Pediatric Dermatology Consult

By Ellen S. Haddock, MBA, and Lawrence F. Eichenfield, MD

Molluscum

Molluscum typically presents as smooth, flesh-colored, flat-topped papules 2-8 mm in diameter with central whitish area, which is composed of the causative molluscum pox virus. While central depressions called umbilications are common, they may not be present in early molluscum lesions.^1,2 Lesions most often occur on the trunk and arms, but can occur anywhere.3-5 Individuals usually have multiple lesions, which may be clustered especially in areas of skin-to-skin contact.^5,6 Molluscum lesions can be itchy.

Molluscum is a benign viral skin infection caused by the molluscum contagiosum virus, which is a member of the poxvirus family. Molluscum infections are common, affecting 5%-11% of children.^5,7 Molluscum most often affects children younger than 8-years-old,⁵ with an average age of 5.8 years.⁸ The infection is spread through skin-to-skin contact with other individuals and by autoinoculation, which means that the infection can be spread from one area of an individual's skin to another when he or she scratches a lesion and then touches another area. It also can be spread by contact with fomites like towels and sponges.1 An association between public swimming pool use and molluscum infection has been reported, but this may have more to do with shared towels and equipment like kick-boards than transmission through the water itself.9 Molluscum sometimes is spread through contact sports like wrestling⁶ and between children sharing a bath.⁹ In adults, in whom molluscum is much less common because of acquired immunity,10 molluscum may be sexually transmitted or associated with HIV; however, this is rarely the case in children.¹

Children with atopic dermatitis have increased risk of molluscum infection in part because breaks in their skin and pruritus facilitate autoinoculation through scratching.¹¹ Not uncommonly, molluscum lesions become inflamed, with tenderness, erythema, and crust. In a study by Berger et al., 22% of patients had inflamed molluscum lesions.³ The appearance of inflamed molluscum lesions may raise concern about bacterial infection, but more often, the inflammation is a sign that the immune system is reacting to the viral infection and has almost "won the battle."¹⁰ After inflamed molluscum lesions develop, the total number of molluscum lesions typically declines,3 and some consider inflamed molluscum lesions to be a "beginning of the end sign," indicating that the infection may soon resolve.¹⁰ If the child is afebrile, lesions are itchy and painless, skin culture is negative, and there is no lymphangitis or spreading erythema, the inflammation is more likely a sign of impending resolution than bacterial secondary infection, and the urge to prescribe antibiotics should be resisted.¹⁰

As seen in this case, some patients with molluscum (5%) develop a diffuse, monomorphous, papular, or papulovesicular eruption that is an id reaction.3 This may appear to be eczema-like, lichenoid in appearance, or mimicking Gianotti-Crosti syndrome (papular acrodermatitis of childhood).³ It typically affects the arms and legs, is bilateral, and may be pruritic. The id reaction may occur in conjunction with inflamed molluscum, as is true in this case. The diffuse eruption can sometimes be mistaken for a sudden increase in the number of molluscum lesions, but the papular dermatitis lesions do not have the flat-topped dome-shape nor white centers.³ On average, the id reaction lasts about 6 weeks, after which both it and the primary molluscum lesions typically resolve.³ Although not seen in this case, more than a third of molluscum patients develop a pruritic, erythematous, eczematous area around molluscum lesions, termed molluscum dermatitis or eczema molluscatum, which may be more prominent than the molluscum itself.³ The eczematous patch typically surrounds molluscum lesions but also may occur at distant sites.¹² This reaction is especially common in patients with atopic dermatitis, 51% of whom develop it.³ It is considered a hypersensitivity reaction and may be asymptomatic or minimally pruritic.¹² Molluscum dermatitis suggests that the immune system has taken notice of the infection and is fighting it¹³; however, it does not necessarily indicate impending resolution.³

Differential diagnosis

The differential diagnosis for molluscum includes herpes simplex, warts, and milia.¹⁴ Like molluscum, herpes simplex lesions can have central umbilication, but the lesions are vesicular rather than solid. Warts typically have a rough, jagged surface in contrast to the smooth surface of molluscum lesions. Milia tend to be smaller and not flat topped. They are more common in infants and adults than in children and primarily affect the face.

Inflamed molluscum lesions and molluscum dermatitis can be mistaken for atopic dermatitis, and molluscum-associated id reactions may exacerbate atopic dermatitis. Inflamed molluscum and molluscum with id reaction could be confused with scabies, which may become crusted and also may be accompanied by id reaction. Presence of serpiginous linear burrows would suggest scabies rather than molluscum, and the diagnosis of scabies can be confirmed by scraping a burrow and looking for a mite or its feces under a microscope.

Prognosis and treatment

Molluscum infections typically resolve spontaneously in months to years (average duration, 13 months),¹⁴ so treatment may not be required. The goal of treatment is to accelerate the resolution of the infection, but some studies have found that common treatments may not shorten the time to resolution.¹¹ However, if there is substantial pruritus, lesions are cosmetically undesirable, or a child has atopic dermatitis and is at increased risk for autoinoculation, treatment may be warranted.¹⁵ Furthermore, molluscum lesions can scar, so prevention of autoinoculation may help minimize scarring.¹⁶

Few high-quality studies of the efficacy of molluscum treatments exist, and a 2009 Cochrane review found insufficient evidence to recommend any therapy for molluscum. The most common treatment used by pediatric dermatologists is cantharidin,¹⁷ and this treatment also is available to primary care practitioners. This option is preferred over other destructive methods such as curettage or liquid nitrogen cryotherapy because it is not painful or traumatic and is well tolerated by pediatric patients.⁸ Parent and physician satisfaction with the therapy is high; 78%-95% of parents would use cantharidin treatment again for molluscum recurrence.^4,8,18 Originally extracted from the blister beetle but now synthesized commercially,¹⁹ cantharidin causes vesiculation at the dermoepidermal junction6 by destroying intercellular connections.4 Vesiculation of the skin causes extrusion of the molluscum body, which facilitates resolution of the lesion.¹⁹ The cantharidin formulation is applied directly to molluscum lesions with the wooden end of a cotton-tipped applicator.⁴ Patients may be directed to wash it off after 4-6 hours. Blistering is an expected, desired outcome. A minority of patients may experience mild temporary pain (7%), more significant blistering (2.5%), burning (less than 1%), pruritus (less than 1%), or irritation (less than 1%).⁴ There is a risk of scarring and pigmentary changes, but these risks also exist for untreated lesions.¹⁹ Cantharidin treatment is repeated approximately every 4 weeks, and 90% of cases resolve after an average of 2.1 treatments.¹⁸ Topical retinoids can be used in an attempt to trigger an irritant response by the immune system, and they are the preferred therapy for facial lesions, but they are inconsistently effective.4 Randomized controlled trials found that imiquimod, a previously popular treatment is not effective,²⁰ and the evidence for cimetidine is contradictory.^21,22 Molluscum dermatitis and id reaction can be treated with medium strength topical steroids. 

References

1. Viral diseases of the skin, in "Hurwitz Clinical Pediatric Dermatology," 4 ed. (New York: Elsevier, 2011, pp. 348-69). .
2. Molluscum, in "Red Book Report of the Committee on Infectious Diseases," 2015.

Ms. Haddock is a medical student at the University of California, San Diego, and a research associate at Rady Children's Hospital-San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Eichenfield and Ms. Haddock state they have no relevant financial disclosures.

By Ellen S. Haddock, MBA, and Lawrence F. Eichenfield, MD

Molluscum

Molluscum typically presents as smooth, flesh-colored, flat-topped papules 2-8 mm in diameter with central whitish area, which is composed of the causative molluscum pox virus. While central depressions called umbilications are common, they may not be present in early molluscum lesions.^1,2 Lesions most often occur on the trunk and arms, but can occur anywhere.3-5 Individuals usually have multiple lesions, which may be clustered especially in areas of skin-to-skin contact.^5,6 Molluscum lesions can be itchy.

Molluscum is a benign viral skin infection caused by the molluscum contagiosum virus, which is a member of the poxvirus family. Molluscum infections are common, affecting 5%-11% of children.^5,7 Molluscum most often affects children younger than 8-years-old,⁵ with an average age of 5.8 years.⁸ The infection is spread through skin-to-skin contact with other individuals and by autoinoculation, which means that the infection can be spread from one area of an individual's skin to another when he or she scratches a lesion and then touches another area. It also can be spread by contact with fomites like towels and sponges.1 An association between public swimming pool use and molluscum infection has been reported, but this may have more to do with shared towels and equipment like kick-boards than transmission through the water itself.9 Molluscum sometimes is spread through contact sports like wrestling⁶ and between children sharing a bath.⁹ In adults, in whom molluscum is much less common because of acquired immunity,10 molluscum may be sexually transmitted or associated with HIV; however, this is rarely the case in children.¹

Children with atopic dermatitis have increased risk of molluscum infection in part because breaks in their skin and pruritus facilitate autoinoculation through scratching.¹¹ Not uncommonly, molluscum lesions become inflamed, with tenderness, erythema, and crust. In a study by Berger et al., 22% of patients had inflamed molluscum lesions.³ The appearance of inflamed molluscum lesions may raise concern about bacterial infection, but more often, the inflammation is a sign that the immune system is reacting to the viral infection and has almost "won the battle."¹⁰ After inflamed molluscum lesions develop, the total number of molluscum lesions typically declines,3 and some consider inflamed molluscum lesions to be a "beginning of the end sign," indicating that the infection may soon resolve.¹⁰ If the child is afebrile, lesions are itchy and painless, skin culture is negative, and there is no lymphangitis or spreading erythema, the inflammation is more likely a sign of impending resolution than bacterial secondary infection, and the urge to prescribe antibiotics should be resisted.¹⁰

As seen in this case, some patients with molluscum (5%) develop a diffuse, monomorphous, papular, or papulovesicular eruption that is an id reaction.3 This may appear to be eczema-like, lichenoid in appearance, or mimicking Gianotti-Crosti syndrome (papular acrodermatitis of childhood).³ It typically affects the arms and legs, is bilateral, and may be pruritic. The id reaction may occur in conjunction with inflamed molluscum, as is true in this case. The diffuse eruption can sometimes be mistaken for a sudden increase in the number of molluscum lesions, but the papular dermatitis lesions do not have the flat-topped dome-shape nor white centers.³ On average, the id reaction lasts about 6 weeks, after which both it and the primary molluscum lesions typically resolve.³ Although not seen in this case, more than a third of molluscum patients develop a pruritic, erythematous, eczematous area around molluscum lesions, termed molluscum dermatitis or eczema molluscatum, which may be more prominent than the molluscum itself.³ The eczematous patch typically surrounds molluscum lesions but also may occur at distant sites.¹² This reaction is especially common in patients with atopic dermatitis, 51% of whom develop it.³ It is considered a hypersensitivity reaction and may be asymptomatic or minimally pruritic.¹² Molluscum dermatitis suggests that the immune system has taken notice of the infection and is fighting it¹³; however, it does not necessarily indicate impending resolution.³

Differential diagnosis

The differential diagnosis for molluscum includes herpes simplex, warts, and milia.¹⁴ Like molluscum, herpes simplex lesions can have central umbilication, but the lesions are vesicular rather than solid. Warts typically have a rough, jagged surface in contrast to the smooth surface of molluscum lesions. Milia tend to be smaller and not flat topped. They are more common in infants and adults than in children and primarily affect the face.

Inflamed molluscum lesions and molluscum dermatitis can be mistaken for atopic dermatitis, and molluscum-associated id reactions may exacerbate atopic dermatitis. Inflamed molluscum and molluscum with id reaction could be confused with scabies, which may become crusted and also may be accompanied by id reaction. Presence of serpiginous linear burrows would suggest scabies rather than molluscum, and the diagnosis of scabies can be confirmed by scraping a burrow and looking for a mite or its feces under a microscope.

Prognosis and treatment

Molluscum infections typically resolve spontaneously in months to years (average duration, 13 months),¹⁴ so treatment may not be required. The goal of treatment is to accelerate the resolution of the infection, but some studies have found that common treatments may not shorten the time to resolution.¹¹ However, if there is substantial pruritus, lesions are cosmetically undesirable, or a child has atopic dermatitis and is at increased risk for autoinoculation, treatment may be warranted.¹⁵ Furthermore, molluscum lesions can scar, so prevention of autoinoculation may help minimize scarring.¹⁶

Few high-quality studies of the efficacy of molluscum treatments exist, and a 2009 Cochrane review found insufficient evidence to recommend any therapy for molluscum. The most common treatment used by pediatric dermatologists is cantharidin,¹⁷ and this treatment also is available to primary care practitioners. This option is preferred over other destructive methods such as curettage or liquid nitrogen cryotherapy because it is not painful or traumatic and is well tolerated by pediatric patients.⁸ Parent and physician satisfaction with the therapy is high; 78%-95% of parents would use cantharidin treatment again for molluscum recurrence.^4,8,18 Originally extracted from the blister beetle but now synthesized commercially,¹⁹ cantharidin causes vesiculation at the dermoepidermal junction6 by destroying intercellular connections.4 Vesiculation of the skin causes extrusion of the molluscum body, which facilitates resolution of the lesion.¹⁹ The cantharidin formulation is applied directly to molluscum lesions with the wooden end of a cotton-tipped applicator.⁴ Patients may be directed to wash it off after 4-6 hours. Blistering is an expected, desired outcome. A minority of patients may experience mild temporary pain (7%), more significant blistering (2.5%), burning (less than 1%), pruritus (less than 1%), or irritation (less than 1%).⁴ There is a risk of scarring and pigmentary changes, but these risks also exist for untreated lesions.¹⁹ Cantharidin treatment is repeated approximately every 4 weeks, and 90% of cases resolve after an average of 2.1 treatments.¹⁸ Topical retinoids can be used in an attempt to trigger an irritant response by the immune system, and they are the preferred therapy for facial lesions, but they are inconsistently effective.4 Randomized controlled trials found that imiquimod, a previously popular treatment is not effective,²⁰ and the evidence for cimetidine is contradictory.^21,22 Molluscum dermatitis and id reaction can be treated with medium strength topical steroids. 

References

1. Viral diseases of the skin, in "Hurwitz Clinical Pediatric Dermatology," 4 ed. (New York: Elsevier, 2011, pp. 348-69). .
2. Molluscum, in "Red Book Report of the Committee on Infectious Diseases," 2015.

Ms. Haddock is a medical student at the University of California, San Diego, and a research associate at Rady Children's Hospital-San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Eichenfield and Ms. Haddock state they have no relevant financial disclosures.

By Ellen S. Haddock, MBA, and Lawrence F. Eichenfield, MD

Molluscum

Molluscum typically presents as smooth, flesh-colored, flat-topped papules 2-8 mm in diameter with central whitish area, which is composed of the causative molluscum pox virus. While central depressions called umbilications are common, they may not be present in early molluscum lesions.^1,2 Lesions most often occur on the trunk and arms, but can occur anywhere.3-5 Individuals usually have multiple lesions, which may be clustered especially in areas of skin-to-skin contact.^5,6 Molluscum lesions can be itchy.

Molluscum is a benign viral skin infection caused by the molluscum contagiosum virus, which is a member of the poxvirus family. Molluscum infections are common, affecting 5%-11% of children.^5,7 Molluscum most often affects children younger than 8-years-old,⁵ with an average age of 5.8 years.⁸ The infection is spread through skin-to-skin contact with other individuals and by autoinoculation, which means that the infection can be spread from one area of an individual's skin to another when he or she scratches a lesion and then touches another area. It also can be spread by contact with fomites like towels and sponges.1 An association between public swimming pool use and molluscum infection has been reported, but this may have more to do with shared towels and equipment like kick-boards than transmission through the water itself.9 Molluscum sometimes is spread through contact sports like wrestling⁶ and between children sharing a bath.⁹ In adults, in whom molluscum is much less common because of acquired immunity,10 molluscum may be sexually transmitted or associated with HIV; however, this is rarely the case in children.¹

Children with atopic dermatitis have increased risk of molluscum infection in part because breaks in their skin and pruritus facilitate autoinoculation through scratching.¹¹ Not uncommonly, molluscum lesions become inflamed, with tenderness, erythema, and crust. In a study by Berger et al., 22% of patients had inflamed molluscum lesions.³ The appearance of inflamed molluscum lesions may raise concern about bacterial infection, but more often, the inflammation is a sign that the immune system is reacting to the viral infection and has almost "won the battle."¹⁰ After inflamed molluscum lesions develop, the total number of molluscum lesions typically declines,3 and some consider inflamed molluscum lesions to be a "beginning of the end sign," indicating that the infection may soon resolve.¹⁰ If the child is afebrile, lesions are itchy and painless, skin culture is negative, and there is no lymphangitis or spreading erythema, the inflammation is more likely a sign of impending resolution than bacterial secondary infection, and the urge to prescribe antibiotics should be resisted.¹⁰

As seen in this case, some patients with molluscum (5%) develop a diffuse, monomorphous, papular, or papulovesicular eruption that is an id reaction.3 This may appear to be eczema-like, lichenoid in appearance, or mimicking Gianotti-Crosti syndrome (papular acrodermatitis of childhood).³ It typically affects the arms and legs, is bilateral, and may be pruritic. The id reaction may occur in conjunction with inflamed molluscum, as is true in this case. The diffuse eruption can sometimes be mistaken for a sudden increase in the number of molluscum lesions, but the papular dermatitis lesions do not have the flat-topped dome-shape nor white centers.³ On average, the id reaction lasts about 6 weeks, after which both it and the primary molluscum lesions typically resolve.³ Although not seen in this case, more than a third of molluscum patients develop a pruritic, erythematous, eczematous area around molluscum lesions, termed molluscum dermatitis or eczema molluscatum, which may be more prominent than the molluscum itself.³ The eczematous patch typically surrounds molluscum lesions but also may occur at distant sites.¹² This reaction is especially common in patients with atopic dermatitis, 51% of whom develop it.³ It is considered a hypersensitivity reaction and may be asymptomatic or minimally pruritic.¹² Molluscum dermatitis suggests that the immune system has taken notice of the infection and is fighting it¹³; however, it does not necessarily indicate impending resolution.³

Differential diagnosis

The differential diagnosis for molluscum includes herpes simplex, warts, and milia.¹⁴ Like molluscum, herpes simplex lesions can have central umbilication, but the lesions are vesicular rather than solid. Warts typically have a rough, jagged surface in contrast to the smooth surface of molluscum lesions. Milia tend to be smaller and not flat topped. They are more common in infants and adults than in children and primarily affect the face.

Inflamed molluscum lesions and molluscum dermatitis can be mistaken for atopic dermatitis, and molluscum-associated id reactions may exacerbate atopic dermatitis. Inflamed molluscum and molluscum with id reaction could be confused with scabies, which may become crusted and also may be accompanied by id reaction. Presence of serpiginous linear burrows would suggest scabies rather than molluscum, and the diagnosis of scabies can be confirmed by scraping a burrow and looking for a mite or its feces under a microscope.

Prognosis and treatment

Molluscum infections typically resolve spontaneously in months to years (average duration, 13 months),¹⁴ so treatment may not be required. The goal of treatment is to accelerate the resolution of the infection, but some studies have found that common treatments may not shorten the time to resolution.¹¹ However, if there is substantial pruritus, lesions are cosmetically undesirable, or a child has atopic dermatitis and is at increased risk for autoinoculation, treatment may be warranted.¹⁵ Furthermore, molluscum lesions can scar, so prevention of autoinoculation may help minimize scarring.¹⁶

Few high-quality studies of the efficacy of molluscum treatments exist, and a 2009 Cochrane review found insufficient evidence to recommend any therapy for molluscum. The most common treatment used by pediatric dermatologists is cantharidin,¹⁷ and this treatment also is available to primary care practitioners. This option is preferred over other destructive methods such as curettage or liquid nitrogen cryotherapy because it is not painful or traumatic and is well tolerated by pediatric patients.⁸ Parent and physician satisfaction with the therapy is high; 78%-95% of parents would use cantharidin treatment again for molluscum recurrence.^4,8,18 Originally extracted from the blister beetle but now synthesized commercially,¹⁹ cantharidin causes vesiculation at the dermoepidermal junction6 by destroying intercellular connections.4 Vesiculation of the skin causes extrusion of the molluscum body, which facilitates resolution of the lesion.¹⁹ The cantharidin formulation is applied directly to molluscum lesions with the wooden end of a cotton-tipped applicator.⁴ Patients may be directed to wash it off after 4-6 hours. Blistering is an expected, desired outcome. A minority of patients may experience mild temporary pain (7%), more significant blistering (2.5%), burning (less than 1%), pruritus (less than 1%), or irritation (less than 1%).⁴ There is a risk of scarring and pigmentary changes, but these risks also exist for untreated lesions.¹⁹ Cantharidin treatment is repeated approximately every 4 weeks, and 90% of cases resolve after an average of 2.1 treatments.¹⁸ Topical retinoids can be used in an attempt to trigger an irritant response by the immune system, and they are the preferred therapy for facial lesions, but they are inconsistently effective.4 Randomized controlled trials found that imiquimod, a previously popular treatment is not effective,²⁰ and the evidence for cimetidine is contradictory.^21,22 Molluscum dermatitis and id reaction can be treated with medium strength topical steroids. 

