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NORMAL heat loss
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Sweating
Breathing
Vasodilation
Cold environment
HEAT LOSS = decreased body temperature
ABNORMAL heat loss
Excessive sweating
Extremely cold environment
HOMEOSTASIS = normal body temperature (35.6–37.8°C)
Patients with a fever
ABNORMAL heat gain
1. Excessive metabolic processes
a. Drugs
2. Preventing heat loss—mostly through
preventing of sweating
a. Hot environment
b. High humidity
c. Inhibiting sweating (drugs)
HEAT GAIN = increased body temperature
NORMAL heat gain
Metabolic processes
Exercise
Shivering
Vasoconstriction
SECTION TWO
147
Figure 10.3 Mechanisms of thermoregulation and dysregulation.
point of the thermoregulatory centre, but occurs owing
to raising the body temperature above the normal
set point. It can be caused by heatstroke, neuroleptic
malignant syndrome, malignant hyperthermia and
stimulants such as amphetamines and cocaine.
Fever is produced when a stimulus from either
outside (external) or inside (internal) the body is
detected by the body’s immune system as foreign,
and a host of immune responses occur. External
stimuli are usually in the form of infectious agents or
drugs, whereas internal stimuli may be in the form of
antibodies or damaged tissue. These (perceived) foreign
objects activate the cells of the immune system to
release chemical mediators called cytokines, including
tumour necrosis factor alpha (TNF- α), interferon, IL-
1 and IL- 6. These cytokines act on the hypothalamus
to reset the set point to a higher temperature or to
‘turn up the thermostat’. Some bacterial proteins can
act directly on the thermoregulatory centre in the
hypothalamus to cause the same effect.
Elevation of the internal set point results in a higher
core body temperature and causes the individual to
feel cold. This leads to increased generation of heat
and reduction of heat loss in the form of peripheral
vasoconstriction and shivering. Rigors are a form of
severe shivering.
there always a need to be so quick to reduce it?
Benefits of having a high temperature include
an increase in the phagocytic and bactericidal
activity of neutrophils and the cytotoxic effects
of lymphocytes, impairment of the growth and
virulence of bacteria and evidence of survival benefit
for individuals with an elevated body temperature
in response to infection.
On the other hand, there are negative effects of a
raised body temperature. Oxygen consumption and
fluid and calorie requirements increase; increased
metabolic activity can increase stress if organs are
failing; inflammatory cytokines increase muscle
breakdown; and fever can reduce mental acuity,
cause delirium and trigger convulsions, especially in
children.
Therefore, there is an indication to treat fever in
those who are pregnant, in children, in those with
impaired organ function or those with a very high
temperature of >41.5°C.
Fever can be treated by increasing heat loss
through physical cooling or by resetting the
upregulated hypothalamic set point using
antipyretics.
The patterns of fever
Should you always treat a fever?
Because fever is a physiological response of the
body, it must have some inherent value, and so is
Fever can reveal a characteristic pattern in
some diseases and this pattern of rise and fall
of temperature may be a clue for diagnosis
(Fig. 10.4).
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Patients with a fever
Sustained/continuous: Persistent rise in temperature with
minimal (<1°C) diurnal variation.
Causes: Pneumonia, meningitis, urinary tract infection, brucella
Sustained fever
Normal range
Intermittent: Exaggeration of the normal circadian rhythm. If
the variation between high and low is extremely large it is
called hectic.
Causes: Deep seated infection, abscesses, kala-azar,
malignancy, drug fever
Intermittent fever
Normal range
Relapsing: Febrile episodes are separated by intervals of
normal temperature.
Causes: Malaria, borrelia (relapsing fever), tuberculosis,
lymphoma
Relapsing fever
Step-ladder fever: A type of sustained fever where the temperature
rises gradually to a higher level with every spike.
Causes: Typhoid, typhus
Step-ladder
fever
Normal range
1 2
Remittent: Temperature spikes fall daily with diurnal variation of
>2°C, but don’t go down to normal.
Causes: Tuberculosis, infective endocarditis, many viral and
bacterial infections
Remittent fever
Normal range
3 4
Inverse fever: The temperature rises in the early hours of
morning rather than in the evening
Causes: Some cases of miliary tuberculosis
6
Normal range
If this occurs daily, it is called quotidian fever.
Causes: Plasmodium falciparum
A double quotidian fever occurs when there are two spikes
of fever every day, generally once in the morning and once
in the evening.
Causes: Miliary tuberculosis
If it occurs every 48 hours it is called tertian fever.
Causes: Plasmodium falciparum, Plasmodium vivax,
Plasmodium ovale
If it occurs every 72 hours it is called quartan fever.
Causes: Plasmodium malariae
Quartan fever
Normal range
5
Figure 10.4 The patterns of fever.
Approach to a patient with a fever—
causes of fever
Fever is one of the most common presenting features at acute medical facilities around the world.
Although it is a characteristic sign of infection, not
Night sweats: In some diseases, the rise in body temperature is
evident only in the evening or late at night when the patient is woken
up sweating. This pattern is seen when the mild rise in temperature is
added to the normal diurnal evening rise leading to the body
temperature rising beyond the normal level.
