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Topical Calcineurin Inhibitors

Topical calcineurin inhibitors (TCIs), tacrolimus (0.03% and 0.1% ointment) and pimecrolimus (1% cream), serve primarily as second-line, steroid-sparing anti-inflammatory agents in urology and urogynecology.[3][7][35][36] Their off-label genital uses include genital lichen sclerosus, vulvar or penile lichen planus, Zoon balanitis, and other anogenital inflammatory dermatoses.[1][2][3] A novel investigational application is intravesical tacrolimus for refractory IC/BPS.

The defining advantage over topical corticosteroids is no risk of skin atrophy.[3][4]

For related agents, see High-potency topical corticosteroids, Intralesional corticosteroids, Platelet-rich plasma, Intravesical IC/BPS agents, and the clinical Lichen sclerosus article.

US labeling: these products are second-line atopic-dermatitis therapies, not FDA-approved genital LS treatments. Tacrolimus ointment is labeled for moderate to severe atopic dermatitis: adults may use 0.03% or 0.1%, and children aged 2–15 use 0.03% only.[7] Pimecrolimus 1% cream is labeled for mild to moderate atopic dermatitis from age 2.[35] Neither is labeled for children under two, and both labels call for short-term, non-continuous use and stopping when signs resolve. Genital use requires deliberate off-label selection.[7][35]

Mechanism​

TCIs inhibit calcineurin, a calcium-dependent phosphatase required for NFAT-mediated T-cell activation. The resulting block suppresses transcription of IL-2, IL-3, IL-4, IFN-γ, and TNF.[5][6] Additional mast-cell stabilization and suppression of histamine release contribute to the antipruritic effect.[7][8]

TCIs do not induce skin atrophy, striae, telangiectasia, or rebound flares associated with prolonged corticosteroid use.[3][4][36]

Vulvar and anogenital lichen sclerosus — primary indication​

The most extensively studied urogynecologic application.

Second-line positioning: EuroGuiDerm and the German S3 guideline place potent or ultrapotent topical corticosteroids first for genital LS at any age. The German S3 strongly recommends corticosteroids (↑↑) but only weakly suggests off-label TCIs (↑) as second choice or an adjunct when corticosteroids are contraindicated or insufficient.[9][36][38]

Evidence​

StudyDesignFinding
Hengge 2006Phase II multicenter (84 enrolled; 70 evaluable) — tacrolimus 0.1% BID × 16 wkAt week 24, active LS remitted in 43% of evaluable patients (36% of all enrolled), and 34% had partial remission (29% of all enrolled); lesional area and symptom scores declined. Three recurrences were reported during 18 months of follow-up in this uncontrolled series.[10][36]
Funaro 2014 RCTDouble-blind clobetasol 0.05% vs tacrolimus 0.1%Both reduced symptoms; clobetasol significantly more effective for complete absence of signs/symptoms (p = 0.002)[11]
Chi 2011 CochraneSystematic reviewIn one 12-week RCT of 38 women, pruritus and burning/pain differences were not statistically significant; clobetasol produced greater investigator-rated gross improvement.[12][13]
Mazzilli 2018Open study, 10 girls aged 4–9 with vulvar LS — tacrolimus 0.03% BID × 6 wkWell-tolerated; significant improvement in itching, pain, and constipation[14]

Clinical position​

Consider TCIs after reassessing the diagnosis, application technique, adherence and possible neoplasia in disease that is not responding. Appropriate uses include corticosteroid intolerance or contraindication, and selected inadequate response. Do not routinely replace effective corticosteroid maintenance. Pediatric use requires specialist selection.[15][16][36]

Clobetasol 0.05% ointment remains first-line for induction; TCIs are second-line and steroid-sparing.[36] See High-potency topical corticosteroids for the induction framework.

