ABP Pediatric Rheumatology cheat sheet

HLA class I molecules (A, B, C) present endogenous peptides to CD8+ T cells; class II molecules (DR, DQ, DP) present exogenous peptides to CD4+ T cells.

HLA associations: B27 with enthesitis-related JIA and reactive arthritis; DRB104 with rheumatoid factor-positive polyarticular JIA; DRB103 and DRB1*15 with SLE.

NOD-like receptor inflammasomes activate caspase-1, which cleaves pro-IL-1 beta to active IL-1 beta; gain-of-function NLRP3 mutations cause cryopyrin-associated periodic syndromes.

Toll-like receptors recognize pathogen-associated molecular patterns and drive type I interferon and pro-inflammatory cytokine production; type I interferon signatures are prominent in SLE and juvenile dermatomyositis.

Low C3 and C4 with active urinary sediment suggests complement-consuming lupus nephritis; inherited C1q, C2, or C4 deficiency carries high SLE risk, while C5-C9 deficiency predisposes to Neisseria infection.

Loss-of-function FOXP3 mutations abolish regulatory T cells and cause IPEX: immune dysregulation, polyendocrinopathy, enteropathy, X-linked.

Interleukin-6 induces hepatic C-reactive protein synthesis, while TNF-alpha and IL-1 beta drive fever, synovitis, and cachexia; each is a validated therapeutic target.

JAK-STAT signaling transduces signals from type I and II interferons and from IL-6, so JAK inhibitors blunt several cytokine pathways at once.

ILAR categories: systemic, oligoarticular (persistent or extended), polyarticular (rheumatoid factor positive or negative), psoriatic, enthesitis-related, and undifferentiated arthritis.

Oligoarticular JIA involves four or fewer joints in the first six months; the persistent subtype never exceeds four, while the extended subtype exceeds four after six months.

Systemic JIA requires quotidian fever for at least two weeks plus evanescent rash, arthritis, lymphadenopathy, hepatosplenomegaly, or serositis, with infection and malignancy excluded.

Chronic anterior uveitis is usually asymptomatic; slit-lamp screening intervals are set by JIA category, ANA status, and age at onset, typically every 3 to 12 months.

Enthesitis-related arthritis: HLA-B27, male predominance, age over six years, enthesitis, inflammatory back pain; its uveitis is acute, painful, and red rather than silent.

Anti-CCP is more specific than rheumatoid factor for rheumatoid factor-positive polyarticular JIA and predicts erosive disease.

Macrophage activation syndrome: falling ESR and platelet count, markedly elevated ferritin, hypofibrinogenemia, hypertriglyceridemia, elevated liver enzymes, and hemophagocytosis on bone marrow examination.

Chronic inflammation during growth can produce leg-length discrepancy, micrognathia, and cervical spine fusion, particularly in systemic and polyarticular subtypes.

EULAR/ACR 2019 SLE criteria: ANA of at least 1:80 is the entry criterion; weighted clinical and immunologic domains are scored, and at least 10 points with one clinical domain establishes classification.

Childhood-onset SLE shows higher rates of renal and hematologic involvement and more aggressive disease than adult-onset SLE.

Anti-dsDNA titers and low C3/C4 track disease activity; anti-Sm is highly specific; anti-Ro/SSA raises the risk of neonatal lupus and congenital complete heart block.

Lupus nephritis is classified by ISN/RPS biopsy class I to VI; class III or IV proliferative lesions require induction with mycophenolate mofetil or cyclophosphamide plus corticosteroids.

Juvenile dermatomyositis: symmetric proximal weakness, Gottron papules, heliotrope rash, and elevated creatine kinase, aldolase, LDH, and AST; MRI and EMG confirm muscle inflammation.

Myositis-specific antibodies in juvenile dermatomyositis: anti-MDA5 with ulcerative skin disease and interstitial lung disease, anti-NXP2 with calcinosis, anti-TIF1-gamma with extensive skin involvement.

Systemic sclerosis causes Raynaud phenomenon, sclerodactyly, digital ulcers, and interstitial lung disease; scleroderma renal crisis is treated with ACE inhibitors, and high-dose steroids may precipitate it.

Sjogren disease causes keratoconjunctivitis sicca, xerostomia, parotid enlargement, anti-Ro/La antibodies, hypergammaglobulinemia, and increased lymphoma risk; MCTD is defined by anti-U1-RNP.

