Allison Han

 

Streptococcal intertrigo is an inflammatory, superficial eruption of intertriginous skin caused by group A beta-hemolytic streptococci. Frequently misdiagnosed, streptococcal intertrigo more commonly affects infants and toddlers but is rarely reported, especially compared with other Streptococcus pyogenes infections, including impetigo, erysipelas, and cellulitis.¹

Intertrigo, meaning “between” (inter) and “to rub” (terere) in Latin, describes any skin disorder involving two opposing skin surfaces that touch or rub to cause friction.² The continuous chaffing, coupled with moisture trapped within the skin folds, leads to irritation and maceration, which provides an ideal environment for pathogens to thrive. Thus, frictional dermatitides that arise may become secondarily infected with one or more microorganisms, such as Candida albicans, Staphylococcus aureus, Streptococcus pyogenes, and even organisms less commonly associated with cutaneous infection, such as Proteus mirabilis.³

Courtesy Dr. Lawrence F. Eichenfield

Intertrigo caused by Streptococcus pyogenes is classically characterized by fiery erythema and moist maceration. Homogeneous in appearance, lesions are discretely demarcated and notably lack satellite lesions, unlike in candidal intertrigo. Distinctly foul odor and worsening or persistence of rash despite antifungal treatment also are helpful features in distinguishing streptococcal intertrigo from candidal intertrigo.⁴ These characteristics are essential to consider because streptococcal intertrigo is most commonly initially misdiagnosed as candidal intertrigo, which is the most common type of intertrigo.⁵

Streptococcal intertrigo may affect any intertriginous area, but most commonly it affects the folds of the neck; this is likely because of the combination of the deep folds that develop in shorter, infantile necks and the moisture from drool and saliva that pools in the area.^5,6 In addition to these cervical folds, other intertriginous areas commonly are affected, including the inguinal, axillary, popliteal, posterior auricular, perianal, and genital folds.

Perianal streptococcal disease may present in a similar manner as streptococcal intertrigo, manifesting as well-demarcated, beefy red plaques in the skin folds around the anus and, in females, frequently perivaginally.⁷ Unlike streptococcal intertrigo, perianal streptococcal disease is often characterized by pain, pruritus, and fissuring of the involved area.⁸ It is associated with pharyngeal colonization of group A beta-hemolytic streptococci.⁷

Patients may be well appearing, or they may present with irritability and low-grade fever; only one case in the literature has described development of bacteremia secondary to cervical streptococcal intertrigo that had developed in a 12-month-old infant.¹

Diagnosis is straight forward and may be confirmed by a positive streptococcal rapid antigen test of swab specimens of one or more surfaces of affected skin or by culture from a skin swab yielding growth of the organism.^1,5 Skin biopsy is not necessary. If the index of suspicion for candida is high, a potassium hydroxide preparation and culture may be performed. Checking serum anti-DNase B antibodies, antistreptolysin O, and pharyngeal cultures is often unrevealing.⁹ A urinalysis may be performed to assess for poststreptococcal glomerulonephritis if the patient later develops facial or orbital edema, hypertension, hematuria, or lethargy.⁹

Treatment consists of systemic antistreptococcal therapy; oral amoxicillin and penicillin frequently have been used.⁹ Moisture in the area should be reduced with application of absorptive powders and physical barriers, such as zinc oxide, after gentle cleansing of the area.⁵

Of note, in patients with underlying atopic dermatitis, secondary infection with Streptococcus pyogenes may exacerbate atopic dermatitis, resulting in a flare of inflammation that persists even after appropriate therapy of the Streptococcus pyogenes. In these patients, it is reasonable and beneficial to treat with concomitant topical corticosteroids.⁹Streptococcus pyogenes infection also has been identified as a trigger for guttate psoriasis. Thus, if coin-shaped, erythematous lesions with scale are appreciated, a diagnosis of guttate psoriasis should be considered and the presence of a preceding streptococcal infection inquired about.⁵ Although islands of erythema and scale may resemble satellite lesions, it is important to include guttate psoriasis in the differential and not confound these entities because they lead to favoring of differing diagnoses and treatment options.⁴

Other diagnoses to consider when evaluating dermatitides affecting skin folds include: other infectious causes, which may be ruled out by fungal or bacterial culture; inverse psoriasis, which will frequently demonstrate scale; atopic dermatitis, which will be pruritic with history of atopy; irritant or contact dermatitis, which will often have correlating clinical history; seborrheic dermatitis, which will often involve greasiness and scale; and less commonly, acrodermatitis enteropathica, which will be accompanied by diarrhea and hair loss.^2,9 Scabies also may be on the differential if the patient endorses severe pruritus with close contacts with similar symptoms.
 

Ms. Han is a medical student at the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and a professor of dermatology and pediatrics at the university. They had no conflicts of interest or disclosures to report.


References

1. Pediatr Dermatol. 2014 Mar-Apr;31(2):e71-2.

2. Clin Dermatol. 2011 Mar-Apr;29(2):173-9.

3. Pediatrics. 2003 Dec;112(6 pt 1):1427-9.

4. BMJ Case Rep. 2018 Mar 20. doi: 10.1136/bcr-2018-224179.

5. Pediatr Infect Dis J. 2012 Aug;31(8):872-3.

6. J Pediatr. 2015 May;166(5):1318.

7. J Pediatr. 2015 Sep;167(3):687-93.e1-2.

8. Pediatrics in Review. 1991;12(8):248-55.

9. J Pediatr. 2017 May;184:230-1.e1.

 

Streptococcal intertrigo is an inflammatory, superficial eruption of intertriginous skin caused by group A beta-hemolytic streptococci. Frequently misdiagnosed, streptococcal intertrigo more commonly affects infants and toddlers but is rarely reported, especially compared with other Streptococcus pyogenes infections, including impetigo, erysipelas, and cellulitis.¹

Intertrigo, meaning “between” (inter) and “to rub” (terere) in Latin, describes any skin disorder involving two opposing skin surfaces that touch or rub to cause friction.² The continuous chaffing, coupled with moisture trapped within the skin folds, leads to irritation and maceration, which provides an ideal environment for pathogens to thrive. Thus, frictional dermatitides that arise may become secondarily infected with one or more microorganisms, such as Candida albicans, Staphylococcus aureus, Streptococcus pyogenes, and even organisms less commonly associated with cutaneous infection, such as Proteus mirabilis.³

Courtesy Dr. Lawrence F. Eichenfield

Intertrigo caused by Streptococcus pyogenes is classically characterized by fiery erythema and moist maceration. Homogeneous in appearance, lesions are discretely demarcated and notably lack satellite lesions, unlike in candidal intertrigo. Distinctly foul odor and worsening or persistence of rash despite antifungal treatment also are helpful features in distinguishing streptococcal intertrigo from candidal intertrigo.⁴ These characteristics are essential to consider because streptococcal intertrigo is most commonly initially misdiagnosed as candidal intertrigo, which is the most common type of intertrigo.⁵

Streptococcal intertrigo may affect any intertriginous area, but most commonly it affects the folds of the neck; this is likely because of the combination of the deep folds that develop in shorter, infantile necks and the moisture from drool and saliva that pools in the area.^5,6 In addition to these cervical folds, other intertriginous areas commonly are affected, including the inguinal, axillary, popliteal, posterior auricular, perianal, and genital folds.

Perianal streptococcal disease may present in a similar manner as streptococcal intertrigo, manifesting as well-demarcated, beefy red plaques in the skin folds around the anus and, in females, frequently perivaginally.⁷ Unlike streptococcal intertrigo, perianal streptococcal disease is often characterized by pain, pruritus, and fissuring of the involved area.⁸ It is associated with pharyngeal colonization of group A beta-hemolytic streptococci.⁷

Patients may be well appearing, or they may present with irritability and low-grade fever; only one case in the literature has described development of bacteremia secondary to cervical streptococcal intertrigo that had developed in a 12-month-old infant.¹

Diagnosis is straight forward and may be confirmed by a positive streptococcal rapid antigen test of swab specimens of one or more surfaces of affected skin or by culture from a skin swab yielding growth of the organism.^1,5 Skin biopsy is not necessary. If the index of suspicion for candida is high, a potassium hydroxide preparation and culture may be performed. Checking serum anti-DNase B antibodies, antistreptolysin O, and pharyngeal cultures is often unrevealing.⁹ A urinalysis may be performed to assess for poststreptococcal glomerulonephritis if the patient later develops facial or orbital edema, hypertension, hematuria, or lethargy.⁹

Treatment consists of systemic antistreptococcal therapy; oral amoxicillin and penicillin frequently have been used.⁹ Moisture in the area should be reduced with application of absorptive powders and physical barriers, such as zinc oxide, after gentle cleansing of the area.⁵

Of note, in patients with underlying atopic dermatitis, secondary infection with Streptococcus pyogenes may exacerbate atopic dermatitis, resulting in a flare of inflammation that persists even after appropriate therapy of the Streptococcus pyogenes. In these patients, it is reasonable and beneficial to treat with concomitant topical corticosteroids.⁹Streptococcus pyogenes infection also has been identified as a trigger for guttate psoriasis. Thus, if coin-shaped, erythematous lesions with scale are appreciated, a diagnosis of guttate psoriasis should be considered and the presence of a preceding streptococcal infection inquired about.⁵ Although islands of erythema and scale may resemble satellite lesions, it is important to include guttate psoriasis in the differential and not confound these entities because they lead to favoring of differing diagnoses and treatment options.⁴

Other diagnoses to consider when evaluating dermatitides affecting skin folds include: other infectious causes, which may be ruled out by fungal or bacterial culture; inverse psoriasis, which will frequently demonstrate scale; atopic dermatitis, which will be pruritic with history of atopy; irritant or contact dermatitis, which will often have correlating clinical history; seborrheic dermatitis, which will often involve greasiness and scale; and less commonly, acrodermatitis enteropathica, which will be accompanied by diarrhea and hair loss.^2,9 Scabies also may be on the differential if the patient endorses severe pruritus with close contacts with similar symptoms.
 