References

1. Viral diseases of the skin, in "Hurwitz Clinical Pediatric Dermatology," 4 ed. (New York: Elsevier, 2011, pp. 348-69). .
2. Molluscum, in "Red Book Report of the Committee on Infectious Diseases," 2015.

Ms. Haddock is a medical student at the University of California, San Diego, and a research associate at Rady Children's Hospital-San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Eichenfield and Ms. Haddock state they have no relevant financial disclosures.

Dr. Catalina Matiz and David Ginsberg discuss the diagnosis and treatment of phytophotodermatitis. 

Phytophotodermatitis

The term phytophotodermatitis was first used in 1942 by Robert Klaber, but knowledge of this condition dates back as far as 1500 BC.^1,2 It is a nonimmune reaction caused by exposure to chemicals called furocoumarins and psoralens, found in a variety of plants and fruits such as lemons, limes, celery, parsnips, figs, carrots, dill, mustard, and rindweed.^1,2

When these chemicals get in contact with the skin and are then exposed to UV light from the sun, a phototoxic reaction occurs. This reaction leads to cell membrane damage and cell death, which after the acute insult has resolved results in postinflammatory hyperpigmentation that may last months and is not responsive to bleaching skin treatments.^1,2

Studies have shown that long-wave length UV radiation is the best trigger to induce this irritating reaction.² There have been rare reports of photosensitivity reactions due to ingestion of large quantities of plants containing furocoumarins and psoralens.³ Plants known to cause phytophotodermatitis are found in almost every country across the globe, and exposure does not have to just be to the fruit, but contact with the leaves or sap also can induce the reaction.^2-4 Typically after contact with the plant, followed by sun exposure, erythema will begin within 1 to 2 days, followed by bullae and vesicles, which tend to coalesce and burst over the following days. The patient is left with hyperpigmentation.^2-4

Differential diagnosis

This condition can be difficult to diagnose and is often confused with type IV hypersensitivity reaction, eczema, herpes simplex virus (HSV), and burns, potentially leading to suspicion of child abuse.^4,5 A thorough and detailed history is essential to correctly making the diagnosis and ruling out other potential causes.

Because the cause in children is often due to exposure to certain plants, unsupervised time outdoors leading to a rash may lead parents to think of poison ivy or poison oak, which are type IV hypersensitivity reactions.^4,5 Although the rash may appear in a similar time course, the evolution to hyperpigmented patches is a distinguishing feature that helps to make the diagnosis of phytophotodermatitis.⁴ The postinflammatory hyperpigmentation, along with the clinical course, also can help differentiate it from burns and HSV infections, which it sometimes is mistaken for due to the bullous and vesicular lesions.^4,5

Treatment

Counseling for avoidance of the exposure in the future is the most important aspect of treatment in order to prevent recurrences. Depending on the extent of the inflammatory reaction prior to the hyperpigmentation, no treatment may be needed for mild cases, but for more extreme bullous reactions, systemic steroids may be used.⁴

Topical corticosteroids and sun avoidance are the mainstays for treating mild to moderate cases. UV avoidance can be difficult because the long wave-length UV radiation that causes this reaction is not blocked by windows, and therefore it is important to keep affected areas covered even while indoors during daylight hours.⁴

There is no effective treatment for the hyperpigmented lesions. Patients need to be informed that this may resolve in months.

References

1. Br J Dermatol. 1942;54(7):193-211.
2. Clin Dermatol. 1986 Apr-Jun;4(2):102-21.
3. Arch Dermatol. 1990 Oct;126(10):1334-6.
4. J Am Acad Dermatol. 2007 Nov;57(5 Suppl):S88-91.
5. Arch Fam Med. 2000 Jan;9(1):88.

Dr. Matiz is assistant professor of dermatology at Rady Children’s Hospital San Diego–University of California, San Diego, and Mr. Ginsberg is a research associate at the hospital. Dr. Matiz and Mr. Ginsberg said they have no relevant financial disclosures.

Dr. Catalina Matiz and David Ginsberg discuss the diagnosis and treatment of phytophotodermatitis. 

Phytophotodermatitis

The term phytophotodermatitis was first used in 1942 by Robert Klaber, but knowledge of this condition dates back as far as 1500 BC.^1,2 It is a nonimmune reaction caused by exposure to chemicals called furocoumarins and psoralens, found in a variety of plants and fruits such as lemons, limes, celery, parsnips, figs, carrots, dill, mustard, and rindweed.^1,2

When these chemicals get in contact with the skin and are then exposed to UV light from the sun, a phototoxic reaction occurs. This reaction leads to cell membrane damage and cell death, which after the acute insult has resolved results in postinflammatory hyperpigmentation that may last months and is not responsive to bleaching skin treatments.^1,2

Studies have shown that long-wave length UV radiation is the best trigger to induce this irritating reaction.² There have been rare reports of photosensitivity reactions due to ingestion of large quantities of plants containing furocoumarins and psoralens.³ Plants known to cause phytophotodermatitis are found in almost every country across the globe, and exposure does not have to just be to the fruit, but contact with the leaves or sap also can induce the reaction.^2-4 Typically after contact with the plant, followed by sun exposure, erythema will begin within 1 to 2 days, followed by bullae and vesicles, which tend to coalesce and burst over the following days. The patient is left with hyperpigmentation.^2-4

Differential diagnosis

This condition can be difficult to diagnose and is often confused with type IV hypersensitivity reaction, eczema, herpes simplex virus (HSV), and burns, potentially leading to suspicion of child abuse.^4,5 A thorough and detailed history is essential to correctly making the diagnosis and ruling out other potential causes.

Because the cause in children is often due to exposure to certain plants, unsupervised time outdoors leading to a rash may lead parents to think of poison ivy or poison oak, which are type IV hypersensitivity reactions.^4,5 Although the rash may appear in a similar time course, the evolution to hyperpigmented patches is a distinguishing feature that helps to make the diagnosis of phytophotodermatitis.⁴ The postinflammatory hyperpigmentation, along with the clinical course, also can help differentiate it from burns and HSV infections, which it sometimes is mistaken for due to the bullous and vesicular lesions.^4,5

Treatment

Counseling for avoidance of the exposure in the future is the most important aspect of treatment in order to prevent recurrences. Depending on the extent of the inflammatory reaction prior to the hyperpigmentation, no treatment may be needed for mild cases, but for more extreme bullous reactions, systemic steroids may be used.⁴

Topical corticosteroids and sun avoidance are the mainstays for treating mild to moderate cases. UV avoidance can be difficult because the long wave-length UV radiation that causes this reaction is not blocked by windows, and therefore it is important to keep affected areas covered even while indoors during daylight hours.⁴

There is no effective treatment for the hyperpigmented lesions. Patients need to be informed that this may resolve in months.

References

1. Br J Dermatol. 1942;54(7):193-211.
2. Clin Dermatol. 1986 Apr-Jun;4(2):102-21.
3. Arch Dermatol. 1990 Oct;126(10):1334-6.
4. J Am Acad Dermatol. 2007 Nov;57(5 Suppl):S88-91.
5. Arch Fam Med. 2000 Jan;9(1):88.

Dr. Matiz is assistant professor of dermatology at Rady Children’s Hospital San Diego–University of California, San Diego, and Mr. Ginsberg is a research associate at the hospital. Dr. Matiz and Mr. Ginsberg said they have no relevant financial disclosures.

Dr. Catalina Matiz and David Ginsberg discuss the diagnosis and treatment of phytophotodermatitis. 

Phytophotodermatitis

The term phytophotodermatitis was first used in 1942 by Robert Klaber, but knowledge of this condition dates back as far as 1500 BC.^1,2 It is a nonimmune reaction caused by exposure to chemicals called furocoumarins and psoralens, found in a variety of plants and fruits such as lemons, limes, celery, parsnips, figs, carrots, dill, mustard, and rindweed.^1,2

When these chemicals get in contact with the skin and are then exposed to UV light from the sun, a phototoxic reaction occurs. This reaction leads to cell membrane damage and cell death, which after the acute insult has resolved results in postinflammatory hyperpigmentation that may last months and is not responsive to bleaching skin treatments.^1,2

Studies have shown that long-wave length UV radiation is the best trigger to induce this irritating reaction.² There have been rare reports of photosensitivity reactions due to ingestion of large quantities of plants containing furocoumarins and psoralens.³ Plants known to cause phytophotodermatitis are found in almost every country across the globe, and exposure does not have to just be to the fruit, but contact with the leaves or sap also can induce the reaction.^2-4 Typically after contact with the plant, followed by sun exposure, erythema will begin within 1 to 2 days, followed by bullae and vesicles, which tend to coalesce and burst over the following days. The patient is left with hyperpigmentation.^2-4

Differential diagnosis

This condition can be difficult to diagnose and is often confused with type IV hypersensitivity reaction, eczema, herpes simplex virus (HSV), and burns, potentially leading to suspicion of child abuse.^4,5 A thorough and detailed history is essential to correctly making the diagnosis and ruling out other potential causes.

Because the cause in children is often due to exposure to certain plants, unsupervised time outdoors leading to a rash may lead parents to think of poison ivy or poison oak, which are type IV hypersensitivity reactions.^4,5 Although the rash may appear in a similar time course, the evolution to hyperpigmented patches is a distinguishing feature that helps to make the diagnosis of phytophotodermatitis.⁴ The postinflammatory hyperpigmentation, along with the clinical course, also can help differentiate it from burns and HSV infections, which it sometimes is mistaken for due to the bullous and vesicular lesions.^4,5

Treatment

Counseling for avoidance of the exposure in the future is the most important aspect of treatment in order to prevent recurrences. Depending on the extent of the inflammatory reaction prior to the hyperpigmentation, no treatment may be needed for mild cases, but for more extreme bullous reactions, systemic steroids may be used.⁴

Topical corticosteroids and sun avoidance are the mainstays for treating mild to moderate cases. UV avoidance can be difficult because the long wave-length UV radiation that causes this reaction is not blocked by windows, and therefore it is important to keep affected areas covered even while indoors during daylight hours.⁴

There is no effective treatment for the hyperpigmented lesions. Patients need to be informed that this may resolve in months.

References

1. Br J Dermatol. 1942;54(7):193-211.
2. Clin Dermatol. 1986 Apr-Jun;4(2):102-21.
3. Arch Dermatol. 1990 Oct;126(10):1334-6.
4. J Am Acad Dermatol. 2007 Nov;57(5 Suppl):S88-91.
5. Arch Fam Med. 2000 Jan;9(1):88.

Dr. Matiz is assistant professor of dermatology at Rady Children’s Hospital San Diego–University of California, San Diego, and Mr. Ginsberg is a research associate at the hospital. Dr. Matiz and Mr. Ginsberg said they have no relevant financial disclosures.

By Ellen S. Haddock and Lawrence F. Eichenfield, MD

Terra firma-forme dermatosis

The easy removal of this patient’s persistent skin discoloration with an alcohol wipe confirms the diagnosis of terra firma-forme dermatosis. Terra firma-forme dermatosis is a benign skin condition in which dirt-like plaques develop on the skin despite normal hygiene. They cannot be removed with soap and water, but are removed easily with alcohol.

Terra firma means “solid earth” in Latin and refers to the dirt-like appearance of the lesion.^1,2 The condition typically presents with brown or black hyperkeratotic plaques or papules. The hyperpigmented lesions may be papillomatous, verrucous (warty), or have a reticulated (net-like) distribution.3 The condition is usually asymptomatic but occasionally itchy.¹ In the largest published series of 31 patients by Berk et al., the neck, ankles, and face were most commonly affected, but the condition can occur anywhere on the body.⁴ Lesions may be single or multiple and tend to be symmetrically distributed.⁴ The condition seems to be most common in young adults and adolescents, but can occur at any age and affects both genders equally.^2,5

It seems to occur more commonly in darker skin, heavier patients, and concave body areas.^3,6 The condition can last for months (median duration of 4 months in Berk et al.’s series), and by the time patients present to a physician they usually have tried aggressive scrubbing with multiple different soaps.⁴ As in this case, it is not uncommon for patients to receive an unnecessary work-up for diabetes due to concern for acanthosis nigricans.⁴ This work-up can be avoided if practitioners attempt removal with 70% isopropyl alcohol before ordering the diabetic work-up.

Biopsies are not typically performed (and should be abandoned if the lesion disappears when the site is cleansed with alcohol in preparation for biopsy), but hematoxylin and eosin staining shows lamellar hyperkeratosis, orthokeratotic whorls, and increased melanin in the basal layer and hyperkeratotic areas. Keratin globules are seen throughout the stratum corneum.⁷

Electron microscopy shows that the keratin lamellae is immature in some places, with incomplete keratinization and retention of desmosomal attachments.⁷ Overall, the histology is nonspecific and may be indistinguishable from other benign papillomatous conditions including confluent and reticulated papillomatosis (CARP), acanthosis nigricans, and epidermal nevi.⁶

Differential diagnosis

Clinically, the lesion may appear very similar to the brown velvety plaques of acanthosis nigricans, but the latter can be quickly ruled out if the lesion disappears when cleansed with alcohol. The differential diagnosis also includes dermatosis neglecta, CARP, hyperpigmented tinea versicolor, and dirty neck syndrome of atopic dermatitis.^4,7

Dermatosis neglecta is caused by poor hygiene with insufficient skin cleaning. In contrast with terra firma-forme dermatitis, it can be removed with soap and water. Patients with dermatosis neglecta lack a history of aggressive attempts at removal by scrubbing. Dermatosis neglecta looks similar to terra firma-forme dermatosis, but may have a waxy “cornflake-like” scale.² It is most common in the elderly, but also can be seen in children, especially if they have had a cast or brace that prevented washing an area.⁸

CARP may present as brown hyperkeratotic or verrucous papules, but typically occurs on the trunk and has a reticulated pattern, which is less common in terra firma-forme dermatosis.  Typically, it cannot be removed completely with alcohol^10-12 and tends to respond best to treatment with minocycline.¹¹

Hyperpigmented tinea versicolor lesions are usually more discrete and have fine scale, which becomes more prominent when the lesions are scraped. When analyzed with KOH under a microscope, hyphae and spores looking like spaghetti and meatballs can be seen.

Dirty neck syndrome is acquired hyperpigmentation that may develop on the neck of patients with atopic dermatitis. It cannot be removed with alcohol.⁴ It may result from frictional melanosis with melanin incontinence and post-inflammatory hyperpigmentation.¹² The hyperpigmentation is patchy or rippled,¹² whereas terra firma-forme dermatosis more often presents as plaques.

Etiology

The cause of terra firma-forme dermatosis is uncertain. It is thought to be a disorder of keratinocyte retention, in which delayed keratinocyte maturation causes prolonged cell-to-cell adhesion that impairs shedding.^7,8 Discoloration may be due to retained melanin as well as sebum and dirt that build up along with excess keratinocytes.^7-9 Alcohol is a better solvent for this retained material than soap and water. Patients using heavy emollients or oily soaps for conditions like atopic dermatitis may be relatively predisposed to the condition if emollients or oily soaps are not removed completely by bathing; the combination of underlying scale and retained skin care products may make skin more adhesive, disrupting normal keratinocyte shedding and allowing dirt and sebum to accumulate.¹ Atopic dermatitis was the most common comorbid condition for terra firma-forme dermatosis in Berk et al.’s series (12 of 31 patients).⁴

Treatment

Wiping with 70% isopropyl alcohol is both diagnostic and therapeutic, removing the lesion completely. Recurrence is uncommon but possible.³ In rare instances of regularly recurrent lesions, the area can be wiped prophylactically with alcohol weekly.¹

References

1. Indian J Dermatol Venereol Leprol. 2012 May-Jun;78(3):358-60.
2. Pediatr Dermatol. 2011 Jan-Feb;28(1):79-81.
3. Dermatol Pract Concept. 2015 Jul; 5(3): 29-33.
4. Pediatr Dermatol. 2012 May-Jun;29(3):297-300.
5. Eur J Intern Med. 2016 Feb. doi: 10.1016/j.ejim.2016.02.009.
6. J Cutan Pathol. 2012 Feb;39(2):300-1.
7. Arch Dermatol. 1987;123(5):567-9.
8. Pediatr Dermatol. 2015;32(2):e50-3.
9. Arch Dermatol. 2010;146(6):679-80.
10. Arch Dermatol. 2011 Feb;147(2):247-8.
11. Am J Clin Dermatol. 2006;7(5):305-313.
12. Dermatology. 2014;229:174-182.

Ms. Haddock is a medical student at the University of California, San Diego, and a research associate at Rady Children’s Hospital–San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Eichenfield and Ms. Haddock state they have no relevant financial disclosures. Email them at [email protected].

By Ellen S. Haddock and Lawrence F. Eichenfield, MD

Terra firma-forme dermatosis

The easy removal of this patient’s persistent skin discoloration with an alcohol wipe confirms the diagnosis of terra firma-forme dermatosis. Terra firma-forme dermatosis is a benign skin condition in which dirt-like plaques develop on the skin despite normal hygiene. They cannot be removed with soap and water, but are removed easily with alcohol.

Terra firma means “solid earth” in Latin and refers to the dirt-like appearance of the lesion.^1,2 The condition typically presents with brown or black hyperkeratotic plaques or papules. The hyperpigmented lesions may be papillomatous, verrucous (warty), or have a reticulated (net-like) distribution.3 The condition is usually asymptomatic but occasionally itchy.¹ In the largest published series of 31 patients by Berk et al., the neck, ankles, and face were most commonly affected, but the condition can occur anywhere on the body.⁴ Lesions may be single or multiple and tend to be symmetrically distributed.⁴ The condition seems to be most common in young adults and adolescents, but can occur at any age and affects both genders equally.^2,5

It seems to occur more commonly in darker skin, heavier patients, and concave body areas.^3,6 The condition can last for months (median duration of 4 months in Berk et al.’s series), and by the time patients present to a physician they usually have tried aggressive scrubbing with multiple different soaps.⁴ As in this case, it is not uncommon for patients to receive an unnecessary work-up for diabetes due to concern for acanthosis nigricans.⁴ This work-up can be avoided if practitioners attempt removal with 70% isopropyl alcohol before ordering the diabetic work-up.

Biopsies are not typically performed (and should be abandoned if the lesion disappears when the site is cleansed with alcohol in preparation for biopsy), but hematoxylin and eosin staining shows lamellar hyperkeratosis, orthokeratotic whorls, and increased melanin in the basal layer and hyperkeratotic areas. Keratin globules are seen throughout the stratum corneum.⁷

Electron microscopy shows that the keratin lamellae is immature in some places, with incomplete keratinization and retention of desmosomal attachments.⁷ Overall, the histology is nonspecific and may be indistinguishable from other benign papillomatous conditions including confluent and reticulated papillomatosis (CARP), acanthosis nigricans, and epidermal nevi.⁶

Differential diagnosis

Clinically, the lesion may appear very similar to the brown velvety plaques of acanthosis nigricans, but the latter can be quickly ruled out if the lesion disappears when cleansed with alcohol. The differential diagnosis also includes dermatosis neglecta, CARP, hyperpigmented tinea versicolor, and dirty neck syndrome of atopic dermatitis.^4,7

Dermatosis neglecta is caused by poor hygiene with insufficient skin cleaning. In contrast with terra firma-forme dermatitis, it can be removed with soap and water. Patients with dermatosis neglecta lack a history of aggressive attempts at removal by scrubbing. Dermatosis neglecta looks similar to terra firma-forme dermatosis, but may have a waxy “cornflake-like” scale.² It is most common in the elderly, but also can be seen in children, especially if they have had a cast or brace that prevented washing an area.⁸

CARP may present as brown hyperkeratotic or verrucous papules, but typically occurs on the trunk and has a reticulated pattern, which is less common in terra firma-forme dermatosis.  Typically, it cannot be removed completely with alcohol^10-12 and tends to respond best to treatment with minocycline.¹¹

Hyperpigmented tinea versicolor lesions are usually more discrete and have fine scale, which becomes more prominent when the lesions are scraped. When analyzed with KOH under a microscope, hyphae and spores looking like spaghetti and meatballs can be seen.

Dirty neck syndrome is acquired hyperpigmentation that may develop on the neck of patients with atopic dermatitis. It cannot be removed with alcohol.⁴ It may result from frictional melanosis with melanin incontinence and post-inflammatory hyperpigmentation.¹² The hyperpigmentation is patchy or rippled,¹² whereas terra firma-forme dermatosis more often presents as plaques.

