Collagen Vascular Disease in Children

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Dr. Maynard’s presentation on the types of collagen vascular disease in children (presented on 9/22/11).

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Collagen Vascular Disease in Children

  1. 1. Collagen Vascular Disease in Children Roy Maynard, M.D. September 22, 2011
  2. 2. Objectives• Define collagen vascular disease.• Identify 3 collagen vascular diseases that affect children.• Understand the role new biological modifying agents have on treating collagen vascular disease. 2 of 46
  3. 3. Definition• A diverse group of multi-system inflammatory disorders, affecting primarily collagen in the skin and joints. Autoantibody formation and other autoimmune dysfunction suggest a complex immune basis in the pathogenesis of the disease process which remains largely idiopathic 3 of 46
  4. 4. Classification• Vasculitis• Arthritides• Connective tissue disease• Infectious diseases 4 of 46
  5. 5. Collagen Vascular Disease• Systemic Lupus Erythematous• Dermatomyositis• Scleroderma• Juvenile Idiopathic Arthritis 5 of 46
  6. 6. Epidemiology• 150-200 children/million• 0.015 to 0.02% of children• Female preponderance• Fairly uncommon disease in children 6 of 46
  7. 7. Pathogenesis• Molecular mimicry: Infectious agents alter the surface markers of ones own cells leading to them being recognized as foreign by your immune system.• Autoimmunity: Idiopathic alterations in the basic immune system leading to the recognition of cells and tissues as foreign and subsequently attack as foreign. 7 of 46
  8. 8. Treatment• Glucocorticsteroids• Immunosuppressives• Immunomodulators• Anti-inflammatory 8 of 46
  9. 9. Systemic Lupus Erythematosus • Diagnosis – Malar rash – Discoid rash – Photosensitivity – Oral ulcers – Arthritis – Serositis (pleural or pericardial) – Renal (proteinuria) 9 of 46
  10. 10. Systemic Lupus ErythematosusMalar rash http://www.emedicinehealth.com/script/main/art.asp?articlekey=107976 Accessed on 9/19/11 10 of 46
  11. 11. Systemic Lupus Erythematosus• Epidemiology – 0.36 to 0.4 children/100,000 – Girls/boys (4:2 to 7:1) – Rare diagnosis before age 5 – Peaks young adulthood – 15-20% of adults started disease in childhood – Age 12 to 14 years when disease diagnosed 11 of 46
  12. 12. Systemic Lupus Erythematosus • Diagnosis – Neurologic (seizures or psychosis) – Hematologic • Hemolytic anemia • Leukopenia • Lymphopenia • Thrombocytopenia – Immunologic disorder • Positive LE prep • Anti-dsDNA antibody • Anti-Smith antibody • False positive syphilis test • Antinuclear antibody, C3 and C4 – Other organs • Kidneys, lungs, cardiac 12 of 46
  13. 13. Systemic Lupus Erythematosus • Prognosis – In 1950, only 30% survived 5 years – Now 5-year survival > 90% – Pediatric SLE has a worse prognosis than adult SLE – Risk factors for poor outcome include kidney disease, frequent flares, infections, neuropsychiatric manifestations – Lower physical and psychosocial than healthy children 13 of 46
  14. 14. Systemic Lupus Erythematosus • Treatment – Hydroxychloroquine – Azathioprine – Glucocorticoids – NSAID – Chemotherapeutic agents • Methotrexate, Cyclophosphamide – IVIG – Biologicals - rituximab 14 of 46
  15. 15. Dermatomyositis• Autoimmune disease• Primarily affects skin and muscle• Incidence: under age 16, affects 3,000-5,000 children in U.S. 3 new cases per year/million people• Average age of onset is 7 (ages 5 – 10)• Found worldwide, more prevalent in North America• May be more common in African-Americans• Adult version presents age 50 15 of 46
