Approach to the Approach to the clinical syndrome of clinical syndrome of rash & feverrash & fever

The clinical syndrome of fever & rash presents a The clinical syndrome of fever & rash presents a challenging & often urgent diagnostic problem.challenging & often urgent diagnostic problem.

Since a wide variety of disease can present in Since a wide variety of disease can present in this manner, the pediatrician must have both a this manner, the pediatrician must have both a complete grasp of the differential diagnosis & complete grasp of the differential diagnosis & the ability to recognize specific disease the ability to recognize specific disease entities, especially those that are potentially entities, especially those that are potentially life-threatening.life-threatening.

So for the simplicity, we have subdivided So for the simplicity, we have subdivided into four main categories:into four main categories:

1.1. Fever and Petechiae Fever and Petechiae

2.2. Rickettsial Infections Rickettsial Infections

3.3. Lyme diseaseLyme disease

4.4. Major childhood viral exanthemsMajor childhood viral exanthems

Fever and Petechiae Fever and Petechiae

.-Petechiae, which are caused by .-Petechiae, which are caused by extravasation of red blood cells, are non- extravasation of red blood cells, are non- blanching erythematous macular skin blanching erythematous macular skin lesions 1 mm or greater in size .lesions 1 mm or greater in size .

- Febrile infants and children with a - Febrile infants and children with a petechial rash raise the concern of petechial rash raise the concern of invasive bacterial infection caused by invasive bacterial infection caused by Neisseria meningitidisNeisseria meningitidis or other organisms or other organisms

Epidemiology Epidemiology

2% to 20% of children with fever and 2% to 20% of children with fever and petechiae have invasive infectionpetechiae have invasive infection

risk highest if under 2 years old or ill risk highest if under 2 years old or ill appearing.appearing.

Etiology Etiology

BacterialBacterial:: N. meningitidis, Streptococcus N. meningitidis, Streptococcus pneumoniae, Haemophilus influenzaepneumoniae, Haemophilus influenzae type B, type B, Escherichia coliEscherichia coli

ViralViral:: Influenza, parainfluenza, enteroviruses, Influenza, parainfluenza, enteroviruses, EpsteinEpstein--Barr virus Barr virus ((EBVEBV)), dengue, adenovirus, , dengue, adenovirus, respiratory syncytial virus, rotavirusrespiratory syncytial virus, rotavirus

Other infectionsOther infections:: Rocky Mountain spotted Rocky Mountain spotted fever fever ((RMSFRMSF)), ehrlichiosis, scarlet fever , ehrlichiosis, scarlet fever

Differential Diagnosis Differential Diagnosis

Drug eruptionDrug eruption Acute leukemiaAcute leukemia Subacute bacterial endocarditisSubacute bacterial endocarditis Cough/emesis Cough/emesis

HistoryHistory //Physical Physical Examination Examination Close exposure to someone with Close exposure to someone with

meningococcemia.meningococcemia. Serious findings include fever, headache, severely Serious findings include fever, headache, severely

ill appearing, mental status changes, signs of ill appearing, mental status changes, signs of compensated shock (unexplained tachycardia, compensated shock (unexplained tachycardia, widened pulse pressure, bounding pulses)widened pulse pressure, bounding pulses)

Important considerations:Important considerations: What is the What is the distribution? Is the rash along the course of distribution? Is the rash along the course of the superior vena cava secondary to the superior vena cava secondary to vomiting or cough? Did the petechiae occur vomiting or cough? Did the petechiae occur after tourniquet application? Is there after tourniquet application? Is there evidence of pharyngitis or scarlet fever with evidence of pharyngitis or scarlet fever with petechiae only above the nipple line? petechiae only above the nipple line?

Rickettsial Infections Rickettsial Infections Rickettsial infections are categorized as Rickettsial infections are categorized as

followsfollows:: Spotted fever groupSpotted fever group: : Rickettsial pox Rickettsial pox

((Rickettsia akariRickettsia akari)); scrub typhus ; scrub typhus ((RickettsiaRickettsia and and tsutsugamushitsutsugamushi)); Rocky Mountain spotted fever ; Rocky Mountain spotted fever ((Rickettsia rickettsiiRickettsia rickettsii))

Typhus groupTyphus group: : Endemic typhus Endemic typhus ((Rickettsia Rickettsia typhityphi) () (murine or fleamurine or flea--borne typhusborne typhus)); epidemic ; epidemic typhus typhus ((Rickettsia prowazekiiRickettsia prowazekii) () (louselouse--borne borne typhustyphus))

MiscellaneousMiscellaneous: : Ehrlichiosis Ehrlichiosis ((EhrlichiaEhrlichia speciesspecies)); Q fever ; Q fever ((Coxiella burnetiiCoxiella burnetii) )

