Primary systemic infections often present with characteristic mucocutaneous rashes: exanthems and enanthems.
Exanthem and enanthem. An exanthem is eruptive rash associated with a systemic disorder; enanthem, mucosal lesions, associated with systemic disorder often associated with an exanthem. Often caused by viral agents but can also be associated with other infections: (bacterial, parasitic infections, sexually transmitted disease), adverse cutaneous reactions to drugs or toxin, and autoimmune disease.
Etiology and Epidemiology
RNA Viruses. Picornaviridae: Poliovirus, coxsackieviruses, echovirus, enterovirus, hepatitis A virus, rhinovirus. Togaviridae: Rubella virus, attenuated rubella virus in vaccine. Flaviviridae: Dengue, hepatitis C virus. Paramyxoviridae: measles, mumps. Orthomyxoviridae: influenza A, B, and C viruses. Retroviridae: Human T-lymphotrophic virus types I and II, HIV types 1 and 2 (acute HIV syndrome).
DNA Viruses. Parvoviridae: Parvovirus B19 (erythema infectiosum). Hepadnaviridae hepatitis B virus. Adenoviridae. Herpesviridae: HSV types 1 and 2, varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein–Barr virus (EBV), HHV 6 and 7 (exanthem subitum, roseola infantum), Kaposi sarcoma (KS)-associated virus (HHV-8). Poxviridae: Variola (smallpox) virus, orf virus, and MCV.
Bacteria. Group A streptococcus: scarlet fever, toxic shock syndrome. S. aureus: toxic shock syndrome. Legionella, Leptospira, Listeria, Meningococci, Treponema pallidum.
Mycoplasmal Mycoplasma pneumoniae Rickettsiae Rocky Mountain spotted fever. Tick-borne spotted fevers. Rickettsialpox. Murine typhus. Epidemic typhus
Miscellaneous Strongyloides, Toxoplasma.
Skin lesions may be produced by the following:
Direct effect of microbial replication in infected cells.
Host response to the microbe.
Interaction of these two phenomena.
Acute infection syndrome: Fever, malaise, coryza, sore throat, nausea, vomiting, diarrhea, abdominal pain, and headache.
Exanthematous Eruption. Resembles the exanthem occurring with measles or morbilli, i.e., measles-like or “morbilliform.” Also referred to as maculopapular. Characterized by initially discrete, often becoming confluent pink macules and papules (Fig. 27-22). Usually central, i.e., head, neck, trunk, and proximal extremities. Most often progresses centrifugally. Lesions can become hemorrhagic with petechiae, hemorrhagic measles.
Measles-like exanthema Disseminated erythematous macules and papules, typical of the cutaneous changes with many viral infections. Differential diagnosis of an exanthematous or morbilliform adverse cutaneous drug eruption. (A) Typical distribution of lesions on the trunk and extremities. (B) Closeup of pink macules and papules becoming confluent in some areas.
Initially, vesicles with clear fluid. May evolve to pustules. In a few days to a week, roof of vesicle sloughs, resulting in erosions. In varicella, lesions are disseminated and may involve oropharynx. In hand foot and mouth disease, vesicles/erosion occur in oropharynx; painful linear vesicles on palms/soles.
Enanthem. Koplik spots in measles. Petechiae on soft palate (Forchheimer sign). Microulcerative lesions in herpangina due to coxsackievirus A (Fig. 27-27). Palatal petechiae in mononucleosis syndrome of primary EBV or CMV infection. Aphthous ulcer-like lesions occur with primary HIV infection.
External aphthous ulcer-like lesion with primary HIV infection.
Lymphadenopathy. Hepatomegaly. Splenomegaly.
Adverse cutaneous drug eruption (ACDE), systemic lupus erythematosus, Kawasaki syndrome.
Usually made on history and clinical findings. Serology: Acute and convalescent titers most helpful in specific diagnosis. Cultures: If practical.
ICD-9: 056 ○ ICD-10: B06
Etiologic Agent. Rubella virus, an RNA togavirus.
Clinical Manifestation. Characteristic exanthem and lymphadenopathy. Many infections are subclinical.