Ms. Han is a medical student at the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and a professor of dermatology and pediatrics at the university. They had no conflicts of interest or disclosures to report.


References

1. Pediatr Dermatol. 2014 Mar-Apr;31(2):e71-2.

2. Clin Dermatol. 2011 Mar-Apr;29(2):173-9.

3. Pediatrics. 2003 Dec;112(6 pt 1):1427-9.

4. BMJ Case Rep. 2018 Mar 20. doi: 10.1136/bcr-2018-224179.

5. Pediatr Infect Dis J. 2012 Aug;31(8):872-3.

6. J Pediatr. 2015 May;166(5):1318.

7. J Pediatr. 2015 Sep;167(3):687-93.e1-2.

8. Pediatrics in Review. 1991;12(8):248-55.

9. J Pediatr. 2017 May;184:230-1.e1.

 

Streptococcal intertrigo is an inflammatory, superficial eruption of intertriginous skin caused by group A beta-hemolytic streptococci. Frequently misdiagnosed, streptococcal intertrigo more commonly affects infants and toddlers but is rarely reported, especially compared with other Streptococcus pyogenes infections, including impetigo, erysipelas, and cellulitis.¹

Intertrigo, meaning “between” (inter) and “to rub” (terere) in Latin, describes any skin disorder involving two opposing skin surfaces that touch or rub to cause friction.² The continuous chaffing, coupled with moisture trapped within the skin folds, leads to irritation and maceration, which provides an ideal environment for pathogens to thrive. Thus, frictional dermatitides that arise may become secondarily infected with one or more microorganisms, such as Candida albicans, Staphylococcus aureus, Streptococcus pyogenes, and even organisms less commonly associated with cutaneous infection, such as Proteus mirabilis.³

Courtesy Dr. Lawrence F. Eichenfield

Intertrigo caused by Streptococcus pyogenes is classically characterized by fiery erythema and moist maceration. Homogeneous in appearance, lesions are discretely demarcated and notably lack satellite lesions, unlike in candidal intertrigo. Distinctly foul odor and worsening or persistence of rash despite antifungal treatment also are helpful features in distinguishing streptococcal intertrigo from candidal intertrigo.⁴ These characteristics are essential to consider because streptococcal intertrigo is most commonly initially misdiagnosed as candidal intertrigo, which is the most common type of intertrigo.⁵

Streptococcal intertrigo may affect any intertriginous area, but most commonly it affects the folds of the neck; this is likely because of the combination of the deep folds that develop in shorter, infantile necks and the moisture from drool and saliva that pools in the area.^5,6 In addition to these cervical folds, other intertriginous areas commonly are affected, including the inguinal, axillary, popliteal, posterior auricular, perianal, and genital folds.

Perianal streptococcal disease may present in a similar manner as streptococcal intertrigo, manifesting as well-demarcated, beefy red plaques in the skin folds around the anus and, in females, frequently perivaginally.⁷ Unlike streptococcal intertrigo, perianal streptococcal disease is often characterized by pain, pruritus, and fissuring of the involved area.⁸ It is associated with pharyngeal colonization of group A beta-hemolytic streptococci.⁷

Patients may be well appearing, or they may present with irritability and low-grade fever; only one case in the literature has described development of bacteremia secondary to cervical streptococcal intertrigo that had developed in a 12-month-old infant.¹

Diagnosis is straight forward and may be confirmed by a positive streptococcal rapid antigen test of swab specimens of one or more surfaces of affected skin or by culture from a skin swab yielding growth of the organism.^1,5 Skin biopsy is not necessary. If the index of suspicion for candida is high, a potassium hydroxide preparation and culture may be performed. Checking serum anti-DNase B antibodies, antistreptolysin O, and pharyngeal cultures is often unrevealing.⁹ A urinalysis may be performed to assess for poststreptococcal glomerulonephritis if the patient later develops facial or orbital edema, hypertension, hematuria, or lethargy.⁹

Treatment consists of systemic antistreptococcal therapy; oral amoxicillin and penicillin frequently have been used.⁹ Moisture in the area should be reduced with application of absorptive powders and physical barriers, such as zinc oxide, after gentle cleansing of the area.⁵

Of note, in patients with underlying atopic dermatitis, secondary infection with Streptococcus pyogenes may exacerbate atopic dermatitis, resulting in a flare of inflammation that persists even after appropriate therapy of the Streptococcus pyogenes. In these patients, it is reasonable and beneficial to treat with concomitant topical corticosteroids.⁹Streptococcus pyogenes infection also has been identified as a trigger for guttate psoriasis. Thus, if coin-shaped, erythematous lesions with scale are appreciated, a diagnosis of guttate psoriasis should be considered and the presence of a preceding streptococcal infection inquired about.⁵ Although islands of erythema and scale may resemble satellite lesions, it is important to include guttate psoriasis in the differential and not confound these entities because they lead to favoring of differing diagnoses and treatment options.⁴

Other diagnoses to consider when evaluating dermatitides affecting skin folds include: other infectious causes, which may be ruled out by fungal or bacterial culture; inverse psoriasis, which will frequently demonstrate scale; atopic dermatitis, which will be pruritic with history of atopy; irritant or contact dermatitis, which will often have correlating clinical history; seborrheic dermatitis, which will often involve greasiness and scale; and less commonly, acrodermatitis enteropathica, which will be accompanied by diarrhea and hair loss.^2,9 Scabies also may be on the differential if the patient endorses severe pruritus with close contacts with similar symptoms.
 

Ms. Han is a medical student at the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and a professor of dermatology and pediatrics at the university. They had no conflicts of interest or disclosures to report.


References

1. Pediatr Dermatol. 2014 Mar-Apr;31(2):e71-2.

2. Clin Dermatol. 2011 Mar-Apr;29(2):173-9.

3. Pediatrics. 2003 Dec;112(6 pt 1):1427-9.

4. BMJ Case Rep. 2018 Mar 20. doi: 10.1136/bcr-2018-224179.

5. Pediatr Infect Dis J. 2012 Aug;31(8):872-3.

6. J Pediatr. 2015 May;166(5):1318.

7. J Pediatr. 2015 Sep;167(3):687-93.e1-2.

8. Pediatrics in Review. 1991;12(8):248-55.

9. J Pediatr. 2017 May;184:230-1.e1.

 

Rosacea is a chronic inflammatory skin disorder characterized by flushing, telangiectasia, erythema, papules, and pustules, most classically of the central face. Fair-skinned individuals and women are more commonly affected than are men, with age of onset typically around 30 years and older.¹ In children and adolescents, rosacea is rare, especially among prepubertal children, so other papulopustular disorders should be considered when a rosacealike picture is present.² Recurrent chalazia are seen with ocular rosacea and may be a clue to the diagnosis of acne rosacea. Rosacea may be divided into four subtypes, and more than one subtype may be simultaneously present in an individual at one time. An individual’s subtype of rosacea also may transform with time to a different or an additional subtype.

Courtesy Dr. Laurence F. Eichenfield

Erythematotelangiectatic rosacea (subtype I) describes persistent erythema of the central face associated with episodes of transient flushing. The erythema may extend to the periphery of the face, ears, neck, and upper chest, and is the most common sign of rosacea in the adult population. Telangiectasias often are present, but both telangiectasias and erythema may be difficult to appreciate in patients of Fitzpatrick skin types V and VI. Rosacea is thought to be both less common and more frequently left undiagnosed in this population.

Papulopustular rosacea (subtype II) is characterized by the presence of erythematous, dome-shaped papules distributed in crops in the central facial region. Cheeks, nasolabial folds, and the chin are most commonly affected. Pustules may or may not be present, but comedones are notably absent in an exclusively rosacea disease process. If comedones are present, a diagnosis of acne vulgaris should be considered instead of, or in addition to, rosacea. Pediatric patients with rosacea frequently present with papules and/or pustules, following the development of flushing.²

Phymatous rosacea (subtype III) consists of irregular thickening and fibrosis of the skin, with widening of follicles and increased nodularity of the skin surface. Any sebaceous facial region may be affected, though rhinophyma – an enlarged, bulbous nose – is the most classic presentation. Fortunately, children usually are spared from phymatous change, as it tends to occur later in the disease process during adulthood.²

Ocular rosacea (subtype IV) may range in severity from mild blepharitis to severe keratitis and corneal vascularization. Patients may complain of a foreign body sensation. On external exam, lid margin telangiectasias, blepharitis, conjunctivitis, conjunctival injection, and recurrent chalazia may be frequently seen.³ Ocular rosacea may present without any signs of cutaneous disease; it may be the only form of rosacea (15% of patients in one study of 20 patients had only ocular rosacea)⁴ or may herald the development of cutaneous involvement. In fact, in children, ocular rosacea is frequently the first sign of disease. (A total of 55% of patients in the same study had both ocular and cutaneous rosacea, with ocular symptoms manifesting before the cutaneous disease). Thus an index of suspicion for rosacea should be maintained when a child presents with ocular findings.²