Epidemiology Epidemiology Most RMSF infections are in South Atlantic Most RMSF infections are in South Atlantic

coastal, western, and south central statescoastal, western, and south central states RMSF usually occurs from April to September, RMSF usually occurs from April to September,

ehrlichiosis from May to July ehrlichiosis from May to July

Risk Factors Risk Factors Exposure to arthropod vectors: Ticks, mites, Exposure to arthropod vectors: Ticks, mites,

fleas.fleas. Exposure to dogs, wild rodents, rabbits, and Exposure to dogs, wild rodents, rabbits, and

opossums opossums

PathogenesisPathogenesis

Rickettsiae are obligate intracellular pathogens. Rickettsiae are obligate intracellular pathogens. Humans are incidental host.Humans are incidental host.

Systemic capillary and small vessel endothelial Systemic capillary and small vessel endothelial damage results in vasculitis and shock damage results in vasculitis and shock

HistoryHistory //Physical Physical Examination Examination Suspect rickettsial infections in those with flulike illness in Suspect rickettsial infections in those with flulike illness in

spring or summer.spring or summer. High fever, severe frontal headache, malaise, myalgias, and High fever, severe frontal headache, malaise, myalgias, and

vomiting.vomiting. Rash appears 2 to 3 days (range 1 to 14 days) after the onset Rash appears 2 to 3 days (range 1 to 14 days) after the onset

of illness; more likely with RMSF than with ehrlichia.of illness; more likely with RMSF than with ehrlichia. Rash starts on the wrists and ankles and then the palms and Rash starts on the wrists and ankles and then the palms and

soles, face, and trunk It progresses from macular to papular to soles, face, and trunk It progresses from macular to papular to petechial to purpuric.petechial to purpuric.

Hepatomegaly, meningismus, decreased breath sounds with Hepatomegaly, meningismus, decreased breath sounds with rales.rales.

A necrotic eschar ("tache noir" or "black spot"; 30% to 90% of A necrotic eschar ("tache noir" or "black spot"; 30% to 90% of patients) originates at the site of the bite. Look for this in the patients) originates at the site of the bite. Look for this in the scalp with associated regional lymphadenopathy scalp with associated regional lymphadenopathy

Lab Studies Lab Studies Leukopenia, thrombocytopenia, elevated serum Leukopenia, thrombocytopenia, elevated serum

hepatic transaminases, hyponatremia.hepatic transaminases, hyponatremia. Fourfold rise in specific acute and convalescent Fourfold rise in specific acute and convalescent

antibodies by indirect fluorescent antibody assay antibodies by indirect fluorescent antibody assay ((sensitivity greater than 90%sensitivity greater than 90%). ). Antibodies detectable 7 Antibodies detectable 7 to 14 days after onset.to 14 days after onset.

EhrlichiosisEhrlichiosis: : Light microscopy of blood smear reveals Light microscopy of blood smear reveals morulae in neutrophil cytoplasm morulae in neutrophil cytoplasm ((50% of cases).50% of cases).

RMSFRMSF: : If rash present, immunofluorescence or If rash present, immunofluorescence or immunoperoxidase staining of skin biopsy reveals immunoperoxidase staining of skin biopsy reveals RR. . rickettsiirickettsii in vascular endothelium in vascular endothelium ((sensitivity 70% to sensitivity 70% to 90%90%))

Polymerase chain reaction Polymerase chain reaction ((PCRPCR) ) assay available in assay available in some research settings some research settings

Differential Diagnosis Differential Diagnosis

MeaslesMeasles Meningococcemia.Meningococcemia. Secondary syphilis.Secondary syphilis. Viral infections Viral infections ((especially especially

enteroviruses).enteroviruses). Infectious mononucleosis Infectious mononucleosis

Management Management

Early suspicion and prompt therapy is Early suspicion and prompt therapy is vital to a good outcome.vital to a good outcome.

Treat with doxycycline or tetracycline for Treat with doxycycline or tetracycline for 5 to 7 days5 to 7 days

In patients allergic to tetracycline class, In patients allergic to tetracycline class, consider rifampin or fluoroquinolones for consider rifampin or fluoroquinolones for ehrlichiosis and chloramphenicol or ehrlichiosis and chloramphenicol or fluoroquinolones for RMSFfluoroquinolones for RMSF. .

Complications Complications

Venous thrombosisVenous thrombosis PneumonitisPneumonitis PericarditisPericarditis MyocarditisMyocarditis Pleural effusions Pleural effusions

Lyme diseaseLyme disease

Epidemiology Epidemiology The most common vector-borne disease The most common vector-borne disease

in the United Statesin the United States Most cases in June, July, and August.Most cases in June, July, and August. Peak incidence is at age 5 to 14 years Peak incidence is at age 5 to 14 years

Risk Factors Risk Factors

Borrelia burgdorferiBorrelia burgdorferi lives in tick midgut so lives in tick midgut so infection requires more than 24 to 36 infection requires more than 24 to 36 hours of attachment.hours of attachment.