Congenital Rubella Syndrome. Rubella virus infecting a pregnant female, while causing a benign illness in the mother, may result in serious chronic fetal infection and malformation.
Prophylaxis. Childhood immunization is highly effective at preventing infection.
Synonyms: German measles, “3-day measles.”
Etiology and Epidemiology
Rubella virus, an RNA togavirus, member of Rubivirus genus. Attenuated rubella virus used in immunization can cause an illness with rubella-like rash, lymphadenopathy, and arthritis.
Before widespread immunization, most commonly occurred in children <15 years. Currently young adults. Risk factors: Lack of active immunization and lack of natural infection. After immunization began in 1969, incidence decreased by 99% in industrialized countries.
Inhalation of aerosolized respiratory droplets. Moderately contagious. 10–40% of cases asymptomatic. Period of infectivity from end of incubation period to disappearance of rash.
Prodrome usually absent, especially in young children. In adolescents and young adults: anorexia, malaise, conjunctivitis, headache, low-grade fever, and mild upper respiratory tract symptoms. In women, rubella-like illness frequently follows administration of attenuated live rubella virus with arthralgias.
Pink macules, papules (Fig. 27-23). Initially on forehead, spreading inferiorly to face, trunk, and extremities during first day. By second day, facial exanthem fades. By third day, exanthem fades completely without residual pigmentary change or scaling. Truncal lesions may become confluent, creating a scarlatiniform eruption.
Rubella A 21-year-old male. Erythematous macules and papules appearing initially on the face and spreading inferiorly and centrifugally to the trunk and extremities, usually within the first 24 hours. Postauricular and posterior cervical lymph nodes were enlarged. Lesions becoming confluent on the cheeks while clearing on the forehead. Truncal lesions appear 24 hours after onset of facial lesions.
Petechiae on soft palate (Forchheimer sign) during prodrome (also seen in infectious mononucleosis).
Enlarged during prodrome. Postauricular, suboccipital, and posterior cervical lymph nodes enlarged and possibly tender. Mild generalized lymphadenopathy may occur. Enlargement usually persists for 1 week but may last for months.
Arthritis in adults; possible effusion. Arthralgia, especially in adult women after immunization.
Congenital Rubella Syndrome
Congenital heart defects; cataracts; microphthalmia, microcephaly, hydrocephaly, deafness.
Other viral exanthems, ACDE, and scarlet fever.
Acute rheumatic fever, rheumatoid arthritis, erythema infectiosum.
Clinical diagnosis; can be confirmed by serology. Virus can be isolated from throat, joint fluid aspirate.
In most persons, rubella is a mild, inconsequential illness. However, when rubella occurs in a pregnant woman during the first trimester, the infection can be passed transplacentally to the developing fetus. Approximately half of infants who acquire rubella during the first trimester of intrauterine life will show clinical signs of damage from the virus.
Rubella is preventable by immunization. Previous rubella should be documented in young women: if antirubella antibody titers are negative, rubella immunization should be given.
ICD-9: 055 ○ ICD-10: B05
A highly contagious childhood viral disease characterized by fever, coryza, cough; an exanthema; conjunctivitis; pathognomonic enanthem (Koplik spots).
Significant morbidity and mortality occur in acute and chronic course.
Childhood immunization is highly effective at preventing infection.
Synonyms: Morbilli, rubeola.
Etiology and Epidemiology
Measles virus, member of RNA genus Morbillivirus and family Paramyxoviridae.
Measles is no longer endemic in United States, Europe, Canada, and Japan; cases result from importation of measles. Hyperendemic in many developing nations, resulting in 164,000 deaths in 2008.
Current outbreaks in the United States occur in inner city unimmunized preschool-age children, school-age persons immunized at an early age, and imported cases.
Transmission spread by respiratory droplet aerosols produced by sneezing and coughing. Infected persons contagious from several days before onset of rash up to 5 days after lesions appear. Attack rate for susceptible contacts >90–100%. Asymptomatic infection uncommon.