Causes: Tuberculosis, leukaemia, lymphoma,
autoimmune disorders
7
Temperature-pulse disparity: This is the counter-intuitive response
of a slower pulse associated with a high fever, commonly associated
with typhoid fever.
8
all fever has an associated infectious cause. It is also
a feature of a number of non- infectious inflammatory diseases (autoimmune connective tissue
and autoinflammatory disease and vasculitis) and
neoplasms. It may also occur as a drug reaction.
In a significant number of cases, the temperature
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149
Box 10.2
Infections
Non- infectious inflammatory diseases
− Autoimmune inflammatory
− Autoinflammatory
− Vasculitis
Malignancy
Miscellaneous causes such as drug reactions
Undiagnosed
subsides spontaneously and no cause is identified
(Box 10.2).
The likelihood that fever is caused by an infection
differs from one area of the world to another and
reflects the burden of disease in the particular
country (Fig. 10.5). It is also important to remember
that the very young and the very old may have a
serious infection without producing a fever.
Causes of fever
History
As with any medical condition, the starting point of
diagnosis is a detailed and meticulous history. The
history taking should follow a logical scheme to
ensure important questions are not missed; causes
of fever have a broad aetiology and can present as
multisystem diseases. Taking a ‘fever history’ is
unlike most other history taking, as it does not focus
on a particular body system. Aspects of the personal,
general and specific histories of all other systems
need to be explored.
All histories should begin with an introduction,
stating clearly your designation as a trainee, student
or observer. Ensure you have the correct patient and
that the patient understands the language. If the
patient is a minor or a guardian or parent is present,
be aware that certain sensitive questions may have
to be asked at a later time when you are alone with
the patient.
Main presenting complaint
Patients presenting with fever will often have a raft
of associated complaints, many or all of which may
be perceived as the main problem to the patient. It
is therefore prudent to refer to the fever as the main
presenting complaint and the associated complaints
as part of the systematic history.
History of the presenting complaint
Details of the fever itself should be taken and the
pattern described as continuous, intermittent or
recurrent as noted above. Ask whether the fever is
worse in the morning or at night. Some open- ended
questions should be followed by direct questions to
elicit the finer distinguishing characteristics of the
fever. Remember that the taking of antipyretics, antiinflammatories or antibiotics can mask a fever, so ask
the patient if he has taken any medication. Enquire
as to the duration of fever, which should reflect
when the patient first noticed having a fever. This
differs from the onset of fever that may be sudden
or gradual; the former more likely to represent a
more virulent disease, whereas the latter suggests a
more indolent one. A description of the fever should
include the presence or absence of rigors (profound
chills associated with exaggerated shivering and
chattering of teeth), which usually indicates a
rapidly rising temperature found in malaria or severe
bacterial sepsis.
High fever of more than 39°C is the initial
symptom in most patients with adult onset Still’s
disease (AOSD). The classic fever pattern is one
or two daily febrile spikes exceeding 39°C, usually
occurring late in the day. At times the fever is
continuous or, less commonly, there is an early
morning spike.
Personal history
Although the patient’s name, age and date of birth
are used as identifiers, the country of birth and
countries of residence are the first questions of the
infection history. These are important both in respect
to disease exposures and disease protection in the
form of childhood and other vaccinations. Rates
of diseases such as tuberculosis (TB) are higher in
people who were born or resided in a country with
a high incidence of tuberculosis, even if they have
left the country. Vaccination schedules differ among
countries and because of this, immunity to certain
childhood diseases may vary.
History of associated and constitutional
symptoms
These include the presence of any of the following:
Headache is a non- specific symptom and does
not differentiate the cause of the fever. A severe
headache associated with photophobia or
vomiting could indicate meningitis. Vasculitides
affecting the head and neck vessels may present
with headache.
Muscle ache (myalgia) is again a non- specific
finding present in all causes of fever. If infectious,
myalgia is more suggestive of infection with
intracellular pathogens, particularly viral
infections and malaria.
Joint pain (arthralgia) is an additional non-
specific symptom, which may be caused by
multiple infectious and non- infectious aetiologies.
In a patient complaining of arthralgia, one should
distinguish between mono- arthralgia (single joint)
and poly- arthralgia (multiple joint) involvement.
Presence or absence of a rash is particularly
important to enquire about, because many
infections and autoimmune disorders are
associated with a typical rash, both in pattern
and evolution. The rash may not be present at
the time of consultation or it may have changed
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Patients with a fever
Causes of fever - India
6%
15%
9%
20%
Figure 10.5 Causes of fever in India and Europe.
50%
Infections
Neoplasms
Connective
tissue diseases
Miscellaneous
Undiagnosed
Causes of fever - Europe
21%
over the course of the illness. Ask details about
the rash history, finding out where on the body it
began, its associations, where it spread, whether
the lesions changed over time and, if no longer
present, how it resolved. Further details to help
the diagnosis include details on the colour, type
of lesion (e.g. vesicle, pustule, lacey) and whether
it was pruritic, painful or neither. If the rash is
intermittent, patients can be asked to photograph
it with their mobile phone, and may have done so
of their own accord.
