2. One disease entity which explains all the signs and symptoms

3. Staff Conference Cherie Marie A. Tecson, M.D. 18 July 2008 R.C.

4. General Data 9 year old male Filipino Roman Catholic Chief complaint: Joint pain

5. History of Present Illness 2 years PTC (+) joint pains, swelling and warmth, migratory, for 2-3 days (+) fever 7 months PTC (+) chest pain (+) easy fatigability (+) persistent joint pains, swelling and warmth 3 months PTC (+) easy fatigability (+) 2-pillow orthopnea (+) joint pains, swelling and warmth 1 month PTC Persistence of joint pains, swelling and warmth

6. Review of Systems (+) weight loss, ~10% (-) oral ulcers (-) skin lesions (-) blurring of vision Past Medical History (+) Measles at 1 yo Family Medical History (-) similar illness

7. Physical Examination

9. Dynamic precordium Apex beat at the 5 th left intercostal space, midclavicular line (+) grade 3/6 holosystolic murmur at the apex (+) grade 2/6 systolic murmur over the left parasternal border

10. Physical Examination

11. Initial Impression Congestive heart failure functional class I secondary to Acute Rheumatic Fever with Severe Carditis

12. Course in the OPD Problem 1: Acute Rheumatic Fever with Severe Carditis Aspirin, 300mg/tab, 2-2-2-1 Captopril (1.3) 25mg/tab, ½ tab BID

15. 2d Echo

16. Course at the OPD Problem 1: Acute Rheumatic Fever with Severe Carditis Rheumatic Heart Disease Two weeks after initial consult, (+) persistent joint pains Ibuprofen 500mg/cap, 1 cap TID Nonreactive RA factor Negative ANA

17. Course at the OPD 2) Chronic Arthritis (+) migratory, polyarticular Not relieved by Aspirin and Ibuprofen (+) intermittent fever during attacks RA factor: nonreactive ANA factor: negative

18. Salient Features 9 year old male Chronic arthritis Treated as a case of RHD No resolution of joint pains

19. Objectives 1) To formulate an approach to the diagnosis of a patient with joint pains and cardiac disease 2) To differentiate the clinical and laboratory findings of JIA and RF 3) To discuss the management plan of a patient with JIA and RF

20. Approach to Diagnosis

21. Systemic Lupus Erythematosus Episodic, mutisystem, autoimmune disease Inflammation of blood vessels and connective tissue (+) ANA, antibodies to dsDNA Diagnosis is clinical and supported by laboratory abnormalities Cassidy, J., Petty, R., Laxer, R., Lindsley, C. Textbook of Pediatric Rheumatology. Elsevier Saunders. Philadelphia, 2005.

22. Disease Entity Characteristic Arthritis Cardiac Involvement Other Features SLE Small joints of the hands, wrists, elbows, shoulders, knees, ankles Short in duration Myalgia or muscle weakness characteristic Pericarditis (80%) Rarely accompanied by cardiomegaly Classic lesion: Libman-Sacks endocarditis Malar rash, Discoid rash, Photosensitivity, Oral Ulcers, Serositis, Renal, Neurologic, Hematologic Immunologic disorder, ANA Cassidy, J., Petty, R., Laxer, R., Lindsley, C. Textbook of Pediatric Rheumatology. Elsevier Saunders. Philadelphia, 2005. Crozier IG, Li E, Milne MJ and Nichols G : Cardiac involvement in systemic lupus erythematosus detected by echocardiography. Am J Cardiol, 65:1145, 1990.

23. Ankylosing Spondylitis Chronic inflammatory disease of the axial and peripheral skeletons Radiologic evidence of bilateral inflammation of sacroiliac joints Cassidy, J., Petty, R., Laxer, R., Lindsley, C. Textbook of Pediatric Rheumatology. Elsevier Saunders. Philadelphia, 2005.

24. Disease Entity Characteristic Arthritis Cardiac Involvement Other Features AS Buttocks, thighs, groin, heels or around shoulders Spontaneous resolution Joint involvement <4 Seronegativity to rheumatoid factor Uncommon Aortic insufficiency Aortitis Conduction disturbance Cardiomyopathy Altered diastolic function Family history, enthesitis, radiologic evidence of sacroiliac joints Cassidy, J., Petty, R., Laxer, R., Lindsley, C. Textbook of Pediatric Rheumatology. Elsevier Saunders. Philadelphia, 2005. Gragham DC and Smythe HA : The carditis and aortitis of ankylosing spondiylitis. Bull Rheum Dis, 9:171- 1958.

