Rheumatology

Question 1

rheumatologic diseases

Answer 1

• characterized by autoimmunity and inflammation
• Symptoms can include arthritis (synovitis), enthesitis, serositis, myositis and vasculitis, as well as activation of reticuloendothelial system (causing lymphadenopathy, hepatosplenomegaly)
• chronic inflammation can lead to growth delay and disability
• differential diagnosis includes active infections, post-infectious phenomena, and malignancies
• Connective tissue diseases
  
  • systemic lupus erythematosus
  • dermatomyositis
  • juvenile idopathic arthritis
• Hypersensitivity syndromes
  
  • Henoch-Schönlein purpura
  • serum sickness (e.g., drug-related)
• ANCA-associated vasculitis
  
  • Wegener granulomatosis
  • Polyarteritis nodosa
  • Churg-Strauss syndrome
• Giant cell arteritis
  
  • temporal arteritis
  • Takayasu arteritis
• others
  
  • Behçet syndrome
  • Kawasaki disease
  • hypocomplementemic urticarial vasculitis
  • spondyloarthropathies

Question 2

systemic lupus erythematosus

Answer 2

• Deposition of immune complexes in tissue which activates lymphocytes, neutrophils, and complement
• Multisystem inflammatory disease may include joints, serous linings, skin, kidneys, and the central nervous system
• Epidemiology:
  
  • female-predominant
  • median age of pediatric SLE patients ~ 12 years
    
    • uncommon before age 4 years
  • pediatric presenting symptoms may be vague

Question 3

systemic lupus erythematosus findings

Answer 3

• most common findings in children
  
  • fever
  • abdominal complaints
  • malar rash and/or oral ulcers
  • musculoskeletal arthritis or arthralgias
  • hematologic anemia, leukopenia, thrombocytopenia
• renal findings in children
  
  • hematuria
  • proteinuria
  • mild hypertension
  • diffuse proliferative glomerulonephritis
• neurologic findings in children
  
  • headache
  • psychosis
  • peripheral or cranial neuropathy
  • sometimes more vague presentation
  • FULL history and physical exam important in teens
    
    • screening CBC, ESR reasonable in vague complaints
  • more dramatic neurologic presentations include stroke, seizures, chorea, coma
• hematologic findings in children
  
  • thrombocytopenia, hemolytic anemia, leukopenia
• cardiopulmonary findings in children
  
  • increased risk of atherosclerosis and coronary artery disease
  • increased risk of pericarditis, endocarditis
  • pleural effusions

Question 4

ACR diagnostic criteris for systemic lupus erythematosus

Answer 4

• 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;
• photosensitive rash – skin rash as a result of unusual reaction to sunlight
• Naso-oral ulcers – ulceration usually painless
• arthritis – nonerosive arthritis involving 2 or more peripheral joints, characterized by tenderness, swelling, or effusion
• serositis – pleuritis or pericarditis
• renal disorder – persistent proteinuria, cellular casts
• neurologic disorder – seizures or psychosis
• hematologic disorder – hemolytic anemia, leukopenia, lymphopenia, thrombocytopenia
• immunologic disorder – anti-phospholipid Ab, anti-DNA, anti-Sm, false positive syphilis serology
• anti-nuclear antibody – abnormal titer of ANA by immunofluorescence or an equivalent assay
• Diagnosis is when 4 of these are present.
• Note: The Systemic Lupus International Collaborative Clinics has also published a modification of the ACR criteria which can also be used for diagnosis.

Question 5

laboratory findings of systemic lupus erythematosus

Answer 5

• laboratory
  
  • diagnosis
    
    • ANA
    • CBC with leukopenia, anemia
    • complement level
    • ESR
  • disease severity
    
    • anti-dsDNA antibody more specific
      
      • also antibodies to Sm nuclear antigen
    • antiphospholipid antibodies as
      
      • anti-cardiolipin antibody, lupus anticoagulant or false positive RPR or VDRL for over 6 months
  • urinalysis and renal function (BUN, Cr)
  • Renal biopsy if lupus is confirmed to assess and stage lupus nephritis
    
    • renal disease is a major component of SLE in children

Question 6

systemic lupus erythematosus tx

Answer 6

• therapy
  
  • corticosteroids
  • cyclophosphamide – early therapy improves survival
  • rituximab - monoclonal antibody against CD20 - limits B Cell ability to produce antibodies
  • steroid-sparing agents
    
    • azathioprine
    • mycophenolate mofetil
  • non-steroidal anti-inflammatory drugs
    