Etiology

The cause of terra firma-forme dermatosis is uncertain. It is thought to be a disorder of keratinocyte retention, in which delayed keratinocyte maturation causes prolonged cell-to-cell adhesion that impairs shedding.^7,8 Discoloration may be due to retained melanin as well as sebum and dirt that build up along with excess keratinocytes.^7-9 Alcohol is a better solvent for this retained material than soap and water. Patients using heavy emollients or oily soaps for conditions like atopic dermatitis may be relatively predisposed to the condition if emollients or oily soaps are not removed completely by bathing; the combination of underlying scale and retained skin care products may make skin more adhesive, disrupting normal keratinocyte shedding and allowing dirt and sebum to accumulate.¹ Atopic dermatitis was the most common comorbid condition for terra firma-forme dermatosis in Berk et al.’s series (12 of 31 patients).⁴

Treatment

Wiping with 70% isopropyl alcohol is both diagnostic and therapeutic, removing the lesion completely. Recurrence is uncommon but possible.³ In rare instances of regularly recurrent lesions, the area can be wiped prophylactically with alcohol weekly.¹

References

1. Indian J Dermatol Venereol Leprol. 2012 May-Jun;78(3):358-60.
2. Pediatr Dermatol. 2011 Jan-Feb;28(1):79-81.
3. Dermatol Pract Concept. 2015 Jul; 5(3): 29-33.
4. Pediatr Dermatol. 2012 May-Jun;29(3):297-300.
5. Eur J Intern Med. 2016 Feb. doi: 10.1016/j.ejim.2016.02.009.
6. J Cutan Pathol. 2012 Feb;39(2):300-1.
7. Arch Dermatol. 1987;123(5):567-9.
8. Pediatr Dermatol. 2015;32(2):e50-3.
9. Arch Dermatol. 2010;146(6):679-80.
10. Arch Dermatol. 2011 Feb;147(2):247-8.
11. Am J Clin Dermatol. 2006;7(5):305-313.
12. Dermatology. 2014;229:174-182.

Ms. Haddock is a medical student at the University of California, San Diego, and a research associate at Rady Children’s Hospital–San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Eichenfield and Ms. Haddock state they have no relevant financial disclosures. Email them at [email protected].

By Ellen S. Haddock and Lawrence F. Eichenfield, MD

Terra firma-forme dermatosis

The easy removal of this patient’s persistent skin discoloration with an alcohol wipe confirms the diagnosis of terra firma-forme dermatosis. Terra firma-forme dermatosis is a benign skin condition in which dirt-like plaques develop on the skin despite normal hygiene. They cannot be removed with soap and water, but are removed easily with alcohol.

Terra firma means “solid earth” in Latin and refers to the dirt-like appearance of the lesion.^1,2 The condition typically presents with brown or black hyperkeratotic plaques or papules. The hyperpigmented lesions may be papillomatous, verrucous (warty), or have a reticulated (net-like) distribution.3 The condition is usually asymptomatic but occasionally itchy.¹ In the largest published series of 31 patients by Berk et al., the neck, ankles, and face were most commonly affected, but the condition can occur anywhere on the body.⁴ Lesions may be single or multiple and tend to be symmetrically distributed.⁴ The condition seems to be most common in young adults and adolescents, but can occur at any age and affects both genders equally.^2,5

It seems to occur more commonly in darker skin, heavier patients, and concave body areas.^3,6 The condition can last for months (median duration of 4 months in Berk et al.’s series), and by the time patients present to a physician they usually have tried aggressive scrubbing with multiple different soaps.⁴ As in this case, it is not uncommon for patients to receive an unnecessary work-up for diabetes due to concern for acanthosis nigricans.⁴ This work-up can be avoided if practitioners attempt removal with 70% isopropyl alcohol before ordering the diabetic work-up.

Biopsies are not typically performed (and should be abandoned if the lesion disappears when the site is cleansed with alcohol in preparation for biopsy), but hematoxylin and eosin staining shows lamellar hyperkeratosis, orthokeratotic whorls, and increased melanin in the basal layer and hyperkeratotic areas. Keratin globules are seen throughout the stratum corneum.⁷

Electron microscopy shows that the keratin lamellae is immature in some places, with incomplete keratinization and retention of desmosomal attachments.⁷ Overall, the histology is nonspecific and may be indistinguishable from other benign papillomatous conditions including confluent and reticulated papillomatosis (CARP), acanthosis nigricans, and epidermal nevi.⁶

Differential diagnosis

Clinically, the lesion may appear very similar to the brown velvety plaques of acanthosis nigricans, but the latter can be quickly ruled out if the lesion disappears when cleansed with alcohol. The differential diagnosis also includes dermatosis neglecta, CARP, hyperpigmented tinea versicolor, and dirty neck syndrome of atopic dermatitis.^4,7

Dermatosis neglecta is caused by poor hygiene with insufficient skin cleaning. In contrast with terra firma-forme dermatitis, it can be removed with soap and water. Patients with dermatosis neglecta lack a history of aggressive attempts at removal by scrubbing. Dermatosis neglecta looks similar to terra firma-forme dermatosis, but may have a waxy “cornflake-like” scale.² It is most common in the elderly, but also can be seen in children, especially if they have had a cast or brace that prevented washing an area.⁸

CARP may present as brown hyperkeratotic or verrucous papules, but typically occurs on the trunk and has a reticulated pattern, which is less common in terra firma-forme dermatosis.  Typically, it cannot be removed completely with alcohol^10-12 and tends to respond best to treatment with minocycline.¹¹

Hyperpigmented tinea versicolor lesions are usually more discrete and have fine scale, which becomes more prominent when the lesions are scraped. When analyzed with KOH under a microscope, hyphae and spores looking like spaghetti and meatballs can be seen.

Dirty neck syndrome is acquired hyperpigmentation that may develop on the neck of patients with atopic dermatitis. It cannot be removed with alcohol.⁴ It may result from frictional melanosis with melanin incontinence and post-inflammatory hyperpigmentation.¹² The hyperpigmentation is patchy or rippled,¹² whereas terra firma-forme dermatosis more often presents as plaques.

Etiology

The cause of terra firma-forme dermatosis is uncertain. It is thought to be a disorder of keratinocyte retention, in which delayed keratinocyte maturation causes prolonged cell-to-cell adhesion that impairs shedding.^7,8 Discoloration may be due to retained melanin as well as sebum and dirt that build up along with excess keratinocytes.^7-9 Alcohol is a better solvent for this retained material than soap and water. Patients using heavy emollients or oily soaps for conditions like atopic dermatitis may be relatively predisposed to the condition if emollients or oily soaps are not removed completely by bathing; the combination of underlying scale and retained skin care products may make skin more adhesive, disrupting normal keratinocyte shedding and allowing dirt and sebum to accumulate.¹ Atopic dermatitis was the most common comorbid condition for terra firma-forme dermatosis in Berk et al.’s series (12 of 31 patients).⁴

Treatment

Wiping with 70% isopropyl alcohol is both diagnostic and therapeutic, removing the lesion completely. Recurrence is uncommon but possible.³ In rare instances of regularly recurrent lesions, the area can be wiped prophylactically with alcohol weekly.¹

References

1. Indian J Dermatol Venereol Leprol. 2012 May-Jun;78(3):358-60.
2. Pediatr Dermatol. 2011 Jan-Feb;28(1):79-81.
3. Dermatol Pract Concept. 2015 Jul; 5(3): 29-33.
4. Pediatr Dermatol. 2012 May-Jun;29(3):297-300.
5. Eur J Intern Med. 2016 Feb. doi: 10.1016/j.ejim.2016.02.009.
6. J Cutan Pathol. 2012 Feb;39(2):300-1.
7. Arch Dermatol. 1987;123(5):567-9.
8. Pediatr Dermatol. 2015;32(2):e50-3.
9. Arch Dermatol. 2010;146(6):679-80.
10. Arch Dermatol. 2011 Feb;147(2):247-8.
11. Am J Clin Dermatol. 2006;7(5):305-313.
12. Dermatology. 2014;229:174-182.

Ms. Haddock is a medical student at the University of California, San Diego, and a research associate at Rady Children’s Hospital–San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Eichenfield and Ms. Haddock state they have no relevant financial disclosures. Email them at [email protected].

By Catalina Matiz, M.D., and David Ginsberg

Eczema cocksackium

Eczema coxsackium (EC) is an atypical variant of hand, foot, and mouth disease (HFMD) that occurs in patients with atopic dermatitis lesions. HFMD is a common viral exanthema seen in pediatric populations, predominantly in children under 5 years of age, and is most commonly caused by coxsackievirus A16 in the United States.1-3 Enterovirus 71 is also a common cause of HFMD in Asian countries, and in rare cases has been linked to more severe neurologic manifestations.2,3 

Over the past several years, infection by coxsackievirus A6 (CVA6) has been responsible for HFMD outbreaks in multiple countries around the globe.1-5 This particular strain of coxsackievirus is known for causing atypical HFMD, which has several overlapping variations. The variants of atypical HFMD caused by CVA6 include eczema coxsackium (EC), widespread vesiculobullous and erosive lesions, purpuric lesions, and Gianotti-Crosti-like eruptions.2 EC is the result of a CVA6 infection in a child with a history of atopic dermatitis (AD). The infection in these patients is a more severe form of HFMD, presenting with eczema herpeticum (EH)-like lesions, with some combination of vesicles, papules, and erosions, in areas affected by atopic dermatitis.2,3 This is in contrast to classic HFMD, which commonly presents with oral erosions, and small vesicles limited to the hands, feet, and buttocks.1,2 

In addition to the dermatologic manifestations, patients with EC also can present with other symptoms including fever and oropharyngeal pain.2,3 Any of the variants of atypical HFMD can present with lesions, including erosions, vesicles, and bullae, in areas of skin irritation such as sunburns, irritant dermatitis, lacerations, and tinea pedis.2 

Differential diagnosis

The differential diagnosis for EC includes EH, impetiginized atopic dermatitis, varicella, and erythema multiforme major.2-4 EH is typically the highest on the differential because the presentation of EC is described as an EH-like rash and on occasion it is difficult to differentiate the two.2 When diagnosing EC, the history plays an important role, and it is imperative to question whether the patient has come into contact with anyone with cold sores to help rule out EH. It is recommended to perform testing for herpes simplex virus (HSV), either by culture, polymerase chain reaction (PCR), or direct immunofluorescence if the diagnosis is not straightforward.2,5 To confirm the diagnosis of EC, CVA6 PCR can be performed.4 The ideal sample would be from vesicular fluid because the same sample also could be used to test for HSV to help rule out EH, but throat swabs and stool samples also can be used.2 As lesions in EH can sometimes be superinfected with bacteria such as Staphylococcus aureus or streptococcus, a bacterial swab for culture and sensitivities is also recommended prior to starting empiric antimicrobial therapy.

Treatment

Because EC was only characterized several years ago, and the majority of the cases reported have been self-limiting, there has been little research done looking into the best treatment. The majority of the literature recommends treating symptomatically in a similar fashion to an eczema flare including daily moisturizing, bleach baths, and topical corticosteroids as needed.6 There has been a report that using wet wraps with lower-strength corticosteroids is an effective treatment method for severe cases.6 Treatment with acyclovir and oral antimicrobials is recommended if the diagnosis of EH is in question and HSV and bacterial testing are pending. 

References

1. JAMA. 2012;308(4):335.
2. Pediatrics. 2013 Jul;132(1):e149-57. 
3. PIDJ. 2014 Apr;33(4):e92-98.
4. Virol J. 2013 Jun 24;10:209.
5. Lancet Infect Dis. 2014 Jan;14(1):83-6.
6. J Allergy Clin Immunol Pract. 2014 Nov-Dec;2(6):803-4.

Dr. Matiz is assistant professor of dermatology at Rady Children’s Hospital San Diego–University of California, San Diego and Mr. Ginsberg is a research associate at the hospital. Dr. Matiz and Mr. Ginsberg said they have no relevant financial disclosures.

By Catalina Matiz, M.D., and David Ginsberg

Eczema cocksackium

Eczema coxsackium (EC) is an atypical variant of hand, foot, and mouth disease (HFMD) that occurs in patients with atopic dermatitis lesions. HFMD is a common viral exanthema seen in pediatric populations, predominantly in children under 5 years of age, and is most commonly caused by coxsackievirus A16 in the United States.1-3 Enterovirus 71 is also a common cause of HFMD in Asian countries, and in rare cases has been linked to more severe neurologic manifestations.2,3 

Over the past several years, infection by coxsackievirus A6 (CVA6) has been responsible for HFMD outbreaks in multiple countries around the globe.1-5 This particular strain of coxsackievirus is known for causing atypical HFMD, which has several overlapping variations. The variants of atypical HFMD caused by CVA6 include eczema coxsackium (EC), widespread vesiculobullous and erosive lesions, purpuric lesions, and Gianotti-Crosti-like eruptions.2 EC is the result of a CVA6 infection in a child with a history of atopic dermatitis (AD). The infection in these patients is a more severe form of HFMD, presenting with eczema herpeticum (EH)-like lesions, with some combination of vesicles, papules, and erosions, in areas affected by atopic dermatitis.2,3 This is in contrast to classic HFMD, which commonly presents with oral erosions, and small vesicles limited to the hands, feet, and buttocks.1,2 

In addition to the dermatologic manifestations, patients with EC also can present with other symptoms including fever and oropharyngeal pain.2,3 Any of the variants of atypical HFMD can present with lesions, including erosions, vesicles, and bullae, in areas of skin irritation such as sunburns, irritant dermatitis, lacerations, and tinea pedis.2 

Differential diagnosis

The differential diagnosis for EC includes EH, impetiginized atopic dermatitis, varicella, and erythema multiforme major.2-4 EH is typically the highest on the differential because the presentation of EC is described as an EH-like rash and on occasion it is difficult to differentiate the two.2 When diagnosing EC, the history plays an important role, and it is imperative to question whether the patient has come into contact with anyone with cold sores to help rule out EH. It is recommended to perform testing for herpes simplex virus (HSV), either by culture, polymerase chain reaction (PCR), or direct immunofluorescence if the diagnosis is not straightforward.2,5 To confirm the diagnosis of EC, CVA6 PCR can be performed.4 The ideal sample would be from vesicular fluid because the same sample also could be used to test for HSV to help rule out EH, but throat swabs and stool samples also can be used.2 As lesions in EH can sometimes be superinfected with bacteria such as Staphylococcus aureus or streptococcus, a bacterial swab for culture and sensitivities is also recommended prior to starting empiric antimicrobial therapy.

Treatment

Because EC was only characterized several years ago, and the majority of the cases reported have been self-limiting, there has been little research done looking into the best treatment. The majority of the literature recommends treating symptomatically in a similar fashion to an eczema flare including daily moisturizing, bleach baths, and topical corticosteroids as needed.6 There has been a report that using wet wraps with lower-strength corticosteroids is an effective treatment method for severe cases.6 Treatment with acyclovir and oral antimicrobials is recommended if the diagnosis of EH is in question and HSV and bacterial testing are pending. 

References

1. JAMA. 2012;308(4):335.
2. Pediatrics. 2013 Jul;132(1):e149-57. 
3. PIDJ. 2014 Apr;33(4):e92-98.
4. Virol J. 2013 Jun 24;10:209.
5. Lancet Infect Dis. 2014 Jan;14(1):83-6.
6. J Allergy Clin Immunol Pract. 2014 Nov-Dec;2(6):803-4.

Dr. Matiz is assistant professor of dermatology at Rady Children’s Hospital San Diego–University of California, San Diego and Mr. Ginsberg is a research associate at the hospital. Dr. Matiz and Mr. Ginsberg said they have no relevant financial disclosures.

By Catalina Matiz, M.D., and David Ginsberg

Eczema cocksackium

Eczema coxsackium (EC) is an atypical variant of hand, foot, and mouth disease (HFMD) that occurs in patients with atopic dermatitis lesions. HFMD is a common viral exanthema seen in pediatric populations, predominantly in children under 5 years of age, and is most commonly caused by coxsackievirus A16 in the United States.1-3 Enterovirus 71 is also a common cause of HFMD in Asian countries, and in rare cases has been linked to more severe neurologic manifestations.2,3 

Over the past several years, infection by coxsackievirus A6 (CVA6) has been responsible for HFMD outbreaks in multiple countries around the globe.1-5 This particular strain of coxsackievirus is known for causing atypical HFMD, which has several overlapping variations. The variants of atypical HFMD caused by CVA6 include eczema coxsackium (EC), widespread vesiculobullous and erosive lesions, purpuric lesions, and Gianotti-Crosti-like eruptions.2 EC is the result of a CVA6 infection in a child with a history of atopic dermatitis (AD). The infection in these patients is a more severe form of HFMD, presenting with eczema herpeticum (EH)-like lesions, with some combination of vesicles, papules, and erosions, in areas affected by atopic dermatitis.2,3 This is in contrast to classic HFMD, which commonly presents with oral erosions, and small vesicles limited to the hands, feet, and buttocks.1,2 

In addition to the dermatologic manifestations, patients with EC also can present with other symptoms including fever and oropharyngeal pain.2,3 Any of the variants of atypical HFMD can present with lesions, including erosions, vesicles, and bullae, in areas of skin irritation such as sunburns, irritant dermatitis, lacerations, and tinea pedis.2 

Differential diagnosis

The differential diagnosis for EC includes EH, impetiginized atopic dermatitis, varicella, and erythema multiforme major.2-4 EH is typically the highest on the differential because the presentation of EC is described as an EH-like rash and on occasion it is difficult to differentiate the two.2 When diagnosing EC, the history plays an important role, and it is imperative to question whether the patient has come into contact with anyone with cold sores to help rule out EH. It is recommended to perform testing for herpes simplex virus (HSV), either by culture, polymerase chain reaction (PCR), or direct immunofluorescence if the diagnosis is not straightforward.2,5 To confirm the diagnosis of EC, CVA6 PCR can be performed.4 The ideal sample would be from vesicular fluid because the same sample also could be used to test for HSV to help rule out EH, but throat swabs and stool samples also can be used.2 As lesions in EH can sometimes be superinfected with bacteria such as Staphylococcus aureus or streptococcus, a bacterial swab for culture and sensitivities is also recommended prior to starting empiric antimicrobial therapy.

Treatment

Because EC was only characterized several years ago, and the majority of the cases reported have been self-limiting, there has been little research done looking into the best treatment. The majority of the literature recommends treating symptomatically in a similar fashion to an eczema flare including daily moisturizing, bleach baths, and topical corticosteroids as needed.6 There has been a report that using wet wraps with lower-strength corticosteroids is an effective treatment method for severe cases.6 Treatment with acyclovir and oral antimicrobials is recommended if the diagnosis of EH is in question and HSV and bacterial testing are pending. 

References

1. JAMA. 2012;308(4):335.
2. Pediatrics. 2013 Jul;132(1):e149-57. 
3. PIDJ. 2014 Apr;33(4):e92-98.
4. Virol J. 2013 Jun 24;10:209.
5. Lancet Infect Dis. 2014 Jan;14(1):83-6.
6. J Allergy Clin Immunol Pract. 2014 Nov-Dec;2(6):803-4.

Dr. Matiz is assistant professor of dermatology at Rady Children’s Hospital San Diego–University of California, San Diego and Mr. Ginsberg is a research associate at the hospital. Dr. Matiz and Mr. Ginsberg said they have no relevant financial disclosures.

BY ELLEN S. HADDOCK AND LAWRENCE F. EICHENFIELD, M.D.

Pediatric Dermatology Consult: Pernio

Itchy localized areas of swelling on the bilateral hands with erythematous papules and crusting is consistent with pernio, as seen in the presentation of the teen boy described on p. 2. Pernio is a localized abnormal inflammatory response to cold and damp conditions, also known as chilblains, derived from the old English words for chill and sore.¹ Damp air is thought to enhance the air conductivity of cold.² Pernio typically presents with erythematous to blue-violet macules, papules, and nodules on the bilateral fingers and toes. When occurring on the feet, it is sometimes called trench foot or kibes.¹ The nose and ears also can be affected.³ Lesions may develop 12-24 hours after exposure to damp or chilly weather, typically at temperatures above freezing.⁴

This patient’s pernio may have been triggered by recent stormy winter weather; being from within San Diego County, he had no exposure to snow. Lesions often are tender and may be accompanied by pruritus, pain, or a burning sensation, but they can be asymptomatic.³ Lesions may blister and ulcerate, and can become secondarily infected.⁵ Brownish or yellowish discoloration may be seen.¹ Proposed diagnostic criteria requires localized erythema and swelling of the acral sites for more than 24 hours, as well as either onset during the cool months of the year or improvement with warming the affected area.³

Pernio is most common in adults, with a mean age of 38 years in one series.³ It also occurs in children but is uncommon, with only eight cases diagnosed at the University of Colorado over a 10-year period.⁶ Adult patients are primarily female,³ while the gender distribution in children is equal.⁶ Because pernio is triggered by cold and damp weather, it is not surprising that pernio occurs more often in cold climates.³ Raynaud’s phenomenon, smoking, and anorexia nervosa (due to lack of insulating fat) seem to be risk factors.^1,3

Pernio typically is a benign primary disorder thought to result from cold-induced vasospasm, which leads to hypoxia and triggers a localized inflammatory reaction.⁷ Lesions of primary pernio usually resolve in a few weeks to months.^4,6 However, pernio can be secondarily associated with systemic diseases including lupus (5% of patients in one of the largest series), non-lupus connective tissue disorders (4%), hematologic malignancy (3%), solid organ malignancy (2%), hepatitis, and Epstein-Barr virus.³ In these cases, pernio may be more persistent and hyperviscosity may contribute to its pathogenesis.^8,9

Approximately a third of patients have laboratory abnormalities such as anemia, abnormal blood smear, autoantibodies, or serum monoclonal proteins,³ which may facilitate diagnosis of an underlying systemic disease. Not all pernio patients with connective tissue disease autoantibodies have clinical features of connective tissue disease, but these may manifest later.^3,9 Laboratory abnormalities including cryoglobulinemia, cold agglutinins, rheumatoid factor, and antineutrophilic antibody also are seen in children;^6,10 however, there are no reports of childhood pernio being associated with connective tissue disease or other systemic illness, although long-term studies are lacking.