Rosacea is clinically diagnosed when at least one diagnostic or two major phenotypic criteria are present.¹ Presence of fixed centrofacial erythema or phymatous change are adequate for definitive diagnosis, while flushing, papules and pustules, telangiectasia, and ocular manifestations are considered major phenotypic criteria. In addition, presence of sensitive, easily irritated skin, with frequent stinging or burning, may support a diagnosis of rosacea. Skin biopsy is generally unnecessary, as the histopathologic findings are nonspecific: perivascular and perifollicular inflammatory infiltrates in papulopustular rosacea, dilated blood vessels in the erythematotelangiectatic rosacea, and sebaceous gland hyperplasia and dermal fibrosis in phymatous rosacea.⁵

Other dermatitides resembling rosacea include steroid rosacea, perioral dermatitis, and idiopathic facial aseptic granuloma. Steroid rosacea, also known as iatrosacea, describes an eruption of erythema, papules, and telangiectasias that is clinically indistinguishable from rosacea.⁶ It results from chronic use of topical steroids, generally high potency, or abrupt withdrawal of steroids. Steroid rosacea should be treated by discontinuation of the steroid via tapered withdrawal.⁷ Perioral dermatitis, also known as periorificial dermatitis, may also appear rosacea-form. It usually is located around the perioral and perinasal areas, but may extend to the periocular area.⁸ Idiopathic facial septic granuloma describes erythematous to violaceous nodules of the cheeks and eyelid in children, with chalazia frequently present; it is thought to be associated with rosacea.⁹

Although the exact pathophysiology of rosacea is unknown, it is clear that the dysregulation of the innate immune system plays a key role in the pathogenesis of rosacea. Studies have found that patients with rosacea have increased expression of cathelicidin, and its activating serine protease, kallikrein.⁵ Interestingly, UV light, a known trigger of rosacea, induces expression of cathelicidin and its inflammatory cascade.⁵ Neurovascular signaling is also aberrantly upregulated; vanilloid and ankyrin receptors have been shown to be active in rosacea, and are activated by rosacea-exacerbating stimuli, such as heat, inflammation, and spices. Higher levels of Demodex folliculorum and Staphylococcus epidermis also have been consistently found on the skin of rosacea patients, compared with healthy subjects, though it is unclear what role these pathogens play in the development of rosacea.

Treatment of rosacea is very important given its profound impact on quality of life; one study found that the odds ratio for depression in individuals with rosacea is 4.81.¹⁰ Patient education is essential, and patients should be encouraged to identify specific triggers so they can minimize exposure when feasible. Common triggers include hot and cold temperature, sunlight, wind, spicy foods, alcohol, exercise, emotional stress, and certain medications such as niacin. Topical steroids frequently are exacerbating, so patients should be encouraged to avoid them and use moisturizers often, given their skin’s increased transepidermal water loss and susceptibility to irritation. In addition, sunscreens are essential to reduce inflammation from reactive oxygen species, which aggravate rosacea.¹¹ For pharmaceutical therapeutics, topical sodium sulfacetamide, metronidazole, and azelaic acid have been shown to be effective in rosacea. For persistent erythema, topical alpha-adrenergic receptor agonists including brimonidine tartrate and oxymetazoline have been shown to reduce erythema by vasoconstricting blood vessels, although some products are associated with a rebound erythema on treatment discontinuation. For moderate to severe rosacea, low-dose oral doxycycline at anti-inflammatory doses (less than 50 mg daily) is the mainstay of therapy. Other oral antibiotics and topical permethrin have been used, and topical ivermectin 1% cream has been approved for inflammatory rosacea.¹¹ Oral beta-blockers also have been successfully used in some patients to reduce erythema and flushing, as well as isotretinoin for refractory, severe rosacea with improvement.

Allison Han is a medical student at the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. There are no conflicts of interest or financial disclosures for Ms. Han or Dr. Eichenfield.

References

1. J Am Acad Dermatol. 2018 Jan;78(1):148-55.

2. Cutis. 2016 Jul;98(1):49-53.

3. J Eur Acad Dermatol Venereol. 2017 Oct;31(10):1732-8.

4. J Fr Ophtalmol. 2011 Dec;34(10):703-10.

5. J Am Acad Dermatol. 2015 May;72(5):749-58.

6. Indian J Dermatol. 2011 Jan;56(1):30-2.

7. Cutis, 2004. 74(2):99-103.

8. Pediatr Dermatol. 1992 Mar;9(1):22-6.

9. Pediatr Dermatol. 2015 Jul-Aug;32(4):e136-9.

10. Br J Dermatol. 2005 Dec;153(6):1176-81.

11. J Am Acad Dermatol. 2015 May;72(5):761-70.

 

Rosacea is a chronic inflammatory skin disorder characterized by flushing, telangiectasia, erythema, papules, and pustules, most classically of the central face. Fair-skinned individuals and women are more commonly affected than are men, with age of onset typically around 30 years and older.¹ In children and adolescents, rosacea is rare, especially among prepubertal children, so other papulopustular disorders should be considered when a rosacealike picture is present.² Recurrent chalazia are seen with ocular rosacea and may be a clue to the diagnosis of acne rosacea. Rosacea may be divided into four subtypes, and more than one subtype may be simultaneously present in an individual at one time. An individual’s subtype of rosacea also may transform with time to a different or an additional subtype.

Courtesy Dr. Laurence F. Eichenfield

Erythematotelangiectatic rosacea (subtype I) describes persistent erythema of the central face associated with episodes of transient flushing. The erythema may extend to the periphery of the face, ears, neck, and upper chest, and is the most common sign of rosacea in the adult population. Telangiectasias often are present, but both telangiectasias and erythema may be difficult to appreciate in patients of Fitzpatrick skin types V and VI. Rosacea is thought to be both less common and more frequently left undiagnosed in this population.

Papulopustular rosacea (subtype II) is characterized by the presence of erythematous, dome-shaped papules distributed in crops in the central facial region. Cheeks, nasolabial folds, and the chin are most commonly affected. Pustules may or may not be present, but comedones are notably absent in an exclusively rosacea disease process. If comedones are present, a diagnosis of acne vulgaris should be considered instead of, or in addition to, rosacea. Pediatric patients with rosacea frequently present with papules and/or pustules, following the development of flushing.²

Phymatous rosacea (subtype III) consists of irregular thickening and fibrosis of the skin, with widening of follicles and increased nodularity of the skin surface. Any sebaceous facial region may be affected, though rhinophyma – an enlarged, bulbous nose – is the most classic presentation. Fortunately, children usually are spared from phymatous change, as it tends to occur later in the disease process during adulthood.²

Ocular rosacea (subtype IV) may range in severity from mild blepharitis to severe keratitis and corneal vascularization. Patients may complain of a foreign body sensation. On external exam, lid margin telangiectasias, blepharitis, conjunctivitis, conjunctival injection, and recurrent chalazia may be frequently seen.³ Ocular rosacea may present without any signs of cutaneous disease; it may be the only form of rosacea (15% of patients in one study of 20 patients had only ocular rosacea)⁴ or may herald the development of cutaneous involvement. In fact, in children, ocular rosacea is frequently the first sign of disease. (A total of 55% of patients in the same study had both ocular and cutaneous rosacea, with ocular symptoms manifesting before the cutaneous disease). Thus an index of suspicion for rosacea should be maintained when a child presents with ocular findings.²

Rosacea is clinically diagnosed when at least one diagnostic or two major phenotypic criteria are present.¹ Presence of fixed centrofacial erythema or phymatous change are adequate for definitive diagnosis, while flushing, papules and pustules, telangiectasia, and ocular manifestations are considered major phenotypic criteria. In addition, presence of sensitive, easily irritated skin, with frequent stinging or burning, may support a diagnosis of rosacea. Skin biopsy is generally unnecessary, as the histopathologic findings are nonspecific: perivascular and perifollicular inflammatory infiltrates in papulopustular rosacea, dilated blood vessels in the erythematotelangiectatic rosacea, and sebaceous gland hyperplasia and dermal fibrosis in phymatous rosacea.⁵

Other dermatitides resembling rosacea include steroid rosacea, perioral dermatitis, and idiopathic facial aseptic granuloma. Steroid rosacea, also known as iatrosacea, describes an eruption of erythema, papules, and telangiectasias that is clinically indistinguishable from rosacea.⁶ It results from chronic use of topical steroids, generally high potency, or abrupt withdrawal of steroids. Steroid rosacea should be treated by discontinuation of the steroid via tapered withdrawal.⁷ Perioral dermatitis, also known as periorificial dermatitis, may also appear rosacea-form. It usually is located around the perioral and perinasal areas, but may extend to the periocular area.⁸ Idiopathic facial septic granuloma describes erythematous to violaceous nodules of the cheeks and eyelid in children, with chalazia frequently present; it is thought to be associated with rosacea.⁹

Although the exact pathophysiology of rosacea is unknown, it is clear that the dysregulation of the innate immune system plays a key role in the pathogenesis of rosacea. Studies have found that patients with rosacea have increased expression of cathelicidin, and its activating serine protease, kallikrein.⁵ Interestingly, UV light, a known trigger of rosacea, induces expression of cathelicidin and its inflammatory cascade.⁵ Neurovascular signaling is also aberrantly upregulated; vanilloid and ankyrin receptors have been shown to be active in rosacea, and are activated by rosacea-exacerbating stimuli, such as heat, inflammation, and spices. Higher levels of Demodex folliculorum and Staphylococcus epidermis also have been consistently found on the skin of rosacea patients, compared with healthy subjects, though it is unclear what role these pathogens play in the development of rosacea.

