tacrolimus and Ichthyosis

The uremic pruritus is a very painful symptom suffered by chronic haemodialysis patients and is observed in 22 to 74% of the subjects. The causes of uremic pruritus have not yet been clarified. During the last 20 to 30 years it has been focused on altogether 5 different pathophysiological hypotheses: stimulating influences (e.g. calcium phosphate deposits in the epidermis), stimuli (e.g. secondary hyperparathyroidism), neuropathic injuries (e.g. disturbance of the cutaneous innervation in patients with uremic peripheral neuropathy), and central nervous changes (e.g. accumulation of endorphins in uremic patients which is associated with increasing pruritus), and immunologic conditions. The last mentioned immunological hypothesis has increasing importance, not at least based on the fact that the application of a topical calcineurin inhibitor (tacrolimus) improves the uremic pruritus. However, this fact could not be confirmed in a recent prospective placebo-controlled study from the USA. Only after kidney transplantation with a functioning transplant the uremic pruritus is stopped. That is why no causal therapy exists so far. Actually, the uremic pruritus has to be treated by topical and systemic means in a symptomatic and polypragmatic way only. Urea represents one of the most important "natural moisturizing factors" which are responsible for the hydration of the skin. It has been demonstrated that older patients have decreased urea levels within the stratum corneum of the epidermis, whereas in patients with terminal kidney insufficiency - despite dryness of the skin - as a paradox finding elevated levels of urea have been assessed in the stratum corneum. Because of this reason, the meaning of urea as part of the "natural moisturizing factors" system is not understood, until now. However, there are very promising results of clinical phase II studies showing a significant effect of topical application of 2.5% L-arginine hydrochlorid ointment - a semi-essential amino acid - on improvement of dryness and, in particular, on improvement of pruritus in haemodialysis patients.

Topics: Antipruritics; Arginine; Calcineurin Inhibitors; Capsaicin; Controlled Clinical Trials as Topic; Humans; Ichthyosis; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Ointments; Prospective Studies; Pruritus; Renal Dialysis; Skin; Tacrolimus; Urea; Uremia

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.

Topics: Administration, Topical; Child; Child, Preschool; Dermatologic Agents; Drug Therapy, Combination; Female; Hair; Humans; Ichthyosis; Immunosuppressive Agents; Infant; Male; Remission Induction; Syndrome; Tacrolimus

Hydration and integrity of the horny layer is essential to normal skin function.. Comparison of the hydrating properties of three moisturizers with pimecrolimus cream vehicle.. Four test preparations (high-quality skin cream, cold cream emulsion, emollient oil, pimecrolimus cream vehicle) were applied to four different regions of the forearms and legs. Transepidermal water loss (TEWL) was assessed by evaporimetry at baseline, and 3 and 6 hours after arm application, and electrical capacitance was assessed by corneometry at baseline, and 1, 2, 3 and 6 hours after leg application.. Corneometry assessment - in terms of efficacy in moisturizing the skin, test preparations were ranked (best to worst): high-quality skin cream (45.9 arbitrary units versus 75.3; p < 0.001) > pimecrolimus vehicle cream (46.6 versus 61.5; p < 0.001) > emollient oil (43.5 versus 54.8; p = 0.006) > cold cream emulsion (44.8 versus 49.9; p = 0.738). Untreated skin (control) had a mean capacitance of 44.8 units at baseline and 48.5 units at endpoint. Evaporimetry (assessment of TEWL) revealed no significant differences between control and any test preparation at any timepoint.. Pimecrolimus cream vehicle has skin hydration properties comparable with highly effective commercially available products. No test preparation had a significant effect on TEWL.

Topics: Administration, Cutaneous; Adult; Analysis of Variance; Dermatologic Agents; Double-Blind Method; Emollients; Female; Humans; Ichthyosis; Male; Middle Aged; Pharmaceutical Vehicles; Probability; Skin Absorption; Skin Care; Tacrolimus; Water; Young Adult

Topics: Administration, Topical; Dose-Response Relationship, Drug; Drug Administration Schedule; Follow-Up Studies; Humans; Ichthyosis; Infant, Newborn; Skin Absorption; Tacrolimus

We report a case of ichthyosis linearis circumflexa (ILC) without the typical atopic manifestations and deformities of the hair shaft. The patient responded positively to treatment with topical tacrolimus, suggesting that abnormalities in the immunoregulatory mechanism may be involved in the pathogenesis of ILC.

Topics: Administration, Cutaneous; Adult; Back; Humans; Ichthyosis; Immunosuppressive Agents; Male; Tacrolimus