- Email: [email protected]
Erythematous Macules and Papules
Erythematous Macules and Papules
69
69
Erythematous Macules and Papules Brittany S. Barros and Andrea L. Zaenglein
APPROACH Differentiating rashes due to infection from other common cutaneous eruptions, particularly adverse drug eruptions, can be difficult. Recognizing the differences in presentation and using proper terminology for erythematous exanthems are the initial steps. The commonly used (and often overused) term maculopapular describes a rash that has both macular and papular components at some time during the course of the disease. Morbilliform (i.e., measles-like) is used to describe uniform lesions that have coalesced. Scarlatiniform is used when the exanthem resembles scarlet fever (i.e., has a sandpaper feel and is confluent in the flexural areas). If lesions are generalized but remain discrete, the term rubelliform may be used. Secondary characteristics should be added to further describe the exanthem; annular, lacy, reticulated, evanescent, urticarial, petechial, and purpuric are useful descriptors. Color is described in shades, and erythema can range from faint pink to violaceous red. Many of the classic exanthems, such as measles, rubella, and erythema infectiosum, are associated with macules or papules on the skin. Differentiating common and uncommon causes of infectious rashes often is difficult because the patterns are not always unique to a specific infectious agent. Detailed and accurate history taking is vital to making a correct diagnosis (Box 69.1). The patient’s age and pre-existing conditions are important because many infectious rashes occur predominantly within a specific age range or in the context of another illness.
ETIOLOGIC AGENTS, EPIDEMIOLOGY, AND PATHOGENESIS Macular and papular exanthems can result from numerous infectious causes. An extensive list of viral and nonviral causes is shown in Box 69.2.
BOX 69.1 Questions Used to Elucidate the Causes of Exanthems • • • • • • • • • • • • • • • • •
What time of year did the rash start? Where on the body did the rash start, and how has it evolved? Is the eruption localized or generalized? Does the rash come and go? Over what timeframe? Is the rash worse at a specific time of day? Is the rash made worse by the sun? Is there an associated enanthem? Is the rash pruritic, painful, or asymptomatic? Are there other symptoms, such as joint swelling, fever, adenopathy, vomiting, cough, headache, or photophobia? Is there a recent history of use of any medications, including over-the-counter medications? Has there been a recent illness? Has there been recent exposure to another person with a similar illness? Is the child in group childcare or school? Are immunizations up to date? Is there an immunocompromising condition or drug? Where was the child born? Has there been recent travel? Has there been recent exposure to pets, wildlife, or biting insects? What evaluations, including laboratory studies and cultures, have been done already? Has treatment been given? Was the treatment effective?
FIGURE 69.1 Discrete, confluent, erythematous, pink, blanchable papules are associated with enterovirus infection.
In children, enteroviruses are by far the most common cause of morbilliform rash with febrile illness, especially for those younger than 1 year of age1 (Fig. 69.1). Enteroviruses have a marked seasonality, with an increase in prevalence in the summer and a large peak in August and autumn. Parvovirus B19, the etiologic agent of erythema infectiosum, is the maculopapular rash most commonly identified in children 4 through 10 years of age.2 The exanthem is typified by bright red macules on the cheeks that spare the nasolabial folds (Fig. 69.2), followed by the development of reticulated lacy pink macules and thin papules on the extremities that can persist for up to 3 weeks. Measles occurs as sporadic imported cases or in high-profile outbreaks in the United States and is still prevalent worldwide. Measles is characterized by the classic morbilliform rash accompanied by fever and the three Cs: cough, conjunctivitis, and coryza.3 Maculopapular rashes in children also can be indirectly related to an infectious agent. An estimated 1.2% to 12% of children develop cutaneous adverse reactions to medications, especially antibiotics.4 Many
FIGURE 69.2 Bilateral, bright red, macular erythema of the cheeks is typical of parvovirus infection.
