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AN OVERVIEW OF MUCOCUTANEOUS SYMPTOM COMPLEX ANTONIO E. CHAN, M.D. September 5, 2007 DEFINITION A febrile illness in children associated with skin manifestation (exanthem) and mucous membrane involvement (conjunctiva, throat, respiratory or gastrointestinal tract) • An exanthem is a skin eruption occurring as an integral part of an infectious disease. The corresponding changes in the mucous membranes is an enanthem • Accurate diagnosis not always possible on preliminary examination - judgment should be deferred until rash develops CLASSIFICATION • Maculopapular eruption • Vesiculobullous or vesiculopustular • Petechial or purpuric eruption MORPHOLOGIC TYPES OF RASH • Macule is a flat, circumscribed non-palpable discoloration of the skin; less than 1 cm. in diameter. Often evolve into papules •
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Papules are small nodular elevations of the skin less than 1 cm. in diameter. Vesicles: small blisters containing clear fluid Pustules: small elevations of skin containing pus Petechiae: small hemorrhages beneath the epidermis Ecchymoses: larger areas of hemorrhages Crust/scab: concealed exudate on skin Wheal: localized effusion of fluid into the skin causing a raised, white or pinkish white zone with a halo of erythema Erythema: a diffuse or localized redness of the skin Exanthem – skin eruption occurring as an integral part of an infectious disease Enanthem – changes in the mucous membrane
DESCRIPTIVE DERMATOLOGIC TERMS • Discrete (Rubelliform) • Confluent (Morbilliform) • Reticulated (lace-like network) • Multiform (Polymorphous) • Generalized (widespread) GENERAL STATEMENTS • Many different types of viruses, treponemes, chlamydia, rickettsiae, mycoplasma, bacteria, fungi, protozoan and metazoan agents cause illness with associated cutaneous manifestations • Many possible etiologic agents; hence, no unified epidemiology exist. • Maculopapular rashes are non-specific - a review of epidemiologic and physical findings is most helpful in establishing a diagnosis • These are the most common primary lesions seen during acute febrile illness in children • Associated with mild, febrile upper respiratory or gastrointestinal tract illness • Most exanthematous illnesses in children are benign • Enteroviruses are the leading cause of infection-related exanthematous diseases • Their differential diagnoses is critical because the early cutaneous manifestations of potentially fatal bacterial and rickettsial diseases frequently are similar • Many conditions that will ultimately manifest purpuric, vesicular, urticarial or ulcerative cutaneous lesions may first appear as erythematous macules or papules PATHOGENESIS 1. Dissemination of infectious agents by blood (viremia, bacteremia) which results in secondary infection at the cutaneous site a. Direct result of infectious agents in the epidermis, dermis or dermal capillary endothelium b. An immune response between the organism and antibody or cellular factors in the cutaneous location. 2. Dissemination of known specific toxins of infectious agents 3. A combination of these mechanisms
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VIRAL CAUSES OF MACULOPAPULAR ERUPTIONS • Rubeola virus – Typical, Modified, Atypical • Rubella virus - German measles • HHV 6 & 7 – Roseola infantum (Exanthem Subitum) • Parvovirus B19 – Erythema infectiosum •
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Enteroviral infection – Enterovirus 71 – Coxsackievirus – A2, A4, A5, A7, A9, A10, A16, B1B5 – Echovirus – 1-7, 11-14, 16-19, 22, 24, 25, 30, 38 Epstein Barr Virus – Infectious mononucleosis
BACTERIAL CAUSES OF MACULOPAPULAR ERUPTIONS • Streptococcus pyogenes – Scarlet fever • Salmonella typhi – Typhoid fever • •
Staphylococcus aureus – SSSS, TEN N. meningitidis – Meningococcemia
OTHER CAUSES OF MACULOPAPULAR ERUPTIONS • Kawasaki disease • Drug Eruption
Essential Elements of History • Demographic data – Age – Geographic area: Rickettsial infection (not present in Phil) • Exposure – Ill contacts – Travel (in endemic areas like Rickettsial infxn) – Pets, wildlife, insects (esp. ticks) à cat scratch disease, rat bite fever, rickettsia (tick bite) – Medications and drugs (sulfonamides) – Immunizations • Features of the rash – Temporal associations (onset of rash relative to fever) – Progression and evolution – Location and distribution – Pain or pruritus • Associated signs & symptoms – Prodromal signs & symptoms – Pathognomonic sign • History of previous illness (infectious)
