected organs  IC of IgA1 is the ONLY subtype  Immune complexes activate complement (alternative)

 Hinge region O-linked glycans of IgA1 are deficient in galactose and/or sialic acid content  Renal mesangial cells bind galactose/sialic acid deficient hinge regions  Berger’s disease (IgA nephropathy) also involves IgA1 exclusively

 Classic Tetrad: May develop over days to weeks  Rash (100%)  Arthralgias (82%)  Abdominal pain (63%) ▪ GI bleeding (33%)  Renal disease (40%) Medicine (Baltimore) 1999 Nov;78(6):

 Presenting feature by %  Rash 74%  Arthralgias 15%  Abdominal pain 12%

ACR 1990  Palpable Purpura  Age at onset < 20 years  Acute abdominal pain  Biopsy:  Granulocytes in walls of small arterioles / venules  > or = 2 criteria  90% Sensitivity/Specificity EULAR / PRES 2005  Palpable purpura without coagulopathy or decreased platelets AND  Diffuse abdominal pain  Arthritis or arthralgia  Bopsy with IgA deposition

 Erythematous, macular or urticarial wheals  petechia/palpable purpura  NORMAL clotting studies and platelets  Appears in crops  Symmetric distribution  Gravity/pressure dependent areas such as lower extremities

 Localized subcutaneous edema in dependent and periorbital areas seen in children < 3 years old  Differential diagnosis of palpable purpura:  Mixed Cryoglobulinemia  Hypersensitivity vasculitis

 Occur in up to 84% of patients  Uncommon sole presenting symptom at presentation  Transient, migratory oligoarthritis (1-4 joints)  Lower extremities > upper extremity joints  More common in hips, knees and ankles  Non-destructive arthritis (no chronic damage)

 Prominent periarticular swelling with no synovitis  Significant pain + limited range of motion  Differential diagnosis (DDx):  Juvenile Idiopathic arthritis (JIA)  Rheumatoid arthritis (RA)  Systemic Lupus Erytematous (SLE)

MILD SYMPTOMS  Nausea / vomiting  Abdominal pain  Transient paralytic leus SEVERE SYMPTOMS  GI bleed  Bowel ischemia and necrosis  Intussusception  Bowel perforation

 Develops typically within 8 days of the rash  GI symptoms precede the rash in 15-35% of cases  Abdominal pain = submucosal hemorrhage + edema  Guaiac + stool is seen in 56% of patient  Massive GI hemorrhage is rare  Purpuric lesions may be seen on endoscopy

 Most common gastrointestinal complication of HSP  Incidence of 3.5%  Edema and hemorrhage contributes to development  Limited to small bowel in 60% of cases  Initial screening test: Ultrasound  Differential diagnosis: Appendicitis

 Occurs in % of children (more prevalent in adults)  2 days to 4 weeks after onset of systemic symptoms  Hematuria is most common presentation  With or without red blood cell (RBC) casts  Nephrotic range proteinuria, ↑ creatinine and or hypertension  ↑ risk of progressive disease (adults)

 % of glomeruli with crescents has prognostic significance  > 50%  37% progressed to end stage renal disease (ESRD)  18% with chronic renal insufficiency (CRI)  Differential diagnosis :  Berger’s Disease

 Correlation between disease severity and biopsy findings  Asymptomatic hematuria: focal mesangial proliferation  Proteinuria: cellular proliferation  Nephrotic range proteinuria: crescents J Am Soc Nephrol 1999 Dec;10(12):

 2-38% involvement  Presentation mimics testicular torsion  Pain, tenderness and swelling  Evaluate with ultrasound or radionuclide scanning  Testicular torsion will show ↓ blood flow versus normal blood flow in HSP

 Similar manifestations as in children  Two main differences between adults and children:  Intussusception is rare in adults  Adults have ↑ risk of developing significant renal involvement including end-stage renal disease

 Clinical manifestations (know the Tetrad)  Classification criteria  Gold Standard is biopsy  Demonstration of LCV with IgA deposition = HSP

 Biopsy obtained in children:  Unusual presentation or significant renal disease  Biopsy in adults:  Due to lower incidence, confirmation by biopsy is more important

 Superficial dermis biopsy sufficient  Goal to obtain skin lesions less than 24 hour-old  Leukocytoclastic vasculitis in post capillary venules with IgA deposition = pathognomonic of HSP

 Obtain in severe renal involvement or uncertain diagnosis  Characterized by IgA deposition in mesangium  Immunoflorence studies  IgG, fibrin, C3  Mesangial proliferation to crescentic glomerulonephritis (GN)  Biopsy generally parallels clinical disease severity

 No lab test is diagnostic for HSP  Labs obtained tend to be non-specific  Normal coagulation studies and platelets  This differentiates HSP from other diseases  Need to obtain renal function and urinalysis at a diagnosis

 Obtain in patients with significant abdominal symptoms  Plain abdominal X-ray:  May demonstrate dilated bowel loops  Ultrasound:  ↑ bowel wall thickness, hematomas and intussusception

 Complete recovery 94% children, 89% of adults  Supportive treatment in vast majority  Rest  Hydration  NSAIDS

 Hospitalization indicated:  Inability to maintain adequate hydration with oral intake  Severe abdominal pain  Significant gastrointestinal bleeding  Changes in mental status  Severe joint involvement limiting ambulation  Renal insufficiency (↑ Creatinine), HTN, nephrotic syndrome

 Use is controversial  Benefits include:  Shortened duration of abdominal pain  ↓ risk of intussusception  ↓ risk of recurrence  ↓ risk of renal involvement

 Results of benefit mixed in studies  Absence of definitive evidence of long term benefits  Only used in patients with severe symptoms requiring hospitalization  Prednisone 1-2 mg/kg/day, max dose of mg/day  Inflammation will be improved but the pathophysiology of the disease does not appear to be affected

 Gastrointestinal  Corticosteroids not proven to decrease risk of intussusception  Using corticosteroids after intussusception has occurred may obscure the signs of compromised bowel viability Medicine (Baltimore) 1999 Nov;78(6):

 Should only be considered in patients with:  Marked proteinuria and/or impaired renal function  Therapies for cresentic nephritis:  High dose methylprednisolone  oral prednisone for 3 months has shown benefit  Azathioprine and corticosteroids  Cyclophosphamide

 Recurrence occurs in 1/3 rd of children  Occurs within 4 months of initial episode  Usually milder and briefer and occur in patients:  Nephritis  Evidence of acute inflammation  Patients who received corticosteroids

 Most common systemic vasculitis in children  90% of cases occur in the pediatric group  Etiology: Unknown  Pathogenesis: End organ IgA immune complex (IC) deposition  Complications: Renal, GI

 Clinical Diagnosis:  Palpable purpura without thrombocytopenia  Abdominal pain  Renal disease  Arthritis  Treatment: Typically symptomatic and self limited  Unclear role of corticosteroids in TX  No specific agent proven efficacious for persistent renal disease

 Niaudet P, et al. Renal manifestations of Henoch- Schönlein purpura. Uptodate  Dedeoglu F, et al. Clinical manifestations and diagnosis of Henoch-Schönlein purpura. Uptodate  Dedeoglu F, et al. Management of Henoch-Schönlein purpura. Uptodate 2012.