Virus enters cells of respiratory tract, replicates locally, spreads to regional lymph nodes, and disseminates hematogenously to skin and mucous membranes, where it replicated. Modified measles, a milder form of the illness, may occur in individuals with preexisting partial immunity induced by active or passive immunization. Persons deficient in cellular immunity are at high risk for severe measles.
Fever. Malaise. Upper respiratory symptoms (coryza, hacking bark-like cough). Photophobia, conjunctivitis with lacrimation. Periorbital edema. As exanthem progresses, systemic symptoms subside.
On the fourth febrile day, erythematous macules and papules appear on forehead at hairline, behind ears; spread centrifugally and inferiorly to involve the face, trunk (Fig. 27-24), extremities, palms/soles, reaching the feet by third day. Initial discrete lesions may become confluent, especially on face, neck, and shoulders. Lesions gradually fade in order of appearance, with subsequent residual yellow-tan stain or faint desquamation. Exanthem resolves in 4–6 days.
Measles with exanthem (A) Erythematous macule, first appearing on the face and neck where they become confluent, spreading to the trunk and arms in 2–3 days where they remain discrete. In contrast, rubella also first appears initially on the face but spreads to the trunk in 1 day. Koplik spots on the buccal mucosa were also present. Erythematous papules have become confluent on the face on the fourth day. Measles with Koplik spots (B) Red papules on buccal mucosa opposite premolars prior of appearance of exanthema. (From the CDC.)
Cluster of tiny bluish-white spots on red background, appearing on or after second day of febrile illness, are seen on buccal mucosa opposite premolar teeth, i.e., Koplik spots that are pathognomonic of measles. Appear before exanthem. Also: entire buccal/inner labial mucosa may be inflamed.
Conjunctivitis, injected, red.
Generalized lymphadenopathy. Diarrhea, vomiting. Splenomegaly
Milder clinical findings with preexisting partial immunity.
Occurs in individuals immunized with formalin-inactivated measles vaccine, subsequently exposed to measles virus. Exanthem begins peripherally and moves centrally; can be urticarial, maculopapular, hemorrhagic, and/or vesicular. Systemic symptoms can be severe.
Measles in Host With Defense Defects
Rash may not occur. Pneumonitis and encephalitis more common.
Disseminated Maculopapular Eruption
Morbilliform drug eruption, scarlet fever. Kawasaki syndrome.
Clinical diagnosis confirmed by serology. Multinucleated giant cells in secretions. Isolate virus from blood, urine, and pharyngeal secretions. Detect measles antigen in respiratory secretions by immunofluorescent staining. Detects genomic sequences of measles virus RNA in serum, throat swabs, and cerebrospinal fluid (CSF).
Self-limited infection in most patients. Mortality rate in developing countries up to 10%. Age-specific rates of complications highest among children <5 years old and adults >20 years. Sites of complications: respiratory tract, central nervous system (CNS), tract. Complications more common in malnourished children, the unimmunized, and those with congenital immunodeficiency and leukemia. Acute complications (10% of cases): otitis media, pneumonia (bacterial or measles), diarrhea, measles encephalitis, and thrombocytopenia. Chronic complication: subacute sclerosing panencephalitis (Dawson encephalitis).
Prophylactic immunization. Supportive care.
ICD-9: 047 ○ ICD-10: B34.1
Etiologic Agents. Intestinal viruses echovirus 9 and 16, coxsackie A 16 virus, and enterovirus 71 (EV71).
Enteroviral Infections with Rash:
Echovirus 9 (E9): Discrete pink macules and papules resembling rubella ± fever.
Echovirus 16: exanthem, roseola-like (confluent pink papules) ± fever.
Coxsackievirus A16, EV71: hand foot and mouth disease.
A1–10, 16, 22, CB1–5; EV6, 9, 11, 16, 17, 25; EV71: Herpangina.
Other enteroviruses reported to cause erythema multiforme: vesicular, urticarial, petechial, and purpuric rashes.
ICD-9: 074.3 ○ ICD-10: 074.3
Systemic viral infection characterized by ulcerative enanthem; vesicular exanthem on the distal extremities; mild constitutional symptoms.
