Cardinal Manifestations of Disease:
Dr. Meg-angela Christi Amores
Fever and Hyperthermia
• hypothalamic thermoregulatory center –
regulates body temperature (core BT 37 C)
• A.M. temperature of >37.2°C (>98.9°F) or a
P.M. temperature of >37.7°C (>99.9°F) would
define a fever
• Rectal temperatures are generally 0.4°C
(0.7°F) higher than oral readings
• Elevation of body temperature that exceeds
the normal daily variation
• occurs in conjunction with an increase in the
hypothalamic set point
• Vasoconstriction in hands and feet, feeling
cold, shivers = heat conversion and production
• until the temperature of the blood bathing the
hypothalamic neurons matches the new
thermostat setting
• Pathogenesis
– Pyrogens – substances that cause fever
• Exogenous (microbial products, microbial toxins, or
whole microorganisms)
• Endogenous a.k.a Cytogenic Pyrogens (IL-1, IL-6, tumor
necrosis factor (TNF), ciliary neurotropic factor (CNTF),
and interferon (IFN) )
– Elevation of Hypothalamic Set point
• levels of prostaglandin E2 (PGE2) are elevated in
hypothalamic tissue and the third cerebral ventricle
• uncontrolled increase in body temperature
that exceeds the body's ability to lose heat
• setting of the hypothalamic thermoregulatory
center is unchanged
• does not involve pyrogenic molecules
• Exogenous heat exposure and endogenous
heat production
Fever and Rash
• presents a diagnostic challenge
Measles – Rubeola, rash starts at the hairline 2–
3 days into the illness and moves down the
body, sparing the palms and soles
Koplik's spots - seen during the first 2 days
Rubella – German measles, also spreads from
the hairline downward, but tend to clear from
originally affected areas as it migrates, and it
may be pruritic
Fever and Rash
• erythema infectiosum (fifth disease) - human
parvovirus B19, primarily affects children 3–12
years old; develops after fever has resolved as
a bright blanchable erythema on the cheeks
– more diffuse rash (often pruritic) appears the next
day on the trunk and extremities and then rapidly
develops into a lacy reticular eruption that may
wax and wane
Fever and Rash
• systemic lupus erythematosus - typically
develop a sharply defined, erythematous
eruption in a butterfly distribution on the
cheeks (malar rash)
• Still's disease - manifests as an evanescent
salmon-colored rash on the trunk and
proximal extremities that coincides with fever
Types of lesions
Macules - flat lesions defined by an area of changed color
Papules - raised, solid lesions <5 mm in diameter
plaques ->5 mm in diameter with a flat, plateau-like surface
nodules ->5 mm in diameter with a rounded configuration
Wheals (urticaria, hives) - papules or plaques that are pale
pink and may appear annular (ringlike) as they enlarge
• Vesicles (<5 mm) and bullae (>5 mm) are circumscribed,
elevated lesions containing fluid
• Pustules are raised lesions containing purulent exudate
Fever and Rash
Fever of Unknown Origin (FUO)
Classic Definition
• 1) temperatures of >38.3°C (>101°F) on
several occasions
• (2) a duration of fever of >3 weeks
• (3) failure to reach a diagnosis despite 1 week
of inpatient investigation
Fever of Unknown Origin
New Classification
• (1) classic FUO
• (2) nosocomial FUO
• (3) neutropenic FUO
• (4) FUO associated with HIV infection
Classic FUO
• temperatures of >38.3°C on several occasions
• a duration of fever of >3 weeks
• outpatient visits or 3 days in the hospital without
elucidation of a cause or 1 week of "intelligent
and invasive" ambulatory investigation
Undiagnosed – 30%
Infections (e.g. Tuberculosis) – 26%
Non-infectious Inflammatory (e.g.PR, SLE)– 24%
Neoplasms – 12.5%
• Nosocomial FUO – more than 50% are
– Intravascular lines, septic phlebitis, and prostheses
are all suspect
– Multiple blood, wound, and fluid cultures are
– Threshold for CT scans, ultrasonography, 111In
WBC scans, noninvasive venous studies is low
• Neutropenic FUO
– Neutropenic patients are susceptible to focal
bacterial and fungal infections, to bacteremic
infections, to infections involving catheters
(including septic thrombophlebitis), and to
perianal infections
– Candida and Aspergillus infections are common
– 50–60% of febrile neutropenic patients are
infected, and 20% are bacteremic
• HIV- associate FUO
– Due to HIV alone
– due to Mycobacterium avium or Mycobacterium
intracellulare, tuberculosis, toxoplasmosis, CMV
infection, Pneumocystis infection, salmonellosis,
cryptococcosis, histoplasmosis, non-Hodgkin's
lymphoma, and (of particular importance) drug
Hypothermia and Frostbite
• Accidental hypothermia - unintentional drop
in the body's core temperature below 35°C
• Primary accidental hypothermia is a result of
the direct exposure of a previously healthy
individual to the cold
• Heat loss occurs through five mechanisms:
– radiation (55–65% of heat loss)
– conduction (10–15% of heat loss, but much
greater in cold water)
– convection (increased in the wind)
– Respiration
– evaporation (which are affected by the ambient
temperature and the relative humidity)
• Hypothermia is confirmed by measuring the
core temperature, preferably at two sites.
• cardiac monitoring should be instituted, along
with attempts to limit further heat loss
• Supplemental oxygenation is always
• For the next meeting, read on Cardinal
Manifestations of Disease : DYSPNEA
• Harrison’s Principles of Internal Medicine 17th

Cardinal Manifestations of Disease