Transcript ClinicoPathological Conference 93-03-24 林世朋 / 蔡明志大夫

ClinicoPathological
Conference
93-03-24
林世朋 / 蔡明志大夫
三 軍 總 醫 院 小 兒 部
Chief complaints
 A 4-day-old
girl had suffered from fever
since two days ago
Present illness (1)
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The 4-day-old female newborn was a fullterm and was
delivered vaginally through thick meconium, with Apgar score
of 9 at 1 minute and 9 at 5 minute.
She developed a fever of 38.6 ‘C at 2 days of age, but was
relatively well without cardiopulmonary compromise.
She was sent to hospital for help where septic workup was
done including lumbar puncture. Viral cultures were submitted
because of several papulovesicular lesions noted on her back.
Ampicillin & gentamicine therapy was started at 2 days of age
and acyclovir was added at 4 days of age.
All cultures including viral culture were negative.
Present illness (2)
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Then she was transferred to another hospital for further
evaluation.
In addition, the mother had mild fever at the time of delivery,
and was treated with antibiotics briefly before discharge.
By telephone interview, the mother said that she was still
febrile 1 week after delivery with the main symptoms of
malaise, abdominal pain and headache.
She denied respiratory symptoms, vomiting, diarrhea and skin
rash. The father believed that she was jaundiced.
Present illness (3)
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The baby continued to appear pale, ill and febrile. On
the baby’s 10th day of life, the mother visited the
nursery.
 With ill appearance, she told us that she had headache
and neck pain.
 The father stated that she was having personality
changes that began the week before delivery.
 The mother was then admitted to our hospital and
evaluations revealed the diagnosis.
Past, personal and family histories
 Fullterm
with gestational age of 38 weeks
via vaginal delivery.
 Apgar scores : 9 & 9 at 1st & 5th minutes,
respectively ; BBW : 3100 g
 Mother history : a 24-year-old gravida 3,
para 1 to 2 mother.
 Contact history : unknown
 Traveling history : unknown
 Family history : unknown
Physical examinations
(4 days of life)
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Vital signs :
HR : 130 /min ; RR: 40 /min ; BT: 38.6 ‘C
General appearance : pale and ill-looking, fussy
but consolable
Skin : several scabbing lesions on her scalp.
Chest : clear and symmetric breathing sound;
tachypnea: (-) ; retraction :(-)
Abdomen : palpable liver edge, 4 cm below the
right costal margin in the midclavicular line;
palpable spleen tip, 3 cm below the left costal
margin.
Genitalia : bilateral inguinal lymph nodes 0.5 cm
in diameter
Laboratory findings (1)
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At 3 days of age :
WBC : 13400 /mm3
Platelet : 96000 /mm3
Neutrophil : 48%
Lymphocytes : 17 %
Band form : 29% (<15 %)
 ALT : 20 U/L (6-50 U/L)
 CSF study :
WBC: 4 /mm3 (all mononuclear cells)
Protein : 91 mg/dl (84 ± 45 mg/dL)
Glucose : 49 mg/dl (46 ±10 mg/dL)
Laboratory findings (2)
 At
6 days of life
CBC : essentially unchanged
AST : 66 U/L (35-140 U/L)
ALT : 54 U/L (6-50 U/L)
r- GT : 555 U/L (13-147 U/L)
Problems of neonate
Major problems :
 Fever
 Skin lesions (papulovesicular)
over the back;
scabbing lesions on the
scalp
 Hepatosplenomegaly
 Lymphadenopathy over
inguinal regions
Minor problems :
 Predominant band form
of WBC
 Thrombocytopenia
 Heavy meconium stain
Problems of mother
Major problems :
 Personality changes
 Fever when delivery s/p
antibiotic therapy
 Still fever, malaise,
abdominal pain and
headache
 Headache and neck pain.
Minor problems :
 Jaundice
Questions ??
 Neonate
:
1. any other abnormal physical findings ?
2. head circumference ?
3. ophthalmoscopic examination ?
4. other laboratory findings (Hg, bilirubin etc..)
5. CxR ?
6. CNS image studies ?
Question ??
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Mother :
1. PROM ? Amnionitis ?
2. Liver function ? Bilirubin levels ?
3. fever source ? Genital cultures ?
4. culture results ?
5. physical findings ? Neurologic findings ?
6. Lumbar puncture ? CSF studies results?
7. past & personal histories ? VDRL ?
8. travel & contact histories ?
