Immunodeficiency Flashcards
- What are the key components of the innate and adaptive immune systems in children?
Innate: Neutrophils, macrophages, NK cells, complement
- Adaptive: T and B lymphocytes, antibodies
- What are the warning signs of primary immunodeficiency in pediatrics?
≥8 ear infections/year, ≥2 serious sinus infections/year, ≥2 pneumonias/year, persistent thrush, FTT, IV antibiotics needed, family history
- What are the common types of primary antibody deficiencies?
Include: X-linked agammaglobulinemia, selective IgA deficiency, CVID, hyper-IgM syndrome
- What is the presentation of X-linked agammaglobulinemia (Bruton disease)?
Bruton: X-linked, absent B cells, low IgG/A/M
- Recurrent bacterial infections, no tonsils/lymph nodes
- Onset after 6 months
- What is the clinical presentation of selective IgA deficiency?
Most common PID; often asymptomatic
- May present with recurrent sinopulmonary infections, allergies, GI infections (Giardia)
- What are the features and complications of common variable immunodeficiency (CVID)?
CVID: Decreased IgG, IgA ± IgM
- Presents in adolescence/adulthood with infections, autoimmunity, lymphadenopathy, risk of lymphoma
- What are the main causes of combined immunodeficiency in children?
Combined: SCID, Wiskott-Aldrich, Ataxia-telangiectasia, DiGeorge syndrome, HIV
- What are the features of Severe Combined Immunodeficiency (SCID)?
SCID: Failure to thrive, chronic diarrhea, opportunistic infections
- Very low lymphocyte count
- Needs bone marrow transplant
- What is DiGeorge syndrome and how does it present?
22q11.2 deletion
- Features: Hypocalcemia, cardiac defects, thymic hypoplasia, cleft palate, facial dysmorphism
- What are the diagnostic steps in evaluating suspected immunodeficiency in a child?
Initial: CBC with diff, immunoglobulin levels, lymphocyte subsets
- Further: Specific antibody titers, complement testing, genetic testing
- What are the clinical features and inheritance of Wiskott-Aldrich syndrome?
Wiskott-Aldrich: X-linked, mutation in WAS gene
- Triad: Eczema, thrombocytopenia (small platelets), recurrent infections
- Increased risk of malignancy
- What are the main types and features of complement deficiencies in children?
Complement deficiencies:
- Early (C1–C4): Autoimmunity (e.g., lupus)
- Terminal (C5–C9): Recurrent Neisseria infections
- What is chronic granulomatous disease (CGD) and how does it present?
CGD: NADPH oxidase deficiency
- Presents with recurrent skin/lung/liver abscesses, osteomyelitis, catalase+ organisms (e.g., Staph, Aspergillus)
- How is CGD diagnosed and managed?
Diagnosis: Dihydrorhodamine (DHR) or nitroblue tetrazolium test
- Management: Antibiotic prophylaxis, interferon-gamma, BMT in severe cases
- What is the difference between primary and secondary immunodeficiency?
Primary: Genetic/intrinsic defect (e.g., SCID, CVID)
- Secondary: Acquired from infections (HIV), chemotherapy, malnutrition
- What infections are associated with T-cell vs B-cell deficiencies?
T-cell: Viral, fungal, opportunistic infections (e.g., Candida, CMV)
- B-cell: Recurrent bacterial infections (e.g., Strep pneumoniae)
- What are the diagnostic clues to autoimmune lymphoproliferative syndrome (ALPS)?
ALPS: Chronic non-malignant lymphadenopathy/splenomegaly, autoimmune cytopenias, ↑double negative T cells (CD3+CD4–CD8–)
- What are the types and clinical criteria for juvenile idiopathic arthritis (JIA)?
JIA: ≥6 weeks arthritis in <16 yrs
- Types: Oligoarticular, polyarticular (RF+ or RF–), systemic (Still’s), enthesitis-related, psoriatic
- What are the features and management of systemic-onset JIA (Still’s disease)?
Still’s: Quotidian fever, salmon-pink rash, arthritis, hepatosplenomegaly, ↑ferritin
- Treat with NSAIDs, steroids, IL-1/IL-6 inhibitors
- What is the presentation and treatment of oligoarticular JIA?
Oligoarticular JIA: ≤4 joints (commonly knees, ankles), girls <6 yrs
- Risk of uveitis, ANA+, treat with NSAIDs ± methotrexate
- What are the features and treatment of polyarticular JIA?