When lesions are biopsied, histopathology shows nonspecific dermal edema with superficial and deep perivascular lymphocytic infiltrate.^3,4

Differential diagnosis

The differential diagnosis for pernio includes Raynaud’s phenomenon, frostbite, herpetic whitlow, and purpura caused by cryoproteinemia. In Raynaud’s, pallor and cyanosis are followed by erythema, but the discoloration is more sharply demarcated and episodes are typically shorter, lasting hours rather than days.^1,8 In this case, progression of the lesions over weeks and the lack of sudden skin color change when holding a cold drink make Raynaud’s unlikely. Frostbite, in which the tissue freezes and necroses, can be distinguished by history.¹¹

When lesions have blistered, herpetic whitlow also may be on the differential, but herpetic whitlow vesicles typically cluster or coalesce into a single bulla while pernio lesions are more discrete. Cryoproteinemia causes lesions on acral sites exposed to the cold, but its onset is sudden and lesions are purpuric with a reticular (net-like) pattern.¹² In adults, cutaneous thromboemboli also can present similarly to pernio,¹³ but thromboemboli are unlikely in children.

Clinical findings of pernio in the setting of lupus erythematosus is called chilblains lupus erythematosus. Confusingly, the condition called lupus pernio is actually a cutaneous manifestation of sarcoidosis, not lupus, and its erythematous or violaceous lesions occur on the nose and central face, not the hands and feet.¹³

Work-up

For pernio patients without systemic symptoms or signs of underlying systemic disease, laboratory workup or skin biopsy are not necessary.^3,4 When history or physical exam is concerning for a systemic condition, preliminary workup should include complete blood count, peripheral blood smear, serum protein electrophoresis, cold agglutinins, and antinuclear antibody.³ Rheumatoid factor, antiphospholipid antibodies, and cryoglobulins also can be considered. Laboratory workup should be performed if pernio persists beyond the cold season, as persistent pernio may be associated with systemic illness.^4,9

This patient’s recent weight loss was concerning for underlying systemic disease, so a laboratory workup including complete blood count, serum protein electrophoresis, cold agglutinins, antinuclear antibody, rheumatoid factor, and cryoglobulins was performed. Cryoglobulinemia was detected. All other lab values were within normal limits. Although cryoglobulinemia is rare in adults,^3,14 it was detected in approximately 40% of the children in two pediatric series.^6,10 Cryoglobulins, which can be produced in response to viral infection, may suggest a precipitating viral illness, with transient cryoproteinemia amplifying cold injury.⁶ Although the significance of laboratory abnormalities in pediatric pernio is unclear, because associated systemic disease has not been reported in children, some practitioners recommend long-term monitoring in light of the association between lab abnormalities and systemic disease in adults.¹⁰

Treatment

Most pernio (82% in one series) resolves when affected skin is warmed and dried, without additional treatment required.³ Corticosteroids, such as 0.1% triamcinolone cream, sometimes are given to hasten the healing of the lesions, but their benefit is unproven.⁶ The second-line treatment for persistent pernio is calcium channel blockers such as nifedipine.^3,15 This patient’s pernio quickly improved after he began wearing gloves to keep his hands warm. On re-examination 2 weeks later, his hands were warm and the erythematous nodules had resolved, leaving only some scale at the sites of prior lesions (Figure 3). Some patients relapse annually during the cool months.¹¹

References

1. Pediatrics. 2005 Sep;116(3):e472-5. doi: 10.1542/peds.2004-2681.
2. Journal of Medical Case Reports. 2014 Nov;8:381. doi: 10.1186/1752-1947-8-381.
3. Mayo Clin Proc. 2014 Feb;89(2):207-15.
4. Clin Exp Dermatol. 2012 Dec;37(8):844-9.
5. J Paediatr Child Health. 2013 Feb;49(2):144-7.
6. Pediatr Dermatol. 2000 Mar-Apr;17(2):97-9.
7. Am J Med. 2009 Dec;122(12):1152-5.
8. J Amer Acad Dermatol. 1990 Aug;23(Part 1):257-62.
9. Medicine (Baltimore). 2001 May;80(3):180-8.
10. Arch Dis Child. 2010 Jul;95(7):567-8.
11. Br J Dermatol. 2010 Sep;163(3):645-6.
12. Cutaneous manifestations of microvascular occlusion syndromes, in “Dermatology,” 3rd ed. (Philadelphia, 2012, pp 373-4).
13. Environmental and sports-related skin diseases, in “Dermatology,” 3rd ed. (Philadelphia, 2012).
14. J Am Acad Dermatol. 2010 Jun;62(6):e21-2.
15. Br J Dermatol. 1989 Feb;120(2):267-75.

Ms. Haddock is a medical student at the University of California, San Diego, and a research associate at Rady Children’s Hospital, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, and Professor of Medicine and Pediatrics at the University of California, San Diego. Dr. Eichenfield and Ms. Haddock said they have no relevant financial disclosures.

BY ELLEN S. HADDOCK AND LAWRENCE F. EICHENFIELD, M.D.

Pediatric Dermatology Consult: Pernio

Itchy localized areas of swelling on the bilateral hands with erythematous papules and crusting is consistent with pernio, as seen in the presentation of the teen boy described on p. 2. Pernio is a localized abnormal inflammatory response to cold and damp conditions, also known as chilblains, derived from the old English words for chill and sore.¹ Damp air is thought to enhance the air conductivity of cold.² Pernio typically presents with erythematous to blue-violet macules, papules, and nodules on the bilateral fingers and toes. When occurring on the feet, it is sometimes called trench foot or kibes.¹ The nose and ears also can be affected.³ Lesions may develop 12-24 hours after exposure to damp or chilly weather, typically at temperatures above freezing.⁴

This patient’s pernio may have been triggered by recent stormy winter weather; being from within San Diego County, he had no exposure to snow. Lesions often are tender and may be accompanied by pruritus, pain, or a burning sensation, but they can be asymptomatic.³ Lesions may blister and ulcerate, and can become secondarily infected.⁵ Brownish or yellowish discoloration may be seen.¹ Proposed diagnostic criteria requires localized erythema and swelling of the acral sites for more than 24 hours, as well as either onset during the cool months of the year or improvement with warming the affected area.³

Pernio is most common in adults, with a mean age of 38 years in one series.³ It also occurs in children but is uncommon, with only eight cases diagnosed at the University of Colorado over a 10-year period.⁶ Adult patients are primarily female,³ while the gender distribution in children is equal.⁶ Because pernio is triggered by cold and damp weather, it is not surprising that pernio occurs more often in cold climates.³ Raynaud’s phenomenon, smoking, and anorexia nervosa (due to lack of insulating fat) seem to be risk factors.^1,3

Pernio typically is a benign primary disorder thought to result from cold-induced vasospasm, which leads to hypoxia and triggers a localized inflammatory reaction.⁷ Lesions of primary pernio usually resolve in a few weeks to months.^4,6 However, pernio can be secondarily associated with systemic diseases including lupus (5% of patients in one of the largest series), non-lupus connective tissue disorders (4%), hematologic malignancy (3%), solid organ malignancy (2%), hepatitis, and Epstein-Barr virus.³ In these cases, pernio may be more persistent and hyperviscosity may contribute to its pathogenesis.^8,9

Approximately a third of patients have laboratory abnormalities such as anemia, abnormal blood smear, autoantibodies, or serum monoclonal proteins,³ which may facilitate diagnosis of an underlying systemic disease. Not all pernio patients with connective tissue disease autoantibodies have clinical features of connective tissue disease, but these may manifest later.^3,9 Laboratory abnormalities including cryoglobulinemia, cold agglutinins, rheumatoid factor, and antineutrophilic antibody also are seen in children;^6,10 however, there are no reports of childhood pernio being associated with connective tissue disease or other systemic illness, although long-term studies are lacking.

When lesions are biopsied, histopathology shows nonspecific dermal edema with superficial and deep perivascular lymphocytic infiltrate.^3,4

Differential diagnosis

The differential diagnosis for pernio includes Raynaud’s phenomenon, frostbite, herpetic whitlow, and purpura caused by cryoproteinemia. In Raynaud’s, pallor and cyanosis are followed by erythema, but the discoloration is more sharply demarcated and episodes are typically shorter, lasting hours rather than days.^1,8 In this case, progression of the lesions over weeks and the lack of sudden skin color change when holding a cold drink make Raynaud’s unlikely. Frostbite, in which the tissue freezes and necroses, can be distinguished by history.¹¹

When lesions have blistered, herpetic whitlow also may be on the differential, but herpetic whitlow vesicles typically cluster or coalesce into a single bulla while pernio lesions are more discrete. Cryoproteinemia causes lesions on acral sites exposed to the cold, but its onset is sudden and lesions are purpuric with a reticular (net-like) pattern.¹² In adults, cutaneous thromboemboli also can present similarly to pernio,¹³ but thromboemboli are unlikely in children.

Clinical findings of pernio in the setting of lupus erythematosus is called chilblains lupus erythematosus. Confusingly, the condition called lupus pernio is actually a cutaneous manifestation of sarcoidosis, not lupus, and its erythematous or violaceous lesions occur on the nose and central face, not the hands and feet.¹³

Work-up

For pernio patients without systemic symptoms or signs of underlying systemic disease, laboratory workup or skin biopsy are not necessary.^3,4 When history or physical exam is concerning for a systemic condition, preliminary workup should include complete blood count, peripheral blood smear, serum protein electrophoresis, cold agglutinins, and antinuclear antibody.³ Rheumatoid factor, antiphospholipid antibodies, and cryoglobulins also can be considered. Laboratory workup should be performed if pernio persists beyond the cold season, as persistent pernio may be associated with systemic illness.^4,9

This patient’s recent weight loss was concerning for underlying systemic disease, so a laboratory workup including complete blood count, serum protein electrophoresis, cold agglutinins, antinuclear antibody, rheumatoid factor, and cryoglobulins was performed. Cryoglobulinemia was detected. All other lab values were within normal limits. Although cryoglobulinemia is rare in adults,^3,14 it was detected in approximately 40% of the children in two pediatric series.^6,10 Cryoglobulins, which can be produced in response to viral infection, may suggest a precipitating viral illness, with transient cryoproteinemia amplifying cold injury.⁶ Although the significance of laboratory abnormalities in pediatric pernio is unclear, because associated systemic disease has not been reported in children, some practitioners recommend long-term monitoring in light of the association between lab abnormalities and systemic disease in adults.¹⁰

Treatment

Most pernio (82% in one series) resolves when affected skin is warmed and dried, without additional treatment required.³ Corticosteroids, such as 0.1% triamcinolone cream, sometimes are given to hasten the healing of the lesions, but their benefit is unproven.⁶ The second-line treatment for persistent pernio is calcium channel blockers such as nifedipine.^3,15 This patient’s pernio quickly improved after he began wearing gloves to keep his hands warm. On re-examination 2 weeks later, his hands were warm and the erythematous nodules had resolved, leaving only some scale at the sites of prior lesions (Figure 3). Some patients relapse annually during the cool months.¹¹

References

1. Pediatrics. 2005 Sep;116(3):e472-5. doi: 10.1542/peds.2004-2681.
2. Journal of Medical Case Reports. 2014 Nov;8:381. doi: 10.1186/1752-1947-8-381.
3. Mayo Clin Proc. 2014 Feb;89(2):207-15.
4. Clin Exp Dermatol. 2012 Dec;37(8):844-9.
5. J Paediatr Child Health. 2013 Feb;49(2):144-7.
6. Pediatr Dermatol. 2000 Mar-Apr;17(2):97-9.
7. Am J Med. 2009 Dec;122(12):1152-5.
8. J Amer Acad Dermatol. 1990 Aug;23(Part 1):257-62.
9. Medicine (Baltimore). 2001 May;80(3):180-8.
10. Arch Dis Child. 2010 Jul;95(7):567-8.
11. Br J Dermatol. 2010 Sep;163(3):645-6.
12. Cutaneous manifestations of microvascular occlusion syndromes, in “Dermatology,” 3rd ed. (Philadelphia, 2012, pp 373-4).
13. Environmental and sports-related skin diseases, in “Dermatology,” 3rd ed. (Philadelphia, 2012).
14. J Am Acad Dermatol. 2010 Jun;62(6):e21-2.
15. Br J Dermatol. 1989 Feb;120(2):267-75.

Ms. Haddock is a medical student at the University of California, San Diego, and a research associate at Rady Children’s Hospital, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, and Professor of Medicine and Pediatrics at the University of California, San Diego. Dr. Eichenfield and Ms. Haddock said they have no relevant financial disclosures.

BY ELLEN S. HADDOCK AND LAWRENCE F. EICHENFIELD, M.D.

Pediatric Dermatology Consult: Pernio

Itchy localized areas of swelling on the bilateral hands with erythematous papules and crusting is consistent with pernio, as seen in the presentation of the teen boy described on p. 2. Pernio is a localized abnormal inflammatory response to cold and damp conditions, also known as chilblains, derived from the old English words for chill and sore.¹ Damp air is thought to enhance the air conductivity of cold.² Pernio typically presents with erythematous to blue-violet macules, papules, and nodules on the bilateral fingers and toes. When occurring on the feet, it is sometimes called trench foot or kibes.¹ The nose and ears also can be affected.³ Lesions may develop 12-24 hours after exposure to damp or chilly weather, typically at temperatures above freezing.⁴

This patient’s pernio may have been triggered by recent stormy winter weather; being from within San Diego County, he had no exposure to snow. Lesions often are tender and may be accompanied by pruritus, pain, or a burning sensation, but they can be asymptomatic.³ Lesions may blister and ulcerate, and can become secondarily infected.⁵ Brownish or yellowish discoloration may be seen.¹ Proposed diagnostic criteria requires localized erythema and swelling of the acral sites for more than 24 hours, as well as either onset during the cool months of the year or improvement with warming the affected area.³

Pernio is most common in adults, with a mean age of 38 years in one series.³ It also occurs in children but is uncommon, with only eight cases diagnosed at the University of Colorado over a 10-year period.⁶ Adult patients are primarily female,³ while the gender distribution in children is equal.⁶ Because pernio is triggered by cold and damp weather, it is not surprising that pernio occurs more often in cold climates.³ Raynaud’s phenomenon, smoking, and anorexia nervosa (due to lack of insulating fat) seem to be risk factors.^1,3

Pernio typically is a benign primary disorder thought to result from cold-induced vasospasm, which leads to hypoxia and triggers a localized inflammatory reaction.⁷ Lesions of primary pernio usually resolve in a few weeks to months.^4,6 However, pernio can be secondarily associated with systemic diseases including lupus (5% of patients in one of the largest series), non-lupus connective tissue disorders (4%), hematologic malignancy (3%), solid organ malignancy (2%), hepatitis, and Epstein-Barr virus.³ In these cases, pernio may be more persistent and hyperviscosity may contribute to its pathogenesis.^8,9

Approximately a third of patients have laboratory abnormalities such as anemia, abnormal blood smear, autoantibodies, or serum monoclonal proteins,³ which may facilitate diagnosis of an underlying systemic disease. Not all pernio patients with connective tissue disease autoantibodies have clinical features of connective tissue disease, but these may manifest later.^3,9 Laboratory abnormalities including cryoglobulinemia, cold agglutinins, rheumatoid factor, and antineutrophilic antibody also are seen in children;^6,10 however, there are no reports of childhood pernio being associated with connective tissue disease or other systemic illness, although long-term studies are lacking.

When lesions are biopsied, histopathology shows nonspecific dermal edema with superficial and deep perivascular lymphocytic infiltrate.^3,4

Differential diagnosis

The differential diagnosis for pernio includes Raynaud’s phenomenon, frostbite, herpetic whitlow, and purpura caused by cryoproteinemia. In Raynaud’s, pallor and cyanosis are followed by erythema, but the discoloration is more sharply demarcated and episodes are typically shorter, lasting hours rather than days.^1,8 In this case, progression of the lesions over weeks and the lack of sudden skin color change when holding a cold drink make Raynaud’s unlikely. Frostbite, in which the tissue freezes and necroses, can be distinguished by history.¹¹

When lesions have blistered, herpetic whitlow also may be on the differential, but herpetic whitlow vesicles typically cluster or coalesce into a single bulla while pernio lesions are more discrete. Cryoproteinemia causes lesions on acral sites exposed to the cold, but its onset is sudden and lesions are purpuric with a reticular (net-like) pattern.¹² In adults, cutaneous thromboemboli also can present similarly to pernio,¹³ but thromboemboli are unlikely in children.

Clinical findings of pernio in the setting of lupus erythematosus is called chilblains lupus erythematosus. Confusingly, the condition called lupus pernio is actually a cutaneous manifestation of sarcoidosis, not lupus, and its erythematous or violaceous lesions occur on the nose and central face, not the hands and feet.¹³

Work-up

For pernio patients without systemic symptoms or signs of underlying systemic disease, laboratory workup or skin biopsy are not necessary.^3,4 When history or physical exam is concerning for a systemic condition, preliminary workup should include complete blood count, peripheral blood smear, serum protein electrophoresis, cold agglutinins, and antinuclear antibody.³ Rheumatoid factor, antiphospholipid antibodies, and cryoglobulins also can be considered. Laboratory workup should be performed if pernio persists beyond the cold season, as persistent pernio may be associated with systemic illness.^4,9

This patient’s recent weight loss was concerning for underlying systemic disease, so a laboratory workup including complete blood count, serum protein electrophoresis, cold agglutinins, antinuclear antibody, rheumatoid factor, and cryoglobulins was performed. Cryoglobulinemia was detected. All other lab values were within normal limits. Although cryoglobulinemia is rare in adults,^3,14 it was detected in approximately 40% of the children in two pediatric series.^6,10 Cryoglobulins, which can be produced in response to viral infection, may suggest a precipitating viral illness, with transient cryoproteinemia amplifying cold injury.⁶ Although the significance of laboratory abnormalities in pediatric pernio is unclear, because associated systemic disease has not been reported in children, some practitioners recommend long-term monitoring in light of the association between lab abnormalities and systemic disease in adults.¹⁰

Treatment

Most pernio (82% in one series) resolves when affected skin is warmed and dried, without additional treatment required.³ Corticosteroids, such as 0.1% triamcinolone cream, sometimes are given to hasten the healing of the lesions, but their benefit is unproven.⁶ The second-line treatment for persistent pernio is calcium channel blockers such as nifedipine.^3,15 This patient’s pernio quickly improved after he began wearing gloves to keep his hands warm. On re-examination 2 weeks later, his hands were warm and the erythematous nodules had resolved, leaving only some scale at the sites of prior lesions (Figure 3). Some patients relapse annually during the cool months.¹¹

References

1. Pediatrics. 2005 Sep;116(3):e472-5. doi: 10.1542/peds.2004-2681.
2. Journal of Medical Case Reports. 2014 Nov;8:381. doi: 10.1186/1752-1947-8-381.
3. Mayo Clin Proc. 2014 Feb;89(2):207-15.
4. Clin Exp Dermatol. 2012 Dec;37(8):844-9.
5. J Paediatr Child Health. 2013 Feb;49(2):144-7.
6. Pediatr Dermatol. 2000 Mar-Apr;17(2):97-9.
7. Am J Med. 2009 Dec;122(12):1152-5.
8. J Amer Acad Dermatol. 1990 Aug;23(Part 1):257-62.
9. Medicine (Baltimore). 2001 May;80(3):180-8.
10. Arch Dis Child. 2010 Jul;95(7):567-8.
11. Br J Dermatol. 2010 Sep;163(3):645-6.
12. Cutaneous manifestations of microvascular occlusion syndromes, in “Dermatology,” 3rd ed. (Philadelphia, 2012, pp 373-4).
13. Environmental and sports-related skin diseases, in “Dermatology,” 3rd ed. (Philadelphia, 2012).
14. J Am Acad Dermatol. 2010 Jun;62(6):e21-2.
15. Br J Dermatol. 1989 Feb;120(2):267-75.

