Mechanical/orthopedic problems: Joint hypermobility, benign joint hypermobility syndrome, localized hypermobility, Marfan syndrome, Ehlers–Danlos syndrome, irritable hip (transient synovitis), Perthes’ disease, other osteochondritis, slipped upper femoral epiphysis, chondromalacia patella, anterior patella syndrome, back pain

Inflammatory disorders: JIA, JRA, spondyloarthritis, psoriatic arthritis, SLE (lupus), juvenile dermatomyositis, IBD, MCTD, linear scleroderma, progressive systemic sclerosis, panniculitis, CRMO/SAPHO syndromes, vasculitis, KD, HSP

Infection/postinfective: Transient synovitis, rheumatic fever, septic arthritis, osteoarticular tuberculosis, brucella/lyme/fungal arthritis

Hematologic problems: Sickle cell disease, other hemoglobinopathies, hemophilia

Neoplasia: Leukemia, neuroblastoma, metastatic disease, primary bone tumors

Idiopathic pain syndromes: Nocturnal idiopathic pain syndrome (growing pains), reflex sympathetic dystrophy, widespread idiopathic pain syndrome, fibromyalgia

Metabolic disorders: Gout, mucopolysaccharidoses, mucolipidosis type III, Fabry’s disease, alkaptonuria, Lesch–Nyhan syndrome

Other: Sarcoidosis, immune complex deposition, cystic fibrosis, serum sickness, septicemia, immunodeficiency related, drug induced

Color and Clarity

Viscosity

WBC (cells/mm3)

PMN (%)

Miscellaneous Findings

Noninflammatory

Normal

Yellow and clear

Very high

<200

<25

Traumatic arthritis

Xanthochromic and turbid

High

<2,000

<25

Debris

Inflammatory

Chronic arthritis

Yellow and cloudy

Decreased

15,000–20,000

75

Reactive arthritis

Yellow and opaque

Decreased

20,000

80

Pyogenic

Tuberculous arthritis

Yellow-white and cloudy

Decreased

25,000

50–60

Acid-fast bacteria

Septic arthritis

Serosanguinous and turbid

Decreased

50,000–300,000

>75

Low glucose, bacteria present

Systemic lupus erythematosus (SLE)

ANA

Anti-dsDNA

Anticardiolipin Ab (lupus anticoagulant)

Anti-Smith Ab

57%/93%

97%/57%

Yes/No

High/25%–30%

Moderate

95%

Low

97%

Drug-induced lupus

Antihistone Ab1

High/95%

High

Scleroderma

ANA

Anticentromere

Anti–Scl-70

54%/85%

99.9%/65%

100%/20%

High

High

High

MCTD

ANA

Anti-U1 ribonucleoprotein (RNP)1

No/93%

High/Moderate

High

High

Polymyositis, Dermatomyositis

CK

Anti–Jo-1 Ab

Muscle biopsy

No/High

Yes/30%–50%

Yes/Moderate

Low

High

High

Sjögren’s syndrome

ANA

Anti-SSA/Ro (type A)2

Anti-SSB/La (type B)

52%/48%

87%/8%–70%

94%/16%–40%

Moderate

40%

40%

Wegner’s granulomatosus

Anti-proteinase 3 Ab

c-ANCA Ab

High/moderate

50%/95%

High

High

Percent of cases

60

30

10

Clinical presentation

≤4 joints involved; predominantly knees, ankles, fingers, wrists, and elbows in an asymmetric fashion

>4 joints involved; large and small joints;

Variable number/types of joints involved; concomitant arthritis, quotidian fever, and salmon-colored evanescent rash that is sometimes pruritic; rash appears as fever subsides; HSM, LAD, serositis; ↓ H/H, ↑ plt, ↑ WBC; elevated inflammatory markers; ↑ transaminases

Age of onset

Peak 1–2 yo; early childhood

Peak 1–3 yo; all ages

No peak; throughout childhood

Sex ratio (♀:♂)

5:1

3:1

1:1

Systemic involvement

Absent; major morbidity is uveitis

Generally mild; possible unremitting articular involvement

Often self-limited; 50% with chronic and destructive arthritis

Occurrence of chronic uveitis

5%–15%

5%

Rare

⊕RF

⊕ANA

Rare

75%–85%3

10%2

40%–50%

Rare

10%

Prognosis

Excellent except eyesight

Guarded to moderately good

Moderate to poor

Treatment

• NSAIDS
  
• ± intra-articular steroid injections
  
• MTX

• NSAIDS + therapies below
  
• Corticosteroids
  
• MTX, sulfasalazine, azathioprine
  
• Biologic agents: TNF-α inhibitors (infliximab, etanercept, adalimumab; IL-1 receptor antagonists), IL-1 inhibitor (anakinra)

Additional options for treatment

Other biologic agents: abatacept (FDA approved for adults); rituximab (FDA approved for adults)

