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Linear and Serpiginous Lesions
Chapter 17
Linear and Serpiginous Lesions Epidermal Nevus Syndrome Nevus unius lateralis Systemized epidermal nevus
L
inear and serpiginous presentations of skin disease represent distinctive patterns that are so unique that a diagnosis can often be made without a biopsy or any further testing. In this short chapter, not all linear diseases may be discussed because many rare congenital disorders may present with linear configurations but would be beyond the scope of this practical discourse. It is also important to note that linear and serpiginous patterns should not be confused with sporotrichoid patterns of infection, which appear linear due to lymphatic spread. The sporotrichoid pattern is covered in Chapter 18.
What medications do you take?
IMPORTANT HISTORY QUESTIONS
What is the distribution of the lesions?
Were the lesions present at birth or shortly after birth?
This is an important question because many linear conditions are congenital in nature and were present in the neonatal period (e.g., linear epidermal nevus, incontinentia pigmenti). Is there a family history of a similar lesion?
In the appropriate clinical circumstances, an affirmative answer would support the diagnosis of incontinentia pigmenti, an X-linked dominant genetic disorder. However, it is important to note that a negative response does not exclude incontinentia pigmenti because spontaneous mutations are common. How long have the lesions been present?
Some lesions persist for life (e.g., linear epidermal nevus), whereas others have a finite duration (e.g., lichen striatus).
This is an important question in patients for whom linear bleomycin-induced erythema or hyperpigmentation is suspected. Is there a history of recent travel?
This question is designed to include or exclude cutaneous larva migrans. This condition is especially prevalent in the southeast United States and in other subtropical or tropical climates.
IMPORTANT PHYSICAL FINDINGS A distribution that follows the lines of Blaschko supports assessment of a linear epidermal nevus or other epithelial hamartoma, whereas cutaneous larva migrans is more common on acral skin. What color are the lesions?
Linear epidermal nevi are often yellow-brown or brown, flagellate erythema due to bleomycin or cutaneous larva migrans is erythematous, and linear morphea may be white or yellow-white. Do any lesions demonstrate vesicles or blisters?
Vesiculobullous lesions may be seen in incontinentia pigmenti or cutaneous larva migrans. Although not discussed in this chapter, allergic contact dermatitis may also demonstrate linear vesiculobullous lesions. Does the lesion demonstrate induration on palpation?
Linear morphea is characterized by marked induration due to thickening of the collagen.
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Lichen Striatus ICD10 code L44.2 INTERNAL DISORDER
What Are the Lines of Blaschko?
There is no easy answer because the lines of Blaschko do not conform to any known anatomic features. Instead, the lines of Blaschko are somewhat circularly defined as lines that congenital linear abnormalities follow. It has been suggested that the lines are due to cutaneous mosaicism of different clones of cells.
box), with some cases manifesting more than one parallel line of involvement (Fig. 17.3). • Typically, the condition is asymptomatic, but it may be pruritic in about 10% of cases. • Rare patients may demonstrate extension to a contiguous fingernail or toenail, with onychodystrophy manifesting as thinning, splitting, longitudinal ridging, or onycholysis (Fig. 17.4).
Pathogenesis
Diagnosis
Lichen striatus is an uncommon, self-limited dermatosis, of unknown cause; it affects mostly children. Some studies have suggested a more frequent personal or familial atopic diathesis in affected patients.
• The history and clinical appearance are usually diagnostic. • A skin biopsy is not usually required, but, if the presentation is atypical, a biopsy may be performed. The histologic findings will support the diagnosis, but exclusive pathognomonic findings do not exist.
Clinical Features • Some studies have reported a slight female preponderance, whereas others studies have reported that both genders are equally affected. • Most cases occur in preschool children, with a mean age of 3 years, but the condition can also occur in adolescents and young adults as well. • A unilateral (and rarely bilateral) eruption affects the lower limbs (one-third of cases), followed by the upper limbs, trunk and, rarely, the face (~10%). • The eruption begins as discrete skin-colored, pink, or red papules (Fig. 17.1), with variable overlying scale. In darker skin types, the condition may appear hyperpigmented (Fig. 17.2) or hypopigmented. • Less often, the condition may resemble lichen planus or psoriasis. • Lesion are grouped as continuous or discontinuous lines that generally follow the lines of Blaschko (see
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Treatment • Reassurance is usually all that is necessary because the condition is self-limited and typically disappears in weeks or months (rarely years), without permanent sequelae. • Weak to midstrength topical steroids may be used for pruritus.
Clinical Course The mean duration of disease is 6 to 9 months; however, rare patients may have lesions for up to 3 years. Hypopigmentation may persist for months, even after the lesion resolves. Rare patients may suffer a relapse or even multiple relapses.
Chapter 17 Linear and Serpiginous Lesions 291
Fig. 17.1.
Patient with early lesions of lichen striatus composed of red linear papules. (From the William Weston Collection, Aurora, CO.)
Fig. 17.2.
Fig. 17.3.
Fig. 17.4.
