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Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii
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Review paper
Application of tacrolimus in the treatment of skin diseases other than atopic dermatitis

Wojciech Silny
,
Anna Sadowska
,
Aleksandra Dańczak-Pazdrowska
,
Adriana Polańska

Post Dermatol Alergol 2011; XXVIII, 1: 41–45
[Polish version: Post Dermatol Alergol 2011; XXVIII, 1: 47–52]
Online publish date: 2011/03/07
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Introduction

For more than half a century immunosuppressive preparations have been used to treat inflammatory diseases and in transplantation to obtain long-term tolerance of the transplanted organ. In dermatological treatment the main drugs of anti-inflammatory and immunosuppressive action are corticosteroids (CS). Their prolonged use may lead to numerous side effects (e.g. skin atrophy, telangiectasia, perioral dermatitis, metabolic disorders). Often the phenomenon of tachyphylaxis and also exacerbation of skin lesions after discontinuation of the preparation may be observed [1]. A breakthrough for treating inflammatory conditions was the introduction of tacrolimus. It is a macrolide, formerly known as FK-506. It was first isolated in 1984 from the bacterium Streptomyces tsukubaensis [2]. The drug has strong immunosuppressive properties, which have been used in transplantation. In dermatology, the fact that tacrolimus can be used topically is very important. In 1994 initial reports describing the effectiveness of calcineurin inhibitor for the treatment of atopic dermatitis (AD) were published [3]. The drug was registered in Poland 10 years ago, and currently is available in the form of an ointment: 0.03% and 0.1%. Tacrolimus proved to be particularly effective in the treatment of localized lesions within the face and neck, where the use of local CS resulted in many side effects. Several multi-centre, short-and long-term studies in patients with atopic dermatitis were performed, on both adults and children, and quick resolution of the inflammation and reduction of itching after using tacrolimus were detected [4-8]. Recently, there have been more reports concerning proactive therapy in patients with a diagnosis of AD. A study conducted by Reitamo et al. showed good results after application of tacrolimus twice a week within the skin after resolution of active lesions [9]. Long-term use of anti-inflammatory preparations in small doses can prevent relapse, improve the quality of life of AD patients and reduce treatment costs. Prominent local efficacy in the treatment of AD has led to attempts to use tacrolimus in the treatment of other dermatological diseases.

Mechanism of action of tacrolimus

Tacrolimus belongs to the macrolide group, which exert their effect by inhibiting the activation of calcineurin. During the presentation of antigen to T cells there occurs an increase of calcium ion concentration and the induction of synthesis of the cytoplasmic portion of the lymphocyte-stimulated nuclear factor (nuclear factor of activated lymphocytes – NFAT). Calcium ions bind to calmodulin. This complex activates calcineurin, which causes dephosphorylation of the cytoplasmic NFAT fragment. This leads to its penetration into the nucleus and connection with a fragment of nuclear NFAT. This complex, by affecting the promoter regions of multiple genes, allows transcription of proinflammatory cytokines such as interleukin (IL)-2, IL-3, IFN-, and TGF-, and increased expression of receptors such as the receptor for IL-2. The described mechanism involves lymphocytes, mast cells and neutrophils. The action of tacrolimus depends on its connection to the cytoplasmic protein macrophilin 12, also called FKBP (FK binding protein), forming a complex that blocks calcineurin, preventing dephosphorylation of the NFAT cytoplasmic portion, and inhibits the further stages of lymphocyte activation. As a result, there is no transcription of mRNA for proinflammatory cytokines. The strength of binding of tacrolimus to FKBP is approximately three times greater than pimecrolimus [10, 11] (Fig. 1).

Side effects of tacrolimus

Side effects of tacrolimus concern mainly the reactions occurring immediately after drug application. They are itching and burning. Those complaints are transient and are reduced in continued use. No increased incidence of bacterial, viral or fungal infection while treating with tacrolimus was detected [12]. There was no effect of tacrolimus on inhibition of the cutaneous immune response [4]. In 2006, the Food and Drug Administration (FDA) accepted the supplemented information about calcineurin inhibitors, concerning the possible, but uncertain risk of developing skin cancer and lymphoma. However, most dermatological societies found that the FDA's concerns are unfounded and not supported by relevant clinical evidence [13]. There are single reports of diagnosis of Kaposi's varicelliform eruption in a child with atopic dermatitis during treatment with another calcineurin inhibitor, pimecrolimus [14]. It is worth emphasising that combining application of tacrolimus with exposure to UV is not recommended. This medicine is not photosensitive. Tacrolimus does not inhibit collagen synthesis, does not provoke atrophy of the epidermis, and does not damage the skin barrier. It can be safely used for many months, including around the face and neck, both in adults and children [15].

