What Are TC Inhibitors and How Do They Help With The Effects of Eczema?

TCIs block calcineurin from activating T-cells, suppressing inflammation and relieving eczema flare symptoms.

TCIs have fewer side effects than steroids, have a lower infection and long-term cancer risks than JAK Inhibitors, and are non-invasive, unlike monoclonal antibodies.

Eczema is a chronic skin condition that affects millions of people worldwide, causing symptoms like itchiness, redness, and inflammation


There are many available tools that can help with the symptoms of eczema and success with any one tool can vary by person making sorting through all the options a challenge. 


To accelerate finding the right treatment for you, this article aims to provide a comprehensive overview of Topical calcineurin inhibitors (TCIs), explaining what they are, how they work, their different types, usage, benefits, and potential side effects.

What Are TC Inhibitors?

Topical Calcineurin Inhibitors (TCIs) are  types of treatment for the symptoms of eczema that work by altering the immune system function.(CAS 2006) They are "topical" meaning they are applied to the skin, and "calcineurin inhibitors" because they slow or stop calcineurin use in the body. 


TCIs are usually prescribed as a second-line treatment when other common treatments like topical steroids, are not effective or have many side effects.(GUT 2013)(CAS 2006) However, they can also be used as a first-line therapy in conjunction with topical steroids, especially in patients with steroid phobia (corticophobia), or facial or flexural lesions. However, you should not use TCIs and topical steroids in the same part of your body at the same time unless instructed to by a physician.

How TC Inhibitors Work

Calcineurin is a substance produced in the human body that is used to activate (“fire up”) T-cells.(DUT 2016) T-cells are types of white blood cells that are part of our adaptive immune system. In eczema, T-cells play a role in attacking a trigger that has passed through a weak skin barrier.(ANN 2014) They are responsible for the inflammation in an eczema flare.  


TCIs block calcineurin from activating T-cells, suppressing the inflammatory response and alleviating symptoms of a flare, but they do not remove the trigger or strengthen the skin barrier to block new triggers.GUT 2013)(TSU 2012)


If you think of your body as a community of cells that send messages to each other, then you can think of TCIs as being able to plug the ears of the T-cells, and, for a time, the T-cells cannot hear a call to arms in contrast with corticosteroids (aka “steroids” like hydrocortisone) which plug the ears of T-cells and also a broader set of cells in the body, including cells outside the immune system. 


The broader reach of steroids can cause a host of side effects while the targeted nature of TCIs can cause challenges in dosing. 

The Different Types of TC Inhibitors

There are two main types of TCIs currently available, tacrolimus (Protopic) and pimecrolimus (Elidel).(GUT 2013) Both medications work similarly by inhibiting calcineurin and suppressing inflammation but they differ in terms of potency and formulation.

Tacrolimus is available in two strengths, 0.03% and 0.1%, and is typically prescribed for moderate to severe eczema. Pimecrolimus comes in a 1% cream formulation and is often used for milder cases. The safety profile of pimecrolimus is comparable to tacrolimus but tacrolimus has been shown to be more effective and faster acting.(PAL 2005)

Your healthcare provider will determine which TCI is best suited to your specific needs based on factors like the severity of your eczema and the location of affected skin.

How to use TC Inhibitors

Using TCIs is relatively straightforward. After washing your hands, apply a thin layer of the prescribed medication to the affected areas of your skin as directed by your healthcare provider. Do not cover the treated skin with bandages or dressings unless instructed to do so. Make sure to follow your healthcare provider's recommendations on frequency and duration of treatment, as overusing TCIs can increase the risk of side effects.


As TCIs suppress the immune system, they have the potential to exacerbate skin infections. It is not recommended to apply TCIs to infected skin, whether it is infected with bacteria or viruses (such as chickenpox, cold sores, or warts).

The Benefits & Advantages of TC Inhibitors

TCIs can be a good alternative to consider when deciding how to manage the symptoms of an eczema flare.(GUT 2013) 


One study that followed over 300 patients with moderate to severe atopic eczema for 12 months of use of tacrolimus showed that TC inhibitors are effective treatments: (REI 2000)

  • After 1 week, over half of the patients had a “marked or excellent” improvement in their condition

  • After 6 months, the mean severity score had reduced from 23.7 to 6.1, a reduction of 75%

  • After 12 months, 86% of the patients had a “marked or excellent” improvement in their condition

However, long-term treatment for eczema should focus on preventing triggers and strengthening the skin barrier.

TCIs vs Steroids

Corticosteroids affect a broad selection of cells in the body beyond those in the immune system. Using them topically can limit some of the effects within the body. 


