Pyrexia of unknown origin "PUO"

 Definition:
 A case presented with pyrexia as a predominant clinical feature of 10 days or longer duration without an obvious cause.
 It may be acute (if pyrexia persists for few days) or chronic (if pyrexia persists for 3 weeks or longer).

Causes:
 I- Infective:
 A) Non specific e.g:
 Cryptic abscesses in liver, abdomin, pelvis and retroperitoneal or mediastinal sites.
 Infective endocarditis.
 Urinary tract infection.
 Ear, sinus or dental infections.
 Osteomyelitis.
 B) Specific e.g:
 Bacterial: T.B., brucellosis, typhoid F., leptospirosis (Weil’s disease), secondary syphilis.
 Viral: viral hepatitis, glandular fever, yellow fever, CMV, HIV.
 Rickettsial: typhus and Q fever.
 Chlamydial and Bortonella: psittacosis and cat scratch fever.
 Fungal: candidiasis, histoplasmosis, cryptococcosis and aspergillosis.
 Protozoal: malaria, amaebiasis, toxoplasmosis, trypanosomiasis and leishmaniasis.
 Helminthic: filariasis and fasciola.
 II- Non-infective:
 Haematological: e.g leukemia, purpura, haemolytic anaemia and lymphoma.
 Autoimmune and collagen: e.g rheumatic fever, rheumatoid arthritis, SLE, polyarteritis nodosa, dermatomyositis and ulcerative colitis.
 Endocrine: e.g thyrotoxicosis and familial mediteranean fever.
 Malignancy: sarcoma, carcinoma, hepatoma and hypernephroma.
 Miscellaneous:
 Liver cirrhosis and alcoholic hepatitis.
 Gout (rare).
 Granulomas e.g sarcoidosis, Crohn's disease.
 Drug reaction.
 CNS abnormalities e.g infiltration of heat regulating center in hypothalamus by neoplasm or granuloma (rare).
 Malingering.
Laboratory Diagnosis
 Haematological:
 Hb for anaemia.
 Platelets for purpura.
 WBCs: total and differential count.
 Neutrophilia in pyrogenic infection.
 Neutropenia in malaria; typhoid; leishmaniasis and SLE.
 Lymphocytosis in viral infection, typhoid and brucellosis.
 Monocytosis in TB; atypical monocytes in IMN.
 Blast cells in leukemia.
 Thin and thick blood film in malaria; filaria; trypanosomiasis.
 ESR: > 100 mm/h in T.B; collagen and malignancy.
 Microbiological:
 Blood culture for typhoid, brucellosis, leptospirosis and infective endocarditis.
 Urine and stool culture for UTI, gastrointestinal infections, salmonellosis, brucellosis, leptospirosis. In sterile pyuria: T.B. of genitourinary tract is suspected.
 Throat swab if rheumatic fever is suspected, negative culture not exclude rheumatic fever.
 Bone marrow culture for typhoid, brucellosis, T.B.
 Serology:
 Paired serum samples are required to look for rising antibody titer four folds. Occasionally, a single high titer maybe suggestive of recent infection e.g IgM for toxoplasma.
 Some serological tests for diagnosing PUO:
 Widal test for typhoid (diagnostic titre > 1/80).
 Brucella agglutination and CFT (diagnostic titre >1/80).
 ASO titre for rheumatic fever (diagnostic titre > 250 Todds U/ml).
 Latex co-agglutination to detect Ag as Streptococcal, Staph. species, Neisseria, Candida and Rota viruses.
 ELISA techniques for detection of microbial antigens e.g. Chlamydial Ag, HB Ag & HIV Ag and microbial antibodies e.g. CMV Ab, HBAb and T.B. (IgA, IgG, IgM).
 Fluorescent treponemal antibody, fluorescent amaebic antibody and fluorescent leishmanial antibody test.
 PCR technique for HCV-RNA, HBV-DNA, T.B-DNA, CMV & HSV.

 3) Biochemical:
 Liver function tests.
 Thyroid function tests.
 Alpha Feto Protein (AFP) for hepatoma.
 Uric acid for gout.
 C) Biopsy:
 Bone marrow, lymph nodes, liver and transbronchial lung biopsies for culture and cytology.
 D) Skin tests: e.g
 Mantoux test for TB.
 Kveim test for sarcoidosis.
 Histoplasmin test for Histoplasmosis.
 Frei test for Chlamydia (lymphogranuloma venereum).
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