Often we have to look beyond to see what we are supposed to

1. Often we have to look beyond to see what we are supposed to�

2. L. Nandini Moorthy, MD MS Pediatric Rheumatology 2009 Pediatric Board Review Course

3. Case 1: One swollen joint A three year old Caucasian girl presents with two-month history of swollen left knee No history of fevers No rash No weight loss No other joints are involved CBC and differential within range CMP, ESR, CRP, Ig within range LDH within range ANA titer 1:320 RF negative

4. JIA Definition Objective arthritis in = 1 joint(s) for = six weeks Children = 16 years = 6 mo necessary to examine the clinical features [exception: SoJIA]

5. Oligo-articular onset JIA ~Pauciarticular JIA (PaJIA) Commonest subtype (� 50%) 1-5 years of age Girls > boys Arthritis in = four joints Large joints-knees, ankles, elbows Usually spares hips Rarely affects wrists, & small joints of hands & feet

7. Differential Diagnosis of PaJIA Other causes of oligoarthritis: Reactive arthritis Lyme arthritis Septic arthritis Trauma Neoplastic disease Dactylitis (< 4 ?psoriatic arthritis)

8. PaJIA-Course and Complications Benign course, good prognosis Recurrences ~ 20% May progress to extended-oligoarticular arthritis requiring aggressive treatment Discrepancy in limb lengths Persistent inflammation Orthotic/surgical correction Fixed flexion contractures PT & OT

10. Case 2: Many swollen joints Consider the case of a 6 year old girl who presents with multiple swollen joints, morning stiffness and mild anemia. You must think of Polyarticular JIA.

11. Extended Oligoarticular JIA~ Polyarticular JIA (PoJIA) 30% -40% of JIA Girls > boys Bimodal peaks: 2-5 years & 10-14 years Insidious onset, sometimes acute, with progressive involvement of >/=5 joints in the first 6 months In younger children, onset is usually pauciarticular AM stiffness and fatigue May have low-grade fever Arthritis intermittent or persistent RF+ve or RF-ve Small joints of hands & feet Tenosynovitis of flexor tendon sheaths

13. PoJIA Labs may be normal or suggest an inflammatory state Anemia High ESR Hypergammaglobulinemia Leukocytosis 5-10% RF + 40-50 % ANA + [Cassidy, 2001] Late-onset PoJIA Subset of RF+ girls mimics adult RA Chronic course into adulthood

14. PoJIA-Differential diagnosis Infectious causes of polyarthritis Viral Septic Lyme Other Serum sickness Other rheumatic diseases Inflammatory Bowel Disease (IBD) Systemic Lupus Erythematosis (SLE) Dermatomyositis Sarcoidosis Scleroderma Spondyloarthropathies (enthesitis, axial involvement) Rarer causes Malignancy Other immunodeficiences

15. PoJIA-Course & Complications Guarded prognosis Adolescent girls RF+ with late-onset, rapidly progressive erosive arthritis �often have RA like disease as adults Early involvement of small joints of hands & feet Persistent inflammation Subcutaneous nodules RF + Destructive hip disease among other joints & eventual disability Contractures & ankylosis Short stature (more in children) Often require joint replacements Chronic uveitis � 5% [Cassidy, 2001]

19. SoJIA- Course & Complications Systemic features may persist for 4-6 months with varying degrees of joint involvement Prognosis Complete recovery Polyarticular pattern Persistent inflammation &/ or chronic destructive arthritis Long standing SoJIA Micrognathia, c-spine fusion and destructive hip disease Short stature & FTT Uveitis - rare Amyloidosis -rare in the US Macrophage Activation Syndrome More common in children

20. Gastrointestinal diseases IBD Crohns UC ASCA, ANCA Celiac disease (TTG, Endomysial, Gliadin ab)

21. Enthesitis-related arthritis Spondyloarthropathy Commonly complain of: Pain in the back & heel Morning stiffness Arthritis & /or enthesitis with any 2 of the following: Sacroiliac joint tenderness, Inflammatory spinal pain or both Positive family history Acute anterior uveitis Arthritis onset in boys > 8 yrs HLA-B 27 (higher likelihood of developing debilitating ankylosing spondylitis)

