Type 1 Neurofibromatosis (von Recklinghausen Disease)
Type 1 neurofibromatosis (NF1), or von Recklinghausen disease, is a genetic disorder that is well known for its clinical features. Effective treatment modalities for NF1 have not yet been established. The advent of new treatment options for NF1 such as topical vitamin D3 analogues, lovastatin, rapamycin (or sirolimus), and imatinib mesylate has added new dimensions that require further investigation to provide the greatest benefit to patients.
Practice Points
- Histopathology and magnetic resonance imaging are useful in diagnosing type 1 neurofibromatosis (NF1).
- Newer treatments like statins and tyrosine kinase inhibitors are worth exploring in NF1.
Freckling of the skin folds is the most common of the cardinal criteria for NF1. Other sites include under the neck and breasts, around the lips, and trunk. Their size ranges from 1 to 3 mm, distinguishing them from CALMs. Considered nearly pathognomonic, NF1 generally occurs in children aged 3 to 5 years in the axillae or groin.15,24
Cutaneous neurofibromas generally are cutaneous/dermal tumors that are dome shaped, soft, fleshy, and flesh colored to slightly hyperpigmented. Subcutaneous tumors are firm and nodular. Neurofibromas usually do not become apparent until puberty and may continue to increase in size and number throughout adulthood. Pregnancy also is associated with increased tumor growth.25 The tumors are comprised of Schwann cells, fibroblasts, mast cells, and perineural cells. There also is an admixture of collagen and extracellular matrix.26 The cutaneous and extracutaneous manifestations of NF1 are outlined in Table 1 and Table 2.27-31
Management
Type 1 neurofibromatosis needs to be differentiated from other conditions based on careful clinical examination. Additionally, histopathologic examination of the lesions, imaging studies (eg, MRI), echocardiography, regular skeletal roentgenogram, and detailed ophthalmologic examination are important to look for any visceral involvement. Painful and bleeding tumors and cosmetic enhancement warrant surgical intervention, including various surgical techniques and lasers.32,33 Application of sunscreen may make pigmentary alterations less noticeable over time. Although not often located on the face, CALMs also may be amenable to various makeup products. Various studies have demonstrated improvement of freckling and CALMs with topical vitamin D3 analogues and lovastatin (β-hydroxy-β-methylglutaryl-CoA reductase inhibitors)34-36; however, this needs further exploration. Rapamycin has demonstrated efficacy in reducing tumor volume in animal studies by inhibiting the mammalian target of rapamycin cellular pathway.37 Imatinib mesylate has demonstrated efficacy both in vivo and in vitro in mouse models by targeting the platelet-derived growth-factor receptors α and β.38
