Fever of unknown origin differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: febris continua e causa ignota; febris e causa ignota; febris E.C.I.; FUO; PUO; pyrexia of unknown origin

Overview

  1. Fever can be the presenting symptom with many diseases, it is therefore important to differentiate fever of unknown origin from all those diseases which present with fever.
  2. Because of the broad range of differential diagnosis they can be grouped into four categories based on their etiology.

Differential diagnosis

Infectious

These patients mostly have a history of hospitalization, surgical procedures, contact with infected person or travel to an endemic place.[2][3]

Examples include:


Infectious

Disease History Physical examination Laboratory or radiological findings
Subacute Bacterial endocartitis Recent dental procedures, Joint pain, decrease weight, Night sweats, back pain
Heart murmur, splinter hemorrhages, Janeway lesions, Roth spots, enlarged spleen.
Elevated WBCs, decreased platelets, Elevated ESR , presence of Cryoglobulins
Abscess GI, genitourinary, Pelvic procedure or infection , fever, chills, decrease weight, night sweats.
RUQ tenderness ( subphrenic Abscess),hepatomegaly (hepatic abscess), splenomegaly ( splenic abscess), tenderness on DRE ( pelvic abscess).
Elevated WBCs and ESR, elevated platelets, Positive CT/MRI findings
Tuberculosis of CNS Previous tuberculosis, Altered mental status, Headace
Morning temperature spikes, relative bradycardia, Abducens palsy.
CSF: Increased lymphocytes, increased RBCs, decreased glucose, increased lactate, positive AFB stain and Culture.
EBV infection Exposure to saliva ( kissing disease ) , upper respiratory tract infection
Enlarged lymph nodes, palatal petechiae, enlarged tonsils, enlarged spleen.
Positive monospot test, decreased WBCs, decreased lymphocytes, atypical lymphocytosis, positive PCR, positive IgM EBV VCA titers, enlarged spleen, increased LFTs.
CMV infection Exposure to body fluids or blood transfusion
Enlarged lymph nodes, palatal petechiae, enlarged tonsils, enlarged spleen.
Negative monospot test, decreased WBCs, decreased lymphocytes, atypical lymphocytosis, positive PCR, increased IgM, increased LFTs
HIV infection Exposure to body fluids (blood, breast milk, semen and vaginal secretions), IV drug abuse, weight loss, night sweats .
Generalized lymphadenopathy, pharyngeal and palatal petechiae.
Decreased lymphocytes, decreased platelets, positive HIV serology and PCR , increased viral load.
Toxoplasmosis Exposure to cat feces or consumption of uncooked meat, joint pain.
Chorioretinitis, enlarged lymph nodes, enlarged spleen.
Atypical lymphocytes, increased IgM titers ( toxoplasma serology), Positive MRI/CT scan finding in brain ( ring enhancing lesions ).
Ehrlichiosis/ Anaplasmosis Recent insect (Tick) exposure, Headache, muscle aches, fatigue,
Relative bradycardia, enlarged spleen.
Decreased WBCs, decreased platelets, inclusions in Monocytes (Ehrlichiosis ) and Granulocytes (Anaplasmosis ), positive serology.
Leptospirosis Exposure to water contaminated with animal (Rodents) urine, common in surfers, Flu like symptoms, Headache.
Calf tenderness, Photophobia, Jaundice, conjunctival suffusion without exudate, enlarged liver.
Increased WBCs, Decreased platelets, increased LFTs, Increased creatinine kinase, positive serology.
Brucellosis Exposure to animals or contaminated dairy products (milk, cheese), Headache, muscle aches, fatigue,
Muscle (Thigh) tenderness, Spine tenderness, enlarged lymph nodes, enlarged spleen.
Positive serology, increased LFTs , Atypical lymphocytes, positive blood culture.
Histoplasmosis Cave exploration, Mississippi and Ohio river valleys location, weight loss, night sweats
Palatal/tongue ulcers, enlarged spleen, enlarged liver.
Decreased WBCs, decreased platelets, increased LFTs, positive serum and urine antigen test.
Q fever Exposure to cattle/sheep amniotic fluid, night sweats, weight loss, prosthetic heart valve.
Relative bradycardia, heart murmur, enlarged spleen.
Decreased platelets, increased LFTs, positive PCR

Malignant

They are mostly accompanied by loss of weight, decrease in appetite, lymph node enlargement and aquagenic pruritic mostly occurring after hot shower.