Polyarticular JIA: ≥5 joints, symmetric, small/large joints, RF+/RF– forms
- RF+ resembles adult RA
- Treat with DMARDs (methotrexate), biologics
- What are the extra-articular manifestations of JIA?
Extra-articular: Uveitis, growth retardation, anemia, fatigue, limb-length discrepancy, constitutional symptoms
- What is the approach to uveitis screening in children with JIA?
Screen all ANA+ children, especially oligoarticular JIA
- Slit-lamp exam every 3–6 months depending on age and ANA status
- What is juvenile dermatomyositis and its hallmark features?
Juvenile dermatomyositis: Proximal muscle weakness, heliotrope rash, Gottron’s papules, calcinosis, difficulty climbing stairs
- What are the diagnostic tests used in juvenile dermatomyositis?
Tests: Elevated CK, aldolase, LDH, AST, EMG, muscle MRI, biopsy
- ANA and anti-Mi-2/anti-MDA5 antibodies may help
- What is pediatric systemic lupus erythematosus (SLE) and its common features?
Pediatric SLE: Malar rash, photosensitivity, oral ulcers, arthritis, nephritis, serositis, hematologic, neuropsychiatric symptoms
- What labs are used to diagnose and monitor pediatric SLE?
Labs: ANA (sensitive), anti-dsDNA (specific), anti-Sm, low complement (C3, C4), proteinuria, CBC, ESR/CRP
- What is the treatment strategy for pediatric SLE?
Treatment: Steroids for flares, hydroxychloroquine for maintenance, immunosuppressants (azathioprine, MMF, cyclophosphamide)
- What are the signs and risks associated with lupus nephritis in children?
Signs: Proteinuria, hematuria, hypertension, edema
- Class III/IV: Risk for CKD
- Biopsy guides treatment
- What are antiphospholipid antibodies and their clinical significance in pediatrics?
Antiphospholipid antibodies: Lupus anticoagulant, anticardiolipin, β2-GP1
- Risk: Thrombosis, miscarriage, stroke, livedo reticularis
- What are vasculitides seen in children and how are they classified?
Vasculitides: Classified by vessel size
- Large (Takayasu), medium (Kawasaki), small (HSP, ANCA-associated)
- What is Henoch-Schönlein purpura (IgA vasculitis) and its clinical features?
HSP: Palpable purpura (buttocks/legs), arthralgia, abdominal pain, renal involvement
- IgA deposition on biopsy
- What is Kawasaki disease and its diagnostic criteria?
Kawasaki: ≥5 days fever + ≥4 of: conjunctivitis, mucositis, rash, extremity changes, lymphadenopathy
- What is the treatment and follow-up for Kawasaki disease?
Treatment: IVIG + aspirin
- Follow-up: Serial echocardiograms for coronary artery aneurysm screening
- What are the features and management of Takayasu arteritis in children?
Takayasu: Large-vessel vasculitis; absent pulses, HTN, limb claudication
- Treat with steroids, immunosuppressants, monitor BP/vascular imaging
- What are the key features of ANCA-associated vasculitis in pediatrics?
ANCA-associated: GPA (Wegener), MPA
- Features: Hematuria, pulmonary hemorrhage, sinusitis
- ANCA positive (c-ANCA/PR3, p-ANCA/MPO)
- What is periodic fever syndromes and how are they recognized?
Periodic fevers: Recurrent fever with stereotyped features
- Genetic syndromes (e.g., FMF, TRAPS, CAPS)
- What is PFAPA syndrome and how is it diagnosed and treated?
PFAPA: Periodic fever, aphthous ulcers, pharyngitis, adenitis
- Diagnosis of exclusion, responds to single-dose steroids
- What are the features of Behçet disease in pediatric patients?
Behçet: Recurrent oral/genital ulcers, uveitis, vasculitis, arthritis
- Pathergy test may be positive
- What is macrophage activation syndrome (MAS) and its association with rheumatic diseases?
MAS: Life-threatening hyperinflammation (esp. in sJIA, SLE)
- High ferritin, cytopenias, liver enzymes, coagulopathy
- Treat with steroids, cyclosporine
- What are the immunological features of inflammatory bowel disease (IBD) in children?
IBD: Dysregulated immune response to gut flora
- ↑TNF-α, IL-6, defective regulatory T cells
- May mimic rheumatologic diseases
- How does primary immunodeficiency present with IBD-like symptoms?
