Dr. Anwar I. El-Sheikh Khalil - By

By:
  Dr. Anwar I. El-Sheikh Khalil
  Consultant Pediatrician and Neonatologist
    C.A.B.P (Arab Board), D-Ped, A.M.S
                Fellowship
    Former Director of Al-Nassr Pediatric
  Deputy Dean Islamic University of Gaza

INFECTIOUS
  DISEASES

Infectious diseases
Cause       Maculopapular rash          Papulovesicular
  Viral     Measles, Rubella,       Small pox
            Roseola infantum        Chicken pox
            Erythema infectiosum    Herpes simplex
            Infect. Mononucleosis   Coxsackie virus
            Echo, Coxsackie virus
Bacterial   Scarlet fever           Impetigo
            Meningococcemia
            Typhoid fever
Fungal      Tinea                   Tinea

Allergic    Insect bite             Insect bite

Parasitic   Scabies                         -

Collagen    SLE, Rheumatoid                 -

Primary Skin Lesions
Macule Change in skin colour but not felt

Papule Palpable skin lesion < 1cm
                          If > 1cm : nodule
Vesicle Raised, fluid filled lesion 0.5 cm : bullus
Pustule Vesicle containing pus

plaques Aggregation of any primary lesions

Macules

papules

Vesicle

bullae

Pustule

Several plaques on the arm

Papules and plaques

Macules and patches

weal

Secondary Skin Lesions
  Scales       Compressed layers of stratum cornium cells
               that are raised on skin surface
  Ulcers       Excavation of necrotic tissue
excoriations   Linear ulcers caused by scratching

  fissures     Splitting or cracking of skin

  crusts       Accumulation of blood,serum,pus and
               epithelial debris on the surface of a weeping
               lesion

scales

ulcer

Scabies

crusts

Primary lesions

 Petechiae: pin point bleeding(platelet
  problem)
 Ecchymosis: large bleeding
 hematoma: large bleeding leading to
  swelling of skin.

Measles

‫انسبج ‪ 14/7/1431‬هـ ‪ -‬انًىافق‬
‫‪26/6/2010‬‬

  ‫‪ ‬أدي حفشٍ انحصبت فٍ يالوٌ إنً وفاة ‪ 82‬شخصا أؼهبهى أطفال‪ ،‬وأصُب أكثز‬
                    ‫يٍ ‪ 17‬أنفا آخزٍَ يُذ حفشٍ انًزض قبم َحى سخت أشهز‪.‬‬
                                                                         ‫‪‬‬
  ‫‪ ‬وقال يذَز خذياث انصحت انىقائُت بىسارة انصحت فٍ يالوٌ سخىرٌ كابىنىسٌ‬
                            ‫إٌ انجهىد حبذل نخطعُى انًعزضٍُ نخطز أكبز‪.‬‬
                                                                         ‫‪‬‬
     ‫‪ ‬وأضاف أَه جزي حسجُم ‪ 82‬وفاة أؼهبهى أطفال و‪ 17496‬حانت حزاكًُت فٍ‬
‫انشهىر انسخت انًاضُت يُذ انبالغ عٍ أول حفش نهحصبت فٍ َُاَز‪/‬كاَىٌ انثاٍَ هذا‬
                                                                      ‫انعاو‪.‬‬
                                                                         ‫‪‬‬
  ‫‪ ‬وأشار انًسؤول انصحٍ إنً أٌ انحكىيت بذأث حًهت حطعُى حزكش عهً انًُاطق‬
            ‫انزَفُت حُث َعُش ‪ %80‬يٍ انسكاٌ انبانػ عذدهى ‪ 13‬يهُىٌ َسًت‬

ETIOLOGY

 RNA virus in the family Paramyxoviridae.
 6 major structural proteins.

EPIDEMIOLOGY
Historically:
 USA:90% of children acquiring the infection before 15 yr
   of age.
 the incidence declined dramatically following the
   introduction of the measles vaccine 1963.
 It is most common in the winter and spring.
 A nationwide : 1989–1991 resulting in >55,000 cases,
   11,000 hospitalizations, and 123 deaths,
 The current rate is

TRANSMISSION
 through the respiratory tract or
  conjunctivae.
 Droplet
 Patients are infectious from 3 days
  before the rash up to 4–6 days after its
  onset.
 90% of the exposed develop measles.
 viable virus may be suspended in air up
  to 1 hr after a source case leaves a
  room.

PATHOLOGY
 necrosis of the respiratory tract epithelium.
 lymphocyte infiltrate.
 small vessel vasculitis on the skin and on the oral mucous
    membranes.
   Histology :
    - intracellular edema and dyskeratosis
    - formation of epidermal syncytial giant cells with up to 26 nuclei.
   Viral particles are identified within the giant cells.
   lymphoid hyperplasia is prominent.
   Warthin-Finkeldey giant cells: pathognomonic for measles, with
    up to 100 nuclei and intracytoplasmic and intranuclear inclusions.

