Henoch scholein purpura

definition ,epidemiology ,causes ,pathophysiology ,signs and symptoms , laboratory and images tests, management ,prognosis

1. Henoch–Schönlein purpura(HSP) Prof. Dr. Saad S Al Ani Senior Pediatric Consultant Head of Pediatric Department Khorfakkan Hospital Sharjah ,UAE [email protected]

2. Introduction Henoch–Schönlein purpura is the most common systemic vasculitis of childhood presenting with a tetrad of: P urpura A rthritis or arthralgia A bdominal pain R enal disease. 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 2

3. Introduction (Cont.) Henoch–Schönlein purpura belongs to the group of non‐granulomatous , predominantly small vessel vasculitides 06/01/2019 Henoch- Schönlein Purpura Prof. Dr. Saad S Al Ani 3  Ozen S, Ruperto N, Dillon MJ  et al . EULAR/ PReS endorsed consensus criteria for the classification of childhood vasculitides.  Ann. Rheum. Dis.  2006;  65 : 936–941.

4. Definition Henoch-Schönlein purpura (HSP) is an acute immunoglobulin A (IgA)–mediated disorder characterized by a generalized vasculitis involving the small vessels of the skin, the gastrointestinal (GI) tract, the kidneys, the joints, and, rarely, the lungs and the central nervous system (CNS) 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 4 https:// emedicine.medscape.com/article/984105-overview

5. New EULAR/PRINTO/PRES endorsed classification of childhood vasculitis New EULAR/PRINTO/PRES endorsed classification of childhood vasculitis I Predominantly large vessel vasculitis Takayasu arteritis II Predominantly medium sized vessel vasculitis Childhood polyarteritis nodosa Cutaneous polyarteritis Kawasaki disease 06/01/2019 Henoch- Schönlein Purpura Prof. Dr. Saad S Al Ani 5

6. New EULAR/PRINTO/PRES endorsed classification of childhood vasculitis (Cont.) III Predominantly small vessel vasculitis (A) Granulomatous Wegener's granulomatosis Churg‐Strauss syndrome (B) Non-Granulomatous Microscopic polyangiitis Henoch–Schönlein purpura Isolated cutaneous leucocytoclastic vaculitis Hypocomplementic urticarial vasculitis 06/01/2019 Henoch- Schönlein Purpura Prof. Dr. Saad S Al Ani 6

7. New EULAR/PRINTO/PRES endorsed classification of childhood vasculitis (Cont.) IV Other vasculitides Behçet disease Vasculitis secondary to infection (including hepatitis B associated polyarteritis nodosa) malignancies, drugs, including hypersensitivity vasculitis Vasculitis associated with connective tissue diseases Isolated vasculitis of the central nervous system Cogan syndrome Unclassified 06/01/2019 Henoch- Schönlein Purpura Prof. Dr. Saad S Al Ani 7

8. Epidemiology HSP is the most common childhood vasculitis Annual incidence varies between 10 and 30 cases per 100 000 children < 17 years (1) The mean age of presentation is 6 years with most cases in children < 10 years of age , 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 8 1.Penny K, Fleming M, Kazmierczak D  et al . An epidemiological study of Henoch‐Schönlein purpura.  Pediatr. Nurs.  2010;  22 : 30–35 .

9. Epidemiology (Cont.) An equal incidence in males and females (2) HSP occurs predominantly in cold months of the year It has been reported worldwide . 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 9 2.González LM, Janniger CK, Schwartz RA. Pediatric Henoch‐Schönlein purpura.  Int. J. Dermatol.  2009;  48 : 1157–1165.

10. Aetiology and Pathogenesis The majority of HSP cases are preceded by an upper respiratory tract infection suggesting a potential infectious trigger. 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 10

11. Aetiology and Pathogenesis (Cont.) The most commonly implicated respiratory pathogens include: Streptococcus Staphylococcus Parainfluenza Association between virtually all respiratory pathogens and HSP (1) 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 11 (1)Weiss PF, Klink AJ, Luan X, Feudtner C.Temporal association of Streptococcus, Staphylococcus, and parainfluanza pediatric hospitalizations and hospitalized cases of Henoch-Schönlein purpura.. J. Rheumatol., 2010

12. The characteristic pathological feature of HSP vasculitis is a deposition of IgA-containing immune complexes in : The vessel walls of affected organs The kidney mesangium. 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 12 Aetiology and Pathogenesis (Cont.)

