Infectious Diseases

Adenovirus

More than 70 distinct types of adenoviruses can produce a variety of clinical illnesses, including conjunctivitis, respiratory tract infections (including coryza, pharyngitis, croup, bronchitis, bronchiolitis, and pneumonia), gastroenteritis, myocarditis, nephritis, cystitis, and encephalitis. An exanthem sometimes accompanies other symptoms and a variety of rashes have been described. The eruption may consist of discrete, nonspecific, blanching, maculopapular lesions, or it may be morbilliform, rubelliform, or, on occasion, petechial. Typically, the rash is generalized when first noticed. The classic clinical constellation consists of conjunctivitis, rhinitis, pharyngitis with or without exudate, and a discrete, blanching, maculopapular rash ( Fig. 13.1 ). Anterior cervical and preauricular lymphadenopathy, low-grade fever, and malaise are common associated findings. The peak season for adenovirus infections in temperate climates is late winter through early summer, and the infection is maximally contagious during the first few days of illness. The incubation period ranges from 6 to 9 days.

Coxsackievirus and Other Enteroviruses

The Enterovirus genus includes coxsackieviruses, echoviruses, and enteroviruses, with many types of each. Coxsackieviruses are the most common cause of hand-foot-and-mouth disease. Patients may have a brief prodrome consisting of low-grade fever, malaise, sore mouth, and anorexia before oral lesions and skin lesions appear in 1 to 2 days. The former usually consist of shallow, yellow ulcers surrounded by red halos. They are found on the labial and buccal mucosal surfaces, the gingivae, tongue, soft palate, uvula, and anterior tonsillar pillars ( Fig. 13.2A and B ). In the early stage of the illness, small vesicles may be seen on the palate or mucosal surfaces. These oral lesions are usually mildly painful. The cutaneous lesions begin as erythematous macules on the palmar aspect of the hands and fingers, the plantar surface of the feet and toes, and the interdigital surfaces. The buttocks may be involved as well. They evolve rapidly to form small, thick-walled, gray vesicles on an erythematous base (see Fig. 13.2C–E ), which may be tender, pruritic, or asymptomatic. More than 90% of patients with disease caused by coxsackievirus have oral lesions, and about two-thirds have the exanthem. In cases in which the cutaneous manifestations are absent, the process is called herpangina and may resemble early herpetic gingivostomatitis (though without the prominent labial component). Hand-foot-and-mouth disease is highly contagious, with an incubation period of approximately 2 to 6 days and duration up to 1 week. The peak season is summer through early fall, which is a time when most enteroviral infections occur in temperate climates.

Other enteroviral syndromes include a mild, nonspecific febrile illness with myalgias, headache, and abdominal pain; generalized exanthems that may be maculopapular, vesicular, or urticarial; aseptic meningitis, encephalitis, acute cerebellar ataxia, and myelitis; pleurodynia; myocarditis; hemorrhagic conjunctivitis; and gastroenteritis.

Herpes Simplex Virus

Herpes simplex virus (HSV) produces infections that primarily involve the skin and mucous membranes, although in neonates, immunocompromised hosts, and rarely non-neonates, infection can result in disseminated disease or central nervous system (CNS) involvement. Like other herpesviruses, HSV enters a latent or dormant stage after initial (primary) infection, residing in local sensory ganglia; once latent, the virus can be reactivated at any time, causing recurrent infection. The two distinct serotypes of HSV are types 1 and 2. HSV-1 is more common and can produce a variety of clinical syndromes. In contrast, HSV-2 is usually a genital pathogen (see Chapter 19 ), although occasionally it is the source of oral lesions and is the more common type associated with neonatal herpes (see the Congenital and Perinatal Infections section later).

Diagnosis of symptomatic HSV infections can often be made on clinical grounds alone, particularly in cases of primary infection. When the diagnosis is in question, early antigen detection from scrapings obtained from the base of a vesicle, viral culture, or polymerase chain reaction (PCR) (see Chapter 8 ) usually confirm the infection. Serology is usually not helpful clinically.

Primary Herpes Simplex Virus Infections

More than 90% of primary infections caused by HSV-1 are subclinical; nevertheless, because the virus is ubiquitous, symptomatic primary infections are common. One of the most prevalent forms of primary infection is herpetic gingivostomatitis. Patients with this condition typically have high fever, irritability, anorexia, and mouth pain; infants and toddlers often drool copiously. The gingivae become intensely erythematous, edematous, and friable and tend to bleed easily. Small, yellow ulcerations with red halos are seen routinely on the buccal and labial mucosa, on the gingivae and tongue, and often on the palate and tonsillar pillars ( Fig. 13.3A and B ). Within a short time, yellowish-white debris builds up on mucosal surfaces and halitosis becomes prominent. Thick-walled vesiculopustular lesions may also develop on the perioral skin (see Fig. 13.3C ). The anterior cervical and tonsillar nodes are enlarged and tender. Symptoms last from 5 to 14 days, but the virus may be shed for weeks after resolution. The illness can vary from mild to marked in severity. Young children with prolonged high fever and intense pain may become dehydrated and should be monitored closely. The diffuseness of the ulceration (especially labial) and mucosal inflammation and the intense gingivitis help to distinguish this disorder from enteroviral herpangina and exudative tonsillitis, as well as from other forms of gingivitis.

