Henoch Schonlein Purpura (2)

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  • 1. Henoch-Schonlein Purpura Jeremy Gitomer MD Division of Pediatric Nephrology
  • 2. Introduction
    • Heberden in 1801 described a 5 yo with edema, abdominal pain, bloody stools, hematuria and “bloody points” all over his body.
    • Schonlein in 1837 named the association of joint pain and purpura as “purpura rheumatica”
    • Henoch in 1874 described patients with purpura, severe abdominal colic, melena and large joint arthritis
  • 3. Introduction
    • HSP is the most common vasculitic disease of childhood
    • HSP is considered to be a form of IgA Nephropathy with extrarenal manifestations.
  • 4. Epidemiology
    • Incidence is 13.5-18/100000
    • Male to female 1.5:1
    • Can occur from 6 months- adulthood
      • 50% of cases are under 5 years of age
    • Wide geographical distribution
    • More common in winter and spring
    • Genetics play a small role
  • 5. IgA Immune System
    • The most abundant immunoglobulin in the body
    • IgA is compartmentalized
      • Secretory
      • Circulating
  • 6. Immunoglobulin A Secretory Component is derived from epithelial surface IgA receptors J Chain produced in the plasma cell
  • 7. Pathogenesis
    • Abnormalities in IgA :
      • Production
      • Clearance
      • Glycosylation
  • 8. IgA Glycosylation
  • 9. Characteristics of Mesangial IgA
    • Predominantly IgA 1
    • Predominantly polymeric
    • Contains J chain
    • Does not contain SC protein
  • 10. Origin of Deposited IgA
    • Enhanced tonsillar production of pIgA 1 has been reported
    • Assessment for pIgA 1 production by in situ hybridization for J chain mRNA in IgA plasma cells shows downregulation in the mucosa and upregulation in the bone marrow
    • If the marrow is the source of pIgA 1 then the link between mucosal infection and hematuria remains unexplained
  • 11. Clinical Presentation
    • Effects predominantly young children, but adults are also affected
    • Peak incidence is 4-5 years of age
    • There is a slight male predominance
    • The condition is more prevalent in the winter and early spring
    • The onset of illness is usually sudden and is preceded by a URI in at least 1/3 of cases
  • 12. Clinical Presentation
    • Classic Triad of symptoms is the most common presentation
      • Purpura
      • Colicky abdominal pain
      • arthritis
    • 50% of children may present with symptoms other than purpura
  • 13. Clinical Manifestations of HSP Szer IS. J Rheumatology 1996:23;1661-1665
  • 14. Influence of Age on Clinical Manifestations Allen et al. Am J Dis Child 1960;99:147-168
  • 15. Dermatologic
    • Begins as erythematous macules
    • Some of which develop raised urticarial papules which soon become purpuric or petechial
    • The eruption is symmetric effecting the extensor surfaces of the lower legs, forearms, buttocks and sparing the trunk.
    • Purpura occasionally affect earlobes, nose and external genitalia.
  • 16. Dermatologic
    • Younger children may only have urticaria
    • Also younger children may present with edema of the feet, dorsum of the hands, face and scalp.
    • As primary lesions fade new crops can present for up to three months from the onset of the disease (and sometimes much longer)
    • Erythema nodosum can occur
    • Blistering lesions can occur
  • 17.  
  • 18.  
  • 19.  
  • 20. Arthralgia
    • 60-84% of children exhibit transient arthralgia and periarticular edema.
      • The knees, ankles, elbows and wrists are most commonly affected
      • Erythema, tenderness or joint effusions may or may not be present in painful joints
    • Arthritis precedes the onset of skin findings in 25% of cases
  • 21. Gastrointestinal Manifestations
    • Gastrointestinal manifestations occur in 50-70% of patients
    • The incidence is 90% in those patients with renal involvement
    • The most common symptom is abdominal colic
    • Abdominal pain precedes rash in 14% of cases
  • 22. GI Manifestations
    • Melena occurs in 50% of patients
    • Hematemesis occurs in up to 30% of patients
    • Massive GI bleeding occurs in 2%-10% of patients
  • 23. Radiographic Findings in 22 Patients with HSP and Abdominal Complaints Glasier et al. AJR: 1981;136:1081-1085
  • 24. GI Manifestations Glasier et al. AJR: 1981;136:1081-1085
  • 25. GI Manifestations Glasier et al. AJR: 1981;136:1081-1085
  • 26. GI Manifestations Glasier et al. AJR: 1981;136:1081-1085
  • 27. Intussusception and HSP
    • The incidence of intussusception in HSP is between 1-2% of all patients with HSP and abdominal pain.
