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Pyrexia of unknown origin (PUO)
Mosul Medical College
Presented by: Dr. Salam Fareed
contents
• Objectives
• Definition
• Classification and causes
• Approach to patient with PUO
• Golden point
• Case scenario
Objectives
•To be able to define PUO, and its tyups.
•To be able to have a plan to approach a patient with Fever when
the basic clinical and laboratory tests did not reveal much as to the
cause of fever
Fever of unknown origin (FUO) :-
is a sustained, unexplained fever despite a
comprehensive diagnostic evaluation. Patients with undiagnosed
FUO generally have a benign longterm course, especially when the
fever is not accompanied by substantial weight loss or other signs
of a serious underlying disease
.
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Classification of PUO
Health care
Neutropinc
HIV
Classic
associated
associated
Classic
• Temperature >38.3 °C (100.9 °F)
• for at least 3 weeks
• with at least 1 week of in-hospital investigation
Causes
1- Infections (30%)
:-
•Abscess at any site; Cholecystitis/cholangitis
•Urinary tract infection: prostatitis
•Dental and sinus infections
•Bone and joint infections
•Imported infections, e.g. malaria, dengue, brucellosis
•Enteric fevers
•Infective endocarditis
•Tuberculosis (particularly extra pulmonary)
•Viral infections (cytomegalovirus-CMV, Epstein-Barr virus-EBV, human
immunodeficiency virus-HIV) and toxoplasmosis
2-Malignancy (20%):-
•
Lymphoma and myeloma
•
Leukemia
3
•
Solid tumors (renal, liver, colon, stomach, pancreas)
3-connective tissue disorders(15%):-
•
Vasculitic disorders (including polyarteritis nodosa and rheumatoid disease with
vasculitis)
•
Temporal arteritis/polymyalgia rheumatica
•
Systemic lupus erythematosus (SLE)
•
Still's disease • Polymyositis
4-Miscellaneous (20%):-
•
Inflammatory bowel disease
•
Liver disease: cirrhosis and granulomatous hepatitis
•
Sarcoidosis
•
Drug reactions
•
Atrial myxoma
•
Thyrotoxicosis
•
Hypothalamic lesions
•
Familial Mediterranean fever
5-Factitious
6-No diagnosis (15%)
Health care associated
Temperature >38.3 °C (100.9 °F) in patients hospitalized ≥72 hours but no fever or
evidence of potential infection at the time of admission, and negative evaluation of at
least 3 days.
Causes
• Drug fever
• thrombophlebitis
• pulmonary embolism
• sinusitis, postoperative complications
(occult abscesses)
• Clostridium difficile enterocolitis
• device- or procedure-related endocarditis
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Neutropenic (immune deficient)
Temperature >38.3 °C (100.9 °F) and neutrophil count <500/µL for >3 days and negative
evaluation after 48 hours.
Causes
• Occult bacterial and opportunistic fungal infections (aspergillosis, candidiasis)
• drug fever
• pulmonary emboli
• underlying malignancy
• cause not documented in 40%-60% of cases
HIV associated
Temperature >38.3 °C (100.9 °F) for >3 weeks (outpatients) or >3 days (inpatients) in
patients with confirmed HIV infection.
Approach to patient with PUO
History
Physical examination
Targeted investigations
History
• Inquire about symptoms involving all major organ systems and get a detailed history of
general symptoms (eg, fever, weight loss, night sweats, headaches, rashes).
• The history can provide important clues to FUO due to surgery, zoonoses, malignancies,
and inflammatory/immune disorders.
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• Record all symptoms, even those that disappeared before the examination. Previous
illnesses (including psychiatric illnesses) and surgeries are important.
Make a detailed evaluation that includes the following:
• Family history
• Immunization status
• Occupational history
• Travel history
• Nutrition (including consumption of dairy products)
• Drug history (over-the-counter medications, prescription medications, illicit substances)
• Sexual history
• Recreational habits
• Animal contacts (including possible exposure to ticks and other vectors)
Physical Examination
• Definitive documentation of fever and exclusion of factitious fever are essential early
steps in the physical examination.
• On physical examination, pay special attention to the eyes, skin, lymph nodes, spleen,
heart, abdomen, and genitalia.
• Pulse-temperature relationships (ie, relative bradycardia) are useful in evaluating for
typhoid fever, Q fever, psittacosis, lymphomas, and drug fevers.
• Repeat a regular physical examination daily while the patient is hospitalized. Pay
special attention to rashes, new or changing cardiac murmurs, signs of arthritis,
abdominal tenderness or rigidity, lymph node enlargement, funduscopic changes, and
neurologic deficits.
Investigations
PUO should be investigated in a stepwise fashion in order of increasing complexity and
invasiveness, starting with blood tests and moving to imaging techniques and, finally,
more invasive procedures such as 'blind' biopsies
• FBC with differential , (ESR) and C-reactive protein (CRP)
• Urea, creatinine and electrolytes
• Liver function tests (LFTs) and γ-glutamyl transferase
• Blood glucose
• Urinalysis, Midstream urine (MSU) for microscopy and culture
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• Creatine phosphokinase
• Malaria blood films
• Faeces culture
• Sputum for routine microscopy and culture and microscopy and culture for mycobacteria
• Blood cultures ×3
• Chest X-ray
• Ultrasound examination of abdomen
• Electrocardiogram (ECG) • Echocardiogram
• Viral (CMV, Infectious mononucleosis, HIV, Hepatitis A, B and C)
• Bacterial (chlamydial infection, Q fever, brucellosis , mycoplasma infection, syphilis,
leptospirosis, Lyme disease, Yersinia infection, streptococcal infection)
• Fungal(Cryptococcus antigen, histoplasmosis, coccidioidomycosis)
• Protozoal and parasitic (toxoplasmosis, amoebiasis, schistosomiasis, leishmaniasis,
trypanosomiasis)
• PCR e.g for tuberculosis, herpes simplex virus (HSV), CMV, HIV, erythrovirus, dengue,
Toxoplasma, Whipple's disease
• Immunology like Autoantibody screen, including anti-double-stranded DNA, anti-
neutrophil cytoplasmic antibody (ANCA), Immunoglobulins,
Complement (C3 and C4) levels &Cryoglobulins
• Imaging like CT/MRI chest and abdomen, skeletal survey , isotope bone scan, labelled
white cell scan
• Biopsy: Bone marrow biopsy, Temporal artery biopsy
Factitious fever
• It is most commonly encountered among young adults with health care experience or
knowledge.
• Evidence of psychiatric problems or a history of multiple hospitalizations at different
institutions is common in patients with factitious fever.
• Rapid changes of body temperature without associated shivering or sweating, large
differences between rectal and oral temperature, and discrepancies between fever, pulse
rate, or general appearance are typically observed in patients who manipulate or
exchange their thermometers.
Golden Point