Patient with hypopigmented lichen striatus with two parallel linear lesions following the lines of Blaschko.
Patient with linear lesions of lichen striatus on the upper thigh demonstrating subtle hyperpigmentation.
Patient with unusually indurated red linear papules, with associated nail dystrophy. (From the William Weston Collection, Aurora, CO.)
Bleomycin-Induced Flagellate Erythema and Hyperpigmentation ICD10 code Y43.1
Pathogenesis Bleomycin is a chemotherapeutic agent that produces a distinct skin eruption with linear erythema that transitions into linear hyperpigmentation. It is most commonly seen at higher cumulative doses, usually in the range of 90 to 285 mg; however, some patients may develop this reaction with the first dose. There is no clear consensus as to how often this adverse reaction transpires, with a reported range in the literature of 6% to 66% of patients who have received the drug. The mechanism whereby the linear lesions are produced is uncertain, but it has been postulated that it is related to scratching because affected patients report pruritus. Attempts to induce lesions with superficial trauma have not always been successful.
Clinical Features • Lesions usually develop within hours to weeks after taking bleomycin. • Primary lesions present as linear erythema, with pruritus (Fig. 17.5). • The lesions transition, usually over days or weeks, into linear hyperpigmented lesions, with some patients having transitional lesions that may appear violaceous (Figs. 17.6 and 17.7). • Some lesions may demonstrate variable scale. • Other less distinctive lesions may include erythema over pressure points, which can also transition into hyperpigmentation, hyperpigmentation of palmar
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DRUG-INDUCED
and flexural creases, and hyperpigmentation of striae distensae (stretch marks).
Diagnosis • Early lesions may be difficult to differentiate from dermatographism, but dermatographism usually resolves within hours, whereas the flagellate erythema of bleomycin persists for an extended duration. • The presence of linear erythema with pruritus and/ or hyperpigmentation in a patient receiving bleomycin is a drug eruption, unless proven otherwise. • Biopsy typically reveals nonspecific findings and is usually not needed to establish the diagnosis.
Treatment • The pruritus can be managed with an antihistamine and/or medium-potency topical corticosteroid, such as triamcinolone. Sedating antihistamines, such as diphenhydramine, are useful at bedtime. • No treatment is reasonable if the patient is comfortable and unconcerned.
Clinical Course This condition represents a self-limited drug reaction. Although the erythema subsides within days, the hyperpigmentation may persist for weeks or months before gradually fading.
Chapter 17 Linear and Serpiginous Lesions 293
Fig. 17.5.
Fig. 17.6.
Patient with characteristic flagellate areas of a pruritic erythema produced by bleomycin.
Patient with intermediate lesions induced by bleomycin, with variable erythema, hyperpigmentation, and a focally violaceous hue.
Fig. 17.7.
Patient with typical flagellate hyperpigmentation weeks after receiving bleomycin. Note that there is also focal subtle scaling.
Linear Epidermal Nevus ICD10 code Q82.3 LINEAR DISORDER
Epidermal Nevus Syndrome
Epidermal nevus syndrome consists of an epidermal nevus (usually extensive), with associated skeletal, neurologic, ocular, and cardiac abnormalities. Central nervous system abnormalities are more common when the epidermal nevus involves the head and neck.
Linear Malformations of Childhood: Differential Diagnosis • • • • • • •
Goltz syndrome Linear adnexal tumors Linear Darier disease Linear epidermal nevus Linear porokeratosis Nevus comedonicus Nevus sebaceus
Pathogenesis Linear epidermal nevus (epidermal nevus) is a localized genetic disorder (OMIM 162900) that is characterized as a localized overgrowth of epithelium in a pattern that follows the lines of Blaschko. About one-third of those with epidermal nevi have FGFR3 mutations that are also found in some seborrheic keratoses.
Clinical Features • Epidermal nevi are usually present at birth or shortly after birth, but rare cases may present in early adulthood. • The lesions may involve any part of the skin. • Once a lesion develops, it may gradually enlarge over years. • The primary lesion is a yellow-brown to brown aggregate of papules, with variable scale and verrucous features that follow the lines of Blaschko. So-called skip areas are often present (Figs. 17.8 and 17.9). • Single or multiple lesions may be present. Sometimes, the process involves half of the body (nevus unius lateralis; Fig. 17.10) or nearly the entire body (systemized epidermal nevus). • Rare cases may involve the oral mucosa (Fig. 17.11).
Diagnosis • In most cases, the clinical presentation is diagnostic. Other congenital linear malformations can be in the clinical differential diagnosis but are not covered in this text (see box). • In problematic cases, the lesion may be biopsied with a 3- to 6-mm punch biopsy. Shave biopsies are not adequate to differentiate epidermal nevi from some of the other clinical possibilities listed in the box.
Treatment • Because the condition is benign, treatment is not required. • Surgical excision is a consideration for select lesions. However, the cost, complications, and cosmetic appearance of the scar must be considered. • Laser ablation is a therapeutic option in some cases. • Topical therapies that may improve the clinical appearance include ammonium lactate, 12%; calcipotriene ointment or cream, 0.005%; and tazarotene cream, 0.1%.
