Fever and rash in children

Fever and rash in children Microchapters
Overview
Classification
Pathophysiology
Causes
Epidemiology and Demographics
Risk Factors
Natural History, Complications, and Prognosis
Diagnosis
Treatment

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ifeoma Anaya, M.D.[2]

Synonyms and keywords: Fever and rash in kids

Overview

Fever and rash are symptoms commonly encountered in pediatrics. Disease states associated with these symptoms are varied. Therefore, a broad knowledge of these diseases is extremely invaluable. Febrile rashes can be classified based on morphology, distribution of spread, pattern of occurrence and cause. Fever results when exogenous (micro-organisms) and endogenous pyrogens interact with the Organum Vasculosum of the Lamina Terminalis (OVLT) causing a rise in body temperature as a result of an increase in the hypothalamic set point. This rise in the hypothalamic set point is due to the increased production of Prostaglandin E2 (PGE2) by endothelial cells of the vascular OVLT located in the preoptic area of the anterior hypothalamus. Fever and rash in kids are caused by infectious (bacterial, viral, fungal, and protozoan) and non-infectious (drug-related eruptions and immune-mediated) causes. Patients of all age groups may develop diseases that present with fever and rash. Most children become susceptible to some of the diseases from 6 months of age when maternal antibodies begin to wane. Common risk factors for the development of diseases that present with fever and rash include contact with ill individuals, poor/depressed immunity, lack of vaccination, very young age (6 months-12 months) and poor hand washing habits.

Classification

• Febrile rashes can be classified based on:
  • Morphology (maculopapular, pustular, vesicular, etc)
  • Distribution of spread (systemic and localized
  • Pattern of occurrence (acute and chronic)
  • Cause (infectious and non-infectious)
• Types of rashes found among pediatric patients include the following: macules, papules, nodules, pustules, vesicles, bullae, petechiae, purpura and ecchymoses.
• Classification of febrille rashes based on rash morphology are as follows:

Fever + Rash Morphology	Disease
Non-blanching lesions (Petechiae, Purpura and Ecchymoses)	a. Meningococcemia b. Rocky Mountain Spotted Fever (RMSF) c. Hemolytic Uremic Syndrome (HUS) d. Henoch-Schonlein Purpura (HSP)
Blanching rash	a. Kawasaki disease b. Juvenile Rheumatoid Arthritis c. Juvenile Dermatomyositis
Vesicular or bullous lesions	a. Erythema multiforme b. Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) c. Staphylococcal Scalded Skin Syndrome (SSSS) d. Disseminated gonococcal disease in adolescents e. HSV I & II
Umbilicated papules and pustules	a. Molluscum contagiosum b. Varicella/Chickenpox
Sandpaper rash	a. Scarlet fever
Viral syndromes(mostly maculopaular)	a. Measles (Rubeola) b. Rubella (German measles) c. Erythema infectiosum (Parvovirus B19) d. Herpangina (Coxsackie) e. Hand-foot-and-mouth disease (Coxsackie) f. Roseola infantum (Human Herpes Virus types 6 or 7)
Limited to certain geographical areas	a. Babesiosis b. Blastomycosis c. Coccidiodomycosis d. Histoplasmosis e. Lyme disease f. Relapsing fever g. Colorado Tick Fever

Pathophysiology

• When core body temperatures vary outside normal ranges, thermoregulatory responses are triggered.
• It is understood that infectious processes accounts for up to 74% of fever in hospitalized patients, the remainder being caused by malignancy, ischemia and drug-related reactions.
• Fever results when exogenous (micro-organisms) and endogenous pyrogens interact with the Organum Vasculosum of the Lamina Terminalis (OVLT) causing a rise in body temperature as a result of an increase in the hypothalamic set point.
• This rise in the hypothalamic set point is due to increased production of Prostaglandin E2 (PGE2) by endothelial cells of the vascular OVLT located in the preoptic area of the anterior hypothalamus. It lacks the Blood-Brain-Barrier (BBB) thus easily accessible to pyrogens. This resultant increased production of PGE2 results in raised body temperature.
• Lipopolysaccharide (LPS) on gram negative bacteria is a common exogenous pyrogen which stimulates the production of endogenous cytokines such as (Interleukin[IL]-1, IL-6 and Tumor Necorsis Factor[TNF]-α) via the Toll-like receptor (TLRs) cascade.
• PGE2 production can also be stimulated via the vagus nerve by inflammatory processes and directly by microbial products through TLRs.
• Skin lesions (rash) could be primarily vascular or from infection spread to tissues (e.g. skin).
• The first step in the formation of a skin lesion/rash is the presence of the micro-organism in the vascular endothelium.
• A macule forms from sustained local dilation of subpapilary dermal blood vessels.
• Edema with infiltration of cells turns a macule to papule.
• Primary epidermal involvement results in vesicles, ulcers and scabs and secondary epidermal changes can lead to desquamation and pigment changes.