445
BOX 69.2 Infectious Conditions That Cause Macular and Papular Exanthems VIRUSES Human Herpesviruses Erythema multiforme Varicella Shingles Mononucleosis Pityriasis rosea Roseola infantum Poxviruses Smallpox Vaccina Orf disease Milker nodules Cowpox Molluscum contagiosum Polyomaviruses Trichodysplasia spinulosa Picornaviruses (Coxsackievirus and Echovirus) Nonspecific exanthems Hand-foot-and-mouth disease Boston exanthem Eruptive pseudoangiomatosis Paramyxoviruses Measles Rubella Parvoviruses Erythema infectiosum Papular-purpuric gloves and socks syndrome Arboviruses West Nile fever Dengue Alphavirus
Cat-scratch disease Bacillary angiomatosis Rat-bite fever Tularemia Brucellosis Ehrlichiosis Anaplasmosis Leptospirosis Lyme disease Secondary syphilis Yaws Pinta RICKETTSIA Epidemic typhus Endemic typhus Rocky Mountain spotted fever Mediterranean spotted fever African tick bite fever Yucatan spotted fever Japanese spotted fever North Asian tick-bite fever Queensland tick typhus Scrub typhus Rickettsialpox Q fever PROTOZOA Amebiasis cutis Leishmaniasis Trypanosomiasis Toxoplasmosis HELMINTHS Trematodes Freshwater swimmers’ itch Saltwater marine dermatitis
Human Papillomaviruses
Nematodes
Warts
Human T-lymphotropic virus 1 infection
Pinworms (can cause generalized papules) Hookworms Larva migrans Onchocerciasis
Conditions With Likely Viral Causes
FUNGI
Gianotti-Crosti syndrome Unilateral laterothoracic exanthem
Dermatophytes
Retroviruses
BACTERIA Impetigo Folliculitis Paronychia Staphylococcal scalded skin syndrome Toxic shock syndromes Scarlet fever Erysipelas Cellulitis Perineal dermatitis Rheumatic fever Erythrasma Actinomycosis Ecthyma Hot tub folliculitis Meningococcemia Gonococcemia Salmonellosis Glanders
Tinea capitis Tinea corporis Tinea faciei Tinea cruris Majocchi granuloma Early Cutaneous or Deep Fungal Infections Blastomycosis Histoplasmosis Coccidioidomycosis Phaeohyphomycosis Chromomycosis Sporotrichosis Fusariosis Aspergillosis Alternaria infection Yeast Candidiasis Tinea versicolor
TABLE 69.1 Common Noninfectious Causes of Macular and Papular Exanthems
FIGURE 69.3 Many cutaneous adverse drug eruptions are indistinguishable from viral exanthems. The generalized, pink, erythematous macules occurred on a 2-year-old child with an upper respiratory infection that was treated with amoxicillin.
cutaneous adverse drug eruptions (CADEs) are indistinguishable from viral exanthems because they have a similar morphology and course (Fig. 69.3). In the case of mononucleosis caused by Epstein-Barr virus, the administration of an antibiotic (classically ampicillin) can lead to a florid maculopapular rash in about 3% of children.5 More severe CADEs, including Stevens-Johnson syndrome and toxic epidermal necrolysis, can manifest with macules and papules before progressing to blistering. Mucosal involvement in this setting should alert the clinician to this possibility. A drug reaction with eosinophilia and systemic symptoms (DRESS) is another severe CADE manifesting with a widespread morbilliform eruption and often with pronounced facial swelling associated with variable systemic involvement, including liver, renal, and pulmonary dysfunction. Type 4 delayed hypersensitivity and reactivation of
Predominantly Papules
Predominantly Macules
Insect bites Acne Keratosis pilaris Miliaria Granuloma annulare Cnidarian stings
Sunburn Dermatomyositis Systemic lupus erythematosus
Macules and Papules Adverse drug eruptions • Urticarial drug reaction • Morbilliform drug reaction • Early Stevens-Johnson syndrome or toxic epidermal necrolysis • Drug reaction with eosinophilia and systemic symptoms (DRESS) Atopic dermatitis Seborrheic dermatitis Guttate psoriasis Contact dermatitis Polymorphous light eruption
human herpesvirus 6 have been postulated in the etiopathogenesis of this CADE.6 Common noninfectious causes of macular and papular exanthems are listed in Table 69.1. These disorders should be considered in the differential diagnosis. All references are available online at www.expertconsult.com.