Ms. Haddock is a medical student at the University of California, San Diego, and a research associate at Rady Children’s Hospital, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, and Professor of Medicine and Pediatrics at the University of California, San Diego. Dr. Eichenfield and Ms. Haddock said they have no relevant financial disclosures.

By Catalina Matiz, M.D., and David Ginsberg

Nummular eczema

Nummular eczema is not an uncommon dermatosis that presents in pediatric and adult patients; its name, which derives from the Latin word nummulus (coin-like), refers to the coined-shape plaques that characterize this condition. It also has been referred to as discoid eczema and nummular dermatitis.¹

The lesions begin as erythematous papules and vesicles that extend into larger oval or circular plaques that often become crusted, and can later progress to dry and scaly plaques.^1,2 Patients often complain of intense pruritus.¹ The lesions can be single or multiple, and more commonly occur on the extensor extremities as well as the trunk, and rarely affect the neck and the head.^1-3 The pathophysiology of nummular eczema is not fully understood. It can occur in patients that exhibit atopic manifestations such as atopic dermatitis and other allergies, but there has been no clear link found between nummular eczema and atopy.^3,4

Many theories exist implicating causative factors including Staphylococcus aureus colonization and xerosis.¹ Similarly, some physicians believe that patch testing can be useful in these patients because of the potential for exacerbation caused by environmental allergens, but there is still no agreement on the ultimate cause.⁵ There is a higher incidence in males than females, and in the pediatric population, it is more common among “school aged” children between the ages of 2-12.⁶ Overall, nummular eczema is more commonly seen in adults, but it can occur at any age.^2,3,6

Differential diagnosis

Nummular eczema is commonly mistaken as tinea corporis.¹ The coined shape lesions, from which nummular eczema gets its name, can resemble the characteristic annular shape plaques of “ring worm,” but a potassium hydroxide (KOH) test or a fungal culture are simple ways to differentiate between the two conditions.

Nummular eczema occasionally can be confused for psoriasis as both entities can present with oval plaques. Psoriasis lesions tend to be pinker and less erythematous than nummular eczema lesions and most psoriasis plaques present with a characteristic silver scale.⁷ Clinically, nummular eczema is frequently associated with extreme pruritus, while in psoriasis the pruritus is less prominent.⁷

A biopsy would yield a more definitive diagnosis in difficult cases. Histologically, nummular eczema resembles other forms of spongiotic dermatitis, while psoriasis has very distinct histological features.⁷ Differentiating between contact dermatitis and nummular eczema relies on a thorough history of known allergies and potential exposure to environmental allergens. If history alone does not yield a definitive diagnosis and a suspicion for contact allergy is high, patch testing could help support one diagnosis over the other.⁵

Treatment

The generally accepted first line therapy includes mid to high potency topical corticosteroids in an ointment preparation or else under occlusion.^1,4 Other topical agents used include tar preparations and calcineurin inhibitors.⁴ Intralesional corticosteroid injection can be used to treat isolated lesions that fail to respond to topical treatments.⁴

As with almost all manifestations of dermatitis, general gentle skin care measures and daily moisturizing are recommended.¹ For more severe cases in older children, narrow-band UVB light therapy can be helpful.¹ Due to their efficacy in treatment of other forms of refractory dermatitis, systemic therapy with cyclosporine, azathioprine, mycophenolate mofetil, and methotrexate can be used in cases in which phototherapy fails or is not accessible.⁴

In cases recalcitrant to topical therapies, secondary staphylococcal infection always should be ruled out and treated with systemic antimicrobials such as first generation cephalosporins.¹

References

1. Eczematous eruptions in childhood in “Hurwitz Clinical Pediatric Dermatology,” 4th ed. (New York, N.Y.: Elsevier, pp. 59-60
2. Acta Derm Venereol. 1961;41:453-60.
3. Acta Derm Venereol. 1969;49(2):189-96.
4. Australas J Dermatol. 2010 May;51(2):128-30.
5. Contact Dermatitis. 1997 May;36(5):261-4.
6. Ped Dermatol. 2012 Oct;29(5):580-3.
7. Dermatol Ther. 2006 Mar-Apr;19(2):73-82.

Dr. Matiz is assistant professor of dermatology at Rady Children’s Hospital San Diego–University of California, San Diego and Mr. Ginsberg is a research associate at the hospital. Dr. Matiz and Mr. Ginsberg said they have no relevant financial disclosures.

By Catalina Matiz, M.D., and David Ginsberg

Nummular eczema

Nummular eczema is not an uncommon dermatosis that presents in pediatric and adult patients; its name, which derives from the Latin word nummulus (coin-like), refers to the coined-shape plaques that characterize this condition. It also has been referred to as discoid eczema and nummular dermatitis.¹

The lesions begin as erythematous papules and vesicles that extend into larger oval or circular plaques that often become crusted, and can later progress to dry and scaly plaques.^1,2 Patients often complain of intense pruritus.¹ The lesions can be single or multiple, and more commonly occur on the extensor extremities as well as the trunk, and rarely affect the neck and the head.^1-3 The pathophysiology of nummular eczema is not fully understood. It can occur in patients that exhibit atopic manifestations such as atopic dermatitis and other allergies, but there has been no clear link found between nummular eczema and atopy.^3,4

Many theories exist implicating causative factors including Staphylococcus aureus colonization and xerosis.¹ Similarly, some physicians believe that patch testing can be useful in these patients because of the potential for exacerbation caused by environmental allergens, but there is still no agreement on the ultimate cause.⁵ There is a higher incidence in males than females, and in the pediatric population, it is more common among “school aged” children between the ages of 2-12.⁶ Overall, nummular eczema is more commonly seen in adults, but it can occur at any age.^2,3,6

Differential diagnosis

Nummular eczema is commonly mistaken as tinea corporis.¹ The coined shape lesions, from which nummular eczema gets its name, can resemble the characteristic annular shape plaques of “ring worm,” but a potassium hydroxide (KOH) test or a fungal culture are simple ways to differentiate between the two conditions.

Nummular eczema occasionally can be confused for psoriasis as both entities can present with oval plaques. Psoriasis lesions tend to be pinker and less erythematous than nummular eczema lesions and most psoriasis plaques present with a characteristic silver scale.⁷ Clinically, nummular eczema is frequently associated with extreme pruritus, while in psoriasis the pruritus is less prominent.⁷

A biopsy would yield a more definitive diagnosis in difficult cases. Histologically, nummular eczema resembles other forms of spongiotic dermatitis, while psoriasis has very distinct histological features.⁷ Differentiating between contact dermatitis and nummular eczema relies on a thorough history of known allergies and potential exposure to environmental allergens. If history alone does not yield a definitive diagnosis and a suspicion for contact allergy is high, patch testing could help support one diagnosis over the other.⁵

Treatment

The generally accepted first line therapy includes mid to high potency topical corticosteroids in an ointment preparation or else under occlusion.^1,4 Other topical agents used include tar preparations and calcineurin inhibitors.⁴ Intralesional corticosteroid injection can be used to treat isolated lesions that fail to respond to topical treatments.⁴

As with almost all manifestations of dermatitis, general gentle skin care measures and daily moisturizing are recommended.¹ For more severe cases in older children, narrow-band UVB light therapy can be helpful.¹ Due to their efficacy in treatment of other forms of refractory dermatitis, systemic therapy with cyclosporine, azathioprine, mycophenolate mofetil, and methotrexate can be used in cases in which phototherapy fails or is not accessible.⁴

In cases recalcitrant to topical therapies, secondary staphylococcal infection always should be ruled out and treated with systemic antimicrobials such as first generation cephalosporins.¹

References

1. Eczematous eruptions in childhood in “Hurwitz Clinical Pediatric Dermatology,” 4th ed. (New York, N.Y.: Elsevier, pp. 59-60
2. Acta Derm Venereol. 1961;41:453-60.
3. Acta Derm Venereol. 1969;49(2):189-96.
4. Australas J Dermatol. 2010 May;51(2):128-30.
5. Contact Dermatitis. 1997 May;36(5):261-4.
6. Ped Dermatol. 2012 Oct;29(5):580-3.
7. Dermatol Ther. 2006 Mar-Apr;19(2):73-82.

Dr. Matiz is assistant professor of dermatology at Rady Children’s Hospital San Diego–University of California, San Diego and Mr. Ginsberg is a research associate at the hospital. Dr. Matiz and Mr. Ginsberg said they have no relevant financial disclosures.

By Catalina Matiz, M.D., and David Ginsberg

Nummular eczema

Nummular eczema is not an uncommon dermatosis that presents in pediatric and adult patients; its name, which derives from the Latin word nummulus (coin-like), refers to the coined-shape plaques that characterize this condition. It also has been referred to as discoid eczema and nummular dermatitis.¹

The lesions begin as erythematous papules and vesicles that extend into larger oval or circular plaques that often become crusted, and can later progress to dry and scaly plaques.^1,2 Patients often complain of intense pruritus.¹ The lesions can be single or multiple, and more commonly occur on the extensor extremities as well as the trunk, and rarely affect the neck and the head.^1-3 The pathophysiology of nummular eczema is not fully understood. It can occur in patients that exhibit atopic manifestations such as atopic dermatitis and other allergies, but there has been no clear link found between nummular eczema and atopy.^3,4

Many theories exist implicating causative factors including Staphylococcus aureus colonization and xerosis.¹ Similarly, some physicians believe that patch testing can be useful in these patients because of the potential for exacerbation caused by environmental allergens, but there is still no agreement on the ultimate cause.⁵ There is a higher incidence in males than females, and in the pediatric population, it is more common among “school aged” children between the ages of 2-12.⁶ Overall, nummular eczema is more commonly seen in adults, but it can occur at any age.^2,3,6

Differential diagnosis

Nummular eczema is commonly mistaken as tinea corporis.¹ The coined shape lesions, from which nummular eczema gets its name, can resemble the characteristic annular shape plaques of “ring worm,” but a potassium hydroxide (KOH) test or a fungal culture are simple ways to differentiate between the two conditions.

Nummular eczema occasionally can be confused for psoriasis as both entities can present with oval plaques. Psoriasis lesions tend to be pinker and less erythematous than nummular eczema lesions and most psoriasis plaques present with a characteristic silver scale.⁷ Clinically, nummular eczema is frequently associated with extreme pruritus, while in psoriasis the pruritus is less prominent.⁷

A biopsy would yield a more definitive diagnosis in difficult cases. Histologically, nummular eczema resembles other forms of spongiotic dermatitis, while psoriasis has very distinct histological features.⁷ Differentiating between contact dermatitis and nummular eczema relies on a thorough history of known allergies and potential exposure to environmental allergens. If history alone does not yield a definitive diagnosis and a suspicion for contact allergy is high, patch testing could help support one diagnosis over the other.⁵

Treatment

The generally accepted first line therapy includes mid to high potency topical corticosteroids in an ointment preparation or else under occlusion.^1,4 Other topical agents used include tar preparations and calcineurin inhibitors.⁴ Intralesional corticosteroid injection can be used to treat isolated lesions that fail to respond to topical treatments.⁴

As with almost all manifestations of dermatitis, general gentle skin care measures and daily moisturizing are recommended.¹ For more severe cases in older children, narrow-band UVB light therapy can be helpful.¹ Due to their efficacy in treatment of other forms of refractory dermatitis, systemic therapy with cyclosporine, azathioprine, mycophenolate mofetil, and methotrexate can be used in cases in which phototherapy fails or is not accessible.⁴

In cases recalcitrant to topical therapies, secondary staphylococcal infection always should be ruled out and treated with systemic antimicrobials such as first generation cephalosporins.¹

References

1. Eczematous eruptions in childhood in “Hurwitz Clinical Pediatric Dermatology,” 4th ed. (New York, N.Y.: Elsevier, pp. 59-60
2. Acta Derm Venereol. 1961;41:453-60.
3. Acta Derm Venereol. 1969;49(2):189-96.
4. Australas J Dermatol. 2010 May;51(2):128-30.
5. Contact Dermatitis. 1997 May;36(5):261-4.
6. Ped Dermatol. 2012 Oct;29(5):580-3.
7. Dermatol Ther. 2006 Mar-Apr;19(2):73-82.

Dr. Matiz is assistant professor of dermatology at Rady Children’s Hospital San Diego–University of California, San Diego and Mr. Ginsberg is a research associate at the hospital. Dr. Matiz and Mr. Ginsberg said they have no relevant financial disclosures.

By Ellen S. Haddock and Lawrence F. Eichenfield, M.D.

Urticaria multiforme

Although not the most classic presentation, this patient’s migrating rash is most consistent with urticaria (hives). Urticaria is dermal edema which causes transient edematous and usually pruritic wheals.^1,2 Each individual lesion lasts less than 24 hours and disappears without leaving a mark. Urticaria is caused by mast cell activation, which leads to release of antihistamines and other substances that increase capillary and venule permeability, allowing fluid to leak into the extravascular space.¹ In children, mast cell activation is usually triggered by infections, drugs, or foods.¹

Classic urticaria consists of large, pruritic plaques and may be associated with airway edema. However, urticaria also can present with annular and polycyclic lesions, which may be less pruritic and are not associated with airway edema.³ This “multiple redness” is distinct from erythema multiforme (EM), although often urticaria is confused with EM. Lesions of EM are annular and typically have purpuric or dusky centers, with each lesion lasting a minimum of 1 week.4 Annular lesions in urticaria usually do not have central duskiness or blisters. Often the centers of annular urticaria lesions are relatively normal and edges are raised. Some urticaria, especially in younger children as in this case, is sometimes called “urticaria multiforme” because the ecchymotic centers are reminiscent of, but distinct from, classic target lesions of EM. Urticaria multiforme is commonly misdiagnosed as EM, with 29% of patients originally misdiagnosed in one study.³

Urticaria multiforme occurs most commonly in infants and preschool-aged children,5 although it has been diagnosed in patients as old as 18 years.6 Patients often have had an antecedent bacterial or viral illness, recent treatment with antibiotics, or recent vaccination (67%, 44%, and 11% of patients, respectively, in one series).⁴ In contrast with classic urticaria, urticaria multiforme has not been associated with food allergy.⁴

In this case, urticaria multiforme was likely caused by a hypersensitivity reaction to amoxicillin. A reaction to nitrofurantoin was less likely because the patient had been taking it continuously for months without any complications.

Differential diagnosis

The differential diagnosis for urticaria multiforme includes EM and a serum sickness–like reaction. The main clue that this patient’s rash was a subtype of urticaria rather than EM was its transience, with individual lesions appearing and disappearing in less than a day.4 In contrast, the lesions of EM are fixed, persisting for a week or longer. While urticaria multiforme may have central ecchymosis (termed “hemorrhagic urticaria”) that looks similar to the dusky centers of EM lesions and persists longer than the transient edematous plaques,1 it resolves quickly with appropriate treatment.4 In contrast, the dusky centers of EM, which are caused by epidermal necrosis, take longer to resolve.4 Dermatographism, if present, would support a diagnosis of urticaria rather than EM. Similarly, facial or acral edema, if present, would support a diagnosis of urticaria multiforme; they are uncommon in EM. In contrast, any necrosis, blistering, or erosions in the centers of the annular lesions or on mucosal membranes would suggest EM, as necrosis, blistering, erosions, and mucosal involvement do not occur in urticaria multiforme.4 We stress that in EM, “the center of the lesion is the center of the action,” while in urticaria, wheals often have relatively normal centers.

Although both urticaria and EM lesions may be pruritic, any burning sensation is more suggestive of EM.4 Urticaria multiforme is often associated with antibiotics, vaccinations, and upper respiratory infections, while EM is most commonly associated with herpes simplex infection.^4,7

Urticaria multiforme also may appear similar to a serum sickness–like reaction, which is another kind of hypersensitivity reaction triggered by the administration of antibiotics. It is most commonly associated with cefaclor, but also is associated with other antibiotics including amoxicillin.8 As with urticaria, hypersensitivity drug eruptions and serum sickness-like reactions may present with purpuric, polycyclic wheals with central clearing. However, as with EM, the lesions of serum sickness–like reactions are fixed, lasting for days to weeks.⁴ Facial or acral angioedema may occur in both urticaria multiforme and serum sickness–like reactions, but serum sickness–like reactions are not associated with dermatographism.⁴  Furthermore, serum sickness–like reactions are typically associated with high-grade fever, myalgia, arthralgia, and lymphadenopathy, which are not seen in urticaria multiforme.^4,5

Diagnosis of urticaria multiforme usually can be made by history and physical exam, so lab testing and skin biopsy typically are not necessary.⁵ If performed, lab work may show modest elevation in erythrocyte sedimentation rate and C-reactive protein, but often these acute-phase reactants are within normal limits, and complete blood count and complete metabolic panel are unremarkable.^3,5 Although urticaria multiforme often is associated with antecedent viral or bacterial infections, work-up for infectious etiology typically is not fruitful or helpful.⁴ If lesions are biopsied, the histology of urticaria multiforme is indistinguishable from other types of acute urticaria, showing dermal edema with perivascular lymphocytic infiltrate.⁹ In contrast, EM shows exocytosis, spongiosis, and epidermal necrosis.⁹

Treatment

The first step in managing urticaria multiforme is discontinuing any unnecessary antibiotic that could be triggering the hypersensitivity reaction. Urticaria multiforme typically resolves within 2 weeks without any treatment and responds to treatment with antihistamines within 24-28 hours.⁵ Treatment with a histamine₁ (H₁) blocker such as hydroxyzine, cetirizine, or diphenhydramine may be sufficient to resolve the eruption, but combination therapy with both an H₁ blocker and an H₂ blocker such as ranitidine can be helpful.4 Treatment with systemic corticosteroids usually is not necessary and should be reserved for severely symptomatic or refractory cases.^4,9

One of the reasons that it is important to distinguish urticaria multiforme from EM is to avoid overtreatment with systemic steroids,³ which are rarely required for urticaria multiforme but are sometimes useful, although controversial, for EM.¹ Additionally, the correct diagnosis is important for providing anticipatory guidance.⁶ Patients diagnosed with serum sickness–like reactions should be counseled to avoid unnecessary exposure to the culprit antibiotic in the future. Patients with urticaria multiforme who were taking an antibiotic at the onset of the eruption may consider avoiding the potential culprit antibiotic in the future, but it is important to keep in mind that urticaria multiforme is more strongly associated with antecedent infection than with antibiotic use, and so antibiotic avoidance may not be necessary unless justified by formal allergy testing. EM minor is more commonly associated with a herpes simplex virus infection than a drug reaction, so antibiotic use is less concerning, but patients should be counseled that recurrence is common and prophylactic treatment with acyclovir may be advised for recurrent disease.¹

References

1. “Neonatal and Infant Dermatology” (Elsevier Health Sciences: New York, 2014, pp. 456-70).
2. CRIAI. 2006;30(1):003-012.
3. Pediatr Dermatol. 1997;14(3):231-4.
4. Pediatrics. 2007;119(5):e1177-83.
5. Pediatr Dermatol. 2011;28(4):436-8.
6. The Journal of Allergy and Clinical Immunology in Practice. 2013;1(5):520-1.
7. Arch Dermatol. 1993;129(1):92-6.
8. “The Hypersensitivity Syndromes” in Hurwitz Clinical Pediatric Dermatology. 4 ed. Elsevier: New York, 2011, pp. 455-84.
9. J Clin Aesthet Dermatol. 2013;6(3):34-9.

Ms. Haddock is a medical student at University of California, San Diego School of Medicine and a research associate at Rady Children’s Hospital, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego and professor of medicine and pediatrics at UC San Diego School of Medicine. Dr. Eichenfield and Ms. Haddock said they have no relevant financial disclosures. Email [email protected].

By Ellen S. Haddock and Lawrence F. Eichenfield, M.D.

Urticaria multiforme

Although not the most classic presentation, this patient’s migrating rash is most consistent with urticaria (hives). Urticaria is dermal edema which causes transient edematous and usually pruritic wheals.^1,2 Each individual lesion lasts less than 24 hours and disappears without leaving a mark. Urticaria is caused by mast cell activation, which leads to release of antihistamines and other substances that increase capillary and venule permeability, allowing fluid to leak into the extravascular space.¹ In children, mast cell activation is usually triggered by infections, drugs, or foods.¹

Classic urticaria consists of large, pruritic plaques and may be associated with airway edema. However, urticaria also can present with annular and polycyclic lesions, which may be less pruritic and are not associated with airway edema.³ This “multiple redness” is distinct from erythema multiforme (EM), although often urticaria is confused with EM. Lesions of EM are annular and typically have purpuric or dusky centers, with each lesion lasting a minimum of 1 week.4 Annular lesions in urticaria usually do not have central duskiness or blisters. Often the centers of annular urticaria lesions are relatively normal and edges are raised. Some urticaria, especially in younger children as in this case, is sometimes called “urticaria multiforme” because the ecchymotic centers are reminiscent of, but distinct from, classic target lesions of EM. Urticaria multiforme is commonly misdiagnosed as EM, with 29% of patients originally misdiagnosed in one study.³

Urticaria multiforme occurs most commonly in infants and preschool-aged children,5 although it has been diagnosed in patients as old as 18 years.6 Patients often have had an antecedent bacterial or viral illness, recent treatment with antibiotics, or recent vaccination (67%, 44%, and 11% of patients, respectively, in one series).⁴ In contrast with classic urticaria, urticaria multiforme has not been associated with food allergy.⁴

In this case, urticaria multiforme was likely caused by a hypersensitivity reaction to amoxicillin. A reaction to nitrofurantoin was less likely because the patient had been taking it continuously for months without any complications.

