Fever and Rash Case File

Fever and Rash Case File

Eugene C. Toy MD, Donald Briscoe, MD, FA  AFP, Bruce Britton, MD, Joel J. Heidelbaugh, MD, FA  AFP, FACG

Case 48

An 18-month-old girl is brought to the office by her mother for an acute visit because of a rash. She had a subjective high fever for the past 3 days, along with some mild respiratory symptoms of cough and rhinorrhea. She was given acetaminophen for the fever, but no other medications. The fever has gone down in the past day, but today she developed an erythematous rash that developed suddenly starting on the trunk and spread to the extremities. The child has no significant medical history and no known sick contacts, although she attends day care 3 days a week. On examination, she is mildly fussy but is easily consolable in her mother's lap. On examination, her rash in the areas mentioned above consists of small macules and pa pules that blanch on palpation. The remainder of her examination is unremarkable.

⯈ What is the most likely diagnosis?

⯈ What is the most likely cause of this illness?

⯈ What is the appropriate treatment?

ANSWER TO CASE 48

Fever and Rash

Summary: An 18-month-old girl is brought in for evaluation of a rapidly spreading rash that started after 3 days of fever. She has diffuse, blanching, erythematous macules and papules but otherwise appears well.

• Most likely diagnosis: Roseola
• Most likely cause of the illness: Human herpes virus 6 (HHV-6)
• Treatment: Supportive care only, as the rash is likely to completely resolve in 24 to 48 hours

ANALYSIS

Objectives

1. Be able to identify common rashes associated with viral infections in children.
2. Know the appropriate management of febrile illness associated with rashes in children.

Considerations

This toddler has a history of fever, and rash that is diffuse, erythematous macules and papules. The rash is most likely due to roseola, caused by HHV-6. HHV-6 is a ubiquitous virus that infects most children between 6 months and 3 years, although most infections are asymptomatic. The virus has an incubation period of 1 to 2 weeks and causes a prodromal illness associated with mild respiratory symptoms and a sudden high fever (39°C-40°C), which in rare cases can cause febrile seizures. After a few days of inoculation, the fever typically resolves and the erythematous rash appears.

Approach To:

Fever and Rash

DEFINITIONS

ENANTHEM: An eruption on a mucous membrane as a symptom of a disease

EXANTHEM: An eruption on the skin as a symptom of a disease

CLINICAL APPROACH

Febrile illness and rashes are extremely common presentations in family medicine and pediatric offices. In most cases, these presentations represent mild, self-limited illnesses that require no specific therapy. However, some cases will represent serious infections that require urgent intervention. Rashes associated with fever may be caused by viruses, bacteria, spirochetes, drug reaction, or autoimmune diseases.

The patient history should attempt to identify any exposures that may cause these syndromes, focusing on duration of the illness, other associated constitutional symptoms, sick contacts, history of recent travel, use of medications, or exposure to animals and insects ( eg, ticks). A review of immunization status is critical, as many diseases preventable by vaccines can cause fever and rash. Immunization does not always guarantee complete lifelong immunity, but should confer a less severe presentation of the disease.

A thorough physical examination with a complete skin examination should be performed. Examination findings can both lead to a specific diagnosis and identify complications of the causative agent. For example, the presence of exudative pharyngitis along with fever and rash may suggest scarlet fever caused by a group A Streptococcus infection, while wheezes or rhonchi on lung examination in a patient with crops of vesicles at different stages may lead to a diagnosis of varicella (chicken pox) complicated by pneumonitis.

The ability to accurately describe skin lesions is necessary for classification and in forming a differential diagnosis. Understanding the definitions of macules, papules, pustules, and vesicles allows for increased accuracy in diagnosis and ability to cogently discuss challenging cases with colleagues. See Case 13 for definitions of many of the terms used to describe common skin lesions.