9. Image study (CxR, brain CT)?
10. What kind of antibiotics were used when
delivery ? Drug history ?
Hepatosplenomegaly Lymphadenopathy Skin lesions Thrombocytopenia
Rubella
T. pallidum
Enterovirus
HIV
CMV
HSV
Plasmodium
T. cruzi
Rubella
T. pallidum
HIV
CMV
Rubella
T. pallidum
Enterovirus
Measles
VZV
HSV
Toxoplasmosis
Rubella
T. pallidum
Enterovirus
HIV
CMV
HSV
Toxoplasmosis
Possible organisms:
Rubella
CMV
T. pallidum
HSV
Enterovirus
HIV
Possible Consequences of
Infection of a Mother
Infection of pregnant mother
Fetus not infected
Death as embryo/fetus
Fetus infected
Placenta infected
Congenitally infected live birth
Congenital disease/syndrome
Resolution of symptoms/sequelae
of congenital disease
Persistent infection with
Progressive/late-onset sequelae
Fetus not infected
Normal-appearing infant
Possible organisms
 Bacteria
:
Trepnema pallidum, Mycobacterium
tuberculosis
 Virus :
Rubella, CMV, HSV, HIV, Enterovirus
 Protozoa :
Toxoplasma gondii, Plasmodium
Clinical Features of Prenatal
TORCH Infection
Relative Clinical Features of
TORCH Infection
Congenital Rubella Syndrome
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Affect virtually all organ systems
Manifestations :
1.IUGR (most common)
2.cataracts, frequently associated with microphthalmia
3.myocarditis and structural cardiac defects
(PDA or pulmonary artery stenosis)
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4.”blueberry muffin” skin lesions
5.hearing loss from sensorineural deafness
6.meningoencephalitis
7.pneumonia, hepatitis, bone lucencies, thrombocytopenia
purpura, and anemia.
8.motor and mental retardation
Diagnosis :
1.anti-rubella IgM Ab in neonatal serum
2.culturing rubella virus from the infant (nasopharynx, urine,
or tissue)
Cytomegalic Inclusion Disease
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Congenital CMV infection
Only 5% of all congenitally infected infants have severe cytomegalic
inclusion disease, another 5% have mild involvement, and 90% are
born with subclinical, but still chronic, CMV infection.
Characteristic manifestations :
IUGR, prematurity, hepatosplenomegaly and jaundice,
thrombocytopenia and purpura, and microcephaly and intracranial
calcifications.
Other neurologic problems :
chorioretinitis, sensorineural hearing loss, and mild increases in
CSF protein
Most symptomatic congenital infections and those resulting in
sequelae are caused by primary rather than reactivated infections in
pregnant women
Re-infection with a different strain of CMV can lead to symptomatic
congenital infection.
Asymptomatic congenital CMV infection is likely a leading cause of
sensorineural hearing loss, which occurs in approximately 7% of
infected infants.
Human Immunodeficiency Virus (1)
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Currently, >95% of children with HIV infection acquire the
infection from their mother (vertical transmission); transfusion
of contaminated blood or clotting factor concentrates is
now rarely observed in the USA
Breastfeeding remains a possible risk for transmission.
Infants born to HIV-infected mothers :
1. Risk of infection is 13-39% if no antiretroviral therapy
delivered to mother and infant
2. With appropriate therapy, risk is < 5%
3. Risk factors for vertical transmission include maternal
viral load and degree of immunodeficiency and PROM.
Human Immunodeficiency Virus (2)
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Clinical manifestations :
1. generally asymptomatic for first few months of life;
mean age of onset of symptoms is 1 year
2. Common manifestations include failure to thrive,
hepatosplenomegaly, oral candidiasis, recurrent
diarrhea, recurrent bacterial infections, and PCP
between 3-6 months of age.
3. Anemia, neutropenia, and thrombocytopenia are
common
Possible organisms
 Bacteria
:
Trepnema pallidum, Mycobacterium
tuberculosis
 Virus :
Rubella, CMV, HSV, HIV, Enterovirus
 Protozoa :
Toxoplasma gondii, Plasmodium
Enterovirus---NEONATAL INFECTIONS (1)
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Enterovirus infection frequently is with coxsackieviruses B2–B5 and
echoviruses 6, 9, 11, and 19.
Transmission via :
1. vertically before, during, or after delivery
2. horizontally from other infected family members or by
transmission in hospital nurseries (sporadic or epidemic).
Infection in utero may be associated with placentitis, fetal demise,
neonatal illness, and, possibly, congenital anomalies.