Causes

• Common causes of fever and rash in kids may include:

Infectious	Disease	Causative Organism
Viral	Measles German Measles Erythema infectiosum Roseola infantum Herpangina Hand-foot-and-mouth disease Molluscum contagiosum Chickenpox	Rubeola Rubella Parvovirus B19 Human Herpes Virus 6 & 7 Coxsackie virus Coxsackie virus Poxvirus Varicella Zoster virus
Bacterial	Meningococcemia	Neisseria meningitidis Hemophilus influenzae Streptococcus pneumoniae
	RMSF	Rickettsia rickettsii
	HUS	Enterohemorrhagic E.coli (EHEC)
	Scarlet Fever	Streptococcus pyogenes (Group A Streptococci, GAS)
	Disseminated gonococcal disease in adolescents	Neisseria gonorrhoea
	SSSS TSS	Staphylococcus aureus
	Lyme disease	Borrelia burgdorferi
	Relapsing fever	Borrelia recurrentis
Protozoan	Babesiosis	Babesia microti
Fungal	Histoplasmosis Blastomycosis Coccidiodomycosis Paracoccidiodomycosis	Histoplasma capsulatum Blastomyces dermatitidis Coccidioides immitis Paracoccidioides brasiliensis

Non-Infectious	Disease
Immune-mediated/Autoimmune	Kawasaki Disease Henoch-Schonlein Purpura Juvenile Rheumatoid Arthritis Juvenile Dermatomyositis
Drug-related eruptions	Erythema multiforme SJS TEN

Epidemiology and Demographics

Age

• Patients of all age groups may develop diseases that present with fever and rash.

Race

• There is no racial predilection to diseases that present with fever and rash.

Gender

• No known gender predilection.

• Most children become susceptible to some of the diseases from 6 months of age when maternal antibodies begin to wane.

Risk Factors

• Common risk factors for the development of diseases that present with fever and rash include:
  • Contact with ill individuals
  • Poor/depressed immunity
  • Lack of vaccination
  • Very young age (6 months-12 months)
  • Poor hand washing habits

Natural History, Complications, and Prognosis

Natural History

• The symptoms of diseases associated with fever and rash usually develop in the first few days from contact. The stages/phases of most infectious processes include the:
  • Incubation period (between exposure to an infection and the appearance of the first symptoms).
  • Prodromal phase (period of early symptoms of a disease)
  • Illness (characteristic symptoms of the disease appear at this stage)
  • Decline and
  • Convalescence

Complications

• Common complications of diseases presenting with fever and rash include:
  • Febrille seizures
  • Rhabdomyolysis
  • Shock (septic or hypovolemic)
  • Disseminated Intravascular Coagulation (in Meningococcemia)
  • Reye syndrome (especially in children that have been given aspirin).

Prognosis

• Prognosis is generally excellent for viral syndromes. Prompt diagnosis, treatment and close follow-up of patients presenting with other causes of fever and rash also results in good prognosis.

Diagnosis

• Rapid clinical diagnosis is necessary in severe cases to begin immediate empiric therapy while awaiting test results.

Symptoms

• Besides fever and rash, additional symptoms may include:
  • Cough
  • Sore throat
  • Runny nose
  • Red eyes (conjunctivitis)
  • Irritability
• The above additional symptoms are usually seen in the prodromal phase of most infectious diseases. Other symptoms are:
  • Recent upper respiratory tract infections or diarrheal illness
  • Earpain
  • Pruritus (which could be severe in drug related rashes)
  • Poor appetite
  • Headaches
  • Diarrhea
  • Pallor
  • Pains in certain body areas (arthritis)
• Important details in the history include:
  • Onset and progression of symptoms
  • Site of the rash(central or peripheral)
  • Relation with season(s)
  • Travel history
  • tick bite(s)
  • Contact with an ill person or animal
  • Medication history (most especially sulfonamides, NSAIDs and anticonvulsants)
  • Exposure to forest or other natural environment
  • Also important to evaluate the immune status of the patient

