tacrolimus and Genital-Diseases--Female

Inflammatory mucosal disorders are treated conventionally with potent or superpotent topical corticosteroids. For more than 20 years, topical cyclosporine has been used in the management of oral mucous membrane affections. Recently other topically applied calcineurin inhibitors, namely tacrolimus and pimecrolimus, expanded the armamentarium for the treatment of inflammatory mucosal diseases. This chapter places its main emphasis on the efficacy and safety of topical calcineurin inhibitors in the management of different oral and genital conditions, including anogenital lichen sclerosus (LS), oral and genital lichen planus, plasma cell balanitis and vulvitis, mucous membrane pemphigoid and pemphigus vulgaris, all conditions having usually a protracted course, requiring long-lasting treatment. There is current evidence for the effectiveness of both pimecrolimus and tacrolimus in the topical treatment of inflammatory oral mucosal diseases and genital dermatoses, especially oral lichen planus and genital LS.

Topics: Administration, Topical; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Balanitis; Calcineurin Inhibitors; Carcinogens; Female; Genital Diseases, Female; Humans; Lichen Planus; Lichen Planus, Oral; Lichen Sclerosus et Atrophicus; Male; Mucositis; Paraneoplastic Syndromes; Pemphigoid, Benign Mucous Membrane; Pemphigus; Tacrolimus; Vulvitis

Genital aphthous ulcers of Behcet's disease (BD) are painful and usually resistant to local treatments. Pimecrolimus is an ascomycin macrolactam, used in inflammatory skin diseases.. To discover if pimecrolimus can accelerate the healing of BD genital aphthous ulcers.. Ninety patients with genital aphthous ulcers were enrolled. Only patients treated with colchicine alone were selected. All patients signed a written consent form. Patients were randomly assigned to pimecrolimus or placebo cream, applied twice daily for 1 week. The primary outcome was the healing period. Up to 7 days, it was considered as a positive result. Results were compared by chi-square test. The mean healing time was compared by analysis of variance. Analyses were done both by the 'intention-to-treat' and 'treatment-completed' methods.. Both groups were similar at the entry (gender, age, ulcer size, pain intensity and treatment delay). By intention-to-treat analysis, in the pimecrolimus group, 18 patients had positive and 27 negative results. In the control group, four had positive and 41 negative results. The difference was significant (chi(2) = 10.167, P = 0.001). By treatment-completed analysis, with pimecrolimus, 18 patients had positive and 22 negative results. With placebo, four had positive, and 41 negative results. The difference was significant (chi(2) = 12.574, P = 0.0004). Comparison of mean healing time in the pimecrolimus versus placebo group, demonstrated a significant acceleration both in intention-to-treat analysis (10.7 vs. 20.7 days, F = 17.466, P < 0.0001) and treatment-completed analysis (8.3 vs. 20.7 days, F = 29.289, P < 0.0001).. Pimecrolimus is safe and efficient in the treatment of BD genital ulcers, by accelerating the healing process.

Topics: Administration, Cutaneous; Adolescent; Adult; Behcet Syndrome; Chi-Square Distribution; Dermatologic Agents; Double-Blind Method; Female; Genital Diseases, Female; Genital Diseases, Male; Humans; Iran; Male; Middle Aged; Placebo Effect; Stomatitis, Aphthous; Tacrolimus; Time Factors; Treatment Outcome; Wound Healing; Young Adult

Recurrent and painful genital ulcers are the hallmark of Behçet's disease.. To determine the efficacy of pimecrolimus (PIM) cream on the pain and healing time of genital ulcers.. A total of 76 patients were randomized to either receive PIM cream plus colchicine (COL) tablets (1-2 g/day) or COL tablets (1-2 g/day) alone for 1 month. Clinical evaluations were performed in 68 patients at the baseline and on the 3rd, 7th, 10th, 14th and 28th days of treatment. Also, genital ulcer pain was evaluated using a verbal pain score at each visit. Safety was monitored through adverse event reporting and laboratory tests.. The mean healing time of genital ulcers was shorter in the PIM + COL group (4.2 +/- 1.5 days) than the COL group (4.7 +/- 1.8 days), without statistical significance (p = 0.399). Visual analog scale scores decreased in both groups significantly. Neither of the treatment modalities was found to be superior to the other; however, pain was relieved in 4.2 +/- 0.5 days in PIM + COL group and in 5.5 +/- 1.2 days in COL group in the intention to treat population (p = 0.023). Observed adverse events were transient.. Compared to COL alone, COL + PIM cream shortens the pain duration without any significant effect on healing time.

Topics: Adult; Behcet Syndrome; Colchicine; Dermatologic Agents; Drug Therapy, Combination; Emollients; Female; Genital Diseases, Female; Genital Diseases, Male; Humans; Male; Pain; Pain Measurement; Retrospective Studies; Scrotum; Tablets; Tacrolimus; Treatment Outcome; Turkey; Ulcer; Vagina