Patients with primary herpetic infection involving the skin typically present with fever, malaise, localized lesions, and regional adenopathy. The skin lesions generally result from direct inoculation of previously traumatized skin, for example, at the site of an abrasion, burn, or small cut. Parents, siblings, and playmates with active herpetic lesions (usually cold sores) are often the source, and children with herpes gingivostomatitis may autoinoculate other body sites with their fingers. The lesions consist of deep, thick-walled, painful vesicles on an erythematous base; they are usually grouped but may occur singly. As they evolve over several days, the vesicles become pustular, coalesce, ulcerate, and crust over. As a result, the lesions may simulate those of bacterial impetigo, but the presence of grouped vesicles and the absence of bacteria on Gram stains of vesicular fluid support the clinical diagnosis of herpes.

Although the virus can infect any area of the skin, the lips and fingers (as in herpetic whitlow) are the most common sites of involvement ( Fig. 13.4 ; see Fig. 13.3 ). On occasion, the eyelids and periorbital tissues are affected ( Fig. 13.5 ); this can lead to keratoconjunctivitis, which is diagnosed based on finding characteristic dendritic ulcerations on slit-lamp examination (see Chapter 20 ). Because this complication carries a risk of permanent visual impairment, urgent ophthalmologic consultation is indicated whenever there is any suspicion of ocular herpetic infection.

Eczema Herpeticum (Kaposi Varicelliform Eruption)

Patients with atopic eczema and other forms of chronic dermatitis are at risk for a particularly severe form of primary HSV infection and should avoid contact with people with active herpetic infections. The illness is heralded by the onset of high fever, irritability, and discomfort. Lesions appear in crops and primarily involve areas of skin currently or recently affected by eczema. Typically, they evolve to form pustules, which rupture and form crusts over the course of a few days. On occasion, these lesions become hemorrhagic ( Fig. 13.6 ). Multiple crops can appear over 7 to 10 days, simulating varicella. However, the slower evolution of lesions, the tendency of such lesions to become hemorrhagic, their concentration in eczematous areas, and the persistence of fever and systemic symptoms for as long as 1 week help to distinguish this disorder from varicella. Severity ranges from mild to fulminant and depends in part on the extent of the preceding dermatitis. When the area of involvement is large, fluid losses can be severe and potentially fatal. Accordingly, prompt treatment with intravenous acyclovir is recommended. A significant risk of secondary bacterial infection also exists, which is uncommon in uncomplicated herpetic infections.

Recurrent Herpes Simplex Infection

After primary infection, HSV becomes latent within the ganglia that lie in the region of initial involvement, reactivation of the latent virus results in localized recurrences at or near the site of previous infection. Fever, sunlight, local trauma, menses, and emotional stress are recognized triggers, and because the mouth is the major site of primary infection, labial and perioral lesions (cold sores) are commonly seen. Many patients report a prodrome of localized burning along with stinging or itching before the eruption of grouped vesicles. These vesicles contain yellow, serous fluid and often appear smaller and less thick-walled than primary lesions ( Fig. 13.7 ). After 2 to 3 days the vesicular fluid becomes cloudy, and then crusts form. Although fever and systemic symptoms are absent, regional nodes may be enlarged and tender. The localization of the lesions to a small area helps to distinguish them from those of herpes zoster (varicella). Prodromal symptoms and discomfort help to distinguish recurrent HSV infection from impetigo and contact dermatitis.

Epstein-Barr Virus (Infectious Mononucleosis)

Infectious mononucleosis is an acute, usually self-limited illness of children and young adults caused by Epstein-Barr virus (EBV). Transmission of EBV can occur by saliva, contact (i.e., kissing), sharing eating utensils, transfusions, or organ transplantation. The incubation period usually ranges from 30 to 50 days, although it is shorter (14 to 20 days) in patients with transfusion-acquired infection. In its most typical form, infectious mononucleosis is characterized by fever, fatigue, pharyngitis, lymphadenopathy, splenomegaly, atypical lymphocytosis, and a positive heterophil antibody response. In contrast, young children with EBV infection tend to have either a nonspecific febrile illness clinically indistinguishable from other common viral diseases, or subclinical infection.

