Common Childhood Vasculitides: Henoch Schonlein Purpura and Kawasaki Disease Sharon Bout-Tabaku, MD, MSc Assistant Professor of Pediatrics Nationwide Children’s Hospital

Learning Objectives PRIMARY OBJECTIVES:  Epidemiology  Pathophysiology  Typical disease presentation Clinical presentation and diagnostic criteria Complications and prognosis  Treatment KEY LEARNING POINTS: 1. Outline the epidemiology of Henoch-Schonlein purpura. 2. Understand what is known about the pathophysiology of Henoch-Schonlein purprua. 3. Describe the typical clinical presentation for Henoch-Schonlein purpura. 4. Describe the clinical and laboratory criteria used for diagnosing Henoch-Schonlein purpura. 5. Describe when treatment is indicated for Henoch Schonlein purpura. 6. Understand the potential complications and prognosis for Henoch-Schonlein purpura, including how the prognosis in adults an and children differs. 7. Outline the epidemiology of Kawasaki disease. 8. Describe what is known about the pathophysiology of Kawasaki disease. 9. Understand the classical presentation, potential complications and prognosis of Kawasaki disease. 10. Describe the clinical and laboratory criteria used for diagnosing Kawasaki disease. 11. Explain the treatment for Kawasaki disease.

HSP- Epidemiology

Henoch-Schonlein Purpura (HSP)-Epidemiology  Most common - 49 % of all ped vasculitis  Annual incidence is 22/100,000  Peak age of onset 4-6 years  Boys > girls  Caucasians > African-Americans  Seasons- winter and spring- supporting infectious triggers

HSP - Describe Leukocyotoclastic vasculitis  Variety of immune cells deposited in the small vessel wall  Immune complex deposition, autoantibodies and inflammatory mediators, adhesion molecules

HSP - Pathophysiology What is known? Antigenic precipitant Immune complex deposition of IgA T regulatory cell dysfunction Immunofluorescence studies show IgA, C3, and fibrin deposition within the walls of involved vessels.

HSP – Typical Clinical Presentation  Purpura/petechiae of lower limbs  Plus 1 of the following:  Arthritis (75%) or arthralgias  Abdominal pain –colicky (50-75%)  Histopathology with IgA deposits  Renal disease (20-60%: hematuria, proteinuria)  Lasts 3-4 weeks and 1/3 of children have at least 1 recurrence

HSP Arthritis Glomerular vasculitis Scrotal edema Edema Intussception with bowel necrosis Purpuric rash

HSP - Complications  Intermittent colicky abdominal pain before rash  Intussusception and gastrointestinal bleeding  Edema of eyes, scrotum, hands  Seizure, strokes, pulmonary hemorrhage  Glomerulonephritis with rare end stage renal disease

HSP – Clinical and Diagnostic Findings Lab testing does not help make a diagnosis Although there are petechiae, no thrombocytopenia or coagulopathy Possible thrombocytosis, +/- inflammatory markers, elevated WBC Be concerned if you get an abnormal urine analysis or abnormal Bun and creatinine.

HSP - Treatment  Supportive for majority of cases  Analgesia - acetaminophen or NSAIDs Complicated cases: severe arthritis, GI vasculitis, renal disease glucocorticoids may shorten course and diminish GI morbidities 6 month prospective trial of glucocorticoids reduced symptoms of renal disease but did not prevent occurrence of renal disease Weekly urine dipsticks for 2 months after HSP to screen for kidney disease Weiss 2010 Ronkainen, 2006 Jauhola 2010

HSP - Prognosis  In general, excellent in children  Rarely renal and abdominal complications  With renal complications the prognosis is variable and should be followed for 5 years  Adults - more recurrences, renal disease, and end stage renal disease

Kawasaki Disease (KD)

KD - Epidemiology  2 nd most common vasculitis - 23 % of all pediatric vasculitis  Annual US incidence is 19/100,000, Japan 218.6/100,000  Peak age of onset 2-3 years (US), 6-11 mo (Japan)  Boys> girls  Asian > African-American > Hispanic > Caucasian  November –May supporting infectious triggers, different in other countries

