Pyrexia of unknown orgin (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 long-
term course, especially when the fever is not
accompanied by substantial weight loss or other
signs of a serious underlying disease
.
Classification of PUO
Classic
Health care
associated
Neutropinc
HIV
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
• 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
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.
• 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
• 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