Penile lichen sclerosus / BXO​

Shieh 2024 J Urol systematic review: topical corticosteroids remain the mainstay of conservative management for penile or urethral LS, with tacrolimus supported as an alternative or adjuvant when escalation is needed.[17] In a prospective observational comparison, 80 men with meatal or penile urethral LS received clobetasol 0.05% or tacrolimus 0.03%, each applied topically and intraurethrally with self-calibration. Among 67 analyzed at 3 months, clobetasol had greater Qmax improvement and fewer additional procedures and skin adverse effects; self-calibration and short follow-up limit interpretation.[45]

Circumcision can resolve foreskin-limited pediatric BXO, but meatal or urethral disease may persist.[18] Evidence for topical immunomodulators preventing recurrent meatal stenosis is limited.[18]

Kim 2012. Among 10 patients with anogenital LS, nine improved objectively: five had >75% improvement and four had 25–75% improvement; one of six patients with extragenital LS had a partial response. Six of nine had symptom relapse during mean 29.3-month follow-up. The series did not test a maintenance regimen.[19]

Vulvar and genital lichen planus​

ACOG Level B: TCIs for LP resistant to topical corticosteroid therapy.[9] In erosive vulvar LP, assess vaginal involvement; vaginal lesions can cause adhesions and stenosis. For vaginal involvement, ACOG advises considering intravaginal corticosteroids with vulvar treatment and regular graded dilator use to help prevent scarring, synechiae and vaginal obliteration (Level C).[9] For vaginal erosive LP, BASHH describes prednisolone suppositories or clobetasol applied on a dilator.[40]

  • Byrd 2004. Retrospective data on tacrolimus for recalcitrant vulvar LP showed effective symptom control, but benefits were not sustained after discontinuation; individualized ongoing treatment may be needed[20]
  • Goldstein 2009. This review of case reports and series suggested tacrolimus and pimecrolimus may help steroid-refractory vulvar LP; the 2024 BASHH guideline grades the small-series evidence 2,C and notes frequent vulvar intolerance and concern for viral reactivation.[3][40]

Other anogenital dermatoses​

ConditionTCI roleEvidence
Plasma cell (Zoon) balanitisTacrolimus 0.1% produced responses within four weeks in a nine-patient series; biopsy when the diagnosis is uncertain and the plaque persists to exclude PeIN/SCCKyriakou 2014 (n = 9); Moreno-Arias 2005; BASHH 2026[21][22][44]
Genital psoriasisOff-label steroid-sparing treatment; short-term benefit in studies mixing facial, inverse and genital sitesAmiri 2023 SR (24 studies, five RCTs); no single pooled genital clearance rate[23][24]
Perianal eczemaTacrolimus 0.1% BID × 2 weeksSchauber 2009 (n = 24) — clinical improvement in all returning patients[25]
Resistant anogenital pruritusTacrolimus — likely via TRPV1 activationYosipovitch 2013[26]

Intravesical tacrolimus for IC/BPS — investigational​

A novel off-label application under active investigation.

  • Mishra 2019 uncontrolled pilot (n = 24 intractable IC/BPS): tacrolimus dissolved in DMSO or sterile water was instilled intravesically; 13/24 were classified as responders on the 12-week Global Response Assessment. Later follow-up ranged from 6 to 63 months, without controlled durability data. Blood levels were checked in only 10 patients; no systemic adverse events were reported, but postinstillation symptom flares sometimes prompted discontinuation and systemic safety remains uncertain.[27]
  • 2025 global consensus lists tacrolimus among immunotherapies for IC/BPS, alongside cyclosporine[28]

Cyclosporine A has stronger evidence in IC/BPS based on Di 2021 network meta-analysis and Giannantoni 2012 European Urology systematic review; intravesical tacrolimus remains early-stage off-label pending controlled trials.[29][30]

See Intravesical IC/BPS agents for the complete instillation armamentarium.

Genital graft-versus-host disease — caution​

The Choi and Elad series below describe cutaneous chronic GVHD and provide indirect evidence for genital disease.[4][31] Baumrin's 2024 organ-specific review places high-potency topical steroid ointment first and describes selected tacrolimus after incomplete response or for severe disease; the US label warns against use in immunocompromised patients and does not recommend it when GVHD causes skin-barrier defects.[33][41]

