Clinicopathologic Case Report

February 2018

Department of Pediatrics
Chong Hua Hospital

MHAM College of Medicine

Group 3A Members:
Lomocso, Julienne
Baconga, Keziah
Goyeneche, Marichelle
Javier, Joffey Morie
Lecciones, Michael Philip
Macapas, Siegfred Keene
Mathew, Chris Mary
Oghayon, Rowell

A.) History and Physical Exam

This is a case of AR, 5 years and 7 months old, male, Roman Catholic, born on June 27, 2012. He
and his family are currently living at Englis V. Rama, Guadalupe, Cebu City. This is currently his 4th
admission in Chong Hua Hospital. Source of information is the mother with 80% reliability.

Chief Complaint: Vesicular Rash and Seizure

Prenatal History
Mother was pregnant with patient at age 31 years, OB score of G1P0. She claimed regular
monthly prenatal checkups with first visit at 1 month age of gestation done at a medical clinic with a
private physician. She had regular follow up visits thereafter. She claimed nonreactive results for
HbsAg and VDRL. She claimed regular intake of multivitamins, iron, calcium and folic acid. She denied
any maternal illness and complications during course of pregnancy.
Natal History
Patient was born full term to a 31 year old mother, OB score of G1P1 via normal spontaneous
delivery at Vicente Sotto Memorial Medical Center. Spontaneous and vigorous cry were noted at birth.
Newborn screening was done with unremarkable results. BCG and HepB0 were given at birth. Vitamin
K and eye prophylaxis were also administered. Mother denied any complications during delivery.

Postnatal History
Patient was exclusively breastfed until 6 months of age. Mixed feeding started thereafter until 2
years old. Semi-solids were introduced at 8 months old. Vaccinations included one dose BCG,
completed doses of Pentavalent vaccine, one dose of Measles vaccine and one dose of MMR. Mother
was not certain if patient was given vaccination for Varicella.

Past Medical History

Denied previous hospitalizations and surgeries. Recent exposure of the patient to playmates,
classmates or friends with skin rashes were not known.

Family History
There was no family history of Hypertension, Diabetes, Asthma and Allergies. Mother denied
family history of seizures and other heredo-familial diseases. No significant deaths in the family were
reported.

Personal-Social History
Patient is currently a kindergarten student. He performs averagely in school but actively
participates in class activities. He also gets along well with classmates.

History of Present Illness

4 days prior to admission, there was onset of nonproductive cough with colds but minimal
watery nasal discharge. No associated fever, vomiting or loose stools. Mother claimed patient had
good appetite and remained active. No medications were given. No consultation done.

3 days prior to admission, cough persisted now productive with whitish sputum. No associated
fever, vomiting or loose stools. No difficulty of breathing observed. Mother denied any night time
awakenings from cough. Patient remained active and playful with no change in appetite.

2 days prior to admission, cough persisted now associated with new-onset fever, Tmax of 38.2 C.
Shortly after fever onset, gradual appearance of generalized maculopapular rash were seen
prominently on the trunk. In the interim, new-onset appearance of pruritic, vesicular rashes appeared
on the trunk spreading to the face, upper and lower limbs. No masses were noted in the head and
neck region. Consult was done with attending physician and patient was diagnosed with Chicken pox.
Patient was advised to rest at home with supportive therapy. No medications were prescribed for the
said condition.
 1 day prior to admission, pruritic vesicular rashes and fever persisted. Mother however, noticed
a decrease in appetite. Hours later, patient was noticed to have localized jerking movements and was
unresponsive prompting ER consult and subsequent admission.

Physical Exam

Patient was examined awake, lethargic but not in respiratory distress. He had no signs of
dehydration. Jerking movements were observed on both upper extremities

Vital signs

BP 90/60 mmHg Weight 18.2 kg Weight-for-height normal (-2 to -1)

HR 130 bpm Height 120 cm BMI 12.64 kg/m2

RR 30 cpm Weight-for-age normal (-1 to 0) BMI for age normal (-2 to -1)

Temp 38 C Height-for-age normal (+2 to +1)

SKIN: warm, good turgor and mobility, (-) pallor, (+) generalized vesicular rash with erythrocytic base
with crust formation all over body

HEENT: anicteric sclerae, pink palpebral conjunctivae, (-) eye discharges, (-) alar flaring, (-) nasoaural
discharges, (-) lymphadenopathies

CHEST AND LUNGS: symmetric, equal chest expansion, (-) chest retractions, normal vocal and tactile
fremitus, clear breath sounds