Clinical Features of Mononucleosis

The illness often begins with a prodrome lasting 3 to 5 days consisting of fatigue, malaise, and anorexia, often in association with headache, sweats, and chills. Photophobia and edema of the eyelids and periorbital tissues may be noted in some patients ( Fig. 13.8A ). The acute phase is usually heralded by a fever, which may show wide daily fluctuations. Pharyngitis and cervical node enlargement then become apparent. The sore throat tends to increase in severity over several days before abating and may be associated with significant dysphagia. Tonsillar and adenoidal enlargement can range from mild to marked, and the tonsillar surface may vary in appearance from one of mild erythema to one of severe exudative inflammation with palatal and uvular edema (see Fig. 13.8B ). Halitosis and palatal petechiae (like group A Streptococcus [GAS]) are common. Approximately one-third of patients show severe pharyngeal manifestations. The anterior cervical lymph nodes are routinely enlarged, and posterior cervical adenopathy is characteristic. In classic cases, the adenopathy becomes generalized toward the end of the first week. Involved nodes are firm, discrete, and mildly to moderately tender. Splenomegaly develops in approximately 50% of patients in the second to third week of illness; 10% have associated hepatic enlargement and transaminases may be elevated.

An exanthem is seen in 5% to 10% of patients with mononucleosis, although this percentage is increased in patients treated with ampicillin or amoxicillin for pharyngeal or respiratory symptoms. The exanthem is usually an erythematous maculopapular rubelliform rash, but can be morbilliform, scarlatiniform, urticarial, hemorrhagic, or even nodular (see Fig. 13.8C and D ).

Rare manifestations or complications of mononucleosis include pneumonitis; hematologic abnormalities, such as direct Coombs test–positive hemolytic anemia and thrombocytopenia; icteric hepatitis; neurologic disorders, such as acute cerebellar ataxia, encephalitis, aseptic meningitis, myelitis, or Guillain-Barré syndrome; and, rarely, myocarditis, and pericarditis. Neurologic and hepatic involvement or widely disseminated disease can be occasionally fulminant, resulting in death, particularly for immunocompromised patients with lymphocyte dysfunction. Other unusual complications include acute upper airway obstruction, resulting from tonsillar and adenoidal hypertrophy and splenic rupture. The latter may occur spontaneously or because of minor trauma, repeated palpation, or the increased intraabdominal pressure associated with defecation. Although younger patients are less subjected to the unusual manifestations and complications of mononucleosis, they are more vulnerable to acute upper airway obstruction because of tonsillar and adenoidal hypertrophy. This is manifested by mouth breathing, retractions with recumbency, and stertorous snoring and apnea during sleep. Moreover, children younger than 5 years old with significant tonsillar and adenoidal enlargement during the EBV infection are more likely to have secondary otitis media and may suffer recurrent bouts of otitis media, tonsillitis, and sinusitis as a result of persistent tonsillar and adenoidal hypertrophy.

Measles (Rubeola)

Measles is a highly contagious, often severe acute illness with a typical prodrome and mode of evolution. Prodromal symptoms consist of fever, malaise, dry (occasionally croupy) cough, coryza, and conjunctivitis with clear discharge and marked photophobia ( Fig. 13.9A ). From 1 to 2 days after onset of prodromal symptoms, a pathognomonic enanthem (Koplik spots) appears on the buccal mucosa (see Fig. 13.9B ). The lesions consist of tiny bluish-white dots surrounded by red halos, which increase in number and then fade over a 2- to 3-day period. The exanthem is seen first on day 3 or 4, as the prodromal symptoms and fever peak in severity. It is a blotchy, erythematous, blanching, maculopapular eruption that appears at the hairline and spreads cephalocaudally over 3 days, ultimately involving the palms and soles (see Fig. 13.9C to F ). Once generalized, the rash becomes confluent over proximal areas but remains discrete distally. Older lesions tend to develop a rusty hue and cease to blanch with pressure. Fading commences after 3 days, with clearing 2 to 3 days later. Fine, branny desquamation of the most severely involved areas may ensue. Generalized adenopathy may be present.

The incubation period for measles is 7 to 21 days, and patients are contagious from approximately 4 days before the appearance of rash until about 4 days after. The attack rate in exposed, susceptible people is greater than 90%. Morbidity is high and mortality not uncommon, especially in low-income countries. The peak season for measles is late winter through early spring. Potential complications (resulting either from extension of the primary infection or from secondary invasion by bacterial pathogens) include otitis media (most frequently), pneumonia, obstructive laryngotracheitis, and acute encephalitis. Administration of measles vaccine is highly effective in preventing this disease. Recent declines in immunization rates in some populations and regions have made imported cases and clusters more common; thus, early consideration and recognition among unimmunized persons is important.

