Gadgetine

a question for Bryan:

jimmystanley

jimmystanley

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hey, i was just wondering if you could link me to some studies on elidel or on immunosuppresants in general Or if you have any personal thoughts about their effectiveness for skin problems and their risks. thanks a lot.
 
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The use of topical tacrolimus and pimecrolimus to treat psoriasis: A review
Noah Scheinfeld JD MD
Dermatology Online Journal 10 (1): 3

Department of Dermatology, St Lukes Roosevelt Hospital, New York NY 10025. Scheinfeld@earthlink.net

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Abstract
Tacrolimus ointment and pimecrolimus cream are approved in the United States for treatment of atopic dermatitis. Tacrolimus and pimecrolimus are both calcineurin inhibitors and function as immunosuppressants. Their mechanisms have been discussed elsewhere. This article will discuss their utility in treating psoriasis.


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Introduction
Tacrolimus ointment and pimecrolimus cream are approved in the United States for treatment of atopic dermatitis. Tacrolimus and pimecrolimus are both calcineurin inhibitors and function as immunosuppressants [1]. Their mechanisms have been discussed elsewhere [2]. This article will discuss their utility in treating psoriasis.

In the treatment of psoriasis, the topical use of tacrolimus and pimecrolimus has promise [3]. As oral agents both tacrolimus[4] and pimecrolimus[5] are effective in the treatment of moderate to severe plaque psoriasis. However, neither medication has yet to be approved by the FDA for this indication. Some have stated that given orally, pimecrolimus is as potent or superior to tacrolimus in treating ACD in mice and rats [6]. No trial comparing these medications in humans has yet to be performed.



Treatment of psoriasis
Neither tacrolimus ointment[7] nor pimecrolimus[8] cream appear effective for treating plaque-type psoriasis when simply applied as commercially available. In tacrolimus this is the case even although percutaneous absorption of tacrolimus is higher in diseased skin as opposed to healthy skin [9]. In a pilot study of 70 patients, 23 in the calcipotriol (0.05 %) twice-daily group, 24 in the tacrolimus (0.3 %) ointment once-daily group, and 23 in the placebo group, tacrolimus was not effective in the treatment of psoriasis [10].



Occlusion
Occlusion makes topical tacrolimus more effective in treating psoriasis. Under occlusion, tacrolimus ointment decreases the erythema and infiltration of descaled psoriatic plaques [11]. Tacrolimus ointment applied in a Finn chamber has been reported as effective in treating plaque psoriasis [12]. Interestingly, one report has noted deep dermatophytosis during topical tacrolimus therapy for psoriasis [13].

Occlusion is also associated with effectiveness of pimecrolimus in treating psoriasis [14, 15]. Pimecrolimus (0.3 % and 1.0 %) under occlusion was used to treat ten patients with chronic plaque-type psoriasis [16]. For control treatment, the corresponding ointment base (placebo) and open-labeled clobetasol-17-propionate ointment (0.05 %) were used. The trial was a randomized, double-blind, within-subject comparison for 2 weeks using the microplaque assay. Evaluation was performed by daily determination of clinical scores for erythema and induration. The results of the study showed that after 2 weeks of treatment, total scores decreased by 92 percent for clobetasol, by 82 percent for pimecrolimus (0.1 %), by 63 percent for pimecrolimus (0.3%), and by 18 percent for the ointment base (placebo).



Changing Formulations
Changing the formulation of tacrolimus and pimecrolimus to increase penetration is also a promising means to increase their effectiveness in treating psoriasis. Tacrolimus ointment was compared to liposomal tacrolimus lotion on in the models of Balb/c skin graft survival and ovalbumin-induced delayed-type hypersensitivity reactions in C57BL/6 mice. Radiotracer studies showed that topical application of liposomal tacrolimus achieved nine times the concentration of tacrolimus ointment at a target site [17]. A two-center, randomized, double-blind, vehicle- and positive-controlled patient study was conducted in 23 adult psoriasis patients; twice daily application to test sites without occlusion for 21 days was done with an ointment formulation of pimecrolimus (1 %), the corresponding vehicle, calcipotriol (0.005 %) ointment, and clobetasol-17-propionate (0.05 %) ointment. Erythema, induration, and scaling (score: 0 [absent] to 4 [severe]) were evaluated. The total sign score was defined as the sum of the erythema, induration and scaling scores (range 0-12). Pimecrolimus 1 percent ointment was significantly (p = 0.03) more effective than the corresponding vehicle, with an improvement in total sign score of 51.4 percent compared with 36 percent. Improvements with calcipotriol and clobetasol-17-propionate were 71.5 percent and 88.3 percent, respectively [18].