Clinical Course Linear epidermal nevi may remain stable or may enlarge gradually, over a period of years or decades.
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Chapter 17 Linear and Serpiginous Lesions 295
Fig. 17.8.
Subtle light brown linear epidermal nevus in a young child that follows the lines of Blaschko.
Fig. 17.9.
Fig. 17.10.
Fig. 17.11.
Extensive dark brown papillomatous epidermal nevus involving half of the body in a child. This variant is often termed nevus unius lateralis.
Yellow-brown linear epidermal nevus in a woman. (From the Fitzsimons Army Medical Center Collection, Aurora, CO.)
Close-up of a patient with a markedly papillomatous linear epidermal nevus of the tongue.
Linear Morphea ICD10 code L94.0 INTERNAL DISORDER
Pathogenesis Morphea, also known as localized scleroderma, is a disorder characterized by thickening of the collagen in the dermis and, to a lesser degree, in the subcutaneous tissue and rarely into the fascia. The pathogenesis is not understood; however, there is evidence to support that this is a limited form of an autoimmune connective tissue disease. Some cases in Europe have been associated with infection by Borrelia spp. There are several clinical presentations of morphea, including linear presentations that are discussed here. Linear presentations account for about 50% or more of childhood cases and 15% of adult cases. Some cases of linear morphea may demonstrate clinical and histologic features of overlying lichen sclerosus et atrophicus (LS&A); the relationship between these two disorders is not clear.
Clinical Features • Studies have reported a modest female preponderance in morphea, with most cases occurring in children, adolescents, and young adults, although persons of any age may be affected. • Lesions are usually linear, solitary, and unilateral, but multiple lesions can occur (Figs. 17.12–17.14). • Lesions are usually asymptomatic, but some patients may manifest pruritus, or even pain or discomfort, particularly in lesions that cross joint spaces. • The primary lesion is usually a skin-colored to violaceous area of induration. Many lesions demonstrate a violaceous color at the periphery. • As lesions evolve, the color may vary from violaceous to hyperpigmented to white or yellow-white. Often, more than one color may be present in the same lesion. • Established lesions can manifest epidermal atrophy and may be shiny, with fine wrinkling.
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• Lesions that cross a joint may impair function and produce contractures (see Fig. 17.14).
Diagnosis • The diagnosis is usually established on clinical grounds, based on the presence of a linear lesion with marked induration on palpation. White lesions may be difficult to differentiate from LS&A. • In problematic cases, a 4- to 6-mm punch or incisional biopsy, which includes subcutaneous tissue, will generally be diagnostic, as long as the clinical suspicion of morphea is communicated to the pathologist or dermatopathologist. • Laboratory tests that may be helpful include a complete blood count (CBC; often a peripheral eosinophilia may be present) and a screening antinuclear antibody (ANA) test, positive in a low titer in about 50% of cases.
Treatment • The treatment used is dependent on the patient’s age, site and extent of involvement, and degree of any functional impairment (e.g., involvement over joints). • Small or limited lesions without any functional impairment are best treated with topical calcipotriene, 0.005% ointment, bid for 2 to 4 months, with or without occlusion, or tacrolimus, 0.1% bid for 2 to 4 months, with or without occlusion. • Larger lesions or lesions with functional impairment are best treated with phototherapy (narrow-band ultraviolet B [UVB] or UVA-1), systemic corticosteroids, or methotrexate.
Clinical Course The clinical course in any individual patient may not be predicted reliably, but about 50% of patients will demonstrate spontaneous remission within 5 years.
Chapter 17 Linear and Serpiginous Lesions 297
Fig. 17.12.
Linear morphea of the back of the neck, with white lichen sclerosus et atrophicus–like hypopigmentation.
Fig. 17.14.
Fig. 17.13.
Patient with hyperpigmentation and hypopigmentation in linear morphea of the upper thigh and lower leg. (From the William Weston Collection, Aurora, CO.)
Patient with end-stage linear morphea, with shiny epidermal atrophy that has produced a contracture across the hand. (From the Joanna Burch Collection, Aurora, CO.)
Cutaneous Larva Migrans ICD10 code B76.9 PARASITE ETIOLOGY
Pathogenesis
Diagnosis
Cutaneous larva migrans is a so-called creeping eruption that occurs when human skin comes into contact with soil containing viable larva of animal hookworms. Ancylostoma braziliense (the cat and dog hookworm) accounts for 95% of cases. In the United States, the highest incidence is seen in Florida and Georgia, where humans have frequent contact with moist sandy soil. Sandboxes are notorious sites of contact for young children, and beaches are common locations for contact for children and adults. The disease is also an occupational hazard for individuals who crawl under houses (e.g., plumbers). The disease is limited to the skin because the larval worms do not have the proper collagenase enzymes to penetrate into the deeper zones of human skin.