Etiology. Enterovirus (picornavirus group, single-stranded RNA, nonenveloped). Commonly: coxsackievirus A16 and EV71.
Demography. Most common in first decade. Outbreaks during warmer months (late summer, early fall) in temperate climes. Highly contagious, spread from person to person by oral–oral and fecal–oral routes.
Pathogenesis. Enteroviral implantation in the GI tract (buccal mucosa and ileum) with extension into regional lymph nodes. Seventy-two hours later viremia occurs with seeding of the oral mucosa and skin of the hands and feet.
Frequently 5–10 painful ulcerative oral lesions, leading to refusal to eat in children. Few to 100 cutaneous lesions appear together or shortly after the oral lesions and may be asymptomatic or painful and tender.
Macules and papules that quickly evolve to vesicles. Characteristically, lesions occur on palms and soles, especially on sides of fingers, toes, and buttocks. Vesicles may have characteristic “linear” shape; tender, painful; usually do not rupture (Fig. 27-25). At other cutaneous sites, vesicles can rupture, with formation of erosions and crusts. Lesions heal without scarring.
Hand-foot-and mouth disease A 21-year-old male with extensive blister formation on (A) palms and fingers, and (B) soles and toes.
Macules → grayish vesicles, arising on the hard palate, tongue, and buccal mucosa (Fig. 27-26). Vesicles quickly erode to 5- to 10-mm, small, punched out painful ulcers.
Hand-foot-and-mouth disease Multiple, superficial erosions with an erythematous halo on the lower labial mucosa; gingiva is normal. In primary herpetic gingivostomatitis, which presents with similar oral vesicular lesions, painful erosive gingivitis usually occurs as well.
May be associated with high fever, severe malaise, diarrhea, and joint pains. EV17 infections may have associated CNS (aseptic meningitis, encephalitis, meningoencephalitis, flaccid paralysis), and lung involvement.
A sudden outbreak of oral and distal extremity lesions is pathognomonic for hand foot and mouth disease. However, if only the oral lesions are present, the differential diagnosis would include HSV infection, aphthous stomatitis, herpangina, erythema multiforme, and adverse drug reaction.
Usually made on clinical findings. Virus may be isolated from vesicles, throat washings, and stool specimens.
Most commonly, hand foot and mouth disease is self-limited. Rise in serum antibodies eliminates the viremia in 7–10 days. Coxsackievirus has been implicated in cases of myocarditis, meningoencephalitis, aseptic meningitis, paralytic disease, and a systemic illness resembling measles. EV71 infections have higher morbidity/mortality rates due to CNS involvement and pulmonary edema.
Symptomatic and supportive care.
ICD-9: 074.0 ○ ICD-10: B08.5
Etiologic Agent. Coxsackievirus A1–10; coxsackie B1–5; echoviruses; EV71.
Demography. It usually affects children <5 year, prevalent in late summer and early fall in temperate climes.
Clinical Manifestation. Sudden onset of fever, malaise, headache, anorexia, dysphagia, and sore throat.
Enanthem. 1- to 2-mm gray-white papules/vesicles that evolve to ulcers with red halos, and diffuse pharyngeal hyperemia (Fig. 27-27). Distributed on the anterior tonsillar pillars, soft palate, uvula, and tonsils. Usually lasts 4–6 days, and its course is self-limited.
Herpangina Multiple, small vesicles and erosions with erythematous halos on the soft palate; some taste buds on the posterior tongue are inflamed and prominent.
ICD-9: 057.0 ○ ICD-10: B08.3
Childhood exanthem associated with primary human parvovirus b19 (HPVB19) infection.
Characterized by edematous erythematous plaques on the cheeks (“slapped cheeks”); erythematous lacy eruption on the trunk and extremities.
Etiology and Epidemiology
HPVB19 is a small single-stranded, nonenveloped virus. It is present in respiratory tract during the viremic stage of primary infection. Transmission by droplet aerosol.
More common in young. Sixty percent of adolescents and adults are seropositive for antiparvovirus B19 IgG. Symptomatic rheumatic involvement is more common in adult women.