Parvovirus B19 (Erythema Infectiosum, Fifth Disease)

Erythema infectiosum is a mildly contagious illness caused by human parvovirus B19, which principally affects preschool and school-age children. It occurs year-round, with a peak incidence in late winter and early spring. The disorder is characterized primarily by its characteristic exanthem. Fever and constitutional symptoms are unusual. On occasion, headache, nausea, myalgias, and peripheral polyarthralgia (particularly in adolescents and young adult women) are reported. The rash begins on the face, with large, bright red, erythematous patches appearing over both cheeks ( Fig. 13.10A ).

These patches are warm and nontender and have circumscribed borders that are usually macular but may be slightly raised. They are easily distinguished from those of cellulitis and erysipelas (see Figs. 13.32, 13.34, and 13.35 ) by their symmetry and lack of tenderness and by the absence of high fever and toxicity. The facial lesions begin to fade on the next day, and a symmetrical, macular, or slightly raised, lacy, erythematous rash appears on the extensor surfaces of the extremities (see Fig. 13.10B ). Over the next day or so, the rash may spread to the flexor surfaces, buttocks, and trunk. Resolution occurs within 3 to 7 days of onset.

The virus is transmitted primarily by respiratory secretions and, after transmission, it replicates in red blood cell precursors in the bone marrow. It then may cause a biphasic illness, with fever and nonspecific symptoms accompanied by red blood cell suppression occurring approximately 1 week later, followed by the appearance of the classic fifth disease exanthem 1 to 2 weeks thereafter. In the immunocompetent host, viral shedding ceases before the rash presents; thus, these patients are not contagious. Although red blood cell suppression caused by parvovirus does not result in severe anemia in healthy persons, it can be severe in immunocompromised hosts, causing an aplastic crisis in patients with hemoglobinopathies, such as sickle cell disease or other forms of hemolytic anemia.

Roseola Infantum (Human Herpesvirus 6, Exanthem Subitum)

Roseola infantum is a febrile illness that primarily affects children between 6 and 36 months old. The causative agent is human herpesvirus 6 (HHV-6). The clinical course begins abruptly with rapid temperature elevation, which occasionally precipitates a febrile seizure. Anorexia and irritability are the major associated symptoms. Examination reveals no source for the fever, which is usually higher than 102.2°F (39°C). Although most patients do not look toxic, many infants undergo a sepsis workup and lumbar puncture because of the combination of unexplained high fever and marked irritability. Fever and irritability persist generally 3 to 5 days, whereupon the fever abruptly subsides. In most cases an erythematous, maculopapular exanthem appears simultaneously with defervescence, or no more than 1 day before or after fever abates. Lesions are discrete, rose pink macules or maculopapular that begin on the trunk and then spread rapidly to the extremities, neck, face, and scalp ( Fig. 13.11 ). They may last several hours to 1 or 2 days before resolution. Although cases occur year-round, roseola appears to be more common in late fall and early spring. Secondary cases are uncommon, except in institutional settings. The duration of communicability is unclear, but the mean incubation period of HHV-6 is 10 days. Some children may exhibit febrile illness or exanthem alone with HHV-6 infection.

Rubella (German Measles)

Although rubella has little or no prodrome, some infected individuals experience 1 to 5 days of low-grade fever, malaise, adenopathy, headache, sore throat, and coryza. Fever, if present at all, is low grade and rarely lasts more than a day. The exanthem is a discrete, pinkish red, fine maculopapular eruption, which, like measles, typically begins on the face and spreads cephalocaudally ( Fig. 13.12A ). The rash becomes generalized within 24 hours, and then begins to fade, clearing completely by 72 hours. Forchheimer spots, an enanthem consisting of small reddish spots on the soft palate, are seen in some patients on day 1 of the rash and can be helpful in the differential diagnosis (see Fig. 13.12B ). Adenopathy, often generalized, is a common but not invariable feature. The occipital, posterior cervical and postauricular nodes tend to be those most prominently enlarged. Arthritis and arthralgias affecting large or small joints are frequent in adolescent and adult female patients, beginning on day 2 or 3 and typically lasting 5 to 10 days.

Many patients infected with rubella do not manifest a typical syndrome, however, and up to 25% of infected people are asymptomatic yet capable of transmitting virus. In some, the rash may last only 1 day and may involve only the trunk; in others, the exanthem is absent and the patient appears to have pharyngitis or an upper respiratory tract infection. Because infections due to many other viruses including adenoviruses, coxsackieviruses, and echoviruses can produce a rubella-like picture, serologic testing is necessary to establish the diagnosis. Such testing is important if the patient is pregnant or has been in contact with a pregnant woman or if arthritis is a prominent feature, simulating the picture of acute rheumatic fever or rheumatoid arthritis.

