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Pediatrics: General Medicine > Dermatology
Café Au Lait Spots
Article Last Updated: Jun 4, 2008
AUTHOR AND EDITOR INFORMATION
Section 1 of 9  
Author: William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
William D James is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Coauthor(s):
Raj D Sheth, MD, Professor, Departments of Neurology and Pediatrics, Director of Comprehensive Epilepsy Program, Department of Neurology, University of Wisconsin at Madison;
Nazanin Saedi, BA, George Washington University School of Medicine
Editors: Kevin P Connelly, DO, Clinical Assistant Professor, Department of Pediatrics, Division of General Pediatrics and Emergency Care, Virginia Commonwealth University; Medical Director, Paws for Health Pet Visitation Program of the Richmond SPCA; Pediatric Emergency Physician, Emergency Consultants Inc, Chippenham Medical Center; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School; Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences; Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Author and Editor Disclosure
Synonyms and related keywords:
café au lait spots, cafe au lait spots, pigmented macules, axillary freckling, neurofibromatosis, neurofibromatosis type 1, NF1, neurofibromatosis type 2, NF2, Von Recklinghausen disease, peripheral neurofibromatosis, NF2, McCune-Albright syndrome, tuberous sclerosis, Fanconi anemia, optic glioma, Lisch nodules, pseudarthroses, congenital glaucoma, sphenoid wing dysplasia, precocious puberty, aplastic anemia, mental retardation, ash leaf spots, angiofibromas
hemangiomas, cardiac rhabdomyomas, shagreen patches, Russell-Silver syndrome, Silver-Russell syndrome, ataxia telangiectasia, Bloom syndrome, Gaucher disease, Gaucher syndrome, Chiak-Higashi syndrome, Hunter syndrome, Maffucci syndrome, Watson syndrome, Crowe sign, scoliosis, hypoplastic bowing of the legs, osseous lesions in the ribs, pseudoarthritis of the tibia, spina bifida, scalloping of the vertebral body, neurofibromas, lipomata, angiomata, ptosis, pheochromocytoma
Background
Café au lait (CAL) spots are hyperpigmented lesions that may vary in color from light brown to dark brown; this is reflected by the name of the condition, which means "coffee with milk." The borders may be smooth or irregular. The size and number of CAL skin lesions widely vary, and they are usually the earliest manifestations of neurofibromatosis.1 The macules may be observed in infancy, although typically they are very light in infants and can be difficult to appreciate. The skin lesions develop in early infancy, and they may enlarge in size and become obvious after age 2 years. CAL spots are observed in 95% of patients with neurofibromatosis type 1 (NF1), which is the most frequently occurring neurocutaneous syndrome. These spots may also be observed in patients without NF1. Other conditions in which they may be observed include McCune-Albright syndrome, tuberous sclerosis, and Fanconi anemia.
CAL spots and Lisch nodules in the iris are the most characteristic markers of NF1. NF1 should be differentiated from neurofibromatosis type 2 (NF2). NF2 is also referred to as central neurofibromatosis because it is associated with acoustic neuroma. Patients with NF2 may also have CAL spots. NF2 is more likely to be diagnosed in middle-aged persons, unlike NF1, which is typically diagnosed in children. The genes that are responsible for these 2 disorders are on different chromosomes: chromosome 17 in NF1 (encoding neurofibromin) and chromosome 22 in NF2.
Pathophysiology
CAL spots are caused by an increase in melanin content, often with the presence of giant melanosomes. A significant increase in melanocyte density is noted in the CAL spots of patients with NF1 compared with patients who have isolated CAL spots without NF1 involvement. Also, an increase in stem cell factor cytokines is more frequently observed in NF1 CAL spots than non-NF1 CAL spots. The diagnosis of NF1, an autosomal dominant disorder, requires the fulfillment of the Whitehouse criteria, which includes the presence of 6 or more CAL spots in children or adults. To be considered in the diagnosis of NF1, CAL lesions must be at least 15 mm in diameter in patients older than 5 years or over 5 mm in children younger than 5 years. The expression of the disorder can widely vary; members in the same family may have differing degrees of severity.
Frequency
United States
In the newborn period, solitary CAL spots may occur in 0.3% of whites, 3% of Hispanics, and in 18% of blacks.2 In childhood, solitary CAL spots occur in 13% of whites and 27% of blacks. Two or more CAL spots were not observed in any of 4000 white newborns, although they were found in 8% of black newborns. CAL spots that confirm the diagnosis of NF1 occur at an estimated frequency of 1 in 3500 persons.3
International
Solitary CAL spots occur in 0.5% of Arab newborns and in 0.4% of Chinese newborns.2
Mortality/Morbidity
CAL spots are benign and produce no mortality or morbidity.
Race
CAL spots are more frequently observed in children of African American race.
Sex
No sexual predilection is recognized.
Age
Typically, CAL spots are present at birth, although they may be difficult to appreciate. A Wood lamp may improve the ability to visualize these faint spots. By the time the child is aged 2-3 years, CAL spots are clearly visible. The size and number of CAL spots increase with patient age in patients with NF1.