  16. 16. Dermatomyositis• Etiology idiopathic• Combination of genetics and infection• May be partially inherited (genetic predisposition to acquire the disease)• Not contagious• More common in females than males 16 of 46
  17. 17. Dermatomyositis• Signs and symptoms: – Fever – Fatigue – Skin rash – Muscle weakness – Pain – Lung disease – Joint contractures 17 of 46
  18. 18. DermatomyositisHeliotrope rash http://www.pediatricsconsultantlive.com/pedsquiz/content/article/1803329/1691415 Accessed on 9/20/11 18 of 46
  19. 19. Dermatomyositis• Diagnosis: – Clinical diagnosis – Increased CPK, aldolase, SGOT – MRI of involved muscles – Muscle biopsy 19 of 46
  20. 20. Dermatomyositishttp://www.learningradiology.com/caseofweek/caseoftheweekpix2006/cow207lg.jpg Accessed on 9/20/11 20 of 46
  21. 21. Dermatomyositishttp://www.nlm.nih.gov/medlineplus/ency/imagepages/1866.htm Accessed on 9/20/11 21 of 46
  22. 22. Dermatomyositis• Treatment: – Prednisone – Methotrexate – Hydroxychloroquine – Cyclosporine – IVIG – Mycophenolate 22 of 46
  23. 23. Dermatomyositis• Prognosis: – Most children go into remission within 2 years – Pulmonary involvement heralds poor prognosis – Increased risk for malignancy – Joint contractures are a long term complication – Some do not respond well to medications 23 of 46
  24. 24. Scleroderma• Autoimmune disease• Normal tissues replaced with dense, thick scar tissue• Skin most common site• Kidneys, heart, lung, GI tract 24 of 46
  25. 25. Scleroderma• 5,000 – 7,000 children in U.S.• Only 1.5% develop disease before age 10• 7% develop disease between age 10 to 19• 2/3 are female• Immune system triggers other cells to produce excessive collagen• Idiopathic• Not contagious 25 of 46
  26. 26. Pediatric Scleroderma• Two types: – Localized scleroderma • Skin (linear and morphea) – Systemic scleroderma • multiple organs 26 of 46
  27. 27. Pediatric Scleroderma• Localized Scleroderma: – Most common form in children – Usually skin only, occasionally underlying muscle – Linear type appears as a band usually on extremities, may limit motion when crosses a joint – Morphea type - patches, waxy skin with an ivory or white color – Both appear white with purple borders 27 of 46
  28. 28. Scleroderma• Signs and symptoms: – Loss of stretch in skin – Discoloration of skin – Thinning of the skin – Contractures of fingers – Joint inflammation – Raynaud’s phenomenon – Ulcers on fingertips – Dysphagia and other GI tract problems – Fatigue, muscle weakness 28 of 46
  29. 29. Sclerodermahttp://www.skinpatientalliance.ca/en/skin-conditions-diseases/connective-tissue-disorders Accessed on 9/20/11 29 of 46
  30. 30. Scleroderma• Diagnosis: – Clinical diagnosis – Skin biopsy – Autoimmune blood testing – Swallow study – Lung testing – Cardiac echo 30 of 46
  31. 31. Linear Scleroderma http://bjo.bmj.com/content/91/10/1311/F1.large.jpg Accessed on 9/20/11 31 of 46
  32. 32. Scleroderma• Treatment: – Prednisone – Methotrexate – NSAID – Environmental – Physical therapy 32 of 46
  33. 33. Scleroderma• Prognosis: – Chronic and slowly progressive – Months to years – Localized vs. systemic – May stabilize without progression for years 33 of 46
  34. 34. Juvenile Idiopathic Arthritis• Clinical manifestations: – Fever – Rash – Serositis – Joint involvement pain, swelling, stiffness, limping – Growth delay/weight loss – Psoriasis – Uveitis, eye pain, vision disturbances 34 of 46
  35. 35. Juvenile Idiopathic Arthritishttp://www.google.com/imgres?q=juvenile+idiopathic+arthritis&hl=en&sa=X&rlz=1R2ADFA_enUS410&tbm=isch&prmd=imvnsb &tbnid=27oK6oBuClFabM:&imgrefurl=http://www.isteroids.com/blog/canakinumab-effective-for-systemic-juvenile- idiopathic- arthritis/&docid=L5cA1hDwO1EF4M&w=200&h=114&ei=gwN5TvKEJ8Watwey0cT2Dw&zoom=1&biw=1440&bih=730&ia ct=rc&dur=225&page=1&tbnh=91&tbnw=160&start=0&ndsp=20&ved=1t:429,r:12,s:0&tx=89&ty=61) Accessed on 9/19/11 35 of 46