The incidence of rubella peaks in late winter and early spring, and the disease is contagious in patients from a few days before to a few days after appearance of the exanthem. The incubation period ranges from 14 to 21 days. Complications are rare in childhood and include arthritis, purpura with or without thrombocytopenia, and mild encephalitis. The major complication results from spread of the virus to susceptible pregnant women and their fetuses, resulting in congenital rubella syndrome (see the Congenital and Perinatal Infections section).

Varicella (Chickenpox)

Varicella in the normal pediatric host is usually a self-limited albeit highly contagious illness caused by the varicella-zoster virus. A brief prodrome of low-grade fever, upper respiratory tract symptoms, and malaise may occur, followed rapidly by the appearance of a pruritic exanthem. Lesions appear in crops and evolve rapidly over several hours. Most patients have three crops, although the range is one to five. Initial crops involve the trunk and scalp, and subsequent crops are distributed more peripherally; thus, the mode of spread is centrifugal. The presence of scalp lesions with the initial crop is often helpful to diagnose a patient who presents early in the disease. Lesions begin as tiny erythematous papules that rapidly enlarge to form thin-walled, superficial central vesicles surrounded by red halos ( Fig. 13.13A ). Vesicular fluid changes promptly from clear to cloudy; then drying begins, resulting in an umbilicated appearance. As the surrounding erythema fades, a central crust or scab is formed, which sloughs after several days. A hallmark of this exanthem is the finding of lesions in multiple stages of evolution within a relatively small geographic area of the skin (see Fig. 13.13B ). In general, all scabs have sloughed by 10 to 14 days. Scarring usually does not occur unless lesions become secondarily infected. It is important to recognize that in patients with preexisting dermatologic problems, the lesions of varicella, like other viral exanthems, tend to appear first and cluster most heavily at sites of prior skin irritation, such as the diaper area or sites of eczematous dermatitis (see Fig. 13.13C and D ).

An enanthem is commonly seen and consists of thin-walled vesicles that rapidly rupture to form shallow ulcers (see Fig. 13.13E ). Other mucosal surfaces may be affected as well. Although skin lesions are pruritic, those on the oral, rectal, or vaginal mucosa and those involving the external auditory canal or tympanic membrane can be painful. Systemic symptoms are generally mild, although low-grade to moderate fever may be present during the first few days. In most cases, pruritus is the child’s major complaint. In adolescents and adults, the illness is more likely to be severe with prominent systemic symptoms and more extensive exanthematous involvement.

Varicella occurs year-round with peak incidences in late autumn and late winter through early spring. The period of communicability begins 1 to 2 days before the appearance of lesions and lasts until all lesions have crusted over. The incubation period ranges from 10 to 21 days, with high secondary attack rates in susceptible children and adults. The most common complication is secondary bacterial infection of skin lesions. Streptococcus pyogenes superinfection of varicella lesions ranges from mild cellulitis to myositis, sepsis, and purpura fulminans ( Fig. 13.14A ). Other complications, although rare, include pneumonia, hepatitis, and encephalitis. The onset of these complications is typically heralded by a secondary fever spike concurrent with increase in general systemic symptoms. In patients with encephalitis, an altered level of consciousness along with other signs of neurologic dysfunction occurs. Reye syndrome, an encephalopathy of unclear etiology, is now a very rare complication that can occur as a child is recovering from acute varicella, particularly when receiving concomitant aspirin. Repetitive vomiting is followed by an altered level of consciousness in which periods of lethargy alternate with periods of delirium or combativeness.

In the immunocompromised host with deficient cellular immunity, untreated varicella can be severe or even fatal, with CNS, pulmonary, or generalized visceral involvement. Skin lesions may appear hemorrhagic and tend to remain vesicular for a prolonged period (see Fig. 13.14B and C ). IV acyclovir is indicated for these patients.

Herpes Zoster (Shingles)

Varicella-zoster virus, like all herpesviruses, persists after primary infection. The virus establishes latency in sensory nerve root cells and can reactivate in response to mechanical and thermal trauma, other infections, decreased T-cell immunity, and older age. In the reactivated form, herpes zoster, lesions consist of grouped, thin-walled vesicles on an erythematous base, which are distributed along the course of a spinal or cranial sensory nerve root in typically a dermatomal distribution ( Fig. 13.15 ). They evolve from macule to papule to vesicle and then to a crusted stage over a few days. Hyperesthesia or nerve root pain may precede, accompany, or follow the eruption and does not correlate with the severity of the rash. Pain, if present at all in pediatric patients, is rarely severe and is generally short-lived, unless a cranial nerve dermatome is involved, in which case pain can be excruciating. Fever and constitutional symptoms may or may not be part of the picture, but regional adenopathy is common.