    • 50% of intussusceptions in HSP are ileoilial
      • In contrast, in children without HSP, ileocolic intussusceptions are found in 90-95% of cases
    • High resolution ultrasound is the diagnostic study of choice (ileoilial intussusception may not be detected by barium enema)
  • 28. GI Manifestations Intussusception Reduced Intussusception Obstructed proximal ileum Glasier et al. AJR: 1981;136:1081-1085
  • 29. Other GI Manifestations
    • Pancreatitis
    • Biliary necrosis
    • Biliary hydrops
    • Hemorrhagic ascites
    • Bowel necrosis
    • Duodenitis
    • Hemorrhagic duodenitis
  • 30. GU Manifestations
    • Acute scrotal swelling secondary to inflammation and hemorrhage of the scrotal vessels occurs in 10-30% of males with HSP
    • Scrotal edema is common
    • Purpuric lesions on the scrotum are common
  • 31. GU Manifestations
  • 32. Pulmonary Manifestations
    • Pulmonary hemorrhage is a rare but often fatal complication of HSP
    • Acute interstitial lung disease, as demonstrated by a decrease in TLCO (56% of predicted), was noted in 28/29 patients with HSP without pulmonary symptoms.
      • Chaussain et al. J Ped 1992;121:12-16.
  • 33. CNS Manifestations
    • Cerebritis
    • Coma
    • Paresis
    • Subacute encephalopathy
    • Subdural hematoma
    • Cortical hemorrhage
    • Cerebral infarction
    • Peripheral neuropathy
  • 34. Renal Manifestations
    • The incidence has been reported to be between 20-100%.
    • Two large studies in which routine urine analysis was performed upon admission demonstrated an incidence of 41 and 61%
    • Patients with abdominal involvement are more likely to have renal involvement
      • Relative Risk is 7.5
  • 35. Renal Manifestations
    • Microscopic hematuria and minimal proteinuria
    • Hematuria and heavy proteinuria
    • Nephrotic syndrome
    • Nephritic syndrome
    • Nephrotic-Nephritic syndrome
  • 36. Criteria for Diagnosis of HSP
    • ACR established criteria in 1990
    • Children must have palpable purpura without thrombocytopenia
    • Adults must have 2 of the following:
      • Age <20 years at onset
      • Palpable purpura
      • Bowel angina
      • Biopsy evidence of granulocytes in the walls of arterioles or venules
  • 37. Differential Diagnosis
    • Systemic lupus erythematosus
    • Polyarteritis nodosa
    • Wegener’s granulomatosis
    • Testicular torsion
    • Acute surgical abdomen
    • Hypersensitivity vasculitis
    • Sepsis with purpura
  • 38. Laboratory Investigation
    • Urine analysis
    • Urine for protein and creatinine
    • Occult blood should be checked in the stool
    • Serum total protein and albumin
    • Serum creatinine
    • ANCA in patients with appropriate histories
    • IgA levels are useless
  • 39. Laboratory Investigations
    • Testicular ultrasound when associated with testicular pain
    • Abdominal series and abdominal ultrasound when severe abdominal cramping present
    • CXR
    • Pulmonary function tests if the patients have symptoms
    • ACA IgA isotype
  • 40. Kidney Biopsy
    • Generally not performed for routine cases
    • Indications are:
      • Severe nephritic syndrome
      • Persistent heavy proteinuria
      • Atypical presentations
  • 41. Morphologic Classification of HSP Glomerulonephritis ISKDC
    • I. Minimal glomerular abnormalities
    • II. Pure mesangial proliferation
    • III. Crescents/Segmental lesions <50%
    • IV. Crescents/Segmental lesions 50-75%
    • V. Crescents/Segmental lesions >75%
    • VI. Pseudomesangiocapillary
    • II-VI also categorized as (a)focal or (b) diffuse mesangial proliferation
  • 42. HSP Light
  • 43. Epithelial Crescent
  • 44. Epithelial Crescents
  • 45. Immunofluorescence
  • 46. Electron Microscopy
  • 47. Extrarenal Pathology
    • Skin biopsies of affected areas demonstrate a leukocytoclastic vasculitis with perivascular infiltration of polymorphs and mononuclear cells.
    • Necrosis of small blood vessels may also be seen
    • Immunostaining reveals IgA in most purpuric skin lesions and also in unaffected areas.
    • Similar findings are present in the gut and lungs of affected individuals
  • 48. Natural History for HSP without Nephritis
    • Generally HSP is a self limited illness.