Weight loss in a patient with a fever suggests a
more chronic process and is a classic feature of YB
(consumption) or malignancy.
A full systematic history should be included
looking for a pattern of disease in systemic
infectious or non- infectious disease, or a specific
organ source of infection (e.g. cough, abdominal
pain, dysuria, diarrhoea and redness or pain of
skin or soft tissue).
History of behaviours and exposures are
important in infectious diseases
Contact with anyone having similar symptoms
or living with someone who has been treated for
an infection. It is also useful to know about close
contacts who have not been ill.
Living arrangements, including access to clean
water and sanitation, proximity to animals or
rodents. A history of insect or animal bite or
scratches.
Occupation, hobbies and sports, especially those
involving exposure to water, animals or health
care.
Recreational habits, especially illicit drug use or
tattoos.
Sexual habits are vitally important and patients
may need some encouragement to be open and
honest about these risks. Unprotected sexual
practices increase the risk of both sexually
transmitted diseases and blood- borne viruses.
Food habits, including ingestion of unpasteurized
milk or cheese.
23%
Box 10.3
27%
13%
17%
Infections to consider if there is a history of travel
Sub- Saharan Africa—malaria, reproductive tract infection
(RTI), diarrhoeal illness, HIV, rickettsia, haemorrhagic
fevers, TB, hepatitis
South East Asia—dengue, malaria, diarrhoeal illness
Sub- Continent Asia/India—enteric fever, dengue, malaria,
diarrhoeal illness, hepatitis
South America—diarrhoeal illness, RTI, dengue, malaria,
mosquito- borne viruses
Central America/Caribbean—diarrhoeal illness, RTI,
dengue, malaria, mosquito- borne viruses
North America/Europe—influenza, HIV, Lyme, tick- borne
viruses, TB (eastern Europe)
Taking of appropriate prophylaxis, including
vaccinations, either when travelling or at home.
Travel is one of the most important histories
to explore. Details of the destinations include
whether the stay was in an urban or rural setting,
stay was with family or friends, in a hotel or
without facilities (Box 10.3).
Past medical and surgical history
Although all past history is important to obtain,
certain aspects play a more important role as risks
for infections.
Infections are more frequent and more serious
in patients with diabetes. A past history of
rheumatic heart disease increases the risk for
infective endocarditis. Previous TB assumes a risk
of recurrence.
Immune compromise increases the risk, severity
and scope of infections. The patient’s immune
status should be determined, specifically by
asking about underlying diseases, such as human
immunodeficiency virus (HIV); medications, such
as steroids or chemotherapy; or a history of a
splenectomy.
Recent hospitalization is associated with hospital-
acquired multiresistant pathogens.
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151
Surgery, invasive procedures, medical devices,
implants and transfusions all provide a means for
introduction of infectious agents.
Antibiotic use may select for more resistant
pathogens and increases the risk of antibioticassociated diarrhoea. Antibiotics may also provide
protection against infection in certain groups of
immune compromised patients.
A history of immune compromise, radiation,
toxin exposure or certain chronic infections may
increase the risk of certain malignancies.
A family history of non- infectious inflammatory
diseases can indicate a genetic predisposition
that may increase the risk of developing a noninfectious inflammatory disease.
Systematic history
Symptoms focusing on specific organ systems will
provide direction towards the likely diagnosis when
considering infectious causes of fever. Malignancies
may also be found in any organ system. Noninfectious inflammatory diseases tend to affect
multiple systems together, although a single system
may predominate. The following detail focuses on
infectious causes of fever.
Respiratory tract
Upper respiratory tract infection is suggested by
rhinorrhoea, nasal stuffiness, sneezing, sore throat,
cough and a hoarse voice.
Sinusitis is likely to cause facial pain and headache.
Otitis is associated with ear pain, ear discharge
with or without auditory symptoms such as
deafness.
Lower respiratory tract infections present with a
cough, productive of purulent sputum, shortness
of breath, wheeze or chest pain. Haemoptysis
(coughing blood) suggests invasion of or damage
to the blood vessels of the lung. This is present
in TB, invasive fungal infection or non- infectious
causes, such as lung cancer or vasculitis.
Genitourinary tract
Lower urinary tract infection classically presents
with a combination of dysuria, frequency, urgency
and change in smell and colour of urine.
Upper urinary tract infection may have the above
(or a history of the above) with additional loin or
back pain.
Sexually transmitted infections and pelvic
inflammatory disease can present with the same
symptoms as a lower or upper urinary tract
infection, but may have the additional symptoms
of a vaginal or urethral discharge, dyspareunia
(pain during intercourse), anogenital ulcers, genital
warts, painful swelling of the scrotum, pubic itch
or swelling of lymph glands in the groin.
Vaginal candidiasis is not uncommon in women,
particularly those who use vaginal douches or
after a course of antibiotics. It may present as
urinary tract infections do with a whitish vaginal
discharge and vaginal itching.
Bacterial vaginosis is not considered a true
infection, but rather an imbalance of normal
vaginal flora and overgrowth of anaerobes. It
presents with watery, foul- smelling vaginal
discharge.
