WEBCAST TRANSCRIPT

Transcript of "Rash Illness Evaluation"\
Presented by Dr. Jane Seward, 6 December 2002, on the satellite
broadcast of "CDC Bioterrorism Update: Smallpox Preparedness"

(Associated graphics can be found at\
[www.bt.cdc.gov/agent/smallpox/training/webcast/dec2002/files/rash-illness-eval.ppt](http://www.bt.cdc.gov/agent/smallpox/training/webcast/dec2002/files/rash-illness-eval.ppt)
and
[www.bt.cdc.gov/agent/smallpox/training/webcast/dec2002/files/rash-illness-eval.pdf](http://www.bt.cdc.gov/agent/smallpox/training/webcast/dec2002/files/rash-illness-eval.pdf).)

Jane Seward, MBBS, MPH, Medical Epidemiologist, National Immunization
Program, CDC

(Slides 1 and 2 are title and objectives, respectively)

# SEWARD:

Today I am going to discuss evaluation of cases of febrile vesicular or
pustular rash illness. This is important because if a case of smallpox
were ever to occur again in the United States, on the one hand, we would
want to diagnose the case as early as possible so that appropriate
public health actions could be implemented. On the other hand, we want
to minimize lab testing for smallpox virus for suspected smallpox cases
unless they meet the clinical case definition because of the very real
danger of obtaining a false positive lab test. The predictive value of a
positive lab test for smallpox is extremely low when the prevalence of
smallpox is zero.

## Slide 3

Is there a need for a diagnostic algorithm? There have been no naturally
acquired cases of smallpox in the world since 1977, however, there are
serious concerns about the use of smallpox virus as a bio-terrorist
agent. Recommencing smallpox vaccination in the United States is likely
to heighten concerns about febrile vesicular and pustular rash
illnesses.

## Slide 4

In the event of a bio-terrorist release of smallpox virus, effective
public health control strategy requires early recognition of a smallpox
case. Most clinicians have never seen a case of smallpox and therefore
lack experience with making a smallpox diagnosis. Because other rash
illnesses may be confused with smallpox, a diagnostic algorithm or a
standard approach to evaluating rash illness cases would be useful.

## Slide 5

We estimate that there will be approximately 1 million cases of
varicella (or chickenpox) in the U.S. this year and many more millions
of cases of other rash illnesses. If for example, 1 out of every
thousand varicella cases were suspected to be smallpox, there would be
1000 false alarms per year. The public health system cannot handle
thousands of false alarms. We need a strategy with high specificity to
accurately detect the first case of smallpox. This strategy will serve
to minimize laboratory testing for smallpox, which will reduce the risk
of producing a false positive lab test.

## Slide 6

Using this approach, we recognize and accept the fact that the first
case of smallpox will not be diagnosed until day 4-5 of the rash and
also that the 1st case of smallpox will not be diagnosed early (in the
first 4-5 days), in fact, it may be missed altogether, if it presents
atypically as a hemorrhagic, flat/velvety, or highly modified case.

## Slide 7

Let's now review the signs and symptoms of smallpox disease. The
incubation period is 7-17 days. The pre-eruptive stage, known as the
prodrome, generally consists of fever and systemic complaints that occur
1 to 4 days before the rash.

## Slide 8

Although the rash starts as an enathem in the mouth, frequently the
first rash noticed in the exanthem. The lesions start as macules then
progress to papules then to vesicles and finally to pustules. The
pustules crust and form scabs which separate and may leave deep scars.
Let's review the rash stages to make sure that the terms are fully
understood. A macule is a red, flat lesion on the skin that is not
raised above the skin surface. A papule is a red, raised skin lesion
(like a small pimple). A vesicle is a raised skin lesion that contains
clear fluid and a pustule is a raised skin lesion that contains pus. We
will see examples of these types of lesions in the following photographs
of smallpox cases.

