Published on 24/06/2015 by admin

Filed under Internal Medicine

Last modified 24/06/2015

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 0 (0 votes)

This article have been viewed 1158 times


Case vignette

A 66-year-old man of Greek descent has been investigated in hospital for a period of 1 week for a swinging fever of 1 month’s duration and associated headache, weight loss, arthralgia, myalgia and lethargy. He complains of drenching night sweats and rigors. The patient denies any localising symptoms. He has a background history of myocardial infarction treated with angioplasty and stent 1 year ago. He is currently on metoprolol 25 mg twice daily and aspirin 150 mg daily. He denies any allergies or family history of significant illness. He has recently travelled to the west coast of the United States for a family reunion. On examination his pulse rate is 100 bpm and his temperature is 38°C. His temperature chart shows a regular pattern of temperature spikes up to 39°C. No other significant signs are evident.

On further enquiry the patient reveals that he noticed an expanding erythematous maculopapular rash, which disappeared spontaneously. The lesion was painless. According to the detailed description, the lesion had a clear central core and a well-defined border.

Approach to the patient

Pyrexia of unknown origin is defined as intermittent or continuous fever for more than 3 weeks in a patient in whom the cause of the fever has not been identified in spite of repeated investigations for more than a week.


The condition could be due to multiple causes, both infective and non-infective (see box). A detailed physical examination should be carried out, looking first for a focus of sepsis. Look for areas of inflammation in the skin and check for lymphadenopathy and/or hepatosplenomegaly. Look for rashes, inflamed joints, painless mass lesions etc. Study the temperature chart. Perform the examination with a particular focus on the most likely body system to be involved, based on the overall clinical picture.
Some of the commonly encountered causes of undiagnosed persistent fever are occult abscesses in the abdomen, tuberculosis, cytomegalovirus (CMV) infection, HIV infection, haematological malignancy, solid cancer, pulmonary embolism, Wegener’s granulomatosis, undiagnosed vasculitis (especially polymyalgia rheumatica and giant cell arteritis), granulomatous conditions such as sarcoidosis, Still’s disease and drugs. The remainder of the physical examination should be focused on looking for features of non-infective causes of fever.



Very ill patients should be treated as for septicaemia, with broad-spectrum, potent parenteral antibiotic combinations. Otherwise, therapy should be guided by the clinical circumstances and the above investigational results.


Approach to the patient

There is a high likelihood that a patient presented as a long case will have some form of immunodeficiency, either as the primary presentation or as a comorbidity. Immunodeficiency could be granulocytopenia, cellular immunodeficiency (see box) or humoral immunodeficiency (see box).

Causes of humoral immunodeficiency

Therapy for humoral immunodeficiency may include IV infusion of immunoglobulins at regular intervals. Encapsulated bacteria such as Streptococcus pneumoniae and Haemophilus influenzae usually cause sepsis in this setting. In terminal component complement and properdin deficiency, Neisseria meningitidis is the organism that causes the most sepsis.


Search for the focus of sepsis. You should carry out a detailed examination of the systems involved. Check the temperature chart to ascertain the temporal pattern of the fevers. Look for clues to the predisposing condition, such as stigmata of liver disease or chronic renal failure, venepuncture marks of injecting drug use, lymphadenopathy, hepatosplenomegaly, splenectomy scar and central venous catheters.

The following is an outline of some of the different forms of immunodeficiency that can be expected in the long case setting and some information that may be useful in approaching the management of such patients.


A patient is absolutely granulocytopenic by the classic definition when the neutrophil count goes below 0.5 × 109/L. The risk of sepsis is increased in this setting.
If a granulocytopenic patient is febrile, possible foci of sepsis are: oropharynx, lung, distal oesophagus, colon, perianal skin, intravenous cannula site and the urinary tract.


Buy Membership for Internal Medicine Category to continue reading. Learn more here