Gastrointestinal tract
Abdominal pain may be present with almost all
gastrointestinal causes of infections, but may be less
prominent than pain caused by inflammatory or
malignant gastrointestinal diseases. It is important to
characterize the pain, including the site and radiation,
associated abdominal symptoms and relieving and
aggravating factors.
Gastroenteritis, the most common gastrointesti-
nal infection, is associated with abdominal pain
and diarrhoea, with or without vomiting. Characterizing the diarrhoea may help in narrowing the
aetiology owing to the characteristic pathogenesis
of some of the gastrointestinal pathogens. Determining whether the diarrhoea is acute or chronic
can distinguish infective from non- infective
causes. Direct questions to ask about diarrhoea
include frequency, colour and consistency, presence of mucus and/or blood in the stool (rather
than just on the paper).
Hepatitis is usually caused by viral agents, but
can also occur as a complication of medications
or other toxins. Jaundice is the classic sign of
hepatitis, along with a history of exposure to
risk factors involving contact with body fluids or
excretions. Leptospirosis, a rare cause of jaundice,
is caused by an organism that is carried by rats.
Cholecystitis and cholangitis classically present
with pain in the right upper quadrant of the
abdomen associated with nausea with or without
jaundice.
Other forms of intra- abdominal infection, includ-
ing bowel perforation and peritonitis, present
with varying abdominal symptoms, including generalized or localized abdominal pain, bowel distension, diarrhoea, constipation or vomiting.
Nervous system
Headache, photophobia, vomiting, altered consciousness, fits, fainting, muscle weakness, numbness,
paralysis, tremor, abnormal sensation and change of
behaviour can all suggest an infection of the central
nervous system. In neonates and young children the
symptoms of infection are mostly non- specific.
Patients with multisystem non- infectious inflammatory diseases can have central and peripheral
nervous system symptoms. A variety of neurological
complications can be present, including spinal cord
involvement in rheumatoid arthritis, neuropsychiatric involvement in systemic lupus erythematosus
and neurological sequelae in vasculitic disorders.
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Patients with a fever
Certain predisposing factors play a role in various
forms of nervous system infection. A history of
immune suppression, head injury and neurosurgery
should be elicited.
Meningitis is an inflammation of the subarachnoid
space and meninges (membranes covering the
brain and spinal cord) most often secondary to
an infection. It classically presents with headache,
vomiting, neck stiffness and fever. Depending on
the duration of onset, meningitis can be classed
as acute, subacute or chronic. Acute meningitis
develops over hours to days; chronic meningitis
over weeks or longer, and may last for months to
years; subacute meningitis is in between the two,
usually over weeks.
Acute meningitis is most often bacterial, with the
frequency of pathogens differing according to age
group and immune status. Some forms of acute
bacterial meningitis (meningococcal disease) can
present with a typical purpuric non- blanching
rash and may be associated with severe sepsis and
shock. Viral meningitis is usually less severe and
self- limiting and often begins with symptoms of
a viral infection, such as fever, malaise, headache
and muscle aches.
Head injury increases the risk of meningitis
by damaging the protective layer of meninges
and allowing respiratory or skin flora into the
protected subarachnoid space. Neurosurgery
predisposes to infection with the above and also
hospital- acquired pathogens.
Chronic meningitis presents with the same
symptoms as acute, only over a more prolonged
period. Associated features should be sought for
the more common causes of chronic meningitis,
including tuberculosis, cryptococcus and Lyme
disease.
Encephalitis is inflammation of the brain tissue
resulting in an altered level of consciousness,
headache and fever. Additional symptoms may be
present, depending on the site of infection, and they
include seizures, tremors, stroke, hallucinations
and abnormal behaviours. Encephalitis is usually
syphilis) or parasitic (e.g. toxoplasmosis).
Intracranial abscesses are bacterial infections of
the central nervous system (CNS); they include
brain abscess, subdural or extradural empyema,
classified according to their anatomic location.
These abscesses occur secondary to seeding from
a primary site, either from a contiguous one such
as in otitis media, sinusitis, mastoiditis or dental
infection; secondary to haematogenous spread
from a remote site such as endocarditis; after a
head injury or neurosurgery and, rarely, following
meningitis.
Not all patients with nervous system symptoms
and fever have a primary nervous system infection.
Some systemic infections can cause neurological
symptoms, such as severe or cerebral malaria,
neurologic signs in severe typhoid fever and
meningeal signs in HIV seroconversion illness.
Skin and soft tissue
A detailed history of any skin conditions should
be sought, even if this is not present at the time of
consultation. Many skin conditions and rashes have
a characteristic course, may fluctuate or change
over time and therefore a full ‘progress report’ of
the condition can help to guide the diagnosis. The
presence of a rash is more likely to suggest a systemic
rather than a localized condition. Many multisystem
non- infectious inflammatory diseases have an
associated rash, such as the typical butterfly facial
rash of systemic lupus erythematosus and petechial
rash in vasculitic disorders.
Remember to ask about any insect or tick bites;
rashes following a bite (including an eschar at the
bite site) could indicate a vector- borne disease.