## Slide 9

The next few photographs of a smallpox case show the progression of the
rash. Note that on the day 2, the rash is mild, is macular and papular
and could easily be overlooked. If this were the first case, smallpox
would not be considered at this stage.

## Slide 10

On day 4 the rash is more significant and has progressed to the papular
stage with some vesicles. If there had been a febrile prodrome, we may
be considering smallpox in the differential at this point.

## Slide 11

On day 4 and 5, the rash is now vesicular. At this stage, there is an
accumulation of fluid in the vesicles. During the next 24-48 hours. the
clear fluid becomes cloudy and begins to thicken leading to pustules
which reach their maximum size by day 11. Note that in smallpox, the
lesions are all in the same stage of development on that part of the
body. That is, you would not expect to find both vesicles and pustules
on the face but you may see pustules on the face and vesicles on the
trunk.

## Slide 12

Here is another photograph of smallpox pustular lesions that clearly
demonstrates their deep seated nature. One can imagine from the
photograph that these lesions, if pressed on, would feel hard and
pea-like and could be rolled around under the skin.

## Slide 13

The typical pattern of smallpox rash distribution is demonstrated in
this drawing. The lesions are concentrated distally on the head and the
extremities in contrast with the central distribution (more lesions on
the trunk) that is typically seen in varicella.

## Slide 14

Varicella is the disease most likely to be confused with smallpox.

## Slide 15

It is important then to recognize the differentiating features of
varicella. With varicella, there is generally no, or a mild, prodrome
period. However, adults get much sicker with varicella than children do
and they may have a febrile prodrome. There is likely to be no history
of varicella or varicella vaccination. The skin lesions in varicella are
superficial, that is they are located on the skin surface. They are
classically described as "a dew drop on a rose petal". They typically
appear in crops meaning that new lesions appear over several days. This
leads to the next important differentiating feature.

## Slide 16

Lesions are typically in different stages of development. Thus, on any
one part of the body, there may be macules, papules, vesicles and
crusted lesions. The lesions evolve more rapidly than smallpox lesions;
typically they progress from macule to vesicle and even crust within 24
hours, and unlike smallpox, there is a centripetal (central)
distribution of the rash. Lesions appear rarely on the palms of the
hands or soles of the feet and the patient with varicella is rarely
toxic or moribund. Again, adults are more likely to be the exception to
this rule than children. A severe case of varicella may also have so
many lesions that distribution may not be a useful differentiating
feature and there may be lesions on the palms and soles.

## Slide 17

These photographs show varicella rashes. The lesions are superficial and
are in different stages of development. The upper right photo shows the
classic varicella, "dew drop on a rose petal" type lesions. The child in
the lower photograph has pustular and vesicular lesions.

## Slide 18

These 2 photographs are of varicella infection in an adult. Varicella
Lesions can be extensive in adults but if we could examine the lesions
closely, we would see that they are in different stages of development
and that they are superficial.

## Slide 19

Varicella infected lesions may confuse the diagnosis. During the
smallpox eradication era, varicella cases among adults, especially those
with infected lesions were the most difficult to differentiate from
smallpox cases.

## Slide 20

Apart from varicella, other conditions to consider in the differential
diagnosis in a patient with fever and a vesicular or pustular rash are:
disseminated herpes zoster; impetigo; drug eruptions; contact
dermatitis; and erythema multiforme.

## Slide 21

Other rash illnesses included on the rash algorithm poster that should
be considered in the differential diagnosis include: enteroviral
infections (especially, hand, foot and mouth disease); disseminated
herpes simplex virus infections; scabies and insect bites; and molluscum
contagiosum (in immunocompromised patients). The rash algorithm poster
that you will see on the screen shortly lists these diagnoses as well as
clinical clues for every condition.

## Slide 22

Other rare dermatological conditions, acne, secondary syphilis,
rickettsial diseases and diseases like monkeypox that are unlikely to be
seen in the United States may also be rare causes of confusion. If we
start a smallpox vaccination program in the United States, then
generalized vaccine related rashes may raise suspicions of smallpox.