RUBEOLA (MEASLES) • Age: Infants and older children • Mode of transmission: droplet spray during the prodromal period (highly contagious) • Incubation period : 10 – 12 days • Prodromal period (3 – 5 days)
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Conjunctivitis with photophobia Brownish discoloration & branny desquamation Koplik’s spots – grayish white dots usually as small as grains of sand, with slight, reddish areola amm
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Distribution of rash: – Starts behind the ears along the hairline, face then spreads downward over the body – More confluent on the upper part, discrete on the lower part
MODIFIED MEASLES • An attenuated form of infection that may occur in individuals who have received immune globulin after exposure to measles • The clinical manifestations are milder than those of typical infection, and the incubation period is prolonged from 14 to 20 days. ATYPICAL MEASLES • Occurs in individuals infected with natural virus and who previously received killed measles vaccines • Sudden onset of high fever accompanied by abdominal pain, cough, vomiting, and pleuritic chest pain • Koplik spots are rarely present, and rash begins distally and progresses in a cephalad direction, with little involvement of the face and upper part of the trunk RUBEOLA • Diagnosis: Clinical • Treatment: – Supportive – Vitamin A (immunomodulator) • 100,000 IU 6 mos – 1 yr • 200,000 IU > 1 yr • Complications – Otitis media – Pneumonia – Encephalitis – Exacerbate latent PTB • Prevention – Active immunization 9 mos, 15 mos & 4 -6 yr – Passive immunization (gammaglobulin) 0.25 mL / kg max. 15 mL
RUBELLA (GERMAN MEASLES) • Age: Children & young adults – Peak incidence 5 – 14 yrs. old • Mode of transmission: – Oral droplets or transplacental • Incubation period: 14 – 21 days
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Prodromal period: shorter & mild Tender retroauricular, post-cervical lymphadenopathy
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Distribution of rashes are similar to measles but they are discrete and not associated with desquamation Forchheimer spots – red spots are often seen on the palate. Diagnosis: Clinical Treatment: Supportive Complication : None – The most important consequence of rubella is in the pregnant woman “Congenital Rubella Syndrome”
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Clinical Findings in Congenital Rubella Syndrome General IUGR,hepatosplenomegaly, chemical evidence of hepatitis CNS Mental retardation, behavioral disorders, hypotonia, seizures, CSF protein Cardiac PDA, peripheral and valvular, pulmonary stenosis, aortic stenosis, VSD Ocular cataracts,“salt & pepper” retinopathy, corneal clouding, glaucoma Orthopedic radiolucencies in long bones Hematologic transient thrombocytopenia w/ purpura Dermatologic “blueberrymuffin” spots,dermatoglyphic Endocrine Diabetes in 2nd or 3rd decade •
Prevention: – Active immunization 15 mos., 4-6 yrs – Passive immunization for exposed pregnant woman – Gammaglobulin .55 mL/kg
ROSEOLA INFANTUM (EXANTHEM SUBITUM) • Age: 6 mos – 2 yr • Etiologic agent: HHV 6 & 7 • Mode of transmission: Adult saliva • No prodromal period – mild upper respiratory signs, irritability and anorexia, sometime seizures – Nagayama spots, ulcers at the uvulopalatoglossal junction commonly observed in Asian children
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Three-day fever followed by rash at defervescence of fever. Distribution of rash: – Rash starts from the trunk and spreads to the neck, face and proximal extremities amm
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ENTEROVIRAL INFECTION • Age: Infants & Young Children • Mode of transmission: Person-to-person thru fecal-oral or respiratory routes • Causative agents – Coxsackieviruses A2, A4, A5, A7, A9, A10, A16, B1B5; – Echoviruses 1-7, 11-14, 16-19, 22, 24, 25, 30, 38; – Enterovirus 71 • Incubation period: 4 – 7 days • Clinical signs & symptoms – Non-specific – Moderate to high grade fever with respiratory, gastrointestinal or CNS signs & symptoms – Rash variable but starts from face and spreads downward but no desquamation • Treatment : Supportive • Prodrome: – Echovirus 16 (Boston exanthem) prodrome resemble exanthem subitum but fever lower – Fever & constitutional symptoms in Echovirus 4, 6 & 9 may precede but usually coincide with rash appearance • Rash: – May be maculopapular, petechial and vesicular eruptions with Coxsackie A9, A16,A10, A5,B3 and B5 • Diagnosis: Clinical • Treatment: Supportive • Prevention: Basic hygiene (handwashing)