  36. 36. Juvenile Idiopathic Arthritis• Diagnosis: – >6 weeks of arthritis – Less than 16 years of age – Unknown cause R/O Lyme’s, infection, Kawasaki’s Disease, immunodeficiency• Epidemiology: – Most common childhood chronic rheumatic disease – Incidence: 2-20 cases/100,000 – Prevalence: 16-150/100,000 – 0.07–4.01 per 1,000 children worldwide 36 of 46
  37. 37. Juvenile Idiopathic Arthritis (ROY—CLARIFY WEBSITE REFERENCE FROM ORIGINAL SLIDE #38) Accessed on 9/19/11 http://trialx.com/curetalk/wp-content/blogs.dir/7/files/2011/05/diseases/Juvenile_Idiopathic_Arthritis-1.jpg Accessed on 9/20/11 37 of 46
  38. 38. Juvenile Idiopathic Arthritis Drug Des Devel Ther. 2011; 5:61-70• Systemic 5-10• Oligoarthritis 40-50 – Persistent 25-35 – Extended 15-20• Polyarthritis 30-40 – Rheumatoid factor neg 25-35 – Rheumatoid factor pos 5• Psoriatic arthritis 5-10• Other 15-20 38 of 46
  39. 39. Juvenile Idiopathic ArthritisIMAGE 1: http://images.rheumatology.org/image_dir/album75693/md_99-06-0019.tif.jpgIMAGE 2:http://www.google.com/imgres?imgurl=http://www.ajronline.org/content/vol185/issue2/images/large/00_04_1385_07a.jpeg&imgrefurl=http://www.ajronline.org/cgi/content-nw/full/185/2/522/FIG17&usg=__M1LQ2tyC2JT86hM8wz41fj-SGpk=&h=1800&w=1037&sz=257&hl=en&start=23&zoom=1&tbnid=aRD8JZwu9_P_6M:&tbnh=150&tbnw=86&ei=e-pfTqadMYi3twf8v6imCw&prev=/search%3Fq%3Djuvenile%2Bidiopathic%2Barthritis%26start%3D21%26hl%3Den%26sa%3DN%26rls%3Dcom.microsoft:en-us%26rlz%3D1I7ADRA_en%26tbm%3Disch%26prmd%3Divnsb&itbs=1) Accessed on 9/20/11 39 of 46
  40. 40. Juvenile Idiopathic Arthritis• Pathogenesis: – Multifactorial autoimmune – Environmental and genetic factors – Polygenomic – European ancestry may be a risk factor 40 of 46
  41. 41. Juvenile Idiopathic Arthritis• Treatment: – Non-steroidal – Steroids – Disease-modifying anti-rheumatic drugs • Methotrexate blocks folate interaction so decreased DNA, RNA, proteins • Sulfasalazine blocks production of proinflammatory prostaglandins • Leflunamide blocks pyrimidine production, anti-proliferative – Biological Modifying agents 41 of 46
  42. 42. Juvenile Idiopathic Arthritis• Biological Modifying agents: – Etanercept (Enbrel) synthetic protein binds to TNF alpha, prevents TNF from binding to cells – Infliximab (Remicade) monoclonal antibody to TNF – Adalimumab (Humira) human monoclonal antibody against TNF – Abatacept (Orencia) fusion protein blocks stimulation of T cells – Anakinra (Kineret) interleukin-1 receptor antagonist – Tocilizumab (Actemra) monoclonal antibody against interleukin-6 – Rituximab (Rituxan) monoclonal antibody against CD20 positive B cells 42 of 46
  43. 43. Juvenile Idiopathic Arthritis• Prognosis: – Goal is clinical remission – Definition of remission: No active arthritis, fever, rash, serositis, lymphadenitis, uveitis, normal CRP and sed rate, no disease activity for 6 months 43 of 46
  44. 44. Long-Term Complications • Functional limitation • Osteopenia • Nutritional deficiencies • Chronic pain • Psychological distress • Infection • Delayed puberty • Cancer? • Death 44 of 46
  45. 45. Conclusion• Collagen vascular diseases are rare in children• More common in females than males• Not contagious• Etiology largely unknown but genetics and environment may play a role• New biologic agents may improve the outcome for these patients 45 of 46
  46. 46. Q&AThank you for attending! QUESTIONS? 46 of 46

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