History
The presence of numerous café au lait (CAL) spots should raise the suspicion of a genetic disorder. The most common associated systemic illness is neurofibromatosis type 1 (NF1). - The diagnostic criteria for NF1 are met if 2 or more of the following are present:
- Six or more CAL macules larger than 5 mm in greatest diameter in prepubertal individuals and larger than 15 mm in greatest diameter in postpubertal individuals
- Two or more neurofibromas of any type or 1 plexiform neurofibroma
- Freckling in the axillary or inguinal regions
- Optic glioma
- Two or more Lisch nodules (iris hamartomas)
- A distinctive osseous lesion, such as sphenoid dysplasia or thinning of the long bone cortex, with or without pseudoarthrosis
- A first-degree relative with NF-1, according to the above criteria
- Characteristics of NF1 include the following:
- Newborn period
- Pseudarthroses
- Congenital glaucoma
- Sphenoid wing dysplasia
- Early childhood
- Embryonal tumors
- Compression injuries: Plexiform neurofibromas in the mediastinal cavity may cause compression. Back pain in a patient with CAL lesions should always be taken seriously because this symptom may be a sign of a radiculopathy.
- Optic pathway gliomas: These occur by the time the patient is aged 3 years.
- Other syndromes associated with CAL spots include the following:
- McCune-Albright syndrome: Often one large, asymmetric CAL spot with irregular borders is present; this syndrome is associated with polyostotic fibrous dysplasia, which leads to pathologic fractures, precocious puberty, and numerous hyperfunctional endocrinopathies. Early in life, this syndrome may present with a single, large irregular CAL spot. Follow-up observations reveal the endocrine abnormalities.
- Fanconi anemia: CAL spots are present along with mental retardation, aplastic anemia, and risk for malignancy.
- Tuberous sclerosis: CAL spots are present along with Ash leaf spots, facial angiofibromas, hemangiomas, cardiac rhabdomyomas, and shagreen patches.
- Silver-Russell syndrome
- Ataxia telangiectasia
- Bloom syndrome
- Basal cell nevus syndrome
- Gaucher disease
- Chiak-Higashi syndrome
- Hunter syndrome
- Maffucci syndrome
- Multiple mucosal neuroma syndrome
- Watson syndrome
- Whereas small CAL spots are associated with various syndromes, large, solitary, light-brown patches often represent segmental lentigines that are not associated with any neurocutaneous syndromes or developmental anomalies.
Physical
CAL spots are macules that are typically the color made by adding milk to coffee. They may vary in size from a few millimeters, as in axillary freckling, to large macules that measure more than 10 cm in size.
- Large, solitary CAL spots are larger than 0.5 cm. They are found more commonly on the buttocks than any other anatomical location. No other physical findings or syndromes are usually related to solitary CAL spots.
- Axillary freckling (known as Crowe sign) and inguinal freckling are characteristic diagnostic features of NF1.
- Plexiform neurofibromas may underlie CAL spots in NF1. These are large fibrous swellings of the subcutaneous tissue that may cause severe disfigurement of the face or limbs.
- CAL spots are associated with underlying disorders, and physical findings indicative of those disorders include the following:
- Scoliosis
- Hypoplastic bowing of the legs
- Osseous lesions in the ribs
- Pseudoarthrosis of the tibia
- Spina bifida
- Scalloping of the vertebral body
- Lisch nodules
- Neurofibromas
- Lipomata
- Angiomata
- Ptosis
- Ocular abnormalities (including glaucoma and corneal opacifications)
- Pheochromocytoma
Causes
CAL spots associated with NF1 result from an autosomal dominant disorder with high penetrance and variability in the expression of clinical features.
- The NF1 gene is localized to the pericentromeric region of the long arm of chromosome 17. The gene encodes for neurofibromin, which is a GTP-ase activating protein that downregulates cellular proto-oncogene, p21-ras.
- About 50% of individuals with NF1 have a spontaneous mutation. The high incidence of new mutations is thought to result from the large size of the gene, which increases the likelihood of spontaneous mutations.
- Occasionally, patients who have larger gene deletions have a higher incidence of mental retardation and earlier appearance of cutaneous neurofibromas.
Gaucher Disease
McCune-Albright Syndrome
Tuberous Sclerosis
Wiskott-Aldrich Syndrome
Other Problems to be Considered
Congenital nevus
Lab Studies
- Genetic testing is available for the diagnosis of neurofibromatosis type 1 (NF1)-associated café au lait (CAL) lesions.
Histologic Findings
- Hyperpigmentation of basilar keratinocytes is noted.
- Giant melanosomes may be present within keratinocytes.
Medical Care
Café au lait (CAL) lesions do not require medical care. When CAL lesions are associated with neurofibromatosis or another underlying condition, monitoring of associated conditions is required.
Medical/Legal Pitfalls
- The presence of multiple café au lait (CAL) spots should prompt a search for features suggestive of an underlying genetic disorder.
- Early diagnosis and genetic testing/counseling are important because of the genetic transmission of the underlying systemic disorders, if one is present.
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Multiple irregular sized and shaped café au lait lesions. |
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Café Au Lait Spots excerpt Article Last Updated: Jun 4, 2008
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