• The clinical appearance and migratory nature of the burrow (creeping) is distinctive, facilitating diagnosis. • Biopsy of a burrow demonstrates an eosinophilic infiltrate and a burrow just above the basement membrane zone, but larva are rarely seen on biopsy.
Clinical Features • Common sites of involvement include the dorsal feet and interdigital spaces between the toes. • A pruritic papule or dermatitis develops at the site of penetration within one hour. • After a few days or weeks, a linear, serpiginous, slightly indurated, erythematous tract develops as the larva migrates. Usually, the tract is 2 to 4 mm wide, with some lesions being bullous (Figs. 17.15–17.18). The number of burrows may vary from 1 to a record of 2100 burrows in one patient. • Rarely, larvae may track down a hair follicle and produce follicular lesions. • Larvae migrate several millimeters a day. Larvae are 1 to 2 cm ahead of the perceptible end of the lesion. • Additional manifestations include peripheral eosinophilia and, rarely, Loeffler syndrome. • In rare cases, a secondary bacterial infection, including streptococcal cellulitis, may develop.
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Treatment • Treatment of choice for limited disease is the application of 10% to 15% liquid thiabendazole suspension or 10% to 15% topical thiabendazole cream (prepared by a compounding pharmacy), applied qid for 1 week (98% success rate in one study). • In patients with extensive lesions or lesions on the thick skin of the sole, and/or who have failed topical therapy, oral ivermectin is the treatment of choice. Cure rates have varied from 77% to 100% with a single 12-mg oral dose. Other studies have used 200 mg/kg for 3 to 7 days. • Other oral treatment options include albendazole (400 mg qd in a 1-, 3-, or 5-day regimen) and thiabendazole (50 mg/kg per day in a single dose for 2–4 days), with a 99% cure rate in one study. Thiabendazole, although highly effective, is less well tolerated than ivermectin or albendazole and should be utilized only when the other options are not available. • Older references have indicated liquid nitrogen cryotherapy as a treatment, to be applied to the advancing edge of the burrow, but because the organism is always present before the visible body reaction, this therapy has a high failure rate, and we do not recommend its use.
Clinical Course The disease is self-limited, and most larvae die within 2 to 8 weeks—81% of all larvae are dead at 4 weeks. Rare larvae may persist up to 1 year or longer.
Chapter 17 Linear and Serpiginous Lesions 299
Fig. 17.15.
Patient with linear larval burrow on the toe and top of the foot. Note the linear blister at the leading edge. (From the Fitzsimons Army Medical Center Collection, Aurora, CO.)
Fig. 17.16.
Fig. 17.17.
Fig. 17.18.
Child with numerous older burrows present for 4 weeks that had been treated as a dermatitis by both the emergency room clinician and her pediatrician. (From the Fitzsimons Army Medical Center Collection, Aurora, CO.)
Patient with convoluted linear burrows on the bottom of the foot. (From the Fitzsimons Army Medical Center Collection, Aurora, CO.)
Patient with atypical bullous lesion on the instep of the foot. Careful observation of the lesion demonstrates the serpiginous burrow within the blister.
300 Chapter 17 Linear and Serpiginous Lesions
References Lichen Striatus
1. Kim M, Jung HY, Eun YS, et al. Nail lichen striatus: report of seven cases and review of the literature. Int J Dermatol. 2015;54:1255-1260. 2. Patrizi A, Neri I, Fiorentini C, et al. Lichen striatus: clinical and laboratory features of 115 children. Pediatr Dermatol. 2004;21:197-204.
Bleomycin-Induced Erythema and Hyperpigmentation
1. Khmamouchne MR, Debbagh A, Mahfoud T, et al. Flagellate erythema secondary to bleomycin: a new case report and review of the literature. J Drugs Dermatol. 2014;13:983-984. 2. Lee HY, Lim KH, Ryo Y, Song SY. Bleomycin-induced flagellate erythema: a case report and review of the literature. Oncol Lett. 2014;8:933-935.
Linear Epidermal Nevus
1. Chatproedprai S, Wananukul S, Prasarnnaem T, Noppakun N. Epidermal nevus syndrome. Int J Dermatol. 2007;46:858-860.
2. Hafner C, Hartmann A, Vogt T. FGFR3 mutations in epidermal nevi and seborrheic keratoses: lessons from urothelium and skin. J Invest Dermatol. 2007;127:1572-1573.
Linear Morphea
1. Mazori DR, Wright NA, Patel M, et al. Characteristics and treatment of adult-onset linear morphea: a retrospective cohort study of 61 patients in 3 tertiary care centers. J Am Acad Dermatol. 2016;74:577-579. 2. Zwischenberger BA, Jacobe HT. A systematic review of morphea treatments and therapeutic algorithm. J Am Acad Dermatol. 2011;65:925-941.
Cutaneous Larva Migrans
1. Prickett KA, Ferringer TC. What’s eating you? Cutaneous larva migrans. Cutis. 2015;95:126-128. 2. Richey TK, Gentry RH, Fitzpatrick JE, et al. Persistent cutaneous larva migrans due to Ancylostoma species. South Med J. 1996;89:609-611.
