Axillary freckles, also known as Crowe sign, are multiple 1- to 4-cm hyperpigmented lesions in the axillary vault.1 Presence of axillary freckles serves as a valuable diagnostic aid in early detection of neurofibromatosis type 1 (NF1).1 Although freckles associated with NF1 most commonly manifest in the axillary region, they may also present in intertriginous areas, such as the inguinal region, nape of the neck, or the inframammary fold in women.2 NF1, also known as von Recklinghausen disease, was first described by Friedrich Daniel von Recklinghausen in 1882 as an autosomal-dominant neurodermal disorder.3 Approximately 50% of cases of NF1 arise as spontaneous mutations. NF1 is characterized by multiple hyperpigmented macules and neurofibromas as a result of a mutation on the NF1 gene at the 17q11.2 chromosome.3 Axillary freckling is usually detected in affected individuals from 5 to 8 years of age.2
If a diagnosis of NF1 is suspected in a patient presenting with axillary freckles, referral should be made to a clinician skilled in this disorder. The National Institute of Health Consensus Development Conference has formulated diagnostic criteria for NF1, highlighting the crucial involvement of the skin, bone, and nervous system for accurate diagnosis.4 Some of the diagnostic criteria include 6 or more café au lait macules (>0.5 cm in children or >1.5 cm in adults), axillary or groin freckling, ≥2 neurofibromata, optic pathway glioma, ≥2 Lisch nodules, bony dysplasia, and a first-degree relative with NF1.4,5 Genetic testing identifies 95% of mutations in those with NF.6
Julie Grandinetti, PA-C, is on staff at Mount Sinai Medical Center in the Bronx, New York, and Stephen Schleicher, MD, is director of the DermDox Center for Dermatology, as well as associate professor of medicine at Commonwealth Medical College and clinical instructor of dermatology at Arcadia University and Kings College.
- Paller AS, Mancini AJ. Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence. 4th ed. London, UK: Elsevier Saunders; 2011:257-285.
- Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol. 2014;13(8):P834-P843.
- Ghalayani P, Saberi Z, Sardari F. Neurofibromatosis type 1 (von Recklinghausen’s disease): a family case report and literature review. Dent Res J (Isfahan). 2012;9(4):483-488.
- Neurofibromatosis. National Institutes of Health Consensus Development Conference Statement. 1987;6(12):1-19.
- Ferner RE, Huson SM, Thomas N, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet. 2007;44(2):81-88.
- Radtke HB, Sebold CD, Allison C, Larsen Haidle J, Schneider G. Neurofibromatosis type 1 in genetic counseling practice: recommendations of the National Society of Genetic Counselors. J Genet Couns. 2007;16(4):387-407.