exanthemas

Exanthemas in children

Definition

• Exanthemas is a group of diseases with clinical presentations of rash

• “Exanthema” – rash on the skin

• “Enanthema” – rash on mucous membranes

Groups of diseases with exanthemas

• Infectious

• Allergic

• Dermatological

• Autoimmune

• Toxic

• Neurological

• Idiopathic

Infectious causes

1. Namely exanthematous diseases (exanthema is a key presentation of the disease) = childhood exanthemas

2. Diseases, accompanied by exanthema syndrome

Classification scheme of childhood exanthems

1. Measles

2. Scarlet fever

3. Rubella

4. Filatov-Dukes disease (an atypical scarlet fever)

5. Erythema infectiosum = fifth disease, parvoviral B19 infection

6. Roseola infantum = sixth disease, HHV-6

Other infectious diseases with exanthema syndrome

• Chickenpox • Enteroviral infection• Pseudotuberculosis• Meningococcemia• Infectious mononucleosis (beta-lactame

penicillines)• Syphilis • Rocky Mountain spotted fever• Leptospirosis, etc.

Differential features of infectious exanthemas

Features to help differentiate infectious origin of rash from non-infectious

Presence of feverAppearance of symptomsOther clinical symptomsCharacter of rashEpidemiological contactsLaboratory methods, etc.

Types of rash of infectious origin

• Roseolar rash

• Papullar rash

• Small roseolar (pointed) rash

• Macular rash

• Erythema

• Vesicular rash

ROSEOLAR RASH Roseola is a small macula (d=2…5 mm) of pink, red color, often of round shape. it presents widening of the papillary layer of the skin. Disappears at pressing or skin stretching

• INFECTIOUS DISEASES• Roseola infantum• Parvovirus infection • Pseudotuberculosis • Leptospirosis • Typhoid fever • Paratyphoid fever А & Б• Secondary Syphilis

• NON-INFECTIOUS DISEASES

• Insect bites

SMALL ROSEOLAR (POINTED) RASH

Small in diameter, 1 mm, roseolar red elements, which also disappear on pressure. Slightly elevated over the skin, often

appear on hyperemic background.

• INFECTIOUS DISEASES• Scarlet fever • Staphylococcal infection • Kawasaki disease• Pseudotuberculosis

NON-INFECTIOUS DISEASES

• Medicament rash • Toxicodermia

MACULAR RASHMACULE is an element similar to roseola, but larger (5…20 mm), not elevated over the skin. There is «small macular»

(5 – 10 mm) and и «large macular» (11-20 mm), which is used for differential diagnosis.

INFECTIOUS DISEASES• Measles • Rubella • Infectious mononucleosis• Enteroviral infection • Parvoviral infection• Pseudotuberculosis • Leptospirosis • Endemic(tick-born) recurrent fever• Epidemic(louse-born)relapsing fever


• Secondary Syphilis• Medicament rash

PAPULAR RASHPAPULE is a non-cavity superficial rash, elevated over the skin.

Caused by epidermis proliferation and papillar infiltration with vessels widening and localized edema.

• INFECTIOUS DISEASES

• Measles • Infectious mononucleosis• Enteroviral infection • Parvoviral infection• Pseudotuberculosis • Leptospirosis

• NON-INFECTIOUS DISEASES

• Secondary Syphilis• Allergic dermatitis

ERYTHEMA RASHERYTHEMA is a non-cavity superficial hyperemic rash , caused by papillar edema and increased blood supply.

INFECTIOUS DISEASES

• Parvoviral infection

• Scalded skin syndrome

• Kawasaki• Staph and Strep

toxic shock • Scarlet fever • Lyme disease • Cellulitis • Erysipelas


• Allergic dermatitis• SLE • Rheumatic fever

Sclerodermia • Toxic dermatitis• Burnt skin • Toxicodermia of

newborns • Layella syndrome

VESICULAR RASH Vesicles are small rash with cavities filled with

serous, or serous-hemorrhagic fluid

INFECTIOUS DISEASES• Varicella• Herpetic infection, caused by HSV 1 & 2 types• Herpes zoster

HEMORRHAGIC RASH Rash does not disappear at stretching the skin,

can be small (petechiae) or large, can be accompanied by necrosis

INFECTIOUS DISEASES• Meningococcemia• Seldom – pneumococcal infection

Criteria of rash description for exanthemas diseases

1. Character of the elements2. Prevalent localization3. Background skin color4. Time of appearance5. Connection to fever6. Itching 7. Fusion of rash elements 8. Step-wise appearance9. Presence of enanthema10.Disappearance of the rash

MEASLES

MEASLES

Viral infection with airborne way of transmission, cyclical course and presence of syndromes of intoxication, catarrhal inflammation and exanthema.

History

• Before antibiotics - «children’s plague»: only during 1910th in Europe about 1 million deaths due to measles, mostly due to bacterial complications.

• After antibiotics (after 1940th) mortality decreased considerably, but morbidity was still high.

• After vaccination (since 1960th) morbidity also dropped considerably.

Etiology

• Virus was isolated in 1954. • RNA-containing • Paramyxoviridae, genus Morbillivirus• Virus antigenically identical all over the world →

repeated cases only in 0,5-0,3%• Virus is not stable • Highly transmittable • Causes appearance of multinuclear giant cells in

body, e.g., measles pneumonia

Epidemiology• Way of transmission – airborne • Incubational period – 9-17 days (21 if human Ig injected) • The source of infection patient from 2 last days of

incubational period and till 4 days after appearance of rash (10 days in case of complications)

• Maximal contagiosity – during catarrhal period • Index of contagiosity is 100% • Currently, after vaccination, more cases among adults

are seen • Case fatality rate is mostly due to early age children and

cases of encephalitis • Main cause of acquired blindness in children in

developing countries

Pathogenesis

• Entry of infection – respiratory mucous. • First virusemia – on 3rd day of incubational period

(→ anti-measles Ig is effective during first 3 days) • Virus damages respiratory mucosa • Respiratory tract damage and immunosupression

→ bacterial infections• Pneumonia can be early (viral) or late (bacterial) • Immunosupression is seen some time after

recovery

Clinics – periods

1. Incubational period - 9-17 days (21 day after injection of Ig)

2. Catarrhal period – 3-4 days. Syndromes of intoxication and catarrhal inflammation (of respiratory tract, conjunctiva, intestinal). Dry cough, rhinitis, conjunctivitis, slight face edema.

