Original article
Nevus anemicus in neurofibromatosis type 1: A potential new diagnostic criterion

https://doi.org/10.1016/j.jaad.2013.06.039Get rights and content

Background

Children with multiple café-au-lait macules (CALMs) may be followed for years before a second National Institutes of Health clinical criterion of neurofibromatosis type 1 (NF1) develops to confirm the diagnosis.

Objective

We sought to assess the prevalence of nevus anemicus (NA) in NF1 and its association with neuro-ophthalmologic complications.

Methods

This was a prospective multicenter case-control study of 210 consecutive patients with multiple CALMs. Patients with NF1 were matched for age, sex, and center with control subjects. We documented the number, location, and morphologic appearance of NA; dermatologic features of NF1; magnetic resonance imaging results; and family history.

Results

In all, 77 (51%) patients with NF1 had NA compared with 6 (2%) control subjects. NA was not detected in 26 patients with other genodermatoses associated with CALMs. Patients with NF1 and NA were younger than those without NA (median age: 17 years) (P = .002). NA was mostly localized to the upper anterior aspect of the chest. NA was not significantly linked with other clinical manifestations of NF1, including optic glioma and unidentified bright objects.

Limitations

A potential referral bias associated with tertiary care centers is a limitation.

Conclusions

NA appears to have a high prevalence and specificity in NF1 and might serve as a marker for NF1 in children with multiple CALMs.

Section snippets

Patients

This prospective case-control study was conducted from January 2007 to September 2012 in 2 French university hospital centers. All patients were being followed up for significant CALMs, defined as: (1) more than 3 with diameter 0.5 cm or larger in infants; and (2) 6 or more with diameter 0.5 cm or larger in children and 1.5 cm or larger in adults. We chose more than 3 CALMs for infants because CALMS is the first clinical sign of NF1 and more than 3 CALMs are rare (<0.3%) in the absence of an

Results

In all, 210 cases were enrolled in the study (Fig 1). A total of 151 patients from 123 families (group 1) were given the diagnosis of NF1 according to NIH criteria, excluding the CALMs/intertriginous freckling association in the absence of a pathogenic NF1 germline mutation. They were matched with 302 control subjects. In all, 59 patients (group 2) did not match group 1/NF1 criteria, including 26 patients with a diagnosed genodermatosis and 33 patients with an undiagnosed genodermatosis.

Discussion

We present data demonstrating a high prevalence of NA in patients with NF1 (51%) compared with control subjects (2%). The low NA prevalence in our control group is similar to the 1% prevalence estimated in a control population of 298 dermatology patients.28 Although NA is noted as a distinctive clinical feature of NF1 in several reviews,1, 7 few case reports describe NA in patients with NF1.8, 9 The prevalence of NA in NF1 has probably been underestimated for several reasons. First, careful

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    Funding sources: None.

    Conflicts of interest: None declared.

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