Treatment of rosacea is very important given its profound impact on quality of life; one study found that the odds ratio for depression in individuals with rosacea is 4.81.¹⁰ Patient education is essential, and patients should be encouraged to identify specific triggers so they can minimize exposure when feasible. Common triggers include hot and cold temperature, sunlight, wind, spicy foods, alcohol, exercise, emotional stress, and certain medications such as niacin. Topical steroids frequently are exacerbating, so patients should be encouraged to avoid them and use moisturizers often, given their skin’s increased transepidermal water loss and susceptibility to irritation. In addition, sunscreens are essential to reduce inflammation from reactive oxygen species, which aggravate rosacea.¹¹ For pharmaceutical therapeutics, topical sodium sulfacetamide, metronidazole, and azelaic acid have been shown to be effective in rosacea. For persistent erythema, topical alpha-adrenergic receptor agonists including brimonidine tartrate and oxymetazoline have been shown to reduce erythema by vasoconstricting blood vessels, although some products are associated with a rebound erythema on treatment discontinuation. For moderate to severe rosacea, low-dose oral doxycycline at anti-inflammatory doses (less than 50 mg daily) is the mainstay of therapy. Other oral antibiotics and topical permethrin have been used, and topical ivermectin 1% cream has been approved for inflammatory rosacea.¹¹ Oral beta-blockers also have been successfully used in some patients to reduce erythema and flushing, as well as isotretinoin for refractory, severe rosacea with improvement.

Allison Han is a medical student at the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. There are no conflicts of interest or financial disclosures for Ms. Han or Dr. Eichenfield.

References

1. J Am Acad Dermatol. 2018 Jan;78(1):148-55.

2. Cutis. 2016 Jul;98(1):49-53.

3. J Eur Acad Dermatol Venereol. 2017 Oct;31(10):1732-8.

4. J Fr Ophtalmol. 2011 Dec;34(10):703-10.

5. J Am Acad Dermatol. 2015 May;72(5):749-58.

6. Indian J Dermatol. 2011 Jan;56(1):30-2.

7. Cutis, 2004. 74(2):99-103.

8. Pediatr Dermatol. 1992 Mar;9(1):22-6.

9. Pediatr Dermatol. 2015 Jul-Aug;32(4):e136-9.

10. Br J Dermatol. 2005 Dec;153(6):1176-81.

11. J Am Acad Dermatol. 2015 May;72(5):761-70.

 

Rosacea is a chronic inflammatory skin disorder characterized by flushing, telangiectasia, erythema, papules, and pustules, most classically of the central face. Fair-skinned individuals and women are more commonly affected than are men, with age of onset typically around 30 years and older.¹ In children and adolescents, rosacea is rare, especially among prepubertal children, so other papulopustular disorders should be considered when a rosacealike picture is present.² Recurrent chalazia are seen with ocular rosacea and may be a clue to the diagnosis of acne rosacea. Rosacea may be divided into four subtypes, and more than one subtype may be simultaneously present in an individual at one time. An individual’s subtype of rosacea also may transform with time to a different or an additional subtype.

Courtesy Dr. Laurence F. Eichenfield

Erythematotelangiectatic rosacea (subtype I) describes persistent erythema of the central face associated with episodes of transient flushing. The erythema may extend to the periphery of the face, ears, neck, and upper chest, and is the most common sign of rosacea in the adult population. Telangiectasias often are present, but both telangiectasias and erythema may be difficult to appreciate in patients of Fitzpatrick skin types V and VI. Rosacea is thought to be both less common and more frequently left undiagnosed in this population.

Papulopustular rosacea (subtype II) is characterized by the presence of erythematous, dome-shaped papules distributed in crops in the central facial region. Cheeks, nasolabial folds, and the chin are most commonly affected. Pustules may or may not be present, but comedones are notably absent in an exclusively rosacea disease process. If comedones are present, a diagnosis of acne vulgaris should be considered instead of, or in addition to, rosacea. Pediatric patients with rosacea frequently present with papules and/or pustules, following the development of flushing.²

Phymatous rosacea (subtype III) consists of irregular thickening and fibrosis of the skin, with widening of follicles and increased nodularity of the skin surface. Any sebaceous facial region may be affected, though rhinophyma – an enlarged, bulbous nose – is the most classic presentation. Fortunately, children usually are spared from phymatous change, as it tends to occur later in the disease process during adulthood.²

Ocular rosacea (subtype IV) may range in severity from mild blepharitis to severe keratitis and corneal vascularization. Patients may complain of a foreign body sensation. On external exam, lid margin telangiectasias, blepharitis, conjunctivitis, conjunctival injection, and recurrent chalazia may be frequently seen.³ Ocular rosacea may present without any signs of cutaneous disease; it may be the only form of rosacea (15% of patients in one study of 20 patients had only ocular rosacea)⁴ or may herald the development of cutaneous involvement. In fact, in children, ocular rosacea is frequently the first sign of disease. (A total of 55% of patients in the same study had both ocular and cutaneous rosacea, with ocular symptoms manifesting before the cutaneous disease). Thus an index of suspicion for rosacea should be maintained when a child presents with ocular findings.²

Rosacea is clinically diagnosed when at least one diagnostic or two major phenotypic criteria are present.¹ Presence of fixed centrofacial erythema or phymatous change are adequate for definitive diagnosis, while flushing, papules and pustules, telangiectasia, and ocular manifestations are considered major phenotypic criteria. In addition, presence of sensitive, easily irritated skin, with frequent stinging or burning, may support a diagnosis of rosacea. Skin biopsy is generally unnecessary, as the histopathologic findings are nonspecific: perivascular and perifollicular inflammatory infiltrates in papulopustular rosacea, dilated blood vessels in the erythematotelangiectatic rosacea, and sebaceous gland hyperplasia and dermal fibrosis in phymatous rosacea.⁵

Other dermatitides resembling rosacea include steroid rosacea, perioral dermatitis, and idiopathic facial aseptic granuloma. Steroid rosacea, also known as iatrosacea, describes an eruption of erythema, papules, and telangiectasias that is clinically indistinguishable from rosacea.⁶ It results from chronic use of topical steroids, generally high potency, or abrupt withdrawal of steroids. Steroid rosacea should be treated by discontinuation of the steroid via tapered withdrawal.⁷ Perioral dermatitis, also known as periorificial dermatitis, may also appear rosacea-form. It usually is located around the perioral and perinasal areas, but may extend to the periocular area.⁸ Idiopathic facial septic granuloma describes erythematous to violaceous nodules of the cheeks and eyelid in children, with chalazia frequently present; it is thought to be associated with rosacea.⁹

Although the exact pathophysiology of rosacea is unknown, it is clear that the dysregulation of the innate immune system plays a key role in the pathogenesis of rosacea. Studies have found that patients with rosacea have increased expression of cathelicidin, and its activating serine protease, kallikrein.⁵ Interestingly, UV light, a known trigger of rosacea, induces expression of cathelicidin and its inflammatory cascade.⁵ Neurovascular signaling is also aberrantly upregulated; vanilloid and ankyrin receptors have been shown to be active in rosacea, and are activated by rosacea-exacerbating stimuli, such as heat, inflammation, and spices. Higher levels of Demodex folliculorum and Staphylococcus epidermis also have been consistently found on the skin of rosacea patients, compared with healthy subjects, though it is unclear what role these pathogens play in the development of rosacea.

Treatment of rosacea is very important given its profound impact on quality of life; one study found that the odds ratio for depression in individuals with rosacea is 4.81.¹⁰ Patient education is essential, and patients should be encouraged to identify specific triggers so they can minimize exposure when feasible. Common triggers include hot and cold temperature, sunlight, wind, spicy foods, alcohol, exercise, emotional stress, and certain medications such as niacin. Topical steroids frequently are exacerbating, so patients should be encouraged to avoid them and use moisturizers often, given their skin’s increased transepidermal water loss and susceptibility to irritation. In addition, sunscreens are essential to reduce inflammation from reactive oxygen species, which aggravate rosacea.¹¹ For pharmaceutical therapeutics, topical sodium sulfacetamide, metronidazole, and azelaic acid have been shown to be effective in rosacea. For persistent erythema, topical alpha-adrenergic receptor agonists including brimonidine tartrate and oxymetazoline have been shown to reduce erythema by vasoconstricting blood vessels, although some products are associated with a rebound erythema on treatment discontinuation. For moderate to severe rosacea, low-dose oral doxycycline at anti-inflammatory doses (less than 50 mg daily) is the mainstay of therapy. Other oral antibiotics and topical permethrin have been used, and topical ivermectin 1% cream has been approved for inflammatory rosacea.¹¹ Oral beta-blockers also have been successfully used in some patients to reduce erythema and flushing, as well as isotretinoin for refractory, severe rosacea with improvement.

Allison Han is a medical student at the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. There are no conflicts of interest or financial disclosures for Ms. Han or Dr. Eichenfield.

References

1. J Am Acad Dermatol. 2018 Jan;78(1):148-55.

2. Cutis. 2016 Jul;98(1):49-53.

3. J Eur Acad Dermatol Venereol. 2017 Oct;31(10):1732-8.

4. J Fr Ophtalmol. 2011 Dec;34(10):703-10.

5. J Am Acad Dermatol. 2015 May;72(5):749-58.

6. Indian J Dermatol. 2011 Jan;56(1):30-2.

7. Cutis, 2004. 74(2):99-103.

8. Pediatr Dermatol. 1992 Mar;9(1):22-6.

9. Pediatr Dermatol. 2015 Jul-Aug;32(4):e136-9.

10. Br J Dermatol. 2005 Dec;153(6):1176-81.

11. J Am Acad Dermatol. 2015 May;72(5):761-70.

 

Morphea, also known as localized scleroderma, is a rare fibrosing disorder of the skin and the underlying tissue that encompasses a variety of distinct subtypes classified by pattern and depth of lesion involvement. It may involve fat, fascia, muscle, and bone, and rarely, the central nervous system. Morphea is easily differentiated from systemic sclerosis by its primarily cutaneous involvement, although a minority of patients may have associated extracutaneous findings. Systemic sclerosis describes a well-defined disorder of skin sclerosis with a specific pattern of internal organ involvement.

