Pyrexia of unknown origin


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A practical approach for evaluating PUO in paediatrics.

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  • Although not diagnostic, at times fever curves can be suggestive. Hectic fevers, because of wide swings in temperature, are often associated with chills and sweats. This pattern is thought to be very suggestive of an abscess or pyogenic infection such as pyelonephritis and ascending cholangitis, but may also be seen with tuberculosis, hypernephromas, lymphomas, and drug reactions.Continuous or sustained fever is usually not associated with true chills or rigors. It is characteristic of typhoid fever or typhus, although commonly seen in bacterial endocarditis, tuberculosis, fungal disease, and bacterial pneumonia. Noninfectious etiologies include neoplasms, connective tissue disease, and drug fever.Relapsing fevers may be seen in rat-bite fever, malaria, cholangitis, infections with Borreliarecurrentis, Hodgkin's disease (Pel-Ebstein fever), and other neoplasms.Historically, some diseases are described as having characteristic fever patterns. The double quotidian fever of gonococcalendocarditis has two spikes in a 24-hour period. Fever at 48-hour intervals suggests Plasmodium vivax or P. ovale; 72-hour intervals suggest P. malariae, while P. falciparum often has an unsynchronized intermittent fever.Most fevers follow the usual diurnal pattern. Disseminated tuberculosis, typhoid fever, and polyarteritisnodosa are important exceptions in which reversal of the usual diurnal pattern ("typhus inversus" pattern) can be observed. A reversed pattern is also seen with old age and with salicylate ingestion.Contrary to widely held beliefs, the height of temperature elevation has little diagnostic significance. Although thermoregulatory defects should certainly be thought of when temperatures exceed 40.5°C, infection, either alone (39%) or coexisting with a thermoregulatory defect (32%), has been found in 71% of patients with extreme (41.1°C or greater) pyrexia.Drug fevers also may exceed 40.5°C and may simulate septicemia. Drugs causing fever (Table 211.1) may do so by administration-related mechanisms (e.g., amphotericin, phlebitis, fluid contamination), pharmacologic action of the drug (e.g., Jarish–Herxheimer reaction, tumor cell necrosis with chemotherapeutic agents), alteration of thermoregulation (see Table 211.2), idiosyncratic susceptibility (e.g., malignant hyperthermia), or drug-specific hypersensitivity (e.g., penicillin, methyldopa, quinidine). Patients with drug fever may appear well or quite ill and may or may not have a relative bradycardia. Rapid resolution of fever is seen with discontinuation of the medication in the vast majority of cases.As a rule, the pulse rate rises about 15 beats/min for each degree centigrade of fever. When this expected rise is not seen, a relative bradycardia exists and, in the absence of beta-adrenergic blockers, suggests one of the diseases listed in
  • Pyrexia of unknown origin

    2. 2. Answer this:The commonest cause of PUO is: a) A common disease presenting in atypical way. b) A rare disease presenting in atypical way. c) A common disease presenting typically. d) A rare disease presenting typically. The answer is ..A
    3. 3. Normal Body Temperature The hypothalamus is the heat-regulating center of the body and helps in maintaining a stable body temperature. The normal body temperature ranges from 37.0 degree C and 37.5 degree C with evening temperatures being 0.5-1.0 degree C higher than in the morning. Oral temperature is about 0.4 degree C below as compared to rectal temperature and axillary temperature is about 1 degree C below rectal temperature. In infants and young children, a rectal temperature with a glass- mercury or digital-electronic thermometer is considered the gold standard for taking temperatures.
    4. 4. How to define fever clinically? Persistent elevation of body temperature above the normal levels in an individual. The child has fever if:o Rectal temperature >100.4 degrees F (38 C)o Oral temperature >99.7 degrees F (37.6 C)o Axillary temperature >99 degree F (37 C)
    5. 5. Type of fever (fever patterns) Intermittent fever - Fever that touches normal for a few hours during the day. It is seen in malaria, acute pyelonephritis, local boils and furuncles. Remittent fever - Fever that fluctuates more than 1.5 degree F in 24 hours without touching normal. Continuous fever - Fever that does not touch normal and fluctuates less than 1.5 degree F in a day. It is seen in enteric fever, Bacterial endocarditis, viral pneumonia.