    • hydroxychloroquine
    • dapsone

Question 7

challenges in children with SLE

Answer 7

• challenges in children with SLE
  
  • poor compliance
  • renal disease – 30% will go on to renal failure
    
    • those in renal failure have a 50% 5-year survival rate
  • neurologic complications
  • intercurrent infections

Question 8

neonatal lupus

Answer 8

• A different disorder from SLE
• Neonates receive transplacental IgG from mother that causes autoimmune response
• Symptoms:
  
  • Rash
  • Heart block (prolonged PR interval)
  • Cytopenias
  • Hepatomegaly
• Diagnosis:
  
  • Detection of the antibodies:
    
    • Anti Ro and Anti La are most common
    • Other antibodies including anti RNP sometimes seen
  • EKG
• Treatment:
  
  • Corticosteroids
  • IVIG
  • Cardiac pacing if significant heart block
  • Rash will resolve as autoantibodies subside. Heart block can be permanent.

Question 9

juvenile idiopathic arthritis

Answer 9

• most prevalent chronic rheumatologic disease of childhood
  
  • prevalence 1:1000, onset peaks at 1-3 years and at 8-12 years
  • 3 types (International League of Associations for Rheumatology Classifications)
    
    • oligoarticular (~50%) - <4 joints (in the first 6 months)
      
      • Persistent and extended types
    • polyarticular (~40%) - >5 joints
      
      • RF negative and positive subtypes
    • systemic-onset
  • non-migratory arthropathy with a tendency to involve large joints or proximal interphalangeal joints lasting over chronic period of months
• pain usually worse in the morning
• joint swelling with diminished mobility
• complicated by uveitis
  
  • most common treatable cause of blindness in childhood
  • ANA-positive children are more likely to have chronic uveitis
• difficult diagnosis on acute presentation
• oligoarticular types occur in young girls and preadolescent boys
• arthritis is usually symmetric and involves one or more large joints (knees)
• mild systemic complaints may exist such as low grade fever, anemia, and malaise
• Differential includes reactive and post-infectious arthritis

Question 10

oligoarticular JIA

Answer 10

• more common in girls
• clinical manifestations
  
  • arthritis of the large joints (knee > ankle > wrist)
  • uveitis is the only systemic manifestation
  • involves less than five joints
  • ANA often positive, rheumatoid factor usually negative
  • may have no fever or abnormalities of inflammatory markers (WBC, ESR, CRP)
• complications
• 30% get uveitis
  
  • uveitis untreated may progress toward blindness
  • inflammation may cause bony changes that distort growth
• outcome
  
  • Treatment is NSAIDs and intra-articular steroids for most
  • >90% have complete remission

Question 11

polyarticular onset JIA

Answer 11

• more common in girls
• manifestations (ages 2-5 years)
  
  • progressive involvement of joints
  • symmetrical joint involvement
    
    • small joints of the hands & feet
    • ankles, wrists, & knees
    • may cause fusion of the cervical spine
  • uveitis - 10%
  • can present with systemic symptoms
    
    • malaise, fever, growth retardation, anemia, elevated inflammatory markers
• manifestations (ages 10-14 yrs)
  
  • arthritis of rapid onset
  • small joints of hands and feet typically involved
  • adolescents that are rheumatoid-factor positive probably have adult rheumatoid arthritis
• outcome
  
  • Treatment with methotrexate and NSAIDs
  • >50% have complete remission

Question 12

systemic onset JIA

Answer 12

• laboratory findings
  
  • leukocytosis
  • thrombocytosis
  • anemia
  • elevated ESR
  • AST/ALT elevation, hypoalbuminemia
  • complications
  • macrophage activation syndrome
    
    • uncontrolled proliferation of lymphocytes and macrophages
  • prone to sequelae of chronic systemic inflammation
    
    • growth retardation
    • osteoporosis

Question 13

dermatomyositis

Answer 13

• inflammatory disease of muscle and skin
• clinical manifestations
  
  • weakness in proximal muscle distribution
  • tenderness of muscles
  • absent deep tendon reflexes
  • flexion contractures and muscle deformities
  • rash
    
    • heliotrope rash of upper eyelids (red-purple color)
    • Gottron’s papules
      
      • extensor surfaces knuckles, elbows, knees
      • start as erythema, progressing to scales
• laboratory findings
  
  • elevated muscle-source enzymes
    
    • creatinine kinase
    • aldolase
  • muscle biopsy
• electromyography
• MRI
• treatment
  
  • physical therapy
  • medications
    
    • steroid anti-inflammatories
    • methotrexate
    • refractory cases
      
      • IVIG
      • cyclosporine