Some PIDs (e.g., CGD, IL-10R deficiency) present with early-onset colitis, perianal disease
- Suspect in atypical or refractory cases
- What is the link between celiac disease and autoimmunity in children?
Celiac disease: Associated with type 1 DM, thyroiditis, IgA deficiency
- Screen with anti-TTG IgA and total IgA
- What are the clinical features and antibodies in autoimmune hepatitis in pediatrics?
Autoimmune hepatitis: Elevated LFTs, fatigue, jaundice
- Antibodies: ANA, anti-SMA, anti-LKM1
- Liver biopsy confirms
- What is the role of biologic therapies in pediatric rheumatologic diseases?
Biologics (e.g., anti-TNF, IL-1/6 blockers) target cytokines in JIA, SLE, autoinflammatory diseases
- Require infection screening
- What are the risks and benefits of TNF inhibitors in children?
TNF inhibitors: Effective for arthritis, IBD
- Risks: TB reactivation, infections, demyelination, malignancy (rare)
- What is the vaccination guideline for immunosuppressed pediatric patients?
Inactivated vaccines safe; avoid live vaccines while on biologics or high-dose steroids
- Ensure pre-treatment immunizations
- How is growth affected in pediatric rheumatologic conditions?
Chronic inflammation + steroids/MTX can impair growth
- Biologics may improve growth by controlling disease
- What is the approach to chronic pain syndromes in pediatric rheumatology?
Chronic pain: Consider amplified musculoskeletal pain syndrome (AMPS), fibromyalgia
- Treat with CBT, PT, avoid opioid use
- What are red flag symptoms suggesting systemic autoimmune disease in a child?
Red flags: Prolonged fever, weight loss, rash, cytopenias, proteinuria, arthritis, photosensitivity, serositis
- What is HLH (hemophagocytic lymphohistiocytosis) and its triggers in children?
HLH: Hyperinflammatory syndrome due to immune dysregulation
- Triggers: Infections (EBV), malignancy, autoimmune diseases, genetic forms (PRF1, UNC13D)
- What are the diagnostic criteria for HLH in pediatric patients?
HLH criteria (≥5 of 8): Fever, splenomegaly, cytopenias, ↑ferritin, ↑triglycerides, ↓fibrinogen, hemophagocytosis, low NK activity, elevated soluble IL-2R
- What is the difference between MAS and HLH?
MAS is a form of HLH seen in sJIA/SLE
- HLH is broader, with genetic and secondary types
- Overlapping features but HLH more often with infections/malignancy
- What are early signs of systemic autoimmune disease in infants and toddlers?
Infants: Rashes, cytopenias, hepatosplenomegaly, nephrotic syndrome, early-onset arthritis
- Consider neonatal lupus (anti-Ro exposure)
- What is the role of ANA, anti-dsDNA, and ENA panel in pediatric rheumatology?
ANA: Screening for autoimmune disease
- dsDNA: Specific for SLE
- ENA: Anti-Ro, La, Sm, RNP (MCTD, Sjögren, SLE)
- How is immunoglobulin therapy used in pediatric immunodeficiencies and autoimmune diseases?
IVIG: Used for antibody deficiencies (XLA, CVID), Kawasaki, ITP, Guillain-Barré, inflammatory myopathies
- Provides passive immunity or immune modulation
- What are the clinical features and genetics of hyper-IgE syndrome?
Hyper-IgE (Job syndrome): STAT3 mutation (AD)
- Features: Recurrent skin/lung abscesses, eczema, retained teeth, coarse facies, high IgE
- What are the features and management of juvenile scleroderma?
Juvenile scleroderma: Localized (morphea) or systemic
- Features: Skin tightening, Raynaud, pulmonary fibrosis
- Treat with immunosuppressants
- What is mixed connective tissue disease (MCTD) in children?
MCTD: Overlap of SLE, scleroderma, polymyositis
- Features: Raynaud, arthritis, muscle weakness, anti-U1 RNP antibodies
- What is the significance of HLA associations in pediatric autoimmune disorders?
HLA associations: HLA-B27 (enthesitis-related JIA), HLA-DR3 (celiac), HLA-DR2/3 (SLE)
- Help with diagnosis, prognosis
- What are the key features of Sjögren syndrome in pediatric patients?