KD - Describe  Medium sized vasculitis  Vessels with fibrinoid necrosis  Early neutrophilic infiltrate in microvasculature then spreads to larger vessel  Coronary arteries mostly affected  Lamina elastica disrupted leading to aneurysm

KD - Inflammation of the artery

KD - Pathophysiology  What is known?  Remains controversial  Superantigen leads to massive T lymphocyte stimulation  Oligoclonal IgA immune response  Genetic polymorphisms implicate T cell activation

KD – Typical Clinical Presentation

KD-Typical clinical presentation

KD-Clinical presentation Bilateral, non- exudative conjunctivitis Oropharnygeal changes Strawberry tongue Diffuse erythema of the mouth Red, cracked lips

KD-Clinical Presentation Cervical lymphadenopathy (> 1.5 cm, unilateral) Polymorphous rash Peripheral extremity edema and desquammation

KD - Non-typical Presentation  Incomplete KD  Fever ≥ 5 days with 2 or 3 of the clinical criteria  Atypical KD  Fulfill KD criteria but have unusual features (e.g., renal failure)

KD - Complications  Pancarditis  Coronary aneurysm  Gall bladder hydrops  Aseptic meningitis  Arthritis  Facial nerve palsy

KD - Coronary Aneurysm Ultrasound images of dilated coronary Stenotic aneurysm and collaterals

KD – Clinical and Diagnostic Findings  Lab testing is supportive  Acute phase reactants are high - ESR and CRP  WBC, mostly neutrophils  Anemia  Platelets - up to 1,000,000  Hypoalbuminemia  Transaminases  Sterile pyuria

KD - Prognosis  Children without cardiac disease or transient do well  Recurrence < 3%  5% develop coronary aneurysms  Children with cardiovascular disease (aneurysms) have long term risks  50% regress within first 2 years, but risk of later potential atherosclerosis or stenosis

KD - Treatment  IVIG one dose and high dose aspirin  After 48 hours of no fever- low dose aspirin  Treatment failure  Repeat IVIG  If refractory, corticosteroids +/- infliximab Echocardiogram - at diagnosis, 2 weeks into illness and then 6-8 weeks Newburger, 2007 Newburger, 2004

KD - Treatment and Monitoring  Small aneurysm- stay on low dose aspirin until regression of the aneurysm  Large aneurysm - stay on low dose aspirin and may require anti- coagulation  No cardiac disease – cardiovascular risk assessment and counseling every 5 years  Transient disease- cardiovascular risk assessment and counseling every 3-5 years

Summary 1. Henoch-Schonlein purpura. HSP is most common in boys and Caucasians, occurs in the Winter and Spring. It occurs in children aged 4-6 years. 2. Know that you can see IgA deposition in the vessels on immunofluorescent staining in the small vessels 3. Know the typical presentation which is a purpuric/petechial rash with arthritis, abdominal pain, kidney disease or typical pathology findings. 4. Is usually a self limiting disease that needs analgesics but if there is severe disease corticosteroids may diminish the duration and severity 5. The complications can be life threatening especially if bowel disease leads to bowel necrosis or if renal disease occurs. Renal disease and recurrent HSP is usually worse in adults. 6. Kawasaki disease is the 2 nd most common. It occurs mostly In boys, Asian and also in the Winter- spring months. Children with KD are usually younger that those with HSP. 7. KD is Immune mediated affecting the medium sized vessels 8. Know the classification criteria for Typical KD, fever for at least 5 days and at least 4 of the other 5 criteria There are many complications and the worst is coronary disease which confers a worse prognosis. 9. Laboratory criteria can be supportive of your clinical diagnosis of KD. Thrombocytosis is typical along with high inflammatory markers. Liver transaminases can be abnormal 10. Know that you must use IVIG and high dose aspirin once the diagnosis is made. You can retreat with IVIG if the first one does not stop the fevers. An echocardiogram must be done early in the disease and then periodically after that.

Thank you for completing this module  If you have any questions, I am available. 

References  Weiss, PF. Pediatric Vasculitis. Pediatric Clinics N America(59)  Scuccimarri, R. Kawasaki Disease. Pediatric Clinics N America(59)  Cassidy J, Petty R et al. Textbook of Pediatric Rheumatology. 6 th edition, 2010.

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