23. QUESTIONWhat screening test will you send a 14 yo male teen withHLA B 27 +ve arthritis?

24. Consider HLA B 27 associated Aortitis and AR HLA B27 is a risk factor for endocardial and myocardial damage in patients with B27-JA, even in the presence of only mild articular disease. Patients with B27-JA should be screened by color-flow Doppler echocardiography for the presence of aortic regurgitation and myocardial inflammation with increased mitral blood flow velocity at atrial contraction due to impaired myocardial relaxation. Regular monitoring may be required. These patients might benefit from early pharmacologic intervention by afterload reduction (i.e., with ACE inhibitors). All patients with juvenile arthritis and Endocarditis prophylaxis should be instituted when necessary.

25. Psoriatic Arthritis Arthritis & psoriasis Or arthritis with at least two of the following: Dactylitis Nail abnormalities Family history of psoriasis. May run a course ~PoJIA & require aggressive treatment Associated with uveitis

27. Pathogenesis Cytokine dysequilibrium -- increased IL-1, TNF

28. KEY CONCEPTS- JIA Characteristics NOT typically associated with the arthritis of JRA------severe pain, inability to weight bear, nocturnal wakening, and hot, erythematous joints. Uveitis is the often asymptomatic inflammation of the uveal tract, most commonly seen in 20-30% of ANA positive, pauciarticular-JIA girls Macrophage Activation Syndrome is a complication seen in systemic-JIA, resulting in DIC, encephalopathy, respiratory distress syndrome, renal failure and worsening serositis. Bone marrow biopsy may reveal the presence of histiocytes actively phagocytosing red cells and platelets Ref: Mead Johnson Board Tutor

29. Remember!!! If a JRA patient has an autoantibody, it confers a worse prognosis Pauci-JRA + ANA = uveitis risk Poly-JRA + rheumatoid factor (RF) =erosive adult RA (REF: Mead Johnson Board Tutor)

30. Management NSAIDS Disease Modifying Agents (DRUGS) Joint Replacement Physical and Occupation therapy Ophthalmologic monitoring Social support, education and family counseling

31. NSAIDS Naproxen Nabumetone Diclofenac Indomethacin Ibuprofen, Naprosyn, Celebrex and Tolmentin are approved for children Used for all types Usually sufficient for PaJIA, mild spondyloarthropathy & mild cases of other types. Follow LFTs, UA Watch for GI, skin and psychiatric symptoms

32. Disease Modifying Anti-Rheumatic Drugs (DMARD) Novel Biologics Etaanercept Adalimumab Abatacept Infliximab I/articular steroid injection Steroids

33. NOVEL BIOLOGICS Etanercept (Enbrel) is a recombinant fusion dimeric protein (sTNFR) Infliximab (Remicade) -Monoclonal Anti-TNF antibody (murine component) Combination of Etanercept and Methotrexate Adalimumab (Humira): Fully humanized TNF alpha Mab with human derived heavy and light chain variable regions and human IgG constant regions. Anakinra (Kineret): IL-1 Receptor antagonist blocks cellular activation Abatacept (Orencia) Adverse events � TB, Fungal, VZV

34. Not every bird is this easily identifiable�

35. The swollen joint

38. Work-up All three children have an unremarkable exam except for arthritis Complete blood count and differential, electrolytes, blood urea nitrogen, creatinine, and urine analysis are within normal limits Erythrocyte sedimentation rate ranges from 30-40 mm/hour The X-rays of the respective joints shows only soft tissue swelling They all started non-steroidal anti-inflammatory drugs

39. Diagnosis and management Patient 3 tested positive for Lyme Western Blot IgG; Treated with oral Doxycycline for Lyme disease. Patient 4 had elevated Antistreptolysin-O titre and anti-strep-DNAse B antibodies and had normal electrocardiogram and echocardiogram; Was started on oral Penicillin treatment and prophylaxis for Post-Streptococcal Reactive Arthritis. Patient 5 had stool culture positive for Salmonella; Treated with Amoxicillin for Reactive Salmonella Arthritis.

