Fever of Unknown Origin and Adult Onset Still

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Fever of Unknown Originand Adult Onset Stills
Disease (AOSD)

• AM Report
• Eric Edwards, M.D.
• September 4, 2007

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Fever of Unknown Origin Definition

• NOT febrile illness without initially obvious
  etiology
• Classical definition (Petersdorf and Beeson,
  1961)
• Fever gt 38.3 on several occasions
• Durationgt3 weeks
• Failure to reach a diagnosis after one week of
  inpatient investigation

or at least 3 outpatient visits (refined
definition)
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Patient Subtypes

• Classical
• Nosocomial (Hospitalizedgt24h, no fever PTA)
• C. Difficile, PE, drugs
• Immune Deficient (ANClt500)
• Bacteremia, Fungal, HSV
• HIV
• M. Avium, PCP, CMV, lymphoma, Kaposis, drugs

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Differential Diagnosis

• Infections
• Malignancies
• Autoimmune Disease
• Miscellaneous
• Drugs
• Hepatitis
• DVT

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Roth AR and Basello GM. Am Fam Physician. 2003
Dec 168(11)2223-8.
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Roth AR and Basello GM. Am Fam Physician. 2003
Dec 168(11)2223-8.
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Causes of FUO(in India)

• Infectious 53
• 1 TB (45)
• Neoplasm 17
• 1 NHL (47)
• Collagen Vasc. 11
• 1 SLE 45
• Miscellaneous 5
• Undiagnosed 14

Kejariwal D et al. J Postgrad Med. 2001 Apr-Jun
47(2) 104-7.
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FUO by the Decades
1950s
1970s
1980s
1990s
Mourad O et al. Arch Int Med. 2003 Mar
10163(5)545-51.
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Minimal Diagnostic Criteria

• HP
• CBC Diff
• Blood Cultures x 3
• Chem10
• LFTs

• U/A and Microscopy
• Urine culture
• Chest X-ray
• Hepatitis serologies (if abnormal LFTs)

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Other Basic Tests

• ESR/CRP
• Peripheral Smear
• ANA
• Rheumatoid Factor
• HIV
• CMV IgM
• Mono Spot
• PPD

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Imaging

• Abdominal CT
• Chest CT
• Nuclear Imaging
• Lower Extremity Dopplers
• TTE/TEE

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Invasive Procedures

• Lumbar Puncture
• Liver Biopsy
• Temporal Artery Biopsy
• Bone Marrow Biopsy
• Lymph Node Biopsy
• Surgical Exploration of the Abdomen

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Roth AR and Basello GM. Am Fam Physician. 2003
Dec 168(11)2223-8.
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Adult Onset Stills Disease

• Epidemiology
• Rare (0.16/100000)
• 60 female
• Affects all ages
• Pathogenesis
• Poorly understood
• Genetic component?
• Infectious trigger?
• Characteristics
• Daily, high spiking fevers (85-100)
• Arthritis (68-94)
• Evanescent rash (51-87)
• No specific diagnostic study
• Diagnosis is based on the presentation of
  characteristic features and the exclusion of
  similar conditions

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Diagnostic Criteria (Yamaguchi)

• Major
• Fevergt39, lasting gt1 week
• Arthralgias or arthritis lasting gt2 weeks
• Typical rash
• WBCgt10,000 with gt80 PMNs

• Minor
• Sore throat
• Lymphadenopathy and/or splenomegaly
• Abnormal LFTs
• Negative ANA and RF
• Exclusions
• Infections
• Malignancy
• Rheumatic Disease

Diagnosis Five criteria, at least two major
(83-91 sens., 90 spec., 70 PPV, 95 NPV)
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AOSD and Ferritin

• Ferritin is an acute phase reactant
• 80 have gt5x elevation in ferritin
• Non-specific
• Low Glycosylated ferritin (GF) is more specific
• GFlt20 Ferritin gt5x nl93 specific
• Only 43 sensitive

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Treatment

• NSAIDs
• Monotherapy is effective in only 10
• Steroids
• 75 will respond favorably
• Methotrexate
• TNF blocking agents
• Etanercept
• Infliximab

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Prognosis

• Three distinct patters (111)
• Self limited
• Most patients achieve remission within one year
• Intermittent
• Recurrent flares with complete remission between
• Flares may be years apart
• Recurrences tend to be milder than initial
  episode
• Chronic
• Articular manifestations can be severe
• 2/3 may need at least one total joint replacement

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References

• 1. Roth AR et al. Approach to the Patient with
  Fever of Unknown Origin. Am Fam Physician. 2003
  Dec 168(11)2223-28.
• 2. Mourad O et al. A Comprehensive Evidence Based
  Approach to Fever of Unknown Origin. Arch Int
  Med. 2003 Mar 10163545-51.
• 3. Bor, DH. Approach to the Adult with Fever of
  Unknown Origin. www.utdol.com.
• 4. Kejariwal D et al. Pyrexia of Unknown Origin
  A Prospective Study of 100 Cases. J Postgrad Med.
  2002 Apr-Jun48(2)155-6.
• 5. Efthimiou P et al. Diagnosis and Management of
  Adult Onset Stills Disease. Ann Rheum Dis. 2006
  May65564-72.
• 6. Uppal SS et al. Ten Years of Clinical
  Experience with Adult Onset Stills Disease Is
  the Outcome Improving? Clin Rheumatol. 2007
  Jul26(7)1055-60.