Linear and Serpiginous Lesions Epidermal Nevus Syndrome Nevus unius lateralis Systemized epidermal nevus
L
inear and serpiginous presentations of skin disease represent distinctive patterns that are so unique that a diagnosis can often be made without a biopsy or any further testing. In this short chapter, not all linear diseases may be discussed because many rare congenital disorders may present with linear configurations but would be beyond the scope of this practical discourse. It is also important to note that linear and serpiginous patterns should not be confused with sporotrichoid patterns of infection, which appear linear due to lymphatic spread. The sporotrichoid pattern is covered in Chapter 18.
What medications do you take?
IMPORTANT HISTORY QUESTIONS
What is the distribution of the lesions?
Were the lesions present at birth or shortly after birth?
This is an important question because many linear conditions are congenital in nature and were present in the neonatal period (e.g., linear epidermal nevus, incontinentia pigmenti). Is there a family history of a similar lesion?
In the appropriate clinical circumstances, an affirmative answer would support the diagnosis of incontinentia pigmenti, an X-linked dominant genetic disorder. However, it is important to note that a negative response does not exclude incontinentia pigmenti because spontaneous mutations are common. How long have the lesions been present?
Some lesions persist for life (e.g., linear epidermal nevus), whereas others have a finite duration (e.g., lichen striatus).
This is an important question in patients for whom linear bleomycin-induced erythema or hyperpigmentation is suspected. Is there a history of recent travel?
This question is designed to include or exclude cutaneous larva migrans. This condition is especially prevalent in the southeast United States and in other subtropical or tropical climates.
IMPORTANT PHYSICAL FINDINGS A distribution that follows the lines of Blaschko supports assessment of a linear epidermal nevus or other epithelial hamartoma, whereas cutaneous larva migrans is more common on acral skin. What color are the lesions?
Linear epidermal nevi are often yellow-brown or brown, flagellate erythema due to bleomycin or cutaneous larva migrans is erythematous, and linear morphea may be white or yellow-white. Do any lesions demonstrate vesicles or blisters?
Vesiculobullous lesions may be seen in incontinentia pigmenti or cutaneous larva migrans. Although not discussed in this chapter, allergic contact dermatitis may also demonstrate linear vesiculobullous lesions. Does the lesion demonstrate induration on palpation?
Linear morphea is characterized by marked induration due to thickening of the collagen.
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Lichen Striatus ICD10 code L44.2 INTERNAL DISORDER
What Are the Lines of Blaschko?
There is no easy answer because the lines of Blaschko do not conform to any known anatomic features. Instead, the lines of Blaschko are somewhat circularly defined as lines that congenital linear abnormalities follow. It has been suggested that the lines are due to cutaneous mosaicism of different clones of cells.
box), with some cases manifesting more than one parallel line of involvement (Fig. 17.3). • Typically, the condition is asymptomatic, but it may be pruritic in about 10% of cases. • Rare patients may demonstrate extension to a contiguous fingernail or toenail, with onychodystrophy manifesting as thinning, splitting, longitudinal ridging, or onycholysis (Fig. 17.4).
Pathogenesis
Diagnosis
Lichen striatus is an uncommon, self-limited dermatosis, of unknown cause; it affects mostly children. Some studies have suggested a more frequent personal or familial atopic diathesis in affected patients.
• The history and clinical appearance are usually diagnostic. • A skin biopsy is not usually required, but, if the presentation is atypical, a biopsy may be performed. The histologic findings will support the diagnosis, but exclusive pathognomonic findings do not exist.
Clinical Features • Some studies have reported a slight female preponderance, whereas others studies have reported that both genders are equally affected. • Most cases occur in preschool children, with a mean age of 3 years, but the condition can also occur in adolescents and young adults as well. • A unilateral (and rarely bilateral) eruption affects the lower limbs (one-third of cases), followed by the upper limbs, trunk and, rarely, the face (~10%). • The eruption begins as discrete skin-colored, pink, or red papules (Fig. 17.1), with variable overlying scale. In darker skin types, the condition may appear hyperpigmented (Fig. 17.2) or hypopigmented. • Less often, the condition may resemble lichen planus or psoriasis. • Lesion are grouped as continuous or discontinuous lines that generally follow the lines of Blaschko (see
290
Treatment • Reassurance is usually all that is necessary because the condition is self-limited and typically disappears in weeks or months (rarely years), without permanent sequelae. • Weak to midstrength topical steroids may be used for pruritus.
Clinical Course The mean duration of disease is 6 to 9 months; however, rare patients may have lesions for up to 3 years. Hypopigmentation may persist for months, even after the lesion resolves. Rare patients may suffer a relapse or even multiple relapses.
Chapter 17 Linear and Serpiginous Lesions 291
Fig. 17.1.
Patient with early lesions of lichen striatus composed of red linear papules. (From the William Weston Collection, Aurora, CO.)
Fig. 17.2.
Fig. 17.3.
Fig. 17.4.