## Slide 23

The goal of the rash illness algorithm is to provide a systematic
approach to evaluation of cases of febrile vesicular or pustular rash
illness. The algorithm uses clinical features of smallpox to establish
major and minor criteria and uses these criteria to classify cases of
vesicular/pustular rash illness into risk categories (likelihood of
being smallpox).

## Slide 24

The following case investigation tools are available to assist in
evaluating a suspected smallpox case: the rash algorithm poster is
available through state health departments. It can also be viewed and
ordered from the CDC website and a black and white version can be
printed from the website. An accompanying protocol can also be
downloaded and printed.

## Slide 25

The poster looks like this. It is available in 2 sizes, a wall size of
2ft by 3ft and a smaller size 11 x 17 inches. The poster shows images of
smallpox (in this corner) and chickenpox (in this corner); lists
features that differentiate chickenpox from smallpox and common
conditions that might be confused with smallpox. Finally, it presents a
method for classifying cases according to their risk of smallpox using
major and minor criteria for smallpox.

## Slide 26

A worksheet for collecting standard information on the case being
evaluated is also available through state health departments and can be
downloaded and printed from the CDC website.

## Slide 27

The worksheet looks like this. When CDC receives a call on a febrile
rash illness case, we direct the caller to this form and suggest that
they use it to gather relevant information on the case.

## Slide 28

The Smallpox Surveillance Clinical Case Definition is an illness with
acute onset of fever \> 101 degrees Fahrenheit followed by a rash
characterized by firm, deep-seated vesicles or pustules in the same
stage of development without other apparent cause.

## Slide 29

There are 3 major criteria for the clinical diagnosis of smallpox that
correspond to the 3 essential components of the clinical case
definition: 1) A prodrome that begins 1-4 days before rash onset and
includes fever \>101 degrees F (38.3 degrees C) and at least one of the
following symptoms: prostration, headache, backache, chills, vomiting,
abdominal pain. 2) Presence of classic smallpox lesions: firm, round,
deep-seated vesicles or pustules. As previously mentioned, they have a
"shotty" feel, like rolling a pea around under the skin. 3) All the
lesions are in same stage of development (on one part of the body). This
means that all lesions on the arm or all lesions on the trunk would be
all vesicles, all pustules, or all crusted lesions---not a mixture of
different skin lesions.

## Slide 30

We created five minor criteria that are characteristic of smallpox
cases: 1) the lesions have a centrifugal (distal) distribution; 2) the
first lesions appear on the oral mucosa, face, or forearms; 3) the
patient appears toxic or moribund (typically a patient is so sick that
they are bed ridden); 4) the rash has a slow evolution (each stage lasts
for 1-2 days so it takes more than a week to reach the height of the
pustular stage; and 5) there are lesions on the palms of the hands
and/or the soles of the feet.

## Slide 31

The major and minor criteria are combined to classify cases of rash
illness as seen in this poster. Depending on the major and minor
criteria present, the case is classified as high risk (red boxes),
moderate risk (yellow boxes) or low risk (green boxes) for smallpox. The
poster and protocol suggest evaluation steps and public health actions
based on the level of assessed risk.

## Slide 32

Firstly, if a patient presents at an emergency room or a hospital with a
fever and an acute, generalized vesicular or pustular rash illness,
airborne and contact precautions should be immediately instituted and
the infection control team alerted if the patient is admitted. This is
standard practice for a case of varicella or measles. In a doctor's
office, they should be isolated in a room with the door closed. Review
the clinical presentation of the patient and assess if the illness is
high, moderate or low risk for smallpox according to the major and minor
criteria.

## Slide 33

Any patient presenting with all 3 major criteria is classified as high
risk for smallpox. Again, these criteria are: prodrome 1-4 days before
rash onset; classic smallpox lesions (firm and deep seated); and all
lesions in same stage of development (that means all vesicles, all
pustules, all scabbing etc) on one part of the body. Examine several
different areas of the patient to assess this criterion. For example, on
the face, are all lesions of the same type? On the trunk?