    6. 6.  A&B-Continuous fever C-Remittent D-Intermittent E-Relapsing fever F-Undulant fever
    7. 7. Liebermeisters rule The pulse rate rises about 15 beats/min for each degree centigrade of fever
    8. 8. Causes of Relative Bradycardia. Factitious fever Drug fever Legionnaires disease Psittacosis Typhoid fever (Fagets sign) Mycoplasma pneumonia Brucellosis Dengue Yellow fever Tuberculous meningitis Blackwater fever (Falciparum malaria with profound hemolysis)
    9. 9. Fever with Eponyms Pontiac fever---  Legionella pneumophila Shanghai fever---  Pseudomonas Brazilian purpuric fever---(pink  Hemophilus aegyptius eye) Havernhill fever---  Streptobacillus monoliformis Oroya fever---  Bartonella bacilliformis (Carrions d/s) Q fever---  Coxiella burnetti Colorado tick fever---  Orbivirus Trench fever---  Rochalimaea quintana (five day fever) Monkey fever -  Kayasanur forest disease Glandular fever -  IMN (EBV) Goal Fever -  R. prowazaki
    10. 10. PUO: Terminolgy Petersdorf and Beeson Criteria Old Definition: 1. Fever higher than 38.3oC on several occasions. 2. Duration of fever – 3 weeks 3. Uncertain diagnosis after one week of study in hospital New Definition:  Eliminated the in-hospital evaluation requirements → 3 outpatient visits, or 3 days in hospital. … Ambulatory as well as in hospital
    11. 11. Definition ExpansionDurack and Street Classification1. Classical PUO2. Nosocomial PUO3. Neutropenic PUO4. HIV-Associated5. Transplant
    12. 12.  Nosocomial PUO in hospital patients with fever of 38.3°C on several occasions caused by a process not present or incubating on admission where initial cultures are negative and diagnosis unknown after 3 days investigation. Neutropenic PUO includes patients with fever as above with <1 x 109 neutrophils with initial negative cultures and diagnosis uncertain after 3 days. HIV-associated PUO includes HIV-positive patients with fever as above for 4 weeks as outpatients or 3 days as inpatients, with an uncertain diagnosis after 3 days investigation where at least 2 days have been allowed for cultures to incubate.
    13. 13. Bacterial vs Viral feversBacterial Viral Leukocytosis  Uncommon Shift to left  Uncommon High grade fever  Low grade fever Neutropenia  uncommon Raised ESR and CRP  Uncommon Response to antibiotics  Usually self limiting
    14. 14. Common causes of FUO The causes are subdivided into 4 categories:o (1) infectious diseases, (40-60%)o (2) autoimmune diseases, (10-20%)o (3) malignancies, ando (4) miscellaneous.o Children younger than 6 years are most likely to have FUO resulting from an infection; autoimmune diseases start to become more common after 6 years, although infection remains the most frequent cause of FUO
    15. 15. FUO: Etiology: Bacterial Bacterial endocarditis  Pyelonephritis Bartonellosis  Salmonellosis Brucellosis  Sinusitis Chlamydia  Subdiaphragmatic abscess  Lymphogranuloma  Tuberculosis venereum  Tularemia  Psittacosis  Q fever Leptospirosis  Rickettsial diseases Liver abscess  Q fever Mastoiditis (chronic)  Rocky Mountain spotted fever
    16. 16. Viral & Fungal Etiology Cytomegalovirus  Malaria Epstein-Barr virus  Sarcoidosis (infectious  Toxoplasmosis mononucleosis)  Visceral larva migrans Hepatitis viruses  Visceral leishmaniasis Blastomycosis (nonpulmonary) Histoplasmosis (disseminated)
    17. 17. Autoimmune and malignancy Polyarteritis nodosa Systemic idiopathic juvenile arthritis Systemic lupus erythematosus Hodgkin disease Leukemia or lymphoma Neuroblastoma
    18. 18. Drug Fever Pharmacologic action of the drug (e.g., Jarish–Herxheimer reaction, tumor cell necrosis with chemotherapeutic agents Drugs effects on thermoregulation (e.g.,MOA inhibitors) Drug Administration–Related Fever (e.g.,Amphtericin B, Bleomycin) Fever Related to Pharmacologic Action of the Drug (e.g., Jarisch- Herxheimer reaction) Idiosyncratic Reactions (Malignant hyperthermia,NMS) Hypersensitivity (e.g., penicillin, methyldopa, quinidine)