It is important to distinguish a generalized rash
illness from a localized skin or soft tissue lesion.
The latter is more likely to be asymmetrical or
unilateral, involve tissues deeper than the skin,
affect surrounding structures and be associated with
localized enlarged lymph nodes.
Some examples of localized infections include:
Impetigo is a contagious infection caused by
staphylococci or, occasionally, streptococci,
found mainly in preschool children or in other
ages associated with playing contact sports. It
usually starts as a small pustule around the nose
or mouth which bursts, oozes fluid and leaves
a golden crust. It characteristically occurs in
groups of lesions.
Cellulitis is a bacterial infection of the skin
involving deeper structures most commonly
affecting the leg. Other causes of a red or swollen
leg should be excluded before the diagnosis
is made. Cellulitis is rarely bilateral. Certain
groups of people are at increased risk, including
diabetics. It can affect any area of the body and
facial cellulitis should be managed as a medical
emergency.
Necrotizing fasciitis is a severe and rapidly spread-
ing form of cellulitis. It is a medical emergency
and requires urgent surgical as well as antibiotic
management. Pain that is disproportionate to the
visible inflammation or swelling is an important
clue to the presence of necrotizing fasciitis.
A history of human or animal bite or scratch
preceding the infection is important to elicit
because specific pathogens are associated with
these, including blood- borne virus transmission.
Musculoskeletal system
Bone, joint and muscle pain can form part of the
constitutional symptoms of infectious and noninfectious diseases.
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Joint infections occur in both native and prosthetic
joints. A history of joint replacement or joint
procedure, such as arthroscopy, increases the risk
of infection developing in the joint. In a patient
complaining of arthralgia, one should distinguish
between mono- arthralgia (single joint) and polyarthralgia (multiple joint) involvement. Monoarthralgia is more likely to be a septic arthritis in the
affected joint whereas poly- arthralgia suggests a more
systemic disease. Many viral infections and collagen
vascular diseases present with poly- arthralgia.
Bone infection (osteomyelitis) can occur in any
bone in the body, either as a primary infection
or secondary to an overlying skin or soft tissue
infection or previous surgical procedure. Bone
pain, swelling, deformities, pus draining through
the skin overlying a bone or a persistent soft tissue
infection close to a bone should alert you to the
possibility of this diagnosis.
Adult onset Still’s disease presents with a classic
triad of persistent high spiking fevers, joint pain
and a distinctive evanescent salmon pink, macular
or maculopapular rash that peaks with the rise
in the temperature. The rash occurs mainly on
the trunk and extremities, but rarely involves the
palms of the hands, the soles of the feet or the face.
Joint pains may range from arthralgia to a severe
arthritis. Other features include lymphadenopathy,
hepatomegaly and splenomegaly, sore throat
and constitutional symptoms, such as anorexia,
arthralgia, myalgia, fatigue and weight loss. The
classic fever pattern is one or two daily febrile
spikes exceeding 39°C, usually occurring late
during the day. At times the fever is continuous or,
less commonly, spikes in the early morning.
Although fever and constitutional symptoms occur
in around half the patients with polymyalgia rheumatica, they are rarely the dominating features.
Cardiovascular system
Infective endocarditis is an infection of the
endocardium or lining of the heart. The most
common form of this infection is infection of
the heart valves. Symptoms are usually nonspecific and the diagnosis should be considered in
patients with damaged or prosthetic heart valves
or those patients with risk factors for recurrent
bacteraemias (e.g. poor dentition, intravenous
drug use, long- term use of a intravascular device
or underlying bowel cancer).
Myocarditis, an inflammation of the muscle of
the heart, is usually caused by viral infections.
Symptoms are non- specific and may include chest
pain, shortness of breath or palpitations.
Vascular infection can occur as primary vascular
infection of the endothelium or secondary to
damage caused by catheters or cannulas, trauma
or surgery. Occasionally vascular grafts, such as for
aortic aneurysm, can become infected.
Examination
General assessment
Examination should begin when you first make visual
contact with the patient. Get a general impression of
whether the patient looks well, unwell or severely ill.
Summaries of the pertinent features are described in
Table 10.1.
Systematic assessment
A systematic and thorough examination of all organ
systems may be necessary to elicit the cause of the
fever. Both autoimmune disorders and systemic
infections may produce clinical findings in multiple
organ systems, and the pattern and collection of
signs should be able to be collated into a single cause
most of the time. It is not unusual for those with
compromised immune systems or those who have
travelled to have more than one infection at a time.
Skin and mucous membranes
Rashes are of particular importance and many
infectious diseases present with a rash. Describe
the location of the rash. Is it generalized, localized,
symmetrical or asymmetrical? Rashes may indicate
either a localized or generalized infection. Some
rashes are typical of the causative infection; a few
examples are given in Table 10.2.
