Pediatrics 11: 4-year-old male with fever and adenopathy

User: Maryam Fadah

Email: 201315184@uaeu.ac.ae
Date: March 8, 2020 9:00PM

Learning Objectives

Upon completion of the case, the student should be able to:

Perform an age-appropriate history and physical examination for a child with fever and rash.
Generate an age-appropriate differential diagnosis for fever and rash in a child.
Describe clinical findings associated with important causes of fever and rash.
Generate an age-appropriate differential diagnosis for fever and irritability.
Summarize the diagnosis and treatment of Group A streptococcal pharyngitis.
List causes of unilateral cervical adenopathy
List and define terms commonly used to describe rashes.
Summarize diagnostic criteria, clinical features, pathophysiology, natural history, complications, treatment, and follow-up care
of Kawasaki disease.

Knowledge

Pediatric Vital Signs

As a child gets older, the normal ranges for vital signs change, making it important to look at age-appropriate reference values.

The normal heart rate for a 4-year-old is 65 to 135 beats per minute (average heart rate 110 bpm).

Causes of Unilateral Cervical Lymphadenopathy

The following can all cause unilateral cervical lymphadenopathy:

Reactive
cervical Occurs in response to an oral infectious or inflammatory process
adenitis

Lymphadenopathy with Kawasaki disease is most often unilateral, with lymph nodes often larger than 1.5
Kawasaki cm in diameter, although less commonly diffuse lymphadenopathy can occur.
disease
Enlarged lymph nodes are nonfluctuant.

Typically seen in children ages one to five years with a history of a recent upper respiratory tract infection.

Bacterial Staphylococcus aureus and Streptococcus pyogenes are the organisms most commonly identified.
cervical
adenitis Patients may have high fevers and a toxic appearance.

Overlying cellulitis and development of fluctuance are common.

Infections caused by the bacterium Bartonella henselae can be asymptomatic or symptomatic.

The infection usually is introduced by a scratch from a cat or kitten, with subsequent infection of the node
Cat scratch or nodes draining that site.
disease
The site most commonly involved is the axilla, followed by cervical, submandibular, and inguinal areas.

Usually a self-limited disease, with regression of the lymph node in four to six weeks.

Mycobacterial infections can cause diffuse lymphadenopathy or isolated lymphadenitis.

Lymphadenitis is the most common manifestation of nontuberculous mycobacteria in children, with a peak
age of presentation of 2 to 4 years.

Tuberculosis is the most common cause of mycobacterial lymphadenitis in children over 12 years of age.
Mycobacterial Children with these infections usually appear well with minimal if any constitutional signs and symptoms.
infection
The overlying skin may be erythematous initially, but left untreated often becomes violaceous as the nodes

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 enlarge.

Nodes may rupture through the skin, resulting in a draining sinus tract.

Treatment is surgical excision, as incision and drainage can also result in a sinus tract.

Strawberry Tongue

"Strawberry tongue," an erythematous tongue with prominent papillae, is a characteristic finding of:

Streptococcal pharyngitis
Kawasaki disease
Toxic shock syndrome

Though this finding can be seen in infectious mononucleosis, it is usually in the presence of a concomitant streptococcal
pharyngitis.

Diagnostic Criteria for Kawasaki Disease

In addition to high fever for at least five days, four of the following five criteria are needed for a diagnosis of Kawasaki disease:

Changes in oral mucosa (dry or cracked lips, injected pharynx, or strawberry tongue)
Extremity changes (redness/swelling)
Unilateral cervical lymphadenopathy
Rash
Conjunctivitis (bilateral, nonpurulent)

The one least likely to be present is cervical adenopathy.

Though irritability is very common, it is not part of the diagnostic criteria.

Other illnesses with similar clinical features should be considered before the diagnosis of Kawasaki is made, since the principal
clinical findings are not specific. Children who do not meet the criteria may have an incomplete form of KD.

Kawasaki Disease

Kawasaki disease (KD) is an acute inflammatory panvasculitis of unknown etiology. It is thought that the disease results from an
autoimmune response to a not yet identified infectious trigger. KD is a disease of childhood, with the typical age of patients 15-18
months old; 80% of KD patients are under the age of 5 years. KD "outbreaks" follow seasonal patterns, and children of Asian
descent have a higher incidence of KD (suggesting both infectious and genetic influences).

There are three distinct phases of illness:

1. Acute phase: onset through ~10 days. Fever and clinical findings are present, with serologic evidence of systemic
inflammation (elevated acute phase reactants).
2. Subacute phase: 10 days through ~3 weeks. Fever resolves and clinical findings largely subside (often with peeling of hands
and feet). Serologic evidence of inflammation continues.
3. Convalescent phase: 3 weeks through 6-8 weeks. All clinical findings have resolved. Continued serologic evidence of
inflammation.

Beyond 6-8 weeks, serologic evidence for inflammation has resolved. KD causes a panvasculitis, impacting any blood vessels,
although there is a predilection for small and medium-sized vessels (especially the coronary arteries for unclear reasons). This
vasculitis can lead to aneurysmal dilation, particularly during the subacute phase of illness.