Kawasaki disease: fever for at least five days plus four or more of conjunctivitis, oral mucous membrane changes, polymorphous rash, extremity changes, and cervical adenopathy; incomplete forms occur in infants.

Kawasaki treatment: intravenous immunoglobulin 2 g/kg as a single infusion plus aspirin, ideally within 10 days of onset; corticosteroids are added for high-risk coronary features.

IgA vasculitis (Henoch-Schonlein purpura): palpable purpura below the waist, arthritis, abdominal pain, and IgA nephropathy; monitor blood pressure and urinalysis for at least six months.

Childhood polyarteritis nodosa is ANCA-negative, affects medium-sized vessels, and causes livedo, subcutaneous nodules, digital ischemia, myalgia, and renovascular hypertension.

ANCA: proteinase-3 (c-ANCA) with granulomatosis with polyangiitis; myeloperoxidase (p-ANCA) with microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis.

Takayasu arteritis presents in adolescent females with hypertension, blood pressure discrepancy, diminished pulses, and elevated ESR; MR or CT angiography shows stenosis or vessel wall thickening.

Behcet disease: recurrent oral aphthae plus at least two of genital ulcers, eye lesions, skin lesions, or a positive pathergy test.

Coronary artery z-scores determine Kawasaki risk category and guide the duration of antiplatelet therapy and the frequency of cardiology follow-up.

Familial Mediterranean fever: MEFV gain-of-function variants cause 1 to 3 day attacks of fever with peritonitis, pleuritis, arthritis, or erysipelas-like rash; daily colchicine prevents attacks and AA amyloidosis.

Cryopyrin-associated periodic syndromes (FCAS, Muckle-Wells, CINCA/NOMID): NLRP3 mutations cause cold-triggered urticaria, fever, arthralgia, and in severe forms central nervous system and skeletal disease; IL-1 blockade is treatment.

TNF receptor-associated periodic syndrome: TNFRSF1A variants cause attacks lasting more than seven days with migratory rash, periorbital edema, myalgia, and serositis; etanercept or IL-1 blockade is used.

Mevalonate kinase deficiency (hyper-IgD syndrome): MVK variants cause recurrent fever with lymphadenopathy, aphthous ulcers, and abdominal pain; serum IgD may be elevated.

PFAPA: age two to five years, regular 3 to 6 day cycles, aphthous stomatitis, pharyngitis, and cervical adenitis; a single corticosteroid dose aborts the episode and tonsillectomy is an option in refractory cases.

Between autoinflammatory attacks the child is well, growth is normal, and acute-phase reactants may normalize; persistent abnormalities suggest infection, malignancy, or immunodeficiency instead.

IL-1 blockade with anakinra or canakinumab is the most effective targeted therapy for hereditary autoinflammatory syndromes driven by inflammasome activation.

Growing pains: bilateral lower-extremity pain in children aged 3 to 12 years, occurring in the evening, responding to massage, and never accompanied by limping, swelling, or abnormal examination findings.

Red flags in a limping child: fever, night pain, focal bone tenderness, weight loss, and refusal to bear weight mandate imaging and laboratory testing to exclude infection or malignancy.

Juvenile primary fibromyalgia and amplified musculoskeletal pain: diffuse pain, nonrestorative sleep, fatigue, allodynia, and normal inflammatory markers and imaging.

Complex regional pain syndrome: disproportionate pain after minor trauma with allodynia and sudomotor or vasomotor changes; first-line treatment is intensive physical and occupational therapy, not opioids.

A Beighton score of 6 or more out of 9 defines hypermobility in children; symptomatic hypermobility is managed with strengthening and proprioceptive training rather than activity restriction.

Osgood-Schlatter disease and Sever disease are traction apophysitides of adolescence, diagnosed clinically by focal tenderness and managed with activity modification.

Legg-Calve-Perthes disease is avascular necrosis of the proximal femoral epiphysis in boys aged 4 to 8 years; limp and groin pain occur, radiographs may lag, and MRI clarifies early disease.

Septic arthritis: fever, exquisite joint pain, refusal to bear weight; joint aspiration yields purulent fluid and the joint requires urgent drainage plus intravenous antibiotics.

Lyme arthritis: monoarthritis, usually of the knee, in an endemic area with positive Borrelia burgdorferi serology; oral antibiotics usually achieve resolution without chronic damage.