INFECTIOUS MONONUCLEOSIS • Age: Any age group – 90% of children contract EBV infection by 6 years of age – 40%-50% of adolescents have previously experienced EBV infection
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ERYTHEMA INFECTIOSUM • Age: School aged children & Adults • Etiologic agent: Parvovirus B19 • Mode of transmission: respiratory route thru large droplets • Incubation period 4 – 28 days • Mild prodromal period – Low-grade fever, headache, mild upper respiratory symptoms – Joint symptoms common in older adolescents & adults. esp women – Primary target is the erythroid cell line - Transient aplastic crisis - 2nd week • Rash in three stages (17-18 days) 1. Red, flushed cheeks with circumoral pallor (“slapped check” appearance) 2. Maculopapular eruption over upper and lower extremities (the rash assumes a lacelike appearance as it fades) 3. An evanescent stage characterized by subsidence of the eruption followed by recurrence precipitated by a variety of skin irritants (over 1 – 3 wks) • Affected children are not ill-appearing • Older children and adult often complain of mild pruritus • Rash resolves spontaneously without desquamation
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Slapped cheek appearance • • •
Diagnosis: Clinical Treatment: Supportive Prevention: None
Reticulated lesions
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Etiologic agent: Epstein Barr virus – Has latent and lytic life cycle Mode of transmission: saliva (close contact (kissing), mothers fondling their children, toddlers sharing toys) Incubation period : 30 – 50 days Clinical manifestation – Primary infection with EBV in childhood is subclinical or accompanied by mild non-specific symptoms (in <4 yrs. of age) – 30% to 50% of primary infections in adolescence or early adulthood are symptomatic – The disease in children is generally mild, in adults, it is more severe with more protracted course – The major clinical manifestations include fever, sore throat/ pharyngitis, and lymphadenopathy; hepatosplenomegaly, jaundice and rash – Prodromal period lasts 1 to 2 weeks – Infection is heralded by 3 to 5 days of mild headache, malaise, myalgia and fatigue – Followed by the onset of fever, lymphadenopathy and severe sore throat – Other symptoms – abdominal pain and edema of the eyelids – Body temperature rises to 39.40C and falls over a variable period averaging 6 days (younger children are more likely to be afebrile or have only minimal temperature elevation – Generalized lymphadenopathy is a hall mark of IM (90% of cases) – The anterior, posterior cervical and submandibular lymphadenopathy is most common – The lymph nodes are usually single, firm, tender, 2 -4 cm in diameter and not matted. – Sore throat is the cardinal symptom – The tonsils are enlarged, reddened and covered with exudates in more than 50% of cases – Moderate splenomegaly occurs in approx. 50% of cases between the 2nd & 3rd weeks of illness – Hepatitis involvement is common. – Hepatomegaly - 10% - 15% – Hyperbilirubinemia – 25% – Moderate elevation of transaminases – > 80% – The rash appears (3% to 19%) during the first few days of illness, lasts 1 to 6 days can be erythematous, macular, papular or morbilliform, usually located on the trunk and arms, rarely on the palms – 80% of infected patients treated with ampicillin or amoxacillin experienced “ampicillin rash” Diagnosis – Clinical triad (Exudative pharyngitis, cervical lymphadenopathy and splenomegaly – Presence of atypical lymphocytes in the peripheral blood – Serologic test - + Heterophile antibody (appears during 1st or 2nd wk of illness) Exudative pharyngitis Cervical lymphadenopathy Hoagland’s sign: Lid edema Atypical lymphocytes (Downey cell) Confirmatory test – Presence of antibody for specific antigens – IgM antibodies to viral capsid antigen (VCA) are transient whereas IgG antibodies for VCA persist for life – Antibodies against the early antigen (EA) complex appear later in the course of acute infection and disappear after 6 months Confirmatory test – Antibodies against Epstein Barr nuclear antigen (EBNA) complex appear more slowly, they often take from 1 to 6 months to become detectable and levels rise during convalescence. amm