## Slide 34

The clinician's response to a high risk case should be to request an
Infectious Diseases and/or dermatology consultation to confirm the high
risk status. If the high risk status is confirmed, then alert the local
or state health department and obtain digital photos if possible. After
concurrence, the state health department will alert CDC to arrange for
specimen collection and testing at CDC and to discuss management advice
until the case is confirmed. State health departments are developing
state smallpox response plans that would be initiated once a case of
smallpox is laboratory confirmed. If a case is high risk, it fits the
clinical case definition and therefore should be considered a probable
case of smallpox until smallpox virus laboratory results are completed.
For such a case, DO NOT PERFORM OTHER LAB TESTING TO RULE OUT OTHER
DIAGNOSES.

## Slide 35

Moderate risk for smallpox would be a patient presenting with a
vesicular or pustular rash and reporting a prodrome and one other major
criteria, or prodrome and at least 4 minor smallpox criteria.

## Slide 36

The response for a moderate risk case is to request an infectious
diseases and possibly dermatology consultation to confirm the risk
status. Lab testing for varicella and other rash diseases should be
conducted as appropriate at the hospital, local or state health lab or
through a private lab. Rapid lab tests for varicella zoster virus are
the DFA test where results can be available within an hour or PCR which
takes 4-8 hours. A Tzanck smear can often be performed locally which
will confirm an alpha herpes virus infection within an hour. A skin
biopsy may be useful and can also be performed and read by pathologist
rapidly. Obtain digital photos if possible. Re-evaluate risk level at
least daily as risk level to determine if risk level has changed.

## Slide 37

Low risk for smallpox would be a patient presenting with a vesicular or
pustular rash and reporting no febrile prodrome prior to rash eruption
or reports a prodrome, and less than four minor smallpox criteria.

## Slide 38

The response for a low-risk patient is management and lab testing as
clinically indicated.

## Slide 39

In an era of no smallpox cases in the world, the goal of smallpox
surveillance is to recognize the first case of smallpox early in the
course of illness (or as soon as it meets the clinical case definition)
without generating a high number of false alarms. With no cases of
smallpox disease (or zero prevalence), the predictive value of a
positive lab test is essentially zero. If we test cases of rash illness
that do not fit the case definition for smallpox, we will sooner or
later get a false positive lab result. We need to minimize that risk
given the extremely serious consequences of such a result. We need to
recognize the first case of smallpox early without disrupting the health
care and public health systems and without increasing public anxiety.

## Slide 40

Now I will review CDC's rash illness response team's experience using
the algorithm. There have been 23 rash illness calls for suspected
smallpox cases to CDC since January 2002 that have been evaluated using
this diagnostic algorithm. The calls were received from 14 states and
New York City. Seventeen cases were adults and 6 were children. There
have been no cases classified as high risk and therefore there have been
no indications for smallpox virus testing. Four cases were considered
moderate risk and the other 19 cases were low risk.

## Slide 41

More than half of the reported cases have been varicella infections
including 2 cases that resulted in death (including 1 low-risk case).
Twelve of the diagnoses were confirmed by lab and/or pathology; the
other 11 were clinically diagnosed. Apart from varicella, other
diagnoses included drug reaction, erythema multiforme, disseminated
herpes zoster, disseminated Herpes simplex virus, and other
dermatological conditions

## Slide 42

The CDC experience with implementation of the rash algorithm is that the
clinician should rule in varicella zoster virus as this is the most
common condition that has raised suspicions for smallpox. Very
importantly, this algorithm has limited testing for smallpox virus by
providing a standard approach to evaluation of suspected smallpox cases.

## Slide 43

Our experience with evaluating cases of suspected smallpox is similar to
experience from earlier this century from the United Kingdom and
Somalia. The majority of suspected cases in these series were
chickenpox; other diagnoses included those described on the poster and
those we that have been reported to CDC this year. Note that vaccinia is
included in these series. As we commence smallpox vaccination in the
United States, we will need to consider vaccine complications in the
differential of generalized febrile vesicular pustular rashes and
enquire about recent smallpox vaccination or contact with a vaccinee.