KEY REFERENCES 1. Centers for Disease Control and Prevention. Enterovirus surveillance—United States, 1970–2005. MMWR Surveill Summ 2006;55:1–20. 2. Dyer J. Childhood viral exanthems. Pediatr Ann 2007;36:21–29. 3. Zipprich J, Winter K, Hacker J, et al. Measles outbreak—California, December 2014–February 2015. MMWR Morb Mortal Wkly Rep 2015;64:153–154. 4. Segal AR, Doherty KM, Leggott J, et al. Cutaneous reactions to drugs in children. Pediatrics 2007;120:e1082–e1096. 5. Chovel-Sella A, Ben Tov A, Lahav E, et al. Incidence of rash after amoxicillin treatment in children with infectious mononucleosis. Pediatrics 2013;131:e1424–e1427. 6. Noguera-Morel L, Hernández-Martín Á, Torrelo A. Cutaneous drug reactions in the pediatric population. Pediatr Clin North Am 2014;61:403–426.
Erythematous Macules and Papules
REFERENCES 1. Centers for Disease Control and Prevention. Enterovirus surveillance—United States, 1970–2005. MMWR Surveill Summ 2006;55:1–20. 2. Dyer J. Childhood viral exanthems. Pediatr Ann 2007;36:21–29. 3. Zipprich J, Winter K, Hacker J, et al. Measles outbreak—California, December 2014–February 2015. MMWR Morb Mortal Wkly Rep 2015;64:153–154.
69
4. Segal AR, Doherty KM, Leggott J, et al. Cutaneous reactions to drugs in children. Pediatrics 2007;120:e1082–e1096. 5. Chovel-Sella A, Ben Tov A, Lahav E, et al. Incidence of rash after amoxicillin treatment in children with infectious mononucleosis. Pediatrics 2013;131:e1424–e1427. 6. Noguera-Morel L, Hernández-Martín Á, Torrelo A. Cutaneous drug reactions in the pediatric population. Pediatr Clin North Am 2014;61:403–426.
447.e1
69
69
Erythematous Macules and Papules Brittany S. Barros and Andrea L. Zaenglein
APPROACH Differentiating rashes due to infection from other common cutaneous eruptions, particularly adverse drug eruptions, can be difficult. Recognizing the differences in presentation and using proper terminology for erythematous exanthems are the initial steps. The commonly used (and often overused) term maculopapular describes a rash that has both macular and papular components at some time during the course of the disease. Morbilliform (i.e., measles-like) is used to describe uniform lesions that have coalesced. Scarlatiniform is used when the exanthem resembles scarlet fever (i.e., has a sandpaper feel and is confluent in the flexural areas). If lesions are generalized but remain discrete, the term rubelliform may be used. Secondary characteristics should be added to further describe the exanthem; annular, lacy, reticulated, evanescent, urticarial, petechial, and purpuric are useful descriptors. Color is described in shades, and erythema can range from faint pink to violaceous red. Many of the classic exanthems, such as measles, rubella, and erythema infectiosum, are associated with macules or papules on the skin. Differentiating common and uncommon causes of infectious rashes often is difficult because the patterns are not always unique to a specific infectious agent. Detailed and accurate history taking is vital to making a correct diagnosis (Box 69.1). The patient’s age and pre-existing conditions are important because many infectious rashes occur predominantly within a specific age range or in the context of another illness.
ETIOLOGIC AGENTS, EPIDEMIOLOGY, AND PATHOGENESIS Macular and papular exanthems can result from numerous infectious causes. An extensive list of viral and nonviral causes is shown in Box 69.2.
