Samatha Madhavarapu 21 m/o F with limping HPI • Intermittent limp of R leg started 6 weeks ago. • Constant limp since 3 days • Worse upon awakening • Stiffness in R knee. • Transient warmth and redness + • Not able to bear weight initially, improves over 2 hrs. • Was outdoors in Upstate at BBQ 8 weeks ago • No fever, rash, recent URI • No trauma, diarrhea, HPI Contd… PMH: None FH: grand father has seizure disorder. No bone/joint problems Immunizations: UTD NKDA Meds: Tylenol PRN pain. Labs done 6 weeks ago: wbc7.6, 33.9/66.3, ESR 18, xray R knee Normal. Physical Exam Vital signs: HEENT : Normal Heart , Lungs ,Abdomen: Normal Skin: No rash R knee: decreased extension, no swelling, no redness, no warmth. Other Jts: FROM. LABS BMP: 136/4.9/ 101/22/12/0.4/139/10.5 Total Protein/ Albumin: 7.5/4.7 LFT: 0.2/01, 38/19, 244 CBC: 7.3/ 12/36.3/392 ESR: 15 Other Labs CRP: 0.2 ANA negative Lyme Ab titre: 1.2 Anti CCP antibody: 8.3 HLA B 27: Negative RF: 20.0 Ultrasound of Knees: Small R knee jt effusion DD of Arthritis in Children Rheumatic & Congenital & Metabolic Inflammatory Diseases Disorders Seronegative Bone & Cartilage Spondyloarthropathies Disorders Infectious Illnesses Neoplastic Disorders Reactive Arthritis Hematologic Disorders Immunodeficiencies Pain Syndromes Juvenile Rheumatoid Arthritis JRA most common rheumatic disease of childhood Synovitis of peripheral joints manifested as swelling JRA is not a single disease, but a category of diseases. Criteria for Classification of JRA Age of onset: < 16 yrs Arthritis in > or = 1 joint Duration of the Disease: > or = 6 weeks Onset type is defined by type of articular involvement in the first 6 months after onset: Poly arthritis: > or = 5 inflamed joints Oligo arthritis: < or = 4 inflamed joints Systemic Disease: arthritis with intermittent fever Classification of Chronic Arthritis in Children ACR, ELAR & ILAR classification Only ACR criteria have been statistically validated. Characteristic ACR ELAR ILAR Onset Types 3 6 6 Age of onset of arthritis < 16 yr <16 yr <16 yr Duration of arthritis >= 6 wk >= 3mn >= 6wk Juvenile Ankylosing Doesn’t includes Includes Spondylitis include Juvenile Psoriatic Arthritis Doesn’t includes includes include Inflammatory Bowel Doesn’t includes includes Disease include Exclusion of other diseases YES YES YES Etiology • Unknown • Immunogenetic Susceptibility (Specific HLA subtypes) • External Triggers - Viruses( EBV, Parvo virus B19, Rubella) - Hyperreactivity to self antigens(type 2 collagen) - Enhanced T-cell reactivity to heat schock proteins of bacteria. Epidemiology Incidence of JRA: 13.9/100,000 Sex: Pauci and poly articular disease more in girls Systemic onset –equal frequency in boys and girls Race: Prevalnce of JIA lower in Urban African – American compared to Caucasians Oligo 40% newly diagnosed cases in Caucasians. Blacks with JRA were older and less likely to test positive for ANA or to have uveitis, more likely to test positive for Ig M RF Pathogenesis • Synovitis: Villous hypertrophy & edema of subsynovial tissues. • Vascular endothelial hyperplasia • Infiltration of mononuclear and plasma cells. • Pannus formation with erosion of cartilage and bone. • Recriutment of T-cells specific to synovial non specific antigens., facilitated by specific HLA types. Clinical Features Onset insidious or abrupt Morning stiffness and gelling Easy fatiguability Joint pain (not very severe) and swelling, limited joint movt, not erythematous. May have preceding illness Oligoarthritis/Pauciarticular • Affects 4 or fewer joints • Typically larger joints (knees, ankles, wrists). • Starts with 1 joint • Monoarticular involvement of hip, upper extremity large joints never presenting sign in JRA. • If knee is affected-limping+, esp morning • Chronically- atrophy of extensor muscles of thigh, tight hamstrings & knee flexion contractures. • Associated with HLA-DR8 Polyarthritis/Polyarticular • Minimum 5 joints should be effected. • Both large & small jts of upper and lower extremities • Resembles adult RA and HLA profile. • Associated with HLA –DR4 • Rheumatoid nodules in severe form • Micrognathia- chronic TM joint disease • C-Spine involvement- atlantoaxial subluxation Systemic Onset • Arthritis with visceral involvement • Characteristic intermittent spiking fevers to >/= 39c for >/= 2 weeks. • Febrile episode assoc with evenescent (< 1 hr) macular rash, linear or circular, 2-5 mm, over trunk & proximal extremities. • Arthralgia, myalgia • Hepatosplenomegaly,Lymaphadenopathy • Serositis/pericardial effusion • Photophobia (uveitis), irregular iris due to synechiae Oligoarthritis Chr. uveitis Labs CBC with diff: Lymphopenia,Thrombocytosis,microcytic anemia. Neutropenia is uncommon. ESR: - Always elevated with systemic JRA. - Usually elevated with polyarticular but within reference range in pauci articular. - When elevated, ESR helps to monitor success of medical treatment Labs contd ANA: Positive in 40-85% with oligo/poly articular Unusual with systemic onset