  • Choi 2001 case series (n = 18 steroid-refractory chronic cutaneous GVHD): tacrolimus 0.1% improved pruritus or erythema in 13 (72%), often as a bridge to systemic therapy[4]
  • Elad 2003. 7 of 10 patients with steroid-dependent chronic cutaneous GVHD responded to tacrolimus 0.03–0.1%[31]
  • Rostagno 2022 scoping review concluded no topical intervention has strong evidence in GVHD; topical therapies serve as adjuncts to systemic treatment[32]

The FDA label does not recommend topical tacrolimus when cutaneous GVHD causes a skin-barrier defect that may increase systemic absorption. Toxic tacrolimus levels have been reported with occlusive dressings.[33][34]

Safety​

Adverse effects​

ConcernDetails
Local irritationBurning, stinging, or pruritus is most common in the first days of tacrolimus use and typically improves as atopic dermatitis lesions resolve; vulvar series also report intolerance and early discontinuation.[3][5][6][7]
Active or new infection at application siteResolve bacterial or viral infection before treatment and reassess genital herpes or candidiasis arising during use. Infections such as genital herpes and vulvovaginal candidiasis occurred in 2% of 84 tacrolimus-treated LS patients.[7][35][36]
FDA boxed warning"Long-term safety of topical calcineurin inhibitors has not been established." Rare cases of malignancy (skin and lymphoma) have been reported, and a causal relationship has not been established. The label directs avoiding continuous long-term use and, for pimecrolimus, use in children under 2[7][35]
No skin atrophyKey advantage over corticosteroids for chronic anogenital use[3]
Systemic absorptionTacrolimus absorption is generally low in atopic dermatitis studies, but barrier defects and large treated areas increase exposure. The label does not recommend use when a skin-barrier defect, including in cutaneous GVHD or Netherton's syndrome, may increase absorption; occlusive dressings should not be used. Postmarketing acute renal failure has been reported, and the label advises caution in patients predisposed to renal impairment.[7][33]
Avoid on premalignant / malignant lesionsPer FDA label (pimecrolimus label states these can present as dermatitis); avoid in immunocompromised patients[7][35]
Sun protectionThe tacrolimus label advises minimizing natural or artificial sunlight exposure during treatment[7]
Pregnancy / breastfeedingThe 2024 BASHH vulval guideline advises against TCIs for vulvar LS or LP during pregnancy or breastfeeding; choose a guideline-supported topical corticosteroid regimen when treatment is needed.[40]

Malignancy evidence: in the Adams 2026 TriNetX cohort (6,227 TCI-exposed LS patients), TCI exposure was not associated with increased vulvar dysplasia or malignancy at any time point, and risk did not differ significantly from clobetasol; clobetasol exposure was associated with a lower 2-year vulvar malignancy risk than in matched corticosteroid-naïve LS patients (RR 0.62).[37] Adults in the European JOELLE cohort showed little evidence linking TCIs to skin cancer or lymphoma, though a cutaneous T-cell lymphoma signal for tacrolimus (IRR 1.80) and modest excesses for pimecrolimus persisted and confounding by indication is likely; results in children were inconclusive.[39] See clinical LS malignancy risk for the study and its limits.

Tacrolimus vs pimecrolimus​

AgentStrengthPractical differentiators
Tacrolimus ointment 0.03% / 0.1%Both strengths are labeled from age 16 for atopic dermatitis; only 0.03% is labeled at ages 2–15; adult genital LS studies commonly use 0.1% off-labelMost LS, LP and Zoon balanitis data are for tacrolimus; a 2009 vulvar review suggests pimecrolimus may cause less application-site burning or stinging than tacrolimus[3][7][36]
Pimecrolimus cream 1%Single strengthIn one 12-week vulvar LS RCT, symptom differences were not statistically significant, while clobetasol produced greater investigator-rated gross improvement; selected second-line use when appropriate corticosteroid treatment cannot be used[12][13]

