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Lichen Sclerosus Treatment Series: Calcineurin Inhibitors

Lichen Sclerosus Treatment Series: Calcineurin Inhibitors


We are continuing our lichen sclerosus treatment series today by looking at topical calcineurin inhibitors. In previous posts, I discussed topical corticosteroids and their associated side effects. Be sure to check out those posts first!

In today's post, you will learn:

  • What topical calcineurin inhibitors (calcineurin inhibitors or TCIs for short) are
  • How calcineurin inhibitors work
  • Their side effects and risks
  • And so much more!

*This post is evidence-based; I draw on the medical literature to share what you need to know about calcineurin inhibitors and lichen sclerosus. Importantly, what I share is my interpretation of the science and data.

What the Heck are Topical Calcineurin Inhibitors (TCIs)?

TCIs are topical, non-steroidal immunosuppressant medications. Topical means the medicine is applied directly to the body in a cream or ointment base instead of taking an oral medication. An immunosuppressant medication works to keep your immune system functioning optimally. For example, these medications can help calm an overactive immune system.

In the case of lichen sclerosus, we are dealing with a local overactive immune response. To learn more about lichen sclerosus, you can watch my video here, or if you are more science-inclined, you can check out this webinar by Dr. Goldstein and Dr. Krapf. A local immune response in the basement layer of the vulvar skin sets off a massive inflammatory reaction responsible for many of the skin changes and symptoms of lichen sclerosus. Thus, if you calm the overactive immune response, you control the inflammation. When you control the inflammation, you can better manage lichen sclerosus and get into remission

Therefore, because calcineurin inhibitors can suppress immune system activity, TCIs have been studied and used to treat many immune-mediated skin conditions, such as lichen sclerosus (Corazza et al., 2021).

The main calcineurin inhibitors used for lichen sclerosus are Pimecrolimus and Tacrolimus.

What does the Science Say?

Overall, the studies are pretty promising and show that topical calcineurin inhibitors can be a good option for folks (Corazza et al., 2021).

A double-blind, randomized study by Goldstein et al. 2011 compared the before and after biopsies of folks with vulvar lichen sclerosus. Participants were split into two groups. One group used Clobetasol (steroid), and the other group used Pimecrolimus (calcineurin inhibitor). 18 people were treated with Pimecrolimus for 12 weeks, and 20 were treated with Clobetasol for 12 weeks (ibid, 2-3). Since the study was blinded, neither group knew which treatment they used. 

Success was evaluated by comparing before and after biopsies from each patient to see whether there was a reduction in inflammation. The researchers also looked at secondary measures, including questionnaires and patient symptom reporting.

When comparing the two groups, they found that Clobetasol and Pimecrolimus were both effective in reducing inflammation. However, they note that Clobetasol performed slightly better in reducing inflammation. They conclude that Clobetasol should be the first-line treatment and Pimecrolimus should be the second-line treatment for folks who cannot tolerate or do not want to use steroids.

Side Effects and Calcineurin Inhibitors

Burning and Stinging

The primary documented side effect of calcineurin inhibitors are stinging and burning. Specifically, this side effect is experienced after you apply the medication. How long someone will experience the burning and stinging will vary (see below for lived-experienced). 

This burning sensation is usually more pronounced during the first few weeks of application and often fades as you continue using it (Corazza et al., 2021). It is essential to know this information so that you do not stop using your medication as prescribed by your doctor (ibid).

Lived Experiences with TCIs – What I've Heard from the LS Community

I have heard mixed things about calcineurin inhibitors from folks using them in the LS community.

Image of people from different races and ethnicities standing together in a room with red brick walls with smiles on their faces. This image represents the diverse and powerful LS community out there.

For example, some folks say they did not experience burning or stinging. They are happy with their treatment.

Other folks say it did burn and sting for the first week, but that sensation reduced over time, and after a few weeks, it felt fine. Overall, they are happy with their treatment.