13. Deposited immune complexes activate the alternative complement pathway (with deposition of C3) and recruit inflammatory cells causing glomerulonephritis (1,2) 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 13 Aetiology and Pathogenesis (Cont.) (1) Sanders JT, Wyatt RJ. IgA nephropathy and Henoch Schönlein purpura nephritis Curr . Opin. Pediatr., 2008 (2) Novak J, Julian BA, Tomana M. IgA glycosylation and IgA immune complexes in the pathogenesis of IgA nephropathy.Semin . Nephrol., 2008

14. Deposition of IgA1-containing immune complexes in other sites (skin, gut, joints) leads to organ-specific clinical manifestations of HSP . 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 14 Aetiology and Pathogenesis (Cont.)

15. Clinical Manifestations HSP is a systemic vasculitis with multiorgan involvement. The classic tetrad of signs and symptoms includes: 1 / Palpable purpura 2 / Arthritis or arthralgia 3 / Abdominal pain 4/ Renal disease 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 15

16. Typical prodrome of HSP The typical prodrome of HSP includes the following: Headache Anorexia Fever 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 16

17. The Most common symptoms Rash (95-100% of cases ) especially involving the legs; this is the hallmark of the disease Abdominal pain and vomiting (35-85%) Joint pain (60-84 %) especially involving the knees and ankles Subcutaneous edema (20-50%) Scrotal edema (2-35%) Bloody stools 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 17

18. Palpable purpura Skin involvement is present in all children with HSP (1) Petechiae and palpable purpura are the most common Other skin rashs: E rythematous M acular U rticarial B ullous have also been observed. 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 18 (1) González LM, Janniger CK, Schwartz RA. Pediatric Henoch-Schönlein purpura. Int . J. Dermatol., 2009

19. Palpable purpura (Cont.) Purpura is characteristically distributed symmetrically over : Extensor surfaces of the lower limbs , Buttocks Forearms 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 19

20. 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 20 Mayo Clinic

21. 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 21 Obgyn Key

22. Palpable purpura (Cont.) Recurrence of purpura, which might be associated with more severe renal involvement, is observed in of children with HSP 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 22

23. Arthritis/arthralgia Arthritis/arthralgia is present in three quarters of children with HSP (1)   Joint involvement is usually oligoarticular with large joints of the lower extremities (knee, ankle, hip) most commonly affected 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 23 Trapani S, Micheli A, Grisolia F  et al . Henoch Schonlein purpura in childhood: epidemiological and clinical analysis of 150 cases over a 5‐year period and review of literature.  Semin. Arthritis Rheum.  2005;  35 : 143–153.

24. Arthritis/arthralgia (Cont.) There is usually prominent periarticular S welling , T enderness and P ain E rythema and joint E ffusion are rare   Arthritis is non‐deforming and heals without chronic damage within a few weeks. 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 24

25. Abdominal pain Approximately two thirds of children with HSP develop abdominal pain (1) Usually diffuse , increasing after meals , and sometimes associated with nausea and vomiting 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 25 (1)   Choong CK, Beasley SW. Intra‐abdominal manifestations of Henoch‐Schönlein purpura.  J. Paediatr . Child Health 1998;  34 : 405–409 .

26. Abdominal pain (Cont.) The most severe gastrointestinal complication is intussusception , affecting 3–4% patients with HSP In 60% of these cases, it is limited to small bowel Clinical presentation of intussusception is characterised by severe abdominal pain , often colicky in nature and vomiting . 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 26

27. Abdominal pain (Cont.) Other significant, though less common gastrointestinal complications are: Gangrene of the bowel Bowel perforation Massive haemorrhage 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 27

28. Renal involvement Renal involvement is reported in 20–55% of children with HSP (1,2) Isolated microscopic haematuria ( most common   ) Proteinuria of variable degree Nephrotic syndrome ( in severe cases ) 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 28   (2)Jauhola O, Ronkainen J, Koskimies O et  al . Renal manifestations of Henoch‐Schönlein purpura in a 6‐month prospective study of 223 children.  Arch. Dis. Child.  2010;  95 : 877–882 . (1) Narchi H. Risk of long term renal impairment and duration of follow up recommended for Henoch‐Schonlein purpura with normal or minimal urinary findings: a systematic review.  Arch. Dis. Child.  2005;  90 : 916–920 .