25. Behçet’s Disease Relapsing systemic vasculitis that is rare in children Unknown cause Usual course is of exacerbations and remissions Cassidy, J., Petty, R., Laxer, R., Lindsley, C. Textbook of Pediatric Rheumatology. Elsevier Saunders. Philadelphia, 2005. Kliegman, R., Behrman, R., Jenson, H., Stanton, B. Nelson’s Textbook of Pediatrics, 18 th Edition. Saunders, 2007.

26. Disease Entity Characteristic Arthritis Cardiac Involvement Other Features Behçet’s disease Acute onset Recurrent Asymmetric Polyarticular Large joints Uncommon Pericarditis Myocarditis Arrhytmias Triad of aphthous stomatitis, genital ulceration, uveitis, superficial thrombophlebitis Higashihara M, Mori M, Takeuchi A, et. al. : Myocarditis in Behçet's disease a case report and review of the literature. J Rheumatol, 9:630, 1982 James DG and Thomson A : Recognition of the diverse cardiovascular manifestations in Behçet's disease. Am Heart J, 13:45, 1982. Cassidy, J., Petty, R., Laxer, R., Lindsley, C. Textbook of Pediatric Rheumatology. Elsevier Saunders. Philadelphia, 2005.

27. Acute Rheumatic Fever Most common form of acquired heart disease Accounts for ~50% of all cardiovascular disease, ~50% of all cardiac admissions in many developing countries Kliegman, R., Behrman, R., Jenson, H., Stanton, B. Nelson’s Textbook of Pediatrics, 18 th Edition. Saunders, 2007.

28. Acute Rheumatic Fever

29. Jaccoud’s Arthritis Rare form of nonerosive, deforming arthropathy ascribed to Rheumatic Fever Subluxation and ulnar deviation at the metacarpophalangeal joints Pathognomonic "hook" lesion on the radial side of the affected metacarpal heads Zvaifer NJ: Chronic post-rheumatic fever (Jaccoud’s) arthritis. N. Engl J Med 267: 10-14, 1962 Cosh, J: The heart and the rheumatic diseases. Rheum. Phys. Med., 1972, 11, 267.

30. Disease Entity Characteristic Arthritis Cardiac Involvement Other Features Acute Rheumatic Fever Large joints Migratory, additive Self-limiting course Swelling, warmth, erythema and pain Rarely lasts more than 1 week in any one joint Hallmark: sensitivity to salicylates Usually occurs within one week of arthritis Involves all layers of the heart Hallmark lesion: rheumatic carditis, valvular insufficiency Syndenham’s Chorea Erythema marginatum Subcutaneous nodules Fever Elevated ESR and CRP Prolonged PR interval Cassidy, J., Petty, R., Laxer, R., Lindsley, C. Textbook of Pediatric Rheumatology. Elsevier Saunders. Philadelphia, 2005. Kliegman, R., Behrman, R., Jenson, H., Stanton, B. Nelson’s Textbook of Pediatrics, 18 th Edition. Saunders, 2007.

31. Review of Signs and Symptoms Carditis Arthritis Nonreactive RA factor Negative ANA Persistently elevated ASO titers Elevated CRP 2D echo: LAE, LVE, thickened non- coaptating mitral valve with severe MR, mild AR Failure to respond to salicylates

32. Juvenile Idiopathic Arthritis Arthritis persistent for at least 6 weeks in a child <16 years of age Classification is made at 6 months after diagnosis into one of seven disease categories Cardiac involvement is found in 4.5% of cases Petty RE, Southwood TR, Manners P, Braum J, Glass DN, Goldenberg J, et al, and the International League of Associations for Rheumatology. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 2004; 31:390–2.

33. Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med. 2001;344:907-916.

34. Does our patient have JIA or RHD

35. Cardiac involvementJIARHD Most common lesionPericarditis (7-10%)Valvular endocarditis 2D EchoPericardial effusion (50%)Hallmark: mitral insufficiency (76%) EpidemiologyCommon in seronegative patients with systemic form of disease or seropositive patients with severe destructive articular disease Cardiac involvement is essential in diagnosis SymptomatologyUsually asymptomaticSymptomatic Valve involvementInvolvement of mitral valve in seronegative, polyarticular disease is rare, multivalvular involvement rarely seen Multivalvular involvement, usually mitral and aortic disease (97%) JIA or RHD? Svetsson, H., Bjorkhem, G., Elborgy, R. Cardiac involvement in juvenile rheumatoid arthritis. Acta Pediatr Scand. 1983, 72, 345-350. Bernstein, B., Takahashi, M., Hanson, V. Cardiac involvement in juvenile rheumatoid arthritis. J Pediatr 1974; 85 313-317.