CARDIOVASCULAR: adynamic precordium, distinct S1 and S2, PMI at 5th intercostal space,
midclavicular line, (-) murmur

ABDOMEN: soft, flat, non-tender, no rigidity, (+) normal active bowel sounds, non-palpable liver and
spleen; (+) diffuse vesicular rash and crusted lesions

GUT: grossly male, (-) kidney punch sign, (-) genital discharges

EXTREMITIES: strong peripheral pulses, capillary refill time <2 sec, muscle strength 3/5 all extremities

NEUROLOGIC: GCS9 (E4V1M4); pupils isocoric, reactive to light

Admitting Impression

Pediatric Community Acquired Pneumonia A/B

Varicella Infection

Simple Febrile Seizures probably secondary to infection

B.) Differential Diagnosis

Problem 1: Cough

PCAP A/B Upper Respiratory

Tract Infection

5 years old/male

Cough

Problem 2: Skin Rashes

Pneumonia, Nonbullous Varicella Infection

Severe Impetigo

5 year old/male common in <5 years old common in any age group

any age group 2-5 years old

Cough x 7 days,
persistent;
(-)/(+) (+) prodromal symptoms
initially dry
present before rash onset
evolves to (+)
productive
 Fever (+) (+) (+) 1-2 days before rash
onset

Generalized (-) rashes described to

maculopapular maculopapular
(+)
rash evolves to evolves to vesicular
vesicular rash; (-) with clear-yellow fluid
centripetal and ruptures as
spread honey-colored crusts

No masses of (-) (+)/(-)

head and neck lymphadenopathies
(+)/(-) lymphadenopathies
region

No loose stools, (-) (+)/(-) (+)/(-)

vomiting

(+) localized
jerking
(-) (-) (-)
movements

Course on Admission:

Chest Xray PAL - Mild inflammatory process on both Paracardiac and Retrocardiac areas

HGT taken - 24 mg/dL

Start IVF D10 38 mL, given for 2 cycles via slow IV push to be prepared as follows:

D50W 4.2 mL

D5W 33.8 mL

Repeat HGT result: 126 mg/dL

Medications:

1.)Cefuroxime 750 mg/vial diluted with 10 mL PNSS, 500 mg to given q8hours

2.)Acyclovir 10 mg/kg, 400 mg/tab; 1 tab q 6hours since Varicella is part of our clinical
impression
3.)Cetirizine 5 mg/5ml, 1.5 ml OD for itchiness
4.) Paracetamol 250 mg/5 ml, 5 ml q4hours for Temperature >38 C
C.) Course in the Wards

S O A P

Febrile episode x 1 Tmax of 38.6 Asleep, calm, not in respiratory Dosage of Cefuroxime adjusted to 750 mg IVTT
distress q8hours
(at 6 pm) PCAP A/B

1st Hospital (+) Dry cough Varicella Infection

Day Vital signs: HR 120, RR 21 Continue
(-) Jerking movements on both Simple Febrile
upper extremities Temp 36.4 and O2sat 98 seizures secondary to 1.) Acyclovir
infection
2.) Cetirizine

Fair appetite 3.) Paracetamol

Awake, calm, not in respiratory

distress
Febrile episode x 1 Tmax of 38 Continue medications

2nd Hospital (at 6 am) 1.) Cefuroxime 750 mg IVTT q8hour

Day Skin: Vesicular rashes starting to
Clinically improving 2.) Acyclovir
dry up
Cough, occasional 3.)Cetirizine

4.) Paracetamol
C/L: Clear breath sounds
Improving appetite
 May go home

Take home medications:

Awake, active, playful

No febrile episodes for past 24 Cefuroxime 250 mg/5 mL; 5 mL BID PO after meals
hours for 6 more days
Skin: Crusting of vesicular lesions Clinically Improving

Less frequent bouts of cough Acyclovir 400 mg/tab; 1 tab q6h for 3 more days
3rd Hospital HEENT: No nasoaural discharge PCAP A/B, resolving
Day

Increasing appetite Paracetamol 250 mg/5 mL; 5 mL q4h if Temp >38 C

C/L: Clear breath sounds Varicella Infection

Cetirizine 5mg/5mL, 4.5 ml OD PO at bedtime or as

needed for itchiness
D.) Approach to Viral Exanthems

Skin lesions are common manifestations of various systemic illnesses hence it’s important to
discuss the primary skin lesions in order to have a precise clinical picture. Exanthem is a general term
used to describe any rash or eruption that occurs in the skin while Enanthem is any rash or eruption
that occurs in mucosal membranes.