Physical Examination

• Findings on examination include:
  • Illness severity
  • Type of rash, its location and distribution
  • Lymphadenopathy
  • Conjuctival, oral and genital changes
  • Nuchal rigidity (especially in older kids)
  • Nikolsky's sign
  • Areas of tenderness (e.g. at the joints)
  • Hepatomegaly, splenomegaly
  • Hypotension
  • Tachycardia

Laboratory Findings

• Laboratory findings needed to support diagnosis or determine illness severity of some diseases are as follows:
  • Complete blood count with differentials which might reveal anemia, thrombocytopenia, elevated white blood cell count.
  • Factor assays showing low coagulation factors in severe Meningococcemia with Disseminated Intravascular Coagulation (DIC)
  • Serum chemistries: electrolyte imbalance in (HUS, Meningococcemia)
  • Labs to isolate offending organisms in infectious diseases for targeted antibiotics regimen are;
    • Nasal/throat swab for rapid strep test and/or culture
    • Blood cultures
    • Stool and urine microscopy/culture/sensitivity
    • Cerebrospinal fluid (CSF) analysis
    • Antibody and PCR assays- RMSF
    • Skin biopsy of lesions in HSP showing leukocytoclastic vasculitis
    • Immunofluorescence
• Immunohistochemistry for diagnosing Systemic mycoses (fungal infections related to certain geographical areas).
• The viral syndromes, Varicella, Molluscum contagiosum, Lyme disease, the Immune-mediated vasculitis and Drug related eruptions rely heavily on a good history and physical examination findings to make a diagnosis.
• Peripheral thick and thin blood smear shows Babesia microti.

Electrocardiogram

• There are no ECG findings associated with fever and rash.

X-ray

• Might be useful in managing severely ill individuals to look for complications but not routinely needed to make diagnosis.

Echocardiography or Ultrasound

• There are no echocardiography findings associated with fever and rash but can be used to monitor for coronary aneurysm in a patient with Kawasaki disease.

CT scan

• There are no CT scan findings associated with any of the diseases.

MRI

• There are no MRI findings associated with fever and rash.

Other Imaging Findings

• There are no other imaging findings associated with fever and rash in children.

Treatment

Medical therapy

• Triaging kids who present with fever and rash into 3 groups on basis of early symptoms and signs is essential for making prompt diagnosis and administering possible treatment regimen. These groups are:
  • Children presenting with severe illness necessitating immediate intervention. This is especially true for the non-blanching lesions.
  • Children presenting with viral syndromes which are easily recognized and require symptomatic treatment and reassurance.
  • Children presenting undifferentiated rashes which could be benign or an unusual presentation of severe illness.
• The first group are usually managed in the hospital with intravenous fluid therapy with/without vasopressor, initiation of empirical antibiotics while awaiting culture results. Third generation Cephalosporin are first line for meningococcemia. Doxycycline is drug of choice for RMSF. Treatment for HUS is supportive with a consultation to the Nephrologist to manage renal failure.
• The second group as earlier mentioned is managed conservatively with measures like antipyretics, fluid therapy, antihistamines to soothe the patient and reassurance to care-givers. Most recover without any complications.
• Majority of children in this group have benign viral illness that resolves spontaneously. Others may have unusual presentations of serious illness and would require close monitoring with further evaluation and easy access to care. Maybe sometimes needful to admit.
• In general, most bacterial diseases are treated with the appropriate antibiotics, antifungal therapy for diseases of fungal origin, viral syndromes tend to resolve spontaneously with symptomatic treatment, drug related eruption require cessation of offending drug with adequate treatment of symptoms and fluid therapy.

Surgery

• Surgical intervention is not recommended for the management of fever and rash in children.

Prevention

• Effective measures for primary prevention of fever and rash in children may include:
  • Vaccination done in a timely manner can prevent occurrence of many childhood illnesses presenting with fever and rash such as the viral symdromes.
  • Hand washing frequently and thoroughly with soap and water.
  • Sneeze and cough into elbows and/or tissues(which should be thrown away).
  • Avoid contact with infected individuals and contaminated surfaces.
  • Wearing clothes to cover upper and lower limbs preventing tick bites.