36. JIA or RHD? ArthritisJIARHD Joint involvementCan involve small jointsRarely involves small joints LaboratoryAbsence of antistreptococcal antibodies High or rising titer of streptococcal antibodies DurationLong durationResolves spontaneously Response to SalicylatesAbsent or less dramaticUsually occurs in 48 hrs ConsequenceOsteoporosis, contracture, wasting, neck stiffness, involvement of small joints No residual damage PainMild to moderateUsually severe EffusionMay be markedUsually mild ErythemaUsually absentCommon CourseProtracted, recurrentResolves spontaneously

37. JIA or RHD? “It is possible for a patient with chronic rheumatic heart disease to develop rheumatoid arthritis by coincidence at a later date, but there is no evidence for an association between the two disorders.” Zvaifer NJ: Chronic post-rheumatic fever (Jaccoud’s) arthritis. N. Engl J Med 267: 10-14, 1962 Cosh, J: The heart and the rheumatic diseases. Rheum. Phys. Med., 1972, 11, 267. Grahme, R., Mitchell, A. B. S., and Scott, J. T. (1970). Chronic Post-rheumatic Fever (Jaccoud's) Arthropathy. Ann. rheum. Dis., 29, 622.

39. Treatment of RHD Benzathine Penicillin every 21 days to control activity Anticongestive measures Balloon valvuloplasty Surgical replacement or repair of affected valves Cassidy, J., Petty, R., Laxer, R., Lindsley, C. Textbook of Pediatric Rheumatology. Elsevier Saunders. Philadelphia, 2005. Kliegman, R., Behrman, R., Jenson, H., Stanton, B. Nelson’s Textbook of Pediatrics, 18 th Edition. Saunders, 2007.

40. Treatment of JIA Anti-inflammatory medications Immunomodulatory medications Physical, occupational therapy Occasional need for surgery Nutritional support Psychosocial and educational partnership Hashkes, P., Laxer, R. Medical Treatment of Juvenile Idiopathic Arthritis. JAMA, 2000, 23, 13. Kliegman, R., Behrman, R., Jenson, H., Stanton, B. Nelson’s Textbook of Pediatrics, 18 th Edition. Saunders, 2007.

41. Treatment of JIA Objectives of Treatment of Chronic Arthritis in Children Immediate Relieve discomfort Preserve function Prevent deformities Control inflammation Long-term Minimize side effects of disease and treatment Promote normal growth and development Rehabilitate Educate Kliegman, R., Behrman, R., Jenson, H., Stanton, B. Nelson’s Textbook of Pediatrics, 18 th Edition. Saunders, 2007.

42. Course at the OPD Juvenile Idiopathic Arthritis Started on the following meds: 1) Naproxen 250mg/tab, 1 tab BID 2) Methotrexate 7.5mg/wk, Folic Acid Noted relief of joint pains

43. Additional Plans Periodic slit-lamp ophthalmologic examinations Dietary evaluation and counselling Physical and occupational therapy Intensive monitoring of cardiac function Address hematologic consequences

44. Prognosis Juvenile Idiopathic Arthritis Outcome is generally good 70-90% will have a satisfactory outcome without serious disability 25 to 50% will need surgery Delay in referral associated with a poorer functional outcome Overall death rate is 0.4 to 2% Fukinawa, S., Okuni, M. A nationwide surveillance study of rheumatic diseases among Japanese children. Acta Paedriatica Japan 39: 242-244, 1997 Hashkes, P., Laxer, R. Medical Treatment of Juvenile Idiopathic Arthritis. JAMA, 2000, 23, 13.

45. Prognosis Rheumatic Heart Disease Major morbidity associated exclusively with degree of cardiac damage Mortality occurs predominantly in patients with pancarditis Cardiac surgery has alleviated crippling effect of this complication *Tompkins DG, Boxerbaum B, Liebman J: Long-term prognosis of rheumatic fever patients receiving regular intramuscular benzathine penicillin. Circulation 45: 543-551, 1972

46. In Conclusion Close monitoring is essential Cardiac manifestations of JIA are rare, asymptomatic, and involves single valves, while its arthritis does not respond to salicylates Two disease entities can exist in one patient, and both should be addressed in terms of management

47. Thank you!