COMMON VIRAL INFECTIONS

Roseola

Human herpes virus 6 is a ubiquitous virus that infects most children before the age of 3, although most infections are asymptomatic. The virus has an incubation period of 1 to 2 weeks and causes a prodromal illness associated with mild respiratory symptoms and a high fever that can range from l0l°F to l06°F (37.9°C to 41.1°C). This prodromal illness typically does not last for longer than 5 days. Following defervescence, a characteristic erythematous maculopapular rash appears suddenly on the trunk and spreads rapidly to the extremities, with sparing of the face. The rash commonly disappears in 1 to 2 days. The diagnosis is primarily clinical, based on the history and examination. Due to the short-lived nature of the disease, no treatment is usually required other than reassurance.

Varicella

The varicella zoster virus is a highly contagious virus that causes two clinical syndromes, chicken pox and shingles (zoster). Chicken pox is the more common childhood infection, but can also occur in adolescents and adults, can cause severe disease and complications in adult cases, and is seen more commonly in winter or early spring months. A typical case of chicken pox in children begins with the development of a rash in clusters followed by malaise, fever (38°C-42°C), and anorexia. The initial exanthem is often papules or vesicles on an erythematous base, described as "dewdrops on a rose petal:' The vesicles then progress to shallow, crusted erosions and ulcerations. Patients may also develop enanthems, with lesions on the oral, nasal, or gastrointestinal mucosa. In rare cases, serious complications may develop, which include encephalitis, meningitis, and pneumonitis.

Superinfection of the vesicles with bacteria, most commonly group A Streptococcus and Staphylococcus aureus, is a particularly common and potentially dangerous complication. The contagious period continues 4 to 5 days after the appearance of the rash or until all lesions have crusted over. It takes an average of 10 to 21 days after contact with an infected person for someone to develop chicken pox. The diagnosis of varicella is usually clinical, but may be confirmed with Tzanck smear or identification of the virus by DNA polymerase chain reaction (PCR). Antiviral therapy using acyclovir, valacyclovir, or famciclovir may shorten the course of the illness in patients older than 2 years if started within 24 hours of onset of the exanthem. Varicella vaccination is now universally recommended at 12 to 15 months with a booster dose at 4 years. While the vaccine has significantly reduced the incidence of childhood chicken pox, breakthrough infections can occur in vaccinated individuals. However, these infections are usually much less severe, with fewer vesicles and little to no fever. The varicella vaccine is a live, attenuated virus and should not be given to immunocompromised or pregnant patients.

Shingles, or herpes zoster, is a reactivation of the varicella virus, which remains dormant in the dorsal root ganglia following the initial infection. The reactivated virus causes a vesicular eruption, usually along a single dermatome that does not cross the midline. The reaction can occur at any age, but is more common in the elderly or immunosuppressed. The rash can be extremely painful and can result in chronic postherpetic neuralgia that can last long after resolution of the rash. Antiviral therapy started within 72 hours of onset of the rash may reduce the incidence of the postherpetic neuralgia. A herpes zoster vaccine is now recommended for people over 60 and has been shown to decrease the likelihood of development of zoster.

Erythema lnfectiosum

Parvovirus B19 causes a characteristic syndrome known as erythema infectiosum or fifth disease. This virus tends to infect children younger than 10 years and occurs most commonly in the winter or spring months and is primarily spread by infected respiratory droplets. The child usually presents with a prodrome of mild fever and upper respiratory symptoms prior to outbreak of the rash that typically lasts between 4 to 14 days. The rash usually starts as confluent erythematous macules on the face, which usually spares the nose and periorbital regions. This gives the classic "slapped cheek" appearance that is commonly diagnostic of the infection. The facial rash usually lasts for 2 to 4 days and is followed by a lacy, pruritic exanthem on the trunk and extremities that usually lasts for 1 to 2 weeks, but can have a relapsing course for several months. Parvovirus B19 in adults and older adolescents tends to cause a more severe illness, with rheumatic complaints including arthralgias. In patients with sickle cell disease, parvovirus B19 infection can lead to an aplastic crisis with anemia and leukopenia. The virus can also be transmitted from mother to fetus during pregnancy, resulting in fetal hydrops and pregnancy loss.