Patient with hypopigmented lichen striatus with two parallel linear lesions following the lines of Blaschko.
Patient with linear lesions of lichen striatus on the upper thigh demonstrating subtle hyperpigmentation.
Patient with unusually indurated red linear papules, with associated nail dystrophy. (From the William Weston Collection, Aurora, CO.)
Bleomycin-Induced Flagellate Erythema and Hyperpigmentation ICD10 code Y43.1
Pathogenesis Bleomycin is a chemotherapeutic agent that produces a distinct skin eruption with linear erythema that transitions into linear hyperpigmentation. It is most commonly seen at higher cumulative doses, usually in the range of 90 to 285 mg; however, some patients may develop this reaction with the first dose. There is no clear consensus as to how often this adverse reaction transpires, with a reported range in the literature of 6% to 66% of patients who have received the drug. The mechanism whereby the linear lesions are produced is uncertain, but it has been postulated that it is related to scratching because affected patients report pruritus. Attempts to induce lesions with superficial trauma have not always been successful.
Clinical Features • Lesions usually develop within hours to weeks after taking bleomycin. • Primary lesions present as linear erythema, with pruritus (Fig. 17.5). • The lesions transition, usually over days or weeks, into linear hyperpigmented lesions, with some patients having transitional lesions that may appear violaceous (Figs. 17.6 and 17.7). • Some lesions may demonstrate variable scale. • Other less distinctive lesions may include erythema over pressure points, which can also transition into hyperpigmentation, hyperpigmentation of palmar
292
DRUG-INDUCED
and flexural creases, and hyperpigmentation of striae distensae (stretch marks).
Diagnosis • Early lesions may be difficult to differentiate from dermatographism, but dermatographism usually resolves within hours, whereas the flagellate erythema of bleomycin persists for an extended duration. • The presence of linear erythema with pruritus and/ or hyperpigmentation in a patient receiving bleomycin is a drug eruption, unless proven otherwise. • Biopsy typically reveals nonspecific findings and is usually not needed to establish the diagnosis.
Treatment • The pruritus can be managed with an antihistamine and/or medium-potency topical corticosteroid, such as triamcinolone. Sedating antihistamines, such as diphenhydramine, are useful at bedtime. • No treatment is reasonable if the patient is comfortable and unconcerned.
Clinical Course This condition represents a self-limited drug reaction. Although the erythema subsides within days, the hyperpigmentation may persist for weeks or months before gradually fading.
Chapter 17 Linear and Serpiginous Lesions 293
Fig. 17.5.
Fig. 17.6.
Patient with characteristic flagellate areas of a pruritic erythema produced by bleomycin.
Patient with intermediate lesions induced by bleomycin, with variable erythema, hyperpigmentation, and a focally violaceous hue.
Fig. 17.7.
Patient with typical flagellate hyperpigmentation weeks after receiving bleomycin. Note that there is also focal subtle scaling.
Linear Epidermal Nevus ICD10 code Q82.3 LINEAR DISORDER
Epidermal Nevus Syndrome
Epidermal nevus syndrome consists of an epidermal nevus (usually extensive), with associated skeletal, neurologic, ocular, and cardiac abnormalities. Central nervous system abnormalities are more common when the epidermal nevus involves the head and neck.
Linear Malformations of Childhood: Differential Diagnosis • • • • • • •
Goltz syndrome Linear adnexal tumors Linear Darier disease Linear epidermal nevus Linear porokeratosis Nevus comedonicus Nevus sebaceus
Pathogenesis Linear epidermal nevus (epidermal nevus) is a localized genetic disorder (OMIM 162900) that is characterized as a localized overgrowth of epithelium in a pattern that follows the lines of Blaschko. About one-third of those with epidermal nevi have FGFR3 mutations that are also found in some seborrheic keratoses.
Clinical Features • Epidermal nevi are usually present at birth or shortly after birth, but rare cases may present in early adulthood. • The lesions may involve any part of the skin. • Once a lesion develops, it may gradually enlarge over years. • The primary lesion is a yellow-brown to brown aggregate of papules, with variable scale and verrucous features that follow the lines of Blaschko. So-called skip areas are often present (Figs. 17.8 and 17.9). • Single or multiple lesions may be present. Sometimes, the process involves half of the body (nevus unius lateralis; Fig. 17.10) or nearly the entire body (systemized epidermal nevus). • Rare cases may involve the oral mucosa (Fig. 17.11).
Diagnosis • In most cases, the clinical presentation is diagnostic. Other congenital linear malformations can be in the clinical differential diagnosis but are not covered in this text (see box). • In problematic cases, the lesion may be biopsied with a 3- to 6-mm punch biopsy. Shave biopsies are not adequate to differentiate epidermal nevi from some of the other clinical possibilities listed in the box.
Treatment • Because the condition is benign, treatment is not required. • Surgical excision is a consideration for select lesions. However, the cost, complications, and cosmetic appearance of the scar must be considered. • Laser ablation is a therapeutic option in some cases. • Topical therapies that may improve the clinical appearance include ammonium lactate, 12%; calcipotriene ointment or cream, 0.005%; and tazarotene cream, 0.1%.