Tacrolimus is efficacious in treating psoriasis on face and intertriginous areas
Tacrolimus ointment seems most effective in treating psoriasis where the skin is thin, that is on the face and intertriginous areas. Several case reports indicate that topical tacrolimus is effective in the treatment of facial psoriasis [19, 20]. In one study 21 patients (15 males and 6 females with a mean age of 51.1 years old) with facial psoriasis lesions applied tacrolimus (0.1 %) ointment twice a day for 4 weeks without occlusion. A complete or good response was obtained in 10 (47.6 %) and 9 (42.9 %) patients, respectively. The mean score for erythema decreased from 1.76 to 0.62; the infiltration score decreased from 1.33 to 0.43; and the desquamation score decreased from 0.95 to 0.24 [21]. The safety and efficacy of tacrolimus (0.1 %) ointment for the treatment of psoriasis on the face, intertriginous areas, or both were evaluated in an open-label, clinical trial of 21 patients with psoriasis. A total of 81 percent of patients (17 of 21) experienced complete clearance at day 57 (end of treatment). Only 2 patients reported adverse events, which were limited to itching and the feeling of warmth at the application site [22].



Conclusion
Tacrolimus and pimecrolimus are exciting agents in the treatment of skin disease. Their role in the treatment of psoriasis is still being defined but their use will likely increase. Both agents await additional investigation to determine the ideal formulations for particular body sites in the treatment of psoriasis.

References
1. Reynolds NJ, Al-Daraji WI. Calcineurin inhibitors and sirolimus: mechanisms of action and applications in dermatology. Clin Exp Dermatol. 2002;27: 555-61.

2. Marsland AM, Griffiths CE. The macrolide immunosuppressants in dermatology: mechanisms of action. Eur J Dermatol. 2002;12:618-22.

3. Ruzicka T, Assmann T, Lebwohl M. Potential future dermatological indications for tacrolimus ointment. Eur J Dermatol. 2003;13:331-42.

4. Lebwohl M, Ali S. Treatment of psoriasis. Part 2. Systemic therapies. J Am Acad Dermatol. 2001; 45:649-64.

5. Rappersberger K, Komar M, Ebelin ME, Scott G, Burtin P, Greig G, Kehren J, Chibout SD, Cordier A, Holter W, Richter L, Oberbauer R, Stuetz A, Wolff K. Pimecrolimus identifies a common genomic anti-inflammatory profile, is clinically highly effective in psoriasis and is well tolerated. J Invest Dermatol. 2002;119:876-87.

6. Stuetz A, Grassberger M, Meingassner JG. Pimecrolimus (Elidel, SDZ ASM 981)--preclinical pharmacologic profile and skin selectivity. Semin Cutan Med Surg. 2001;20:233-41.

7. Lazarous MC, Kerdel FA. Topical tacrolimus Protopic. Drugs Today (Barc). 2002;38:7-15.

8. Gupta AK, Chow M. Pimecrolimus: a review. J Eur Acad Dermatol Venereol. 2003;17:493-503.

9. Gupta AK, Adamiak A, Chow M. Tacrolimus: a review of its use for the management of dermatoses. J Eur Acad Dermatol Venereol. 2002;16:100-14.

10. Zonneveld IM, Rubins A, Jablonska S, Dobozy A, Ruzicka T, Kind P, Dubertret L, Bos JD. Topical tacrolimus is not effective in chronic plaque psoriasis. A pilot study. Arch Dermatol. 1998; 134: 1101-2.

11. Remitz A, Reitamo S, Erkko P, Granlund H, Lauerma AI.Tacrolimus ointment improves psoriasis in a microplaque assay. : Br J Dermatol. 1999;141:103-7.

12. Remitz A, Reitamo S, Erkko P, et al. A microplaque assay-based, double-blind trial to compare the efficacy of two tacrolimus ointment formulations with two active and two negative controls in patients with chronic plaque-type psoriasis vulgaris. Br J Dermatol. 1996;135:833.

13. Yamamoto T, Nishioka K. Deep dermatophytosis during topical tacrolimus therapy for psoriasis. Acta Derm Venereol. 2003; 83:291-2.

14. Paul C, Graeber M, Stuetz A. Ascomycins: promising agents for the treatment of inflammatory skin diseases. Expert Opin Investig Drugs. 2000;9:69-77.

15. Paul C, Ho VC. Ascomycins in dermatology. Semin Cutan Med Surg. 1998;17:256-9.

16. Mrowietz U, Graeber M, Brautigam M, Thurston M, Wagenaar A, Weidinger G, Christophers E. The novel ascomycin derivative SDZ ASM 981 is effective for psoriasis when used topically under occlusion. Br J Dermatol. 1998;139:992-6.