Neonatal infection is associated with a range of clinical
manifestations :
--- asymptomatic (the majority)
--- benign febrile illness
--- severe multi-system diseases
Most affected newborns are full-term and previously well;
Maternal history often reveals a recent viral illness, including fever
and, frequently, abdominal pain.
Enterovirus---NEONATAL INFECTIONS (2)
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Symptoms in the neonate may occur throughout the newborn period, with
some beginning as early as day 1 of life; severe disease generally has an
onset within the first 2 wk of life.
Clinical manifestations :
--- fever or hypothermia, irritability, lethargy, anorexia,
--- rash (maculopapular, occasionally petechial or papulovesicular),
jaundice,
--- respiratory symptoms, apnea, hepatomegaly, abdominal
distention, emesis, diarrhea, and decreased perfusion.
Most symptomatic neonates have benign courses, with resolution of fever
in an average of 3 days and of other symptoms in about 1 wk. Occasionally,
a biphasic course may occur.
Laboratory findings:
--- leukocytosis, thrombocytopenia, pleocytosis,
--- elevated transaminases and bilirubin, coagulopathy,
--- pulmonary infiltrates,
--- EKG changes.
Enterovirus---NEONATAL INFECTIONS (3)
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Complications include :
--- CNS necrosis and generalized or focal neurologic compromise
--- arrhythmias, congestive heart failure, myocardial infarction, and
pericarditis;
--- hepatic necrosis and failure; intracranial or other bleeding;
--- adrenal necrosis and hemorrhage; and rapidly progressive
pneumonitis.
--- Myositis, NEC, SIADH, hemophagocytic syndrome, and sudden
death are rare events.
Mortality in those with severe disease is significant and is most often
associated with hepatitis and associated bleeding complications,
myocarditis, or pneumonitis.
Risk factors for severe disease include :
--- illness onset in the first few days of life,
--- maternal illness just prior to or at delivery, prematurity, male sex,
--- infection by echovirus 11 or a coxsackie B virus,
--- positive serum viral culture,
--- absence of neutralizing antibody to the infecting virus,
--- evidence of severe hepatitis and/or multi-system disease.
Congenital syphilis (1)
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Transplacental transmission of Treponema pallidum (spirochetes)
Transmission can occur at any stage of pregnancy; transmission rate
approaching 100%.
Fetal and perinatal death occurs in 40% of affected infants.
Clinical manifestations :
1.early signs : (during the first 2 yr of life)
---hepatosplenomegaly, jaundice, elevated liver enzymes; bile stasis
---diffuse lymphadenopathy
---Coombs negative hemolytic anemia; thrombocytopenia
---osteochondritis (wrist, elbow,ankle & knee) and periostitis (long bone)
---mucocutaneous rash : maculopapular or bullous lesions, followed by
desquamation involving hands and feet
---CNS abnormalities, failure to thrive, chorioretinitis, nephritis
2.late signs: (appear gradually during the first 2 decades)
---result primarily from chronic inflammation of bone, teeth and CNS.
---olympian brow, Higoumenakis sign, saber shins, Hutchinson teeth,
mulberry molars, saddle nose
---Juvenile paresis, Juvenile tabes, Clutton joint
Congenital syphilis (2)
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Diagnosis :
1. nontreponemal tests :
---VDRL, RPR
---detect Ab against a cardiolipin-cholesterol-lecithin
complex
---helpful in screening
---titers elevate when active and decline when treatment
is adequate
2. treponemal tests :
---TPI, FTA-ABS, and MHA-TP
---measure Ab specific to T. pallidum
---confirmatory testing of positive results from
nontreponemal tests.
Malaria
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Plasmodium protozoa (Plasmodium ovale, Plasmodium vivax, Plasmodium
malariae, Plasmodium falciparum).
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Transmitted through :
1. an infected female Anopheles species mosquito.
2. blood transfusion
3. congenitally between mother and fetus (rare)
Clinical manifestations :
1. asymptomatic during the initial phase (incubation period)
2. paroxysms of fever, rigors, sweats, headache, myalgia, back pain,
abdominal pain, nausea, vomiting, diarrhea, pallor and jaundice.
Diagnosis :
1. identification of organisms on Giemsa-stained smears of
peripheral blood
2. monoclonal antibody test
3. PCR
Congenital malaria
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Malaria acquired from the mother prenatally or
perinatally.