Reactive arthritis follows gastrointestinal or genitourinary infection by 1 to 4 weeks, is often HLA-B27 associated, and presents with asymmetric oligoarthritis, enthesitis, and dactylitis.

Parvovirus B19 can produce symmetric polyarthritis that mimics JIA; diagnosis is by IgM serology and symptoms usually resolve within weeks.

Acute rheumatic fever: Jones criteria require evidence of preceding group A streptococcal infection plus carditis, polyarthritis, chorea, erythema marginatum, or subcutaneous nodules.

Primary immunodeficiency clues: recurrent or unusual infections, failure to thrive, chronic diarrhea, and family history; chronic granulomatous disease and complement deficiencies may present with arthritis or osteomyelitis.

Chronic nonbacterial osteomyelitis (CRMO) causes multifocal bone pain with lytic and sclerotic lesions in children, mimicking infection and malignancy; NSAIDs are first-line therapy.

ANA by indirect immunofluorescence on HEp-2 cells: report titer and pattern; titers of 1:80 or higher are positive, but low titers occur in 5 to 15 percent of healthy children.

ESR rises and falls slowly and is affected by anemia, immunoglobulins, and age; CRP rises within hours, falls quickly, and better reflects acute inflammation.

Ferritin is markedly elevated in macrophage activation syndrome and systemic JIA; values above 10,000 ng/mL strongly suggest macrophage activation syndrome in the right clinical setting.

Urinalysis with microscopy and a spot urine protein-to-creatinine ratio are required at every lupus visit to screen for nephritis.

MRI is the most sensitive imaging modality for early synovitis, bone marrow edema, osteomyelitis, and sacroiliitis; plain radiographs show damage only after months of disease.

Musculoskeletal ultrasound detects synovitis and guides intra-articular injection but is operator dependent and cannot assess bone marrow.

Slit-lamp examination is required to detect asymptomatic chronic anterior uveitis in JIA; screening intervals depend on age at onset, JIA category, and ANA status.

Synovial fluid analysis includes cell count and differential, Gram stain, culture, and crystal examination; a white cell count above 50,000 per microliter suggests bacterial infection.

Methotrexate is dosed once weekly with folic acid supplementation; monitor CBC, liver enzymes, and creatinine, and hold the drug for significant cytopenias or transaminase elevation.

Before starting a TNF inhibitor, screen for latent tuberculosis and hepatitis B, update inactivated vaccines, and avoid live vaccines during therapy.

Hydroxychloroquine is used for cutaneous and systemic lupus, is compatible with pregnancy, and requires annual retinal screening after five years of cumulative use.

Tocilizumab blocks the IL-6 receptor and is effective in systemic JIA; monitor for neutropenia, transaminase elevation, and lipid abnormalities.

Anakinra and canakinumab block IL-1 and are first-line targeted agents for systemic JIA, cryopyrin-associated periodic syndromes, and other inflammasomopathies.

Cyclophosphamide used for severe lupus nephritis or vasculitis carries risks of gonadal toxicity, hemorrhagic cystitis prevented by mesna and hydration, and secondary malignancy.

Corticosteroids: monitor growth velocity, blood pressure, glucose, bone mineral density, and eyes; taper after prolonged use and give stress doses during acute illness.

NSAIDs inhibit cyclooxygenase and can cause gastritis, renal impairment, and elevated transaminases; they are avoided in renal insufficiency and used cautiously in inflammatory bowel disease.

The Childhood Health Assessment Questionnaire measures disability across eight domains and includes a discomfort visual analog scale; it is a validated outcome measure in JIA.

Physical therapy for JIA emphasizes range of motion, muscle strengthening, aerobic fitness, and return to activity; prolonged bed rest worsens outcomes.

School reintegration plans such as individualized education programs or 504 plans address attendance, fatigue, physical education modifications, and medication administration.

Transition of care begins in early adolescence with structured readiness assessment and transfers to adult rheumatology around age 18 to 21; gaps in care increase flare risk.

Screen adolescents with rheumatic disease for depression, anxiety, and adherence problems, because these predict worse disease outcomes and poorer transition success.

Growth, nutrition, and bone health require monitoring in children on chronic corticosteroids; vitamin D and calcium supplementation plus weight-bearing exercise are recommended.

Live attenuated vaccines are contraindicated during high-dose corticosteroid or biologic therapy, whereas inactivated influenza and other killed vaccines should be given on schedule.