40. Infection-related arthritis Viral: Ebstein Barr Virus, Rubella, Parvovirus, Hepatitis, Mumps, Herpes, HIV, Echovirus Bacterial: Poststrepococcal arthritis, Rheumatic fever, Gonococcal, Chlamydia, Yersinia, Salmonella, Shigella, Campylobacter, Mycoplasma, Clostridium Lyme disease Septic, Tuberculosis, Fungal, Protozoal Treatment of underlying disease and NSAIDS

41. Polyarticular disease

42. Rash, pustule, and bulla Gonorrhea: rash, pustule, and bulla The rash of disseminated gonococcal infection can occur on any exposed portion of the skin. Since there are usually few gonococcal skin lesions, they must be specifically sought since they can be easily missed on cursory examination. The triad of arthritis, cutaneous lesions (vesicopustules and hemorrhagic lesions), and fever may also be seen in meningococcemia as well as in gonococcemia. Culture of these lesions may be positive for the inciting organism. Left, A pustule with a necrotic center is surrounded by inflammation. Right, A large hemorrhagic blister (bulla), a less common cutaneous lesion, is shown. #9118020 Gonorrhea: rash, pustule, and bulla The rash of disseminated gonococcal infection can occur on any exposed portion of the skin. Since there are usually few gonococcal skin lesions, they must be specifically sought since they can be easily missed on cursory examination. The triad of arthritis, cutaneous lesions (vesicopustules and hemorrhagic lesions), and fever may also be seen in meningococcemia as well as in gonococcemia. Culture of these lesions may be positive for the inciting organism. Left, A pustule with a necrotic center is surrounded by inflammation. Right, A large hemorrhagic blister (bulla), a less common cutaneous lesion, is shown. #9118020

43. Reactive arthritis Non-specific arthritis after Reactive arthritis is a sterile arthritis which is preceded by a gastrointestinal or genitourinary infectious with arithrogenic organisms (Chlamydia, Shigella, Salmonella, Yersinia or Campylobacter) Berlin Diagnostic Criteria Typical peripheral arthritis PLUS Evidence of preceding illness Exclude juvenile idiopathic arthritis and other arthritis of known causes Usually clinical features characteristic of primary infection Reiter�s syndrome is a form of reactive arthritis, complicated by uveitis, conjunctivitis, and urethritis or cervicitis Remember Mneumonic: Can�t See. Can�t Pee. Can�t Climb a Tree

44. IBD associated arthritis

45. To recap�. HLA B 27 associations Spondyloarthropathies Ankylosing Spondylitis Psoriatic disease Reactive arthritis (GU/GI-related infections/Reiters) Acute anterior iritis IBD Cardiac (Aortic)

46. ACUTE RHEUMATIC FEVER May occur 2-3 weeks post-infection, to as long as 2-3 months after strep pharyngitis (as in Syndenham�s chorea) Review Jones Criteria Review prophylaxis NEED TO KNOW THIS CONDITION IN DETAIL!!!!!!!

47. Case 6: A teenage Asian girl with 3 month history of malar rash She also presented with: Palatal ulcers Photosensitivity Fatigue Myalgias and arthralgias Mild anemia ANA titre of 1:320

49. Some facts Incidence: 0.36 -0.9 per 100,000 per year Prevalence: <1- 4.5% of patients in pediatric rheumatology Age: Childhood onset occurs in 15-17 %, Rare (but still occurs) below 5 years Sex: More in females (Male:Female ratio 1:4.5) In younger age group, the ratio is almost equal Race: African-American, Hispanic, Asian, Native Higher incidence/severity of renal/CNS lupus in pediatric onset Episodic, Chronic, Fluctuating Autoantibodies

50. Clinical presentation PRESENTATION - fever, fatigue, weight loss, irritability SKIN Malar rash-Fixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds Discoid rash-Erythematous raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur in older lesions Other types of rash, nail involvement, hair loss (alopecia)