Application of tacrolimus

Efficacy of tacrolimus in the treatment of atopic dermatitis is commonly known and confirmed in numerous studies. The preparation can be administered to substitute for moderately potent CS. The results of AD treatment encourage researchers to test tacrolimus in other dermatological disorders which also have an inflammatory background. The first study on the use of tacrolimus in the treatment of psoriasis vulgaris was in 1998. Tacrolimus was used once a day at a concentration of 0.03%. The control group was treated with 0.005% calcipotriol twice a day. A third group of patients used a placebo. No statistically significant difference between the effectiveness of tacrolimus and placebo was observed. It should be emphasized that tacrolimus was applied once a day at a low concentration, 0.03% [16]. A year later another trial was performed on 16 patients with psoriasis vulgaris. The efficacy of tacrolimus, calcipotriol and betamethasone was compared. Tacrolimus was used within the area of the skin where previously an agent increasing penetration was applied. The result was a significant reduction of erythema and infiltration [17]. Subsequent studies have demonstrated significant efficacy of tacrolimus in the treatment of psoriasis occurring within the face and intertriginous areas [18-22]. In 2009 the National Psoriasis Foundation presented the consensus on the treatment of psoriasis, recommending tacrolimus as a preparation for use in case of long-term inverse psoriasis [23]. Another dermatological disorder in which an attempt of treatment with tacrolimus was made is seborrhoeic dermatitis , for which a significant improvement or complete resolution of skin lesions was obtained [24-25]. In 2007 the results of a study from the Department of Dermatology, Katowice, was published. Tacrolimus was used as a 0.1% ointment, twice daily for up to a month, depending on clinical improvement. Complete resolution of skin symptoms was obtained in all patients [26]. The positive effect of tacrolimus in seborrhoeic dermatitis stems not only from its anti-inflammatory activity, but also in relation to antifungal Malassezia furfur [27]. Tacrolimus was also effective in the treatment of lichen planus (LP). There are several studies that have shown high efficacy of tacrolimus in the treatment of erosive lesions located within the oral mucous membrane [28-30]. Local therapy resulted in significant improvement or complete resolution of lesions. The preparation was also effective in cases of LP lesions occurring within the anogenital area [31, 32]. Also satisfactory results were obtained due to the effect of tacrolimus applied to mucosal lesions in the course of lichen sclerosus (lichen sclerosus – LS) [33]. It should be noted that tacrolimus resolved complaints of burning and itching [34]. The first report about the good effects of therapy with tacrolimus in vitiligo dates from 2002 and concerns the observation of a patient with atopic dermatitis and vitiligo. Tacrolimus used topically because of atopic dermatitis has caused repigmentation [35]. Subsequent research has concerned the planned treatment of vitiligo with tacrolimus [36-38]. Interesting observations were made in 2003, comparing the efficacy of tacrolimus and clobetasol. The percentage of patients who experienced repigmentation was higher in the case of CS. Two-month therapy with clobetasol resulted in adverse effects in the form of telangiectasia and skin atrophy, while after application of tacrolimus only a burning sensation within the treated area was observed [39]. Thus, this confirms the high efficiency and high safety profile of these preparations in comparison to local CS. There have also been studies on combination therapy with tacrolimus and narrow-band UVB irradiation. After several months of therapy, a significant improvement was achieved [40-41]. Good results were also observed after concomitant treatment with the excimer laser [42]. Beneficial effects of treatment with tacrolimus 0.1% were noted in the case of localized scleroderma . It should be emphasized that better results were achieved using tacrolimus under occlusion. In patients with a long history of disease a partial reduction of sclerosis was observed, while in patients suffering for several months the resolution of skin symptoms was observed [43-44]. Reports on the use of tacrolimus in the treatment of different types of alopecia date back to 1995, when total regrowth was observed in a patient after liver transplantation treated generally with tacrolimus [45]. Subsequent studies concerned treatment specifically targeted at alopecia areata or alopecia universalis. In most cases, partial regrowth was observed as a result of topically used tacrolimus [46-48]. In 2009 the efficacy of tacrolimus and betamethasone was compared. In most patients, better results were observed after CS [49]. Treatment of alopecia requires the patient's self-discipline and patience, because therapy is prolonged. The effects of treatment are seen after several weeks of therapy. Eczema is one of the most common dermatological disorders, which repeatedly encounter problems of therapy. There are several studies confirming the efficacy of 0.1% tacrolimus in the treatment of stasis dermatitis and contact dermatitis [50-51]. German researchers have used the presented preparation in patients with eczematous lesions located within the vicinity of the anogenital area with an improvement with twice a day applications [52]. This treatment proved to be safe, without the side effects that accompany the use of steroid preparations. Skin lesions occurring in systemic lupus erythematosus, in its various forms (systemic lupus erythematosus, subacute cutaneous lupus erythematosus, discoid lupus erythematosus), often require the use of topical application of CS, even within the face, neck, and upper part of the chest. Treatment is prolonged and without side effects. Studies on the use of tacrolimus in these disorders produced positive results, and now calcineurin inhibitors are perceived as an alternative treatment [53-57].