Clinical Course Linear epidermal nevi may remain stable or may enlarge gradually, over a period of years or decades.
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Chapter 17 Linear and Serpiginous Lesions 295
Fig. 17.8.
Subtle light brown linear epidermal nevus in a young child that follows the lines of Blaschko.
Fig. 17.9.
Fig. 17.10.
Fig. 17.11.
Extensive dark brown papillomatous epidermal nevus involving half of the body in a child. This variant is often termed nevus unius lateralis.
Yellow-brown linear epidermal nevus in a woman. (From the Fitzsimons Army Medical Center Collection, Aurora, CO.)
Close-up of a patient with a markedly papillomatous linear epidermal nevus of the tongue.
Linear Morphea ICD10 code L94.0 INTERNAL DISORDER
Pathogenesis Morphea, also known as localized scleroderma, is a disorder characterized by thickening of the collagen in the dermis and, to a lesser degree, in the subcutaneous tissue and rarely into the fascia. The pathogenesis is not understood; however, there is evidence to support that this is a limited form of an autoimmune connective tissue disease. Some cases in Europe have been associated with infection by Borrelia spp. There are several clinical presentations of morphea, including linear presentations that are discussed here. Linear presentations account for about 50% or more of childhood cases and 15% of adult cases. Some cases of linear morphea may demonstrate clinical and histologic features of overlying lichen sclerosus et atrophicus (LS&A); the relationship between these two disorders is not clear.
Clinical Features • Studies have reported a modest female preponderance in morphea, with most cases occurring in children, adolescents, and young adults, although persons of any age may be affected. • Lesions are usually linear, solitary, and unilateral, but multiple lesions can occur (Figs. 17.12–17.14). • Lesions are usually asymptomatic, but some patients may manifest pruritus, or even pain or discomfort, particularly in lesions that cross joint spaces. • The primary lesion is usually a skin-colored to violaceous area of induration. Many lesions demonstrate a violaceous color at the periphery. • As lesions evolve, the color may vary from violaceous to hyperpigmented to white or yellow-white. Often, more than one color may be present in the same lesion. • Established lesions can manifest epidermal atrophy and may be shiny, with fine wrinkling.
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• Lesions that cross a joint may impair function and produce contractures (see Fig. 17.14).
Diagnosis • The diagnosis is usually established on clinical grounds, based on the presence of a linear lesion with marked induration on palpation. White lesions may be difficult to differentiate from LS&A. • In problematic cases, a 4- to 6-mm punch or incisional biopsy, which includes subcutaneous tissue, will generally be diagnostic, as long as the clinical suspicion of morphea is communicated to the pathologist or dermatopathologist. • Laboratory tests that may be helpful include a complete blood count (CBC; often a peripheral eosinophilia may be present) and a screening antinuclear antibody (ANA) test, positive in a low titer in about 50% of cases.
Treatment • The treatment used is dependent on the patient’s age, site and extent of involvement, and degree of any functional impairment (e.g., involvement over joints). • Small or limited lesions without any functional impairment are best treated with topical calcipotriene, 0.005% ointment, bid for 2 to 4 months, with or without occlusion, or tacrolimus, 0.1% bid for 2 to 4 months, with or without occlusion. • Larger lesions or lesions with functional impairment are best treated with phototherapy (narrow-band ultraviolet B [UVB] or UVA-1), systemic corticosteroids, or methotrexate.
Clinical Course The clinical course in any individual patient may not be predicted reliably, but about 50% of patients will demonstrate spontaneous remission within 5 years.
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Fig. 17.12.
Linear morphea of the back of the neck, with white lichen sclerosus et atrophicus–like hypopigmentation.
Fig. 17.14.
Fig. 17.13.
Patient with hyperpigmentation and hypopigmentation in linear morphea of the upper thigh and lower leg. (From the William Weston Collection, Aurora, CO.)
Patient with end-stage linear morphea, with shiny epidermal atrophy that has produced a contracture across the hand. (From the Joanna Burch Collection, Aurora, CO.)
Cutaneous Larva Migrans ICD10 code B76.9 PARASITE ETIOLOGY
Pathogenesis
Diagnosis
Cutaneous larva migrans is a so-called creeping eruption that occurs when human skin comes into contact with soil containing viable larva of animal hookworms. Ancylostoma braziliense (the cat and dog hookworm) accounts for 95% of cases. In the United States, the highest incidence is seen in Florida and Georgia, where humans have frequent contact with moist sandy soil. Sandboxes are notorious sites of contact for young children, and beaches are common locations for contact for children and adults. The disease is also an occupational hazard for individuals who crawl under houses (e.g., plumbers). The disease is limited to the skin because the larval worms do not have the proper collagenase enzymes to penetrate into the deeper zones of human skin.
• The clinical appearance and migratory nature of the burrow (creeping) is distinctive, facilitating diagnosis. • Biopsy of a burrow demonstrates an eosinophilic infiltrate and a burrow just above the basement membrane zone, but larva are rarely seen on biopsy.