Viremia develops 6 days after intranasal inoculation of HPVB19 into volunteers who lack serum antibodies to the virus. IgM and then IgG antibodies develop after a week and clear viremia. Significant bone marrow depression can occur at this time. The exanthem begins 17–18 days after inoculation and may be accompanied by arthralgia and/or arthritis; these findings are mediated by immune complexes. In compromised hosts, PVB19 can destroy erythroid precursor cells, causing severe aplastic crisis in adults and hydrops fetalis in the fetus.
Constitutional symptoms more severe in adults, with fever, adenopathy. Arthritis/arthralgias involving small joints of hand, knees, wrists, ankles, feet. Numbness and tingling of fingers.
Edematous, confluent plaques on malar face (“slapped cheeks”) (Fig. 27-28A) (nasal bridge, periorbital regions spared); lesions fade over 1–4 days. Usually absent in adults.
A: Erythema infectiosum: slapped cheek A 10-year-old child. Diffuse erythema and edema of the cheeks with “slapped cheek” facies. B: Erythema infectiosum: reticulated erythema A 10-year-old child. Discrete, erythematous macules with ring formation on the arm.
Appear after facial lesions. Erythematous macules and papules that become confluent, giving a lacy or reticulated appearance (Fig. 27-28B). Best seen on extensor arms; also trunk and neck. Fade in 5–9 days. Reticulated rash may recur. Adults: reticulated macules on extremities.
Less Commonly, morbilliform, confluent, circinate, annular exanthems. Rarely, purpura, vesicles, pustules, palmoplantar desquamation. PVB19 also reported to cause papular purpuric “gloves and socks” syndrome.
Uncommonly, enanthem with glossal and pharyngeal erythema; red macules on buccal and palatal mucosa.
Arthralgia and/or arthritis in 10% of children; typically involving large joints. Arthritis in adult women.
CNS and peripheral neuropathy
occur in persons with altered immunity.
Children with Erythema Infectiosum
Childhood exanthems, Haemophilus influenzae cellulitis, adverse cutaneous drug reaction.
Lyme arthritis, rheumatoid arthritis, rubella.
Usually made on clinical findings. Demonstration of IgM anti-HPVB19 antibodies or IgG seroconversion. Demonstration of HPVB19 in serum. During aplastic crisis: absence of reticulocytes, falling hemoglobin, hypoplasia or aplasia of erythroid series in bone marrow.
“Slapped cheeks” are noted first, fading over 1–4 days. Then, reticulated rash appears on the trunk, neck, and extensor extremities. Eruption lasts 5–9 days but characteristically can recur for weeks or months.
Self-limited, lasting 3 weeks, but may persist for several months or years.
In patients with chronic hemolytic anemias, transient aplastic crisis may occur, manifested by worsening anemia, fatigue, and pallor.
Intrauterine infection may be complicated by nonimmune fetal hydrops secondary to infection of RBC precursors, hemolysis, severe anemia, tissue anoxia, and high-output heart failure. Risk <10% after maternal infection.
Prolonged chronic anemia associated with persistent lysis of RBC precursors. At risk: HIV disease, congenital immunodeficiencies, acute leukemia, organ transplants, systemic lupus erythematosus, and infants <1 year. Responds to intravenous immunoglobulin (IVIg).
ICD-9: 057.8 ○ ICD-10: L44.4
Cutaneous reaction pattern associated with primary infection and immune response to viruses, bacteria, and vaccines.
Viruses: EBV, CMV, hepatitis B virus (ayw strain), coxsackievirus, parainfluenza virus, respiratory syncytial virus, rotavirus, adenovirus, echovirus, pox virus, poliovirus, parvovirus, HIV, hepatitis A virus, hepatitis C virus.
Bacteria: Mycoplasma pneumoniae, Borrelia burgdorferi, Bartonella henselae, group A streptococcus.
Vaccines: influenza, diphtheria, tetanus, pertussis, BCG, H. influenzae type b, oral polio.
Epidemiology. Occurs in children 6 months to 12 years. Manifestation of immune response to transient viremia with immune complex deposition in the skin.
