The Acutely Ill Patient With Fever and Rash Department of Microbiology Micro II-643 Infectious Diseases Victoria Michelen, MD

THE ACUTELY ILL PATIENT
WITH FEVER AND RASH
Department of Microbiology
Micro II-643
Infectious Diseases
Victoria Michelen, MD
Objectives
1) Describe the different types of skin lesions.

2) Describe the most important features of
exanthemas and how to differentiate them
from non infectious illnesses.
3) Describe the epidemiology and
pathophysiology of the common viral
exanthemas.
4) Identify viral and bacterial infections
based on the patient history and clinical
presentation.
Objectives
5) Compare infectious with

noninfectious skin and soft tissue
manifestations.
6) Discuss the clinical features of
the most important pathogens that
cause fever and rash.
7) Describe immunizations for the
prevention of common bacterial or
viral illnesses.
8) Recognize the importance of early
diagnosis of exanthematic diseases.
Rash
Rash = eruption on the skin
Limited number of skin

manifestations that result from a
variety of insults.
The diagnosis cannot be made by

the description of the rash alone.
No skin lesion is pathognomonic

for a specific pathogen.
Rash
The skin manifestations

associated with a specific infectious
agent may be variable.
The different types of skin lesions

may be seen at different times in the
course of one illness.
Rash
Host factors such as neutropenia

and thrombocytopenia may alter the
skin manifestations.
A variety of mechanisms may be

involved in the pathogenesis associated
with infection.
They can develop secondary to

multiplication of organisms within the
skin.
Rash
Micro-organisms can produce toxins that

can directly affect skin structure or can elicit
an inflammatory response in the skin.
Vascular involvement may also play a role.
More than one mechanism may be involved

with a specific pathogen.
Skin lesions involving the skin = exanthems
Skin lesions involving mucous membranes =

enanthems.
Rash
One infectious agent can cause

many dermatological
syndromes and many agents
can present with an
identical dermatological
picture.
Rash
For the purposes of discussion we

will divide rash into six categories:
1- Macules/papules,
2- Diffuse erythema,
3- Vesicles/bullae,
4- Nodules,
5- Petechiae/purpura and
6- Urticaria.
Types of skin lesions:
• Maculae = flat, non palpable.

• Papules = small, solid, palpable.
• Nodules = large papules.
• Vesicles and bullae = small and large
blisters.
• Pustules = small, palpable, filled
with pus.
• Plaques = large, flat, palpable (> 1
cm).
• Purpura = petechiae < 3 mm,
ecchymosis > 3 mm.
Maculae
Papule
Vesiculae
Bullae
Pustule
Petechia
• Text size 36 for main bullets or
paragraphs
– Size 32 for sub-bullets
• Never smaller than 28. If the
text doesn’t fit on the slide in
that size, split into multiple
slides.
Initial Evaluation Concerns
1. May provide the only clue for the

diagnosis
2. May be the hallmark of contagious
disease.
3. May be an early sign of a life-
threatening infection.
History
1. Drug ingestion within past 30

days.
2. Travel history.
3. Occupational exposure.
4. Sun exposure.
5. Immunization history.
6. STI exposure.
7. Prior illnesses and drug
allergies.
8. Exposure to ill persons.
9. Habits, pets, wild rural habitat.
10. Season of the year.
Maculo Papular Rash
1a - Drug eruptions and immune

complex mediated
syndromes.
1b - Viral illnesses.
1a or 1b- Toxic epidermal
necrolysis
• Drug hypersensitivity and

infections(HSV, M. pneumoniae)
• Skin and mucosal involvement
• Nikolsky’s sign (dermal-epidermal

junction)
• Superimposed infection  mortality

to 40%
1a or 1b – Erythema multiforme
1)Target lesions at Knee, elbow, palm, sole.
2) Children: infection by HSV,

Mycoplasma pneumonia, etc.
3) Adults: infection, drug allergy,

idiopathic.
4) Stevens Johnson syndrome = mucosal

involvement with fever.
5) Nikolsky’s sign negative.

