Malady Wise

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Unknown Fever

Maladywise

Definition

Prolonged fever without a diagnosis despite extensive testing

Categories

Infections = 38%

Connective tissue = 21%

Malignancies = 12%

Misc = 6%

No diagnosis = 23%

Infections

A systemic review of 832 cases worldwide showed

Tuberculosis = 34% (presentations that escape detection as extrapulmonary and miliary)

Brucellosis = 10%

Endocarditis = 8% (cultures negative in up to 5%, TOE is positive in 90% of cases)

  • Q fever

  • Whipple’s

  • Brucella

  • Mycoplasma

  • Chlamydia

  • Histoplasma

  • Legionella

  • Bartonella

  • HACEK (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella) need 21 days of incubation on blood cultures

Abscess = 7% (commonly abdomen or pelvis, conditions that predispose are cirrhosis, immunosuppression, recent surgery and diabetes)

Other

  • HIV

  • Herpesviruses e.g. CMV EBV

  • Pneumonia

  • UTI

  • Typhoid

  • Osteomyelitis (vertebral, mandible, discitis)

  • Dental abscesses

  • Fungal (Sporotrichosis)

  • Opportunistic with HIV (CMV, MAC, PCJ, Fungi, Protozoa)

  • Secondary syphilis

  • Disseminated gonoccocemia, meningococcemia, leishmaniasis, yersiniosis

  • Tick-borne (Babesiosis, Lyme, Anaplasmosis, Ehrlichiosis, Borrelia)

  • Pulmonary infections (Q fever, leptospirosis, psittacosis, tularaemia, melioidosis)

  • Helminths

Connective Tissue

Temporal arteritis

Adult-onset Still’s disease (fever, arthritis, rash)

Polyarteritis nodosa

Takayasu’s arteritis

Granulomatosis with polyangiitis

Mixed cryoglobulinemia

Sarcoidosis

SLE

Rheumatoid arthritis

Malignancy

Lymphoma

Leukemia

Multiple Myeloma

Renal cell carcinoma (20% of cases have fever)

Hepatocellular and mets to liver

Atrial myxomas

Sarcoma

Miscellaneous

Drugs (allergic or idiosyncratic reaction)

Factitious

Disordered heat homeostasis (hypothalamic dysfunction following a stroke or ABI, or skin conditions such as ichthyosis)

Alcoholic hepatitis (fever hepatomegaly, jaundice and anorexia)

Venous thrombosis (dyspnoea, pleuritic pain, cough, haemoptysis)

Haematoma with subsequent inflammation

Hyperthyroidism and thyroiditis

Phaeochromocytoma and adrenal insufficiency

Hereditary period fever syndromes (Mediterranean fever, TRAPS)

Diagnostic approach

Study showed 10 potential diagnostic clues per patient from history and exam

3 potential clues from laboratory testing

81% of these clues were misleading

History

  • Travel

  • Animal exposure

  • Immunosuppression

  • Drugs and toxin history

  • Localising symptoms

Blood tests

FBC, Platelets, LFT, UEC

CRP/ESR (ESR>100 = 58% malignancy, 25% infection or systemic)

Blood cultures +/- test for 21 days

Urinalysis

=======

LDH

TB test

HIV

If abnormal LFT then Hepatitises

LDH

Rheumatoid Factor

CK

EBV test

ANA

SPEP

Imaging

Routine CXR (helpful in 8% of cases, false positive in 11% of cases)

CT chest abdo pelvis (CT chest helpful 9%, false positive 8% and CT abdo helpful 12%, false positive in 10%)

PET scan (helpful in 23%, false positive in 10%)

References

UpToDate - Less common causes of FUO [Needs Log In]

UpToDate - Causes of FUO in adults [Needs Log In]

UpToDate - Approach to adults with FUO [Needs Log In]