Sjögren: Rare in children
- Features: Parotid swelling, dry mouth/eyes, dental caries, fatigue
- Anti-Ro/La antibodies often positive
- What is the difference between primary and secondary Sjögren syndrome?
Primary: Occurs without other autoimmune disease
- Secondary: Associated with SLE, RA, systemic sclerosis
- What are the features of enthesitis-related arthritis (ERA) in children?
ERA: Subtype of JIA, affects entheses (Achilles, plantar fascia), knees, hips
- Common in boys >6 yrs
- May evolve to ankylosing spondylitis
- What is the association between HLA-B27 and ERA or other spondyloarthropathies?
HLA-B27: Strongly associated with ERA, ankylosing spondylitis, reactive arthritis
- Present in up to 90% of pediatric AS cases
- What are common uveitis-related complications in pediatric rheumatology?
Uveitis complications: Posterior synechiae, cataract, glaucoma, vision loss
- Require regular screening and treatment with topical or systemic agents
- How is Raynaud phenomenon evaluated and managed in children?
Raynaud: Triphasic color change (white→blue→red)
- Evaluate with ANA, ESR, nailfold capillaroscopy
- Manage with warmth, CCBs if needed
- What is ANA positivity and its significance in healthy children?
ANA+: Seen in up to 10–15% of healthy children
- Low titers (e.g., 1:40–1:80) may not be significant unless clinical signs present
- What are the typical findings in nailfold capillaroscopy and what do they indicate?
Nailfold capillaroscopy: Detects dilated/abnormal capillaries in scleroderma, dermatomyositis
- Early clue to connective tissue disease
- What are cryoglobulinemias and their manifestations in children?
Cryoglobulinemia: Cold-precipitating immune complexes
- Features: Purpura, arthralgia, nephritis, neuropathy
- Associated with infections, autoimmune diseases
- What are the common medications used in pediatric rheumatology and their side effects?
Drugs: Methotrexate (hepatotoxicity, cytopenias), steroids (growth suppression, osteoporosis), hydroxychloroquine (retinopathy), biologics (infections, TB reactivation)
- What are the immunologic features and management of juvenile systemic sclerosis?
Juvenile systemic sclerosis: Skin tightening, Raynaud, GERD, pulmonary fibrosis, renal crisis
- ANA+, anti-Scl-70 or anti-centromere antibodies
- Treat with immunosuppressants, vasodilators
- What are the types and features of localized scleroderma (morphea) in children?
Morphea: Localized skin sclerosis
- Types: Linear (often on limbs/face), plaque-type, generalized
- May cause growth restriction, joint contractures
- What is the clinical spectrum of autoinflammatory syndromes in pediatrics?
Autoinflammatory syndromes: Recurrent fevers, rashes, arthralgia without high autoantibody levels
- Involve innate immunity (e.g., FMF, TRAPS, CAPS)
- What is the presentation and management of familial Mediterranean fever (FMF)?
FMF: Recurrent fever, serositis (peritonitis, pleuritis), erysipelas-like rash
- AR (MEFV gene)
- Treat with colchicine
- What are the genetic causes and features of TRAPS and CAPS syndromes?
TRAPS: TNFR1 mutation, long fever episodes, rash, myalgia
- CAPS: NLRP3 mutation (includes FCAS, Muckle-Wells)
- IL-1 inhibitors for both
- What are the main complications of systemic vasculitis in children?
Complications: Renal failure (glomerulonephritis), CNS events (stroke, hemorrhage), coronary aneurysms (Kawasaki), intestinal ischemia
- How does pediatric sarcoidosis present and how is it diagnosed?
Sarcoidosis: Rare in children
- Features: Uveitis, arthritis, rash, lymphadenopathy
- Non-caseating granulomas on biopsy
- Treat with steroids
- What is immunosenescence and how does it affect pediatric immunity?
Immunosenescence: Age-related decline in immune function
- In children, typically refers to effects of chronic illness or immunosuppression on immune development
- What is the role of genetic testing in pediatric autoimmune/autoinflammatory diseases?
Genetic testing (targeted panels, WES) useful in early-onset, refractory, or syndromic autoimmune/autoinflammatory cases
- Guides diagnosis and therapy
- What is the differential diagnosis for recurrent fevers in pediatric patients?
Differential: Infections, malignancy, autoimmune disease (SLE, JIA), autoinflammatory syndromes (FMF, PFAPA), immunodeficiencies
