Case

A four year-old African-American girl was brought to the clinic by her mother three days ago with the complaint of a "dark patchy rash".  These patches were not itchy nor were they tender.  The mother claimed that she first noticed them when the child was an infant but did not think much of it, believing that it would run it's course.  It, however, did not resolve and "became more obvious".  The patient was afebrile with non-contributory vitals.  On physical exam several brown macules of varying sizes were found on the trunk and legs.  They were non-tender to palpation and had no crusting.  Four of these patches (three on the right leg and one on the chest) had round fixed raised nodular masses underneath.  The child also had axillary and inguinal freckles.  Eye exam revealed a thin greyish-white area near the iris.  The rest of the exam was non-contributory.  What is the diagnosis?

Diagnosis and Epidemiology

This child was diagnosed with Neurofibromatosis Type 1 (NF-1) because she displayed at least two of the seven criteria for the diagnosis.  NF-1 is a somewhat rare disease (1/3000 births) which can go unnoticed until a child gets older.  It is an autosomal dominant hemartomatous condition that is due to a mutation in the NF-1 gene.  There is no racial predominance and both sexes are effected equally.  The earliest clinical manifestation (as seen in this case) is "Cafe-au-lait" spots.  Later manifestations that are usually not present at birth or infancy include axillary and inguinal freckles as well as subcutaneous neurofibromas (both however were noted in this case).  There are several other hemartomatous manifestations of this condition including lisch nodules in the eye (usueally detected after the age of 10 in over 90% of patients), optic nerve gliomas, and plexiform neurofibromas that are very deep and can cause bone pain.

Treatment

Treatment is symptomatic and involves management of specific manifestations.  Annual physical exams must be performed in order to note any new or changes in prior manifestations.  Referral to Neurology and Opthamology is also a necessity for management of the neural hermatomas and ocular manifestations.  It is very important for the primary care physician to monitor the patient's blood pressure and developmental milestones as these patients are at higher risk for HTN and ADHD than the normal population.  It is also important to the note the develpment of any new joint/bone pains, scoliosis, and parasthesias that may be due to plexiform neurofibromas.  These as well as other bothersome neurofibromas can be surgically resected, but there is still a relatively high recurrence rate.

With respect to medical therapy, there is no specific medical treatment for this condition.  A variety of anti-neoplastic agents have been used, in particular Carboplatin, with very little success in eradicating optic nerve gliomas.  The National Cancer Institute is about to begin a clinical trial on a new drug (R115777) that has been successful in animal studies in blocking the growth of plexiform neurofibromas.

Impact on Lifestyle

Thus although NF-1 is not necessarily a life-threatening condition and most patients can lead a normal lifestyle, it can be emotionally hard on those with visible manifestations.  It is important for the primary care physician to comfort these patients and monitor them for emotional changes with respect to anxiety or depression.