With steroids there is a risk of side effects such as skin thinning or atrophy making TCIs a safer option for treating delicate areas such as the face, neck, or skin folds.(REI 2000) TCIs are also an appealing choice for individuals who cannot tolerate or have contraindications to steroids.

TCIs vs JAK Inhibitors

Janus Kinase (JAK) Inhibitors work to block a variety of messages exchanged between immune cells. If you think of your body as a community of cells that send messages to each other, then you can think of TC have a lower chance of serious infection and comes with lower long-term cancer risks than JAK Inhibitors.  


JAK Inhibitors are more targeted than steroids though, and their effect on a broader set of immune functions can be an advantage. We cover the pros and cons of JAK Inhibitors here.   

TCIs vs Monoclonal Antibodies

Monoclonal antibodies are molecules that work in a targeted way to modulate the immune system. 


Earlier we introduced T-cells as a type of white blood cell that is part of our adaptive immune system. T-cells are born from our bone marrow and are not specialized at birth. As they grow, they adapt to the messages they receive and may convert to “killer” T-cells or “regulatory” T-cells amongst other types of T-cells. 


Killer T-cells act like soldiers and charge to attack the perceived threat. Regulatory T-cells act like officers and assess where the threat is and whether to end the battle. In autoimmune diseases, often the regulatory T-cells are failing to protect the cells of our body from attack.


In the case of eczema treatments, monoclonal antibodies like dupilumab (sold under the brand name Dupixent), work by blocking T-cell conversion into a killer T-cell, by blocking interleukin 4 (IL-4) receptors on the T-cell. 


TCIs are topical medications that are applied directly to the skin, making them a convenient and non-invasive treatment option for skin conditions such as eczema. Dupixent and other monoclonal antibodies are typically given by injection. 


In part because they are delivered topically, TCIs are generally well-tolerated with few side effects, whereas monoclonal antibodies have more long-term side effects by suppressing the immune system throughout the body. TCIs are generally lower cost, and are not animal-derived like monoclonal antibodies.


Monoclonal antibodies can be a referred treatment for the symptoms of eczema in some cases. Learn more about them here.

Side Effects & Drawbacks of TC Inhibitors

While TCIs offer several advantages, they are not without potential drawbacks and side effects. The same study mentioned above summarized the side effects noted:(REI 2000)

  • 47% of patients reported burning sensation at the site of application

  • 24% reported pruritus (itchiness)

  • 12% reported erythema (redness)

Side effects are more likely to occur and more severe when initiating the treatment with symptoms generally resolved within a week of use. 

Other side effects included:

  • Alcohol intolerance or rosacea whilst drinking

  • Localized skin infections

  • Acne

There is also an increased risk of certain skin cancers. Although the risk is increased by 40-fold when compared to the general population, the overall risk is still relatively low (41 per 100,000).(CAS 2018) 

It is important to reduce UV-exposure by covering up skin and wearing sunscreen.

Extra care has to be taken when applying TCIs versus steroids; a reflection of the fact that steroids are available without a prescription.

TCIs are not recommended for children under the age of 2. 

As an immune modulator, one of the main concerns regarding TCIs is the potential risk of developing an infection, skin cancer or lymphoma. It is essential to discuss the risks and benefits of using TCIs with your healthcare provider to make an informed decision.

Are TCIs Worth Considering For Eczema?

Topical calcineurin inhibitors can be a valuable treatment option for managing the symptoms of an eczema flare, particularly for those who have not found success with other treatments or are unable to use them due to side effects or contraindications. The benefits of TCIs include their targeted action, lower risk of skin thinning, and overall efficacy in controlling symptoms.


Like all immune modulating medications, TCIs have potential side effects and drawbacks, such as skin irritation and concern regarding infection, skin cancer, or lymphoma risk. 


TCIs can be a good alternative to consider when deciding how to manage the symptoms of an eczema flare. However, long-term treatment for eczema should focus on preventing triggers and strengthening the skin barrier. These treatments can be used alone or in combination, depending on your specific needs and the severity of your condition. 


As always, consulting with a healthcare professional is the best way to develop a comprehensive and personalized eczema treatment plan.

About the Author(s)

Dr. Nicole Scott, PhD, MPH

Dr. Scott has published 29 peer-reviewed papers regarding human biology and the microbiome. Her work has been cited over 4300 times by other scientists.

She has battled eczema for most of her life and is the Founder of Rulo Skin.

Read her work on Google Scholar

Special Thanks

This article was prepared in collaboration with the Itchhikers Guide

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