    • No treatment is required for the purpura
    • NSAIDs are used to treat arthralgias
      • Steroids are not beneficial
  • 49. Natural History of GI Manifestations Rosenblum et al. Ped 1987;79:1018-1021
  • 50. Treatment GI Manifestations
  • 51. Natural History of Pulmonary Manifestations
    • 29 patients with TLCO measurements
      • 28/29 patients with HSP had decreased TLCO
    • 10 Children had resolution of HSP in 3 months
      • TLCO returned to normal for all patients
  • 52. Natural History of Pulmonary Manifestations
    • 3 children had recurrent skin lesions and urinary abnormalities the first 3 months but had clinically recovered by 6 months
      • TLCO was 45.7% initially, 58% at three months and 97.5% of predicted at 6 months
    • 5 patients never clinically resolved during the study period
      • 3 of the 5 significant TLCO decreases from predicted at the time of study closure
  • 53. Treatment of Pulmonary Manifestations
    • No studies have been performed to see if steroids or other treatments for HSP improve
    • Aggressive immunomodulating therapy should be used in patients with severe pulmonary hemorrhage since it is often life threatening
  • 54. Treatment for Neurologic Manifestations
    • 3 patients with severe cerebritis were treated with plasma exchange and had complete resolution of symptoms
      • Gianviti et al. Arch Dis Child 1996;75:186-190
  • 55. Long Term Renal Outcome of HSN
    • HSP is the diagnosis for 5-15% of patients diagnosed end stage renal disease
    • Stewart followed 270 patients with HSP for 13 years
      • 1% renal morbidity
      • <1% mortality
        • Eur J Pediatr 1988;147:113-115
  • 56. Clinicopathologic Correlation
  • 57. Long Term Renal Outcome for HSNephritis
  • 58. Long Term Renal Outcome of HSNephritis Actual Number of patients (Percent of total)
  • 59. Long Term Renal Outcome of HSNephritis
  • 60.  
  • 61. Oral Steroids to Prevent Nephritis in HSNephritis
  • 62. Pulse Steroids for HSN
    • Niaudet and Habib reported 38 patients with severe nephritis treated with pulse solumedrol.
      • 1-16 years of followup was obtained
      • 27 (71%) patients had completely recovered
      • 3 (8%) had minor urinary abnormalities
      • 4 (11%) had persistent nephropathy
      • 4 (11%) developed ESRD
    Pediatr Nephrol 1998;12:238-243
  • 63. Combined Therapy for HSN
    • Oner described 12 patients with HSP and severe crescentic glomerulonephritis treated with methylprednisolone, oral cyclophosphamide, dipyridamole and prednisolone.
      • 7 (58%) patients went into remission
      • 8 (67%) patients had resolution of nephrosis
      • 9 (75%) patients had resolution of hematuria
      • 1 (8%) patient developed ESRD
    Pediatr Nephrol 1995;9:6-10.
  • 64. Plasma Exchange for HSN
    • Khono treated 9 patients with nephrotic syndrome and decreased GFR solely with plasmapheresis.
        • AJKD 1999 Mar;33(3):427-33
    • Jardim treated 14 patients with severe renal disease with plasma exchange, dipyrimadole, steroids and imuran.
      • 9 patients responded to therapy with improvement in renal function
        • Pediatr Nephrol 1992;6:231-235
  • 65. Intravenous Gamma Globulin for HSN
    • Rostoker et al treated 14 patients diagnosed with IgAN or HSP nephritis.
      • All patients had normal GFR
      • All patients had proteinuria
    • The average proteinuria decreased from 766 mg/day to 171 mg/day during the 6 months of the study.
      • All but 1 patient responded to the IMIG
    Nephron 1995;69:327-334
  • 66. Treatment for Chronic HSN
    • Steroids
    • Fish oil
    • Vitamin E
    • Gluten free diet
    • Tonsillectomy
    • IV/IM IG
    • Combination therapy
  • 67. Recurrence in Transplant
    • Meulders and coworkers reported the course of renal transplantation in 78 patients with ESRD secondary to HSP in 1994
      • Histologic recurrence occurred in 50% of patients
      • Clinical recurrence occurred in 20% of patients
      • Graft failure (12%) and graft loss (9%) were common
      • Waiting for 6 months prior to transplant had no effect on recurrence
    Transplantation 1994;58:1179-1186
  • 68. Conclusions
    • HSP has a variable presentation
    • Most patients will have complete recovery and their long term prognosis is good
    • Patients with severe crescentic GN or cerebritis should receive aggressive immunomodulating therapy
    • Patients need long term follow-up because of the low, but significant, incidence of late renal complications.