Fever and constitutional symptoms, although common in patients with antineutrophil cytoplasmic antibodies (ANCA)- associated vasculitis (AAV), rarely
occur in isolation. Palpable (non- thrombocytopenic)
purpura is present in half the patients. Erythematous
cutaneous nodules, with or without superficial crusting, may occur on the scalp, elbows, hands and feet
(cutaneous extravascular necrotizing granulomas or
Churg- Strauss granulomas) in patients with granulocytosis with polyangiitis (GPA) and eosinophilic
granulocytosis with polyangiitis (EGPA). Subcutaneous nodules, skin ulcers, subungual splinter haemorrhages, digital gangrene and livedo reticularis may be
seen and, mainly in EGPA, urticarial rash (Box 10.4).
Mild fever may accompany around a fifth of
patients with Behçet’s syndrome (BS) with active
lesions. Febrile attacks seem to be associated strongly
with vascular, neurological or joint involvement.
Other features of BS include mouth and genital
ulcers, erythema nodosum- like lesions, pyoderma
gangrenosum, folliculitis and uveitis.
Respiratory tract
Perform a full respiratory examination looking for
signs of upper respiratory tract infection, such as
pharyngitis, tonsillitis, tonsillar abscess (quinsy) or
otitis.
Use palpation, percussion and auscultation to
determine whether there is any suggestion of a
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Patients with a fever
Table 10.1 General examination in patients with fever
Temperature Oral or ear temperature is preferred to axillary to give a closer indication of core temperature. Ear
temperature is 0.5°C higher and axillary temperature is 0.5°C lower than oral temperature. Fever is defined
as a core temperature above normal. In clinical practice this translates to an oral temperature of ≥38.3°C.
Pulse Tachycardia is characteristic during fever. For every 1°C rise in temperature the pulse increases by 10 beats
per minute. A pulse- temperature dissociation is characteristically seen in typhoid, brucellosis, leptospirosis
and diphtheria.
Respiratory rate For every 1°C rise in temperature the respiratory rate rises by 4 breaths per minute. Higher respiratory rates
signify additional lung pathology such as pneumonia.
Blood pressure Hypotension may signify severe sepsis or septic shock.
Lymph nodes Note the pattern and groups involved. Check cervical, axillary and inguinal areas. Describe the consistency
of the nodes. Are they firm, hard, regular, irregular, mobile or fixed? Are enlarged lymph nodes unilateral,
bilateral, above and/or below the diaphragm? Note the size of the lymph nodes and whether a single or
multiple lymph nodes are present. Significant lymphadenopathy is found in TB, brucellosis, toxoplasmosis,
viral infections such as HIV or infectious mononucleosis. They are also a predominant feature of lymphoma
and metastatic spread of malignancies.
Jaundice Examine the conjunctivae, nail beds and skin for evidence of jaundice. This may indicate underlying either
haemolysis, such as in malaria and haemorrhagic fevers, or liver disease as in viral hepatitis, cholangitis
or liver abscess.
Eyes Conjunctivitis may indicate a localized eye infection or be associated with a systemic infection such as
measles. Roth’s spots on the retina may be found in infective endocarditis. Tubercles of miliary TB may be
found on the choroid.
Ears Inflammation and redness of the external ear canal indicates otitis externa, whereas a bulging red eardrum
suggests otitis media. If the eardrum has perforated, fluid or pus may be found in the external ear canal.
Mouth Examination of the mouth may yield a host of information and should include visualization of the inner
cheeks, palate, tongue, pharynx, tonsils, gums and teeth. General oral and dental hygiene should be
noted. Lesions on the wall of the mouth or palate should be characterized as described for skin rashes
below. White lesions may indicate oral thrush; the throat and tonsils should be examined for erythema and
exudates; ulcers in or around the mouth may indicate oral herpes. Dry mouth is a feature of some non-
infectious inflammatory diseases.
Skin The entire surface of the skin should be examined, because a lesion or rash may be present only in an area
hidden to view in a clothed individual. Describe and characterize any rash, petechiae and areas of redness
or swelling. Determine if there are any open wounds, ulcers or bite marks, including an eschar. The presence
of open wounds, intravascular devices or injection sites should be noted and closely examined for signs
of erythema, swelling or tenderness. Intravascular devices may be the source of either localized skin or
disseminated infections.
Hands and nails Splinter haemorrhages on the palms and nail beds require further investigation for infective endocarditis.
Scaly, itchy lesions between the fingers suggest the presence of scabies mites. Typical nail deformities of
non- infectious inflammatory diseases, such as psoriasis, should be noticed.
Table 10.2 Examples of rashes in patients with fever
Maculopapular Scarlet fever, measles (look for conjunctivitis and white lesions in the mouth
Vesicular Herpes simplex, chicken pox, shingles, coxackie virus, allergy
Petechial, purpuric, haemorrhagic, vasculitic Meningococcal (non- blanching), viral haemorrhagic fevers, dengue, splinter
Erythematous Cellulitis, erysipelas, drug allergy
Pustular Staphylococcal, disseminated gonococcal infection
Rash on palm and soles Enteroviral infections, meningococcal infection, spotted fever, typhus, infective
Nodular Erythema nodosum, TB, leprosy, non- infective vasculitis, Behçet’s syndrome
— Koplik’s spots), rubella, erythema infectiosum, roseola, typhus, typhoid (rose
spots), dengue, rickettsial infection
haemorrhages of infective endocarditis, non- infective vasculitis
endocarditis, secondary syphilis, scabies (burrows between fingers and toes)
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Box 10.4
Granulomatosis with polyangiitis (GPA) (Wegener’s
granulomatosis)
Eosinophilic granulomatosis with polyangiitis (EGPA)
(Churg–Strauss syndrome)
Microscopic polyangiitis (PA)
lower respiratory tract infection such as bronchitis,
pneumonia, pleural effusion or empyema, cavitation
or lung abscess.