Environment riskEnvironment risk: Region, climate, : Region, climate, landscape, and close association with landscape, and close association with wildlife.wildlife.

Behavioral riskBehavioral risk: Woodcutting, outdoor : Woodcutting, outdoor activities (more than 30 hours per week) activities (more than 30 hours per week)

Etiology Etiology Lyme disease caused by the spirochete Lyme disease caused by the spirochete B. B.

burgdorferiburgdorferi and transmitted by and transmitted by IxodesIxodes ticks ticks

Pathogenesis Pathogenesis Stage l:Stage l: Localized erythema migrans (EM) Localized erythema migrans (EM)

rash. After the bite, the rash. After the bite, the B. burgdorferiB. burgdorferi organisms spread superficially through the skin organisms spread superficially through the skin and tissue.and tissue.

Stage 2:Stage 2: Early dissemination follows stage 1 Early dissemination follows stage 1 within days or weeks; may result in multiple within days or weeks; may result in multiple skin lesions (disseminated EM) or affect the skin lesions (disseminated EM) or affect the joints, nervous system, or heart.joints, nervous system, or heart.

Stage 3:Stage 3: Late dissemination (affects joints) Late dissemination (affects joints) follows stage within weeks or months.follows stage within weeks or months.

History History History of rash with a slowly expanding skin History of rash with a slowly expanding skin

lesion (EM)lesion (EM) The skin lesion may be accompanied by a The skin lesion may be accompanied by a

history of flulike symptoms (malaise, fatigue, history of flulike symptoms (malaise, fatigue, headache, arthralgias, myalgias, fever, regional headache, arthralgias, myalgias, fever, regional lymphadenopathy) lymphadenopathy)

Physical Examination Physical Examination

Stage 1Stage 1 Rash of EM (more than 5 cm in Rash of EM (more than 5 cm in

diameter).diameter). Usually macular, but may be slightly Usually macular, but may be slightly

raised with occasional central ulceration. raised with occasional central ulceration.

Stage 2Stage 2 NeurologicNeurologic:: Lymphocytic meningitis; subtle Lymphocytic meningitis; subtle

encephalitis; cranial neuropathies encephalitis; cranial neuropathies ((unilateral or unilateral or bilateral, especially 7thbilateral, especially 7th)); optic nerve ; optic nerve involvement leading to blindness involvement leading to blindness ((more more common in childrencommon in children)); motor or sensory ; motor or sensory radiculoneuritis; cerebellar ataxia radiculoneuritis; cerebellar ataxia

Cardiac:Cardiac: Commonly atrioventricular block; Commonly atrioventricular block; occasionally acute myopericarditis; rarely occasionally acute myopericarditis; rarely cardiomegaly or pancarditis - Occurs in 5% of cardiomegaly or pancarditis - Occurs in 5% of untreated patients untreated patients

Joint involvementJoint involvement: Arthritis (knee most : Arthritis (knee most commonly) commonly)

Stage 3Stage 3 Prolonged neurologic abnonnalities including Prolonged neurologic abnonnalities including

motor or sensory radiculoneuritis, cerebellar motor or sensory radiculoneuritis, cerebellar ataxia, subacute encephalopathy, memory ataxia, subacute encephalopathy, memory impainnent, sleep disturbances impainnent, sleep disturbances

Lab Studies Lab Studies If EM is found, no laboratory testing needed.If EM is found, no laboratory testing needed. Antibody testingAntibody testing: Initial testing by ELISA to : Initial testing by ELISA to B. B.

burgdorferiburgdorferi, If IgM or IgG positive, confirm by , If IgM or IgG positive, confirm by Western blotting. ELISA alone has high false-Western blotting. ELISA alone has high false-positive ratepositive rate

PCR of joint fluid (usually not needed) for PCR of joint fluid (usually not needed) for diagnosis of Lyme arthritisdiagnosis of Lyme arthritis

CSF antibodies may be diagnostic of Lyme CSF antibodies may be diagnostic of Lyme meningitis, CSF PCR test has poor sensitivity meningitis, CSF PCR test has poor sensitivity

Differential Diagnosis Differential Diagnosis

EMEM--like rashlike rash: : Tinea corporis, insect bite, Tinea corporis, insect bite, eczema, cellulitis, erythema multiformeeczema, cellulitis, erythema multiforme

Rash and arthritisRash and arthritis: : Serum sickness, Serum sickness, juvenile rheumatoid arthritis, acute juvenile rheumatoid arthritis, acute rheumatic fever, systemic lupus rheumatic fever, systemic lupus erythematosuserythematosus