Skin lesions with accompanying fever often point out to infectious causes and is especially
appreciated in childhood viral exanthems. This said, both comprehensive history taking and complete
physical examination are highlighted to differentiate from those of non-infectious origin. However it’s
important to note that etiologies for infectious rashes may be viral or bacterial.

Table 1. Primary Skin Lesions

Primary Skin Lesion Description

Flat, Non-elevated Lesions

Macule flat, non-elevated lesion up to 1 cm

Patch flat, non-elevated lesion >1 cm

Palpable elevations (Solid)

Patch raised lesion up to 1 cm

Papule raised lesion > 1 cm

knot-like lesion, similar to papule but located

deeper in the dermis or subcutaneous tissue
Nodule

nodule filled with expressible material either

liquid or semisolid
Cyst

Irregular, transient superficial area of localized

skin edema
Wheal

Palpable elevations (Fluid-filled)

Vesicle raised lesion up to 1 cm, filled with serous fluid

Bulla raised lesion >1cm, filled with serous fluid

raised lesion filled with pus (purulent fluid,

yellow proteinaceous material)
Pustule

Source: Bickley, L. (2013). Bate’s Guide to Physical Exam and History Taking. Wolters Kluwer;
Lippincott, Williams and Wilkins.

To clinically diagnose diseases with both fever and skin rashes, good history taking must include
information on exposure to persons with medical illnesses, recent travel, contact with animals,
medications taken, allergic history, comorbidities present in the patient and environmental factors.
Description of skin rashes should not only focus on morphology but should also elaborate on onset,
pattern of spread, localization and arrangement, symmetry, accompanying symptoms such as fever
and pruritus, evolution of lesions and seasonal occurrence.

Febrile rashes are classified into maculopapular rash either centrally or peripherally distributed,
confluent desquamative rash, vesiculobullous, urticarial, nodular and purpuric rashes.

Table 2. Classification of Childhood Exanthems based on History

Childhood Exanthem Name Etiologic Agent

First Disease Measles Rubeola virus

Second Disease Scarlet Fever Streptococcus pyogenes

Third Disease German Measles Rubella Virus

Fourth Disease Staphylococcal Scalded Skin

Syndrome (Filatov-Duke’s
Staphylococcus aureus
disease/Ritter’s disease)

Fifth Disease Erythema Infectiosum Parvovirus B19

Sixth Disease Roseola Infantum HHV-6 and HHV-7

Source: Nelson’s Textbook of Pediatrics, 20 th ed. (2015)

The Handbook of Pediatric Infectious Diseases (Philippine Pediatric Society, 2014) lists viral
exanthems of clinical significance. The following viral exanthems include: (1) Rubeola, (2) Rubella, (3)
Varicella, (4) Roseola and (5) Hand-foot-and-mouth disease. Though not listed, Erythema Infectiosum
is also a notable viral exanthem.

E.) Varicella Infection

Varicella-zoster virus (VZV) is a double-stranded DNA virus In children, varicella infection

presents as a mild disease, however, higher morbidity is associated in young infants, adults and
immunocompromised individuals. It causes 2 clinical entities namely primary infection or chicken pox
and a a reactivation of of latent infection called herpes zoster or shingles. Mode of transmission
occurs via direct contact with droplets or through fomites. Persons infected with varicella are most
contagious 24-48 hours before the onset of rash and until 3-7 days after onset of rash when vesicles
have crusted.

Primary infection occurs as the virus enters the mucosa of the upper respiratory tract as well as
the tonsillar lymphoid tissue. Thereafter incubation period begins as the virus replicates in the
lymphoid tissue, spreads and cause primary viremia to affect other reticulo-endothelial organs.
Second viremia occurs causing the widespread distribution of skin lesions before it returns back to the
oropharynx to infect susceptible individuals a few days before and after rash onset. Both cellular and
humoral immune responses play a role to limit the infection.
 Illness appears 14-16 days from exposure. Prodromal symptoms such as fever, malaise,
abdominal pain 24-48 hour before appearance of rash and usually resolves within 2-4 days after rash
onset. Lesions usually appear first in the scalp, face and trunk. Pruritic maculopapular rash evolves
into clear fluid-filled vesicles. Clouding and umbilication and eventually crusting of lesions begin 24-48
hours. However, new vesicles form as crusting of other lesions occur. Thus the hallmark of varicella
infection is the simultaneous presence of lesions in different stages.