Thoracic dermatomes are involved in most patients, followed in frequency by cervical, trigeminal, lumbar, and facial nerve regions. Cranial nerve involvement may produce a puzzling prodrome consisting of severe headache, facial pain, or auricular pain with no evident cause and lasting up to several days before appearance of the eruption. Lesions appear unilaterally on the tonsillar pillars and uvula with involvement of the maxillary branch of the trigeminal nerve; on the buccal mucosa and palate with involvement of the mandibular division; and on the face, cornea, and tip of the nose with involvement of the ophthalmic branch (see Fig. 13.15D ). When the geniculate ganglion is affected, vesicles are seen in the external auditory canal in concert with facial paralysis. Facial palsy and unilateral hearing loss (Ramsay Hunt syndrome) can occur with zoster of the facial nerve. Although patients with herpes zoster can transmit varicella, contagion is less likely because most patients have lesions on areas that are covered by clothing and the oropharynx is not involved in most cases.

Gianotti-Crosti Syndrome

The eruption of Gianotti-Crosti syndrome, or papular acrodermatitis, although distinctive, often goes unrecognized (or is misdiagnosed). First described in association with anicteric hepatitis B, this exanthem has also been associated with other viruses including EBV, coxsackieviruses, parainfluenza viruses, echoviruses, cytomegalovirus (CMV), and respiratory syncytial virus. Cases usually occur sporadically. Most patients are between 1 and 6 years old.

A mild prodrome consisting of low-grade fever and malaise is typical and may be associated with generalized adenopathy, hepatosplenomegaly (especially with hepatitis B), upper respiratory tract symptoms, or diarrhea. Within a few days, the first of several crops of lesions appear abruptly. The lesions consist of discrete, firm, lichenoid papules with flat tops ( Fig. 13.16A and B ) and range from 1 to 10 mm in diameter, tending to be larger in infants and smaller in older children. Papules can be flesh colored, pink, red, dusky, or coppery. They can be purpuric. They are distributed symmetrically over the extremities (including the palms and soles), buttocks, and face, with relative sparing of the trunk and scalp (see Fig. 13.16B ) although the upper back may be involved. They tend to remain discrete but can become confluent, especially over pressure points (see Fig. 13.16C ), and the Koebner phenomenon may be seen. Pruritus is unusual, and there is no associated mucosal enanthem. The exanthem often clears within 2 to 3 weeks but can persist for 8 weeks or more.

Streptococcal Scarlet Fever

Although most commonly associated with pharyngitis and impetigo, GAS also causes scarlet fever, or scarlatina. Streptococcal infections occur year-round, although pharyngitis and scarlet fever have a peak incidence in winter and spring. The exanthem is caused by a streptococcal erythrogenic toxin. Transmission requires close contact to permit the direct spread of large droplets. The incubation period for scarlet fever ranges from 12 hours to approximately 7 days. The disease is contagious during the acute period, and patients may transmit the organisms during active subclinical infection as well. An average of 50% of family members living with an index case become secondarily infected, and up to half of these have subclinical disease.

Once a severe illness associated with high morbidity and mortality, scarlet fever has become a much milder illness over the past several decades. The classic presentation includes the abrupt onset of fever, chills, malaise, headache, sore throat, and vomiting; abdominal pain may be prominent. Within 12 to 48 hours, an exanthem appears and rapidly generalizes, usually beginning on the trunk and spreading peripherally, but sometimes spreading cephalocaudally, confusing this disease with measles. The face is flushed with perioral pallor ( Fig. 13.17A ). The remaining skin becomes diffusely erythematous and is covered by tiny pinhead-sized papules, with a sunburn appearance of erythroderma. The texture is sandpapery and the erythema blanches with pressure (see Fig. 13.17B ). The skin may be pruritic, but it is not tender. In severe cases, vesicles may form. After generalization, the rash becomes accentuated in skin folds and creases, and 1 to 3 days after its appearance, petechiae may appear in a linear distribution along the creases, forming Pastia’s lines (see Fig. 13.17C ). Examination of the oropharynx in classic cases reveals large, erythematous, exudative tonsils along with palatal erythema and petechiae ( Chapter 24 ). The uvula may be erythematous and edematous as well. The tongue also shows characteristic findings during the first 2 days, with a white coating through which erythematous papillae project (“white” strawberry tongue) (see Fig. 13.17D ). The white coat subsequently peels, leaving a glistening red surface with prominent papillae (“red” strawberry tongue) (see Fig. 13.17E ). Tender cervical adenopathy is noted in 30% to 60% of patients. Without treatment, the rash, fever, and pharyngitis resolve within 1 week; with treatment, improvement is more rapid within days. Desquamation occurs regardless of treatment and begins several days after onset, progressing cephalocaudally (see Fig. 13.17F and G ). The skin is shed in fine, thin flakes (“branny” desquamation, in contrast to the thick flakes that characterize desquamation after staphylococcal exanthems) ( Fig. 13.18 ; see Fig. 13.20 ), and the extent of this process is directly proportional to the intensity of the exanthem.