Examples include:

Autoinflammatory/Rheumatologic

Mostly they have multi organ involvement and lymphadenopathy along with joint symptoms may be present.[4][5]

Examples include:


Disease History Physical examination Laboratory or radiological findings

Miscellaneous

Mostly does not belong to any of the above.

Examples include:


References

  1. ↑ Cunha, Burke A.; Lortholary, Olivier; Cunha, Cheston B. (2015). "Fever of Unknown Origin: A Clinical Approach". The American Journal of Medicine. 128 (10): 1138.e1–1138.e15. doi:10.1016/j.amjmed.2015.06.001. ISSN 0002-9343.
  2. ↑ Cunha, Burke A.; Lortholary, Olivier; Cunha, Cheston B. (2015). "Fever of Unknown Origin: A Clinical Approach". The American Journal of Medicine. 128 (10): 1138.e1–1138.e15. doi:10.1016/j.amjmed.2015.06.001. ISSN 0002-9343.
  3. ↑ Salzberger B, Schneidewind A, Hanses F, Birkenfeld G, Müller-Schilling M (2012). "[Fever of unknown origin. Infectious causes]". Internist (Berl). 53 (12): 1445–53, quiz 1454-5. doi:10.1007/s00108-012-3173-8. PMID 23111594.
  4. ↑ Kümmerle-Deschner JB (2017). "[Autoinflammatory Diseases as a Differential Diagnosis of Fever of Unknown Origin]". Dtsch Med Wochenschr. 142 (13): 969–978. doi:10.1055/s-0043-103468. PMID 28672419.
  5. ↑ Mulders-Manders CM, Simon A, Bleeker-Rovers CP (2016). "Rheumatologic diseases as the cause of fever of unknown origin". Best Pract Res Clin Rheumatol. 30 (5): 789–801. doi:10.1016/j.berh.2016.10.005. PMID 27964789.

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References

Disease History Physical examination Laboratory or radiological findings
Subacute Bacterial endocartitis Recent dental procedures, Joint pain, decrease weight, Night sweats, back pain
Heart murmur, splinter hemorrhages, Janeway lesions, Roth spots, enlarged spleen.
Elevated WBCs, decreased platelets, Elevated ESR , presence of Cryoglobulins
Abscess GI, genitourinary, Pelvic procedure or infection , fever, chills, decrease weight, night sweats.
RUQ tenderness ( subphrenic Abscess),hepatomegaly (hepatic abscess), splenomegaly ( splenic abscess), tenderness on DRE ( pelvic abscess).
Elevated WBCs and ESR, elevated platelets, Positive CT/MRI findings
Tuberculosis of CNS Previous tuberculosis, Altered mental status, Headace
Morning temperature spikes, relative bradycardia, Abducens palsy.
CSF: Increased lymphocytes, increased RBCs, decreased glucose, increased lactate, positive AFB stain and Culture.
EBV infection Exposure to saliva ( kissing disease ) , upper respiratory tract infection
Enlarged lymph nodes, palatal petechiae, enlarged tonsils, enlarged spleen.
Positive monospot test, decreased WBCs, decreased lymphocytes, atypical lymphocytosis, positive PCR, positive IgM EBV VCA titers, enlarged spleen, increased LFTs.
CMV infection Exposure to body fluids or blood transfusion
Enlarged lymph nodes, palatal petechiae, enlarged tonsils, enlarged spleen.
Negative monospot test, decreased WBCs, decreased lymphocytes, atypical lymphocytosis, positive PCR, increased IgM, increased LFTs
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