Courtesy Dr. Lawrence F. Eichenfield

Morphea affects an estimated 0.4 to 2.7 per 100,000 people annually, with a predilection for females.¹ Mean age of onset for pediatric morphea is around 10 years of age,² although a few cases of congenital morphea have been reported, all of the linear morphea variant.³

Classification of the different subtypes of morphea are based on clinical presentation of the lesions. The most widely used system characterizes morphea into linear, circumscribed, generalized, pansclerotic, and mixed morphea subtypes.¹ Mixed morphea describes the presence of two or more patterns of disease and affects 15% of patients. Morphea lesions initially present as erythematous to violaceous patches and plaques that eventually become white and sclerotic, with resulting destruction of the surrounding structures.

Linear scleroderma is the most common subtype of morphea in children and adolescents, affecting 42%-67% of children with morphea.¹ It is characterized by linear plaques, often on the extremities, face, or scalp, that tend to follow Blaschko lines.⁴ These lesions may extend past the dermis to the subcutaneous tissue, muscle, and even bone, resulting in significant deformities. When on the scalp or face, particularly the forehead, the linear lesion may be referred to as the en coup de sabre variant. Ocular and CNS involvement should be of concern in these patients. When subcutaneous atrophy on the unilateral face is present with unaffected overlaying skin, this is known as the Parry-Romberg syndrome or progressive hemifacial atrophy. Involvement of the extremities is common, and unfortunately, may lead to muscle atrophy of the affected limb, contractures in areas overlying joint spaces, and occasionally limb length discrepancies.

Circumscribed morphea describes three or fewer discrete, oval, or round indurated plaques, with central whitening and a violaceous periphery. They generally are found on the trunk. When lesions have deeper involvement, delving past the dermis to involve the underlying fascia and muscle, the patient may experience a “bound down” sensation. Most lesions soften over 3-5 years.

Generalized morphea is used to describe the presence of at least four plaques, larger than 3 cm, that become confluent in at least two different locations on the body. Patients with generalized morphea have higher rates of systemic symptoms such as arthritis and fatigue.

Pansclerotic morphea, the most severe subtype, is characterized by significant body surface area involvement coupled with deep depth of involvement, often to the bone. The widespread blistering associated with pansclerotic morphea may lead to chronic ulceration and, later on, a higher risk of squamous cell carcinoma development. Despite its extensive distribution, pansclerotic morphea does not cause the severe organ and vascular fibrosis that is characteristically seen in systemic sclerosis. Raynaud’s phenomenon, abnormal nailfold capillaries, and sclerodactyly also will be absent in pansclerotic morphea.

Extracutaneous findings are present in up to 22% of patients with morphea.⁵ Arthritis is the most common associated finding, and often is correlated with a positive rheumatoid factor. Neurologic involvement most frequently is seen in patients with facial morphea and may present as seizures, as in this patient. MRI abnormalities such as calcifications and white matter changes may be seen. Other common extracutaneous features include fatigue, vascular abnormalities, and ocular findings, such as uveitis.

Morphea and systemic sclerosis appear similar on histology. In early morphea, lymphocytic perivascular infiltrates may be seen in the reticular dermis. In late morphea, the inflammatory cells are replaced by an abundance of collagen bundles infiltrating the dermis.

Initial inflammation, followed by excess collagen deposition, then fibrosis and atrophy is the hallmark of morphea, although the instigating factor activating this pathway is unknown. Multiple factors have been associated with the development of morphea, including autoimmunity, trauma, Borrelia and cytomegalovirus infections, radiation, and certain medications in case reports. Patients with morphea have higher rates of concomitant autoimmune diseases than that found in the general population⁶ and also have higher rates of autoantibody positivity. In a 750-patient, multicenter study of children with morphea, 42% of patients had positive antinuclear antibodies.⁷
 

Diagnosis

Morphea is diagnosed clinically, based on the characteristic appearance of the lesions. A biopsy may be helpful if the presentation is atypical. Although patients with morphea have higher rates of autoantibody positivity, there are no specific laboratory tests that consistently or reliably offer diagnostic value.⁸ Imaging modalities such as MRI may be utilized to view depth of involvement. Other noninvasive measures, such as thermography and ultrasonography, may be used to determine disease activity.⁹

 

Morphea frequently is misdiagnosed and mistaken for a variety of dermatologic conditions; considerations vary based on the stage of morphea. The inflammatory phase can appear similar to erythema migrans or port wine stains. During the indurated phase, conditions such as lupus panniculitis and graft-versus-host disease may be considered. In the atrophic phase, differential diagnosis includes lichen sclerosus et atrophicus, lipodystrophy, and vitiligo.¹⁰
 

Treatment

Treatment for morphea often is multidisciplinary and depends on the severity of involvement and extent to which it impedes functionality and quality of life. Localized plaques that do not restrict movement may be treated with topical corticosteroids, calcipotriene, and tacrolimus. However, topical corticosteroids should be discontinued if there are no signs of improvement in 2-3 months.

For patients with deforming or functionally significant disease, systemic treatment is advised. Methotrexate with or without systemic corticosteroids has been frequently studied, and is the most commonly recommended systemic therapy.¹¹ Some experts have recommended treatment for at least 2-3 years, with at least 1 year of disease inactivity, before discontinuing treatment. Despite this duration of treatment, up to one-quarter of patients, especially those with linear morphea, will still experience recurrence of disease. Management of morphea may be aided by rheumatology and/or dermatology consultation.

Physical therapy to maintain muscle strength, functional ability, and joint movement often is beneficial to patients who have muscle atrophy and/or contractures in their extremities. Orthopedic surgeons may utilize corrective splints and surgical interventions to address limb length discrepancies and contractures.¹² Plastic surgeons also may be involved to minimize disfigurement and resulting psychosocial distress, especially when the face is involved.
 

Ms. Han is a medical student at the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and a professor of dermatology and pediatrics at the University of California, San Diego. Ms. Han and Dr. Eichenfield had no conflicts of interest or financial disclosures.

References

1. Fett N et al. J Am Acad Dermatol. 2011 Feb;64(2):217-28.

2. Condie D et al. Arthritis Rheumatol. 2014 Dec;66(12):3496-504.

3. Zulian F et al. J Pediatr. 2006 Aug;149(2):248-51.

4. Weibel L et al. Br J Dermatol. 2008 Jul;159(1):175-81.

5. Zulian F et al. Arthritis Rheum. 2005 Sep;52(9):2873-81.

6. Leitenberger JJ et al. Arch Dermatol. 2009 May;145(5):545-50.

7. Zulian F et al. Rheumatology (Oxford). 2006 May;45(5):614-20.

8. Dharamsi JW et al. JAMA Dermatol. 2013 Oct;149(10):1159-65.

9. Zulian F et al. Curr Opin Rheumatol. 2013 Sep;25(5):643-50.

10. Pope E et al. Pediatr Clin North Am. 2014 Apr;61(2):309-19.

11. Strickland N et al. Am Acad Dermatol. 2015 Apr; 72(4): 727-8.

12. Schoch JJ et al. Pediatr Dermatol. 2018. 35(1): 43-6.

 

Morphea, also known as localized scleroderma, is a rare fibrosing disorder of the skin and the underlying tissue that encompasses a variety of distinct subtypes classified by pattern and depth of lesion involvement. It may involve fat, fascia, muscle, and bone, and rarely, the central nervous system. Morphea is easily differentiated from systemic sclerosis by its primarily cutaneous involvement, although a minority of patients may have associated extracutaneous findings. Systemic sclerosis describes a well-defined disorder of skin sclerosis with a specific pattern of internal organ involvement.

Courtesy Dr. Lawrence F. Eichenfield

Morphea affects an estimated 0.4 to 2.7 per 100,000 people annually, with a predilection for females.¹ Mean age of onset for pediatric morphea is around 10 years of age,² although a few cases of congenital morphea have been reported, all of the linear morphea variant.³

Classification of the different subtypes of morphea are based on clinical presentation of the lesions. The most widely used system characterizes morphea into linear, circumscribed, generalized, pansclerotic, and mixed morphea subtypes.¹ Mixed morphea describes the presence of two or more patterns of disease and affects 15% of patients. Morphea lesions initially present as erythematous to violaceous patches and plaques that eventually become white and sclerotic, with resulting destruction of the surrounding structures.

Linear scleroderma is the most common subtype of morphea in children and adolescents, affecting 42%-67% of children with morphea.¹ It is characterized by linear plaques, often on the extremities, face, or scalp, that tend to follow Blaschko lines.⁴ These lesions may extend past the dermis to the subcutaneous tissue, muscle, and even bone, resulting in significant deformities. When on the scalp or face, particularly the forehead, the linear lesion may be referred to as the en coup de sabre variant. Ocular and CNS involvement should be of concern in these patients. When subcutaneous atrophy on the unilateral face is present with unaffected overlaying skin, this is known as the Parry-Romberg syndrome or progressive hemifacial atrophy. Involvement of the extremities is common, and unfortunately, may lead to muscle atrophy of the affected limb, contractures in areas overlying joint spaces, and occasionally limb length discrepancies.

Circumscribed morphea describes three or fewer discrete, oval, or round indurated plaques, with central whitening and a violaceous periphery. They generally are found on the trunk. When lesions have deeper involvement, delving past the dermis to involve the underlying fascia and muscle, the patient may experience a “bound down” sensation. Most lesions soften over 3-5 years.