Diagnosis is simple in classic cases, but the wide spectrum of disease severity and potential manifestations may cause confusion. Fever may be absent or low grade, and malaise may be minimal. Pharyngitis may be mild (without exudate, petechiae, or marked erythema) or absent, even when the throat is the site of infection. In such cases, tongue changes may be absent as well. If streptococcal skin or wound infections are the primary site of infection, the oropharynx is normal. The appearance of the exanthem may vary as well. In some children, it is patchy but most prominent near skinfolds (see Fig. 13.17H ). An occasional child may have diffuse petechiae. Still others may present with fever or nasopharyngitis and urticaria as their initial manifestations. In dark-skinned children, erythema and perioral pallor may be difficult to appreciate and the papules may be larger, thus producing a texture less like that of sandpaper.

Treatment with a 10-day course of penicillin or clindamycin (in penicillin-allergic children) is important for reducing the risk of transmission and preventing rheumatic fever and pyogenic complications, the most common of which include adenitis, otitis, sinusitis, and peritonsillar and retropharyngeal abscesses. Therefore, in patients with fever or nasopharyngitis and urticaria and in children with scarlatiniform eruptions, a screening throat culture for S. pyogenes should be obtained, regardless of the presence or absence of other symptoms. Poststreptococcal glomerulonephritis is however not prevented by antimicrobial therapy.

Staphylococcus aureus Infections Associated With Exanthems

Staphylococcus aureus is a ubiquitous organism that is carried by approximately one-third of the population. Sites of carriage include the nose, gastrointestinal tract, skin, perineum, and nails. Although the hallmark of staphylococcal infection is the abscess, myriad forms of infection are seen, and at least three distinct generalized exanthematous disorders have now been identified: staphylococcal scalded skin syndrome, staphylococcal scarlet fever, and staphylococcal toxic shock syndrome (TSS). In each disease, organisms at the primary site of infection release distinct exotoxins, which then produce the associated rash. Transmission may occur by means of direct contact with persons who are infected or who are carriers or from contaminated fomites. Draining skin lesions, nasal discharge, and contaminated hands constitute particularly important sources of transmission. Traumatic or surgical wounds, burns, insect bites, areas of preexisting dermatitis, viral skin lesions, and prior viral respiratory tract infection all serve as predisposing conditions.

Staphylococcal Scarlet Fever

Staphylococcal infection can produce a scarlatiniform exanthem that is initially indistinguishable from GAS infection. The illness is characterized by fever, irritability, and malaise, followed by the abrupt onset of a generalized erythematous rash, often of sandpapery consistency, with accentuation in the skin creases ( Fig. 13.19A ). In contrast to streptococcal scarlet fever, the involved skin is usually tender, the tongue is normal, and there is no palatal enanthem. Evolution of lesions also differs—within 2 to 5 days the skin begins to crack, fissure, and weep, especially in the perioral and periorbital areas and in skin creases (see Fig. 13.19B ). It sheds in large, thick flakes over 3 to 5 days. Local skin and wound infections are common antecedents, and their presence often enables presumptive identification of staphylococci early in the disease. However, when nasopharyngitis is the source of primary infection, the picture can be difficult to distinguish from streptococcal infection, especially when strawberry tongue and palatal petechiae are absent. The same may be true if a local infection with lymphangitis is the source. In such cases, the tendency for the staphylococcal rash to be tender may be the major clinical distinction. Unless the primary infection is severe enough to warrant parenteral treatment, oral antimicrobial therapy is sufficient.

Furuncle

A furuncle, or boil, is a perifollicular dermal abscess usually caused by S. aureus . It may be the result of extension of superficial folliculitis or of direct inoculation via minor trauma. Hairy areas subject to friction or maceration, as well axillary and inguinal regions with high concentrations of sebaceous glands, are particularly vulnerable. Skin contact with occlusive agents (such as oils, tars, and adhesives) is another common predisposing factor. The incidence of furuncles is much higher in older children and adolescents than in younger children.