Differential diagnosis

The differential diagnosis for urticaria multiforme includes EM and a serum sickness–like reaction. The main clue that this patient’s rash was a subtype of urticaria rather than EM was its transience, with individual lesions appearing and disappearing in less than a day.4 In contrast, the lesions of EM are fixed, persisting for a week or longer. While urticaria multiforme may have central ecchymosis (termed “hemorrhagic urticaria”) that looks similar to the dusky centers of EM lesions and persists longer than the transient edematous plaques,1 it resolves quickly with appropriate treatment.4 In contrast, the dusky centers of EM, which are caused by epidermal necrosis, take longer to resolve.4 Dermatographism, if present, would support a diagnosis of urticaria rather than EM. Similarly, facial or acral edema, if present, would support a diagnosis of urticaria multiforme; they are uncommon in EM. In contrast, any necrosis, blistering, or erosions in the centers of the annular lesions or on mucosal membranes would suggest EM, as necrosis, blistering, erosions, and mucosal involvement do not occur in urticaria multiforme.4 We stress that in EM, “the center of the lesion is the center of the action,” while in urticaria, wheals often have relatively normal centers.

Although both urticaria and EM lesions may be pruritic, any burning sensation is more suggestive of EM.4 Urticaria multiforme is often associated with antibiotics, vaccinations, and upper respiratory infections, while EM is most commonly associated with herpes simplex infection.^4,7

Urticaria multiforme also may appear similar to a serum sickness–like reaction, which is another kind of hypersensitivity reaction triggered by the administration of antibiotics. It is most commonly associated with cefaclor, but also is associated with other antibiotics including amoxicillin.8 As with urticaria, hypersensitivity drug eruptions and serum sickness-like reactions may present with purpuric, polycyclic wheals with central clearing. However, as with EM, the lesions of serum sickness–like reactions are fixed, lasting for days to weeks.⁴ Facial or acral angioedema may occur in both urticaria multiforme and serum sickness–like reactions, but serum sickness–like reactions are not associated with dermatographism.⁴  Furthermore, serum sickness–like reactions are typically associated with high-grade fever, myalgia, arthralgia, and lymphadenopathy, which are not seen in urticaria multiforme.^4,5

Diagnosis of urticaria multiforme usually can be made by history and physical exam, so lab testing and skin biopsy typically are not necessary.⁵ If performed, lab work may show modest elevation in erythrocyte sedimentation rate and C-reactive protein, but often these acute-phase reactants are within normal limits, and complete blood count and complete metabolic panel are unremarkable.^3,5 Although urticaria multiforme often is associated with antecedent viral or bacterial infections, work-up for infectious etiology typically is not fruitful or helpful.⁴ If lesions are biopsied, the histology of urticaria multiforme is indistinguishable from other types of acute urticaria, showing dermal edema with perivascular lymphocytic infiltrate.⁹ In contrast, EM shows exocytosis, spongiosis, and epidermal necrosis.⁹

Treatment

The first step in managing urticaria multiforme is discontinuing any unnecessary antibiotic that could be triggering the hypersensitivity reaction. Urticaria multiforme typically resolves within 2 weeks without any treatment and responds to treatment with antihistamines within 24-28 hours.⁵ Treatment with a histamine₁ (H₁) blocker such as hydroxyzine, cetirizine, or diphenhydramine may be sufficient to resolve the eruption, but combination therapy with both an H₁ blocker and an H₂ blocker such as ranitidine can be helpful.4 Treatment with systemic corticosteroids usually is not necessary and should be reserved for severely symptomatic or refractory cases.^4,9

One of the reasons that it is important to distinguish urticaria multiforme from EM is to avoid overtreatment with systemic steroids,³ which are rarely required for urticaria multiforme but are sometimes useful, although controversial, for EM.¹ Additionally, the correct diagnosis is important for providing anticipatory guidance.⁶ Patients diagnosed with serum sickness–like reactions should be counseled to avoid unnecessary exposure to the culprit antibiotic in the future. Patients with urticaria multiforme who were taking an antibiotic at the onset of the eruption may consider avoiding the potential culprit antibiotic in the future, but it is important to keep in mind that urticaria multiforme is more strongly associated with antecedent infection than with antibiotic use, and so antibiotic avoidance may not be necessary unless justified by formal allergy testing. EM minor is more commonly associated with a herpes simplex virus infection than a drug reaction, so antibiotic use is less concerning, but patients should be counseled that recurrence is common and prophylactic treatment with acyclovir may be advised for recurrent disease.¹

References

1. “Neonatal and Infant Dermatology” (Elsevier Health Sciences: New York, 2014, pp. 456-70).
2. CRIAI. 2006;30(1):003-012.
3. Pediatr Dermatol. 1997;14(3):231-4.
4. Pediatrics. 2007;119(5):e1177-83.
5. Pediatr Dermatol. 2011;28(4):436-8.
6. The Journal of Allergy and Clinical Immunology in Practice. 2013;1(5):520-1.
7. Arch Dermatol. 1993;129(1):92-6.
8. “The Hypersensitivity Syndromes” in Hurwitz Clinical Pediatric Dermatology. 4 ed. Elsevier: New York, 2011, pp. 455-84.
9. J Clin Aesthet Dermatol. 2013;6(3):34-9.

Ms. Haddock is a medical student at University of California, San Diego School of Medicine and a research associate at Rady Children’s Hospital, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego and professor of medicine and pediatrics at UC San Diego School of Medicine. Dr. Eichenfield and Ms. Haddock said they have no relevant financial disclosures. Email [email protected].

By Ellen S. Haddock and Lawrence F. Eichenfield, M.D.

Urticaria multiforme

Although not the most classic presentation, this patient’s migrating rash is most consistent with urticaria (hives). Urticaria is dermal edema which causes transient edematous and usually pruritic wheals.^1,2 Each individual lesion lasts less than 24 hours and disappears without leaving a mark. Urticaria is caused by mast cell activation, which leads to release of antihistamines and other substances that increase capillary and venule permeability, allowing fluid to leak into the extravascular space.¹ In children, mast cell activation is usually triggered by infections, drugs, or foods.¹

Classic urticaria consists of large, pruritic plaques and may be associated with airway edema. However, urticaria also can present with annular and polycyclic lesions, which may be less pruritic and are not associated with airway edema.³ This “multiple redness” is distinct from erythema multiforme (EM), although often urticaria is confused with EM. Lesions of EM are annular and typically have purpuric or dusky centers, with each lesion lasting a minimum of 1 week.4 Annular lesions in urticaria usually do not have central duskiness or blisters. Often the centers of annular urticaria lesions are relatively normal and edges are raised. Some urticaria, especially in younger children as in this case, is sometimes called “urticaria multiforme” because the ecchymotic centers are reminiscent of, but distinct from, classic target lesions of EM. Urticaria multiforme is commonly misdiagnosed as EM, with 29% of patients originally misdiagnosed in one study.³

Urticaria multiforme occurs most commonly in infants and preschool-aged children,5 although it has been diagnosed in patients as old as 18 years.6 Patients often have had an antecedent bacterial or viral illness, recent treatment with antibiotics, or recent vaccination (67%, 44%, and 11% of patients, respectively, in one series).⁴ In contrast with classic urticaria, urticaria multiforme has not been associated with food allergy.⁴

In this case, urticaria multiforme was likely caused by a hypersensitivity reaction to amoxicillin. A reaction to nitrofurantoin was less likely because the patient had been taking it continuously for months without any complications.

Differential diagnosis

The differential diagnosis for urticaria multiforme includes EM and a serum sickness–like reaction. The main clue that this patient’s rash was a subtype of urticaria rather than EM was its transience, with individual lesions appearing and disappearing in less than a day.4 In contrast, the lesions of EM are fixed, persisting for a week or longer. While urticaria multiforme may have central ecchymosis (termed “hemorrhagic urticaria”) that looks similar to the dusky centers of EM lesions and persists longer than the transient edematous plaques,1 it resolves quickly with appropriate treatment.4 In contrast, the dusky centers of EM, which are caused by epidermal necrosis, take longer to resolve.4 Dermatographism, if present, would support a diagnosis of urticaria rather than EM. Similarly, facial or acral edema, if present, would support a diagnosis of urticaria multiforme; they are uncommon in EM. In contrast, any necrosis, blistering, or erosions in the centers of the annular lesions or on mucosal membranes would suggest EM, as necrosis, blistering, erosions, and mucosal involvement do not occur in urticaria multiforme.4 We stress that in EM, “the center of the lesion is the center of the action,” while in urticaria, wheals often have relatively normal centers.

Although both urticaria and EM lesions may be pruritic, any burning sensation is more suggestive of EM.4 Urticaria multiforme is often associated with antibiotics, vaccinations, and upper respiratory infections, while EM is most commonly associated with herpes simplex infection.^4,7

Urticaria multiforme also may appear similar to a serum sickness–like reaction, which is another kind of hypersensitivity reaction triggered by the administration of antibiotics. It is most commonly associated with cefaclor, but also is associated with other antibiotics including amoxicillin.8 As with urticaria, hypersensitivity drug eruptions and serum sickness-like reactions may present with purpuric, polycyclic wheals with central clearing. However, as with EM, the lesions of serum sickness–like reactions are fixed, lasting for days to weeks.⁴ Facial or acral angioedema may occur in both urticaria multiforme and serum sickness–like reactions, but serum sickness–like reactions are not associated with dermatographism.⁴  Furthermore, serum sickness–like reactions are typically associated with high-grade fever, myalgia, arthralgia, and lymphadenopathy, which are not seen in urticaria multiforme.^4,5

Diagnosis of urticaria multiforme usually can be made by history and physical exam, so lab testing and skin biopsy typically are not necessary.⁵ If performed, lab work may show modest elevation in erythrocyte sedimentation rate and C-reactive protein, but often these acute-phase reactants are within normal limits, and complete blood count and complete metabolic panel are unremarkable.^3,5 Although urticaria multiforme often is associated with antecedent viral or bacterial infections, work-up for infectious etiology typically is not fruitful or helpful.⁴ If lesions are biopsied, the histology of urticaria multiforme is indistinguishable from other types of acute urticaria, showing dermal edema with perivascular lymphocytic infiltrate.⁹ In contrast, EM shows exocytosis, spongiosis, and epidermal necrosis.⁹

Treatment

The first step in managing urticaria multiforme is discontinuing any unnecessary antibiotic that could be triggering the hypersensitivity reaction. Urticaria multiforme typically resolves within 2 weeks without any treatment and responds to treatment with antihistamines within 24-28 hours.⁵ Treatment with a histamine₁ (H₁) blocker such as hydroxyzine, cetirizine, or diphenhydramine may be sufficient to resolve the eruption, but combination therapy with both an H₁ blocker and an H₂ blocker such as ranitidine can be helpful.4 Treatment with systemic corticosteroids usually is not necessary and should be reserved for severely symptomatic or refractory cases.^4,9

One of the reasons that it is important to distinguish urticaria multiforme from EM is to avoid overtreatment with systemic steroids,³ which are rarely required for urticaria multiforme but are sometimes useful, although controversial, for EM.¹ Additionally, the correct diagnosis is important for providing anticipatory guidance.⁶ Patients diagnosed with serum sickness–like reactions should be counseled to avoid unnecessary exposure to the culprit antibiotic in the future. Patients with urticaria multiforme who were taking an antibiotic at the onset of the eruption may consider avoiding the potential culprit antibiotic in the future, but it is important to keep in mind that urticaria multiforme is more strongly associated with antecedent infection than with antibiotic use, and so antibiotic avoidance may not be necessary unless justified by formal allergy testing. EM minor is more commonly associated with a herpes simplex virus infection than a drug reaction, so antibiotic use is less concerning, but patients should be counseled that recurrence is common and prophylactic treatment with acyclovir may be advised for recurrent disease.¹

References

1. “Neonatal and Infant Dermatology” (Elsevier Health Sciences: New York, 2014, pp. 456-70).
2. CRIAI. 2006;30(1):003-012.
3. Pediatr Dermatol. 1997;14(3):231-4.
4. Pediatrics. 2007;119(5):e1177-83.
5. Pediatr Dermatol. 2011;28(4):436-8.
6. The Journal of Allergy and Clinical Immunology in Practice. 2013;1(5):520-1.
7. Arch Dermatol. 1993;129(1):92-6.
8. “The Hypersensitivity Syndromes” in Hurwitz Clinical Pediatric Dermatology. 4 ed. Elsevier: New York, 2011, pp. 455-84.
9. J Clin Aesthet Dermatol. 2013;6(3):34-9.

Ms. Haddock is a medical student at University of California, San Diego School of Medicine and a research associate at Rady Children’s Hospital, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego and professor of medicine and pediatrics at UC San Diego School of Medicine. Dr. Eichenfield and Ms. Haddock said they have no relevant financial disclosures. Email [email protected].

Ancillary testing

Complete blood count showed leukocytosis (13.1 th/mcL), with normal differential. The C-reactive protein was elevated (10 mg/dL). The comprehensive metabolic panel was within normal limits. Mycoplasma pneumoniae antibody, IgM was positive, and herpes virus cultures were negative. The chest x-ray showed a dense right upper lobe airspace opacity, concerning for pneumonia, likely with a component of atelectasis.

Discussion

Mycoplasma pneumoniae–induced rash and mucositis (MIRM) is a syndrome of mucocutaneous involvement in conjunction with an M. pneumoniae infection. M. pneumoniae is a bacteria that commonly causes respiratory tract infections. In children, it is a leading cause of atypical pneumonia.^1,2 Extrapulmonary manifestations are common and can involve the skin, heart, kidneys, gastrointestinal system, and nervous system.³ There is a 1-3 week incubation period for infections, which always begin with respiratory symptoms. The most common early symptoms of this infection are cough, malaise, fever, and headaches. Studies show that between 25%-38% of M. pneumoniae infections have mucocutaneous manifestations.^3,4

An overwhelming majority of cases have mucosal involvement while the degree of skin involvement varies. Cutaneous manifestations, which are usually polymorphic, present with vesiculobullous lesions, targetoid macules and papules, or morbilliform eruptions.³ MIRM is seen most often in children and adolescents, but a few adult cases have been reported. About 66% of cases are seen in males, but the reason for this gender predilection is not well understood.3 Overall, MIRM has an excellent prognosis, compared with the other disorders on the differential diagnosis.

Differential diagnosis

MIRM used to be considered along the spectrum of bullous diseases that have mucosal involvement including erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrosis (TEN).^3-6 The distinction can be difficult to identify, given the similarities that all of these diseases share, and many published articles referencing cases of SJS, TEN, and EM actually fit the criteria for MIRM.6 What sets MIRM apart is the predominance of mucosal involvement with minimal skin involvement and the overwhelming overall good prognosis compared with drug induced SJS.³

Although rare cases have moderate cutaneous involvement, MIRM is most notable for oral lesions, which include ulcers, erosions, and vesiculobullae of the lips and buccal mucosa, as well as ocular and genital mucosal involvement in a lower degree.³ For cases with moderate or even mild involvement of the skin, ruling out other diagnoses becomes more difficult, especially since the dermatologic manifestations of targetoid papules and bullae are common to all of them. Testing for M. pneumoniae will strengthen the diagnosis and can be done in a number of ways. Using polymerase chain reaction to measure for M. pneumoniae DNA offers the benefit of being able to detect an infection early in its course because it does not rely on antibody formation.⁴ Other testing methods include M. pneumoniae antigen detection, and IgM or IgG titers.⁴

Treatment

The mainstay of treatment of this bacterial infection is, of course, antibiotics. Azithromycin and erythromycin are the drugs of choice for children. While tetracyclines and fluoroquinolones can be used to treat M. pneumoniae, their use is not recommended in young children.⁴ Systemic corticosteroids can be used in addition to antibiotics, but there is limited data to support its efficacy in these patients.⁷ In milder cases, reports have documented that the course can be self-limited and may improve with only supportive care. Because of the severity of mucosal involvement in some cases, such as the one in our patient, supportive care may include intravenous hydration and total parenteral nutrition if the patient is unable to tolerate oral intake. In more severe cases, IVIG can be beneficial.8 This has been shown to induce rapid improvement in refractory mucositis when antibiotics and supportive mucosal care alone have not been sufficient.⁸

References

1. (J Clin Microbiol. 2015 Jan;53[1]:124-30.)
2. (Clin Microbiol. 2004;17[4]:697-728.)
3. (J Am Acad Dermatol.  2015;72[2]: 239-54.)
4. (Int J Dermatol. 2009 Jul;48[7]:673-80.)  
5. (J Eur Acad Dermatol Venereol. 2015 Mar;29[3]:595-8.)  
6. (J Am Acad Dermatol. 2005 Feb;52[2]:312-5.)
7. (Pediatr Dermatol. 2014 Nov-Dec;31[6]:664-9.)
8. (Acta Paediatr. 2011 Nov;100[11]:e238-40.)

Dr. Matiz is assistant professor of dermatology at Rady Children’s Hospital San Diego–University of California San Diego and Mr. Ginsberg is a research associate at the hospital. They said they had no relevant financial disclosures.

Email them at [email protected].

Ancillary testing

Complete blood count showed leukocytosis (13.1 th/mcL), with normal differential. The C-reactive protein was elevated (10 mg/dL). The comprehensive metabolic panel was within normal limits. Mycoplasma pneumoniae antibody, IgM was positive, and herpes virus cultures were negative. The chest x-ray showed a dense right upper lobe airspace opacity, concerning for pneumonia, likely with a component of atelectasis.

Discussion

Mycoplasma pneumoniae–induced rash and mucositis (MIRM) is a syndrome of mucocutaneous involvement in conjunction with an M. pneumoniae infection. M. pneumoniae is a bacteria that commonly causes respiratory tract infections. In children, it is a leading cause of atypical pneumonia.^1,2 Extrapulmonary manifestations are common and can involve the skin, heart, kidneys, gastrointestinal system, and nervous system.³ There is a 1-3 week incubation period for infections, which always begin with respiratory symptoms. The most common early symptoms of this infection are cough, malaise, fever, and headaches. Studies show that between 25%-38% of M. pneumoniae infections have mucocutaneous manifestations.^3,4

An overwhelming majority of cases have mucosal involvement while the degree of skin involvement varies. Cutaneous manifestations, which are usually polymorphic, present with vesiculobullous lesions, targetoid macules and papules, or morbilliform eruptions.³ MIRM is seen most often in children and adolescents, but a few adult cases have been reported. About 66% of cases are seen in males, but the reason for this gender predilection is not well understood.3 Overall, MIRM has an excellent prognosis, compared with the other disorders on the differential diagnosis.

Differential diagnosis

MIRM used to be considered along the spectrum of bullous diseases that have mucosal involvement including erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrosis (TEN).^3-6 The distinction can be difficult to identify, given the similarities that all of these diseases share, and many published articles referencing cases of SJS, TEN, and EM actually fit the criteria for MIRM.6 What sets MIRM apart is the predominance of mucosal involvement with minimal skin involvement and the overwhelming overall good prognosis compared with drug induced SJS.³

Although rare cases have moderate cutaneous involvement, MIRM is most notable for oral lesions, which include ulcers, erosions, and vesiculobullae of the lips and buccal mucosa, as well as ocular and genital mucosal involvement in a lower degree.³ For cases with moderate or even mild involvement of the skin, ruling out other diagnoses becomes more difficult, especially since the dermatologic manifestations of targetoid papules and bullae are common to all of them. Testing for M. pneumoniae will strengthen the diagnosis and can be done in a number of ways. Using polymerase chain reaction to measure for M. pneumoniae DNA offers the benefit of being able to detect an infection early in its course because it does not rely on antibody formation.⁴ Other testing methods include M. pneumoniae antigen detection, and IgM or IgG titers.⁴

Treatment

The mainstay of treatment of this bacterial infection is, of course, antibiotics. Azithromycin and erythromycin are the drugs of choice for children. While tetracyclines and fluoroquinolones can be used to treat M. pneumoniae, their use is not recommended in young children.⁴ Systemic corticosteroids can be used in addition to antibiotics, but there is limited data to support its efficacy in these patients.⁷ In milder cases, reports have documented that the course can be self-limited and may improve with only supportive care. Because of the severity of mucosal involvement in some cases, such as the one in our patient, supportive care may include intravenous hydration and total parenteral nutrition if the patient is unable to tolerate oral intake. In more severe cases, IVIG can be beneficial.8 This has been shown to induce rapid improvement in refractory mucositis when antibiotics and supportive mucosal care alone have not been sufficient.⁸

References

1. (J Clin Microbiol. 2015 Jan;53[1]:124-30.)
2. (Clin Microbiol. 2004;17[4]:697-728.)
3. (J Am Acad Dermatol.  2015;72[2]: 239-54.)
4. (Int J Dermatol. 2009 Jul;48[7]:673-80.)  
5. (J Eur Acad Dermatol Venereol. 2015 Mar;29[3]:595-8.)  
6. (J Am Acad Dermatol. 2005 Feb;52[2]:312-5.)
7. (Pediatr Dermatol. 2014 Nov-Dec;31[6]:664-9.)
8. (Acta Paediatr. 2011 Nov;100[11]:e238-40.)