52. Renal Clinical nephritis occurs in 75% of children; may present with blood in the urine (hematuria- cannot always see with your eye-need to get urine test), watch for edema and high BP Renal disorder a) Persistent proteinuria greater than 0.5 grams per day or greater than 3+ OR b) Cellular casts--may be red cell, hemoglobin, granular, tubular, or mixed

54. Serositis a) Pleuritis--convincing history of pleuritic pain or rubbing heard by a physician or evidence of pleural effusion OR b) Pericarditis--documented by ECG or rub or evidence of pericardial effusion Cardiac - inflammation of different parts of the heart (pericarditis, myocarditis,valuvilitis), Myocardial infarction (Libman Sacks endocarditis) Lungs Pancreatitis

55. Central Nervous System 20-40% of affected children, depression, difficulty in concentrating, cognitive impairment (~52% of children), lupus headache, seizures etc. a) Seizures--in the absence of offending drugs or known metabolic derangements; e.g., uremia, ketoacidosis, or electrolyte imbalance OR b) Psychosis--in the absence of offending drugs or known metabolic derangements, e.g., uremia, ketoacidosis, or electrolyte imbalance

56. Antiphospholipid antibody syndrome Autoimmune disorder (persistent antiphospholipid antibodies, e.g., anticardiolipin anti- body, lupus anticoagulant) Thromboembolic phenomenon (DVT, stoke, MI) or pregnancy morbidity Classified as primary (no underlying disorder) or secondary (most commonly seen in SLE) Treatment is life-long anticoagulation

57. Laboratory exam General Hematologic disorder Hemolytic anemia--with reticulocytosis OR Leukopenia--less than 4,000/mm<>3<> total on 2 or more occasions OR Lyphopenia--less than 1,500/mm<>3<> on 2 or more occasions OR Thrombocytopenia--less than 100,000/mm<>3<> in the absence of offending drugs Evidence of immune dysfunction Bleeding and clotting abnormalities Liver functions Sedimentation rate (inflammation) Blood and protein in urine

58. Low complements- C3, C4 Autoantibodies -ANA, Anti-ds-dna, ENA Antiphospholipids Immunologic disorder a) Positive LE cell preparation OR b) Anti-DNA: antibody to native DNA in abnormal titer OR c) Anti-Sm: presence of antibody to Sm nuclear antigen OR d) False positive serologic test for syphilis known to be positive for at least 6 months and confirmed by Treponema pallidum immobilization or fluorescent treponemal antibody absorption test

59. The notorious ANA! Antinuclear antibody (ANA) positive in �all� pediatric SLE patients Sensitive but not very specific Positive ANA also commonly see in pauci-JRA, as well other autoimmune disease (dermatomyositis, scleroderma) 5�10% normal children have positive ANA (usually low titer < 1:160)

60. ANA Fluorescence Patterns Rim (peripheral) SLE Homogeneous (diffuse) Drug-induced LE; SLE Nucleolar Scleroderma  Speckled SLE Sjogren�s; MCTD; Scleroderma

61. Approach to management General Routine/flare-worsening Team approach Adequate rest Sun-protection Immunizations Prompt management of infection Subspeciality visits Call doctor prior to any procedure-may need extra antibiotics or steroids Evaluate mood (patients may get depressed!!!)

64. Prognosis Infections, steroid complications, atherosclerosis New treatments and better survival Survival has improved in the past 20 yrs 10-year survival approaches 90% Extent of organ involvement (renal, central nervous system), apparent vasculitis, and multisystemic character of the disease Sepsis (severe life-threatening infection) is the commonest cause of death Atherosclerosis Important determinants: families� ability to cope, socioeconomic status, compliance, teen-related issues, contraception

66. Neonatal lupus erythematosus: rashA 22-year-old woman with systemic lupus erythematosus delivered a healthy child who at 2 weeks of age developed the facial rash seen on the left. The photograph on the right shows the resolution of the rash 3 months later. Neonatal lupus is characterized by transient rashes, thrombocytopenia and neutropenia. These babies are also at risk for developing congenital heart block. The neonatal lupus syndrome is the effect of transplacental passage of maternal antibodies, most commonly anti-Ro. The mother in this case was positive for both anti-Ro and anti-La activity.Neonatal lupus erythematosus: rashA 22-year-old woman with systemic lupus erythematosus delivered a healthy child who at 2 weeks of age developed the facial rash seen on the left. The photograph on the right shows the resolution of the rash 3 months later. Neonatal lupus is characterized by transient rashes, thrombocytopenia and neutropenia. These babies are also at risk for developing congenital heart block. The neonatal lupus syndrome is the effect of transplacental passage of maternal antibodies, most commonly anti-Ro. The mother in this case was positive for both anti-Ro and anti-La activity.