Generalized morphea is used to describe the presence of at least four plaques, larger than 3 cm, that become confluent in at least two different locations on the body. Patients with generalized morphea have higher rates of systemic symptoms such as arthritis and fatigue.

Pansclerotic morphea, the most severe subtype, is characterized by significant body surface area involvement coupled with deep depth of involvement, often to the bone. The widespread blistering associated with pansclerotic morphea may lead to chronic ulceration and, later on, a higher risk of squamous cell carcinoma development. Despite its extensive distribution, pansclerotic morphea does not cause the severe organ and vascular fibrosis that is characteristically seen in systemic sclerosis. Raynaud’s phenomenon, abnormal nailfold capillaries, and sclerodactyly also will be absent in pansclerotic morphea.

Extracutaneous findings are present in up to 22% of patients with morphea.⁵ Arthritis is the most common associated finding, and often is correlated with a positive rheumatoid factor. Neurologic involvement most frequently is seen in patients with facial morphea and may present as seizures, as in this patient. MRI abnormalities such as calcifications and white matter changes may be seen. Other common extracutaneous features include fatigue, vascular abnormalities, and ocular findings, such as uveitis.

Morphea and systemic sclerosis appear similar on histology. In early morphea, lymphocytic perivascular infiltrates may be seen in the reticular dermis. In late morphea, the inflammatory cells are replaced by an abundance of collagen bundles infiltrating the dermis.

Initial inflammation, followed by excess collagen deposition, then fibrosis and atrophy is the hallmark of morphea, although the instigating factor activating this pathway is unknown. Multiple factors have been associated with the development of morphea, including autoimmunity, trauma, Borrelia and cytomegalovirus infections, radiation, and certain medications in case reports. Patients with morphea have higher rates of concomitant autoimmune diseases than that found in the general population⁶ and also have higher rates of autoantibody positivity. In a 750-patient, multicenter study of children with morphea, 42% of patients had positive antinuclear antibodies.⁷
 

Diagnosis

Morphea is diagnosed clinically, based on the characteristic appearance of the lesions. A biopsy may be helpful if the presentation is atypical. Although patients with morphea have higher rates of autoantibody positivity, there are no specific laboratory tests that consistently or reliably offer diagnostic value.⁸ Imaging modalities such as MRI may be utilized to view depth of involvement. Other noninvasive measures, such as thermography and ultrasonography, may be used to determine disease activity.⁹

 

Morphea frequently is misdiagnosed and mistaken for a variety of dermatologic conditions; considerations vary based on the stage of morphea. The inflammatory phase can appear similar to erythema migrans or port wine stains. During the indurated phase, conditions such as lupus panniculitis and graft-versus-host disease may be considered. In the atrophic phase, differential diagnosis includes lichen sclerosus et atrophicus, lipodystrophy, and vitiligo.¹⁰
 

Treatment

Treatment for morphea often is multidisciplinary and depends on the severity of involvement and extent to which it impedes functionality and quality of life. Localized plaques that do not restrict movement may be treated with topical corticosteroids, calcipotriene, and tacrolimus. However, topical corticosteroids should be discontinued if there are no signs of improvement in 2-3 months.

For patients with deforming or functionally significant disease, systemic treatment is advised. Methotrexate with or without systemic corticosteroids has been frequently studied, and is the most commonly recommended systemic therapy.¹¹ Some experts have recommended treatment for at least 2-3 years, with at least 1 year of disease inactivity, before discontinuing treatment. Despite this duration of treatment, up to one-quarter of patients, especially those with linear morphea, will still experience recurrence of disease. Management of morphea may be aided by rheumatology and/or dermatology consultation.

Physical therapy to maintain muscle strength, functional ability, and joint movement often is beneficial to patients who have muscle atrophy and/or contractures in their extremities. Orthopedic surgeons may utilize corrective splints and surgical interventions to address limb length discrepancies and contractures.¹² Plastic surgeons also may be involved to minimize disfigurement and resulting psychosocial distress, especially when the face is involved.
 

Ms. Han is a medical student at the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and a professor of dermatology and pediatrics at the University of California, San Diego. Ms. Han and Dr. Eichenfield had no conflicts of interest or financial disclosures.

References

1. Fett N et al. J Am Acad Dermatol. 2011 Feb;64(2):217-28.

2. Condie D et al. Arthritis Rheumatol. 2014 Dec;66(12):3496-504.

3. Zulian F et al. J Pediatr. 2006 Aug;149(2):248-51.

4. Weibel L et al. Br J Dermatol. 2008 Jul;159(1):175-81.

5. Zulian F et al. Arthritis Rheum. 2005 Sep;52(9):2873-81.

6. Leitenberger JJ et al. Arch Dermatol. 2009 May;145(5):545-50.

7. Zulian F et al. Rheumatology (Oxford). 2006 May;45(5):614-20.

8. Dharamsi JW et al. JAMA Dermatol. 2013 Oct;149(10):1159-65.

9. Zulian F et al. Curr Opin Rheumatol. 2013 Sep;25(5):643-50.

10. Pope E et al. Pediatr Clin North Am. 2014 Apr;61(2):309-19.

11. Strickland N et al. Am Acad Dermatol. 2015 Apr; 72(4): 727-8.

12. Schoch JJ et al. Pediatr Dermatol. 2018. 35(1): 43-6.

 

Morphea, also known as localized scleroderma, is a rare fibrosing disorder of the skin and the underlying tissue that encompasses a variety of distinct subtypes classified by pattern and depth of lesion involvement. It may involve fat, fascia, muscle, and bone, and rarely, the central nervous system. Morphea is easily differentiated from systemic sclerosis by its primarily cutaneous involvement, although a minority of patients may have associated extracutaneous findings. Systemic sclerosis describes a well-defined disorder of skin sclerosis with a specific pattern of internal organ involvement.

Courtesy Dr. Lawrence F. Eichenfield

Morphea affects an estimated 0.4 to 2.7 per 100,000 people annually, with a predilection for females.¹ Mean age of onset for pediatric morphea is around 10 years of age,² although a few cases of congenital morphea have been reported, all of the linear morphea variant.³

Classification of the different subtypes of morphea are based on clinical presentation of the lesions. The most widely used system characterizes morphea into linear, circumscribed, generalized, pansclerotic, and mixed morphea subtypes.¹ Mixed morphea describes the presence of two or more patterns of disease and affects 15% of patients. Morphea lesions initially present as erythematous to violaceous patches and plaques that eventually become white and sclerotic, with resulting destruction of the surrounding structures.

Linear scleroderma is the most common subtype of morphea in children and adolescents, affecting 42%-67% of children with morphea.¹ It is characterized by linear plaques, often on the extremities, face, or scalp, that tend to follow Blaschko lines.⁴ These lesions may extend past the dermis to the subcutaneous tissue, muscle, and even bone, resulting in significant deformities. When on the scalp or face, particularly the forehead, the linear lesion may be referred to as the en coup de sabre variant. Ocular and CNS involvement should be of concern in these patients. When subcutaneous atrophy on the unilateral face is present with unaffected overlaying skin, this is known as the Parry-Romberg syndrome or progressive hemifacial atrophy. Involvement of the extremities is common, and unfortunately, may lead to muscle atrophy of the affected limb, contractures in areas overlying joint spaces, and occasionally limb length discrepancies.

Circumscribed morphea describes three or fewer discrete, oval, or round indurated plaques, with central whitening and a violaceous periphery. They generally are found on the trunk. When lesions have deeper involvement, delving past the dermis to involve the underlying fascia and muscle, the patient may experience a “bound down” sensation. Most lesions soften over 3-5 years.

Generalized morphea is used to describe the presence of at least four plaques, larger than 3 cm, that become confluent in at least two different locations on the body. Patients with generalized morphea have higher rates of systemic symptoms such as arthritis and fatigue.

Pansclerotic morphea, the most severe subtype, is characterized by significant body surface area involvement coupled with deep depth of involvement, often to the bone. The widespread blistering associated with pansclerotic morphea may lead to chronic ulceration and, later on, a higher risk of squamous cell carcinoma development. Despite its extensive distribution, pansclerotic morphea does not cause the severe organ and vascular fibrosis that is characteristically seen in systemic sclerosis. Raynaud’s phenomenon, abnormal nailfold capillaries, and sclerodactyly also will be absent in pansclerotic morphea.

Extracutaneous findings are present in up to 22% of patients with morphea.⁵ Arthritis is the most common associated finding, and often is correlated with a positive rheumatoid factor. Neurologic involvement most frequently is seen in patients with facial morphea and may present as seizures, as in this patient. MRI abnormalities such as calcifications and white matter changes may be seen. Other common extracutaneous features include fatigue, vascular abnormalities, and ocular findings, such as uveitis.

Morphea and systemic sclerosis appear similar on histology. In early morphea, lymphocytic perivascular infiltrates may be seen in the reticular dermis. In late morphea, the inflammatory cells are replaced by an abundance of collagen bundles infiltrating the dermis.