BOX 69.1 Questions Used to Elucidate the Causes of Exanthems • • • • • • • • • • • • • • • • •
What time of year did the rash start? Where on the body did the rash start, and how has it evolved? Is the eruption localized or generalized? Does the rash come and go? Over what timeframe? Is the rash worse at a specific time of day? Is the rash made worse by the sun? Is there an associated enanthem? Is the rash pruritic, painful, or asymptomatic? Are there other symptoms, such as joint swelling, fever, adenopathy, vomiting, cough, headache, or photophobia? Is there a recent history of use of any medications, including over-the-counter medications? Has there been a recent illness? Has there been recent exposure to another person with a similar illness? Is the child in group childcare or school? Are immunizations up to date? Is there an immunocompromising condition or drug? Where was the child born? Has there been recent travel? Has there been recent exposure to pets, wildlife, or biting insects? What evaluations, including laboratory studies and cultures, have been done already? Has treatment been given? Was the treatment effective?
FIGURE 69.1 Discrete, confluent, erythematous, pink, blanchable papules are associated with enterovirus infection.
In children, enteroviruses are by far the most common cause of morbilliform rash with febrile illness, especially for those younger than 1 year of age1 (Fig. 69.1). Enteroviruses have a marked seasonality, with an increase in prevalence in the summer and a large peak in August and autumn. Parvovirus B19, the etiologic agent of erythema infectiosum, is the maculopapular rash most commonly identified in children 4 through 10 years of age.2 The exanthem is typified by bright red macules on the cheeks that spare the nasolabial folds (Fig. 69.2), followed by the development of reticulated lacy pink macules and thin papules on the extremities that can persist for up to 3 weeks. Measles occurs as sporadic imported cases or in high-profile outbreaks in the United States and is still prevalent worldwide. Measles is characterized by the classic morbilliform rash accompanied by fever and the three Cs: cough, conjunctivitis, and coryza.3 Maculopapular rashes in children also can be indirectly related to an infectious agent. An estimated 1.2% to 12% of children develop cutaneous adverse reactions to medications, especially antibiotics.4 Many
FIGURE 69.2 Bilateral, bright red, macular erythema of the cheeks is typical of parvovirus infection.
445
BOX 69.2 Infectious Conditions That Cause Macular and Papular Exanthems VIRUSES Human Herpesviruses Erythema multiforme Varicella Shingles Mononucleosis Pityriasis rosea Roseola infantum Poxviruses Smallpox Vaccina Orf disease Milker nodules Cowpox Molluscum contagiosum Polyomaviruses Trichodysplasia spinulosa Picornaviruses (Coxsackievirus and Echovirus) Nonspecific exanthems Hand-foot-and-mouth disease Boston exanthem Eruptive pseudoangiomatosis Paramyxoviruses Measles Rubella Parvoviruses Erythema infectiosum Papular-purpuric gloves and socks syndrome Arboviruses West Nile fever Dengue Alphavirus
Cat-scratch disease Bacillary angiomatosis Rat-bite fever Tularemia Brucellosis Ehrlichiosis Anaplasmosis Leptospirosis Lyme disease Secondary syphilis Yaws Pinta RICKETTSIA Epidemic typhus Endemic typhus Rocky Mountain spotted fever Mediterranean spotted fever African tick bite fever Yucatan spotted fever Japanese spotted fever North Asian tick-bite fever Queensland tick typhus Scrub typhus Rickettsialpox Q fever PROTOZOA Amebiasis cutis Leishmaniasis Trypanosomiasis Toxoplasmosis HELMINTHS Trematodes Freshwater swimmers’ itch Saltwater marine dermatitis
Human Papillomaviruses
Nematodes
Warts
Human T-lymphotropic virus 1 infection
Pinworms (can cause generalized papules) Hookworms Larva migrans Onchocerciasis
Conditions With Likely Viral Causes
FUNGI
Gianotti-Crosti syndrome Unilateral laterothoracic exanthem
Dermatophytes
Retroviruses
BACTERIA Impetigo Folliculitis Paronychia Staphylococcal scalded skin syndrome Toxic shock syndromes Scarlet fever Erysipelas Cellulitis Perineal dermatitis Rheumatic fever Erythrasma Actinomycosis Ecthyma Hot tub folliculitis Meningococcemia Gonococcemia Salmonellosis Glanders
Tinea capitis Tinea corporis Tinea faciei Tinea cruris Majocchi granuloma Early Cutaneous or Deep Fungal Infections Blastomycosis Histoplasmosis Coccidioidomycosis Phaeohyphomycosis Chromomycosis Sporotrichosis Fusariosis Aspergillosis Alternaria infection Yeast Candidiasis Tinea versicolor
TABLE 69.1 Common Noninfectious Causes of Macular and Papular Exanthems
FIGURE 69.3 Many cutaneous adverse drug eruptions are indistinguishable from viral exanthems. The generalized, pink, erythematous macules occurred on a 2-year-old child with an upper respiratory infection that was treated with amoxicillin.