69. Juvenile Dermatomyositis (JDM) Vasculitis frequent & often severe Calcinosis common in recovery phase Polymyositis uncommon Malignancy rare

70. Epidemiology Incidence: 0.5 per 100, 000/year ~20% Onset in childhood 4-10 years; Boys 6 years; Girls 6, 10 years F:M - 1.4:1 to 2.7:1; higher for >/=10yrs Widely distributed Blacks > Whites

71. Clinical features Constitutional: Fever 38-40C, easily fatigued, anorexia, malaise, wt loss MSKS: symmetric proximal- weakness of LE limb girdle; anterior neck flexors/back & abdo; Gowers Pelvic girdle- stairs, Trendelenburg- weak hip adductors Pathognomonic rashes such as Heliotrope (purple, puffy eyelids) and Gottron�s papules (scaly, red papules over knuckles). Almost all children have characteristic skin and muscle abnormalities DTRs usually nl Insidious onset more common, with progressive muscle weakness and pain over months, but acute onset in 1/3 of patients (possible pharyngeal/palatal involvement). May demonstrate positive Gower�s sign of proximal muscle weakness. Constitutional: Fever 38-40C, easily fatigued, anorexia, malaise, wt loss Parents: Child irritable, gross motor function alteration, milestone regression MSKS: symmetric proximal- weakness of LE limb girdle; anterior neck flexors/back & abdo Inability to hold head upright/maintain a sitting posture/stop walking/unable to dress/climb stairs Muscle pain or stiffness- moderate P/E-shoulder, hip, neck flexor, abdo; tender, edematous, indurated, unable to rise from supine position w/o rolling over, sitting, get out of bed w/o assistance, unable to squat, Gowers Pelvic girdle- stairs, Trendelenburg- weak hip adductors Severe (10%) distal musculature unable to move pharyngeal, hypopharyngeal, palatal, esophageal hypomotility- difficulty swallowing, dysphonia, palatal speech, nasal regurgitation- threat of aspiration DTRs usually nlConstitutional: Fever 38-40C, easily fatigued, anorexia, malaise, wt loss Parents: Child irritable, gross motor function alteration, milestone regression MSKS: symmetric proximal- weakness of LE limb girdle; anterior neck flexors/back & abdo Inability to hold head upright/maintain a sitting posture/stop walking/unable to dress/climb stairs Muscle pain or stiffness- moderate P/E-shoulder, hip, neck flexor, abdo; tender, edematous, indurated, unable to rise from supine position w/o rolling over, sitting, get out of bed w/o assistance, unable to squat, Gowers Pelvic girdle- stairs, Trendelenburg- weak hip adductors Severe (10%) distal musculature unable to move pharyngeal, hypopharyngeal, palatal, esophageal hypomotility- difficulty swallowing, dysphonia, palatal speech, nasal regurgitation- threat of aspiration DTRs usually nl

72. Clinical features Severe (10%) Threat of aspiration Calcinosis Other: Lymphadenopathy, arthritis, hepatosplenomegaly, dyspnea, dysphagia, non-specific rashes Visceral vasculitis (pancreatitis, melena, hematemesis, perforation)- poor prognosis--rapidly leads to death Lipodystrophy ~20% (assoc. with insulin resistance)

73. Diagnosis Diagnosis requires pathognomonic rash and two of the other criteria: 1. Symmetric weakness of proximal muscles 2. Characteristic cutaneous changes consisting of heliotrope discoloration of the eyelids with periorbital edema, and Gottron�s papules 3. Elevation of one or more skeletal muscle enzymes 4. EMG characteristic of myopathy and denervation 5. Muscle biopsy documenting histologic evidence of necrosis and inflammation