A handful of folks did say the burning was too intense, and they stopped treatment. 

Remember, LS is an individualized condition; we will all respond differently to different medications. 

Pro-Tip from a calcineurin inhibitor user: If you are worried about burning, try putting your tube of TCIs in the fridge so that it is cold when you apply it. Doing so blunts the burning sensation for this individual.

Risks and Benefits

As discussed in my previous post on steroids, it is essential always to be aware of the risks and benefits of every medication. Moreover, trust me, I know it's frustrating that no medication is risk-free. All medications come with risks and benefits. This is why it is essential to be aware of both to make the best decisions for your body.

The two main risks documented in the literature are the development of squamous cell carcinoma and vulvar cancer. Let us review both.

Vulvar Cancer Risk

If you read my post on steroids, you know that having lichen sclerosus means you are at a slightly increased risk of developing vulvar cancer. If you want to learn more about this, check out my blog post here.

However, current research on steroids suggests that consistent and proper use of topical corticosteroids can reduce the likelihood of developing vulvar cancer.

OK, but what about TCIs?

Unfortunately, we just do not have the data on this yet, so I cannot share a definitive answer from the medical community.

One *may* infer that if steroids reduce the likelihood of developing vulvar cancer by significantly reducing inflammation, and if TCIs also significantly reduce inflammation (albeit slightly less than steroids), then TCIs *may* also reduce the likelihood of developing vulvar cancer. However, this is an inference and is not based on evidence-based information.

Squamous Cell Carcinoma

There is a risk that calcineurin inhibitors *may* cause squamous cell carcinoman(SCC). A case study of a single individual using TCIs concluded with the authors stating:

It may be safest to restrict topical immunosuppressives to patients with LS who cannot use topical corticosteroids because of the risk of potentiating SCC (Fischer & Bradford, 2007).

However, this is a single case study, and it was published quite a while ago in 2007.

More recently, a 2021 review paper by Corraza et al. noted that based on the current evidence, short-term application of calcineurin inhibitors does not appear to increase the risk of squamous cell carcinoma.

The 2021 European Guidelines state:

The long-term risks need to be studied because of concerns about the possibility of topical immunosuppression increasing the risk of malignancy (van der Meijden et al., 2021). In other words, because there is not nearly as much research on TCIs as there is on steroids, we do not completely understand the full scope of long-term risks, and we need more studies on this. 

We need more studies exploring this potential connection between TCIs and squamous cell carcinoma. Further, this is something to consider when weighing the risks and benefits of this treatment.

Why are Calcineurin Inhibitors Considered a Second-Line Treatment?

There is agreement within the medical community that TCIs are a second-line treatment for lichen sclerosus, which is safe for both adults and children with vulvar lichen sclerosus (Corazza et al., 2021). The main reason is that steroids slightly outperform TCIs in their ability to decrease inflammation (Krapf et al., 2020).

Another reason is that there is more research on steroids than calcineurin inhibitors. This *may* make some doctors more inclined to prescribe steroids over TCIs, but this is just my guess and not stated in the medical literature.

I have heard doctors and LS specialists say it is their second-line treatment because of the burning and stinging in some patients who use calcineurin inhibitors. The burning and stinging may cause some patients to discontinue using their medication (Corazza et al., 2021). 


In sum, calcineurin inhibitors are considered by *most* of the medical community to be a safe and effective second-line treatment for both adults and children with vulvar lichen sclerosus. The main side effects are burning and discomfort upon application, which tend to fade and disappear after a couple of weeks. Risks to consider include the *potential* connection between TCIs and squamous cell carcinoma (no concrete evidence yet to suggest this) and the fact that we do not have any studies showing calcineurin inhibitors can reduce the risk of vulvar cancer. Always be sure to weigh the benefits versus the risks in choosing a treatment plan, and be sure to discuss concerns with your healthcare provider.

If you use TCIs, let us know in the comments if you find them helpful!