    19. 19. Approach to PUO:History Specifics of the history should include the following: • Duration and characteristics of the fever (number of spikes per day, timing of the temperature elevation, whether the temperature returns to normal or below normal) • Travel history or exposure to people who have traveled to regions endemic for particular diseases (typhoid, malaria, tuberculosis, RMSF) • Exposure to any animals (cat-scratch disease, rat-bite fever, leptospirosis) • Exposure to unpasteurized dairy products (brucellosis) • Presence of rashes, conjunctivitis, mucous membrane changes, and arthritis (juvenile arthritis, Kawasaki syndrome, SLE) • Presence of associated cough, weight loss, or lymphadenopathy (lymphoma, leukemia, neuroblastoma)
    20. 20. Physical Examination Rectal temperature, respiratory rate, heart rate, and blood pressure measurements should be obtained. Inspection of the pharynx for hyperemia and exudate, of the tympanic membranes for chronic otitis media, transillumination of the sinuses for sinusitis, a search for a purulent nasal discharge, and auscultation of the chest for localized wheezing are all important. In the older child, an examination of the teeth to exclude dental caries and periodontal disease should be included. A new cardiac murmur may be a clue to rheumatic fever or infective endocarditis. Lymphadenopathy, especially if generalized, may suggest a viral infection, such as infectious mononucleosis, cytomegalovirus infection, toxoplasmosis, or HIV infection. Joints must be examined meticulously for swelling, restricted range of motion, and tenderness. Skin rashes may suggest a viral disease or an autoimmune disease such as juvenile idiopathic arthritis.
    21. 21. Interesting Scenarios Repeated fevers,absence of tears,smooth tongue: Riley-Day syndrome fever cycle periodicity as multiples of 7 days, that is, most commonly at 21 or 28-day intervals:Cyclical Neutopenia Hyperimmunoglobulinemia D and periodic fever syndrome (HIDS): The syndrome is characterized by recurrent attacks of fever, typically occurring every 4 to 8 weeks. Febrile episodes last about 5 days and can be associated with cervical lymphadenopathy, abdominal pain, and headache. Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenopathy (PFAPA): characterized by periodic episodes of high fevers lasting 3 to 6 days with recurrence every 21 to 28 days
    22. 22. Investigations:Level 1 Sedimentation rate • Complete blood count with differential (evaluation for anemia, thrombocytopenia, presence of blasts) • Metabolic panel, including BUN, creatinine, liver function tests, lactate dehydrogenase, and uric acid levels • Urinalysis and urine culture • Chest x-ray and tuberculin skin test • Epstein-Barr virus and cytomegalovirus serology • Viral culture of the nasopharynx and eyes (if clinically warranted)
    23. 23. Level 2 Echocardiogram. Evaluate for coronary artery brightness or aneurysms associated with Kawasaki disease and pericardial effusion associated with various rheumatologic conditions, including SLE. Abdominal or pelvic computed tomography. Detection of occult abscesses or granulomatous lesions Bone scan. Evaluation for occult osteomyelitis or discitis Serology. As clinically indicated by history or physical exam ANA, double-stranded DNA, compliment levels (if history or physical suggests SLE)
    24. 24. Level 3 Bone marrow aspiration, looking for infiltrative process or to culture a variety of organisms (such as brucellosis, tuberculosis, or disseminated fungal infection). • Biopsy of suspicious skin lesions or lymph nodes. • Endoscopy and biopsy
    25. 25. Recap points:  Petersdorf & Beeson criteria  Durrack & Street classification  Think common etiologies first  Examination and investgations based on the history
    26. 26. References1. Nelson Textbook of Pediatrics, 18th ed. Chapter:1752. Sarah S.Long Principles and Practice of Pediatric infectious diseases: 114-1223. Mendel Douglas Principles and Practice of Pediatric infectious diseases: 536-5494. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition.Walker HK, Hall WD, Hurst JW:Chapter 2115. AAP Textbok of Pediatric care: Chapter 1826. Pediatric infectious disease secrets By Joel D. Klein, Theoklis E. Zaoutis: Chapter 36.