Treatment of rosacea with tacrolimus ointment is ambiguous. In 2003 the results of therapy of steroid-induced rosacea were published. Combined use of oral tetracycline and tacrolimus resulted in an improvement of dermatological status [58]. Another study showed a reduction in erythema, without a reduction of maculopapular lesions [59]. An immunosuppressive effect of tacrolimus on the proliferation of Demodex folliculorum is also reported [60]. In the same year a case report concerning induction of rosaceiform dermatitis during treatment of facial inflammatory dermatoses with tacrolimus ointment was published. Three individuals were observed to have changes in the type of rosacea [61]. There are also reports of local therapy with tacrolimus bullous diseases. It should be emphasized that good results were obtained after application of tacrolimus 0.03% ointment applied to the conjunctiva in pemphigus [62] and a 0.03% suspension in the case of lesions located within the oral mucous membrane [63]. Publications concerning therapy of bullous pemphigoid with tacrolimus also confirm the efficacy of the drug [64, 65]. The first report on the effectiveness of tacrolimus in the treatment of pyoderma gangrenosum is from 1991. The drug was applied systemically to yield beneficial effects, in the absence of improvements in relation to other methods [66]. Results with the 0.1% ointment treatment are also satisfactory. Most studies are based on combination therapy with CS [67, 68]. Tacrolimus is a very useful method in reducing subjective symptoms, especially itching [69]. Diseases in which tacrolimus has proved to be an effective method of therapy are annular granuloma, sarcoidosis, incontinentia pigmenti, pityriasis alba, necrobiosis lipoidica, keloids, angiolymphoid, and venous ulcers. However, reports on those subjects are single. It is necessary to conduct further research. In each case a dermatological improvement was observed.

To conclude, tacrolimus is used in the treatment of many dermatological diseases. It helps to eliminate or partially replace local corticosteroids, especially in such regions as the face, neck, and groin. It is a safe drug, but further studies need to be conducted to confirm the safety and efficacy, and possible extension to new diseases, other than those described.

References

 1. Drake LA, Dinehart SM., Farmer ER, et al. Guidelines for care for the use of topical glucocorticoids. J Am Acad Dermatol 1996; 35: 615-9.  

2. Kino T, Hatanaka H, Hashimoto M, et al. FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro. J Antibiot 1987; 40: 1256-65.  

3. Nakagawa H , Etoh T, Ishibashi Y, et al. Tacrolimus ointment for atopic dermatitis. Lancet 1994; 24, 344: 883.  

4. Reitamo S, Wollenberg A, Schopf E, et al. Safety and efficacy of 1 year of tacrolimus ointment monotherapy in adults with atopic dermatitis. Arch Dermatol 2000; 136: 999-1006.  

5. Boguniewicz M, Fiedler VC, Raimer S, et al. A randomized, vehicle-controlled trial of tacrolimus ointment for treatment of atopic dermatitis in children. Pediatric Tacrolimus Study Group. J Allergy Clin Immunol 1998; 102: 637-44.  

6. Kang S, Lucky AW, Pariser D, et al. Long-term safety and efficacy of tacrolimus ointment for the treatment of atopic dermatitis in children. J Am Acad Dermatol 2001; 44: S58-64.  