Palpate for tenderness over the sinuses or mastoids.
Harshening of normal breath sounds may indicate
inflammation of the bronchi in bronchitis. The
presence of consolidation in the lung indicating
pneumonia can be determined by finding dullness
to percussion along with increased vocal resonance
of crepitation and/or bronchial breathing. Pleural
effusion or empyema is suggested by dullness to
percussion and decreased or absent vocal resonance.
Cavitation or abscess formation suggesting TB
produces an increase in resonance.
The presence of rhinorrhoea, nasal congestion,
sneezing, cough and a hoarse voice suggest a viral
upper respiratory tract infection.
ANCA- associated vasculitis
Cardiovascular system
The diagnosis of infective endocarditis is based on
the modified Duke’s criteria. Although relying
mainly on investigations for confirmation, certain
clinical signs are suggestive and should be looked
for in patients with risk factors. These include new
valvular regurgitation, temperature more than 38°C,
splinter and conjunctival haemorrhages, Janeway
lesions (small, non- tender red lesions on the palms or
soles) and Osler’s nodes (painful, red raised lesions
on hands and feet) (see Box 13.25.)
Infected thrombophlebitis or vasculitis may
occur secondary to a cannula or catheter insertion
into a vein or as a primary infection of the vessels
by certain pathogens (Campylobacter fetus, nontyphi Salmonellae), usually in immunocompromised
patients.
Genitourinary tract
Examine for suprapubic and renal angle tenderness
in suspected cases of urinary tract infection. Note
the presence or absence of a urinary catheter.
Genital examination should be performed with
a chaperone present, if requested, or when a male
clinician is examining a female patient.
Female genital examination is best performed in
lithotomy position to enable ease of examination.
External examination should note any evidence of
redness, swelling, vaginal, urethral or anal discharge,
vesicles, ulcers, warts or foreign bodies. Unilateral
swelling of the labia may indicate an abscess of the
Bartholin’s gland, which can be palpated only when
enlarged.
The groin should be examined for evidence of
lymphadenopathy or diseases such as tinea, candida
or pubic lice.
Speculum examination allows examination of the
cervix as well as the vaginal vault. If a discharge is
present, describe its consistency. Candidiasis is white
and cheesy, whereas trichomonas infection gives a
frothy greenish fish- smelling discharge. A purulent
discharge coming from the cervix is suggestive of
gonococcal infection, whereas chlamydia causes a
more mucoid or mucopurulent discharge. Cervical
warts may appear as flat or raised.
If anal lesions or symptoms are present, a
proctoscope can be used to examine the rectal
mucosa.
A bimanual examination is required for palpation
of cervical excitation tenderness, fallopian or uterine
tenderness in suspected pelvic inflammatory disease.
Male genital examination includes examination
of the penis, scrotum, testes, epididymis, spermatic
cord and anorectum. External examination should
note the presence of any ulcers, warts, excoriations
or rashes. Examine the urethral meatus for any
discharge or ulcer not visible on external examination.
Examine the scrotum for redness, swelling, ulcers or
other lesions. Tenderness on palpation of the testes
and/or epididymis may suggest epididymo- orchitis.
Gastrointestinal tract
Abdominal examination begins by inspection of
the patient with an exposed abdomen between the
xiphisternum and symphysis pubis (allowing for
patient privacy).
Determine if ascites or abdominal swelling is
present and whether the abdomen is tender. Palpate
for the presence of hepatomegaly, splenomegaly or
a distended gall bladder and whether any of these
organs are tender.
Splenomegaly may be present in many diseases,
caused by either an increase in its function or by direct
infiltration. Infectious causes of increased function
are owing to immune stimulation in response to the
infection and include infectious mononucleosis, viral
hepatitis, AIDS, typhoid, brucellosis, tuberculosis,
histoplasmosis, infective endocarditis, leptospirosis,
leishmaniasis and malaria.
Infective causes of hepatomegaly include infectious
mononucleosis, liver abscess, amoebic infection, hydatid cyst, malaria, leptospirosis and actinomycosis.
Viral hepatitis rarely causes an enlarged liver.
Nervous system
Global examination of the nervous system includes
cognitive as well as physical function. The level
of consciousness can be determined using the
Glasgow Coma Score. Reduced, altered or fluctuating levels of consciousness may be present in
any infection of the central nervous system, but is
more likely in encephalitis and brain abscess than
in meningitis.
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Patients with a fever
The characteristic triad signs of meningitis include
nuchal rigidity (neck stiffness), photophobia and
headache. To detect neck stiffness, passively bend
the patient’s chin towards the chest. This will elicit
pain by stretching the inflamed meninges leading
to resistance in movement. Other signs caused by
pain on stretching the inflamed meninges include
Brudzinski’s and Kernig’s signs.