29. Renal involvement (cont.) Hypertension might develop ( at the onset or during recovery ). Renal function is usually normal The occasional patient might present with a progressive glomerulonephritis with significant renal impairment . 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 29

30. Other less common clinical manifestations of HSP C erebral vasculitis S crotal or testicular haemorrhage I nterstitial pulmonary haemorrhage (1). D istal ureteric vasculitis resulting in ureteric stenosis 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 30 (1)Ha TS, Lee JS. Scrotal involvement in childhood Henoch‐Schönlein purpura .   Acta Paediatr .  2007;  96 : 552–555.

31. Diagnosis of HSP Is based on the presence of purpura (palpable) or petechiae (without thrombocytopenia) with lower limb predominance (mandatory criterion) plus at least one of the flowing four features : 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 31 Ozen S,  Pistorio A,  Iusan SM  et al . EULAR/PRINTO/PRES criteria for Henoch‐Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II.Final classicication criteria.  Ann. Rheum. Dis. 2010;  69 : 798–806 .

32. Diagnosis of HSP (Cont.) ( 1) Abdominal pain ( 2) Arthritis or Arthralgia ( 3) Leukocytoclastic vasculitis or Proliferative glomerulonephritis with predominant deposition of IgA histologically ( 4) Renal involvement ( haematuria, red blood cell casts or proteinuria ) 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 32 Ozen S,  Pistorio A,  Iusan SM  et al . EULAR/PRINTO/PRES criteria for Henoch‐Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II.Final classicication criteria.  Ann. Rheum. Dis. 2010;  69 : 798–806.

33. Laboratory tests Laboratory tests are complementary in assessing renal involvement Urinalysis Urine microscopy Serum creatinine 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 33

34. Imaging studies Imaging studies are helpful in the: Evaluation of abdominal involvement Potential complications (intussusception). 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 34

35. Ultrasound examination of the abdomen in a child with HSP 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 35 http:// www.ultrasoundcases.info/Monthly-Case.aspx?month=147&show=1

36. Histopathology In children with incomplete or unusual presentation, biopsy of the affected organ (skin, kidney) confirms the diagnosis. 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 36

37. Histopathology (cont.) 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 37 Glomerular arteriole showing a vasculitis with fibrinoid necrosis of the vessel wall (arrow) and swelling of the endothelial cells (E). Surrounding the vessel there is granulomatous inflammation (G) (haematoxylin and eosin, ×400). https:// bjo.bmj.com/content/89/9/1221.2.full

38. Management of HSP Management of HSP includes: Supportive care Symptomatic therapy Immunosuppressive treatment ( in some cases) 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 38

39. Supportive care The basic principles of supportive care consist of: M aintenance of good hydration S ymptomatic pain relief Monitoring for the development of complications 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 39

40. Symptomatic therapy Non‐Steroidal Anti‐Inflammatory Drugs ( NSAIDs ) can be used for arthritis/arthralgia Early glucocorticosteroids( GCS ) treatment : shortened duration of abdominal pain decreased risk of intussusception decreased risk of surgical intervention (1) GCS treatment cannot be recommended in all patients with HSP since the majority will improve spontaneously 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 40 (1)Weiss PF, Klink AJ,  Localio R  et al . Corticosteroids may improve clinical outcomes during hospitalization for Henoch‐Schönlein purpura.  Pediatrics 2010;  126 : 674–681.

41. Glucocorticosteroids (Cont.) Pulse intravenous methylprednisolone followed by 3 to 6‐month course of oral steroids is most commonly used in patients with rapidly progressive glomerulonephritis or nephrotic syndrome ( usually accompanied by crescents on kidney biopsy ), 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 41 Niaudet P, Habib R. Methylprednisolone pulse therapy in the treatment of severe forms of Schönlein‐Henoch purpura nephritis.  Pediatr. Nephrol.  1998;  12 : 238–243.