VZV is transported via sensory axons to the dorsal root ganglia where the virus establishes a
latent infection. In the advent of suppressed immunity, there is increased reactivation of the infection
causing Herpes Zoster or Shingles. Vesicular lesions are clustered in within 1-2 adjacent dermatomes.
Elderly patients begins with burning pain followed by clusters of lesions in dermatomal patterns. Most
common complication in infected adults is postherpetic neuralgia. This however is rare in children.
Neonatal varicella is described in newborns born to pregnant mothers who acquired the infection 5
days prior the delivery or 2 days after. This is the result of transplacental spread of the virus which
occurs up to 48 hours before the onset of maternal rashes. Breakthrough varicella occurs those in
individuals who were vaccinated more than 42 days before rash onset. This type of infection is caused
by a wild-type virus. Atypical rashes are seen which are predominantly maculopapular while vesicles
are not commonly see. The illness is also milder, with shorter duration of illness, absence of fever and
fewer complications.

Complications of Varicella infection include pneumonia, secondary bacterial infections,

encephalitis and cerebellar ataxia. Secondary bacterial infections of the skin are usually caused by
group A Streptococcus and Staphylococcus aureus. Recrudescence of fever after skin lesions may
indicate a secondary bacterial infection (Nelson’s Textbook of Pediatrics, 2015).

Diagnosis of Varicella is primarily clinical. Laboratory test are not necessary but a complete blood
count picture of varicella infection would show leukopenia on the first 3 days and then lymphocytosis.
Varicella infection is self-limited and drug treatment is not routinely recommended. Supportive
management is usually advised. However, Acyclovir has proven safety and efficacy for the treatment
of this disease. Recommended dose of Oral Acyclovir is 20mg/kg/dose in 4 divided doses for 5 days
preferably initiated within 24 hours of rash onset. Intravenous Acyclovir is indicated in severe disease
and for immunocompromised patients at a dose of 500 mg/m2 every 8hr for 7-10 days until no new
lesions appear. For Acyclovir resistant patients, intravenous Foscarnet can be given at 120mg/kg/day
every 8 hours for 3 weeks. Treatment for Herpes Zoster include Acylovir (800 mg PO, 5 times a day for
5-7 days), Famciclovir (500 mg PO, three times a day for 7 days) and Valacyclovir (1,000 mg three
times a day PO for 7 days) to reduce duration of illness and complications.

Prognosis is good but infants and adults are more likely to have severe disease when infected.
Most complications of those who died from Varicella infection include pneumonia, central nervous
system complications, secondary infections and hemorrhagic conditions.

Prevention includes administration of Varicella vaccine, which contains a live, attenuated strain
of the virus. The vaccine is given subcutaneously. The Pediatric Infectious Disease Society of the
Philippines (PIDSP), recommends to administer a 2 dose regimen given at 12-15 months and at 4-6
years old. Minimum interval for children ages 12 and younger is 3 months while for older children, 4
weeks. It should be emphasized that the vaccine is contraindicated in pregnant women, those with
history of anaphylactic reaction to the vaccine, those with cell-mediated immune deficiencies,
persons receiving immunosuppressive therapy and those who have a family history of congenital or
hereditary immunodeficiencies. Post-exposure prophylaxis can be given to healthy children within 3-5
days after exposure. For newborns of infected mothers, they should receive VariZIG (0.5 vial for <2kg
and 1 vial for >2kg). VariZIG can also be given to pregnant mothers without evidence of immunity,
hospitalized premature infants <28 weeks age of gestation or weight <1,000 g.
References:

Kliegman, R., et al. (2016). Nelson Textbook of Pediatrics, 20th ed. United States: Elsevier
Publishing, Inc.