COMMON BACTERIAL INFECTIONS

Group A β-Hemolytic Streptococcus

Group A β-hemolytic Streptococcus (GABS) is associated with numerous diseases, particularly in children. It is the causative agent of streptococcal pharyngitis and its complications, which include rheumatic fever and postinfectious glomerulonephritis. It can also cause impetigo, erysipelas, and cellulitis. Invasion and multiplication within the fascia can lead to necrotizing fasciitis.

The rash of scarlet fever usually starts approximately 2 days after the onset of sore throat and fever. The rash consists of punctate, raised, erythematous eruptions that can become confluent (Pastia lines) and feel like sandpaper. The rash tends to start on the upper trunk and spreads to the rest of the trunk and the extremities. The exanthem can also be associated with an enanthem, causing the appearance of a "strawberry tongue:' The rash fades and desquamation typically occurs 4 to 5 days after the first appearance of the rash.

GABS infections can be confirmed by rapid antigen testing or culture via a pharyngeal swab. Serologic tests commonly demonstrate marked leukocytosis with neutrophilia with normal or increased eosinophilia, and elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and antistreptolysin O titer. The first-line treatment for GABS infections is penicillin, with cephalosporins or macrolides as alternatives in the penicillin-allergic patient. Patients are commonly no longer contagious within 48 hours after starting antibiotics and should be counseled that they can return to school or work if afebrile and on antibiotics for at least 24 hours. Exposed individuals should be monitored for fever and other symptoms for at least a week and should receive treatment if they have a positive throat culture. Household and close contacts with similar symptoms should be empirically treated.

Neisseria meningitidis

Neisseria meningitidis (meningococcus) can cause an acute, life-threatening infection, often associated with a rash, and is spread through respiratory secretions. Meningococcemia causes a severe illness with high fevers, hypotension, and altered mental status. Most people with meningococcemia progress to develop frank bacterial meningitis, with associated signs of meningeal irritation. The rash of meningococcemia often starts as an erythematous maculopapular eruption that does not blanch with compression which progresses to form petechiae. The petechiae may coalesce into purpura in a condition known as purpura fulminans that can result in gangrene and amputation of limbs when associated with disseminated intravascular coagulation. Other complications include adrenal hemorrhage, deafness, and cerebral and renal infarctions.

Persons with suspected meningococcemia should be immediately hospitalized and quarantined, usually in the intensive care unit. The ABCs (airway, breathing, and circulation) should be urgently evaluated, blood and cerebrospinal fluid cultures collected, and empiric antibiotic therapy instituted until an organism is isolated via culture and drug sensitivities are obtained. Treatment should not be delayed

by performing a lumbar puncture, as early and appropriate antibiotic treatment markedly improves the outcome of meningococcal infections. A common empiric regimen for presumed meningitis in infants less than 30 days old is ampicillin plus gentamicin, while for adults, vancomycin plus ceftriaxone should be used. Antibiotic coverage can be later tailored based on culture results. The first choice for cultureproven meningococcal meningitis is penicillin G. A meningococcal vaccine is now recommended for routine childhood immunization and also should be offered to patients at risk for the disease (eg, asplenia, those living in dormitories or military barracks). Close contacts of someone with meningococcal infection should be offered prophylaxis with ciprofloxacin or rifampin.

TICK-BORNE DISEASES

Rocky Mountain Spotted Fever

Rocky Mountain spotted fever (RMSF) is an acute, life-threatening infection caused by the organism Rickettsia rickettsii, which is transmitted via various species of tick. The infection occurs more often in the summer months, when people are more likely to be outdoors. Despite its name, RMSF is most common in the southeastern United States, but does occur throughout the United States, Canada, Mexico, Central America, and parts of South America. The early phase of the illness causes nonspecific signs and symptoms such as fever, headache, myalgias, arthralgias, and fatigue. Some patients, especially children, may complain of abdominal pain. The classic exanthem is a macular, papular, or petechial eruption that starts on the wrists and ankles and spreads both centrally and to the palms and soles. The rash usually develops between the third and fifth day of the illness. Serologic evaluation often reveals a low white blood cell count, low platelet count, hyponatremia, and elevated liver transaminases. The diagnosis is confirmed with serology, but this is not helpful in the acute setting. Due to its severity, a high suspicion for RMSF should be maintained and likely cases of the illness treated empirically with doxycycline. Early treatment is important as there is an associated risk of fatal outcome after day 5 of the illness and therapy should be continued for at least 3 days after the patient becomes afebrile.