3. Rash period - since 4th-5th day. Intoxication and catarrhal syndrome still increase. Croup or dyspepsia in young children can appear

4. Pigmentation period

Clinics

Pathognomic sigh – Filatov-Koplik spots: whitish small points on the inner cheek mucosa at the level of premolares, not removable (focal necrosis of epithelium). Appears on the 1st day of the disease, disappears by the 3rd day. Can be on epithelium of conjunctiva and vagina

Filatov-Koplik spots

Clinics – rash characteristics

1. Character of the elements – macular-papulous 2. Prevalent localization – all over the body 3. Background skin color – normal 4. Time of appearance – 3rd – 4th day of the disease 5. Connection to fever – intoxication increases 6. Itching – very rare7. Fusion of rash elements – yes 8. Step-wise appearance – 3 days (face → trunk →

extremities) 9. Presence of enanthema – Koplik spots (first 3 days) and

palate enanthema (concurrent with rash) 10.Disappearance of the rash – pigmentation

MEASLES

Classification

1. Typical (mild, moderate, severe) and atypical (abortive, mitigated, low-grate, asymptomatic) – 5-7%.

• Mild: fever under 38,5С, mild intoxication and rash

• Moderate: fever 39С, vomiting, prominent rash• Severe: seizures, loss of consciousness, fever

40 and higher

2. With / without complications

Abortive and mitigated forms

• Abortive and mitigated forms: catarrhal period is 1-2 days or absent, almost no intoxication. Rash is 1-2 days, pale, scanty, without step-wise appearance, mild pigmentation. Koplik spots can be absent. Develops after injection of Ig, blood preparations or incomplete vaccination.

Complications

1. Etiology:

• viral (measles virus)

• bacterial;

2. Time of appearance:

• early – catarrhal and rash periods;

• late – pigmentation period;

Complications – cont.3. Topics: • respiratory system (pneumonia, sinusitis,

laryngitis, laryngo-tracheitis, bronchitis, bronchiolitis, pleuritis),

• gastro-intestinal (stomatitis, enteritis, colitis), • nervous system (encephalitis,

meningoencephalitis, meningitis, psychosis), • eyes (conjunctivitis, blepharitis, keratitis, kerato-

conjunctivitis), • ears (otitis, mastoididtis), skin (pyodermia,

phlegmona), • urinary tract (pyelitis, cystitis, pyelonephritis).

Complications – encephalitis

• Rare complication• Mostly after severe cases, but can be after mild

and moderate • Mostly in adults • Mortality up to 25%• Possible consequences: paresis, intellectual

deficit, epilepsy.

Measles is proved to play role in development of slow sclerosing panencephalitis

Complications – bacterial

• Mostly under 3 years of age (→ antibiotics are indicated in most cases).

• Usually, the earlier → the more severe

• Can mask by clinical presentation of measles itself

Laboratory diagnosis

• CBC: leucopenia, lymphocytosis

• Cytology of nasal discharge – typical multinuclear giant cells

Required confirmation: • Virusology – PCR and IFA (in rash period

can already be negative)

• Serological – titer of IgM increases, IgG → measles in anamnesis

Differential diagnosis

• Catarrhal period – acute respiratory viral infections;

• Rash period – rubella, scarlet fever, enteroviral infection, pseudotuberculosis, meningococcemia, allergic exanthema, ampicillin usage at infectious mononucleosis.

Treatment

• Regime – mouth and eyes washing• Etiotropic therapy (ribavirin) – unclear efficacy,

recommended for encephalitis cases • Vitamin A • Antibiotics (children under 3 years of age,

immunodeficient or development of complications)

• Detoxication• Symptomatic

Hospitalization of all children under 2 years of age

Prophylaxis

Active

• Alive attenuated vaccine (MMR) – at 1 and 6 years.

• After vaccination, a measles-like syndrome can develop – these children are not contagious

• Urgent vaccination after contact- first 5 days

Prophylaxis

Passive

• Anti-measles Ig – first 3 days after contact

• Indications: 3 months - 2 years of age without vaccination or disease in the past; patients with chronic infections and immunosupression, pregnant.

Contagious period

Since the last days of incubation period – till 4th days (10th day in case of complications) after appearance of the rash on the skin

Isolation

• Till the 4th day after appearance of the exanthema (uncomplicated cases)

• Till the 10th day after appearance of the exanthema (complicated cases)

RUBELLA

RUBELLA

Viral infection – acquired (airborne, mild clinical presentation and benign outcome) or inborn (transplacental transmission, severe defects of the fetus)

Etiology

• Virus was isolated in 1962• RNA-containing • Togaviridae, genus Rubivirus• Virus antigenically identical all over the

world → repeated cases very rare• Virus is not stable

Epidemiology• Way of transmission – airborne • Incubational period – 9-21 days• Most cases in children of 2 to 9 years • The source of infection is a patient from 1-2

weeks of incubational period and till 3 weeks of the disease

• Inborn rubella – can be contagious up till 1-2 years

• Can be isolated from respiratory secretions, blood, urine

• Index of contagiosity is 80-90% • Most cases - in winter and spring

Inborn rubella - pathogenesis

1. Direct cytopathic action on the fetus (lens and cochlear cells)

2. Mitosis activity delay

Critical periods: • brain – 3-11 weeks of gestation, • eyes and heart – 4-7 weeks, • ears – 7-12 weeks

If rubella at 2 months – more risk of catarrhact and heart defects; in 3-4 months - CNS defects

Inborn rubella – clinics

Typical Triad:

1. Deafness

2. Blindness

3. Heart defects

Very often + Brain defects, defects of any organ and system, thrombocytopenia, developmental delay …

Clinics – periods

1.Incubational period - 9-21 day

2.Prodromal period – can be several hours; mild intoxication and catarrhal period, lymph nodes enlargement

3.Rash period - 3-4 days

4.Convalescence period

Clinics

1. Intoxication syndrome : mild; fever under 37,5 – 1-2 days

2. Exanthema syndrome

3. Lymphadenitis – posterior cervical and occipital lymph nodes


1. Character of the elements – pale macular2. Prevalent localization – face, back, buttocks, extension

surfaces of the extremities3. Background skin color – normal 4. Time of appearance – 1st day of the disease 5. Connection to fever – mild if any fever 6. Itching – no7. Fusion of rash elements – no 8. Step-wise appearance – no9. Presence of enanthema –palate enanthema

