Netherton syndrome is a rare disorder inherited in an autosomal recessive 
pattern consisting of ichthyosiform dermatosis, hair shaft abnormalities 
(trichorrhexis invaginata), and an atopic diathesis. Patients with Netherton 
syndrome have been found to have a mutation on chromosome 5q32 in a gene named 
SPINK5 (serine protease inhibitor, Kazal type-5), which encodes an inhibitor of 
serine proteases called LEKTI. We report a female patient with previously 
undiagnosed Netherton syndrome who presented to participate in a clinical 
research trial investigating the benefit of topical tacrolimus 0.03% ointment 
[Protopic (Fujisawa Pharmaceutical Co. Ltd., Japan)] for the treatment of atopic 
dermatitis. This patient was confirmed to have a gene mutation in SPINK5. 
Current literature suggests a relative contraindication for use of topical 
tacrolimus in patients with Netherton syndrome owing to concern for increased 
systemic absorption of the drug. Our patient was not able to tolerate topical 
tacrolimus owing to local irritation, and did not derive any benefit from 
therapy. Though rare, when evaluating patients with a possible diagnosis of 
atopic dermatitis, an index of suspicion for Netherton Syndrome must be 
maintained. History and overall clinical findings, especially in regards to 
examination of the hair, will aid in diagnosis.