In endemic areas, congenital malaria is an important
cause of abortions, miscarriages, stillbirth, premature
births, IUGR and neonatal deaths.
Congenital malaria usually occurs in a nonimmune
mother with P. vivax or P. malariae, although it can be
observed with any of the human malaria species.
Symptoms and signs most commonly occurs between
10-30 days of age (14hr to several months of age)
Clinical manifestations :
fever, restlessness, drowsiness, pallor, jaundice, poor
feeding, vomiting, diarrhea, cyanosis and
hepatosplenomegaly.
Mycobacteria infection (1)
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Mycobacterium tuberculosis complex : M. tuberculosis, M bovis, M
africanum, M. microti, and M. canetti
Transmission :
1. person to person by airborne mucus droplet (most adults no longer
transmit the organism within several days to 2 wk after chemotherapy)
2. M. bovis may penetrate GI mucosa or invade lymphatic tissue of
oropharynx (human infection is rare as a result of pasteurization of milk &
effective TB control program for cattle)
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Pregnancy and the newborn :
1.congenital tuberculosis is rare because the most common result of
female genital tract tuberculosis is infertility.
2.primary infection just before or during pregnancy is more likely to
cause congenital infection than is reactivation of a previous infection.
3.tubercle bacilli first reach fetal liver, then pass into fetal circulation
and infect many organs.
4.congenital tuberculosis may also be caused by aspiration or
ingestion of infected amniotic fluid.
Mycobacteria infection (2)
Lymphohematogenous (disseminated) disease :
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Tubercle bacilli are disseminated to distant sites, including liver, spleen,skin
and lung apices, in all cases of tuberculosis infection.
Lymphohematogenous spread is usually asymptomatic.
Clinical manifestations :
---hepatomegaly, splenomegaly
---lymphadenitis in superficial or deep nodes
---papulonecrotic tuberculids appearing on the skin
---bone and joints or kidneys also may become involved
---meningitis occurs only late in the course of the disease
Miliary disease (the most clinically significant form of disseminated TB)
---occurs when massive numbers of tubercle bacilli are released into
bloodstream, causing disease in two or more organs.
---occur within 2-6 mo of the initial infection
---lesions are often larger and more numerous in the lungs, spleen,
liver and bone marrow than other tissues.
---chronic or recurrent headache (meningitis)
---abdominal pain or tenderness (tuberculous peritonitis)
---cutaneous lesions papulonecrotic tuberculids, nodules, or purpura.
Mycobacteria infection (3)
Tuberculous Meningitis
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Tuberculosis of the CNS accounts for about 5% of extrapulmonary cases. It
is seen most often in young children but also develops in adults, especially
those who are infected with HIV.
From hematogenous spread or rupture of a subependymal tubercle into the
subarachnoid space .
may present subtly as headache and mental changes or acutely as confusion,
lethargy, altered sensorium, and neck rigidity.
Typically, the disease evolves over 1 or 2 weeks, a course longer than that
of bacterial meningitis; Hydrocephalus is common .
Lumbar puncture is the cornerstone of diagnosis.
In general, CSF reveals a high leukocyte count, a protein content of 100 to
800 mg/dL, and a low glucose concentration.
AFB are seen on direct smear of CSF sediment in only 20% of cases, but
repeated lumbar punctures increase the yield. Culture of CSF is diagnostic
in up to 80% of cases.
CT and MRI may show hydrocephalus and abnormal enhancement of basal
cisterns or ependyma
---Congenital tuberculosis--
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symptoms may be present at birth but more commonly begin by
the 2nd or 3rd wk of life.
clinical manifestations:
respiratory distress, fever, hepatic or splenic enlargement, poor
feeding, lethargy or irritability, lymphadenopathy, abdominal
distention, failure to thrive, ear drainage, and skin lesions.
Many infants have an abnormal chest radiograph, most often a miliary
pattern.
Some with no pulmonary findings early in the course of the disease later
develop profound radiologic and clinical abnormalities.
Clinical presentation of TB in newborn is similar to that caused by bacterial
sepsis and other congenital infection, such as syphilis, toxoplasmosis and
CMV.
Diagnosis :
acid-fast stain of gastric aspirate, middle-ear discharge, bone marrow,
tracheal aspirate, or biopsy tissue (especially liver)
Impression
 1.Mycobacteria
tuberculosis
 2.Enterovirus infection
Diagnostic procedure
 AFB
and culture of CSF from mother &
gastric aspirate from neonate
 PCR for enterovirus
Thank you !!