Prescribing summary​

ConditionFirst-lineTCI roleTCI regimenDuration
Lichen sclerosus (vulvar or penile)Clobetasol 0.05% ointmentSelected off-label second-line useSpecialist-directed tacrolimus, commonly 0.1% in adultsReassess and reduce frequency after control; not automatic indefinite BID[9][10]
Vulvar / genital lichen planusClobetasol 0.05% ointmentSecond-line when steroid-refractoryTacrolimus BID initially in Byrd’s vulvar series (0.1% prescribed; 5/16 initially used compounded 0.03%)Ongoing frequency varied; symptoms often recur on discontinuation[9][20]
Plasma cell (Zoon) balanitisConsider clobetasol propionate or Trimovate once or twice daily and refer for circumcision (BASHH 2026, 1,D)Alternative for recalcitrant disease or when circumcision is declinedTacrolimus 0.1% ointmentReassess response at four weeks[21][44]
Genital psoriasisVulvar: weak- to moderately potent TCS (BASHH 2024, 1,B); penile: moderate-potency TCS (BASHH 2026, 1,C)[40][44]Off-label steroid-sparing option; any maintenance is individualizedTacrolimus 0.1% BID or pimecrolimus 1% BID in published short coursesReassess response; long-term genital maintenance data are limited[23][24]
Perianal eczemaLow-potency TCSAlternative if corticosteroid refractoryTacrolimus 0.1% BID × 2 weeksShort course[25]
Atopic-dermatitis-associated refractory pruritus aniAddress cause; skin care and appropriate topical corticosteroidSelected off-label option after prior treatment failureTacrolimus 0.03% BID, studied against petrolatumFour-week course with reassessment[26][42]
IC/BPS (refractory)Individualized AUA-guideline careInvestigationalNo validated instillation formulation or schedule; Mishra changed vehicle and number of doses during the pilotSpecialist research protocol with safety monitoring only[27]
Genital chronic GVHDHigh-potency topical corticosteroid ointment for local diseaseA 2024 specialist review describes vulvar tacrolimus after incomplete steroid response or for severe disease; the US label says not to use it in immunocompromised patients and does not recommend it with GVHD-related skin-barrier defectsThe review describes vulvar tacrolimus 0.1% BID; avoid occlusion and monitor blood levels if use proceeds despite these cautionsReassess local response; systemic treatment depends on overall GVHD severity[33][34][41]

Evidence Summary​

IndicationEvidence and limitsKey source
Vulvar LS (general)Small RCTs and uncontrolled studies; clobetasol remains preferredChi 2011 Cochrane[12]; Funaro 2014[11]; Hengge 2006[10]
Penile or urethral LSSystematic review and short observational comparison; limited controlled evidenceShieh 2024[17]; Choudhury 2023[45]
Pediatric LSSmall case seriesMazzilli 2018[14]
Vulvar lichen planusRetrospective series and guideline adviceByrd 2004[20]; ACOG 224[9]
Plasma cell balanitisSmall case seriesKyriakou 2014[21]
Genital psoriasisSystematic review; limited direct comparative evidenceAmiri 2023[23]
Intravesical tacrolimus for IC/BPSUncontrolled pilotMishra 2019[27]
GVHDCase series and toxicity reports; label cautionChoi 2001[4]; Olson 2014 toxicity report[34]

Clinical Positioning​

  • TCIs are second-line, steroid-sparing agents for chronic anogenital inflammatory dermatoses; their defining feature is no skin atrophy, which can support selected intermittent use in chronic disease.[3][9]
  • Clobetasol remains first-line in LS.[11][12][11][12]
  • In pediatric LS, corticosteroids remain first line. Small TCI series support selected specialist use.[9][14]
  • Counsel about application-site burning. Burning or itching may occur early; in a 29-woman vulvar LS pimecrolimus series, three stopped in the first week because of intense pruritus or inadequate response.[3][5][6]
  • Explain the boxed warning accurately. Malignancy causality has not been established, and long-term safety is unknown. Avoid continuous long-term application and premalignant or malignant lesions; the tacrolimus label says it should not be used in immunocompromised patients.[7]
  • Pimecrolimus is less effective than clobetasol for LS gross improvement — consider it only as a selected second-line option, with response monitoring.[12][13]
  • For Zoon balanitis, circumcision is an option for persistent disease; remission is not assured. Tacrolimus remains a nonsurgical option for patients declining or unable to undergo circumcision. In a retrospective cohort, complete remission was recorded in 12/27 patients with known outcomes after circumcision; with tacrolimus, 41/67 had partial remission and 2/67 complete remission. Treatment groups overlapped and follow-up differed.[21][43]
  • Intravesical tacrolimus for IC/BPS is investigational (Mishra 2019: 13/24 met the Global Response Assessment responder definition at 12 weeks; later follow-up ranged from 6 to 63 months without a controlled durability estimate).[27] Cyclosporine has stronger evidence in this setting.[27][29]
  • Avoid occlusive dressings and use in skin-barrier disorders with increased systemic absorption risk, including cutaneous GVHD. Toxic blood levels have been reported after extensive application under occlusion in patients with GVHD.[33][34]
  • Avoid application on premalignant or malignant lesions. Evaluate unresponsive or atypical vulvar lesions with biopsy before escalating immunomodulatory therapy; CTCL and early vulvar SCC can masquerade as dermatitis or LS.[7][9]
  • Sun protection. Minimize natural and artificial sunlight exposure during tacrolimus treatment, as the product label directs.[7]