1b Measles (rubeola): RNA virus
• Epidemic winter-spring disease

• Typical measles: elementary
school; IP ~ 10 days.
• Prodromus ( contagious), fever (4 days),
malaise, headache.
• Koplik spots.
• Maculopapular centrifugal rash.
• Typical measles in adults: confusion and
delayed dx
Atypical measles:
Centripetal distribution, no Koplik

spots and pneumonia linked to:
Killed vaccine use (1963-1967).
T-cell sensitivity and  antibody

levels.
1b - Rubella (German measles):
RNA virus
• Higher attack rate: 5 to 9 year-old-age.

• Respiratory route in spring and winter.
• I.P ~ 2 to 3 weeks.
• Transmission ~ 10 days before RASH-
14 days after.
• Pruriginous rash of 3 to 5 days
duration and lymphadenopathy.
• Congenital (TORCH).
1b - Erythema infectiosum ( 5th disease) =
Human Parvovirus B 19
1rst stage: slapped cheek.
2nd stage: morbilliform rash upper

extremities x 2 weeks with relapses;
gloves and socks.
STAR complex.
Anemia crisis in patients with hemolytic

disorders and in fetus.
1b - Roseola infantum
(Exanthema subitum)
• HHV 6 and 7.
• Common viral rash in

childrenunder the age of two.
• High fever with preserved general

state for 3 -5 days followed by pink
papular rash on the trunk x 2 days.
• Febrile seizures.
1a – 1b? – Mucocutaneous Syndrome:
Kawasaki
• Systemic vasculitis of unknown origin.

• Children < 5 years of age.
• Fever x 5 days plus four of the following:
Bilateral conjunctiva injection
Mucosal changes
Non vesicular rash
Desquamation at extremities
Cervical lymphadenopathy
• Negative Nikolsky’s sign
• Complication: Coronary artery disease
2- Nodular lesions (dermis)
May contain inflammatory cells,

organisms, tumor cells, etc.
2a - Infectious: Fungi and

Bacteria.
2b - Infectious origin or related:

Erythema nodosum,
Erythema induratum.
2b - Erythema Nodosum
• Tender erythematous, non suppurative

ellipsoidal nodules < 1 cm to few cms.
• Usually localized in the anterior
surface of the legs.
• Heal in days to weeks.
• Etiology:
Streptoccocus, TB, fungi, etc.

Pregnancy, SLE, Sarcoidosis
2b - Erythema Induratum
• Painful, red, suppurative

nodules at posterior ankles.
• Hypersensitivity to TB distant
bacilli.
3 - Vesicular Eruptions:
HSV is the most common.

It is clustering of painful vesicles
that progresses to mucocutaneous
ulcerations.
Transmission: contact
Prevention: Counseling
3 - Chickenpox (Varicella);
DNA virus
• Five to 9 year-old- age children in

winter and spring.
• Transmission: contact and airborne.
• I.P. ~ 14 to 21 days.
• Pruriginous rash, different stages.
• centrifugal distribution.
• Fetal transmission.
• Antivirals.
•
3- Herpes zoster virus (shingles)
• Dermatomal distribution
• Painful lesions
• Contact transmission
• Vaccine
3- Coxsackievirus (especially S
16 A)
• I.P. 4-6 days; no scabbing

• Small children, rare in adults.
• Contagious by: oral secretions,
blisters content and feces.
• Diff. diagnosis: HSV and VZV
• Complications: myocarditis,
meningitis, etc.
4 - Petechial and Purpuric
Eruptions
4a - Noninfectious:
thrombocytopenia,
necrotizing vasculitis
(palpable purpura).
4b - Infectious:
Viruses (VHF, etc.);
Bacteria (N. meningitidis)
4a - Noninfectious palpable
purpura
4b - Viral Hemorrhagic Fever:
Dengue
• Four serologically related RNA

viruses.
• Fifty to 100 million cases/year.
• After an IP of 5 to 8 days, fever,
chills, malaise, backache,
headache, ocular pain.
• Maculopapular pruriginous rash.
• Hemorrhagic dengue: petechial
rash or frank bleeding.
• Dengue shock.
4b – Meningitis by Neisseria
meningitidis
• Winter and spring epidemics.