PATHOGENESIS
 4 phases: incubation period, prodromal illness, exanthematous phase, and
  recovery.
 Incubation:
  -measles virus migrates to regional lymph nodes.
  -primary viremia : virus spreads to the reticuloendothelial system.
  -secondary viremia spreads virus to body surfaces.
 prodromal illness:
   - begins following the secondary viremia.
   - associated with epithelial necrosis and giant cell formation in body tissues.
       - killing of cells including CNS
       - viral replication
 exanthematous phase: -with onset of the rash, antibody production begins and
  viral replication and symptoms begin to subside.
  -Measles virus also infects CD4+ T cells, resulting in suppression of the Th1
  immune response.

CLINICAL

            MANIFESTATIONS
   I.P: 8–12 days
 high fever, an enanthem, cough, coryza, conjunctivitis, and a prominent
  exanthem.
 the prodromal phase begins with a mild fever followed by the onset of
  conjunctivitis with photophobia, coryza, a prominent cough and increasing
  fever.
 Koplik spots (enanthem):
  -pathognomonic sign of measles
  -appears 1 to 4 days prior to the onset of the rash
  - first appear as discrete red lesions with bluish white spots in the center on
  the inner aspects of the cheeks at the level of the premolars.
  -may spread to involve the lips, hard palate, and gingiva.
  -may occur in conjunctival folds and in the vaginal mucosa.
  -reported in 50–70% of cases but probably occur in the great majority

CLINICAL
MANIFESTATIONS
 Symptoms increase for 2–4 days until
  the 1st day of the rash.
 The rash begins around the forehead
  (around the hairline), behind the ears,
  and on the upper neck as a red
  maculopapular eruption.
 spreads downward to extremities,
  reaching the palms and soles in up to
  50% of cases.

CLINICAL
MANIFESTATIONS
 With the onset of the rash, symptoms begin to
    subside.
   rash fades over about 7 days in the same
    progression.
   leaving a fine desquamation of skin.
   cough lasts the longest, often up to 10 days. In
    more severe cases,
    generalized lymphadenopathy may be present,
    with cervical and occipital lymph nodes

INAPPARENT MEASLES INFECTION
 Subclinical infection:
  -In individuals with passively acquired antibody,as with blood products
  -rash may be indistinct, brief, or, rarely, entirely absent.
  -also who received vaccine when exposed to measles may develop a rash but
  few other symptoms.
  - Persons with inapparent or subclinical measles do not shed measles virus and
  do not transmit infection to household contacts.
 atypical measles: severe measles at the time of receiving original formalin-
  inactivated measles vaccine
  - Patients had onset of high fever and headache followed by the appearance of
  a maculopapular rash on the extremities that become petechial and purpuric
  and progressed in a centripetal direction.
  -frequently complicated by pneumonia and pleural effusions.
  - development of circulating immune complexes that formed due to an abnormal
  immune response to the vaccine.

LABORATORY FINDINGS

 The diagnosis is clinical.
 Laboratory:
   - decr. Total WBCs and lymphocytes.
 If complicated by bacterial infection, the
  ESR and CRP levels are normal

DIAGNOSIS

 serum (IgM) antibody.
 - appears 1–2 days after the onset of the
  rash and remains for 1 mo.
 4-fold rise in IgG.
 Viral isolation from blood, urine, or
  respiratory secretions
 PCR.

DIFFERENTIAL DIAGNOSIS
   rubella,
   adenoviruses,
   enteroviruses,
   Epstein-Barr virus.
   Exanthem subitum (in infants)
   erythema infectiosum (in older children)
   Mycoplasma pneumoniae
   Gp A streptococcus
   Kawasaki syndrome
   Drug eruptions

COMPLICATIONS
 Morbidity and mortality from measles are greatest in
  patients

Complications by Age for Reported Measles Cases,
                                   USA 1987–2000

                                                           NO.(%) OF PERSONS WITH COMPLICATION BY AGE GROUP

COMPLICATION       OVERALL (67,032 CASES)   30 yr
                                            (n = 28,730)        (n = 6,492)    (n = 18,580)   9,161)          (n = 4,069)

Any                19,480 (29.1)            11,883 (41.4)       1,173 (18.1)   2,369 (12.8)   2,656 (29.0)    1,399 (34.4)

Death              177 (0.3)                97 (0.3)            9 (0.1)        18 (0.1)       26 (0.3)        27 (0.7)