See Also​

References​

1. Cury Martins J, Martins C, Aoki V, et al. "Topical tacrolimus for atopic dermatitis." Cochrane Database Syst Rev. 2015;(7):CD009864. doi:10.1002/14651858.CD009864.pub2

2. Vakharia PP, Silverberg JI. "New and emerging therapies for paediatric atopic dermatitis." Lancet Child Adolesc Health. 2019;3(5):343–353. doi:10.1016/S2352-4642(19)30030-6

3. Goldstein AT, Thaçi D, Luger T. "Topical calcineurin inhibitors for the treatment of vulvar dermatoses." Eur J Obstet Gynecol Reprod Biol. 2009;146(1):22–29. doi:10.1016/j.ejogrb.2009.05.026

4. Choi CJ, Nghiem P. "Tacrolimus ointment in the treatment of chronic cutaneous graft-vs-host disease: a case series of 18 patients." Arch Dermatol. 2001;137(9):1202–1206. doi:10.1001/archderm.137.9.1202

5. Eichenfield LF, Tom WL, Berger TG, et al. "Guidelines of care for the management of atopic dermatitis: Section 2. Management and treatment of atopic dermatitis with topical therapies." J Am Acad Dermatol. 2014;71(1):116–132. doi:10.1016/j.jaad.2014.03.023

6. Prucha H, Schnopp C, Akdis C, et al. "Pimecrolimus, a topical calcineurin inhibitor used in the treatment of atopic eczema." Expert Opin Drug Metab Toxicol. 2013;9(11):1507–1516. doi:10.1517/17425255.2013.819343

7. DailyMed. Tacrolimus ointment prescribing information, updated April 15, 2026. Label. Accessed September 12, 2026.

8. Rallis E, Korfitis C, Gregoriou S, Rigopoulos D. "Assigning new roles to topical tacrolimus." Expert Opin Investig Drugs. 2007;16(8):1267–1276. doi:10.1517/13543784.16.8.1267

9. American College of Obstetricians and Gynecologists. "Diagnosis and management of vulvar skin disorders: ACOG Practice Bulletin Summary, Number 224." Obstet Gynecol. 2020;136(1):222–225. doi:10.1097/AOG.0000000000003945

10. Hengge UR, Krause W, Hofmann H, et al. "Multicentre, phase II trial on the safety and efficacy of topical tacrolimus ointment for the treatment of lichen sclerosus." Br J Dermatol. 2006;155(5):1021–1028. doi:10.1111/j.1365-2133.2006.07446.x

11. Funaro D, Lovett A, Leroux N, Powell J. "A double-blind, randomized prospective study evaluating topical clobetasol propionate 0.05% versus topical tacrolimus 0.1% in patients with vulvar lichen sclerosus." J Am Acad Dermatol. 2014;71(1):84–91. doi:10.1016/j.jaad.2014.02.019

12. Chi CC, Kirtschig G, Baldo M, et al. "Topical interventions for genital lichen sclerosus." Cochrane Database Syst Rev. 2011;(12):CD008240. doi:10.1002/14651858.CD008240.pub2

13. Chi CC, Kirtschig G, Baldo M, et al. "Systematic review and meta-analysis of randomized controlled trials on topical interventions for genital lichen sclerosus." J Am Acad Dermatol. 2012;67(2):305–312. doi:10.1016/j.jaad.2012.02.044

