Chapter 019. Fever of Unknown Origin (Part 4)

Specialized Diagnostic StudiesClassic FUO A stepwise flow chart depicting the diagnostic workup and therapeutic management of FUO is provided in Fig. 19-1. In this flow chart, reference is made to "potentially diagnostic clues," as outlined by de Kleijn and colleagues; these clues may be key findings in the history (e.g., travel), localizing signs, or key symptoms. Certain specific diagnostic maneuvers become critical in dealing with prolonged fevers. If factitious fever is suspected, electronic thermometers should be used, temperature-taking should be supervised, and simultaneous urine and body temperatures should be measured. Thick blood smears should be examined for Plasmodium; thin...
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Chapter 019. Fever of Unknown Origin (Part 4) Chapter 019. Fever of Unknown Origin (Part 4) Specialized Diagnostic Studies Classic FUO A stepwise flow chart depicting the diagnostic workup and therapeuticmanagement of FUO is provided in Fig. 19-1. In this flow chart, reference is madeto potentially diagnostic clues, as outlined by de Kleijn and colleagues; theseclues may be key findings in the history (e.g., travel), localizing signs, or keysymptoms. Certain specific diagnostic maneuvers become critical in dealing withprolonged fevers. If factitious fever is suspected, electronic thermometers shouldbe used, temperature-taking should be supervised, and simultaneous urine andbody temperatures should be measured. Thick blood smears should be examinedfor Plasmodium; thin blood smears, prepared with proper technique and qualitystains and subjected to expert microscopy, should be used to speciate Plasmodiumand to identify Babesia, Trypanosoma, Leishmania, Rickettsia, and Borrelia. Anytissue removed during prior relevant surgery should be reexamined; slides shouldbe requested, and, if need be, paraffin blocks of fixed pathologic material shouldbe reexamined and additional special studies performed. Relevant x-rays should bereexamined; reviewing of prior radiologic reports may be insufficient. Serumshould be set aside in the laboratory as soon as possible and retained for futureexamination for rising antibody titers. Figure 19-1 Approach to the patient with classic FUO. aPotentially diagnosticclues, as outlined by de Kleijn and colleagues (1997, Part II), may be keyfindings in the history, localizing signs, or key symptoms. ANA, antinuclearantibody; CBC, complete blood count; CMV, cytomegalovirus; CRP, C-reactiveprotein; CT, computed tomography; Diff, differential; EBV, Epstein-Barr virus;ESR, erythrocyte sedimentation rate; FDG, fluorodeoxyglucose F18; NSAIDs,nonsteroidal anti-inflammatory drugs; PET, positron emission tomography; PMN,polymorphonuclear leukocyte; PPD, purified protein derivative; RF, rheumatoidfactor; SPEP, serum protein electrophoresis; TB, tuberculosis; TIBC, total iron-binding capacity; VDRL, Venereal Disease Research Laboratory test. bNeedlebiopsy of liver as well as any other tissue indicated by potentially diagnosticclues. cInvasive testing could involve laparoscopy. dEmpirical therapy is a lastresort, given the good prognosis of most patients with FUO persisting without adiagnosis. Febrile agglutinins is a vague term that in most laboratories refers toserologic studies for salmonellosis, brucellosis, and rickettsial diseases. Thesestudies are seldom useful, having low sensitivity and variable specificity. Multipleblood samples (no fewer than three and rarely more than six, including samples foranaerobic culture) should be cultured in the laboratory for at least 2 weeks toensure that any HACEK group organisms that may be present have ample time togrow (Chap. 140). Lysis-centrifugation blood culture techniques should beemployed in cases where prior antimicrobial therapy or fungal or atypicalmycobacterial infection is suspected. Blood culture media should be supplementedwith L-cysteine or pyridoxal to assist in the isolation of nutritionally variantstreptococci. It should be noted that sequential cultures positive for multipleorganisms may reflect self-injection of contaminated substances. Urine cultures,including cultures for mycobacteria, fungi, and CMV, are indicated. In the settingof recurrent fevers with lymphocytic meningitis (Mollarets meningitis),cerebrospinal fluid can be tested for herpesvirus, with use of the polymerase chainreaction (PCR) to amplify and detect viral nucleic acid (Chap. 172). A recentreport described a highly multiplexed oligonucleotide microarray using PCRamplification and containing probes for all recognized vertebrate virus species andfor 135 bacterial, 73 fungal, and 63 parasitic genera and species. The eventualclinical validation of such microarrays will further diminish rates of undiagnosedFUO of infectious etiology.