Complications of Kawasaki Disease

The complications associated with Kawasaki disease-and the approximate percentages of patients who develop these
complications-are as follows:

Complication Percentage of KD Patients Who Experience

Aseptic meningitis or other central nervous system 90% of patients develop neurologic manifestations, which can range
manifestations from irritability to aseptic meningitis

Coronary artery aneurysm 20-25% of untreated patients

Liver dysfunction (as evidenced by elevated

40%
transaminases and a decreased albumin)

Arthritis 30%

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 Hydrops of the gallbladder 10%
Of these potential complications, the risk with the greatest morbidity is the vasculitis that can lead to the development of coronary
aneurysms. The main purpose of the treatment of Kawasaki disease is to minimize this risk.

Timing

Kawasaki disease is an inflammatory panvasculitis; that vasculitis predisposes to the development of aneurysms. Aneurysms can
form in any vascular bed, although for unclear reasons there is a predilection for coronary artery aneurysms in KD. The greatest
risk for the development of CA aneurysms is in the subacute phase of illness (beyond 10 days), and aneurysms almost always
develop within four weeks of the onset of the disease. Aneurysms that form during this time are at risk for thrombosis due to the
concurrent thrombocytosis.

Monitoring

All patients should receive a baseline echocardiogram during the acute phase, both to look for the presence of aneurysms and to
provide a baseline for future comparison.

Clinical Skills

Dermatologic Nomenclature

The following are terms that are commonly used to describe rashes with accuracy:

Macule Flat, circumscribed discoloration < 1 cm (> 1 cm is a patch)

Papule Elevated, circumscribed solid lesion < 1 cm

Vesicle Circumscribed, elevated lesion containing clear-colored fluid < 1 cm

Pustule Small, well-defined bump containing purulent material

Plaque Broad, elevated lesion (or confluence of papules) > 1 cm

Desquamation Shedding of the outer layer of skin surface

Management

Treatment of Kawasaki Disease

Aspirin and intravenous immune globulin (IVIG) have been the standard therapy for Kawasaki disease for many years.

Aspirin

High-dose aspirin (80-100 mg/kg/day, divided into four doses) is administered for its anti-inflammatory properties.
Aspirin shortens the febrile course of the illness but has no effect on the development of aneurysms.
Following defervescence, low-dose aspirin (3-5 mg/kg/day given in a single dose) is administered for its anti-platelet effects.
Aspirin is discontinued altogether after a total of six to eight weeks if no coronary artery changes are seen in follow-up
echocardiograms. If there are coronary artery abnormalities, low dose aspirin is continued indefinitely as an anti-platelet
agent.

IVIG

The use of IVIG in Kawasaki disease has decreased the incidence of coronary artery aneurysms from 20-25% to 2-4%.
A single dose of IVIG at a dose of 2 g/kg administered over ten to twelve hours has been shown to be more effective in
reducing the risk of coronary artery aneurysms than multiple lower doses.

Other antipyretics are usually not effective for fever control. Furthermore, use of ibuprofen has been shown to antagonize the
irreversible platelet inhibition induced by aspirin and therefore should be avoided in children with coronary aneurysms taking
aspirin for its antiplatelet effects.

Antibiotics have not been shown to have any effect on the clinical course.

The role of steroids is unclear. For years, steroids were felt to have no role, or even to be detrimental. Newer studies suggest that
they may have a role in the acute management, and additional information is needed. Other immunomodulators targeting more
specific arms of the inflammatory cascade are being studied (see references below for more information); no treatment has
proven superior to IVIG and aspirin, which thus remains the standard of care.

Follow-up Care for Kawasaki Disease

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 Cardiology follow-up

If coronary artery aneurysms develop, they usually do so during the subacute phase of illness and almost always by four
weeks of onset of the acute illness. A follow-up visit at one to two weeks is recommended.

Aspirin

Once the febrile phase of Kawasaki disease resolves, children are typically prescribed a low dose of aspirin to be taken for
six to eight weeks.
Since aspirin can cause gastrointestinal bleeding and other problems, parents should watch for warning signs, such as a
stomachache or blood in the stool.

Influenza vaccine

Children taking aspirin are at risk for Reye syndrome (a potentially fatal illness that causes multi-organ damage) if infected
with certain viruses, including influenza and varicella. Parents should avoid exposure to anyone with known flu or chicken
pox, and children should receive the intramuscular flu vaccine.

Studies

Laboratory evaluation of Kawasaki Disease

Although Kawasaki disease is a clinical diagnosis, there are laboratory findings that are supportive of this diagnosis, especially
when the diagnosis is not as clear as Jason's. These include:

CBC with differential

WBC: The white blood count is usually elevated, with a predominance of neutrophils.

Hgb/Hct: A normochromic, normocytic anemia is common.

Platelets: Thrombocytosis is a common feature of Kawasaki disease - usually starting in the second week of the illness.

Liver enzymes

Liver enzymes (transaminases) can be elevated. Serum albumin level is frequently low in Kawasaki disease.