Initial inflammation, followed by excess collagen deposition, then fibrosis and atrophy is the hallmark of morphea, although the instigating factor activating this pathway is unknown. Multiple factors have been associated with the development of morphea, including autoimmunity, trauma, Borrelia and cytomegalovirus infections, radiation, and certain medications in case reports. Patients with morphea have higher rates of concomitant autoimmune diseases than that found in the general population⁶ and also have higher rates of autoantibody positivity. In a 750-patient, multicenter study of children with morphea, 42% of patients had positive antinuclear antibodies.⁷
 

Diagnosis

Morphea is diagnosed clinically, based on the characteristic appearance of the lesions. A biopsy may be helpful if the presentation is atypical. Although patients with morphea have higher rates of autoantibody positivity, there are no specific laboratory tests that consistently or reliably offer diagnostic value.⁸ Imaging modalities such as MRI may be utilized to view depth of involvement. Other noninvasive measures, such as thermography and ultrasonography, may be used to determine disease activity.⁹

 

Morphea frequently is misdiagnosed and mistaken for a variety of dermatologic conditions; considerations vary based on the stage of morphea. The inflammatory phase can appear similar to erythema migrans or port wine stains. During the indurated phase, conditions such as lupus panniculitis and graft-versus-host disease may be considered. In the atrophic phase, differential diagnosis includes lichen sclerosus et atrophicus, lipodystrophy, and vitiligo.¹⁰
 

Treatment

Treatment for morphea often is multidisciplinary and depends on the severity of involvement and extent to which it impedes functionality and quality of life. Localized plaques that do not restrict movement may be treated with topical corticosteroids, calcipotriene, and tacrolimus. However, topical corticosteroids should be discontinued if there are no signs of improvement in 2-3 months.

For patients with deforming or functionally significant disease, systemic treatment is advised. Methotrexate with or without systemic corticosteroids has been frequently studied, and is the most commonly recommended systemic therapy.¹¹ Some experts have recommended treatment for at least 2-3 years, with at least 1 year of disease inactivity, before discontinuing treatment. Despite this duration of treatment, up to one-quarter of patients, especially those with linear morphea, will still experience recurrence of disease. Management of morphea may be aided by rheumatology and/or dermatology consultation.

Physical therapy to maintain muscle strength, functional ability, and joint movement often is beneficial to patients who have muscle atrophy and/or contractures in their extremities. Orthopedic surgeons may utilize corrective splints and surgical interventions to address limb length discrepancies and contractures.¹² Plastic surgeons also may be involved to minimize disfigurement and resulting psychosocial distress, especially when the face is involved.
 

Ms. Han is a medical student at the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and a professor of dermatology and pediatrics at the University of California, San Diego. Ms. Han and Dr. Eichenfield had no conflicts of interest or financial disclosures.

References

1. Fett N et al. J Am Acad Dermatol. 2011 Feb;64(2):217-28.

2. Condie D et al. Arthritis Rheumatol. 2014 Dec;66(12):3496-504.

3. Zulian F et al. J Pediatr. 2006 Aug;149(2):248-51.

4. Weibel L et al. Br J Dermatol. 2008 Jul;159(1):175-81.

5. Zulian F et al. Arthritis Rheum. 2005 Sep;52(9):2873-81.

6. Leitenberger JJ et al. Arch Dermatol. 2009 May;145(5):545-50.

7. Zulian F et al. Rheumatology (Oxford). 2006 May;45(5):614-20.

8. Dharamsi JW et al. JAMA Dermatol. 2013 Oct;149(10):1159-65.

9. Zulian F et al. Curr Opin Rheumatol. 2013 Sep;25(5):643-50.

10. Pope E et al. Pediatr Clin North Am. 2014 Apr;61(2):309-19.

11. Strickland N et al. Am Acad Dermatol. 2015 Apr; 72(4): 727-8.

12. Schoch JJ et al. Pediatr Dermatol. 2018. 35(1): 43-6.

 

Confluent and reticulated papillomatosis of Gougerot and Carteaud, also known as Gougerot-Carteaud syndrome, is an uncommon skin disorder of young individuals characterized by hyperkeratotic or verrucous brown papules or plaques that coalesce centrally and by a reticulated pattern peripherally. It was first described by two French dermatologists, Gougerot and Carteaud, in 1927.¹ Initially, the distinct entity of CARP was contested, with some dermatologists believing it to be a variant of acanthosis nigricans. However, CARP is now recognized as a distinct, though rare, dermatosis.

Dr. Lawrence F. Eichenfield

CARP commonly affects teens and young adults, with a mean age of onset of 15 years and without gender predilection.²The most common skin findings of CARP are somewhat verrucous or slightly hyperkeratotic brown papules a few millimeters in diameter. They are closely set together to form plaques in the center of the involved area, while those on the periphery of the involved area form a characteristic reticulated pattern. Papules are often scaly, although verrucous papules, especially those found in intertriginous areas, may develop a velvety appearance. Macules and patches may be present as well. The most common areas of involvement include the central chest and back with lesions extending in a rhomboidal fashion superoinferiorly, as well as the neck and axillae.¹ Uncommonly, pubic and facial skin may be affected.² Skin lesions are frequently hyperpigmented; however, cases of hypopigmented variants have been reported in darker-skinned individuals, although these cases have often been misdiagnosed as tinea versicolor.³ The majority of patients are asymptomatic, although some report mild pruritus. Care often is sought for cosmetic concerns.

Histopathology reveals findings similar to those that may be found in acanthosis nigricans and epidermal nevi. Classic characteristics of CARP include hyperkeratosis, papillomatosis, increased basal melanin pigmentation, and mild acanthosis. Occasionally, there may be perivascular lymphocytic infiltrates in the superficial dermis.^3,4

The etiology of CARP is unknown. CARP’s resolution in response to antibiotics and the isolation of two bacterial actinomycetes, Rhodococcus and Dietzia papillomatosis, from skin scrapings of CARP patients have led some to believe that its etiology is bacterial. However, no bacterial species have been consistently isolated from CARP patients. The prevailing theory of the past was that CARP was an abnormal host response to the fungus Malassezia furfur. Inconsistent detection of the fungus in skin scrapings, as well as persistence of the skin lesions after fungal clearance with antifungal therapy, has debunked this theory. An underlying disorder of keratinization resulting in hyperproliferation also has been suggested given reports of familial CARP and electron microscopy studies demonstrating focal-enhanced expression of keratin-16 in the stratum granulosom.⁵ Other theories include a cutaneous response to underlying endocrinopathies, ultraviolet light, and localized amyloidosis.¹
 

Diagnosis and differential

CARP is poorly recognized by clinicians and frequently initially misdiagnosed due to its similar appearance to other disorders, most commonly tinea versicolor and acanthosis nigricans. Davis et al. proposed criteria for diagnosis of CARP requiring 1) presence of scaly, reticulated and papillomatous brown macules and patches; 2) distribution over the upper trunk and neck; 3) negative fungal staining of scales; 4) no improvement following antifungal treatment; and 5) improvement following minocycline.²

Tinea versicolor may appear similar to CARP, but unlike CARP, will respond to antifungal treatment and may demonstrate hyphae and yeast on KOH preparation. Acanthosis nigricans and CARP both may present with velvety, hyperpigmented plaques in individuals of obese habitus or with insulin resistance, but peripheral reticulation will be absent in acanthosis nigricans. However, acanthosis nigricans and CARP may coexist, and this coexistence is not uncommonly seen in individuals with obesity and/or insulin resistance. Darier’s disease may look similar to cases of CARP without pigmentary change, but it often will have accompanying nail changes. Macular or lichen amyloidosis may present with pruritic brown macules or papules, but skin biopsy will have positive amyloid staining. The use of 70% alcohol swabbing to diagnose terra firma-forme dermatosis, with lesions disappearing with swabbing, is classic and used to differentiate it from CARP. Other conditions to consider include seborrheic dermatitis, epidermal nevi, verruca plana, epidermodysplasia verruciformis, and acne vulgaris.^1,2,4
 

Treatment

Minocycline is the first-line treatment for CARP: 80% of patients may have complete resolution with minocycline, while the remainder experience at least 50% clearance of skin lesions.² However, recurrence after stopping minocycline treatment is not uncommon. The mechanism by which minocycline works is unknown. Second-line treatment for those who cannot tolerate minocycline are macrolide antibiotics.⁶ Other treatment options with reported success include oral isotretinoin and topical retinoids, including tretinoin gel and tazarotene cream.^3,7 Appropriate strength topical corticosteroids may be used for pruritus.

Ms. Han is a medical student at the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego, as well as the vice chair of the department of dermatology and a professor of dermatology and pediatrics at UC San Diego. They report having no conflicts of interest or financial disclosures. Email them at [email protected].

References

1. Clin Cosmet Investig Dermatol. 2016 Aug 25;9:217-23.

2. Br J Dermatol. 2006 Feb;154(2):287-93.

3. Arch Dermatol. 2012 Apr;148(4):505-8.

4. J Am Acad Dermatol. 2003 Dec;49(6):1182-4.

5. Arch Dermatol. 2002 Feb;138(2):276-7.

6. J Am Acad Dermatol. 2001;44(4):652-5.

7. Am J Clin Dermatol. 2006;7(5):305-13.
 

 

Confluent and reticulated papillomatosis of Gougerot and Carteaud, also known as Gougerot-Carteaud syndrome, is an uncommon skin disorder of young individuals characterized by hyperkeratotic or verrucous brown papules or plaques that coalesce centrally and by a reticulated pattern peripherally. It was first described by two French dermatologists, Gougerot and Carteaud, in 1927.¹ Initially, the distinct entity of CARP was contested, with some dermatologists believing it to be a variant of acanthosis nigricans. However, CARP is now recognized as a distinct, though rare, dermatosis.

Dr. Lawrence F. Eichenfield

CARP commonly affects teens and young adults, with a mean age of onset of 15 years and without gender predilection.²The most common skin findings of CARP are somewhat verrucous or slightly hyperkeratotic brown papules a few millimeters in diameter. They are closely set together to form plaques in the center of the involved area, while those on the periphery of the involved area form a characteristic reticulated pattern. Papules are often scaly, although verrucous papules, especially those found in intertriginous areas, may develop a velvety appearance. Macules and patches may be present as well. The most common areas of involvement include the central chest and back with lesions extending in a rhomboidal fashion superoinferiorly, as well as the neck and axillae.¹ Uncommonly, pubic and facial skin may be affected.² Skin lesions are frequently hyperpigmented; however, cases of hypopigmented variants have been reported in darker-skinned individuals, although these cases have often been misdiagnosed as tinea versicolor.³ The majority of patients are asymptomatic, although some report mild pruritus. Care often is sought for cosmetic concerns.

