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Title: ClinicoPathological Conference


1
ClinicoPathological Conference
  • 93-03-24
  • ??? / ?????
  • ? ? ? ? ? ? ? ?

2
Chief complaints
  • A 4-day-old girl had suffered from fever since
    two days ago

3
Present illness (1)
  • 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.

4
Present illness (2)
  • 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.

5
Present illness (3)
  • The baby continued to appear pale, ill and
    febrile. On the babys 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.

6
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

7
Physical examinations(4 days of life)
  • 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

8
Laboratory findings (1)
  • At 3 days of age WBC 13400 /mm3Platelet
    96000 /mm3Neutrophil 48Lymphocytes 17
    Band form 29 (lt15 )
  • 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)

9
Laboratory findings (2)
  • At 6 days of lifeCBC essentially
    unchangedAST 66 U/L (35-140 U/L)ALT 54
    U/L (6-50 U/L)r- GT 555 U/L (13-147 U/L)

10
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

11
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

12
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 ?

13
Question ??
  • 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 ?

14
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Possible Consequences of Infection of a Mother
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Possible organisms
  • Bacteria Trepnema pallidum, Mycobacterium
    tuberculosis
  • Virus Rubella, CMV, HSV, HIV, Enterovirus
  • Protozoa Toxoplasma gondii, Plasmodium

21
Clinical Features of Prenatal TORCH Infection
22
Relative Clinical Features of TORCH Infection
23
Congenital Rubella Syndrome
  • 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)4.blueberry
    muffin skin lesions5.hearing loss from
    sensorineural deafness6.meningoencephalitis7.pne
    umonia, hepatitis, bone lucencies,
    thrombocytopenia purpura, and anemia.8.motor
    and mental retardation
  • Diagnosis 1.anti-rubella IgM Ab in neonatal
    serum2.culturing rubella virus from the infant
    (nasopharynx, urine, or tissue)

24
Cytomegalic Inclusion Disease
  • 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.

25
Human Immunodeficiency Virus (1)
  • Currently, gt95 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 infant2. With
    appropriate therapy, risk is lt 53. Risk factors
    for vertical transmission include maternal
    viral load and degree of immunodeficiency and
    PROM.

26
Human Immunodeficiency Virus (2)
  • Clinical manifestations 1. generally
    asymptomatic for first few months of life
    mean age of onset of symptoms is 1 year2. 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

27
Possible organisms
  • Bacteria Trepnema pallidum, Mycobacterium
    tuberculosis
  • Virus Rubella, CMV, HSV, HIV, Enterovirus
  • Protozoa Toxoplasma gondii, Plasmodium

28
Enterovirus---NEONATAL INFECTIONS (1)
  • Enterovirus infection frequently is with
    coxsackieviruses B2B5 and echoviruses 6, 9, 11,
    and 19.
  • Transmission via 1. vertically before, during,
    or after delivery2. 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.

29
Enterovirus---NEONATAL INFECTIONS (2)
  • 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.

30
Enterovirus---NEONATAL INFECTIONS (3)
  • 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.

31
Congenital syphilis (1)
  • 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, nephritis2.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

32
Congenital syphilis (2)
  • Diagnosis 1. nontreponemal tests ---VDRL,
    RPR ---detect Ab against a cardiolipin-cholester
    ol-lecithin complex ---helpful in
    screening ---titers elevate when active and
    decline when treatment is adequate2.
    treponemal tests ---TPI, FTA-ABS, and MHA-TP
    ---measure Ab specific to T. pallidum
    ---confirmatory testing of positive results from
    nontreponemal tests.

33
Malaria
  • Plasmodium protozoa (Plasmodium ovale, Plasmodium
    vivax, Plasmodium malariae, Plasmodium
    falciparum).
  • 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 blood2.
    monoclonal antibody test3. PCR

34
Congenital malaria
  • 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.

35
Mycobacteria infection (1)
  • 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)
  • 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.congenita
    l tuberculosis may also be caused by aspiration
    or ingestion of infected amniotic fluid.

36
Mycobacteria infection (2)
  • Lymphohematogenous (disseminated) disease
  • 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)---cutaneo
    us lesions papulonecrotic tuberculids, nodules,
    or purpura.

37
Mycobacteria infection (3)
  • Tuberculous
    Meningitis
  • 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

38
---Congenital tuberculosis---
  • 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)

39
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40
Impression
  • 1.Mycobacteria tuberculosis
  • 2.Enterovirus infection

41
Diagnostic procedure
  • AFB and culture of CSF from mother gastric
    aspirate from neonate
  • PCR for enterovirus

42
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