Dr. Matiz is assistant professor of dermatology at Rady Children’s Hospital San Diego–University of California San Diego and Mr. Ginsberg is a research associate at the hospital. They said they had no relevant financial disclosures.

Email them at [email protected].

Ancillary testing

Complete blood count showed leukocytosis (13.1 th/mcL), with normal differential. The C-reactive protein was elevated (10 mg/dL). The comprehensive metabolic panel was within normal limits. Mycoplasma pneumoniae antibody, IgM was positive, and herpes virus cultures were negative. The chest x-ray showed a dense right upper lobe airspace opacity, concerning for pneumonia, likely with a component of atelectasis.

Discussion

Mycoplasma pneumoniae–induced rash and mucositis (MIRM) is a syndrome of mucocutaneous involvement in conjunction with an M. pneumoniae infection. M. pneumoniae is a bacteria that commonly causes respiratory tract infections. In children, it is a leading cause of atypical pneumonia.^1,2 Extrapulmonary manifestations are common and can involve the skin, heart, kidneys, gastrointestinal system, and nervous system.³ There is a 1-3 week incubation period for infections, which always begin with respiratory symptoms. The most common early symptoms of this infection are cough, malaise, fever, and headaches. Studies show that between 25%-38% of M. pneumoniae infections have mucocutaneous manifestations.^3,4

An overwhelming majority of cases have mucosal involvement while the degree of skin involvement varies. Cutaneous manifestations, which are usually polymorphic, present with vesiculobullous lesions, targetoid macules and papules, or morbilliform eruptions.³ MIRM is seen most often in children and adolescents, but a few adult cases have been reported. About 66% of cases are seen in males, but the reason for this gender predilection is not well understood.3 Overall, MIRM has an excellent prognosis, compared with the other disorders on the differential diagnosis.

Differential diagnosis

MIRM used to be considered along the spectrum of bullous diseases that have mucosal involvement including erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrosis (TEN).^3-6 The distinction can be difficult to identify, given the similarities that all of these diseases share, and many published articles referencing cases of SJS, TEN, and EM actually fit the criteria for MIRM.6 What sets MIRM apart is the predominance of mucosal involvement with minimal skin involvement and the overwhelming overall good prognosis compared with drug induced SJS.³

Although rare cases have moderate cutaneous involvement, MIRM is most notable for oral lesions, which include ulcers, erosions, and vesiculobullae of the lips and buccal mucosa, as well as ocular and genital mucosal involvement in a lower degree.³ For cases with moderate or even mild involvement of the skin, ruling out other diagnoses becomes more difficult, especially since the dermatologic manifestations of targetoid papules and bullae are common to all of them. Testing for M. pneumoniae will strengthen the diagnosis and can be done in a number of ways. Using polymerase chain reaction to measure for M. pneumoniae DNA offers the benefit of being able to detect an infection early in its course because it does not rely on antibody formation.⁴ Other testing methods include M. pneumoniae antigen detection, and IgM or IgG titers.⁴

Treatment

The mainstay of treatment of this bacterial infection is, of course, antibiotics. Azithromycin and erythromycin are the drugs of choice for children. While tetracyclines and fluoroquinolones can be used to treat M. pneumoniae, their use is not recommended in young children.⁴ Systemic corticosteroids can be used in addition to antibiotics, but there is limited data to support its efficacy in these patients.⁷ In milder cases, reports have documented that the course can be self-limited and may improve with only supportive care. Because of the severity of mucosal involvement in some cases, such as the one in our patient, supportive care may include intravenous hydration and total parenteral nutrition if the patient is unable to tolerate oral intake. In more severe cases, IVIG can be beneficial.8 This has been shown to induce rapid improvement in refractory mucositis when antibiotics and supportive mucosal care alone have not been sufficient.⁸

References

1. (J Clin Microbiol. 2015 Jan;53[1]:124-30.)
2. (Clin Microbiol. 2004;17[4]:697-728.)
3. (J Am Acad Dermatol.  2015;72[2]: 239-54.)
4. (Int J Dermatol. 2009 Jul;48[7]:673-80.)  
5. (J Eur Acad Dermatol Venereol. 2015 Mar;29[3]:595-8.)  
6. (J Am Acad Dermatol. 2005 Feb;52[2]:312-5.)
7. (Pediatr Dermatol. 2014 Nov-Dec;31[6]:664-9.)
8. (Acta Paediatr. 2011 Nov;100[11]:e238-40.)

Dr. Matiz is assistant professor of dermatology at Rady Children’s Hospital San Diego–University of California San Diego and Mr. Ginsberg is a research associate at the hospital. They said they had no relevant financial disclosures.

Email them at [email protected].

Tinea versicolor

Tinea versicolor – also called pityriasis versicolor – is a benign superficial fungal skin infection caused by Malassezia. It presents as well-demarcated, oval, finely scaling macules, patches, or thin plaques, which can be hypopigmented, hyperpigmented, or erythematous.^1,2,3 . The name, tinea versicolor, highlights the variability in the color of lesions.⁴

Scale may be minimal, but becomes more noticeable when lesions are scraped, which is called the “evoked scale sign.”⁵ The lesions may be asymptomatic or slightly pruritic.¹ Lesions range in size from several millimeters to several centimeters and may coalesce.6 They are most commonly found on the chest, back, upper arms, and neck,^2,7 but in children the face may be affected.^1,3,8 Hypopigmented lesions may be most noticeable during the summer when the surrounding uninvolved skin darkens with sun exposure.9 Tinea versicolor is not contagious, but pigmentary changes may cause cosmetic concerns, and the condition may persist for years if not treated.^2,4

Malassezia is a dimorphic fungus that is part of the normal skin flora in its yeast form, but if Malassezia converts to its hyphal form, it is able penetrate the stratum corneum and cause the tinea versicolor rash.^1,10 The reason for the conversion from yeast to hyphal form is not fully understood.¹¹Malassezia is lipophilic, so it thrives when sebum production is high, which is why tinea versicolor most commonly develops in adolescence or young adulthood, although it may be seen in younger children and older adults.¹² Genetic predisposition, warm and humid environments, oily skin, use of oily creams, use of corticosteroids, hyperhidrosis, physical activity, malnutrition, immunosuppression, and exposure to sunlight increase susceptibility.^1,13,14

Tinea versicolor is most commonly caused by Malassezia globosa and Malassezia furfur.^13,15,16 Hypopigmentation may be caused by Malassezia’s production of azelaic acid, which inhibits the dopa-tyrosinase reaction that is part of melanin synthesis.^15,17,18 Hyperpigmentation may result from inflammation.^15,18 The evoked scale sign results from the production of keratinase, which disrupts the stratum corneum.⁵

Tinea versicolor often can be diagnosed by its characteristic clinical appearance and may fluoresce golden under a Wood’s ultraviolet lamp.¹⁹ Diagnosis can be confirmed by microscopic examination of skin scrapings treated with potassium hydroxide (KOH), which will have a “spaghetti and meatball” appearance, with the hyphae resembling spaghetti and spores resembling meatballs.¹ For young children, removing scale with transparent tape can be a good alternative to scraping skin with a blade.^2,19

Differential diagnosis

Postinflammatory pigment changes, both hypo and hyper, usually lack scale, may be anywhere on the body, and should have the same distribution as some original inflammation.

Pityriasis alba presents with hypopigmented patches, typically on the face, and has a more subtle “blotchy” appearance, without discrete oval patches. Pityriasis rosea may appear similar to tinea versicolor with erythema and scale, but it typically begins with a single, large herald patch, and scale is primarily at the outer border of the lesions.¹

Tinea corporis (“ringworm”), which is caused by a dermatophyte, is more distinctly ring shaped with a scaly, vesicular, papular, or pustular border and there is often a clear center that may not scale when scraped.^5,9 It is much more commonly localized, except in immunosuppressed patients or if mistreated with topical corticosteroids. Vitiligo lesions are completely depigmented, rather than just hypopigmented, and lack scale.¹ Psoriasis scale is thicker and is visible without any provocation.  

Treatment

First-line treatments for tinea versicolor include ketoconazole shampoo, selenium sulfide lotion or shampoo, and zinc pyrithione shampoo, which are left on for 5-10 minutes before rinsing.^1,20 Any of these treatments is a fine first choice, as all are effective, and there are no robust data establishing the superiority of any single treatment.20 The typical treatment duration is 1-4 weeks.¹ Longer treatment durations yield better cure rates.20 Ketoconazole and selenium sulfide also are available in foam formulations.11 Shampoo and foam formulations have the benefit of easily covering a large affected area.

Alternatively, terbinafine cream can be applied twice daily for a week or ketoconazole cream can be applied twice daily for 1-4 weeks.^1,21 It is advisable to treat the whole trunk, neck, arms, and legs down to the knees, even if only a small area is involved.^14,22 Antifungal treatments are well tolerated, with skin irritation and contact allergy being the most common adverse effects.1 Selenium sulfide has a strong odor.1

Hypopigmentation and hyperpigmentation can persist for months after the active infection has resolved and do not necessarily indicate a treatment failure.^2,20 However, because Malassezia is a part of the normal skin flora, recurrence is common, occurring in 60%-80% of patients within 2 years.¹⁴ Recurrence or persistence of an active infection can be proven by a positive KOH scrape test. If a first treatment fails, a different first-line topical medication should be tried.1 Referral to a dermatologist is recommended if the eruption is unresponsive to two treatments.1

Oral antifungals such as itraconazole, fluconazole, and pramiconazole are effective for tinea versicolor, but have more adverse effects than topicals and interact with other medications because of their inhibition of the cytochrome P450 system, so they are used only for refractory or widespread disease.^1,11 In 2013, the Food and Drug Administration issued a black box warning against oral ketoconazole due its ability to cause life-threatening hepatotoxicity and adrenal insufficiency^1,23,24; it should not be used to treat tinea versicolor. Topical ketoconazole is safe and remains a first-line treatment for tinea versicolor, as discussed above.24 Oral terbinafine is not effective for tinea versicolor despite its efficacy as a topical treatment.¹¹

Patients with recurrent tinea versicolor can try preventive therapy with ketoconazole shampoo, zinc pyrithione shampoo, or selenium sulfide lotion or shampoo one to four times per month.1 Oral antifungals also are effective for prevention of recurrence, but should be used only if the condition is refractory to topical prophylaxis.^20,25 It is important to remember that hypopigmentation and hyperpigmentation may persist for months after resolution of active infection; absence of hyphae on skin scraping prepared with KOH confirms absence of active disease.^15,16 

References

1. BMJ. 2015;350:h1394. doi:10.1136/bmj.h1394.
2. Lancet. 2004 Sep 25-Oct 1;364(9440):1173-82.
3. Pediatr Dermatol. 1991;8(1):9-12.
4. J Eur Acad Dermatol Venereol. 2002;16(1):19-33.
5. Arch Dermatol. 2009;145(9):1078.
6. Vitiligo and other disorders of pigmentation, in: “Dermatology,” Vol 1. 3rd ed. (Philadelphia: Elsevier Saunders, 2012, pp.1041-2.)
7. Am J Clin Dermatol. 2000 Mar-Apr;1(2):75-80.
8. Mycoses. 1995;38(5-6):227-8.
9. “Skin Disorders Due to Fungi,” in: Hurwitz Clinical Pediatric Dermatology 4th ed. (Philadelphia: Saunders, 2011, pp. 396-403).
10. Infect Control Hosp Epidemiol. 2002 Apr;23(4):212-6.
11. Expert Opin Pharmacother. 2014 Aug;15(12):1707-13.
12. Clin Microbiol Rev. 2002 Jan;15(1):21-57.
13. Clin Dermatol. 2010 Mar 4;28(2):185-9.
14. J Am Acad Dermatol. 1994 Sep;31(3 Pt 2):S18-20.
15. Int J Dermatol. 2014 Feb;53(2):137-41
16. Mycopathologia. 2006 Dec;162(6):373-6.
17. J Invest Dermatol. 1978 Sep;71(3):205-8.
18. Int J Dermatol. 1992 Apr;31(4):253-6.
19. Pediatr Dermatol. 2000 Jan-Feb;17(1):68-9.
20. Arch Dermatol. 2010 Oct;146(10):1132-40.
21. Dermatology (Basel). 1997;194(1):22-4. doi:10.1159/000246179.
22. Red Book Plus: 2009 Report of the Committee on Infectious Disease.
23. http://www.fda.gov/Drugs/DrugSafety/ucm362415.htm    
24. J Cutan Med Surg. 2015 Jul-Aug;19(4):352-7.
25. Arch Dermatol. 2002 Jan;138(1):69-73.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego and professor of dermatology and pediatrics at the University of California, San Diego. Ms. Haddock is a medical student at the University of California, San Diego, and a research associate at the hospital. Dr. Eichenfield and Ms. Haddock said they have no relevant financial disclosures.

Email to [email protected].

Tinea versicolor

Tinea versicolor – also called pityriasis versicolor – is a benign superficial fungal skin infection caused by Malassezia. It presents as well-demarcated, oval, finely scaling macules, patches, or thin plaques, which can be hypopigmented, hyperpigmented, or erythematous.^1,2,3 . The name, tinea versicolor, highlights the variability in the color of lesions.⁴

Scale may be minimal, but becomes more noticeable when lesions are scraped, which is called the “evoked scale sign.”⁵ The lesions may be asymptomatic or slightly pruritic.¹ Lesions range in size from several millimeters to several centimeters and may coalesce.6 They are most commonly found on the chest, back, upper arms, and neck,^2,7 but in children the face may be affected.^1,3,8 Hypopigmented lesions may be most noticeable during the summer when the surrounding uninvolved skin darkens with sun exposure.9 Tinea versicolor is not contagious, but pigmentary changes may cause cosmetic concerns, and the condition may persist for years if not treated.^2,4

Malassezia is a dimorphic fungus that is part of the normal skin flora in its yeast form, but if Malassezia converts to its hyphal form, it is able penetrate the stratum corneum and cause the tinea versicolor rash.^1,10 The reason for the conversion from yeast to hyphal form is not fully understood.¹¹Malassezia is lipophilic, so it thrives when sebum production is high, which is why tinea versicolor most commonly develops in adolescence or young adulthood, although it may be seen in younger children and older adults.¹² Genetic predisposition, warm and humid environments, oily skin, use of oily creams, use of corticosteroids, hyperhidrosis, physical activity, malnutrition, immunosuppression, and exposure to sunlight increase susceptibility.^1,13,14

Tinea versicolor is most commonly caused by Malassezia globosa and Malassezia furfur.^13,15,16 Hypopigmentation may be caused by Malassezia’s production of azelaic acid, which inhibits the dopa-tyrosinase reaction that is part of melanin synthesis.^15,17,18 Hyperpigmentation may result from inflammation.^15,18 The evoked scale sign results from the production of keratinase, which disrupts the stratum corneum.⁵

Tinea versicolor often can be diagnosed by its characteristic clinical appearance and may fluoresce golden under a Wood’s ultraviolet lamp.¹⁹ Diagnosis can be confirmed by microscopic examination of skin scrapings treated with potassium hydroxide (KOH), which will have a “spaghetti and meatball” appearance, with the hyphae resembling spaghetti and spores resembling meatballs.¹ For young children, removing scale with transparent tape can be a good alternative to scraping skin with a blade.^2,19

Differential diagnosis

Postinflammatory pigment changes, both hypo and hyper, usually lack scale, may be anywhere on the body, and should have the same distribution as some original inflammation.

Pityriasis alba presents with hypopigmented patches, typically on the face, and has a more subtle “blotchy” appearance, without discrete oval patches. Pityriasis rosea may appear similar to tinea versicolor with erythema and scale, but it typically begins with a single, large herald patch, and scale is primarily at the outer border of the lesions.¹

Tinea corporis (“ringworm”), which is caused by a dermatophyte, is more distinctly ring shaped with a scaly, vesicular, papular, or pustular border and there is often a clear center that may not scale when scraped.^5,9 It is much more commonly localized, except in immunosuppressed patients or if mistreated with topical corticosteroids. Vitiligo lesions are completely depigmented, rather than just hypopigmented, and lack scale.¹ Psoriasis scale is thicker and is visible without any provocation.  

Treatment

First-line treatments for tinea versicolor include ketoconazole shampoo, selenium sulfide lotion or shampoo, and zinc pyrithione shampoo, which are left on for 5-10 minutes before rinsing.^1,20 Any of these treatments is a fine first choice, as all are effective, and there are no robust data establishing the superiority of any single treatment.20 The typical treatment duration is 1-4 weeks.¹ Longer treatment durations yield better cure rates.20 Ketoconazole and selenium sulfide also are available in foam formulations.11 Shampoo and foam formulations have the benefit of easily covering a large affected area.

Alternatively, terbinafine cream can be applied twice daily for a week or ketoconazole cream can be applied twice daily for 1-4 weeks.^1,21 It is advisable to treat the whole trunk, neck, arms, and legs down to the knees, even if only a small area is involved.^14,22 Antifungal treatments are well tolerated, with skin irritation and contact allergy being the most common adverse effects.1 Selenium sulfide has a strong odor.1

Hypopigmentation and hyperpigmentation can persist for months after the active infection has resolved and do not necessarily indicate a treatment failure.^2,20 However, because Malassezia is a part of the normal skin flora, recurrence is common, occurring in 60%-80% of patients within 2 years.¹⁴ Recurrence or persistence of an active infection can be proven by a positive KOH scrape test. If a first treatment fails, a different first-line topical medication should be tried.1 Referral to a dermatologist is recommended if the eruption is unresponsive to two treatments.1

Oral antifungals such as itraconazole, fluconazole, and pramiconazole are effective for tinea versicolor, but have more adverse effects than topicals and interact with other medications because of their inhibition of the cytochrome P450 system, so they are used only for refractory or widespread disease.^1,11 In 2013, the Food and Drug Administration issued a black box warning against oral ketoconazole due its ability to cause life-threatening hepatotoxicity and adrenal insufficiency^1,23,24; it should not be used to treat tinea versicolor. Topical ketoconazole is safe and remains a first-line treatment for tinea versicolor, as discussed above.24 Oral terbinafine is not effective for tinea versicolor despite its efficacy as a topical treatment.¹¹

Patients with recurrent tinea versicolor can try preventive therapy with ketoconazole shampoo, zinc pyrithione shampoo, or selenium sulfide lotion or shampoo one to four times per month.1 Oral antifungals also are effective for prevention of recurrence, but should be used only if the condition is refractory to topical prophylaxis.^20,25 It is important to remember that hypopigmentation and hyperpigmentation may persist for months after resolution of active infection; absence of hyphae on skin scraping prepared with KOH confirms absence of active disease.^15,16 

References

1. BMJ. 2015;350:h1394. doi:10.1136/bmj.h1394.
2. Lancet. 2004 Sep 25-Oct 1;364(9440):1173-82.
3. Pediatr Dermatol. 1991;8(1):9-12.
4. J Eur Acad Dermatol Venereol. 2002;16(1):19-33.
5. Arch Dermatol. 2009;145(9):1078.
6. Vitiligo and other disorders of pigmentation, in: “Dermatology,” Vol 1. 3rd ed. (Philadelphia: Elsevier Saunders, 2012, pp.1041-2.)
7. Am J Clin Dermatol. 2000 Mar-Apr;1(2):75-80.
8. Mycoses. 1995;38(5-6):227-8.
9. “Skin Disorders Due to Fungi,” in: Hurwitz Clinical Pediatric Dermatology 4th ed. (Philadelphia: Saunders, 2011, pp. 396-403).
10. Infect Control Hosp Epidemiol. 2002 Apr;23(4):212-6.
11. Expert Opin Pharmacother. 2014 Aug;15(12):1707-13.
12. Clin Microbiol Rev. 2002 Jan;15(1):21-57.
13. Clin Dermatol. 2010 Mar 4;28(2):185-9.
14. J Am Acad Dermatol. 1994 Sep;31(3 Pt 2):S18-20.
15. Int J Dermatol. 2014 Feb;53(2):137-41
16. Mycopathologia. 2006 Dec;162(6):373-6.
17. J Invest Dermatol. 1978 Sep;71(3):205-8.
18. Int J Dermatol. 1992 Apr;31(4):253-6.
19. Pediatr Dermatol. 2000 Jan-Feb;17(1):68-9.
20. Arch Dermatol. 2010 Oct;146(10):1132-40.
21. Dermatology (Basel). 1997;194(1):22-4. doi:10.1159/000246179.
22. Red Book Plus: 2009 Report of the Committee on Infectious Disease.
23. http://www.fda.gov/Drugs/DrugSafety/ucm362415.htm    
24. J Cutan Med Surg. 2015 Jul-Aug;19(4):352-7.
25. Arch Dermatol. 2002 Jan;138(1):69-73.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego and professor of dermatology and pediatrics at the University of California, San Diego. Ms. Haddock is a medical student at the University of California, San Diego, and a research associate at the hospital. Dr. Eichenfield and Ms. Haddock said they have no relevant financial disclosures.