Diarrhea           5,482 (8.2)              3,294 (11.5)        408 (6.3)      627 (3.4)      767 (8.4)       386 (9.5)

Encephalitis       97 (0.1)                 43 (0.2)            9 (0.1)        13 (0.1)       21 (0.2)        11 (0.3)

Hospitalization    12,876 (19.2)            7,470 (26.0)        612 (9.4)      1,612 (8.7)    2,075 (22.7)    1,107 (27.2)

Otitis media       4,879 (7.3)              4,009 (14.0)        305 (4.7)      338 (1.8)      157 (1.7)       70 (1.7)

Pneumonia          3,959 (5.9)              2,480 (8.6)         183 (2.8)      363 (2.0)      554 (6.1)       379 (9.3)

COMPLICATIONS
 Pneumonia is the most common cause of death in measles.
     - giant cell pneumonia caused directly by the viral infection
     - 2ry bacterial infection:S. pneumoniae, H. influenzae, and S. aureus.
     - bronchiolitis obliterans.
   Croup, tracheitis, and bronchiolitis: requires intubation and ventilatory support
    until the infection resolves.
   Acute otitis media is the most common complication of measles
   Sinusitis and mastoiditis
   Viral and/or bacterial tracheitis
   Suppression of PPD skin test
   increased rate of activation of pulmonary tuberculoses.
   Diarrhea, vomiting, dehydration: giant cell formation in the epithelium.
   Appendicitis: obstruction of the lumen by lymphoid hyperplasia.

COMPLICATIONS
     Febrile seizures occur in

COMPLICATIONS
 Myocarditis is a rare complication.
 bacteremia, cellulitis, and toxic shock syndrome.
 Measles during pregnancy associated with high
  maternal morbidity, fetal wastage and stillbirths,
  and congenital malformations in 3% of live born
  infants.

Subacute Sclerosing Parencephalitis (SSPE)
 SSPE is a chronic complication of measles
 delayed onset and nearly always fatal.
 result from a persistent infection with an altered measles virus that is
    harbored intracellularly in the CNS for several years.
   After 7–10 yr regains virulence and attacks the cells in the CNS
   This “slow virus infection” results in inflammation and cell death,
    leading to neurodegenerative process
   The incidence:1:100,000
   age of onset: early age,

Clinical manifestations of SSPE
   SSPE begin insidiously 7–13 yr after primary measles infection.
   Subtle changes in behavior or school performance appear, including irritability,
    reduced attention span, or temper outbursts.
   This initial phase (stage I) may at times be missed because of brevity or mildness of
    the symptoms.
   Fever, headache, or other signs of encephalitis are absent.
   2nd stage is massive myoclonus. This coincides with extension of the inflammatory
    process site to deeper structures in the brain, including the basal ganglia. Involuntary
    movements and repetitive myoclonic jerks begin in single muscle groups but give way
    to massive spasms and jerks involving both axial and appendicular muscles.
    Consciousness is maintained.
   In the 3rd stage, involuntary movements disappear and are replaced by
    choreoathetosis, immobility, dystonia, and lead pipe rigidity that result from
    destruction of deeper centers in the basal ganglia.
   Sensorium deteriorates into dementia, stupor, then coma.
   Stage IV is characterized by loss of critical centers that support breathing, heart rate,
    and blood pressure.
   Death soon ensues. Progression through the clinical stages may follow courses
    characterized as acute, subacute, or chronic progressive.

Diagnosis of SSPE
 (1) measles antibody detected in CSF,
 (2) characteristic electroencephalographic findings, or
 (3) typical histologic findings and/or isolation of virus or
  viral antigen in brain tissue obtained by biopsy or
  postmortem examination.
 CSF analysis reveals normal cells but elevated IgG and
  IgM antibody titers in dilutions of >1 : 8.
 Electroencephalographic patterns are normal in stage I,
  but in the myoclonic phase suppression-burst episodes
  are seen that are characteristic of but not pathogenomic.
 Brain biopsy is no longer routinely indicated for diagnosis
  of SSPE.

Management of SSPE

 primarily supportive like other
  neurodegenerative diseases.
 A recent clinical trial of the use of oral inosiplex
  (isoprinosine) alone to oral inosiplex and
  intraventricular interferon-α2b .
 Most die within 1–3 yr of onset from infection or
  loss of autonomic control mechanisms.
 Prevention of SSPE depends on prevention of
  primary measles infection through the use of
  vaccine.