Clinical Features • Common sites of involvement include the dorsal feet and interdigital spaces between the toes. • A pruritic papule or dermatitis develops at the site of penetration within one hour. • After a few days or weeks, a linear, serpiginous, slightly indurated, erythematous tract develops as the larva migrates. Usually, the tract is 2 to 4 mm wide, with some lesions being bullous (Figs. 17.15–17.18). The number of burrows may vary from 1 to a record of 2100 burrows in one patient. • Rarely, larvae may track down a hair follicle and produce follicular lesions. • Larvae migrate several millimeters a day. Larvae are 1 to 2 cm ahead of the perceptible end of the lesion. • Additional manifestations include peripheral eosinophilia and, rarely, Loeffler syndrome. • In rare cases, a secondary bacterial infection, including streptococcal cellulitis, may develop.
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Treatment • Treatment of choice for limited disease is the application of 10% to 15% liquid thiabendazole suspension or 10% to 15% topical thiabendazole cream (prepared by a compounding pharmacy), applied qid for 1 week (98% success rate in one study). • In patients with extensive lesions or lesions on the thick skin of the sole, and/or who have failed topical therapy, oral ivermectin is the treatment of choice. Cure rates have varied from 77% to 100% with a single 12-mg oral dose. Other studies have used 200 mg/kg for 3 to 7 days. • Other oral treatment options include albendazole (400 mg qd in a 1-, 3-, or 5-day regimen) and thiabendazole (50 mg/kg per day in a single dose for 2–4 days), with a 99% cure rate in one study. Thiabendazole, although highly effective, is less well tolerated than ivermectin or albendazole and should be utilized only when the other options are not available. • Older references have indicated liquid nitrogen cryotherapy as a treatment, to be applied to the advancing edge of the burrow, but because the organism is always present before the visible body reaction, this therapy has a high failure rate, and we do not recommend its use.
Clinical Course The disease is self-limited, and most larvae die within 2 to 8 weeks—81% of all larvae are dead at 4 weeks. Rare larvae may persist up to 1 year or longer.
Chapter 17 Linear and Serpiginous Lesions 299
Fig. 17.15.
Patient with linear larval burrow on the toe and top of the foot. Note the linear blister at the leading edge. (From the Fitzsimons Army Medical Center Collection, Aurora, CO.)
Fig. 17.16.
Fig. 17.17.
Fig. 17.18.
Child with numerous older burrows present for 4 weeks that had been treated as a dermatitis by both the emergency room clinician and her pediatrician. (From the Fitzsimons Army Medical Center Collection, Aurora, CO.)
Patient with convoluted linear burrows on the bottom of the foot. (From the Fitzsimons Army Medical Center Collection, Aurora, CO.)
Patient with atypical bullous lesion on the instep of the foot. Careful observation of the lesion demonstrates the serpiginous burrow within the blister.
300 Chapter 17 Linear and Serpiginous Lesions
References Lichen Striatus
1. Kim M, Jung HY, Eun YS, et al. Nail lichen striatus: report of seven cases and review of the literature. Int J Dermatol. 2015;54:1255-1260. 2. Patrizi A, Neri I, Fiorentini C, et al. Lichen striatus: clinical and laboratory features of 115 children. Pediatr Dermatol. 2004;21:197-204.
Bleomycin-Induced Erythema and Hyperpigmentation
1. Khmamouchne MR, Debbagh A, Mahfoud T, et al. Flagellate erythema secondary to bleomycin: a new case report and review of the literature. J Drugs Dermatol. 2014;13:983-984. 2. Lee HY, Lim KH, Ryo Y, Song SY. Bleomycin-induced flagellate erythema: a case report and review of the literature. Oncol Lett. 2014;8:933-935.
Linear Epidermal Nevus
1. Chatproedprai S, Wananukul S, Prasarnnaem T, Noppakun N. Epidermal nevus syndrome. Int J Dermatol. 2007;46:858-860.
2. Hafner C, Hartmann A, Vogt T. FGFR3 mutations in epidermal nevi and seborrheic keratoses: lessons from urothelium and skin. J Invest Dermatol. 2007;127:1572-1573.
Linear Morphea
1. Mazori DR, Wright NA, Patel M, et al. Characteristics and treatment of adult-onset linear morphea: a retrospective cohort study of 61 patients in 3 tertiary care centers. J Am Acad Dermatol. 2016;74:577-579. 2. Zwischenberger BA, Jacobe HT. A systematic review of morphea treatments and therapeutic algorithm. J Am Acad Dermatol. 2011;65:925-941.
Cutaneous Larva Migrans
1. Prickett KA, Ferringer TC. What’s eating you? Cutaneous larva migrans. Cutis. 2015;95:126-128. 2. Richey TK, Gentry RH, Fitzpatrick JE, et al. Persistent cutaneous larva migrans due to Ancylostoma species. South Med J. 1996;89:609-611.