4MB Clinical Problem-Solving

Dr. Gerard Flaherty

Dept. of Medicine
42-yr-old ♂
Presenting Complaint:
Pyrexia of Unknown Origin
Definition
 “Illness of more than three weeks’
duration, fever higher than 38.3°C
(101°F) on several occasions, and
diagnosis uncertain after one week of
study in hospital.” (Petersdorf and
Beeson, 1961)
Definition
 “Fever that does not resolve
spontaneously in the period expected
for self-limited infection and whose
cause cannot be ascertained despite
considerable diagnostic effort.” (Arnow
and Flaherty, 1997)
History
 ?Night sweats
 ?Weight loss
 ?Pruritus
 Symptoms of underlying illness
 Previous illnesses
 Medications
 Occupational exposures
 Pets
 Foreign travel
 Family history
Physical Examination
 Vital signs (?relative  Lymphadenopathy
bradycardia)  Clubbing
 ?Jaundice  Joint swelling
 Anaemia  Rash
 ?Hyperpigmentation  Thickened temporal artery
 Abdominal tenderness  Iritis
 Hepatosplenomegaly  Mouth ulcers
 Abdominal mass  Leg swelling (?DVT)
 ENT examination  Thyroid tenderness
 Examine teeth  Signs of thyrotoxicosis
 ?Murmurs  Gouty tophi
 ?Wounds  Tender prostate on PR exam
 Auscultate chest  Testicular tenderness
76-yr-old ♂ with headache and scalp
tenderness.
Give the diagnosis.
Minimum diagnostic work-up to qualify as PUO

 Full history  ACE

 Repeated examination  Blood cultures ×3
 FBC  CMV serology
 SMAC, including LDH  Monospot
 ESR  Mantoux test
 Antinuclear antibodies  Chest radiograph
 Rheumatoid factor  Ultrasound Abdomen
 HIV serology  CT Abdomen
 MSU
Further Investigations
 Discontinue as many medications as possible
 Tumour markers
 Echocardiogram
 Gallium-67 or indium-111-labelled white cell scan
 Excision biopsy
 Laparotomy
 Temporal artery biopsy
 Sputum for acid-fast bacilli
 Bone marrow biopsy
Infective endocarditis
Differential Diagnosis
Disease categories
1. Infection
2. Neoplasia
3. Collagen vascular diseases
 The causes of Pyrexia of Unknown
Origin are usually familiar diseases with
uncommon presentations rather than
rare disorders.
 Failure to utilise findings correctly, delay
in requesting appropriate tests, and
misinterpretation of results all
contribute to missed diagnoses.
Infection (a partial list!)
Intraabdominal abscess; Appendicitis; Cholecystitis;
Cholangitis; Mesenteric lymphadenitis; Tubo-ovarian abscess;
Intracranial abscess; Sinusitis; Mastoiditis; Otitis media; Dental
abscess; Chronic pharyngitis; Tracheobronchitis; Lung abscess;
Septic jugular phlebitis; Mycotic aneurysm; Endocarditis; IV
catheter infection; Vascular graft infection; Wound infection;
Osteomyelitis; Infected joint prosthesis; Pyelonephritis;
Prostatitis; TB; Lyme disease; Relapsing fever; Syphilis; Q
fever; Legionella; Salmonella; Listeria; Campylobacter;
Brucellosis; Psittacosis; Chlamydia pneumoniae; Gonorrhoea;
Meningococcaemia; Actinomycosis; Whipple’s disease;
Candidaemia; Cryptococcus; Histoplasma; Coccidioidomycosis;
Blastomycosis; Aspergillosis; Pneumocystis carinii; Visceral
leishmaniasis; Malaria; Babesiosis; Toxoplasmosis;
Schistosomiasis; Toxocariasis; Amoebiasis; Hydatid cyst;
Trypanosomiasis; CMV; HIV, Herpes simplex; Epstein-Barr virus.
Hepatic abscess
Neoplasia
 Pyrexia of unknown origin has been
reported in association with 46 different
malignancies.
e.g. Lymphoma
Renal-cell carcinoma
Collagen vascular diseases
Adult Still’s disease; SLE; Cryoglobulinaemia; Reiter’s
syndrome; Rheumatic fever; Giant cell arteritis /
Polymyalgia rheumatica; Wegener’s granulomatosis;
Ankylosing spondylitis; Behçet’s disease; Polyarteritis
nodosa; Sjögren’s syndrome; Polymyositis;
Rheumatoid arthritis; Erythema multiforme;
Erythema nodosum; Relapsing polychondritis; Mixed
connective-tissue disease; Takayasu’s arteritis; Felty’s
syndrome; Eosinophilic fasciitis.
Rheumatoid arthritis
30-yr-old ♀ with arthralgia and pleuritic
chest pain.
Give the diagnosis.
Miscellaneous
Haematoma; Thrombosis; Aortic dissection; Femoral
aneurysm; Dressler’s syndrome; Atrial myxoma; Drug fever;
Familial Mediterranean fever; Familial Hibernian fever;
Inflammatory bowel disease; Sarcoidosis; Subacute thyroiditis;
Hyperthyroidism; Addison’s disease; Hypothalamic
hypopituitarism; Gout; Pseudogout; Cirrhosis; Chronic active
hepatitis; Alcoholic hepatitis; Kawasaki’s disease; Gaucher’s
disease; Fabry’s disease; Cholesterol emboli; Sickle cell disease;
Cyclic neutropenia; Hamman-Rich syndrome; Hypersensitivity
pneumonitis; Extrinsic allergic alveolitis; Stroke; Brain tumour;
Encephalitis; Psychogenic fever; Factitious fever.
24-yr-old ♂ with dyspnoea and a painful
red eye.
Give the diagnosis.
38-yr-old ♀ with bloody diarrhoea and
arthralgia.
Give the diagnosis.
Management of underlying conditions
References

1. Arnow PM, Flaherty JP (1997) Fever of

unknown origin. Lancet 350: 57-80.
Next week….

Headache