The Diagnostic and Clinical Significance of Café-au-lait Macules

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Definition

Café-au-lait, also referred to as café-au-lait spots or café-au-lait macules, present as well-circumscribed, evenly pigmented macules and patches that range in size from 1 to 2 mm to greater than 20 cm in greatest diameter (Fig. 1). In light-skinned persons, the color appears light brown, or “coffee with milk,” whereas in darker-skinned patients the color may appear as a medium to dark brown hue. Morphologically, café-au-lait have often been described as appearing either oval and

Epidemiology and natural history

Solitary café-au-lait are common birthmarks. The presence of more than one café-au-lait, however, is less common. The frequency of multiple lesions, which has significance regarding the requirement for additional evaluation, has been examined in several population-based studies. Overall, the presence of one or more café-au-lait appears more common in African Americans than in Caucasians. The overall prevalence of at least one café-au-lait was noted to be present in 2.5% of neonates among 18,155

Pathogenesis

Although café-au-lait may be seen anywhere on the body, they appear to be most common on the torso and occur rarely on the face, suggesting that sunlight exposure is not involved in the pathogenesis. An increase in the secretion of hepatocyte growth factor (HGF) and stem cell factor (SCF) by dermal fibroblasts has been reported in café-au-lait associated with NF-1, suggesting that these growth factors may be associated with the increased epidermal melanization observed in at least some

Differential diagnosis

Although café-au-lait are usually readily diagnosed on examination, occasionally they may be difficult to differentiate from other pigmented lesions (Table 1). At times, café-au-lait may be difficult to distinguish from other pigmented birthmarks, including congenital melanocytic nevi, speckled lentiginous nevus, Becker nevus, and forms of pigmentary mosaicism such as nevoid hypermelanosisand segmental pigmentation disorder. Acquired pigmentary lesions, including ephelides (freckles), lentigo,

Evaluation

Presentation of a child with café-au-lait macules to the primary care provider, geneticist, or dermatologist is a common scenario. Two prospective cohort studies have attempted to define the predictive value of the number and morphology of café-au-lait macules in children with regard to eventual diagnosis of NF-1 or other disorders associated with café-au-lait. In one study, a cohort of 41 children with 6 or more café-au-lait greater than 5 mm in diameter was followed prospectively.14 The

Clinical presentations

Although neurofibromatosis-1 is the most common and well-recognized syndrome associated with café-au-lait, they have been associated with several other syndromes, including neurofibromatosis-2 (NF-2), McCune-Albright syndrome, and Noonan syndrome. A review of the features of many of the syndromes associated with café-au-lait is presented in Table 2. Although comprehensive, this list is not exhaustive, and for many of these syndromes the evidence that café-au-lait occur with more frequency than

Treatment

Treatment of café-au-lait is not required for medical reasons, but is often requested by patients and caregivers for cosmetic concerns, in particular with large, segmental café-au-lait or when café-au-lait are present on the face. There is no uniformly successful treatment modality for removing café-au-lait. Several medical lasers have been used for the treatment of café-au-lait, all with variable clinical results. Complications of laser surgery include discoloration of the skin and scarring,

Summary

Café-au-lait are common pigmented skin lesions in children. Although most café-au-lait present as 1 or 2 hyperpigmented macules or patches in an otherwise healthy child, the presence of multiple café-au-lait, large segmental café-au-lait, associated facial dysmorphism, other cutaneous anomalies, or unusual findings on physical examination should suggest the possibility of an associated syndrome. While NF-1 is the most common syndrome seen in children with multiple café-au-lait, other syndromes

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