Kasper, D., et al. (2015). Harrison’s Principles of Internal Medicine, 19th ed. United States:
McGraw-Hill Publishing

Wolf, K., et al. (2013). Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology, 7 th ed.
United States: McGraw-Hill Publishing

Philippine Pediatric Society, Inc. (2014). Handbook of Pediatric Infectious Diseases. Diliman,
Quezon City
Table 3. Common Childhood Viral Exanthems

Erythema Hand-foot-and-mouth
Infectiosum Disease
Name Rubeola Rubella Varicella Roseola

German Measles/ Primary infection: Exanthema

3-Day Measles/ Chickenpox subitum/Sixth
Other name Measles/First disease Fifth disease None
disease
Third disease Reactivation: Zoster
(Shingles)

Etiology

Rubeola virus Rubella virus Varicella-Zoster Virus HHV-6 and HHV-7 Parvovirus B19 Coxsackievirus A16;

Enterovirus 71

Droplets from
nasopharyngeal
Mode of Droplets Direct or contact droplet of Respiratory Respiratory Contact with
secretions;
Transmission respiratory secretions and droplets; Congenital droplets; nasopharyngeal and
Fomites; Vertical
fluid of skin lesions; Vertical respiratory secretions;
transmission
transmission Fomites
Fomites
 Exanthem:

Exanthem: Exanthem: Exanthem: Initial stage: Exanthem:

Maculopapular rash Slapped-cheek
Maculopapular rash Exanthem: Rose-colored, Tender
(cephalocaudal and appearance
(cephalocaudal and non-pruritic maculopapular rash
centrifugal spread) Vesiculopustular rash, (facial flushing)
centrifugal spread) morbiliform rash, and vesicles on hand,
faces without pruritic
evanescent Second stage: fingers, mouth, feet
branny,fades with desquamation
but characteristic evolution
Characteristic desquamation (centripetal spread) Lacy,
of stages is seen
Lesion reticulated rash
Enanthem:
Enanthem: Macular-Papular-Pustula
on extensor
Enanthem: Enanthem: Scattered vesicles on
Forchheimer spots (centripetal spread); surfaces, spares
tongue, buccal
Koplik spots (blue-white (rose-colored Nagayama spots palms and soles
crusting of lesions mucosa, posterior
pinpoint lesions on buccal lesions on (ulcers at
Third stage: palate, gingiva, lips
mucosa opposite lower oropharynx) uvulopalatoglossal
molars) junction) Wax and wane
of rashes

Source: Nelson’s Textbook of Pediatrics, 20th ed. (2015)

Table 3. Common Childhood Viral Exanthems (continued)

Erythema Hand-foot-and-mouth
Infectiosum Disease
Name Rubeola Rubella Varicella Roseola

8-12 days
Incubation Most infectious:
Period
3 days before and 4-6 days
after rash onset
4 Phases:
1.) Incubation Period- virus
migrates to lymph nodes;
Clinical
primary and secondary
Manifestation
viremia
2.) Prodromal Phase - virus
shedding; high fever and 3Cs
(brassy cough, coryza,
conjunctivitis);
3.) Exanthematous Phase
4.) Recovery Phase
Pathology:
Warthin-Finkeldey giant cells
14-16 days
16-18 days Most infectious: HHV-6: 9-10 days
Most infectious: 1-2 days before rash HHV-7: unknown 4-28 days 3-6 days
and 3-7 days after rash
5 days before and 6
(crusted lesions)
days after rash onset
2 Clinical Entities: Low grade fever,
headache and
1.) Postnatal Rubella Prodromal symptoms Abrupt onset of May be associated
respiratory symptoms
such as low-high grade high grade fever with high fever, severe
-mild; low grade fever
fever and malaise for 3 days (crisis) malaise, diarrhea and
with lymph node
appear 1-2 days before and fades over 1 joint pains
enlargement: Hallmark:
rash onset and resolves day (lysis)
suboccipital,
2-4 days after rash 3-stage rash
postauricular and
onset Maculopapular rash,
anterior cervical 1.) Facial flushing
Followed by rapidly evolve into
(slapped cheek
2.) Congenital appearance of vesicles
appearance)
Rubella Appearance of rash rose-colored,
initially maculopapular non-pruritic, 2.) Diffuse macular
-due to maternal
evolves to vesicular non-blanching erythema on trunk Vesicles are tender,
infection most
until crusting of lesions morbiliform rash and limbs linear usually don’t
severe: 1st 8 weeks
rupture
AOG 3.) Lacy reticulated
rash
 Most common complication: Secondary bacterial
Acute Otitis Media infections of skin
Most serious Common Cardiac and Central
Most common cause of complication: Severe complicaton: complications of nervous system
Most common
death: Pneumonia Encephalitis Varicella Pneumonia Parvovirus B19 involvement
complication:
Complication infection:
Final fatal outcome: (post-infectious or Most common Convulsions
Bronchiolitis obliterans progressing form) complication in Zoster:

Postherpetic neuralgia

Source: Nelson’s Textbook of Pediatrics, 20th ed. (2015)