Netherton syndrome: Successful use of topical tacrolimus and pimecrolimus in four siblings

Abstract

Netherton's syndrome (NS) is a rare autosomal recessive disease comprised of ichthyosis in the form of ichthyosis linearis circumflexa, hair shaft defects and atopic manifestations with an elevated IgE level. Various therapeutic options have been used in NS with variable success. Tacrolimus and pimecrolimus belong to the family of calcineurin inhibitors. They bind cytoplasmic proteins and the resulting complex binds calcineurin, inhibiting its ability to dephosphorylate the nuclear factor of activated T cells, thus suppressing gene transcription. There have been conflicting reports of the usefulness of tacrolimus in NS patients, with systemic absorption being the main adverse outcome. Here we report four Saudi siblings (two boys and two girls) with NS who were treated with topical tacrolimus and pimecrolimus with good control of their skin disease without any toxic effect. To our knowledge, this is the second report of the use of topical pimecrolimus in NS in the English literature.

Proteolytic Activation Cascade of the Netherton Syndrome–Defective Protein, LEKTI, in the Epidermis: Implications for Skin Homeostasis

“…In addition, they gain upon the design of a previously unreported and effective therapeutic intervention for NS, based on the replacement of the missing LEKTI polypeptides. The currently utilized therapies for this life-threatening and disabling disease are only aimed at reducing the clinical symptoms (Saif and Al-Khenaizan, 2007;Renner et al, 2009). Nevertheless, in spite of the encouraging results (Di et al, 2010;Roedl et al, 2011), the ex-vivo gene transfer cannot be envisaged as an imminent therapeutic option.…”

Topical Corticosteroids and Topical Calcineurin Inhibitors in the Treatment of Atopic Dermatitis: Focus on Percutaneous Absorption

“…34 Owing to the concern about increased absorption, TCIs are contraindicated in patients with Netherton syndrome. 35 Elevated concentrations of tacrolimus were recently reported in a patient with erythrodermic AD and large BSA involvement.…”

Prenatal diagnosis of Comel-Netherton syndrome with PGD, case report and review article

“…Low dose oral corticosteroids, etretinate and psoralen ultraviolet A therapy was also used. Topical tacrolimus will likely achieve minimal benefit, and may be contraindicated for patients with extensive skin involvement with concern for systemic absorption [22,31].…”