Lyme Disease

Lyme disease is endemic in many areas of the United States, including New England and the mid-Atlantic region. The causative spirochete, Borrelia burgdorferi, is transmitted via the bite of deer ticks of the Ixodes species. Because the ticks are very small, infected persons are often unaware of a history of a tick bite. The characteristic rash, erythema migrans, develops 3 to 30 days following infection. The exanthem is typically an expanding erythematous macule with central clearing, often described as appearing like a "bull's eye:' Early dissemination of the disease can present as multiple secondary erythema migrans, diffuse arthralgias and myalgias, Bell palsy, aseptic meningitis, carditis, and rarely as complete heart block. Late disease is most characteristically marked by polyarthritis. Diagnosis is confirmed via serologic antibody testing. The treatment of choice for Lyme disease is doxycycline, amoxicillin, or cefuroxime. Patients treated with appropriate antibiotic therapy in the early stages of Lyme disease commonly recover completely and without lasting sequelae. Approximately 10% to 20% of patients who presented late in the disease, despite appropriate antibiotic therapy, may have persistent or recurrent symptoms known as posttreatment Lyme disease syndrome.

Table 48-1 provides a summary of some of the most common causes of the presentation of rash and fever in children.

COMPREHENSION QUESTIONS

48.1 A 4-year-old boy is brought to your office by his mother for evaluation of a rash on his face that his mother first noticed the day prior to presentation. His mother comments that it looks like somebody "slapped him." The mother reports that he has had a cold for the last couple of days. The child's physical examination is unremarkable except for an erythematous macular rash over both cheeks. The mother admits that the child is behind on his immunization schedule. Which of the following is the most likely cause?

A. Varicella-zoster virus

B. Parvovirus B19

C. Human herpes virus 6

D. Rubella virus

E. Child abuse and you should contact social services immediately

48.2 A 6-year-old girl is brought to your office by her mother because of a rash first noticed 1 week ago. Her mother reports that several children in her child's school have chicken pox but that her child has received all of her immunizations including two doses of the varicella vaccine. You observe the child actively playing with the toys in your waiting room before both the mother and child are brought back to the examination room. T he child has a temperature of 100.4°F (38.0°C), a pulse of 90 beats/min, a blood pressure of 100/70 mm Hg, and a respiration rate of 20 breaths/min. T he physical examination is unremarkable except for approximately 20 vesicles on erythematous bases sparsely scattered on the child's trunk and limbs. Which of the following is the most appropriate treatment?

A. Supportive care

B. Antiviral therapy

C. Antibiotic therapy

D. Immune globulin

48.3 You are on duty when an 18-year-old man is brought to the emergency room (ER) from his college dorm by his roommate. He is confused and cannot give a history. He has a temperature of 104.0°F ( 40.0°C), pulse of 110 beats/min, blood pressure of 90/60 mm Hg, and a respiration rate of 24 breaths/

min. His head cannot be moved because of severe nuchal rigidity. Multiple petechiae are observed on his buttocks and legs. What is the most appropriate advice to give to this patient's roommate?

A. Reassurance that he does not require prophylaxis.

B. Take acyclovir for prophylaxis.

C. Take penicillin for prophylaxis.

D. Take rifampin for prophylaxis.

E. Take cefuroxime for prophylaxis.

48.4 A 7 -year-old boy is brought to a hospital in Charlotte, North Carolina with a fever of 104.0°F (40.0°C). A maculopapular rash is seen on his wrists and ankles but the palms and soles are spared. His laboratory results show leukopenia, hyponatremia, and elevated liver transaminases. His parents say that he was on a camping trip 1 week ago but they vigorously used insect repellants and filtered all of their water. His father came in contact with poison oak, but the boy denies any pruritus. Which of the following is the best treatment for this patient's rash?