Anti–IL-6 monoclonal, antibody tozilizumab, currently under investigation

General informations

Presentation

Presents late childhood to adolescence; ♂:♀ is 3:1

Age at presentation varies with causative organism (urogenital Chlamydia generally presents later than disease from enteric Salmonella, Shigella, Yersinia, or Campylobacter); ♂ > ♀

Chronic arthritis ± psoriasis in patient <16 yo (if no psoriasis, two of the following three need to be present: dactylitis, nail changes, or 1st-degree relative with psoriasis); presents preschool or late childhood; ♀ > ♂

Clinical Manifestations

Articular

• Lower extremity (hips, SI joint) > upper extremity involvement; intermittent joint stiffness and musculoskeletal pain; enthesitis particularly around knee/foot; peripheral joint exam may be same as oligoarticular JIA
  
• Axial skeleton findings:
  
  
  
  • Schober test: limited forward lumbar flexion3
    
  • Patrick test: assess SI joint tenderness4
    
  • Chest wall excursion may be ↓

• Asymmetric oligoarthritis (knees, ankles, feet; rarely wrists and digits)
  
• Enthesitis (especially involving the Achilles tendon and plantar fascia)
  
• Axial skeleton affected in less than half

• Asymmetric, oligoarticular joint involvement; commonly large and small joints
  
  
  
  • Small joints of the hands and feet
    
    
    
    • Dactylitis (arthritis of a digit with tenosynovitis)
      
    • Arthritis can be quite painful; associated with irreversible joint destruction and deformity
  
  
• <5% axial spinal involvement
  
• Enthesitis contributes to pain

Extra-articular

Minimal constitutional sx and signs:

• May have c/o sleep disturbance due to pain
  
• Most frequent are eye-related sx/signs5

Consider IBD if bloody diarrhea, abdominal pain, erythema nodosum, pyoderma gangrenosum, or aphthous stomatitis are present

• Eye: Sterile conjunctivitis, anterior uveitis (20%)
  
• GI: Sterile ileitis/colitis
  
• GU: Urethritis and cervicitis rare (↑ frequency with Chlamydia)
  
• Mucocutaneous: Painless ulceration of glans and psoriaform lesions on plantar surface of feet may occur with urogenital causes, oral ulcers
  
• ± constitutional symptoms: fever, fatigue, and weight loss

• ∼50% develop arthritis prior to psoriasis
  
• Nail changes may include pitting, ridging, onycholysis, and hyperkeratosis
  
• Conjunctivitis in 20% and iritis in 7%

Diagnosis (thorough H&P ± additional workup/studies suggested below)

Laboratory evaluation

CBC (± ↓ H/H, ↑ WBC, ↑ plt), ESR and CRP (± ↑), HLA-B27 (90% ⊕; associated with severe disease); consider full IBD evaluation

• Diagnosis is clinical.
  
• HLA-B27 positivity is common in patients with axial disease and enthesitis

Radiologic studies

X-ray guided by exam (may be normal but with disease progression will see soft-tissue changes);

MRI with contrast of SI joints (bone marrow edema, granulation tissue or cortical erosion→ joint irregularity and narrowing)

X-ray guided by exam (may show soft-tissue swelling → if severe arthritis persists, erosions, syndesmophytes, subchondral cysts, and joint destruction)

Treatment

NSAIDs first-line; MTX, azathioprine, sulfasazine, anti–TNF-α agents based on severity

Treat underlying infection; NSAIDs; first-line corticosteroids for severe disease

Same as Juvenile Ankylosing Spondylitis

Need 4 out of 11 criteria to be serially present at the time of presentation

1. 
   

   Malar rash (also known as a “butterfly” rash—flat or raised erythematous rash that spares the nasolabial folds)

   
   
2. 
   

   Discoid rash (erythematous raised patches with keratotic scaling and follicular plugging)

   
   
3. 
   

   Photosensitive rash (sun-exposed areas)

   
   
4. 
   

   Oral ulcers (oral or nasopharyngeal painless ulcerations)

   
   
5. 
   

   Nonerosive arthritis ≥2 peripheral joints

   
   
6. 
   

   Blood abnormalities (cytopenia, including Coomb’s positive hemolytic anemia, leucopenia [<4000 cells/mm3], lymphopenia [<1500 cells/mm3], and/or thombocytopenia [<100,000/mm3])

   
   
7. 
   

   Serositis (pleuritis, pericarditis)

   
   
8. 
   

   Renal involvement (proteinuria >0.5 g/day or >3+ protein, cellular casts)

   
   
9. 
   

   Positive ANA (in the absence of a drug exposure that can cause a false-positive ANA: hydralazine, procainamide, minocycline, INH, penicillin, sulfonamides, and anticonvulsants)

   
   
10. 
    

    Immunologic manifestation (any of the following: anti-dsDNA, anti-Smith, antiphospholipid antibodies, or anticardiolipin antibodies, lupus anticoagulant, or a false-positive syphilis serologic test for 6 mo, confirmed negative by Treponema pallidum immobilization/fluorescent treponemal antibody absorption test)

    
    
11. 
    

    Neurologic disease (psychosis or seizures in the absence of drugs or metabolic derangements)