(concurrent with rash, Forscheirmer spots) 10. Disappearance of the rash – no residuals

Classification

1. Typical (mild, moderate, severe) and atypical (low-grate, asymptomatic)


3. Acquired or inborn

Complications

• Arthritis and arthralgias – 1-2 week of the disease, more often in females

• Encephalitis (1:6 000) –- on the 5-8th day

• Thrombocytopenic purpura – 1-2nd week

Complications

• Encephalitis : fever to 40, symptoms of encephalitis

• Mortality rate is 15-20%

• Recovery takes 2-3 months, can be residual symptoms


• CBC: Plasmocytes (Turke cells)– to 10-20%

Required confirmation• Virusology – PCR and IFA, nasal

secretion, CSF

• Serological – increase of IgM titer Ig M – positive 12 weeks after disease;

Ig G - anamnestic


I. Infectious causes:

•Measles, esp. mitigated

•Scarlet fever

•Exanthema subitum

•Parvoviral infection

•Varicella

•Infectious mononucleosis

•Pseudotuberculosis

•CMV

•Acute toxoplasmosis

•Enteroviral infection

•Leptospirosis

•Rosenberg erythema

•Trichinellosis

•Syphilis


II. Not – infectious causes:

• Reaction to measles vaccine

• Allergic dermatitis

• Drug reactions

Treatment

• Uncomplicated forms - no treatment

• At arthralgias – NSAIDs

• Encephalitis and meningitis – appropriate treatment

Prophylaxis

Active • Alive attenuated vaccine (MMR) – at 1 and 12-

14 (girls) years. • Contraindicated in pregnant, 3 months before

pregnancy, immunodeficient, at hypersensitivity to amynoglicozides and yolk

Passive • In pregnant women, but low efficacy

Contagious period

Since last 1-2 weeks of incubation period – till 2-4 weeks after appearance of the disease

Isolation

• 4 first days of the disease; inborn rubella - 2 years

• At contact with pregnant woman without rubella in the past – Ab evaluation twice in dynamics

SCARLET FEVER

Scarlet fever

Acute infectious disease caused by

β-hemolytic Streptococcus Group A

and presented with

(1) intoxication syndrome,

(2) tonsillitis,

(3)exanthema

Etiology

• β-hemolytic Streptococcus, group A • Produces exotoxin (Dick’s) →

responsible for clinics (Rash)• If anti-toxic immunity is absent →

scarlet fever• If anti-toxic immunity is present →

tonsillitis, pharyngitis, carriage, etc.

Epidemiology• Antroponous infection• Source of the infection – patient with scarlet

fever, any other streptococcal infection or carriage

• Autumn – spring months, periods of every 2 years

• Mostly – children under 8-9 years of age• Main way of transmission – airborne; can

be also contact and food-borne • Easiest transmission – in close rooms

Epidemiology

• Index of contagiosity is 40%

• The patient is contagious since first clinics till 24 hours after start of antibiotic therapy

• Mild cases and carriers are more dangerous epidemically

• Due to usage of antibiotics, nowadays repeated cases are possible

Pathogenesis

• Entry of infection – tonsillar mucous, seldom – macerated or burnt skin (atypical forms) → local inflammation

• Catarrhal, lacunar or necrotic tonsillitis and toxin adsorption from the entry → intoxication and rash

Pathogenesis

3 main pathogenetic components of scarlet fever:

1. Toxic

2. Septic

3. Allergic

PathogenesisToxic component: • Intoxication syndrome (fever, vomiting,

headache)• Activated sympatic tonus (red dermographism,

tachycardia, skin dryness, elevated blood pressure)

• Rash • In severe cases - hemodynamic disturbances,

adrenal hemorrhages, brain edema

Pathogenesis

Septic component:

• Necrotic changes at the infection entry (necrotic tonsillitis)

• Septic purulent complications (sinusitis, otitis, pneumonia, purulent lymphadenitis, septic arthritis, etc.)

PathogenesisAllergic component: Sensibilization to β-hemolytic Streptococcus

and damaged tissue antigens. Appears in the 2-3rd week of the disease

• Polymorphic skin rash• Acute allergic lymphadenitis• Glomerulonephritis• Rheumatic fever, myocarditis• Sinoviitis.

Immunity Permanent non-specific antitoxic &

Transient type-specific antimicrobial ↓

Repeated cases of scarlet fever are rare (in cases of inadequate production of antitoxic

antibodies) but

any other streptococcal infections in the future possible (tonsillitis, erysipelas, otitis,

pneumonia, etc.)

Clinics

1. Incubational period - 2-7 days

2. Rash period - since 1st day: Intoxication syndrome + tonsillitis + rash

3. Recovery period

Clinics – rash characteristics1. Character of the elements – pointed macular m2. Prevalent localization – cheeks, side surfaces of the body,

flexion surfaces of the extremities, inquinal area; nasolabial triangle is pale

3. Background skin color – hyperemic 4. Time of appearance – 1st day of the disease 5. Connection to fever – intoxication of the first day 6. Itching – no7. Fusion of rash elements – no 8. Step-wise appearance – no 9. Presence of enanthema – scarlet hyperemia of tonsillitis 10.Disappearance of the rash – scaled desquamation of palms

and feet and branny desquamation of the rest of the body

SCARLET FEVER

Pathognomic skin symptoms

• Pastia’s sign – increased brownish (tiny hemorrhages) lines in the physiological folds of the body

• Filatov’s sign - Pale nasolabial triangle

Tonsillitis

• Most often – lacunar

• Bright localized hyperemia of the pharynx (“burning pharynx”)

• Strawberry tongue – forms by the 3rd day of the disease

Classification

1. Typical (mild, moderate, severe) and atypical (extratonsillar)

• Mild: fever under 38,5С, mild intoxication, rash and tonsillitis

• Moderate: fever 39С, vomiting, prominent tonsillitis and rash

• Severe: fever 40 and higher, loss of consciousness, septic and toxic complications


Complications

1. Toxic

2. Septic

3. Allergic

Toxic complications

• Hemodynamic disturbances

• Adrenal hemorrhages

• Brain edema

• Septic shock syndrome

Septic complications

• Pneumonia

• Otitis

• Sinusitis

• Necrotic tonsillitis

• Paratonsillar and retropharyngeal abscesses

• Purulent lymphadenitis

• Septic arthritis, etc.