cutaneous adverse drug eruptions (CADEs) are indistinguishable from viral exanthems because they have a similar morphology and course (Fig. 69.3). In the case of mononucleosis caused by Epstein-Barr virus, the administration of an antibiotic (classically ampicillin) can lead to a florid maculopapular rash in about 3% of children.5 More severe CADEs, including Stevens-Johnson syndrome and toxic epidermal necrolysis, can manifest with macules and papules before progressing to blistering. Mucosal involvement in this setting should alert the clinician to this possibility. A drug reaction with eosinophilia and systemic symptoms (DRESS) is another severe CADE manifesting with a widespread morbilliform eruption and often with pronounced facial swelling associated with variable systemic involvement, including liver, renal, and pulmonary dysfunction. Type 4 delayed hypersensitivity and reactivation of
Predominantly Papules
Predominantly Macules
Insect bites Acne Keratosis pilaris Miliaria Granuloma annulare Cnidarian stings
Sunburn Dermatomyositis Systemic lupus erythematosus
Macules and Papules Adverse drug eruptions • Urticarial drug reaction • Morbilliform drug reaction • Early Stevens-Johnson syndrome or toxic epidermal necrolysis • Drug reaction with eosinophilia and systemic symptoms (DRESS) Atopic dermatitis Seborrheic dermatitis Guttate psoriasis Contact dermatitis Polymorphous light eruption
human herpesvirus 6 have been postulated in the etiopathogenesis of this CADE.6 Common noninfectious causes of macular and papular exanthems are listed in Table 69.1. These disorders should be considered in the differential diagnosis. All references are available online at www.expertconsult.com.
KEY REFERENCES 1. Centers for Disease Control and Prevention. Enterovirus surveillance—United States, 1970–2005. MMWR Surveill Summ 2006;55:1–20. 2. Dyer J. Childhood viral exanthems. Pediatr Ann 2007;36:21–29. 3. Zipprich J, Winter K, Hacker J, et al. Measles outbreak—California, December 2014–February 2015. MMWR Morb Mortal Wkly Rep 2015;64:153–154. 4. Segal AR, Doherty KM, Leggott J, et al. Cutaneous reactions to drugs in children. Pediatrics 2007;120:e1082–e1096. 5. Chovel-Sella A, Ben Tov A, Lahav E, et al. Incidence of rash after amoxicillin treatment in children with infectious mononucleosis. Pediatrics 2013;131:e1424–e1427. 6. Noguera-Morel L, Hernández-Martín Á, Torrelo A. Cutaneous drug reactions in the pediatric population. Pediatr Clin North Am 2014;61:403–426.
Erythematous Macules and Papules
REFERENCES 1. Centers for Disease Control and Prevention. Enterovirus surveillance—United States, 1970–2005. MMWR Surveill Summ 2006;55:1–20. 2. Dyer J. Childhood viral exanthems. Pediatr Ann 2007;36:21–29. 3. Zipprich J, Winter K, Hacker J, et al. Measles outbreak—California, December 2014–February 2015. MMWR Morb Mortal Wkly Rep 2015;64:153–154.
69
4. Segal AR, Doherty KM, Leggott J, et al. Cutaneous reactions to drugs in children. Pediatrics 2007;120:e1082–e1096. 5. Chovel-Sella A, Ben Tov A, Lahav E, et al. Incidence of rash after amoxicillin treatment in children with infectious mononucleosis. Pediatrics 2013;131:e1424–e1427. 6. Noguera-Morel L, Hernández-Martín Á, Torrelo A. Cutaneous drug reactions in the pediatric population. Pediatr Clin North Am 2014;61:403–426.
447.e1