Histopathology reveals findings similar to those that may be found in acanthosis nigricans and epidermal nevi. Classic characteristics of CARP include hyperkeratosis, papillomatosis, increased basal melanin pigmentation, and mild acanthosis. Occasionally, there may be perivascular lymphocytic infiltrates in the superficial dermis.^3,4

The etiology of CARP is unknown. CARP’s resolution in response to antibiotics and the isolation of two bacterial actinomycetes, Rhodococcus and Dietzia papillomatosis, from skin scrapings of CARP patients have led some to believe that its etiology is bacterial. However, no bacterial species have been consistently isolated from CARP patients. The prevailing theory of the past was that CARP was an abnormal host response to the fungus Malassezia furfur. Inconsistent detection of the fungus in skin scrapings, as well as persistence of the skin lesions after fungal clearance with antifungal therapy, has debunked this theory. An underlying disorder of keratinization resulting in hyperproliferation also has been suggested given reports of familial CARP and electron microscopy studies demonstrating focal-enhanced expression of keratin-16 in the stratum granulosom.⁵ Other theories include a cutaneous response to underlying endocrinopathies, ultraviolet light, and localized amyloidosis.¹
 

Diagnosis and differential

CARP is poorly recognized by clinicians and frequently initially misdiagnosed due to its similar appearance to other disorders, most commonly tinea versicolor and acanthosis nigricans. Davis et al. proposed criteria for diagnosis of CARP requiring 1) presence of scaly, reticulated and papillomatous brown macules and patches; 2) distribution over the upper trunk and neck; 3) negative fungal staining of scales; 4) no improvement following antifungal treatment; and 5) improvement following minocycline.²

Tinea versicolor may appear similar to CARP, but unlike CARP, will respond to antifungal treatment and may demonstrate hyphae and yeast on KOH preparation. Acanthosis nigricans and CARP both may present with velvety, hyperpigmented plaques in individuals of obese habitus or with insulin resistance, but peripheral reticulation will be absent in acanthosis nigricans. However, acanthosis nigricans and CARP may coexist, and this coexistence is not uncommonly seen in individuals with obesity and/or insulin resistance. Darier’s disease may look similar to cases of CARP without pigmentary change, but it often will have accompanying nail changes. Macular or lichen amyloidosis may present with pruritic brown macules or papules, but skin biopsy will have positive amyloid staining. The use of 70% alcohol swabbing to diagnose terra firma-forme dermatosis, with lesions disappearing with swabbing, is classic and used to differentiate it from CARP. Other conditions to consider include seborrheic dermatitis, epidermal nevi, verruca plana, epidermodysplasia verruciformis, and acne vulgaris.^1,2,4
 

Treatment

Minocycline is the first-line treatment for CARP: 80% of patients may have complete resolution with minocycline, while the remainder experience at least 50% clearance of skin lesions.² However, recurrence after stopping minocycline treatment is not uncommon. The mechanism by which minocycline works is unknown. Second-line treatment for those who cannot tolerate minocycline are macrolide antibiotics.⁶ Other treatment options with reported success include oral isotretinoin and topical retinoids, including tretinoin gel and tazarotene cream.^3,7 Appropriate strength topical corticosteroids may be used for pruritus.

Ms. Han is a medical student at the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego, as well as the vice chair of the department of dermatology and a professor of dermatology and pediatrics at UC San Diego. They report having no conflicts of interest or financial disclosures. Email them at [email protected].

References

1. Clin Cosmet Investig Dermatol. 2016 Aug 25;9:217-23.

2. Br J Dermatol. 2006 Feb;154(2):287-93.

3. Arch Dermatol. 2012 Apr;148(4):505-8.

4. J Am Acad Dermatol. 2003 Dec;49(6):1182-4.

5. Arch Dermatol. 2002 Feb;138(2):276-7.

6. J Am Acad Dermatol. 2001;44(4):652-5.

7. Am J Clin Dermatol. 2006;7(5):305-13.
 

 

Confluent and reticulated papillomatosis of Gougerot and Carteaud, also known as Gougerot-Carteaud syndrome, is an uncommon skin disorder of young individuals characterized by hyperkeratotic or verrucous brown papules or plaques that coalesce centrally and by a reticulated pattern peripherally. It was first described by two French dermatologists, Gougerot and Carteaud, in 1927.¹ Initially, the distinct entity of CARP was contested, with some dermatologists believing it to be a variant of acanthosis nigricans. However, CARP is now recognized as a distinct, though rare, dermatosis.

Dr. Lawrence F. Eichenfield

CARP commonly affects teens and young adults, with a mean age of onset of 15 years and without gender predilection.²The most common skin findings of CARP are somewhat verrucous or slightly hyperkeratotic brown papules a few millimeters in diameter. They are closely set together to form plaques in the center of the involved area, while those on the periphery of the involved area form a characteristic reticulated pattern. Papules are often scaly, although verrucous papules, especially those found in intertriginous areas, may develop a velvety appearance. Macules and patches may be present as well. The most common areas of involvement include the central chest and back with lesions extending in a rhomboidal fashion superoinferiorly, as well as the neck and axillae.¹ Uncommonly, pubic and facial skin may be affected.² Skin lesions are frequently hyperpigmented; however, cases of hypopigmented variants have been reported in darker-skinned individuals, although these cases have often been misdiagnosed as tinea versicolor.³ The majority of patients are asymptomatic, although some report mild pruritus. Care often is sought for cosmetic concerns.

Histopathology reveals findings similar to those that may be found in acanthosis nigricans and epidermal nevi. Classic characteristics of CARP include hyperkeratosis, papillomatosis, increased basal melanin pigmentation, and mild acanthosis. Occasionally, there may be perivascular lymphocytic infiltrates in the superficial dermis.^3,4

The etiology of CARP is unknown. CARP’s resolution in response to antibiotics and the isolation of two bacterial actinomycetes, Rhodococcus and Dietzia papillomatosis, from skin scrapings of CARP patients have led some to believe that its etiology is bacterial. However, no bacterial species have been consistently isolated from CARP patients. The prevailing theory of the past was that CARP was an abnormal host response to the fungus Malassezia furfur. Inconsistent detection of the fungus in skin scrapings, as well as persistence of the skin lesions after fungal clearance with antifungal therapy, has debunked this theory. An underlying disorder of keratinization resulting in hyperproliferation also has been suggested given reports of familial CARP and electron microscopy studies demonstrating focal-enhanced expression of keratin-16 in the stratum granulosom.⁵ Other theories include a cutaneous response to underlying endocrinopathies, ultraviolet light, and localized amyloidosis.¹
 

Diagnosis and differential

CARP is poorly recognized by clinicians and frequently initially misdiagnosed due to its similar appearance to other disorders, most commonly tinea versicolor and acanthosis nigricans. Davis et al. proposed criteria for diagnosis of CARP requiring 1) presence of scaly, reticulated and papillomatous brown macules and patches; 2) distribution over the upper trunk and neck; 3) negative fungal staining of scales; 4) no improvement following antifungal treatment; and 5) improvement following minocycline.²

Tinea versicolor may appear similar to CARP, but unlike CARP, will respond to antifungal treatment and may demonstrate hyphae and yeast on KOH preparation. Acanthosis nigricans and CARP both may present with velvety, hyperpigmented plaques in individuals of obese habitus or with insulin resistance, but peripheral reticulation will be absent in acanthosis nigricans. However, acanthosis nigricans and CARP may coexist, and this coexistence is not uncommonly seen in individuals with obesity and/or insulin resistance. Darier’s disease may look similar to cases of CARP without pigmentary change, but it often will have accompanying nail changes. Macular or lichen amyloidosis may present with pruritic brown macules or papules, but skin biopsy will have positive amyloid staining. The use of 70% alcohol swabbing to diagnose terra firma-forme dermatosis, with lesions disappearing with swabbing, is classic and used to differentiate it from CARP. Other conditions to consider include seborrheic dermatitis, epidermal nevi, verruca plana, epidermodysplasia verruciformis, and acne vulgaris.^1,2,4
 

Treatment

Minocycline is the first-line treatment for CARP: 80% of patients may have complete resolution with minocycline, while the remainder experience at least 50% clearance of skin lesions.² However, recurrence after stopping minocycline treatment is not uncommon. The mechanism by which minocycline works is unknown. Second-line treatment for those who cannot tolerate minocycline are macrolide antibiotics.⁶ Other treatment options with reported success include oral isotretinoin and topical retinoids, including tretinoin gel and tazarotene cream.^3,7 Appropriate strength topical corticosteroids may be used for pruritus.

Ms. Han is a medical student at the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego, as well as the vice chair of the department of dermatology and a professor of dermatology and pediatrics at UC San Diego. They report having no conflicts of interest or financial disclosures. Email them at [email protected].

References

1. Clin Cosmet Investig Dermatol. 2016 Aug 25;9:217-23.

2. Br J Dermatol. 2006 Feb;154(2):287-93.

3. Arch Dermatol. 2012 Apr;148(4):505-8.

4. J Am Acad Dermatol. 2003 Dec;49(6):1182-4.

5. Arch Dermatol. 2002 Feb;138(2):276-7.

6. J Am Acad Dermatol. 2001;44(4):652-5.

7. Am J Clin Dermatol. 2006;7(5):305-13.