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TYPICAL SEROLOGIC FINDINGS RELATED TO THE STAGE OF EBV INFECTION Stage of infection Presence of Antibody Primary VCA IgM or IgG (usually high) ±EA (usually high), no EBNA Convalescent or Past VCA IgG ± EA (low), EBNA Reactivation VCA IgG (high) ± EA (high), EBNA • •
Treatment: – Bed rest & symptomatic management Complications: Rare – Airway obstruction – Subcapsular splenic hemorrhage – Splenic rupture
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TYPHOID FEVER • Age: Any age group • Etiologic agent: Salmonella typhi • Mode of transmission: Food & water contaminated with human feces • Incubation period: 7 – 14 days • The clinical manifestations of enteric fever depend on age • In infants and young children (<5 yrs.), enteric fever is relatively rare • Mild fever and malaise misinterpreted as viral syndrome • Diarrhea misinterpreted as acute gastroenteritis • In school-aged children and adolescent, the onset of illness is insidious •
SCARLET FEVER • Age: School-age children • Etiologic agent: Group A Streptococcus producing erythrogenic toxin A, B, & C • Mode of transmission: Respiratory route (close contact) • Incubation period: 3 – 4 days
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Clinical Characteristics – Fever, pharyngitis and cervical lymphadenitis and rash – The rash appears within 24-48 hr after onset of symptoms – Begins on the neck and spreads over the trunk and extremities in 24 hours – Diffuse, finely papular, erythematous eruption and blanches on pressure – More intense on elbow, axillae and groin – Goose-pimple appearance and feels rough – Rash fades on the 3rd or 4th day followed by desquamation – Petechiae on the soft palate and posterior pharynx, uvula is red, stippled, and swollen
Diagnosis: – Clinical – Throat swab C & S Treatment: Penicillin
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During the 1st week of illness – Initial symptoms of fever, malaise, anorexia, myalgia, headache, and abdominal pain ( 2 –3 days) – Diarrhea may be present initially but constipation later becomes a more prominent symptom – Temperature increases in a stepwise fashion, unremitting and high within one week During the 2nd week of illness – High fever is sustained – Fatigue, anorexia, cough & abdominal symptoms increase in severity – Patient appears acutely ill, disoriented and lethargic – Delirium and stupor may be observed
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The physical findings include: – Relative bradycardia, disproportionate to high fever – Hepatomegaly, splenomegaly and distended abdomen with diffuse tenderness are very common – Macular or maculopapular rash appears on the lower chest and abdomen and lasts for 2–3 days
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During the 3rd & 4th weeks of illness – Intestinal hemorrhage and perforation commonly occur – Fever begins to show morning remissions, and there is gradual decline in fever spikes
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If no complications occur, the symptoms and physical findings resolve within 2-4 weeks, but malaise and lethargy may be present for an additional 1-2 mos. Patient may be emaciated by the end of the illness
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Rose spots – Occurs in 50% of patients; appears on the 7th or 10th day – Discrete erythematous and 1-5 mm in diameter, slightly raised lesions that blanch on pressure
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Diagnosis: – Confirmed by culture – Multiple sites should be sampled for culture, because no single specimen culture has a yield of 100% – Early in the course of the illness, blood culture – positive in 40% to 60% – After the first week of illness • Urine culture - positive in 7% • Stool culture – positive in 35% to 37% • Bone marrow culture – positive in 80% to 90%, the single most sensitive method of diagnosis – Serologic test (Widal test or Typhidot) result not so reliable amm
