Blaschko Lines:Following "Lines of Evidence" to a Rash Diagnosis

Many factors can be considered in attempting to establish the cause of a skin disorder. These include the color, morphology, and location of the lesions; associated symptoms, such as itching and fever; and exposure to drugs or to other children who have a rash. Linearity of the lesions may also suggest the diagnosis.

Common examples of linearity include:

• Linear vesicular dermatitis caused by exposure to poison ivy.

• Painful, vesicular lesions of herpes zoster.

• Pigmentary demarcation (known as Futcher or Voigt lines) often seen along the lateral edge of the biceps in persons with dark skin. Oval patches in a "Christmas tree" distribution over the back seen in pityriasis rosea.

Some skin disorders follow known anatomic linear patterns. The lesions of herpes zoster follow the generally predictable pattern of dermatomal lines (Figure 1). The lesions of pityriasis rosea follow the distribution of skin cleavage lines (or Langer lines) (Figure 2). Langer lines are thought to represent the principal axis of orientation of collagen fibers in the dermis; incisions along these lines have been thought to result in the least amount of scarring.

Figure 1 - Herpes zoster on the upper torso of a 5-month-old girl is shown. The virus was acquiredin utero as a result of maternal chickenpox during pregnancy. The rash can involve several sensory dermatomes, is unilateral, and rarely crosses themidline.

Figure 2 -

Pityriasis rosea

on the back of a 17-year-old girl is shown. The most common presenting sign is aherald patch (inset) usually found on the trunk-as in this patient-and less often on the neck and proximalextremities. The long axes of the lesions are along skin cleavage lines (Langer lines).

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Figure

Other disorders follow a linear distribution that does not correspond with dermatomes or skin cleavage lines. For instance, the distribution of poison ivy dermatitis is often linear, reflecting a linear deposition of Rhus antigen (or urushiol) on the person's skin.

Still other skin disorders are linear but not explainable in any of these ways. Could Blaschko lines explain the linearity of these disorders?

HISTORICAL OVERVIEW

In 1901, the German dermatologist Alfred Blaschko described a system of cutaneous lines that represented the typical pattern that linear nevi appeared to follow.¹ Because many skin disorders that followed these lines were present at birth, Blaschko suspected that they had an embryonic origin.

About 60 years later, British cytogeneticist Mary Lyon proposed that the mottled appearance of female mice heterozygous for coat color genes might be explained by the random inactivation of 1 female X chromosome, leading to functional mosaicism.¹ This theory was extended to the coloration of tortoiseshell and calico cats, and Lyon suggested that X-linked human skin diseases showed similar patterns. About 15 years later, Jackson and Happle proposed that functional X-chromosomal mosaicism by means of random X inactivation was the mechanism underlying cutaneous diseases that follow Blaschko lines.^2,3 Current thinking suggests that Blaschko lines depict the directed route of embryonic ectodermal cell migration, which illustrates how epidermal cells originate in the neural crest and move toward the periphery in embryos by directional proliferation in keratinocytes and migration in melanocytes.³ Cells expressing a normal X chromosome make up normal skin, whereas cells expressing an abnormal X chromosome constitute contrasting, abnormal skin in the distribution of Blaschko lines.

Other causes of mosaicism (such as postzygotic somatic mutations occurring early in embryogenesis) can also result in linear skin disorders following Blaschko lines. The extent of skin involvement depends on the proportion and distribution of cells with the genetic abnormality and on the developmental stage when the mutation took place.⁴ The skin involvement and patterning are more widespread with mutations that occur earlier in embryogenesis but may be confined to a single anatomical region with later mutations.⁴

DISTRIBUTION OF PIGMENTATION

Blaschko lines track distinct patterns (Figure 3). They follow a dorsal "V" shape over the spine and back, an "S" shape over the lateral and anterior areas of the trunk, an arc from the chest to the shoulders, a spiral shape on the scalp, and a linear longitudinal pattern on the extremities. On the face, Blaschko lines typically run perpendicularly on the forehead, along the lateral aspects of the nose, and down to the chin. They do not correspond to dermatomes, cranial nerve distribution, skin cleavage lines (Langer lines), skin tension lines, embryonic clefts, the lines of lymphatic drainage or blood supply, or hair tracts.

Figure 3 - This diagram demonstrates the distribution of

Blaschko lines

.

ASSOCIATED SKIN DISORDERS

A variety of skin disorders can follow Blaschko lines, including inflammatory, dysplastic, dyskeratotic, and pigmentary conditions. Figure 4 illustrates pigmentary mosaicism following Blaschko lines in a 6-month-old baby with hypomelanosis of Ito. Figure 5 shows a pigmented epidermal nevus along Blaschko lines in the axilla of a 4-year-old girl with Proteus syndrome.

Figure 4 -

Hypomelanosis of Ito

, a manifestation of pigmentary mosaicism, is shown.

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Figure 5 -

An epidermal nevus

, a manifestation of Proteus syndrome, is shown.

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When examining a child with a skin disorder that follows a linear pattern, try to determine whether it follows dermatomal lines or the lines of skin cleavage but remember to consider Blaschko lines. Recognizing a linear pattern that corresponds to Blaschko lines may help you follow the "lines of evidence" and make the correct diagnosis.

References:

• Traupe H. Functional X-chromosomal mosaicism of the skin. Rudolph Happle and the lines of Alfred Blaschko. Am J Med Genet. 1999;85:324-329.

• Happle R. X-chromosome inactivation: role in skin disease expression. Acta Paediatr Suppl. 2006; 95:16-23.

• Moss C. Cytogenetic and molecular evidence for cutaneous mosaicism: the ectodermal origin of Blaschko lines. Am J Med Genet. 1999;85:330-333.

• Siegel DH, Sybert VP. Mosaicism in genetic skin disorders. Pediatr Dermatol. 2006;23:87-92.

• Leung AKC, Kong JCW. What's your diagnosis? Pityriasis rosea. Consultant For Pediatricians. 2008; 7:116-120.

• Williams GP, Dean S. Hyperpigmented macules. Consultant For Pediatricians. 2005;4:314-323.