Allergic complications

• Rheumatic fever

• Myocarditis

• Poststreptococcal glomerulonephritis

• Polymorphic skin rash

• Acute allergic lymphadenitis

• Sinoviitis


• CBC: leucocytosis, neurophiles, bands, elevated ESR

• Throat culture (confirmative) – positive for β-hemolytic Streptococcus Group A

• Serological – increase of titer of antostreptolysin O, anti-DNAsa in dynamics


• Allergic exanthema

• Pseudotuberculosis• Measles

• Enteroviral infection

• Syphilis

• Rubella

• Meningococcemia

• Ampicillin usage at infectious mononucleosis.

Treatment

• Diet – allergy free, mechanical and thermal mild (tonsillitis)

• Antibiotics !!! 1. Penicillins – 10 days 2. Macrolides – at allergy to penicillins 3. Cephalosporins – at complications

• Detoxication• Anti-histamine drugs • Symptomatic

Prophylaxis

No vaccination

All contact patients – throat Cx & treatment of the carriers

Treatment of other streptococcal diseases

Contagious period

The last 1-2 days of incubation period – till 24 hours after beginning of adequate antibiotic therapy

Isolation

• 21 days from the beginning of the disease (term of possible complication development)

• On the 21st day – urinalysis and ECG

CHICKEN POX

Chicken Pox

Acute infectious disease caused by Varicella-Zoster virus (VZV) from Herpesviridae with airborne way of transmission, with predominant involvement of epithelium and nervous system and presented with syndromes of intoxication and exanthema

Classification of Herpesviridae

1. HSV-12. HSV-23. VZV4. EBV5. CMV6. Herpesvirus – 6 type 7. Herpesvirus – 7 type 8. Herpesvirus – 8 type

History

• Before 16th century chicken pox was not differentiated from smallpox → the name of the disease

Disease forms

1. Varicella - primary infection, with virusemia

2. Herpes Zoster – reactivation of virus from neural ganglia

Etiology

• Varicella-Zoster virus (VZV)

• DNA-containing

• Carriage can be life-long

• Very unstable (15 minutes at room air)

• Very volatile and highly transmittable

Epidemiology

Almost all children become positive by 10-14 yearsSource of the infection – patient with varicella or

herpes zoster Contagiousness starts from 10th day of incubation

and ends after 5th day after the last rash appearance

Transmission is airborne, seldom – transplacentarIndex of contagiosity is 95-98%Most of the cases – pre-school children Mostly in autumn – winterRepeated cases – in 2-3%

Pathogenesis

• Entry of infection – upper respiratory mucous

• Virusemia → skin and mucus epithelium → characteristic rash

Pathogenesis of rash

1. Capillary dilation → macula2. Serous edema → papula 3. Damage of spike layer of the skin → cell

dystrophy and necrosis → intercellular fluid collection → vesicles. Basement of vesicles is infiltrated with monocytes and lymphocytes → typical hyperemia around vesicles

4. Resorption of exudate → crusts

Pathogenesis

• All the mucous membranes of the body: macula → papula → erosion. Clinical presentations – croup, dyspepsia, dysuria

• Tropism to nervous system:Vertebral ganglia → Herpes Zoster

Brain cortex → encephalitis

Cerebellum → cerebellitis

• Immunodeficiencies → visceral forms (hepatitis, pneumonitis, carditis, etc.)

Clinics – periods

1. Incubational period - 9-21 day

2. Rash period - depends on severity, from 3-4 days to 2 weeks

3. Convalescence period (“crusts period”)

Clinics – syndromes

• Intoxication syndrome – spikes of fever with every new rash elements. Fever, fatigue, malaise, irritability, vomiting

• Exanthema syndrome


1. Character of the elements – false polymorphism (macula → papula → vesicle → crust)

2. Prevalent localization – all over the body, including hair part of the head and excluding palms and feet

3. Background skin color – normal 4. Time of appearance – first days of the disease 5. Connection to fever – fever spikes with waves of new

elements appearance 6. Itching – yes7. Fusion of rash elements – no 8. Step-wise appearance – no, but repetitive waves9. Presence of enanthema – on all mucous membranes 10.Disappearance of the rash – temporal depigmentation or mild

scars after pustules or crusts removal

CHICKEN POXCHICKEN POX

CHICKEN POX

HERPES ZOSTER

ClassificationType Severity Course

Typical Mild Without complications

Atypical:

Rudimentary Hemorrhagic Gangrenous Generalized (visceral)

Bullious

Pustulous

Moderate With complications

Severity

Severity

• Mild – subfebrile fever, scarce to moderate elements

• Moderate – fever to 390С, numerous elements, including mucous membranes

• Severe – fever up to 40, prominent rash and intoxication, neurotoxocosis and encephalitic reactions

Atypical forms

Rudimental - after receiving antibodies (Ig or plasma injection) short before disease.

Scarce rash, vesicles may be absent, no intoxication.

Atypical formsGeneralized = visceral – in immunodeficient

patients

Severe intoxication, inflammation of inner organs caused by VZV (hepatitis, pneumonitis, carditis, nephritis, etc.

High mortality. On autopsy – necrosis foci in lungs, pancreas, adrenals, thymus, spleen, etc.

Atypical forms

Hemorrhagic form – in children with hemorrhagic diseases, hemoblastoses, patients on corticosteroids or cytostatics.

Hemorrhagic vesicles, hemorrhages into mucous and inner organs.

Prognosis is serious.

Atypical forms

Gangrenous form – in children with defects of taking care of, usually with secondary infections

inflammation around hemorrhagic vesicles with development of deep growing ulcers

Complications

1. Primary (caused by VZV)

2. Secondary (caused by bacterial infections)

Primary Complications

• Encephalitis

• Meningoencephalitis

• Myelitis

• Nephritis

• Myocarditis

CNS complications

Early complications• Develop on the first days of the disease• Severe encephalitis with high mortality• Hyperthermia, seizures, loss of consciousness, focal

signs

Late complications • Develop at the “crusts” period • Do not depend on the severity of the previous

varicella • Most often – cerebellitis

Cerebellitis

• Most often form of the varicella encephalitis • Develops after several days of normal

temperature • Clinics:

cerebellar signs – ataxia, aphasia, tremor, nistagm;

can be fatigue, headache, vomiting, fever. meningeal signs not prominent or absent

• SCF normal or mild changes • Recovery during several days or weeks

Other complications • Reye syndrome • Croup• Thrombocytopenia • VZV pneumonia (adults and teenagers mostly) • Carditis • Keratitis • Arthritis• Glomerulonephritis • Nephrotic syndrome • Pancreatits • Orchitis

Secondary complications

• Cellulitis • Pustulous and

bullous forms • Phlegmona • Abscess • Impetigo

• Bullious pyodermia

• Erysipelas

• Lymphadenitis

• Stomatitis

• Conjunctivitis

• Croup (seldom)

Chicken Pox in Newborns

• If mother develops chicken pox within 5 days before delivery or few days after, the newborn will develop severe forms with generalization and high mortality rate. Incubation period in newborns is 6-16 days.