7. Paller A, Eichenfield LF, Leung DY, et al. A 12-week study of tacrolimus ointment for the treatment of atopic dermatitis in pediatric patients. J Am Acad Dermatol 2001; 44: S47-57.  

8. Patel RR, Vander Straten MR, Korman NJ. The safety and efficacy of tacrolimus therapy in patients younger than 2 years with atopic dermatitis. Arch Dermatol 2003; 139: 1184-6.  

9. Reitamo S, Allsopp R. Treatment with twice-weekly tacrolimus ointment in patients with moderate to severe atopic dermatitis: results from two randomized, multicentre, comparative studies. J Dermatolog Treat 2010; 21: 34-44.

10. Bochelen D, Rudin M, Sauter A. Calcineurin inhibitors FK506 and SDZ ASM 981 alleviate the outcome of focal cerebral ischemic/reperfusion injury. J Pharmacol Exp Ther 1999; 288: 653-9.

11. Czarnecka-Operacz M, Silny W. Nowe leki w miejscowej terapii atopowego zapalenia skóry. Pol Merk Lek 2003; 84: 682-4.

12. Fleischer AB, Ling M, Eichenfield L, et al. Tacrolimus ointment for the treatment of atopic dermatitis is not associated with an increase in cutaneous infections. J Am Acad Dermatol 2002; 47: 562-70.

13. Ring J, Barker J, Behrendt H, et al. Review of the potential photo-cocarcinogenicity of topical calcineurin inhibitors: position statement of the European Dermatology Forum. J Eur Acad Dermatol Venerol 2005; 19: 663-71.

14. Lesiak A, Kopeć A, Chruściel A, et al. Wyprysk opryszczkowaty Kaposiego u dziecka z atopowym zapaleniem skóry w trakcie leczenia pimekrolimusem (1% krem). Post Dermatol Alergol 2010; 27: 135-9.

15. Nowicki R. Co nowego w leczeniu atopowego zapalenia skóry? Post Dermatol Alergol 2009; 26: 350-3.

16. Zonneveld IM, Rubins A, Jabłońska S, et al. Topical tacrolimus is not effective in chronic plaque psoriasis. A pilot study. Arch Dermatol 1998; 134: 1101-2.

17. Remiz A, Reitamo S, Erkko P, et al. Tacrolimus ointment improves psoriasis in a microplaque assay. Br J Dermatol 1999; 141: 101-7.

18. Freeman AK, Linowski GJ, Brady C, et al. Tacrolimus ointment for the treatment of psoriasis on the face and intertriginous areas. J Am Acad Dermatol 2003; 48: 564-8.

19. Lebwohl M, Freeman AK, Chapman MS, et al. Tacrolimus ointment is effective for facial and intertriginous psoriasis. J Am Acad Dermatol 2004; 51: 723-30.

20. Ezquerra GM, Sanchez R, Herrera Acosta E, et al. Topical tacrolimus for the treatment of psoriasis on the face, genitalia, intertriginous areas and corpolar plaques. J Drugs Dermatol 2006; 5: 334.

21. Brune A, Miller DW, Lin P et al. Tacrolimus ointment is effective for psoriasis on the face and intertriginous areas in pediatric patients. Pediatr Dermatol 2007; 24: 76-80.

22. Liao YH, Chiu HC, Tseng YS, Tsai TF. Comparison of cutaneous tolerance and efficacy of calcitriol 3 microg g(-1) ointment and tacrolimus 0.3 mg g(-1) ointment in chronic plaque psoriasis involving facial or genitofemoral areas: a double-blind, randomized controlled trial. Br J Dermatol 2007; 157: 1005-12.

23. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol 2009; 60: 643-59.

24. Braza TJ, DiCarlo JB, Soon SL, et al. Tacrolimus 0.1% ointment for seborrhoeic dermatitis: an open-label pilot study. Br J Dermatol 2003; 148: 1242-4.

25. Meshkinpour A, Sun J, Weinstein G. An open pilot study using tacrolimus ointment in the treatment of seborrheic dermatitis. J Am Acad Dermatol 2003; 49: 145-7.

26. Kamińska-Winciorek G, Brzezińska-Wcisło L. Miejscowe stosowanie takrolimusu jako alternatywna terapia łojotokowego zapalenia skóry – badanie pilotażowe. Post Dermatol Algol 2007; 5: 211-4.