## Slide 44

Smallpox vaccination may result in complications in either the vaccinee
and/or close contacts. Two of these complications present as generalized
rashes where fever may also be present. Generalized vaccinia is a
benign, self limiting condition that, in a 10 state survey conducted in
the late 1960s, was reported to occur at a rate of approximately 240
cases per million primary vaccinees. The generalized rash occurs 6 to 9
days after vaccination; the lesions are smaller and more superficial
than classic smallpox lesions; they mature more rapidly and they are
more likely to be confused with modified smallpox. The distribution of
the lesions follows no set pattern and is not typically greater on the
face and distal extremities as is characteristic of smallpox. A history
of recent smallpox vaccination will help raise suspicion of this
complication.

## Slide 45

Eczema vaccinatum is a rare but more serious and life threatening
complication of smallpox vaccination that may occur in the vaccinee or
in a close contact 5 to 19 days following vaccination. From the 10 state
survey, the rate of eczema vaccinatum was 40 cases per million primary
vaccinees.

## Slide 46

In addition, 10 to 20 cases occurred in contacts of every million
primary vaccinees. The rash commences in abnormal areas of skin and then
spreads all over the body but does not follow the centrifugal (or
distal) pattern of smallpox. When evaluating cases of febrile vesicular
or pustular rash illness, the patient should be asked if they received
smallpox vaccine recently or if they have been in close contact with
someone who was vaccinated.

## Slide 47

For cases that are not high risk for smallpox, laboratory capacity is
needed to diagnose conditions that may be confused with smallpox
especially moderate risk cases which may cause more concern. Lab and
pathology capacities at the local level may include Tzanck smear, skin
biopsy and less commonly, DFA for varicella. Capacity to perform rapid
varicella zoster virus diagnostics (DFA or PCR) is now available in
every state health lab.

## Slide 48

Other tests that may be useful are electron microscopy (looking for a
pox virus, a herpes virus or other viruses) which may be available in
academic medical centers, and tests for Herpes simplex virus infections.

## Slide 49

Testing for vaccinia should be considered if there is a history of
recent smallpox vaccination or close contact with a vaccinee. Other
tests should be performed as clinically indicated.

## Slide 50

Support for local health departments and private physicians who are
evaluating a case of rash illness suspected to be smallpox is provided
by state health departments via their 24 hour emergency phone number; by
providing rapid laboratory testing for varicella an other rash
illnesses; and by providing infectious disease and dermatology
expertise.

The Centers for Disease Control and Prevention has on-call-staff
available 24 hour a day, 7 days a week, every day of the year to assist
state health departments. The on call staff have smallpox disease
experts available for consultation. CDC can also provide laboratory
support as requested.

## Slide 51

A final reminder, as already mentioned, The smallpox algorithm poster is
available through state health departments and can be viewed and printed
from the CDC website and can be ordered through the CDC on line ordering
system.

## Slide 52

CDC has developed a written protocol to accompany the poster and a
worksheet that can be used for investigation of febrile vesicular
pustular rash illnesses suspected to be smallpox. They are also
available through state health departments and can be downloaded and
printed from the CDC smallpox website.

# SEWARD:

In summary, the diagnostic algorithm is an important tool for evaluating
cases of febrile vesicular or pustular rash illness suspected to be
smallpox. Understanding the clinical features of smallpox disease and
smallpox look alike illnesses, especially varicella, is important for
evaluating these cases so that their risk of being smallpox can be
assessed in a systematic way and an appropriate clinical and public
health response can occur.

END

For more information, visit
[www.cdc.gov/smallpox](http://www.cdc.gov/smallpox), or call the CDC
public response hotline\
at (888) 246-2675 (English), (888) 246-2857 (Español), or (866) 874-2646
(TTY)