• If mother develops chicken pox earlier than 5 days before delivery, the newborn will produce mild or rudimental forms.


1. In typical clinical forms, laboratory confirmation is not required

2. If the diagnosis is in doubt: • “Tzanck” smear with sensitivity of about 60%

(from a vesicle). • VZV antigen from vesicular fluid (IFA)• PCR of vesicle fluid, CSF or blood• Serology – 4-fold increase in repeated titers in10

days


• Herpetic infection

• Impetigo

• Herangina

• Allergic rash

• Meningococcemia

• Toxic dermatitis

Treatment

Mouth washing after every meal;

Skin bathing without scratching;

Topic antiseptic paints are contraindicated unless secondary infection develops;

Corticosteroids are contraindicated, except in late encephalitis.

Treatment

Mild and moderate cases in immunocompetent children – symptomatic therapy:

• NSAIDs for fever (absolutely exclude aspirin – risk of Reye syndrome!) (avoid ibuprofen – risk of necrotizing fasciitis)

• Anti-hystaminic drugs for itching

Treatment

Indications for etiotropic therapy: • Severe course • Visceral, gemorrhagic forms• Patients with immunodeficiencies (HIV,

primary immunodeficiencies, oncology, hematologic diseases, patients on steroids or chemotherapy, after organ transplantation)

• Newborns, first two years of age children (if mother did not have chicken pox)

• Patients older than 12 years

Treatment

Eiotropic therapy – acyclovir Start within first 24 hours! IV:

10-30 mg/kg/day in 100 ml of infusion

PO: 400mg qid for 2-6 years old 800 mg qid for older children

Course 5-7 days

Polyvalent IV Immunoglobulin (0,2-0,5 ml/kg) or specific VZV Immunoglobulin

Treatment

Antibiotics – for secondary complications, gangrenous form

Encephalitis:

Acyclovir

Corticosteroids

Pathogenic treatment

Prophylaxis

Chemoprophylaxis with acyclovir is not effective

Active prophylaxis – live attenuated VZV-vaccine

Children from 1 to 13 years – once

Older children and adults twice in 4-8 weeks (after previous testing for VZV-IgG)

Prophylaxis

Passive prophylaxis : VZIG –1,25 ml/10 kg, IM, once, at first 48-96 hours of incubation. Incubation period can prolong till 28 days. VZIG circulates in the body 2-4 weeks.

Indications: 1. Immunodeficiences, 2. Pregnancy (after previous testing for VZV-IgG),3. Newborns from mothers who developed

varizella within 5 days before and 2 days after delivery.

ROSEOLA INFANTUM, sixth disease

Roseola infantum

Roseola infantum (Human Herpesviruses 6 and 7) is a mild febrile, exanthematous illness occurring almost exclusively during infancy

History

• Roseola was described as a distinct illness at the beginning of the 20th century.

• HHV-6 was discovered in 1986, 22 yr after discovery of the 5th human herpesvirus (Epstein-Barr virus), first – in peripheral blood mononuclear cells (PBMCs) of adult patients with AIDS or lymphoproliferative diseases

• HHV-7 was identified in 1990 in the peripheral blood mononuclear cells of an HIV-uninfected adult

Causative agents

• 2/3 cases - HHV-6 (=exanthem subitum, = sixth disease), also causes other diseases.

• 1/4 cases - HHV-7

• Other cases - viruses (e.g., echovirus 16)

Etiology

• ß-herpesvirus subfamily of herpesviruses (includes HHV-6, HHV-7 & CMV)

• Large double-stranded DNA genome

• Establishment of latency after primary infection

• The principal target cells for HHV-6 and HHV-7 infection in vivo are CD4 T cells

Epidemiology

• HHV-6 mostly occurs early in life: 90% of newborn are HHV-6 seropositive (maternal

antibodies) 4–6 mo of age - 0–60% are seropositive 12 mo of age - 60–90% are seropositive 3–5 yr - 80–100% are seropositive

• Peak of disease is 6–15 mo of age • > 95% of cases - in children younger than 3 yr• Transplacental antibodies are likely to protect

most infants until 6 mo of age.

Epidemiology

• Higher incidence during spring and fall months

• Contact with roseola is rearily reported

• Incubation period averages 10 days (range of 5–15 days).

• Most adults excrete HHV-6 and HHV-7 in saliva → primary sources of virus for children

• No congenital HHV-7 infections have been described

Pathogenesis

• Ports of entry - oral, nasal, or conjunctival mucosa

• HHV-6 can suppress all cellular lineages within the bone marrow

Course – periods 1st period – Intoxication syndrome: Acute beginning High fever: 37.9 to 40°C (101–106°F), average of

39°C (103°F) Irritability, anorexia Normal behavior despite high temperatures Catarrhal syndrome is not prominent

Fever persists for 3–5 days → resolves abruptly (“crisis”)

Occasionally, the fever may gradually diminish over 24–36 hours (“lysis”)

Course – periods2nd period - Exanthema period Rash appears within 12–24hr after fever resolution Rose colored, fairly distinctive. However, it may be

confused with exanthems resulting from rubella, measles, or erythema infectiosum

Begins on the trunk and usually spreads to the neck, face, and proximal extremities

Not pruritic, and no vesicles or pustules develop Lesions typically remain discrete but occasionally

may become almost confluent After 1–3 days, the rash fades Some children experience evanescent rashes that

resolve within a few hours.

