PEDIATRIC DERMATOLOGY

What's your DX?

By Charlotte Moore and Bernard A. Cohen, MD

A 4-month-old girl is referred to you to evaluate a large pigmented birthmark. She was born at full term without complications to a healthy 24-year-old mother. She is otherwise healthy with normal growth and development. There is no family history of pigmented birthmarks, mental retardation, or neurologic or endocrine disease.

On examination you note a healthy, vigorous infant with an irregularly shaped, uniformly pigmented, well-demarcated patch covering her left flank and abdomen.

1. What's the clinical diagnosis?

2. What conditions are associated with this cutaneous finding?

3. How would you counsel the child's parents?

Discussion

This child's pigmented birthmark is typical of a café au lait macule (CALM). These lesions are discrete, uniformly pigmented tan-brown macules and patches of variable shapes and sizes ranging from only a few millimeters to more than 20 cm. The borders may appear smooth or jagged, and the texture of the skin is usually normal.

Any part of the body can develop the lesions. The majority of CALMs, however, appear on the trunk and lower extremities, with the head and neck usually spared.¹ Macules may be present at birth, with new ones appearing during the first two decades. CALMs grow proportionally with general body growth during the first few years of life. After growth stabilizes in early childhood macules persist indefinitely.

Incidence

The incidence of a single CALM ranges from 1.9%² to 19%,³ depending on the study population. Multiple CALMs, in contrast, are uncommon. The incidence of more than two macules ranges from 0.6% to 4.2%.³ Several studies have noted that African-American children have a higher prevalence of two lesions than Caucasian children (4.4% to 5% vs. 0% to 2%)^3,4 and also three lesions (1.8% vs. 0%).⁴ African-American children, however, do not appear to have a higher incidence of associated neurocutaneous syndromes than Caucasians.

The occurrence of CALMs does not vary with gender, and no association has been noted with the presence of macules and the propensity to burn, freckle, or develop nevomelanocytic nevi.⁵

Differential diagnosis

The differential diagnosis includes Mongolian spots, lentigines, nevus spilus, nevocellular nevi, and Becker's nevi. Mongolian spots are easily differentiated from CALMs by their blue-green color and indistinct borders. In contrast to CALMs, lentigines are usually small (less than 1 cm) and have variable salt-and-pepper-like brown pigmentation. Nevus spilus is composed of small dark nevomelanocytic elements scattered in a uniform lighter brown patch. Often mistaken for CALMs, nevocellular nevi can be distinguished by accentuated skin markings caused by nevus cells in the dermis. Becker's nevus, also referred to as hairy epidermal nevus, is an acquired hyperpigmented lesion, which typically develops on the trunk of adolescent boys. After a variable period these lesions usually develop hypertrichosis, which may extend beyond the area of hyperpigmentation. The diagnosis and documentation of large or multiple CALMs is important because they can be associated with the genetic disorders neurofibromatosis and McCune-Albright syndrome.

Neurofibromatosis (NF) is an autosomal dominant disorder with frequent spontaneous mutation. It is estimated to occur in one out of 2,500 to 3,000 live births, regardless of gender or ethnicity.

The diagnosis of NF is based on well-studied clinical criteria, two or more of which must be met: multiple CALMs (six or more spots larger than 5 mm in the prepubertal child or six or more lesions larger than 1.5 cm in the postpubertal child), two or more cutaneous neurofibromas or one plexiform neurofibroma, two or more iris Lisch nodules, skin-fold freckling, optic gliomas, characteristic skeletal dysplasia, and an affected first-degree relative.

The CALMs, which are present at birth, may be the only sign of NF to appear before early childhood. It is important, therefore, that the primary care pediatrician document and follow the number and size of all CALMs.² A thorough NF evaluation is indicated if the size and number criteria are met.

McCune-Albright syndrome is characterized by the clinical triad of polyostotic fibrous dysplasia of bone, hyperfunctional endocrinopathies, and CALMs. The fibrous dysplasia may involve any bone, but most often affects the femur, tibia, pelvis, ribs, and humerus. Endocrine manifestations include precocious puberty (most commonly affecting females), hyperthyroidism, acromegaly, and hypophosphatemic rickets.

Presentation and severity of McCune-Albright syndrome vary greatly. Affected individuals are mosaics—an autosomal dominant gene is believed to be lethal, mutations early in embryologic development cause more extensive disease, and late mutations lead to less severe phenotypes.⁶

In contrast to NF, the CALMs of McCune-Albright syndrome are usually single or few in number. Large CALMs with irregular borders are characteristic. Although the cutaneous markings can be bilateral, they are classically unilateral, stopping abruptly at the midline, and are most extensive on the side of the body with the more severe bone involvement.¹⁰⁷

Most McCune-Albright patients, like NF patients, have CALMs at birth, and the cutaneous manifestations usually precede discovery of the fibrous dysplasia by several years.⁸ As with NF, the early presentation of CALMs in otherwise asymptomatic patients emphasizes the importance of recording the presence, size, and number of CALMs in all newborns.

Associated conditions and outcome

A number of other disorders are thought to be associated with CALMS. A recent review, however, suggests that many of these associations are merely anecdotal.⁴

Although our patient continues to be clinically well, close monitoring for bony and endocrinologic findings is imperative. Unfortunately, no reliable genetic marker for McCune-Albright syndrome is available yet.

REFERENCES

1. Kopf AW, Levine U, Rigel DS, et al: Prevalence of congenital nevus-like nevi, nevi spili, and café au lait spots. Arch Dermatol 1985;121(6):766

2. Alper JC, Holmes LB, Mihm MC: Birthmarks with serious medical significance: Nevocellular nevi, sebaceous nevi, and multiple café-au-lait spots. J Pediatr 1979;95(5 Pt 1):696

3. Whitehouse D: Diagnostic value of the café au lait spot in children. Arch Dis Child 1966;41(217):316

4. Alper JC, Holmes LB: The incidence and significance of birthmarks in a cohort of 4,641 newborns. Pediatr Dermatol 1983;l(l):58

5. McLean DI, Gallagher RP: "Sunburn" freckles, café au lait macules, and other pigmented lesions of schoolchildren: The Vancouver Mole Study. J Am Acad Dermatol 1995;32(4):565

6. Happle R: The McCune-Albright syndrome: A lethal gene surviving by mosaicism. Clin Genet 1986;29:321

7. Benedict PH, Szabo G, Fitzpatrick TB, et al: Melanotic macules in Albright's syndrome and in Neurofibromatosis. JAMA 1968;205:618

8. DeSanctis C, Lala R, Matarazzo P, et al: McCune-Albright syndrome: A longitudinal clinical study of 32 patients. J Pediatr Endocrinol Metab 1999;12(6):817

The next installment of "Pediatric Dermatology: What's your DX?" will appear in April.

MS. MOORE is a fourth year medical student at the Johns Hopkins University School of Medicine, Baltimore.

DR. COHEN, who serves as Section Editor for Pediatric Dermatology: What's your DX?, is Director, Pediatric Dermatology and Cutaneous Laser Center, and Associate Professor of Pediatrics and Dermatology at Johns Hopkins University School of Medicine, Baltimore. He is a Contributing Editor for Contemporary Pediatrics.

 

Bernard Cohen. Pediatric dermatology: What's your DX?. Contemporary Pediatrics 2001;1:45.