27. Nagagawa H, Etoh T, Dakota Y, et al. Tacrolimus has antifungal activities against Malassezia furfur isolated from healthy adults and patients with atopic dermatitis. Clin Drug Invest 1996; 12: 245-50.

28. Vente C, Reich K, Rupprecht R, et al. Erosive mucosal lichen planus: response to topical treatment with tacrolimus. Br J Dermatol 1999; 140: 338-42.

29. Rozycki TW, Rogers RS, Pittelkow MR, et al. Topical tacrolimus in the treatment of symptomatic oral lichen planus: a series of 13 patients. J Am Acad Dermatol 2002; 46: 27-34.

30. Kaliakatsou F, Hodgson TA, Lewsey JD, et al. Management of recalcitrant ulcerative oral lichen planus with topical tacrolimus. J Am Acad Dermatol 2002; 46: 35-41.

31. Kirtschig G, Van Der Meulen AJ, Ion Lipan JW, et al. successful treatment of erosive vulvovaginal lichen planus with topical tacrolimus. Br J Dermatol 2002; 147: 625-6.

32. Watsky K. Erosive perianal lichen planus responsive to tacrolimus. Int J Dermatol 2003; 42: 217-8.

33. Virgili A, Lauriola MM, Mantovani L, et al. Vulvar lichen sclerosus: 11 women treated with tacrolimus 0,1 % ointment. Acta Derm Venereol 2007; 87: 69-72.

34. Wolska H, Błaszczyk M. Takrolimus i pimekrolimus w dermatologii. Cz. II. Leczenie innych niż AZS chorób skóry. Przegl Dermatol 2004; 91: 371-82.

35. Smith DA, Tofte SJ, Hanifin JM. Repigmentation of vitiligo with topical tacrolimus. Dermatology 2002; 205: 301-3.

36. Grimes PE, Soriano T, Dytoc MT. Topical tacrolimus for repigmentation of vitiligo. J Am Acad Dermatol 2002; 47: 789-91.

37. Travis LB, Weinberg JM, Silverberg NB. Successful treatment of vitiligo with 0.1% tacrolimus ointment. Arch Dermatol 2003; 139: 571-4.

38. Tanghetti EA. Tacrolimus ointment 0.1% produces repigmentation in patients with vitiligo: results of a prospective patient series. Cutis 2003; 71: 158-62.

39. Lepe V, Moncada B, Castanedo-Cazares JP, et al. A double-blind randomized trial of 0.1% tacrolimus vs 0.05% clobetasol for the treatment of childhood vitiligo. Arch Dermatol 2003; 139: 581-5.

40. Castendo-Cazares JP, Lepe V, Moncada B. Repigmentation of chronic vitiligo lesions by following tacrolimus plus ultraviolet-B-narrow-band. Photodermatol Photoimmunol Photomed 2003; 19: 35-6.

41. Baldo A, Casula L, Prizio E, et al. Topical tacrolimus and vitiligo: our experience in sixty cases. Gital Dermatol Venereol 2007; 142: 621-5.

42. Kawalek AZ, Spencer JM, Phelps RG. Combined excimer laser and topical tacrolimus for the treatment of vitiligo: a pilot study. Dermatol Surg 2004; 30: 130-5.

43. Mancuso G, Berdondini RM. Topical Tacrolimus in the treatment of localized scleroderma. Eur J Dermatol 2003; 13: 590-2.

44. Mancuso G, Berdondini RM. Localized scleroderma: response to occlusive treatment with tacrolimus ointment. Br J Dermatol 2005; 152: 180-2.

45. Rodriguez Rilo HL, Subbotin VM, Selby RR, Thomson AW. Rapid hair regrowth in refractory alopecia universalis associated with autoimmune disease following liver transplantation and tacrolimus (FK506) therapy. Transplantation 1995; 59: 1350-3.

46. Thiers BH. Topical tacrolimus: treatment failure in a patient with alopecia areata. Arch Dermatol 2000; 136: 124.

47. Feldmann KA, Kunte C, Wollenberg A, et al. Is topical tacrolimus effective in alopecia areata universalis? Br J Dermatol 2002; 147: 1031-2.

48. Thomas J. A study of topical tacrolimus in alopecia areata in children. International Congress of Dermatology, Prague 2009.

