Netherton syndrome with multiple non-melanoma skin cancers.

Netherton syndrome (NS) is a rare autosomal reces-sive genodermatosis caused by SPINK-5 mutations. The SPINK-5 gene encodes the serine protease inhibitor LEKTI and is located on chromosome 5q32. Unopposed degradation of corneodesmosomes is the basis for a severely impaired skin barrier function in patients with NS. Effective treatments for patients with NS are limited. Some success has been achieved with local application of corticosteroids or tacrolimus/pimecrolimus (1). Re-tinoids, acitretin as well as isotretinoin, have been used systemically, with variable benefits, whilst higher doses mostly worsen the disease, probably because of deteriorating effects on the skin barrier (2). Cyclosporine and oral corticosteroids are also prescribed to patients with NS (3, 4). There is one report of the successful use of intravenous immunoglobulins (IVIG), but this therapy has some clear limitations (5). Recently, Maatouk et al. (6) reported clinical improvement in Netherton syndrome with narrowband ultraviolet (UV) B phototherapy. A similar response was observed by Kaminska et al. (7), while clinical improvement induced by UVA1 therapy has been reported by Capezzera et al. (8). Because of these positive results, it may be tempting to use UV therapy readily in patients with NS. However, long-term use of UV is associated with an increased risk of developing skin cancer. Non-melanoma skin cancer is, unfrequently observed in patients with NS. Natsuga et al. (9) only found 3 cases in the literature, out of a total of approximately 150 cases of NS reported (9–13). However, most articles deal with this syndrome in childhood. CASE REPORT We report here a 39-year-old patient with NS who developed multiple skin malignancies. He was born with erythrodermic skin, and in early childhood there was failure to thrive, possibly due to repetitive upper respiratory tract infections. Subsequently his skin became more ichthyosiform, he developed a range of allergies and was diagnosed with trichorrhexis invaginata based on the growth pattern and hair-shaft abnormalities. The clinical diagnosis of NS was always suspected, but only confirmed at the age of 21 years by demonstration of the autosomal recessive mutation 5q32 in the SPINK-5 gene. At the age of 6 years, and after failure of several local therapies (such as local corticosteroids and various emollient creams), the patient was treated with UVA and 8-methoxypsoralen (8-MOP) (PUVA) for 11 months (total cumulative UV dose 362.2 J/cm 2), with limited clinical improvement. One year at the end of PUVA therapy the patient was treated with etretinate 10 …