Acute phase reactants

Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) lack specificity, which limits their utility for diagnostic purposes,
although they can lend support for or against some diagnoses. They frequently play a more useful role in following a disease
process.

In this case, a negative ESR would argue strongly against Kawasaki disease. The persistence of an elevated ESR after the fever
has subsided can help to distinguish Kawasaki disease from other infectious rash/fever illnesses.

Urinalysis

A sterile pyuria, secondary to a sterile urethritis, is associated with Kawasaki disease. A clean-catch urine is likely to show white
cells, whereas a catheterized urine may not (because the white cells come from the urethra).

Clinical Reasoning

Differential Diagnosis for a Child with Fever and a Rash

Disease Description Typical features from H&P

May cause upper respiratory tract infection, pharyngitis,

Adenovirus conjunctivitis, tonsillitis, or otitis media
Viral infection
Infection
Potential for more severe infections in immunocompromised hosts

Fever for at least 5 days

Cervical adenopathy

Nonpurulent conjunctivitis
Kawasaki disease Vasculitis
Nonspecific ("polymorphic") rash

Swelling and erythema of extremities

Mucosal inflammation

Fever

Chills, malaise
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 Meningococcemia Bacterial infection (Neisseria Rash (often petechial)
meningitidis)
May lead to shock and DIC (often rapidly progressing)

After a prodrome of fever (over 38.3 C, or 101 F), cough, coryza,

and conjunctivitis, this maculopapular rash starts on the neck,
behind the ears, and along the hairline.

The rash spreads downward, reaching the feet in two or three

days.
Measles Viral infection
The initial rash appears on the buccal mucosa as red lesions with
bluish white spots in the center (known as Koplik spots). These
have frequently disappeared by the time the patient presents to
medical attention.

Immunization is very effective in preventing this infection.

Fever

Headache
Rocky Mountain Rash (typically starts on ankles and wrists and progresses
Tick-borne bacterial infection
spotted fever centrally and to palms and soles; may be macular or papular at
(Rickettsia rickettsii)
(RMSF) first, quickly becoming petechial; in 5% of cases, there may be no
rash)

Myalgias

Fever

A diffuse, erythematous, finely papular rash (described as having a

"sandpaper" texture) is pathognomonic
Scarlet fever Group A Streptococcus infection
Rash often begins at neck, axillae, and groin and then spreads
over trunk and extremities, typically resolving within four or five
days

Macular rash, or diffuse erythema, often tender, with subsequent

A mucocutaneous disorder caused
Stevens-Johnson by a hypersensitivity reaction to
syndrome medications, infections, or other
illnesses
vesicles or bullae that may progress to erythema multiforme.
Nikolsky sign may be present.
Fever
Mucosal changes (e.g., stomatitis)

Conjunctivitis

Fever lasting 3-5 days

Enteroviral Coxsackievirus, echovirus, Nonspecific rash (which may include the palms and soles)
infection enterovirus
May also cause conjunctivitis, oral ulcers, diarrhea, aseptic
meningitis

"Chicken pox:" rash starts on trunk and spreads to extremities and

head

Each lesion starts as an erythematous macule, then forms a

Viral infection (varicella-zoster papule followed by a vesicle before crusting over
Varicella
virus)
Lesions at various stages of development are seen in the same
area of the body

Immunization is effective in preventing this infection

Also called 5th disease

Low grade fever followed by a rash, which starts as a facial

erythema to the face ("slapped cheek" appearance), which can
Erythema
Viral infection (parvovirus B19) spread to the trunk and extremities and appears lacy
Infectiosum
Can lead to pain and swelling of the extremities, as well as
development of transient pure red cell aplasia which can lead to
severe anemia in patients with underlying hemolytic disease.

"Exanthem subitum." Also called sixth disease

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 Erythematous macules start on trunk and spread to arms and neck
(less commonly face and legs)
Viral infection (human herpesvirus
Roseola
6) Rash is typically preceded by 3 to 4 days of high fevers, which end
as the rash appears

Usually occurs in children under age 2 years

References

CDC Flu Guidelines: https://www.cdc.gov/flu/professionals/index.htm

Catella-Lawson F, Reilly MP, Kapoor SC, et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med. 2001;345
:1809 -1817

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease A Scientific Statement for Health Professionals From the
American Heart Association Circulation. 2017;135:e927-e999

Dominguez SR, Anderson MS. Advances in the treatment of Kawasaki disease. Current Opinions in Pediatrics. February 2013; 25(1):
103-9.

Newburger JW, Takahashi M, Burns JC. Kawasaki disease. Journal of the American College of Cardiology. April 2016; 67(14): 1738-49.

Patel RM, Shulman ST. Kawasaki disease: a comprehensive review of treatment options. Journal of Clinical Pharmacy and
Therapeutics. December 2015; 40(6): 620-5.

Wooditch AC, Aronoff SC. Effect of initial corticosteroid therapy on coronary artery aneurysm formation in Kawasaki disease: a meta-
analysis of 862 children. Pediatrics . 2005;116:989-995.

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