MeningitisMeningitis//neurologic abnormalitiesneurologic abnormalities

Management Management Stage I-EMStage I-EM:: Older than 8 years, doxycycline; 8 years or younger Older than 8 years, doxycycline; 8 years or younger

( or pregnancy), amoxicillin ( or pregnancy), amoxicillin Treat for 14 to 21 days, Alternate for allergy use Treat for 14 to 21 days, Alternate for allergy use

cefuroxime or macrolide cefuroxime or macrolide Stages 2 and 3Stages 2 and 3 Disseminated EM or isolated Bell palsy: Same as for Disseminated EM or isolated Bell palsy: Same as for

stage Istage I Arthritis: Same as for stage I but treat for 28 days, Arthritis: Same as for stage I but treat for 28 days,

Some require ceftriaxoneSome require ceftriaxone Meningitis, other neurologic involvement, or carditis: Meningitis, other neurologic involvement, or carditis:

Ceftriaxone for 21 to 28 days Ceftriaxone for 21 to 28 days

Complications Complications

Untreated localized disease may Untreated localized disease may progress to early or late dissemination progress to early or late dissemination

Major childhood viral Major childhood viral exanthemsexanthems

Major childhood exanthems cause Major childhood exanthems cause systemic illness and a characteristic rashsystemic illness and a characteristic rash

ExanthemsExanthems: : Blanching macular or Blanching macular or papular lesions papular lesions ((less than 1 an in less than 1 an in diameterdiameter))

MorbillifonnMorbillifonn: : Lesions that coalesce Lesions that coalesce ((ee..gg.., , measlesmeasles))

ScarlatinifonnScarlatinifonn: : Lesions with a sandpaper Lesions with a sandpaper feel on palpation feel on palpation ((e,ge,g.., scarlet fever, scarlet fever) )

Etiology Etiology Enteroviruses are most common causeEnteroviruses are most common cause Bacterial causes include group A Bacterial causes include group A

Streptococcus, Staphylococcus aureus,Streptococcus, Staphylococcus aureus, and and Arcanobacterium haemolyticumArcanobacterium haemolyticum

PathogenesisPathogenesis

Most commonly either Most commonly either

11) ) infection of the dermal blood vessel infection of the dermal blood vessel endothelium endothelium ((ee..gg" " measlesmeasles) ) or or

22) ) host immunologic reaction against the host immunologic reaction against the pathogen pathogen ((ee..gg.., parvovirus BI9, parvovirus BI9))

Circulating toxins cause the Circulating toxins cause the scarlatiniform exanthem in scarlatiniform exanthem in S. pyogenesS. pyogenes and and SS. . aureusaureus

HistoryHistory //Physical Physical Examination Examination

Exposure to person with similar illness or Exposure to person with similar illness or pets/animals; recent travel; pets/animals; recent travel; immunizationsimmunizations

Elicit prodromal symptoms and where Elicit prodromal symptoms and where rash started and pattern of spread rash started and pattern of spread

Lab Studies Lab Studies In well-appearing children with fever and exanthema, a careful In well-appearing children with fever and exanthema, a careful

history and examination often leads to the correct diagnosis history and examination often leads to the correct diagnosis without the need for further studies without the need for further studies

Measles: Serology, measles-specific IgMMeasles: Serology, measles-specific IgM Rubella: Serology, rubella-specific IgM; culture from nasal Rubella: Serology, rubella-specific IgM; culture from nasal

specimenspecimen Human herpes virus 6 (HHV-6): Testing not available, com- Human herpes virus 6 (HHV-6): Testing not available, com-

mercial antibody and PCR reaction assays in developmentmercial antibody and PCR reaction assays in development Parvovirus B 19: Serology, parvovirus-specific IgM; PCR in Parvovirus B 19: Serology, parvovirus-specific IgM; PCR in

immunocompromisedimmunocompromised EBV: Serology, EBV-spedfic antibody profile; PCR in EBV: Serology, EBV-spedfic antibody profile; PCR in

immunocompromisedimmunocompromised Enteroviruses: Culture blood/urine early; PCR blood, urine, CSFEnteroviruses: Culture blood/urine early; PCR blood, urine, CSF Adenovirus: Culture and rapid antigen detection on secretions; Adenovirus: Culture and rapid antigen detection on secretions;

PCR blood/urine PCR blood/urine

Management Management

Most childhood exanthems are benign Most childhood exanthems are benign and self-limited, and resolve within and self-limited, and resolve within several daysseveral days

For streptococcal pharyngitis, penicillin or For streptococcal pharyngitis, penicillin or amoxicillin for 10 days amoxicillin for 10 days