74. Diagnostic tests Leukocytosis, chronic anemia -unless GI bleed High CRP, ESR CPK, AST, Aldolase, LDH, ALT ANA ~10-85% MSA & MAA MRI T1-fibrosis, fat infiltration, atrophy T2-fat suppressed-edema/inflammation EMG Muscle biopsy Skeletal muscle perifascicular myopathy non-inflammatory capillaropathy disruption, degeneration, regeneration lymphocytic infiltrate -perimysium, perivascular Blood vessels Vasculitis and noninflammatory vasculopathy Other-Skin, GI, heart, kidney Skeletal muscle perifascicular myopathy non-inflammatory capillaropathy disruption, degeneration, regeneration lymphocytic infiltrate -perimysium, perivascular Blood vessels Vasculitis and noninflammatory vasculopathy Other-Skin, GI, heart, kidney

75. Treatment and Prognosis Presteroid-1/3 1/3 1/3 Steroids Hydroxychloroquine Methotrexate, Cyclosporine, Cyclophosphamide, Azathioprine, anti-TNF IVIG Plasmapheresis Supportive care/wound care PT, OT Calcinosis

76. Rheumatology Case 8 3 year old boy with a 3 day history of swollen, painful ankles Low grade fever Physical examination normal except for swelling, pain on motion, warmth, tenderness of both ankles Found on routine laboratory tests to have moderate hematuria, heavy proteinuria Developed maculopapular purpuric rash

77. Vasculitis

78. Vasculitis Characterized by size of vessel Large (Takayasu) Medium and small (Kawasaki, PAN) Small (SLE, JDM, serum sickness, hypersensitivity, HSP, neoplasm associated) Characterized by cellular infiltrate Giant cells (Takayasu, WG-ANCA) Neutrophils with nuclear debris (HSP)

79. 2nd most common type of vasculitides At least two of the following 4 should be present (ACR criteria 1990): Palpable purpura <20 years Bowel angina (Diffuse abdominal pain that is worse after meals/ bowel ischemia, bloody diarrhea) Wall granulocytes on biopsy

80. Henoch-Schonlein Purpura

81. Cutaneous manifestations occurs in 96-100% Palpable purpuric lesions Dependent/pressure bearing areas Acute, symmetric, erythematous, macular or urticarial Coalesce to form palpable purpura Occur in crops and change color from red to purple to brown

82. Clinical Features GI involvement (1-4 weeks) in 75% Abdominal pain (80%)- colicky, periumbilical: GI bleeding (secondary to gut vasculitis, +/- intussusception) Vomiting, abdominal distention Melena, hematemesis, ileus Submucosal bleeding Intussusception (3%), ileoileal (easily missed by barium enema) Mesenteric vasculitis Rare: pancreatitis, gallbladder hydrops, pseudomembranous colitis Genitourinary complications Musculoskeletal involvement (50-85%) -Arthritis (typically knees, ankles) Glomerulonephritis (hematuria, proteinuria, HTN). �

83. One-third of the children Life threatening/Serious is <10% Within one month of rash Spectrum: mild proteinuria/microscopic hematuria to NS, HTN, renal failure, acute nephritic syndrome Risk factors for renal disease:>7 years of age, persistent pupuric lesions, severe GI complaints, decreased factor XIII activity Focal or segmental mesangial proliferation to crescentric

84. High WBC Nl/high Platelets Normochromic anemia, guaic +ve stools High IgA, high IgA ANCA Low complement D/D- ITP, Acute post strep, SLE, Septicemia, DIC, HUS, Acute Hemorrhagic edema Opposite: IgA deposition in skin

85. Prognosis 1/3�1/2 may have recurrence (6wk-2yr)--rash and abdominal pain Prognosis is usually excellent Poor prognosis: Major indications of renal disease in the first 3 mo after onset or numerous exacerbations assoc. with nephropathy Decreased factor XIII activity Hypertension and renal failure at disease onset Increased number of glomeruli with crescents,macrophage infiltration and tubulointerstitial disease Nephritic or nephrotic syndrome at onset