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Treatment: – Chloramphenicol remains the gold standard of treatment (14 days) Ceftriaxone- short course therapy Complications: – Intestinal hemorrhage – 1 – 10% – Intestinal perforation - .5% to 3% Prevention – – – – –
Chlorination of water Proper sewage disposal Appropriate food handling practices Handwashing Active immunization given at 2 yrs. of age with 62% to 82% efficacy
MUCOCUTANEOUS LYMPH NODE SYNDROME(KAWASAKI DISEASE) • Age: Occurs predominantly in young children < 5 yr • Etiologic agent: unknown (infectious) • Clinical characteristics: – Acute febrile vasculitis of childhood affecting the medium-sized arteries with predilection for the coronary arteries – Clinical phases of Kawasaki disease • Acute febrile phase • Subacute phase • Convalescent phase • Prodrome: – A nonspecific febrile illness with sore throat precedes the rash by 2 – 5 days • Rash: – Generalized, erythematous, maculopapular. The palms and soles are swollen and reddened, eventually peeling after several days or weeks. • Dryness with fissuring and erythema of the lips, red strawberry tongue, and injected pharynx • Conjunctivitis – Bilateral, bulbar, generally nonpurulent • Cervical lymphadenopathy – Usually unilateral – Not explained by other known disease process • Edema and rash • Polymorphous rash • Periungual desquamation or Perianal desquamation may follow in the subacute phase DIAGNOSTIC CRITERIA FOR KAWASAKI DISEASE • Fever lasting for at least 5 days • Presence of at least four of the following 5 signs 1. Bilateral bulbar conjunctival injection, generally non-purulent 2. Changes in the mucosa of the ororpharynx, including injected pharynx, injected and/or dry fissured lips strawberry tongue 3. Changes of the peripheral extremities, such as edema and/or erythema of the hands or feet in the acute phase; or periungual desquamation in the subacute phase 4. Rash, primarily truncal; polymorphous but nonvesicular 5. Cervical adenopathy, ≥1.5 cm, usually unilateral lymphadenopathy
Ann Mitzel Mata Emy Christine Onishi Maria Cecilia Ong Fredrick Monteverde
Notes: DESQUAMATION 1. measles – “Branny” 2. Kawasaki 3. scarlet fever 4. congenital syphilis – not common Roseola infantum – 6-36 months – Disease of infancy – No prodomal period – Coincidental appearance of rash after defervescence – Bulging of fontanels – Pseudo tumor cerebri à SEIZURE – Unusual finding – Can be manifested by any Px highly febrile Erythema Infectiosum – Biphasic 1. Slap cheek 2. Lace-like eruption 3. Reticular pattern à exacerbated by: – Exercise – Temperature – Ampicillin rash Infectious Mononucleosis – Generalized lymphadenopathy – Splenomegaly – Exudative pharyngitis – Laboratory examination to confirm Presumptive dx: 1. CBC – atypical WBC: DOWNEY CELLS 2. (+) heterophil test 3. IgA 4. Antibodies for EBV Enterovirus – Common only during the certain time of the year – Phil – summer; USA – summer or ___ ? Cox A16 – Hand, foot & mouth disease Echo 16: BOSTON EXANTHEM – Maculpapular vesicular rash – Can simulate rashes – But NOT desquamation – Can have 3C’s (coryza, cough, conjunctivitis) – May also show Koplik spots – Px may present with diarrhea Cox A: Pleurodynia – in adult à costochondritis (pain when breath deeply) Group B Cox – aseptic meningitis – Also seen in measles – Seen in viral illnesses – (-) culture Poliovirus under Enterovirus – paralysis SSS (+) Nikolsky sigh – slight pressure, denude skin Kawasaki – Fever of at least 5 days – Common among asian than scarlet – Cause unknown (staph? Carpet mites?) – Complication: ANEURYSMS Typhoid fever – FUO – Adults > children – Trunk predilection – Rash 10 days after fever – Step ladder pattern fever (When peak it stays there for 3 weeks) – Even w/o tx, usually resolve after 3 Culture: weeks Blood – 1st week – Bradycardia ≠ high fever Urine – 2nd week – Intestinal symptoms Stool – 3rd week – Definite: BM culture Measles – Complication: 1. Pneumonia (most common) 2. gastroenteritis – diarrhea precede/accompany/ follow measles (mucosa GIT affected) – Sequelae of measles – Pneumonia – State of ANERGY: temporary state of immunosuppresion – Reactivation RF, latent PTB – Otitis media – Croup laryngotracheobronchitis – Encephalitis (acute, SSPE) – Meningitis – aseptic meningitis
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