Lichen sclerosus is a chronic inflammatory autoimmune disease causing significant sclerosis, atrophy and pruritus. Treatment remains unsatisfactory, with potent corticosteroids being the most effective therapy.. To conduct a multicentre, phase II trial to assess the safety and efficacy of tacrolimus ointment 0.1% for the treatment of lichen sclerosus with a follow-up period of 18 months at 10 university and teaching hospitals in Germany and Austria.. Eighty-four patients (49 women, 32 men and three girls) aged between 5 and 85 years with long-standing, active lichen sclerosus (79 with anogenital and five with extragenital localization) were treated with topical tacrolimus ointment 0.1% twice daily for 16 weeks. Computerized analysis of the lesional area was performed. The primary endpoint was clearance of active lichen sclerosus. Secondary endpoints were time to optimal response, reduction of sclerosis and duration of remission.. The primary endpoint (clearance of active lichen sclerosus) was reached by 43% of patients at 24 weeks of treatment. Partial resolution was reached in 34% of patients. Maximal effects occurred between week 10 and 24 of therapy. Treatment led to a significant reduction of the total lesional area (P < 0.01) and to a significant decline in the total symptom score (P < 0.005). Symptoms (e.g. itching) and findings (erythema, erosions and induration) showed significant improvement. No serious adverse events were observed. There were three (9%) recurrences during the follow-up period.. Topical tacrolimus ointment 0.1% was safe and effective for the treatment of long-standing active lichen sclerosus.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoimmune Diseases; Child; Child, Preschool; Female; Genital Diseases, Female; Genital Diseases, Male; Humans; Immunosuppressive Agents; Lichen Sclerosus et Atrophicus; Male; Middle Aged; Ointments; Severity of Illness Index; Tacrolimus; Treatment Outcome

Lichen sclerosus is a chronic inflammatory dermatosis presenting with significant sclerosis, atrophy and pruritus. The treatment for this condition remains unsatisfactory, with potent corticosteroids being the most effective therapy. In this study, we investigated the efficacy and safety of tacrolimus ointment in patients with genital and extragenital lichen sclerosus. Sixteen patients with active lichen sclerosus (10 with anogenital and six with extragenital localization) were treated with topical tacrolimus ointment twice daily. The therapeutic effects were evaluated according to 3 grades: complete response (>75% improvement), partial response (25-75% improvement), or no response (<25% improvement). Applications were continued until complete disappearance or stabilization of the cutaneous lesions. In addition, we conducted telephone surveys to determine the long-term treatment outcome and relapse rate. Objective response to therapy occurred in nine of 10 patients (90%) with anogenital and one of six patients (16.7%) with extragenital lesions. Out of 10 patients with anogenital lichen sclerosus, five showed more than 75% improvement. Complete, partial and no response were achieved in five (50%), four (40%) and one (10%) patient, respectively. During the follow-up period of a mean of 29.3 months, six of nine patients had a relapse of symptoms. However, most patients with extragenital involvement did not respond to tacrolimus, except one patient showing partial response. No significant adverse effects were observed. Topical tacrolimus ointment was a safe and effective treatment for genital lichen sclerosus and should be used for long-term duration to prevent relapse. However, it was not useful for patients with extragenital lichen sclerosus.

Topics: Adolescent; Adult; Aged; Child; Chronic Disease; Female; Genital Diseases, Female; Genital Diseases, Male; Humans; Immunosuppressive Agents; Lichen Sclerosus et Atrophicus; Male; Middle Aged; Ointments; Tacrolimus; Treatment Outcome; Young Adult

Lichen sclerosus is a chronic inflammatory disease of unknown origin, which affects mostly women in the fifth and sixth decades of life, but can also occur in men and children. The involvement of the oral mucosa alone or together with other forms of presentation is extremely rare, requiring a differential diagnosis with other diseases of the oral cavity, particularly lichen planus. There are less than 30 cases of lichen sclerosus in the oral mucosa described in the literature and there are no reports on malignant transformation so far. We describe a patient with skin, oral and genital lesions of lichen sclerosus.

Topics: Administration, Topical; Aged; Diagnosis, Differential; Female; Genital Diseases, Female; Humans; Immunosuppressive Agents; Lichen Sclerosus et Atrophicus; Mouth Diseases; Tacrolimus

A potent topical steroid is the conventional therapy for genital lichen planus (GLP). Side-effects or steroid resistance can be encountered and second-line therapy such as topical tacrolimus may be required. In our experience tacrolimus may be poorly tolerated in genital skin because of a burning sensation. In addition, there is impairment of Langerhans cell function, raising concerns about its long-term use. These adverse effects may not be as marked with pimecrolimus. To our knowledge, pimecrolimus has not been used in the treatment of GLP.. To assess the efficacy and tolerability of topical pimecrolimus in the treatment of GLP.. Eleven women with GLP were recruited: 10 had erosive vulval disease and one had classical lichen planus of perianal skin. Ten patients had poor disease control, and despite using topical steroids appropriately, two of these also had steroid-related side-effects in adjacent unaffected skin. The eleventh patient had adequate disease control but marked steroid atrophy. Topical pimecrolimus 1% cream (Elidel cream; Novartis, Camberley, U.K.) was applied twice daily to affected areas. Patients were followed up between 4 and 6 weeks later. They remain under regular review and at the time of writing mean follow-up is 5.2 months (range 2-10).. Nine patients (82%) tolerated pimecrolimus, including three patients previously intolerant of tacrolimus. These nine patients showed a clinical response at 4-6 weeks: two showed a complete response with no residual disease activity visible and seven had a partial response. With longer follow-up, six (55%) of the women had a complete response and three (27%) were considered to have a partial response. Eight patients noted symptomatic improvement and one felt that her symptoms were the same as with steroid use. Two patients (18%) with erosive lichen planus were unable to tolerate pimecrolimus due to local irritation.. We have found that topical pimecrolimus 1% cream is an effective treatment for GLP. Local irritation can limit its use, but it may be better tolerated than topical tacrolimus: three of our complete responders had previously been intolerant of tacrolimus. Topical pimecrolimus may be a valuable second-line treatment for patients with steroid-related side-effects or steroid-resistant GLP.

Topics: Administration, Topical; Aged; Aged, 80 and over; Dermatologic Agents; Female; Genital Diseases, Female; Genitalia, Female; Humans; Lichen Planus; Middle Aged; Prospective Studies; Tacrolimus; Treatment Outcome