Discrete, nonpruritic, erythematous, monomorphic papules (Fig. 27-29). Lesions become coalescent. Face, buttocks, and extensor surfaces of extremities; symmetric. Typically, the trunk is spared. Duration is 2–8 weeks.
Gianotti–Crosti syndrome A 6-year-old boy with multiple red papules becoming confluent of the cheeks.
Synonym: Papular acrodermatitis of childhood (PAC)
ICD-9: 061 ○ ICD-10: A90
Arthralgia–rash syndrome with abrupt onset of fever and muscle and joint pains, usually with retro-orbital pain, photophobia, and lymphadenopathy. Rash: early flushing; later macules/papules; purpura.
Increased vascular permeability and plasma leakage from blood vessels into tissues, thrombocytopenia, bleeding manifestations (frank hemorrhage to spontaneous petechiae or elicited by tourniquet test). Plasma leakage causes a rise in hematocrit, effusions, and edema, especially in chest, abdomen (Fig. 27-30).
Dengue hemorrhagic fever A 39-year-old with fever and rash after a trip to Malaysia. Dermal hemorrhage and petechiae on normal tanned (A) and white skin are seen on the buttocks 48 hours later [white islands in a see of red (B)]. (Courtesy of C Hafner et al. Hemorrhagic dengue fever after trip to Malaysia. Hautarzt. 2006;57(8):705–707.)
Occurs when leakage or bleeding, or both, are sufficient to induce hypovolemic shock.
Etiology and Epidemiology
Flavivirus, single-stranded RNA virus. Four distinct dengue serotypes (DEN-1, -2, -3, -4). Arthropod-borne virus (arbovirus). Infection confers lifelong protection against that serotype, but cross-protection between serotypes is of short duration. Infection with virus of a different serotype after the primary attack is more apt to result in severe disease, dengue hemorrhagic fever, or dengue shock syndrome.
Transmitted by the bite of the Aedes aegypti mosquito; less commonly A. albopictus. Mosquito acquires virus by feeding upon viremic human; remains infective for life.
2.5 billion people live in dengue endemic areas; 50–100 million cases of dengue worldwide annually. Most cases occurring in United States are imported in travelers returning from the tropics. Year-round transmission between latitudes 25°N and 25°S. Increased incidence associated with rapid urban population growth, overcrowding, lax mosquito control, and climate change.
of severe syndrome involves preexisting dengue antibody. Virus–antibody complexes formed within a few days of second dengue infection; non-neutralizing enhancing antibodies promote infection of higher numbers of mononuclear cells, followed by release of cytokines, vasoactive mediators, and procoagulants, leading to the disseminated intravascular coagulation.
3–7 days after bite of infected mosquito. Most dengue virus infections are asymptomatic.
High temperature (≥38.5°C) accompanied by headache, vomiting, myalgia, and joint pain. In some cases, a transient macular rash (Fig. 27-30A). Petechiae and bruising may be noted at venipuncture sites (Fig. 27-30B). Lasts for 3–7 days after which most patients recover with complications.
Becomes apparent around the time of defervescence, evidenced by increasing hemoconcentration, hypoproteinemia, pleural effusions, and ascites. Hemorrhagic manifestations occur, manifested by major skin bleeding, gastrointestinal (GI), or vaginal bleeding. Moderate-to-severe thrombocytopenia common, followed by rapid recovery during recovery phase.
Altered vascular permeability resolves after 48–72 hours. A second rash may be appearing during recovery phase, mild macules/papules to severe, pruritic suggesting leukocytoclastic vasculitis. Rash resolves with desquamation over 1–2 weeks. Profound fatigue persists for several weeks after recovery.
Other arborviral infection such as chikungunya and viral exanthems. Disease with local prevalence: typhoid, malaria, leptospirosis, viral hepatitis, rickettsial diseases, and bacterial sepsis.
Consider diagnosis in travelers with febrile illness recently returned from endemic areas. During febrile phase, detection of viral nucleic acid in serum diagnostic. IgM seroconversion between paired samples is confirmatory finding.
Symptomatic supportive therapy (http://www.cdc.gov/dengue/).