Kernig’s sign is positive when the thigh is bent
90 degrees at both the hip and knee, and the knee
is then straightened leading to pain and resistance.
Brudzinski’s sign is positive if the patient involuntary
lifts his legs when the clinician lifts the patient’s
head off the examination bed.
Focal neurological signs could be suggestive of
a space- occupying lesion, such as a brain abscess,
tuberculoma or toxoplasmosis. Focal signs may
also be present owing to cranial nerve involvement
caused by meningitis.
Some forms of nervous system infection have
associated features which should be noted.
Meningococcal meningitis may occur with a typical
purpuric non- blanching rash.
Musculoskeletal system
Joint infections occur in both native and prosthetic
joints. A history of joint replacement or joint
procedure, such as arthroscopy, increases the risk
of infection developing in the joint. In a patient
complaining of arthralgia one should distinguish
between mono- arthralgia (single joint) and polyarthralgia (multiple joint) involvement. Monoarthralgia is more likely to be a septic arthritis in
the affected joint whereas poly- arthralgia suggests
a more systemic disease. Many viral infections
and collagen vascular diseases present with polyarthralgia. Septic arthritis with major pathogens,
such as staphylococci, usually result in a joint that
is extremely painful when movement is attempted.
Bone infection (osteomyelitis) can occur in any bone
in the body, either as a primary infection or secondary
to on overlying skin or soft tissue infection or previous
surgical procedure. Bone pain, swelling, deformities or
pus draining through the skin overlying a bone should
alert you to the possibility of this diagnosis. Spinal
infection can affect the bone itself, as in Pott’s disease
caused by tuberculosis or the intervertebral disc, most
often caused by staphylococcal infection, when spinal
percussion is often tender.
Rheumatic fever can occur in any age group,
but is rare under the age of 3 and above 15 years.
In Western countries, acute rheumatic fever is
generally preceded 2 to 4 weeks by group A
streptococcal (GAS) tonsillopharyngitis, but not by
GAS skin infections. Fever is one of the four minor
manifestations of rheumatic fever and may be high or
low. The period between the GAS infection and the
onset of rheumatic fever is free of clinical features
and C- reactive protein is normal. The most common
major manifestation of rheumatic fever is arthritis
followed by pancarditis, chorea (Sydenham’s),
erythema marginatum and subcutaneous nodules.
Although fatigue is a prominent complaint in
idiopathic inflammatory myositis, fever occurs
mainly in patients with juvenile dermatomyositis and
anti- synthetase syndrome. Other features include
Raynaud’s phenomenon, hyperkeratosis especially
of the radial side of the index fingers (mechanic’s
hands), polyarthritis and interstitial lung disease.
These patients have positive antiaminoacyl- tRNA
synthetase antibodies such as Jo- 1.
About one-fifth of patients with relapsing
polychondritis present with fever and in the absence
of chondritis of the external ear and the nose, the
diagnosis may be difficult to make.
Multisystem diseases
Fever in autoinflammatory periodic syndromes
Apart from Familial Mediterranean Fever (FMF),
the autoinflammatory periodic syndromes are
rarely encountered in routine clinical practice (Box
10.5). Nearly 90% of patients with FMF become
symptomatic before the age of 20 years. However,
genetic testing has helped diagnose mild disease
in adults. More males are affected than females. A
typical acute attack, usually lasting 1 to 3 days, is
characterized by fever, serositis and arthritis or skin
rash. The attacks may recur every few weeks, but may
be as infrequent as every few years. Acute abdominal
pain, owing to acute sterile peritonitis, occurs in 90%
of patients. Pleurisy is another clinical feature, but it
mainly occurs in patients of Armenian origin. The
term FMF is confusing because in a significant number
of cases, there is no family history, no Mediterranean
roots (Arabs, Armenians, Italians and Jews) and fever
may be absent. The patient may present with acute
arthritis or an erysipelas- like erythema (neutrophilic
dermatosis) with mild or even absent fever. The
arthritis may last up to a week.
Nearly two thirds of patients with polyarteritis
nodosa develop fever and constitutional symptoms
(arthralgia, myalgia, malaise and weight loss).
Hypertension, usually mild, is present in up to half
the patients, particularly in those with hepatitis B
viral infection. Cutaneous lesions include livedo
reticularis (Fig. 10.6), ischaemic changes in the digits
(Fig. 10.7), subcutaneous nodules and ulcerations.
Fever and constitutional symptoms may be the
main clinical features in patients with Takayasu’s
arteritis. In more than half the patients, peripheral
pulse is decreased or absent. In a small number of
patients, the inflammation of the wall of the carotid
artery may cause local tenderness (carotidynia).
Fever in patients with systemic lupus erythematosus
(SLE) can prove a challenging clinical problem. Fever
may be a major feature in about two fifths of patients
with active SLE. Infection is not easy to exclude and
the fever may be drug induced. Very rarely the fever
may be caused by lymphoma complicating lupus.
The most challenging situation is when the patient
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