TREATMENT OF MEASLES
   Management of measles is supportive.
   Antiviral therapy is not effective
   Maintenance of hydration, oxygenation, and comfort are goals of
    therapy.
   Antipyretics for comfort and fever control are useful.
   For patients with respiratory tract involvement, airway humidification
    and supplemental oxygen may be of benefit.
   Respiratory failure due to croup or pneumonia may require ventilatory
    support.
   Oral rehydration is effective in most cases, but severe dehydration may
    require intravenous therapy.
   Prophylactic antimicrobial therapy to prevent bacterial infection is not
    indicated.
   Measles infection in immunocompromised patients is highly lethal.
   Ribavirin is active in vitro against measles virus.
   ribavirin is not licensed in the United States for treatment of measles

VITAMIN A
 Vitamin A deficiency in children in developing
  countries has long been known to be
  associated with increased mortality from a
  variety of infectious diseases, including
  measles.
 In USA: 22–72% of children with measles had
  low retinol
 vitamin A therapy in the developing world and
  the United States have demonstrated reduced
  morbidity and mortality from measles.
 The American Academy of Pediatrics suggests
  vitamin A therapy for selected patients with
  measles

Recommendations for Vitamin A Treatment of
Children with Measles

INDICATIONS
 Children 6 mo to 2 yr of age hospitalized with measles
   and its complications (e.g., croup, pneumonia, and
   diarrhea).
  (Limited data are available about the safety and need for
   vitamin a supplementation for infants 6 mo of age with measles who are not already
   receiving vitamin A supplementation and who have any
   of the following risk factors:
 immunodeficiency
 clinical evidence of vitamin A deficiency
 impaired intestinal absorption
 moderate to severe malnutrition

REGIMEN

 The recommended dosage,
  administered as a capsule, is:
- Single dose of 200,000 IU orally for
  children ≥1 yr of age (100,000 IU for
  children 6 mo to 1 yr of age)
- The dose should be repeated the next
  day and again 4 wk later for children with
  ophthalmologic evidence of vitamin A
  deficiency

PROGNOSIS
 In the early 20th century, deaths due to
  measles varied between 2,000 and 10,000, or
  about 10 deaths per 1,000 cases of measles.
 With improvements in health care and
  antimicrobial therapy, better nutrition, and
  decreased crowding, the death to case ratio fell
  to 1 per 1,000 cases.
 Now in USA: 2.5–2.8/1,000.
 Pneumonia and encephalitis were
  complications in most of the fatal cases, and
  immunodeficiency conditions were identified in
  14–16% of deaths.

PREVENTION

 Patients shed measles virus from 7 days after
  exposure to 4–6 days after the onset of rash.
 Exposure of susceptible individuals to measles
  patients should be avoided during this period.
 In hospitals, standard and airborne precautions
  should be observed for this period.
 Immunocompromised patients with measles will
  shed for the duration of the illness, and isolation
  should be maintained throughout

VACCINE
 Measles vaccine monovalent preparation or combined with the
    rubella (MR) or measles-mumps-rubella (MMR) vaccine,
   2nd dose of measles vaccine was added to the schedule.
   The current recommendations include a 1st dose at 12–15 mo
    followed by a 2nd at 4–6 yr of age.
   Seroconversion is slightly lower in children who receive the 1st
    dose before or at 12 mo of age (87% at 9 mo, 95% at 12 mo,
    and 98% at 15 mo) because of persisting maternal antibody.
   For children who have not received 2 doses by 11–12 yr of age,
    a 2nd dose should be provided.
   Infants who receive a dose before 12 mo of age should be
    given 2 additional doses at 12–15 mo and 4–6 yr of age.
   In any event, this 2nd dose of vaccine may be given anytime 4
    wk after the 1st dose.

The National Immunization Schedule in Palestine
 Age                          The Vaccine
 1 d.   BCG   Hep.B1

 1m.          Hep.B2   IPV1
 2m.                   IPV2   OPV1   DPT1 Hib

 4m.                          OPV2   DPT2   Hib

 6m.          Hep.B3          OPV3   DPT3   Hib

 9m.
12m.                                              MMR

15m                                         Hib

18m                           OPV4   DPT4               MMR

  6y.                         OPV     DT
 12y.                                                         Rubella(
                                                               girls)

 15y.                                 dT

POSTEXPOSURE
PROPHYLAXIS
 vaccine administration or immunization with
    immunoglobulin.
   The vaccine is effective in prevention or modification of
    measles if given within 72 hr of exposure.
   Immune globulin may be given up to 6 days following
    exposure to prevent or modify infection.
    Immunocompetent children should receive 0.25 mL/kg
    intramuscularly and immunocompromised children should
    receive 0.5 mL/kg.
   Immune globulin is indicated for susceptible household
    contacts of measles patients, especially infants

References

 Nelson textbook of pediatrics
 Essentials of pediatrics
 Atlas of pediatric clinical diagnosis
 Internet - Different pages.

Thank You