86. Prognosis Renal outcome is variable Minimal lesions->75% recover in 2 years 2/3rds with crescentric GN progress to renal failure within the first year Overall HSP accounts for <1% of children with renal failure of all causes Renal failure can develop up to 10 years after onset 1-5% may develop ESRD

87. Treatment Treatment -usually supportive, since majority have self-limited illness resolving within 4 weeks. Prednisone consideration for severe gut vasculitis Short term steroids (initially IV) for severe GI, urologic manifestations and orchitis 1-2 mg/kg/d for 1 week then taper over 2-3 wks Renal prophylaxis with steroids? Severe renal disease: pulse steroids, azathioprine or cyclophosphamide, urokinase plus warfarin, IVIG, plasmapheresis (Wang et al)

89. Kawasaki Disease An acute febrile illness of childhood with medium and small sized necrotizing vasculitis first described by Kawasaki in 1967

91. KD M>F 6-11 months Asians>Europeans Acute febrile, subacute, covalescent CAA in ~ 5%; many develop coronary artery ectasia Giant aneurysms (>= 8 mm) Stenotic leading to MI Rupture acutely or develop later thrombosis due to stasis of blood flow and the procoagulant endothelial surface ? Anticoagulant therapy

92. KD Phases Acute febrile period lasting approximately 10 days (range 5-25d). Associated rash, carditis, CHF, mucous membrane, conjunctiva, adenitis, abdo pain, hydrops Subacute period of approximately 2-4 weeks Arthritis, perineal and extremity desquamation, coronary artery aneurisms Plt, ESR returns to normal Convalescent phase lasting months Nail changes, aneurisms, arthritis

95. GOALS OF TREATMENT CONTROL INFLAMMATION PREVENT ACUTE MORBIDITY, MORTALITY Coronary aneurysms Peripheral gangrene Myocardial infarct PREVENT CHRONIC MORBIDITY

96. THERAPY ASA 80 to 100 mg/kg per day in 4 doses with IVIG for 3-14 days High-dose ASA and IVIG appear to possess an additive anti-inflammatory effect. Low-dose ASA (3 to 5 mg/kg per day) until no evidence of coronary changes For children with coronary abnormalities, aspirin may be continued indefinitely IVIG limiations Approximate 10% failure rate, 67% respond to retreatment, 22% of 2nd IVIG failures respond to 3rd Studies only show efficacy with regards to CAA if initiated before 12 days Toxicity < 30% side effects (aseptic meningitis, hyperviscosity syndrome, ? recurrence) blood product-historical problem with hepatitis C transmission Cost: $100 + per gramIVIG limiations Approximate 10% failure rate, 67% respond to retreatment, 22% of 2nd IVIG failures respond to 3rd Studies only show efficacy with regards to CAA if initiated before 12 days Toxicity < 30% side effects (aseptic meningitis, hyperviscosity syndrome, ? recurrence) blood product-historical problem with hepatitis C transmission Cost: $100 + per gram

97. THERAPY IVIG (2 g/kg) with aspirin (50�80�100 mg/kg) given within 10 days of fever onset Second infusion of IVIG (2 g/kg) in addition to high-dose aspirin is strongly recommended in all children with persistent or recurrent fever IVIG THERAPY REDUCES CAA�S, MORTALITY Newburger JW et al, NEJM 1991: 324:1633 REDUCES GIANT CAA�S Rowley AH, Duffy CE, Shulman ST, J Pediatr 1988; 113:290 AMELIORATES DISEASE AFTER DAY 10 Marasini M et al, Am J Cardiol 1991; 68:796 IVIG THERAPY REDUCES CAA�S, MORTALITY Newburger JW et al, NEJM 1991: 324:1633 REDUCES GIANT CAA�S Rowley AH, Duffy CE, Shulman ST, J Pediatr 1988; 113:290 AMELIORATES DISEASE AFTER DAY 10 Marasini M et al, Am J Cardiol 1991; 68:796

