Download with Tacrolimus Clinical Experience Ointment in Atopic Dermatitis III

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11 Other Potential Dermatological Indications for Tacrolimus
Steroid Rosacea
The pathogenesis of
steroid rosacea may be
explained by several
Many inflammatory skin diseases such as psoriasis and atopic dermatitis can be
safely and easily treated with topical steroid formulations. However, excessive application of topical steroids can lead to a rosacea-like skin disorder, particularly in the
Steroid rosacea was first described in 1969 by Sneddon [70] and in 1974 by Leyden and Kligman [39]. The disease is characterised by pruritic, inflammatory papules and pustules in typical facial locations such as the central facial, periorbital,
and perioral regions. Patients achieve clearance of the lesions by using the topical
steroid compounds, but as soon as they are withdrawn a strong rebound reaction
can be seen, which initiates a vicious circle for the patient.
The pathogenesis of steroid rosacea may be explained by several mechanisms.
Glucocorticosteroids exert vasoconstrictive effects in the skin by inhibiting the release of the endothelium-derived relaxing factor (EDRF) which acts as a vasodilator.
The vasoconstriction involves the accumulation of several mediators, such as nitric
oxide (NO), with opposing vasodilatory effects. After glucocorticosteroid withdrawal, the vasodilating effects of NO lead to an enlargement of the diameter of the
small vessels. This intensifies the rebound features which are typical of steroid rosacea: erythema, pruritus, and burning [58].
Another pathogenetic factor of the disease may be explained by the immunosuppressive effects of corticosteroids which facilitate the growth of micro-organisms
such as bacteria and yeast fungi, on the skin. These may act as superantigens which,
after withdrawal of topical corticosteroids, enhance proinflammatory cytokinemediated inflammatory cutaneous reactions [38].
The treatment of steroid rosacea is difficult, and it usually takes several weeks
to complete healing. Apart from strict avoidance of topical glucocorticosteroids,
topical (erythromycin, clindamycin) and systemic antibiotics (doxycycline, minocycline) are used to reduce the number of bacteria and the amount of possible
superantigens. Antihistamines provide relief of pruritus and diminish inflammation. In addition, prolonged concomitant and intensive skin care with lotions or
moist packs is essential to resolve the painful and burning inflammatory skin lesions
Goldman described three patients with steroid rosacea who underwent treatment
with topical 0.075% tacrolimus ointment twice daily for 7–10 days in conjunction
with avoidance of topical glucocorticosteroids and rosacea-aggravating substances.
All three patients showed rapid amelioration after 7 days of therapy and only slight
side effects such as burning at the site of application at the beginning of the treatment. After withdrawal of tacrolimus ointment, all three patients showed mild rebound reactions which could be resolved within 3–4 days after additional topical
antibiotic treatment or repeated applications of tacrolimus ointment [20].
The rapid resolution of the inflammatory lesions may be explained by the direct
interaction of tacrolimus with the gene transcription of proinflammatory cytokines
in the skin, as has been shown in atopic and contact dermatitis.