14. Mazzilli S, Diluvio L, Di Prete M, et al. "Tacrolimus 0.03% ointment for treatment of paediatric lichen sclerosus: a case series and literature review." J Int Med Res. 2018;46(9):3724–3728. doi:10.1177/0300060518778219

15. De Luca DA, Papara C, Vorobyev A, et al. "Lichen sclerosus: the 2023 update." Front Med. 2023;10:1106318. doi:10.3389/fmed.2023.1106318

16. Borghi A, Corazza M. "Novel therapeutic approaches and targets for treatment of vulvar lichen sclerosus." Curr Pharm Biotechnol. 2021;22(1):99–114. doi:10.2174/1389201021666200516154310

17. Shieh C, Hakam N, Pearce RJ, et al. "Conservative management of penile and urethral lichen sclerosus: a systematic review." J Urol. 2024;211(3):354–363. doi:10.1097/JU.0000000000003804

18. Nguyen ATM, Holland AJA. "Balanitis xerotica obliterans: an update for clinicians." Eur J Pediatr. 2020;179(1):9–16. doi:10.1007/s00431-019-03516-3

19. Kim GW, Park HJ, Kim HS, et al. "Topical tacrolimus ointment for the treatment of lichen sclerosus, comparing genital and extragenital involvement." J Dermatol. 2012;39(2):145–150. doi:10.1111/j.1346-8138.2011.01384.x

20. Byrd JA, Davis MD, Rogers RS. "Recalcitrant symptomatic vulvar lichen planus: response to topical tacrolimus." Arch Dermatol. 2004;140(6):715–720. doi:10.1001/archderm.140.6.715

21. Kyriakou A, Patsatsi A, Patsialas C, Sotiriadis D. "Therapeutic efficacy of topical calcineurin inhibitors in plasma cell balanitis: case series and review of the literature." Dermatology. 2014;228(1):18–23. doi:10.1159/000357153

22. Moreno-Arias GA, Camps-Fresneda A, Llaberia C, Palou-Almerich J. "Plasma cell balanitis treated with tacrolimus 0.1%." Br J Dermatol. 2005;153(6):1204–1206. doi:10.1111/j.1365-2133.2005.06945.x

23. Amiri D, Schwarz CW, Gether L, Skov L. "Safety and efficacy of topical calcineurin inhibitors in the treatment of facial and genital psoriasis: a systematic review." Acta Derm Venereol. 2023;103:adv00890. doi:10.2340/actadv.v103.6525

24. Armstrong AW, Read C. "Pathophysiology, clinical presentation, and treatment of psoriasis: a review." JAMA. 2020;323(19):1945–1960. doi:10.1001/jama.2020.4006

25. Schauber J, Weisenseel P, Ruzicka T. "Topical treatment of perianal eczema with tacrolimus 0.1%." Br J Dermatol. 2009;161(6):1384–1386. doi:10.1111/j.1365-2133.2009.09345.x

26. Yosipovitch G, Bernhard JD. "Chronic pruritus." N Engl J Med. 2013;368(17):1625–1634. doi:10.1056/NEJMcp1208814

27. Mishra NN, Riedl C, Shah S, Pathak N. "Intravesical tacrolimus in treatment of intractable interstitial cystitis/bladder pain syndrome — a pilot study." Int J Urol. 2019;26(Suppl 1):68–72. doi:10.1111/iju.13978

28. Buford K, Peters KM, Riedl C, et al. "Global consensus on interstitial cystitis/bladder pain syndrome: an update on therapeutic treatments." Neurourol Urodyn. 2025. doi:10.1002/nau.70106

29. Di XP, Luo DY, Jin X, et al. "Efficacy and safety comparison of pharmacotherapies for interstitial cystitis and bladder pain syndrome: a systematic review and Bayesian network meta-analysis." Int Urogynecol J. 2021;32(5):1129–1141. doi:10.1007/s00192-020-04659-w

30. Giannantoni A, Bini V, Dmochowski R, et al. "Contemporary management of the painful bladder: a systematic review." Eur Urol. 2012;61(1):29–53. doi:10.1016/j.eururo.2011.07.069