99. Case 10: 10 year old black male with cough and weight loss for two months Fever for one month Cough for 2 months Increasing tiredness and myalgias Asthma exacerbation Unable to exercise or play as much as he used to Palpable bilateral non-tender cervical lymph nodes Hepatomegaly with mild tenderness Mild wheezing on auscultation Lymphopenia and anemia Negative for HIV, Hepatitis A, B, C and Parvovirus and TB

101. Older vs. Younger children Asymptomatic Clinical presentation can vary greatly Older children --- multisystem disease similar to the adult manifestation, with frequent hilar lymphadenopathy and pulmonary infiltration Early-onset childhood sarcoidosis --- triad of rash, uveitis, and arthritis in patients presenting before age 4 years. Lofgren's syndrome � Erythema Nodosum, bilateral hilar adenopathy, joint symptoms

102. Pediatric Sarcoidosis Lymphadenopathy -most common Intrathoracic - 75 to 90% hilar nodes bilaterally unilateral enlargement paratracheal nodes Peripheral - cervical, axillary, epitrochlear, inguinal Non-tender, non-adherent, with a firm, rubbery texture Chronic cough (2nd most common) Parenchymal disease (infiltrates, effusions, atelectasis), restrictive Half with pulmonary symptoms Dyspnea, cough, chest pain 20% with abnl CXR and minimal/ no symptoms

103. Diagnosis Anemia ~ 5% Leukopenia ~ 30% Eosinophilia ~ 25% High ESR with EN, acute phase Hypercalcemia, hypercalciuria ---2-63% ACE Kveim test CXR, Gallium Anergy to PPD Biopsy- Non-caseating granuloma

104. Linear scleroderma Linear scleroderma: arm Linear scleroderma of the left hand and forearm and the ulnar aspect of the right hand and forearm are seen in this 11-year-old girl. Hypopigmentation and tightening of the skin, diffuse atrophy, and soft-tissue contractures are evident. #0900001Linear scleroderma: arm Linear scleroderma of the left hand and forearm and the ulnar aspect of the right hand and forearm are seen in this 11-year-old girl. Hypopigmentation and tightening of the skin, diffuse atrophy, and soft-tissue contractures are evident. #0900001

105. LOCALIZED SCLERODERMA

107. SYSTEMIC SCLEROSIS Major criterion - sclerodermatous skin changes affecting areas proximal to the metacarpophalangeal or metatarsophalangeal joints Minor criteria are as follows: Sclerodactyly Digital scars resulting from digital ischemia Bibasilar pulmonary fibrosis not attributable to pulmonary disease Diffuse: Interstitial pulmonary fibrosis; Anti Scl 70 ab Limited (CREST): Pulmonary hypertension; Anticentromere ab

108. Blanching of hands- Raynauds Scleroderma: Raynaud's phenomenon, blanching of hands The marked pallor of the fourth and fifth digits on the left hand and of the fifth digit on the right hand is characteristic of Raynaud�s phenomenon. Vasospastic changes are common in systemic sclerosis but may also occur in rheumatoid arthritis, systemic lupus erythematosus, and idiopathic Raynaud�s disease. #9110010Scleroderma: Raynaud's phenomenon, blanching of hands The marked pallor of the fourth and fifth digits on the left hand and of the fifth digit on the right hand is characteristic of Raynaud�s phenomenon. Vasospastic changes are common in systemic sclerosis but may also occur in rheumatoid arthritis, systemic lupus erythematosus, and idiopathic Raynaud�s disease. #9110010

109. Case A 10yo high-achieving Caucasian girl S/P injury to her right foot 2 months ago presents with a swollen and cold right foot to your clinic. She is in a wheelchair and will not let you touch her foot. She is in excruciating pain. Think- Reflex neurovascular dystrophy

110. Hypermobility Benign Hypermobility syndrome Think Marfans Think Ehlers Danlos

111. Marfans Aortic aneurysm or dilation Mitral valve prolapse Bicuspid aortic valve Cysts Cystic medial necrosis Dural ectasia Ectopia lentis Retinal detachment Pneumothorax Obstructive lung disease Sleep apnea Glaucoma

112. Thank You and Good Luck!!!