49. Saleem A, Khan M, Mashori GR, et al. Comparison of effectiveness of topical tacrolimus and betamethasone with soft paraffin in the treatment of patchy alopecia areata. Pak J Med Sci 2009; 25: 833-6.

50. Dissemond J, Knab J, Lehnen M, et al. Successful treatment of stasis dermatitis with topical tacrolimus. Vasa 2004; 33: 260-2.

51. Schliemann S, Kelterer D, Bauer A, et al. Tacrolimus ointment in the treatment of occupationally induced chronic hand dermatitis. Contact Dermatitis 2008; 58: 299-306.

52. Schauber J, Weisenseel P, Ruzicka T. Topical treatment of perianal eczema with tacrolimus 0.1%. Br J Dermatol 2009; 161: 1384-6.

53. Bohm M, Gaubitz M, Luger TA, et al. Topical tacrolimus as a therapeutic adjunct in patients with cutaneous lupus erythematosus. A report of three cases. Dermatology 2003; 207: 381-5.

54. Lampropoulos CE, Sangle S, Harrison P, et al. Topical tacrolimus therapy of resistant cutaneous lesions in lupus erythematosus: a possible alternative. Rheumatology 2004; 43: 1383-5.

55. Sugano M, Shintani Y, Kobayashi K, et al. Successful treatment with topical tacrolimus in four cases of discoid lupus erythematosus. J Dermatol 2003; 33: 887-91.

56. Bansal Ch, Ross AS, Cusack CA. Chronic cutaneous lupus in childhood: a report of two cases and review of the literature. Int J Dermatol 2008; 47: 525-6.

57. Wons A, Haust M, Schneider SW, et al. Efficacy o tacrolimus 0.1% ointment in cutaneous lupus erythematosus – a multicenter, randomized, double-blind, vehicle-controlled trial of 30 patients. Congress of the European Academy of Dermatology and Venereology, Paris 2008.

58. Pabby A, KP An, Laws RA. Combination therapy of tetracycline and tacrolimus resulting in rapid resolution of steroid-induced periocular rosacea. Cutis 2003; 72: 141-2.

59. Bamford JT, Elliott BA, Haller IV. Tacrolimus effect on rosacea. J Am Acad Dermatol 2004; 50: 107-8.

60. Antille Ch, Saurat JH, Lubbe J. Induction of rosaceiform dermatitis during treatment of facial inflammatory dermatoses with tacrolimus ointment. Arch Dermatol 2004; 140: 457-60.

61. Fujiwara S, Okubo Y, Irisawa R, et al. Rosaceiform dermatitis associated with topical tacrolimus treatment. J Am Acad Dermatol 2010; 62: 1050-2.

62. Hall VC, Liesegang TJ, Kostick DA, et al. Ocular mucous membrane pemphigoid and ocular pemphigus vulgaris treated topically with tacrolimus ointment. Arch Dermatol 2003; 139: 1083-4.

63. Vecchietti G, Kerl K, Hugli A, et al. Topical tacrolimus (FK506) for relapsing erosive stomatitis in paraneoplastic pemphigus. Br J Dermatol 2003; 148: 833-4.

64. Gunther C, Wozel G, Meurer M, et al. Topical tacrolimus treatment for cicatrial pemphigoid. J Am Academ Dermatol 2004; 50: 325-6.

65. Calcaterra R, Carducci M, Franco G, et al. Topical tacrolimus treatment for localized pretibial bullous phemphigoid. J Eur Acad Dermatol Venereol 2009; 23: 177-9.

66. Abu-Elmagd K, Jegasothy BV, Ackerman CD, et al. Efficacy of FK506 in the treatment of recalcitrant pyoderma gangrenosum. Transplan Proc 1991; 23: 3328-9.

67. Reich K, Vente C, Neumann C. Topical tacrolimus for pyoderma gangrenosum. Br J Dermatol 1998; 139: 755-7.

68. Chandrasekhara PKS, Jayachadran NV, Thomas J, et al. Successful treatment of pyoderma gangrenosum associated with juvenile idiopathic arthritis with a combination of topical tacrolimus and oral prednisolone. Clin Rheumatol 2009; 28: 489-90.

69. Stander S, Schurmeyer-Horst F, Luger TA, et al. Treatment of pruritic diseases with topical calcineurin inhibitors. Ther Clin Risk Manag 2006; 2: 213-8.
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