• Purpuric lesions: 50 – 90% of patients
with fulminant meningococcemia.
• 2ry to endotoxin endothelial damage.
• Petechial rash at the extremities that
spread to the trunk, head and mucous
membranes followed by DIC.
• Prevention: oral antibiotics and
vaccine.
5 – Other important pathogens that cause
fever and different types of skin rash
5 a - Neisseria gonorrhoeae
5 b - Pseudomonas aeruginosa
5 c - Staphylococcus aureus
5 d - Streptococcal pyogenes
5 e- Rickettsia
5 f - Borrelia burgdorferi
5 g - Candida spps.
5 h - Treponema pallidum
5 i - H. I. V.
5a - Neisseria gonorrhoeae:
disseminated
• Scanty, widely distributed tiny

pustules.
• Distal tenosynovitis.
• Prevention: healthy sex.

5c - Pseudomonas aeruginosa
• Folliculitis 2ry to hot tub or

swimming pool bathing.
• Large follicular-based tender

red papules in areas of exposed
skin.
• Rx: Oral antibiotics, local care.

5d – Group A Streptococcus
Scarlet fever
Pharyngitis, exfoliative
exotoxin sandpaper rash
12 – 48 hours after fever,
Pastia lines, circumoral Pallor.
5e – Rickettsia rickettsii
• Intracellular GN cocobacillus
• RMSF:
Ticks (Dermacentor)
Bites and feces
Most frequent and severe In US (~ not in
Europe)
Spring and fall
Blood stream → vasculitis
No-toxin mechanism
Maculopapular rash at wrists and ankles
petechial, centripetally, about 3 days after
onset of fever.
5f - Borrelia burgdorferi
• Erythema chronicum migrans:

50 – 75% of the patients; usually
localized at the site of the tick (nymph)
bite.
• Annular erythema spreading

centrifugally, dysesthesia.
Multiple, small lesions in the 2nd stage.

5g - Disseminated Candidiasis
• Frequently fatal in the immuno

suppressed patients.
• Firm, not tender papules or nodules
that may become
hemorrhagic.
• Fungi is isolated from lesions and
blood.
5h - Treponema pallidum
• Second stage of syphilis: after four

to ten weeks of 1ry
stage, a non pruriginous, non
painful maculopapular
rash with alopecia.
5i - Human Immunodeficiency
Virus
Lesions usually are prolonged,

aggressive, atypical,
unresponsive and sometimes
coexist multiple pathogens
in the lesions.
– Kaposi sarcoma (HHV 8)

– Norwegian scabies

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THE ACUTELY ILL PATIENT

WITH FEVER AND RASH

1) Describe the different types of skin lesions.

5) Compare infectious with

Rash = eruption on the skin

Limited number of skin

The diagnosis cannot be made by

No skin lesion is pathognomonic

The skin manifestations

The different types of skin lesions

Host factors such as neutropenia

A variety of mechanisms may be

They can develop secondary to

Micro-organisms can produce toxins that

Vascular involvement may also play a role.

More than one mechanism may be involved

Skin lesions involving the skin = exanthems

Skin lesions involving mucous membranes =

One infectious agent can cause

For the purposes of discussion we

• Maculae = flat, non palpable.

1. May provide the only clue for the

1. Drug ingestion within past 30

1a - Drug eruptions and immune

• Drug hypersensitivity and

• Skin and mucosal involvement

• Nikolsky’s sign (dermal-epidermal

• Superimposed infection  mortality

1)Target lesions at Knee, elbow, palm, sole.

2) Children: infection by HSV,

3) Adults: infection, drug allergy,

4) Stevens Johnson syndrome = mucosal

5) Nikolsky’s sign negative.

• Epidemic winter-spring disease

Centripetal distribution, no Koplik

Killed vaccine use (1963-1967).

T-cell sensitivity and  antibody

• Higher attack rate: 5 to 9 year-old-age.

1rst stage: slapped cheek.

2nd stage: morbilliform rash upper

Anemia crisis in patients with hemolytic

• Common viral rash in

• High fever with preserved general

• Systemic vasculitis of unknown origin.

May contain inflammatory cells,

2a - Infectious: Fungi and

2b - Infectious origin or related:

• Tender erythematous, non suppurative

Streptoccocus, TB, fungi, etc.

• Painful, red, suppurative

HSV is the most common.

• Five to 9 year-old- age children in

• I.P. 4-6 days; no scabbing

• Four serologically related RNA

• Winter and spring epidemics.

• Scanty, widely distributed tiny

• Prevention: healthy sex.

• Folliculitis 2ry to hot tub or

• Large follicular-based tender