Titres do not correlate with disease severity. Associated with incraesed risk of uveitis RF: Rare in systemic JRA. Marker of persistence of polyarticular JRA into adulthood., devpt of rheumatoid nodules and poor functioning. Total protein and albumin: levels are often decreased during active disease ALT test: to exclude hepatitis (viral or autoimmune) prior to starting NSAIDS U/A: to r/o infection (trigger of JRA or transient postinfectious arthritis) and nephritis (seen in pts with SLE) Imaging X-ray: When 1 jt is affected , to r/o osteomyelitis or septic arthritis. Soft tissue swelling, regional osteoporosis, osteopenia, sub chondral bone erosions, narrowing of cartilage spaces, fusion of nueral arches. MRI synovial inflammation, early minimal changes seen Echo cardiography: Serositis DEXA: osteopenia X rays Management Multidisciplinary Team for care of children Main goal: maximize daily functioning , minimize drug toxicity. Key predictor of long term outcome is early diagnosis and referral to rheumatology team. Diet: Include 3 servings of calcium rich foods Activity: more active, better the prognosis NSAIDS • Used to treat all subtypes of JRA (40-60% children show improvement). • Mean duration for anti-inflammatory effect in JRA- 30 days • Most with pauci and few with poly respond to NSAID alone . • Rofecoxib , celecoxib (selective Cox-2 inhibitors) ~ similar to naproxen effectiveness • Adverse : nausea, decresead appetite, abd pain. Less gastritis Naproxen induced pseudoporphyria Methotrexate • Safest, most efficacious, least toxic of of 2nd line agents for JRA. • Used in 60% patients with poly JRA • Inhibits DHFR, purine synthesis. • Pts unresponsive to PO MTX benefit from SC or IM administration. • Well tolerated and less toxicity in children. • Pts who respond well have improved growth, functionality, radiographic improvement. Glucocorticoids • For overwhelmingly inflammatory or systemic illness. • Bridge therapy for those who did not respond to conventional therapy • Ocular control of uveitis (drops or injections) • Intra articular use :initial therapy in pts with only 1 or 2 joint involvement • Improvement in symptoms in 2-3 days, which last for at least 6 mo in 60% and 1yr in 45% Anti TNF alpha • Etanercept,: Only one approved for children • Fusion protein with TNF receptor monomer to Fc portion of Ig G1. • Administered SC twice weekly used in active polyarticular JRA who fail MXT therapy. • JRA assoc-chronic uveitis that is inadequately responsive to steroid therapy. • Not to be used with h/o chronic infections • R/o TB before starting rx Sulphasalazine Improved joint inflammation & labs compared to placebo. GI irritation and rash. Steven johnson in pts with active systemic JRA. CI in porphyria and G6PD deficiency Prognostic features • Child with oligo: esp. girls, onset< 6yrs age –chronic uveitis risk • Polyarticular: RF, rheumatoid nodules • Systemic onset: number of joints involved, duration of inflammation, severity of arthritis. • Limb length discrepancy, contractures, • Disability continues into adulthood in 20% • Chronic pain syndromes. • Psychological complications. http://www.youtube.com/watch?v=NqyB-cTxvs8 A 16-month-old boy is brought to your clinic because his mother says he is "walking funny" today. She states that he has been walking for 4 months and is very active, but she is unaware of any trauma or falls. She denies fever or other symptoms. He appears well and has normal vital signs. Physical examination reveals mild tenderness to palpation over the medial aspect of the lower leg just above the ankle. There is no overlying bruising, erythema, or edema, and you can elicit full range of motion in the hips, knees, and ankles. Of the following, the MOST likely diagnosis is a. Aneurysmal Bone Cyst b. Ankle Sprain c. Fracture d. Osteomyelitis e. Transient Synovitis An 11-year-old girl presents 2 weeks after an office visit for a presumed viral illness characterized by fever, malaise, and flushing of the cheeks. Today, her mother notes that she no longer has a fever, but she complains of pain in her knees and elbows. On physical examination, the left knee is slightly swollen and warm but not erythematous. The girl reports pain on movement of both elbows, but there are no physical findings on examination of the elbows or other joints. The remainder of the physical examination findings are normal, except for an oral temperature of 100.6°F (38.1°C). Results of laboratory studies include a white blood cell count of 8.9x103/mcL (8.9x109/L) with 40% polymorphonuclear leukocytes, 45% lymphocytes, and 15% monocytes; hemoglobin of 11.0 g/dL (110.0 g/L); platelet count of 472.0x103/mcL (472.0x109/L); and erythrocyte sedimentation rate of 20 mm/hr. Of the following, the MOST likely pathogen to cause this child's joint complaints is a. Borrelia burgdorferi b. Coxsackievirus c. group A beta-hemolytic streptococci d. influenza A virus e. parvovirus B19 Acknowledgement Dr. Jillian Parekh Dr. Karen Sawitz Questions???