A. Penicillin

B. Acyclovir

C. Ceftriaxone

D. Vancomycin

E. Doxycycline

ANSWERS

48.1 B. This question describes erythema infectiosum, or fifth disease, which is caused by parvovirus B19. It often has a prodrome of fever and upper respiratory systems mistaken by the mother in this question as a "cold:' This child also has the classic "slapped cheek" rash of erythema infectiosum and, while the child does need to be caught up on his immunizations, the child has the classic symptoms of fifth disease and not of the diseases for which children are immunized.

48.2 A. The child has chicken pox caused by the varicella-zoster virus. While the child did receive two doses of the varicella vaccine and the vaccine is effective, sporadic breakthrough cases do occur. However, the cases are usually much less severe and have fewer complications than in unimmunized patients. Supportive care is advised, as this illness in this stage will be self-limited; after a week, antivirals likely have no benefit. Antibiotics and immune globulin have no role in the treatment of this patient.

48.3 D. The patient has meningitis and meningococcemia caused by N meningitidis. The patient is severely affected and is in septic shock. All people in close contact with the patient should receive ciprofloxacin or rifampin prophylaxis.

48.4 E. The patient has Rocky Mountain spotted fever and should be treated with doxycycline. The disease is commonly found in North Carolina and is carried by ticks that the boy could have picked up during the camping trip. RMSF has a characteristic rash that starts on the wrists and ankles and can eventually involve the palms and soles.Typically, the rash of RMSF spreads centripetally from the wrists and ankles to involve the trunk and extremities.

CLINICAL PEARLS

⯈ Shingles that approaches the eye (herpes zoster ophthalmicus), because of a reactivation involving the trigeminal nerve, should be evaluated by an ophthalmologist. A clue that the eye may become involved is seeing characteristic lesions approaching the tip of the nose.

⯈ Many vaccine-preventable illnesses, including measles, rubella, and varicella, have characteristic rashes associated with them. Always get a vaccination history on children presenting with fever and rash. Also, consider the possibility that immigrants from other countries may not be vaccinated if they present with similar symptoms.

REFERENCES

Chen LF, Sexton DJ. W hat's new in Rocky Mountain spotted fever. Infect Dis Clin North Am. 2008; 22(3):415-432. 

Cohen JI. Herpes zoster. N Engl] Med. 2013; 369:255-263. 

Dandache P, Nadelman RB. Erythema migrans. Infect Dis Clin North Am. 2008; 22(2):235-260. 

Ely JW, Stone MS. The generalized rash: part I. Differential diagnosis. Am Fam Physician. 2010; 81(6):726-734. 

Ely JW, Stone MS. The generalized rash: part II. Diagnostic approach. Am Fam Physician. 2010; 81(6):735-739. 

Folster-Holst R, Kreth HW. Viral exanthems in childhood-infectious (direct) exanthems. Part 1: classic exanthems.J Dtsch Dermatol Ges. 2009; 7(4):309-316. Foister-Holst R, Kreth HW. Viral exanthems in childhood-infectious (direct) exanthems. Part 2: other viral exanthems. Dtsch Dermatol Ges. 2009; 7(5):414-419. 

Mann K,Jackson MA. Meningitis. Pediatr Rev. 2008; 29(12):417-429. 

McKinnon HD, Howard T. Evaluating the febrile patient with a rash. Am Fam Physician. 2000; 62: 804-816. 

Shapiro ED. Lyme disease. N Engl] Med. 2014; 370:1724-1731. 

Survey JT, Reamy BV, Hodge J. Clinical presentation of parvovirus B19 infection. Am Fam Physician. 2007; 75(3):373-376. 

Zerr DM, Meier AS, Sdke SS, et al. A population-based study of primary human herpesvirus 6 infection. N Engl] Med. 2005; 352(8):768-776.

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