31. Elad S, Or R, Resnick I, Shapira MY. "Topical tacrolimus — a novel treatment alternative for cutaneous chronic graft-versus-host disease." Transpl Int. 2003;16(9):665–670. doi:10.1007/s00147-003-0594-2

32. Rostagno E, Campanati A, Mordini N, et al. "Phototherapy and topical treatments for cutaneous graft-vs-host disease in haematopoietic stem cell transplantation patients: a scoping review." J Eur Acad Dermatol Venereol. 2022;36(7):1003–1015. doi:10.1111/jdv.18074

33. DailyMed. Tacrolimus ointment prescribing information, updated April 15, 2026: skin-barrier disorders and GVHD precautions. Label. Accessed September 12, 2026.

34. Olson KA, West K, McCarthy PL. "Toxic tacrolimus levels after application of topical tacrolimus and use of occlusive dressings in two bone marrow transplant recipients with cutaneous graft-versus-host disease." Pharmacotherapy. 2014;34(6):e60–e64. doi:10.1002/phar.1418

35. Bausch Health. Elidel (pimecrolimus) Cream 1% prescribing information. Label. The generic pimecrolimus 1% cream label effective April 30, 2026 carries the same boxed warning and second-line atopic-dermatitis indication for non-immunocompromised patients aged 2 years and older.

36. Kirtschig G, Woelber L, Günthert A, et al. "Evidence- and consensus-based guideline on lichen sclerosus." J Dtsch Dermatol Ges. 2026;24(4):566–584. doi:10.1111/ddg.70000. Full German S3 guideline, June 2025.

37. Adams PE, Vikram EP, Curman P, et al. "Topical therapy and vulvar malignancy risk in lichen sclerosus: a large propensity-matched study." Am J Obstet Gynecol. 2026;234(5):1402–1415. doi:10.1016/j.ajog.2025.12.043

38. Kirtschig G, Kinberger M, Kreuter A, et al. "EuroGuiderm guideline on lichen sclerosus-Treatment of lichen sclerosus." J Eur Acad Dermatol Venereol. 2024;38(10):1874–1909. doi:10.1111/jdv.20083

39. Arana A, Pottegård A, Kuiper JG, et al. "Long-term risk of skin cancer and lymphoma in users of topical tacrolimus and pimecrolimus: final results from the extension of the cohort study Protopic Joint European Longitudinal Lymphoma and Skin Cancer Evaluation (JOELLE)." Clin Epidemiol. 2021;13:1141–1153. doi:10.2147/CLEP.S331287

40. Edwards SK, Lewis F, Fernando I, Haddon L, Grover D. "2024 British Association for Sexual Health and HIV (BASHH) UK national guideline on the management of vulval conditions." Int J STD AIDS. 2025;36(5):346–371. doi:10.1177/09564624241311629

41. Baumrin E, Loren AW, Falk SJ, Mays JW, Cowen EW. "Chronic graft-versus-host disease. Part II: disease activity grading and therapeutic management." J Am Acad Dermatol. 2024;90(1):19–36. doi:10.1016/j.jaad.2022.12.023

42. Ucak H, Demir B, Cicek D, et al. "Efficacy of topical tacrolimus for the treatment of persistent pruritus ani in patients with atopic dermatitis." J Dermatolog Treat. 2013;24(6):454–457. doi:10.3109/09546634.2013.800181

43. Jormanainen A, Pasternack C, Pasternack R. "A retrospective study of 129 patients with plasma cell balanitis." JEADV Clin Pract. 2023;2(2):293–299. doi:10.1002/jvc2.141

44. Edwards SK, Shashidharan P, Fernando I, et al. "BASHH national guideline on the management of balanoposthitis (and related penile skin conditions) 2026." Int J STD AIDS. 2026;37(9):969–983. doi:10.1177/09564624261452757

45. Choudhury S, Khare E, Pal DK. "Comparative effect of intraurethral clobetasol and tacrolimus in lichen sclerosus-associated urethral stricture disease." Urol Ann. 2023;15(2):174–179. doi:10.4103/ua.ua_45_22