17. Erdogan M, Wright JR Jr, McAlister VC. Liposomal tacrolimus lotion as a novel topical agent for treatment of immune-mediated skin disorders: experimental studies in a murine model. Br J Dermatol. 2002;146:964-7.

18. Mrowietz U, Wustlich S, Hoexter G, Graeber M, Brautigam M, Luger T. An experimental ointment formulation of pimecrolimus is effective in psoriasis without occlusion. Acta Derm Venereol. 2003;83:351-3.

19. Clayton TH, Harrison PV, Nicholls R, Delap M. Topical tacrolimus for facial psoriasis. Br J Dermatol. 2003;149:419-20.

20. Yamamoto T, Nishioka K. Topical tacrolimus is effective for facial lesions of psoriasis. Acta Derm Venereol. 2000;80:451.

21. Yamamoto T, Nishioka K. Topical tacrolimus: an effective therapy for facial psoriasis. Eur J Dermatol. 2003;13:471-3.

22. Freeman AK, Linowski GJ, Brady C, Lind L, Vanveldhuisen P, Singer G, Lebwohl M. Tacrolimus ointment for the treatment of psoriasis on the face and intertriginous areas. J Am Acad Dermatol. 2003;48:564-8.


© 2004 Dermatology Online Journal
 
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Immunosuppressants and Skin Cancer in Transplant Patients: Focus on Rapamycin
Sylvie Euvrard, MD*, Claas Ulrich, MD, and Nicole Lefrancois, MD
Background. The responsibility of immunosuppressants for the increased risk of skin cancers in organ transplant recipients is widely recognized. Discerning the role of each drug is complicated owing to the fact that most patients generally have combinations of several medications.

Objective. This article will discuss the role of the main immunosuppressants in the pathogenesis of skin cancers.

Methods. This work consists of a review of the most significant publications.

Results. Experimental and clinical studies suggest that corticosteroids, azathioprine, cyclosporine (CsA), and tacrolimus increase the incidence of skin cancer. Each drug may act through two different mechanisms including the impairment of the systemic immunosurveillance and a direct oncogenic effect. CsA was shown to be oncogenic independently of its immunosuppressive effect. By contrast, several works on mice have found that rapamycin inhibits tumor growth while being immunosuppressive. Furthermore, rapamycin was shown to inhibit several UV-induced mechanisms involved in skin carcinogenesis. Preliminary clinical studies have reported a lower incidence of skin malignancy in patients treated with rapamycin compared to CsA from the time of transplantation.

Conclusion. New immunosuppressive strategies for transplant patients with skin cancer are not only based on minimizing immunosuppression. Data suggest that rapamycin could have a protective effect against skin cancer. Further studies are required to assess accurately the efficacy and tolerance of rapamycin in these patients.

SYLVIE EUVRARD, MD, CLAAS ULRICH, MD, AND NICOLE LEFRANCOIS, MD HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS.
 
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Immunosuppressants and Skin Cancer in Transplant Patients: Focus on Rapamycin
Sylvie Euvrard, MD*, Claas Ulrich, MD, and Nicole Lefrancois, MD
Background. The responsibility of immunosuppressants for the increased risk of skin cancers in organ transplant recipients is widely recognized. Discerning the role of each drug is complicated owing to the fact that most patients generally have combinations of several medications.

Objective. This article will discuss the role of the main immunosuppressants in the pathogenesis of skin cancers.

Methods. This work consists of a review of the most significant publications.

Results. Experimental and clinical studies suggest that corticosteroids, azathioprine, cyclosporine (CsA), and tacrolimus increase the incidence of skin cancer. Each drug may act through two different mechanisms including the impairment of the systemic immunosurveillance and a direct oncogenic effect. CsA was shown to be oncogenic independently of its immunosuppressive effect. By contrast, several works on mice have found that rapamycin inhibits tumor growth while being immunosuppressive. Furthermore, rapamycin was shown to inhibit several UV-induced mechanisms involved in skin carcinogenesis. Preliminary clinical studies have reported a lower incidence of skin malignancy in patients treated with rapamycin compared to CsA from the time of transplantation.

Conclusion. New immunosuppressive strategies for transplant patients with skin cancer are not only based on minimizing immunosuppression. Data suggest that rapamycin could have a protective effect against skin cancer. Further studies are required to assess accurately the efficacy and tolerance of rapamycin in these patients.

SYLVIE EUVRARD, MD, CLAAS ULRICH, MD, AND NICOLE LEFRANCOIS, MD HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS.
 
jimmystanley

jimmystanley

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did i read that right...immunosupressors are used to help prevent skin cancer?...enjoyed the first read, thanks for the effort!
 
Serpico

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Wow talk about a resurrection.

20 years later and still scratching our heads about this. Great example of what the pace of science really looks like.
 
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