Other clinical presentations

• Mild cervical or occipital lymphadenopathy• Slight or absent catarrhal syndrome • Seizures (5–10%) at the peak of fever • Infrequently: rhinorrhea, sore throat,

abdominal pain, vomiting, and diarrhea• In Asian countries, ulcers at the

uvulopalatoglossal junction (Nagayama spots) are common in infants with roseola

HHV-7 clinical particularities

• Slightly older age

• Lower mean temperature

• Shorter duration of fever

CNS involvement

• Febrile seizures

• Fontanelle bulging

• Encephalitis and meningoencephalitis (6% of children with unknown-cause encephalitis were CSF positive for HHV-6)

Other clinical forms• Chronic fatigue syndrome • Nonspecific febrile disease• Hepatitis • Mononucleosis-like disease • Hemophagocytic syndrome• Intussusception• Idiopathic thrombocytopenic purpura• Recurrent aphthous stomatitis• Myocarditis• Disseminated disease

Clinical forms in immunocompromised patients

• Encephalitis

• Pneumonitis

Other probable etiologic role

• Multiple sclerosis

• Various malignancies (non-Hodgkin lymphoma, Hodgkin disease, cervical and oral carcinoma, and leukemia)

Diagnosis

• Serology: HHV-6 immunoglobulin (Ig) M and 4-fold increases or decreases in HHV-6 or -7 IgG antibodies

• Virus culture: incubation of PBMCs for days to several weeks (only in research laboratories)

• PCR: serum or cerebrospinal fluid (in PBMCs, saliva, and tissues – can be latent infection)

• In situ hybridization and immunohistochemistry

Laboratory findings

• WBC counts of 8,000–9,000/µL - first few days

• 4,000–6,000/µL - by the time of exanthema

• Relative lymphocytosis (70–90%)

• CSF is normal

• In meningoencephalitis and encephalitis - mild pleocytosis, predominance of mononuclear cells, normal glucose, and normal to slightly elevated protein

Differential doagnosis

After rash appearance:

• Rubella (most similar)

• Measles

• Enteroviruses

• Scarlet fever

• Drug hypersensitivity

Treatment

Etiologic treatment • HHV-6 - ganciclovir, cidofovir, and foscarnet

(but not acyclovir) • HHV-7 - cidofovir and foscarnet Questionable clinical effect !

Indications for etiologic treatment: • Children with neurologic complications • Immunocompromised children

Treatment

Supportive therapy

• Acetaminophen or ibuprofen

• Adequate fluid balance

Prognosis

• Great majority - excellent, no sequelae

• Encephalitis, hepatitis, pneumonitis, disseminated disease, or hemophagocytosis syndrome – high mortality

Prevention

• Healthy immune carriers with latent viral infections transmit infection to susceptible infants and children

• No specific recommendations for prevention

• No vaccine has been developed

PARVOVIRAL INFECTION (INFECTIOUS ERYTHEMA, «fifth disease»)

Parvovirus B19

ERYTHEMA INFECTIOSUM (FIFTH DISEASE) is a benign, self-limited exanthematous illness of childhood

History

1983: Anderson and colleagues identified Parvovirus B19 as the cause of erythema infectiosum or fifth disease

Etiology

• Genus Erythrovirus, family Parvoviridae

• Small DNA viruses

• Relatively heat- and solvent-resistant

Epidemiology

• Common and worldwide• 70% of cases occur between 5 and 15 yr of

age• Seasonal peaks: late winter and spring• Seroprevalence: 40–60% of adults are positive • Transmission: respiratory route • Transmission rate in households: 15 to 30% • Also transmitted by blood products

Pathogenesis

• Primary target - erythroid cell line: lysis of these cells → progressive depletion & transient arrest of erythropoiesis

• No apparent effect on the myeloid cell line

• Erythrocyte P blood group antigen serves as a cellular receptor for the virus

• Also possess this antigen: endothelial cells, placenta, and fetal myocardial cells

Course

Biphasic illness

1st phase: 7 to 11 days after inoculation: • Viremia and nasopharyngeal viral shedding • Fever, malaise, and rhinorrhea• Reticulocyte counts dropping to undetectable levels• Mild, clinically insignificant anemia

But: Individuals with chronic hemolytic anemia often require transfusion

Appearance of specific antibodies causes resolution of symptoms and anemia

Course

2nd phase: 17–18 days after inoculation: • Rash, arthralgia (due to postinfectious immune

response) and possible lymphadenopathy • In impaired humoral immunity → chronic red cell aplasia,

neutropenia, thrombocytopenia, and marrow failure• In children on chemotherapy for leukemia, those with

congenital immunodeficiency states, transplant patients, and those with AIDS are at risk for chronic B19 infections

• In fetus: hydrops and stillbirth, but no teratogenicity (erythroblasts and extramedullary hematopoiesis damage)

Forms of infection

• Many infections - clinically inapparent

• Children - erythema infectiosum

• Adults - acute arthropathy with or without the rash of erythema infectiosum

Clinics - Erythema infectiosum

1. Incubation period: 4 to 28 days (average, 16–17 days)

2. Prodromal phase: – Low-grade fever– Headache – Mild upper respiratory tract infection

Clinics - Erythema infectiosum

3. Exanthema period:

Three stages:

1. Erythematous facial flushing - “slapped-cheek”

2. Spread to trunk and proximal extremities - diffuse macular erythema

3. Central clearing of macular lesions → lacy, reticulated appearance


1. Character of the elements – previous slide 2. Prevalent localization – more prominent on extensor

surfaces, but palms and soles are spared3. Background skin color – normal 4. Time of appearance – 3rd – 4th day of the disease5. Connection to fever – afebrile and not ill-appearing 6. Itching – mild in older children and adults7. Fusion of rash elements – no 8. Step-wise appearance – previous slide 9. Presence of enanthema – palate 10.Disappearance of the rash – spontaneous, no

desquamation

PARVOVIRAL INFECTION (INFECTIOUS ERYTHEMA, «fifth disease»)

Rash characteristics

• The rash tends to wax and wane over 1–3 wk, can recur with exposure to sunlight, heat, exercise, and stress

• Atypical papular, purpuric, vesicular rashes are also described

Other clinical forms

• Arthritis and arthralgia

• Transient aplastic crisis

• In immunocompromised persons

• Fetal infection

• Myocarditis

• Other cutaneous manifestations

Arthritis and arthralgia

Can be: 1. Complication of fifth disease2. The only clinical manifestation of B19 infection