Feel free to drop any questions about TCIs in the comment section below!

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Reach Out to Me

Whether you are debating booking a support call with me, have a quick question, or want to share something related to my content I can be reached via:

Email: Jaclyn@lostlabia.com

DM: @thelostlabiachronicles on Instagram, Facebook, and TikTok.

Support Resources

FREE Lichen Sclerosus Virtual Meetup hosted by myself and Kathy of Lichen Sclerosus Podcast – sign up here.

Feel free to book a 1:1 call with me if you struggle with grief and emotions. Simply click this link to learn more about lichen sclerosus peer support calls.

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LSSN Membership – sign up here.

For a more detailed list of free and paid support resources, check out my LS resources page here.

Sources Cited & Consulted

2021 European Guidelines

Corazza M, Schettini N, Zedde P, Borghi A. Vulvar Lichen Sclerosus from Pathophysiology to Therapeutic Approaches: Evidence and Prospects. Biomedicines. 2021; 9(8):950. https://doi.org/10.3390/biomedicines9080950

Fischer G, Bradford J. Topical immunosuppressants, genital lichen sclerosus and the risk of squamous cell carcinoma. J Reprod Med2007;52:329–331

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, 84–91. 

Goldstein, A.T.; Creasey, A.; Pfau, R.; Phillips, D.; Burrows, L.J. A double-blind, randomized controlled trial of Clobetasol versus Pimecrolimus in patients with vulvar lichen sclerosus. J. Am. Acad. Dermatol. 2011, 64, e99–e104.

Krapf JM, Mitchell L, Holton MA, Goldstein AT. Vulvar Lichen Sclerosus: Current Perspectives. Int J Women's Health. 2020 Jan 15;12:11-20. doi: 10.2147/IJWH.S191200. PMID: 32021489; PMCID: PMC6970240.

More Citations

Lee A, Bradford J, Fischer G. “Long-term Management of Adult Vulvar Lichen Sclerosus: A Prospective Cohort Study of 507 Women”. JAMA Dermatol. 2015 Oct;151(10):1061-7. DOI: 10.1001/jamadermatol.2015.0643. PMID: 26070005. https://pubmed.ncbi.nlm.nih.gov/26070005/ 

Lee, A. and G. Fisher (2018). “Diagnosis and Treatment of Vulvar Lichen Sclerosus: An Update for Dermatologists.” American Journal of Clinical Dermatology. DOI/10.1007/s40257-018-0364-7 https://pubmed.ncbi.nlm.nih.gov/29987650/ 

Lewis FM, Tatnall FM, Velangi SS, Bunker CB, Kumar A, Brackenbury F, Mohd Mustapa MF, Exton LS. British Association of Dermatologists guidelines for the management of lichen sclerosus, 2018. Br J Dermatol. 2018 Apr;178(4):839-853. DOI: 10.1111/bjd.16241. PMID: 29313888. 


    • Jaclyn Lanthier

      That’s a really good question, and, to be honest, I’m not sure. I do not think it would hurt, but you can always discuss it with your health care provider, just in case. I will try and ask around and find out; if I get a response, I’ll let you know. With love, Jaclyn

    • Evelyn

      Just not able to to tolerate Tacrolimus . It was recommended after I had been using clobetasol for a very long time, and not to use any more.
      Keep trying Tacrolimus burning is so severe even after using a week. Is there an alternative, no doubt you know I am very uncomfortable.
      Thank you for your suggestions

      • Jaclyn Lanthier

        So sorry to hear this, that sounds absolutely miserable. It can take a couple of weeks for bodies to adjust, however, if it’s not working for you, we encourage you to discuss the side effects and your options with your healthcare provider. There are different steroids and calcineurin inhibitors available; for some people, it takes some trial and error to find the right medication for their bodies. We outline different treatments and adjunct therapies here – https://lssupportnetwork.org/lichen-sclerosus-treatment/ with Love, Jaclyn

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