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