• Much more common in adults and older adolescents• Females > males• Range from diffuse arthralgias with morning stiffness

to frank arthritis• The joints most often affected: hands, wrists, knees,

and ankles, etc.• Self-limited within 2–4 wk

Transient aplastic crisis

Develops in patients with sickle cell disease, thalassemia, hereditary spherocytosis, and pyruvate kinase deficiency

Incubation period is shorter: coincident with the viremia

Fever, malaise, and lethargySigns and symptoms of profound anemia (pallor,

tachycardia, and tachypnea)Rash is rarely presentConcurrent vaso-occlusive pain crisis

Immunocompromised persons

Chronic infections: Chronic anemia, neutropenia, thrombocytopenia, or complete marrow suppression

Fetal infection

• Nonimmune fetal hydrops and intrauterine fetal demise <5%

• Viral-induced red cell aplasia

• B19 has not been associated with other birth defects

Myocarditis

• In fetuses, infants, children and a few adults

• Outcomes: from complete recovery to chronic cardiomyopathy to fatal cardiac arrest

Other cutaneous manifestations

Papular-purpuric “gloves and socks” syndrome (PPGSS) is distinctly associated with B19 infection:

PruritusPainful edemaErythema of distal extremities (glove and sock

distribution) Acral petechiaeOral lesionsSelf-limited within a few weeks

Diagnosis

• Serologic tests

• Determination of anti-B19 IgM

• Seroconversion of anti-B19 IgG in paired sera

• The virus cannot be isolated by culture

• PCR or nucleic acid hybridization


• Rubella

• Measles

• Enteroviral infections

• Drug reactions

• Juvenile rheumatoid arthritis

• Systemic lupus erythematosus

• Other connective tissue disorders

Treatment

• No specific antiviral therapy

• Anemia and bone marrow failure in immunocompromised children - intravenous immunoglobulin (IVIG)

• Fetuses with anemia and hydrops - intrauterine transfusions

Complications

• Arthralgias or arthritis in adolescents and adults (may persist after resolution of the rash)

• Thrombocytopenic purpura

• Aseptic meningitis

• Hemophagocytic syndrome

Prevention

Children with erythema infectiosum are not infectious at presentation because the

rash and arthropathy represent immune-mediated, postinfectious phenomena

↓

Isolation and exclusion from school or childcare are unnecessary and ineffective

after diagnosis

Prevention

Children with B19-induced red cell aplasia (transient aplastic crisis) are infectious when they present and demonstrate a

more intense viremia

↓

Isolation for at least 1 wk and until after resolution of fever

Prevention

• There are no data to support the use of IVIG for postexposure prophylaxis in pregnant caregivers or immunocompromised children

• No vaccine is available

KAWASAKI DISEASE

Kawasaki Disease

Mucocutaneous lymph node syndrome = infantile polyarteritis nodosa

Acute febrile vasculitis of childhood first described by Dr. Tomisaku Kawasaki in Japan in 1967.

Importance

• The disorder occurs worldwide, with Asians at highest risk

• Approximately 20% of untreated patients develop coronary artery abnormalities including aneurysms, with the potential for the development of coronary artery thrombosis or stenosis, myocardial infarction, aneurysm rupture, and sudden death

• Kawasaki disease has replaced acute rheumatic fever as the leading cause of acquired heart disease in children in the United States and Japan.

Etiology

Causative agent is still unknown

Features to support an infectious origin:

• Age group affected• Occurrence of periodic epidemics• Wavelike geographic spread of illness during the

epidemic• Self-limited nature of the illness• Clinical features of fever, rash, enanthem,

conjunctival injection, and cervical lymphadenopathy• Probable genetic predisposition • Probable passive maternal antibodies → seldom in

kids < than 4 mo• Absence in adults → widespread immunity

Epidemiology

• 3,000 cases are diagnosed annually in the United States

• The incidence of Kawasaki disease in Asian children is substantially higher than in other racial groups, but the illness occurs worldwide in all ethnic groups

• In Japan, more than 170,000 cases have been reported since the 1960s

Epidemiology

• Kawasaki disease is not a new illness; autopsy reports of infantile periarteritis nodosa before the 1960s appear in retrospect to have represented fatal Kawasaki disease.

• The illness occurs predominantly in young children; 80% of patients are younger than 5 yr, and only occasionally are teenagers and adults affected.

Pathogenesis

1. Severe vasculitis of all blood vessels, mostly medium-sized arteries (predilection for coronary arteries)

2. Edema & inflammatory infiltration of vascular wall (PMN, macrophages, lymphocytes and plasma cells)

3. In severe cases - all three layers are involved

Pathogenesis of vasculitis

Destruction of the internal elastic lamina↓

Lost of structural integrity and weakens ↓

Dilatation or aneurysm formation↓

Formation of thrombi ↓

Obstruction of blood flow

Pathogenesis of vasculitis

Healing phase:

Fibrosis: intimal proliferation

↓

Stenotic occlusion of the vessel

Clinical presentation • Fever 5 days and more • Bilateral conjunctivitis (without exudates) • Lips and mouth changes:

– Dryness, erythema and fissures of the lips– Strawberry tongue – Diffuse erythema of mouth and throat mucous

• Changes of hands and feet:– Erythema of hands and feet hands and feet – Indurative edema of erythema – Membranous desquamation, starting around the nails

• Polymorphous rash, mostly on the trunk • Acute non-purulent cervical lymphadenitis • Exclusion of other diseases

Particularities of fever

• High spiking (to 104°F or higher)

• Remittent

• Unresponsive to antibiotics

• Duration is 1–2 wk to 3–4 wk (without treatment)

• Prolonged fever → risk of coronary artery disease

Particularities of rash

• Rash of various forms (maculopapular, erythema multiforme, or scarlatiniform) with accentuation in the groin area

• Perineal desquamation (in acute phase)

• Periungual desquamation of the fingers and toes (1–3 wk after)

Other clinical presentation

Cardiological Pancarditis in acute phase Coronary arteries anomalies Heart failure

Neurological Extreme irritability Aseptic meningitis


Joints Arthritis Arthralgia

Gastro-intestinal

Diarrhea, vomiting, pain Mild hepatitisHydrops of the gallbladder


Respiratory Respiratory syndrome Otitis media Lung infiltrates

Others UrethritisSterile pyuria Edema of testes Periphery gangrene Hearing disturbances Aneurisms of non-coronary vessels of medium size

Particularities of arthritis

• More common in girls

• May occur early in the illness

• May develop during the 2nd–3rd week

• Generally affects hands, knees, ankles, or hips

Particularities of cardiac involvement

• Most important manifestation of Kawasaki disease

• Myocarditis (tachycardia and ↓ ventricular function) - 50% of patients

• Pericarditis (small pericardial effusion) - common during the acute phase

Particularities of coronary artery aneurysms

Up to 25% of untreated patients• During the 2nd–3rd wk of illness• Can be detected by two-dimensional

echocardiography • Giant coronary artery aneurysms (≥8mm

internal diameter) → greatest risk for rupture, thrombosis or stenosis, and myocardial infarction

__________________________________Valvular regurgitation and systemic artery

aneurysms may occur but are uncommon.