42. Indication for GCS usage Persistent n ephrotic syndrome C rescents in more than 50% of glomeruli Severe a bdominal pain Substantial GI h emorrhage Severe soft tissue e dema Severe scrotal e dema N eurologic system involvement Intrapulmonary h emorrhage 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 42

43. Immunosuppressive treatment Immunosuppressive treatment of HSP nephritis is used in patients with severe kidney involvement (nephrotic range proteinuria and/or progressive renal impairment) 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 43

44. Immunosuppressive treatment (cont.)  A current KDIGO guideline suggests adding cyclophosphamide to steroid treatment for crescentic glomerulonephritis 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 44 Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis.  Kidney Int . 2012;  2 : 139–247.  

45. Prognosis of HSP In the majority of children, the outcome of HSP is excellent with spontaneous resolution of symptoms and signs. HSP recurs in approximately one third of patients, typically within 4 months of the initial presentation . 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 45

46. Prognosis of HSP (Cont.) Recurrent purpura can be occasionally associated with joint complaints and episodes of gross haematuria although each subsequent episode is generally milder and shorter . The long‐term morbidity of HSP is related to the degree of HSP nephritis . 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 46

47. Initial follow-up for kidney involvement The aim of the initial follow‐up is to identify patients with worsening kidney involvement and is based on: serial urinalyses blood pressure measurement blood tests to assess kidney function and exclusion of other causes of glomerulonephritis 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 47

48. HSP is : C ommon childhood vasculitis Good outcome in the majority of affected children Small subgroup of children who will develop significant renal impairment S ome of them will eventually progress to ESKD and require kidney transplantation.  06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 48

49. Patients with severe abdominal pain need prompt evaluation and investigations to exclude intussusception In cases with sudden change of mental status, intracranial haemorrhage should be excluded with appropriate imaging 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 49

50. Patients with compromised renal function taking NSAIDs need close monitoring of their: fluid status blood pressure renal function. Mild renal involvement (microscopic haematuria or mild proteinuria) does not require biopsy or immunosuppressive treatment, but these children need close follow‐up. 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 50

51. Reference https:// onlinelibrary.wiley.com/doi/full/10.1111/jpc.12403 Ozen S, Ruperto N, Dillon MJ et al. EULAR / PReS endorsed consensus criteria for the classification of childhood vasculitides. Ann. Rheum. Dis. 2006; 65: 936–941 . Penny K, Fleming M, Kazmierczak D et al. An epidemiological study of Henoch‐Schönlein purpura. Pediatr. Nurs. 2010; 22:  30–35 Weiss PF, Klink AJ, Luan X, Feudtner C.Temporal association of Streptococcus, Staphylococcus, and parainfluanza pediatric hospitalizations and hospitalized cases of Henoch-Schönlein purpura .. J . Rheumatol., 2010 Sanders JT, Wyatt RJ. IgA nephropathy and Henoch Schönlein purpura nephritis Curr. Opin. Pediatr., 2008 Novak J, Julian BA, Tomana M. IgA glycosylation and IgA immune complexes in the pathogenesis of IgA nephropathy.Semin. Nephrol., 2008 González LM, Janniger CK, Schwartz RA. Pediatric Henoch-Schönlein purpura. Int. J. Dermatol., 2009 Trapani S, Micheli A, Grisolia F  et al . Henoch Schonlein purpura in childhood: epidemiological and clinical analysis of 150 cases over a 5‐year period and review of literature.  Semin. Arthritis Rheum.  2005;  35 : 143–153 . Jauhola O, Ronkainen J, Koskimies O et  al . Renal manifestations of Henoch‐Schönlein purpura in a 6‐month prospective study of 223 children.  Arch. Dis. Child.  2010;  95 : 877–882 . 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 51  

52. 06/01/2019 Henoch-Scholein Purpura Prof. Dr. Saad S Al Ani 52 Julie Blais Comeau