The lesion begins as a small dermal nodule around a hair follicle, which initially may produce mild discomfort and itching. As it gradually enlarges, the intensity of pain increases and is aggravated by touching and motion of the involved area. With expansion, the overlying skin becomes reddened, central necrosis begins to occur, and with increased inflammation and pressure, the infection begins to seek egress. In the case of most furuncles, the abscess burrows toward the surface of the skin, which becomes thinned and shiny as the abscess becomes fluctuant ( Fig. 13.27A ). Application of warm compresses can hasten this process. At this point, incision and drainage are indicated. Without intervention, spontaneous drainage of bloody purulent material ultimately occurs in most cases and the patient experiences prompt relief of pain (see Fig. 13.27B ). In areas such as the nape of the neck or upper back, where the overlying skin is thick enough to resist external pointing, the process may take a path of lesser resistance, burrowing outward from the center through the subcutaneous tissues and along fascial planes. If this process is not interrupted by early surgical intervention, the result is a gradual formation of a carbuncle, which consists of an extremely painful, exquisitely tender multilocular mass of interconnected dermal and subcutaneous abscesses, with multiple points of partial drainage at the skin surface. Carbuncle formation is often accompanied by fever, chills, and increasing malaise, and there is a significant risk of secondary bacteremia. Even with treatment, sloughing and extensive scarring tend to result.

Hidradenitis Suppurativa

In hidradenitis suppurativa, an apocrine gland is the site of infection and abscess formation. Hence, these infections usually occur in the axillae, perineum, or areolae of postpubertal adolescents. Keratin plugging of apocrine ducts and their hair follicles appears to be a major predisposing factor; occlusion, maceration, and poor hygiene may exacerbate the problem. The resultant obstruction fosters inflammation and provides a favorable environment for secondary invasion and multiplication of staphylococci and anaerobic bacteria. As the inflammatory process expands, the gland ultimately ruptures and forms an abscess. In contrast to the perifollicular furuncle, this infection is deeper and slower to localize and suppurate. It begins as a firm, mildly tender nodule that enlarges gradually, becoming increasingly uncomfortable and tender. With further enlargement and suppuration, the lesion(s) point to the surface and drain, although some may rupture subcutaneously. Early diagnosis, incision and drainage of fluctuant sites, institution of antimicrobial therapy, and adoption of meticulous hygienic practices may bring the problem under control. Delay in diagnosis, inadequate treatment, or recalcitrant disease can result in recurrence or progression with formation of multiple abscesses and sinus tracts, deep fibrosis, and scarring ( Fig. 13.28 ) that may ultimately necessitate surgical excision.

Breast Abscess

Breast abscesses occur within specific age groups among pediatric patients, with incidence peaks in the neonatal and pubertal groups. The incidence is highest in newborns of greater than 31 weeks’ gestation at the time of birth, owing in part to physiologic hypertrophy of breast tissue as a result of stimulation by maternal hormones. Colonization of the skin or the nasopharynx with potentially virulent organisms ( S. aureus , Streptococcus agalactiae [Group B streptococcus] , or gram-negative coliforms) during birth or in the nursery is another important predisposing factor. Up to 25% of affected infants have overt staphylococcal diaper dermatitis at the time of presentation. Minor local trauma is also thought to be a predisposing factor. Most cases occur during the second or third week after birth in males or females, but infection may occur as late as 8 weeks old in females. The problem first manifests as swelling and tenderness of the affected breast. Unilateral involvement is the rule. With time, local warmth and overlying erythema become evident, and it may be possible to express a purulent discharge from the nipple ( Fig. 13.29A ). Axillary adenopathy may be present as well. Only 25% of infants have low-grade fever, and other systemic symptoms are uncommon unless treatment is delayed. A firm, tender, nonfluctuant nodule may be found on palpation early in the course, and parenteral antibiotic therapy and close monitoring for progression are indicated. Later in the disease, the mass may be clearly fluctuant, indicating suppuration and necrosis requiring prompt surgical incision and drainage. Broad-spectrum antimicrobial coverage should be provided pending culture results. Common organisms include S. aureus (MSSA and MRSA), Escherichia coli, and S. agalactiae; other Gram-negative bacteria or mixed flora are occasionally present. Delay in diagnosis and institution of treatment can result in subcutaneous rupture and cellulitic spread with secondary bacteremia (see Fig. 13.29B ). Delay in surgical drainage of fluctuant lesions can also result in permanent loss of breast tissue, which can produce a cosmetically deforming breast asymmetry in girls that is first noted at puberty.

Breast abscesses may be seen again after puberty. Minor trauma, cutaneous infections, epidermal cysts, and duct blockages appear to be the common antecedent conditions. The clinical picture is similar to that seen in infants. S. aureus is the usual etiology in this group.