Course of Kawasaki disease

Three clinical phases:

1. Acute febrile phase

2. Subacute phase

3. Convalescent phase begins when all

Acute febrile phase

• 1–2 wk of duration

• Fever and the other acute signs of illness

Subacute phase

• Begins when fever and other acute signs have abated - lasts until about the 4th wk

• Irritability, anorexia, and conjunctival injection may persist

• Desquamation, thrombocytosis, the development of coronary aneurysms, and the highest risk of sudden death

Convalescent phase

• Begins when all clinical signs of illness have disappeared and continues until the erythrocyte sedimentation rate (ESR) returns to normal, approximately 6–8 wk after the onset of illness

Predictors of severe outcome• Male gender• Age < 1 yr• Prolonged fever• Recurrent fever after an afebrile period• Following laboratory values at presentation:• Low hemoglobin level• Low platelet level • High neutrophil and band counts• Low albumin level • Low age-adjusted serum IgG level

Diagnostic Criteria for Kawasaki Disease

• Presence of fever for at least 5 days + at least four of five of the other characteristic clinical features of illness

Diagnostic Criteria for Kawasaki Disease

1. Bilateral bulbar conjunctival injection, generally nonpurulent

2. Changes in the mucosa of the oropharynx, 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 nonvesicular5. Cervical adenopathy, =1.5cm, usually unilateral

lymphadenopathy6. Illness not explained by other known disease process

Diagnosis

Atypical or incomplete cases in which a patient has fever with fewer than four other features of the illness and then develops coronary artery disease have been described worldwide. Incomplete cases are most frequent in infants, who unfortunately have the highest likelihood of developing coronary artery disease.

Recognition depends on a high index of suspicion and knowledge of the characteristic clinical features of the illness.


• Scarlet fever• Toxic shock syndrome• Measles• Drug hypersensitivity reactions• Stevens-Johnson syndrome• Juvenile rheumatoid arthritis• Rocky Mountain spotted fever• Leptospirosis

Laboratory Findings

No specific diagnostic test for Kawasaki disease exists

Characteristic laboratory findings• White blood cell count is normal to elevated• Predominance of neutrophils and immature forms• Elevated ESR, C-reactive protein and other acute

phase reactants• Normocytic anemia• Platelet count: normal in the 1st wk and rapidly

increases by the 2nd–3rd wk, sometimes exceeding 1,000,000/mm3

Other laboratory findings

• Antinuclear antibody and rheumatoid factor are negative

• Sterile pyuria

• Mild elevations of the hepatic transaminases

• Cerebrospinal fluid pleocytosis

Frequency of Laboratory Findings

Finding Frequency Comments

Leukocytosis 100% Till 15*10*9, Bands increased

Anemia 50-90% Normochromic

Hypoalbuminemia 10-50%



Increased acute phase proteins

>90% ESR usually >35mm/h

Sterile pyuria 50-90% Can be intermittent

Proteinuria <10%



Transaminases elevation

50%

Bilirubin elevation

<10%

Arthritis 33% without treatment, 8% after Ig injection

Cytosis till 25 000/mm3, neutrophils predominate in 80% of patients



CSF cytosis 40% ≈ 20/mm3, 90% neutrophils, 10% mononuclears, protein and glucose are normal

Thrombocytosis >90% In subacute phase, 500 000 till 2 000 000/mm3

Two-dimensional echocardiography

Monitoring of coronary artery abnormalities:

Terms of performance:

1. At diagnosis

2. After 2–3 wk of illness

3. At 6–8 wk after onset of illness If normal → optional follow-up If abnormal → frequent echocardiographies

and potentially angiography

Treatment

ACUTE STAGE

• Intravenous immunoglobulin 2g/kg over 10–12hr

• Aspirin 80–100mg/kg/24hr divided every 6hr orally until 14th illness day

Treatment

CONVALESCENT STAGE

• Aspirin 3–5mg/kg once daily orally until 6–8 wk after illness onset (till ESR normalization)

Treatment

LONG-TERM THERAPY FOR THOSE WITH CORONARY ABNORMALITIES

• Aspirin 3–5mg/kg once daily orally ± dipyridamole 4–6mg/kg/24hr divided in two or three doses orally (most experts add warfarin for those patients at particularly high risk of thrombosis)

Treatment

ACUTE CORONARY THROMBOSIS

• Prompt fibrinolytic therapy with tissue plasminogen activator, streptokinase, or urokinase under supervision of a pediatric cardiologist

Comments

Patients receiving long-term aspirin therapy are candidates for influenza and VZV vaccines to reduce the risk of Reye syndrome

Intravenous immunoglobulin (IVIG) treatment

• Rapid defervescence and resolution of clinical signs

• Reduce of coronary disease risk from 20–25% in children treated with aspirin alone to 2–4% in those treated with IVIG and aspirin

• Should be administered within the first 10 days of illness

Treatment of non-responders

Non-responders to initial IVIG infusion

↓

Additional infusion of IVIG, 2g/kg

↓

Non-responders to initial IVIG infusion

↓

Cautious use of corticosteroids

Patients with aneurysms

Evaluation: echocardiography stress testing possibly angiographyTreatment: Catheter intervention with percutaneous

transluminal coronary rotational ablation Directional coronary atherectomy Stent implantation

Prognosis

• Depends on coronary disease severity• In Japan, fatality rates are now < 0.1%• 50% of coronary artery aneurysms resolve

within 1–2 yr after illness• Giant aneurysms are unlikely to resolve

and are most likely to lead to thrombosis or stenosis

• Coronary artery bypass grafting may be required

We are done!!!

exanthemas

Health & Medicine

infectious origin of

types of rash

roseolar rash roseola

erythema rash erythema

skin enanthema rash

macular rash macule

group of diseases

groups of diseases