Email to [email protected].

Tinea versicolor

Tinea versicolor – also called pityriasis versicolor – is a benign superficial fungal skin infection caused by Malassezia. It presents as well-demarcated, oval, finely scaling macules, patches, or thin plaques, which can be hypopigmented, hyperpigmented, or erythematous.^1,2,3 . The name, tinea versicolor, highlights the variability in the color of lesions.⁴

Scale may be minimal, but becomes more noticeable when lesions are scraped, which is called the “evoked scale sign.”⁵ The lesions may be asymptomatic or slightly pruritic.¹ Lesions range in size from several millimeters to several centimeters and may coalesce.6 They are most commonly found on the chest, back, upper arms, and neck,^2,7 but in children the face may be affected.^1,3,8 Hypopigmented lesions may be most noticeable during the summer when the surrounding uninvolved skin darkens with sun exposure.9 Tinea versicolor is not contagious, but pigmentary changes may cause cosmetic concerns, and the condition may persist for years if not treated.^2,4

Malassezia is a dimorphic fungus that is part of the normal skin flora in its yeast form, but if Malassezia converts to its hyphal form, it is able penetrate the stratum corneum and cause the tinea versicolor rash.^1,10 The reason for the conversion from yeast to hyphal form is not fully understood.¹¹Malassezia is lipophilic, so it thrives when sebum production is high, which is why tinea versicolor most commonly develops in adolescence or young adulthood, although it may be seen in younger children and older adults.¹² Genetic predisposition, warm and humid environments, oily skin, use of oily creams, use of corticosteroids, hyperhidrosis, physical activity, malnutrition, immunosuppression, and exposure to sunlight increase susceptibility.^1,13,14

Tinea versicolor is most commonly caused by Malassezia globosa and Malassezia furfur.^13,15,16 Hypopigmentation may be caused by Malassezia’s production of azelaic acid, which inhibits the dopa-tyrosinase reaction that is part of melanin synthesis.^15,17,18 Hyperpigmentation may result from inflammation.^15,18 The evoked scale sign results from the production of keratinase, which disrupts the stratum corneum.⁵

Tinea versicolor often can be diagnosed by its characteristic clinical appearance and may fluoresce golden under a Wood’s ultraviolet lamp.¹⁹ Diagnosis can be confirmed by microscopic examination of skin scrapings treated with potassium hydroxide (KOH), which will have a “spaghetti and meatball” appearance, with the hyphae resembling spaghetti and spores resembling meatballs.¹ For young children, removing scale with transparent tape can be a good alternative to scraping skin with a blade.^2,19

Differential diagnosis

Postinflammatory pigment changes, both hypo and hyper, usually lack scale, may be anywhere on the body, and should have the same distribution as some original inflammation.

Pityriasis alba presents with hypopigmented patches, typically on the face, and has a more subtle “blotchy” appearance, without discrete oval patches. Pityriasis rosea may appear similar to tinea versicolor with erythema and scale, but it typically begins with a single, large herald patch, and scale is primarily at the outer border of the lesions.¹

Tinea corporis (“ringworm”), which is caused by a dermatophyte, is more distinctly ring shaped with a scaly, vesicular, papular, or pustular border and there is often a clear center that may not scale when scraped.^5,9 It is much more commonly localized, except in immunosuppressed patients or if mistreated with topical corticosteroids. Vitiligo lesions are completely depigmented, rather than just hypopigmented, and lack scale.¹ Psoriasis scale is thicker and is visible without any provocation.  

Treatment

First-line treatments for tinea versicolor include ketoconazole shampoo, selenium sulfide lotion or shampoo, and zinc pyrithione shampoo, which are left on for 5-10 minutes before rinsing.^1,20 Any of these treatments is a fine first choice, as all are effective, and there are no robust data establishing the superiority of any single treatment.20 The typical treatment duration is 1-4 weeks.¹ Longer treatment durations yield better cure rates.20 Ketoconazole and selenium sulfide also are available in foam formulations.11 Shampoo and foam formulations have the benefit of easily covering a large affected area.

Alternatively, terbinafine cream can be applied twice daily for a week or ketoconazole cream can be applied twice daily for 1-4 weeks.^1,21 It is advisable to treat the whole trunk, neck, arms, and legs down to the knees, even if only a small area is involved.^14,22 Antifungal treatments are well tolerated, with skin irritation and contact allergy being the most common adverse effects.1 Selenium sulfide has a strong odor.1

Hypopigmentation and hyperpigmentation can persist for months after the active infection has resolved and do not necessarily indicate a treatment failure.^2,20 However, because Malassezia is a part of the normal skin flora, recurrence is common, occurring in 60%-80% of patients within 2 years.¹⁴ Recurrence or persistence of an active infection can be proven by a positive KOH scrape test. If a first treatment fails, a different first-line topical medication should be tried.1 Referral to a dermatologist is recommended if the eruption is unresponsive to two treatments.1

Oral antifungals such as itraconazole, fluconazole, and pramiconazole are effective for tinea versicolor, but have more adverse effects than topicals and interact with other medications because of their inhibition of the cytochrome P450 system, so they are used only for refractory or widespread disease.^1,11 In 2013, the Food and Drug Administration issued a black box warning against oral ketoconazole due its ability to cause life-threatening hepatotoxicity and adrenal insufficiency^1,23,24; it should not be used to treat tinea versicolor. Topical ketoconazole is safe and remains a first-line treatment for tinea versicolor, as discussed above.24 Oral terbinafine is not effective for tinea versicolor despite its efficacy as a topical treatment.¹¹

Patients with recurrent tinea versicolor can try preventive therapy with ketoconazole shampoo, zinc pyrithione shampoo, or selenium sulfide lotion or shampoo one to four times per month.1 Oral antifungals also are effective for prevention of recurrence, but should be used only if the condition is refractory to topical prophylaxis.^20,25 It is important to remember that hypopigmentation and hyperpigmentation may persist for months after resolution of active infection; absence of hyphae on skin scraping prepared with KOH confirms absence of active disease.^15,16 

References

1. BMJ. 2015;350:h1394. doi:10.1136/bmj.h1394.
2. Lancet. 2004 Sep 25-Oct 1;364(9440):1173-82.
3. Pediatr Dermatol. 1991;8(1):9-12.
4. J Eur Acad Dermatol Venereol. 2002;16(1):19-33.
5. Arch Dermatol. 2009;145(9):1078.
6. Vitiligo and other disorders of pigmentation, in: “Dermatology,” Vol 1. 3rd ed. (Philadelphia: Elsevier Saunders, 2012, pp.1041-2.)
7. Am J Clin Dermatol. 2000 Mar-Apr;1(2):75-80.
8. Mycoses. 1995;38(5-6):227-8.
9. “Skin Disorders Due to Fungi,” in: Hurwitz Clinical Pediatric Dermatology 4th ed. (Philadelphia: Saunders, 2011, pp. 396-403).
10. Infect Control Hosp Epidemiol. 2002 Apr;23(4):212-6.
11. Expert Opin Pharmacother. 2014 Aug;15(12):1707-13.
12. Clin Microbiol Rev. 2002 Jan;15(1):21-57.
13. Clin Dermatol. 2010 Mar 4;28(2):185-9.
14. J Am Acad Dermatol. 1994 Sep;31(3 Pt 2):S18-20.
15. Int J Dermatol. 2014 Feb;53(2):137-41
16. Mycopathologia. 2006 Dec;162(6):373-6.
17. J Invest Dermatol. 1978 Sep;71(3):205-8.
18. Int J Dermatol. 1992 Apr;31(4):253-6.
19. Pediatr Dermatol. 2000 Jan-Feb;17(1):68-9.
20. Arch Dermatol. 2010 Oct;146(10):1132-40.
21. Dermatology (Basel). 1997;194(1):22-4. doi:10.1159/000246179.
22. Red Book Plus: 2009 Report of the Committee on Infectious Disease.
23. http://www.fda.gov/Drugs/DrugSafety/ucm362415.htm    
24. J Cutan Med Surg. 2015 Jul-Aug;19(4):352-7.
25. Arch Dermatol. 2002 Jan;138(1):69-73.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego and professor of dermatology and pediatrics at the University of California, San Diego. Ms. Haddock is a medical student at the University of California, San Diego, and a research associate at the hospital. Dr. Eichenfield and Ms. Haddock said they have no relevant financial disclosures.

Email to [email protected].

Diagnosis: Staphylococcal scalded skin syndrome (SSSS)

Staphylococcal scalded skin syndrome (SSSS), also known as Ritter’s disease and pemphigus neonatorum, is a blistering skin disease seen most commonly in neonates and young children, but it can be seen in older children and rarely in adults¹. The severity of SSSS can range from mild localized bullae to severe generalized erythroderma and exfoliation. 

The most common early symptoms in neonates and children are fever, malaise, irritability, and skin tenderness followed by erythema at the site of infection, usually in the perioral, periorbital, or umbilical areas¹. The erythema becomes well demarcated, and more erythematous patches develop and spread over the body and subsequently coalesce. One to two days later, fragile bullae form over the erythematous skin, most commonly in intertriginous areas; these bullae rupture easily, leaving behind denuded, erythematous skin, giving the scalded appearance for which the disease is named. 

The causative factor is an exfoliating (epidermolytic) toxin (ET) produced by phage II Staphylococcus aureus2. There are two types of ETs, ETA and ETB. In western countries, the vast majority of toxin-producing strains of S. aureus produce ETA. Both ETA and ETB target and destroy desmoglein-1, a molecule found in desmosomes that plays an important role in cell-cell adhesion in the stratum granulosum of the epidermis². This compromise in the structural integrity of the superficial epidermis is responsible for the fragile nature of the bullae seen in SSSS and the positive Nikolsky sign.

Differential diagnosis

The differential diagnosis includes toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and staphylococcal toxic-shock syndrome (STSS)³. 

TEN is a severe condition, most commonly caused by adverse drug reactions. Unlike in TEN, SSSS patients the lack mucosal involvement and have more superficial epidermal peeling⁴. 

DRESS is also a medication-induced reaction, commonly associated with anticonvulsants and sulfonamides. Only severe cases of DRESS can present similarly to SSSS with exfoliation and erythroderma, but there is often mucosal involvement and signs of visceral organ involvement, most commonly the liver⁵. 

The additional findings inSTSS that help distinguish it from SSSS include petechiae and preferential desquamation of the palms and soles⁶. 

SSSS can usually be diagnosed clinically, but biopsies are important in differentiating difficult cases. Sampling the crusted areas as well as the nasal, periumbilical, and perianal sites for culture and sensitivities is recommended prior to starting antibiotic therapy.

Treatment

For neonates and children with severe disease, inpatient treatment in an intensive care or burn unit setting is sometimes required. SSSS can be caused by both methicillin-sensitive and -resistant strains of S. aureus, so antibiotic treatment must be tailored to the sensitivity. 

In either case, beginning broad-spectrum antibiotic treatment early is essential. For methicillin-sensitive strains, penicillinase-resistant penicillins like flucloxacillin, nafcillin, or oxacillin are the drugs of choice^3,7.

In known MRSA infections or in areas with a high prevalence of resistance and suspected MRSA, clindamycin or vancomycin should be used^3,8. Supportive care in an inpatient setting also is important, especially in younger or sick children because they are more susceptible to sepsis and pneumonia and are at risk for complications because of problems with temperature, fluid, and electrolyte regulation while their skin barrier function is compromised⁷.

References

1. Arch Dis Child. 1998;78(1):85-8. 
2. N Engl J Med. 2006;355(17):1800-10. 
3. J Eur Acad Dermatol Venereol. 2014;28(11):1418-23.  
4. JAAD. 2013;69(2):173.e1-173.e13. 
5. JAAD. 2013;68(5):693.e1-693.e14. 
6. Clin Infect Dis. 2006;42(2):181-5. 
7. Am J Clin Dermatol. 2003;4(3):165-75. 
8. Pediatr Dermatol. 2014;31(3):305-08.

Dr. Matiz is assistant professor of dermatology at Rady Children's Hospital San Diego-University of California San Diego and Mr. Ginsberg is a research associate at the hospital. Dr. Matiz and Mr. Ginsberg said they have no relevant financial disclosures. 

Diagnosis: Staphylococcal scalded skin syndrome (SSSS)

Staphylococcal scalded skin syndrome (SSSS), also known as Ritter’s disease and pemphigus neonatorum, is a blistering skin disease seen most commonly in neonates and young children, but it can be seen in older children and rarely in adults¹. The severity of SSSS can range from mild localized bullae to severe generalized erythroderma and exfoliation. 

The most common early symptoms in neonates and children are fever, malaise, irritability, and skin tenderness followed by erythema at the site of infection, usually in the perioral, periorbital, or umbilical areas¹. The erythema becomes well demarcated, and more erythematous patches develop and spread over the body and subsequently coalesce. One to two days later, fragile bullae form over the erythematous skin, most commonly in intertriginous areas; these bullae rupture easily, leaving behind denuded, erythematous skin, giving the scalded appearance for which the disease is named. 

The causative factor is an exfoliating (epidermolytic) toxin (ET) produced by phage II Staphylococcus aureus2. There are two types of ETs, ETA and ETB. In western countries, the vast majority of toxin-producing strains of S. aureus produce ETA. Both ETA and ETB target and destroy desmoglein-1, a molecule found in desmosomes that plays an important role in cell-cell adhesion in the stratum granulosum of the epidermis². This compromise in the structural integrity of the superficial epidermis is responsible for the fragile nature of the bullae seen in SSSS and the positive Nikolsky sign.

Differential diagnosis

The differential diagnosis includes toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and staphylococcal toxic-shock syndrome (STSS)³. 

TEN is a severe condition, most commonly caused by adverse drug reactions. Unlike in TEN, SSSS patients the lack mucosal involvement and have more superficial epidermal peeling⁴. 

DRESS is also a medication-induced reaction, commonly associated with anticonvulsants and sulfonamides. Only severe cases of DRESS can present similarly to SSSS with exfoliation and erythroderma, but there is often mucosal involvement and signs of visceral organ involvement, most commonly the liver⁵. 

The additional findings inSTSS that help distinguish it from SSSS include petechiae and preferential desquamation of the palms and soles⁶. 

SSSS can usually be diagnosed clinically, but biopsies are important in differentiating difficult cases. Sampling the crusted areas as well as the nasal, periumbilical, and perianal sites for culture and sensitivities is recommended prior to starting antibiotic therapy.

Treatment

For neonates and children with severe disease, inpatient treatment in an intensive care or burn unit setting is sometimes required. SSSS can be caused by both methicillin-sensitive and -resistant strains of S. aureus, so antibiotic treatment must be tailored to the sensitivity. 

In either case, beginning broad-spectrum antibiotic treatment early is essential. For methicillin-sensitive strains, penicillinase-resistant penicillins like flucloxacillin, nafcillin, or oxacillin are the drugs of choice^3,7.

In known MRSA infections or in areas with a high prevalence of resistance and suspected MRSA, clindamycin or vancomycin should be used^3,8. Supportive care in an inpatient setting also is important, especially in younger or sick children because they are more susceptible to sepsis and pneumonia and are at risk for complications because of problems with temperature, fluid, and electrolyte regulation while their skin barrier function is compromised⁷.

References

1. Arch Dis Child. 1998;78(1):85-8. 
2. N Engl J Med. 2006;355(17):1800-10. 
3. J Eur Acad Dermatol Venereol. 2014;28(11):1418-23.  
4. JAAD. 2013;69(2):173.e1-173.e13. 
5. JAAD. 2013;68(5):693.e1-693.e14. 
6. Clin Infect Dis. 2006;42(2):181-5. 
7. Am J Clin Dermatol. 2003;4(3):165-75. 
8. Pediatr Dermatol. 2014;31(3):305-08.

Dr. Matiz is assistant professor of dermatology at Rady Children's Hospital San Diego-University of California San Diego and Mr. Ginsberg is a research associate at the hospital. Dr. Matiz and Mr. Ginsberg said they have no relevant financial disclosures. 

Diagnosis: Staphylococcal scalded skin syndrome (SSSS)

Staphylococcal scalded skin syndrome (SSSS), also known as Ritter’s disease and pemphigus neonatorum, is a blistering skin disease seen most commonly in neonates and young children, but it can be seen in older children and rarely in adults¹. The severity of SSSS can range from mild localized bullae to severe generalized erythroderma and exfoliation. 

The most common early symptoms in neonates and children are fever, malaise, irritability, and skin tenderness followed by erythema at the site of infection, usually in the perioral, periorbital, or umbilical areas¹. The erythema becomes well demarcated, and more erythematous patches develop and spread over the body and subsequently coalesce. One to two days later, fragile bullae form over the erythematous skin, most commonly in intertriginous areas; these bullae rupture easily, leaving behind denuded, erythematous skin, giving the scalded appearance for which the disease is named. 

The causative factor is an exfoliating (epidermolytic) toxin (ET) produced by phage II Staphylococcus aureus2. There are two types of ETs, ETA and ETB. In western countries, the vast majority of toxin-producing strains of S. aureus produce ETA. Both ETA and ETB target and destroy desmoglein-1, a molecule found in desmosomes that plays an important role in cell-cell adhesion in the stratum granulosum of the epidermis². This compromise in the structural integrity of the superficial epidermis is responsible for the fragile nature of the bullae seen in SSSS and the positive Nikolsky sign.

Differential diagnosis

The differential diagnosis includes toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and staphylococcal toxic-shock syndrome (STSS)³. 

TEN is a severe condition, most commonly caused by adverse drug reactions. Unlike in TEN, SSSS patients the lack mucosal involvement and have more superficial epidermal peeling⁴. 

DRESS is also a medication-induced reaction, commonly associated with anticonvulsants and sulfonamides. Only severe cases of DRESS can present similarly to SSSS with exfoliation and erythroderma, but there is often mucosal involvement and signs of visceral organ involvement, most commonly the liver⁵. 

The additional findings inSTSS that help distinguish it from SSSS include petechiae and preferential desquamation of the palms and soles⁶. 

SSSS can usually be diagnosed clinically, but biopsies are important in differentiating difficult cases. Sampling the crusted areas as well as the nasal, periumbilical, and perianal sites for culture and sensitivities is recommended prior to starting antibiotic therapy.

Treatment

For neonates and children with severe disease, inpatient treatment in an intensive care or burn unit setting is sometimes required. SSSS can be caused by both methicillin-sensitive and -resistant strains of S. aureus, so antibiotic treatment must be tailored to the sensitivity. 

In either case, beginning broad-spectrum antibiotic treatment early is essential. For methicillin-sensitive strains, penicillinase-resistant penicillins like flucloxacillin, nafcillin, or oxacillin are the drugs of choice^3,7.

In known MRSA infections or in areas with a high prevalence of resistance and suspected MRSA, clindamycin or vancomycin should be used^3,8. Supportive care in an inpatient setting also is important, especially in younger or sick children because they are more susceptible to sepsis and pneumonia and are at risk for complications because of problems with temperature, fluid, and electrolyte regulation while their skin barrier function is compromised⁷.

References

1. Arch Dis Child. 1998;78(1):85-8. 
2. N Engl J Med. 2006;355(17):1800-10. 
3. J Eur Acad Dermatol Venereol. 2014;28(11):1418-23.  
4. JAAD. 2013;69(2):173.e1-173.e13. 
5. JAAD. 2013;68(5):693.e1-693.e14. 
6. Clin Infect Dis. 2006;42(2):181-5. 
7. Am J Clin Dermatol. 2003;4(3):165-75. 
8. Pediatr Dermatol. 2014;31(3):305-08.

Dr. Matiz is assistant professor of dermatology at Rady Children's Hospital San Diego-University of California San Diego and Mr. Ginsberg is a research associate at the hospital. Dr. Matiz and Mr. Ginsberg said they have no relevant financial disclosures.