A Closer Look At Topical Calcineurin Inhibitors

History of TCIs in Canada

The first TCI was introduced in Canada in 2001, establishing a new class of treatment for eczema. There are two topical therapies available in Canada at this time: tacrolimus (Protopic®) and pimecrolimus (Elidel®).11

How TCIs Work

TCIs work by correcting the immune imbalance occurring in the skin at the site of eczema.  The medication works to reduce inflammation and prevents outbreaks from occurring. Typically, the medication works very quickly, reducing eczema symptoms within days.  Its mechanism of action is based on calcineurin inhibition, which results in the suppression of T cells (a class of white blood cells) and subsequent release of cytokines and other inflammatory agents that can contribute to the symptoms of atopic dermatitis.

The Role of the Skin Barrier12

New insights into the difference between “healthy” skin and eczema-prone skin have focused on the skin barrier.  The skin barrier appears to play a significant role in how effectively the skin functions, and why certain people get eczema while others do not.  In healthy skin with a resilient skin barrier, allergens cannot penetrate deeper into the skin.  Instead, bacteria and irritants are prevented from entering; the skin barrier also helps to protect proper levels of hydration in the skin.  Research into the skin barrier has shown that there is a genetic predisposition to a weakened, defective skin barrier.  This allows allergens to penetrate the skin.  In addition, the defective skin barrier allows for increased interaction with environmental factors such as soap and detergent, house dust mites, hard water, infection and some topical pharmaceutical and cosmetic products.  This can result in a worsening of eczema symptoms, and a further breakdown of the skin barrier.

Recent research into the skin barrier and how protecting it can help to prevent eczema ‘flare ups’ has resulted in new treatment strategies, which focus on preventing new flares as opposed to treating flares as they occur.  This maintenance regimen involves the use of TCI or topical steroid treatments. Health Canada has approved one of the available TCIs as maintenance therapy.  Talk with your doctor; he or she has the most up to date information about eczema treatments.  Discuss the different treatment options available to you to identify the best strategy for controlling your eczema.

Common Side Effects

The most known side effect is a mild burning or tingling sensation at the site of application, typically lasting from 10 to 15 minutes.  This is a transient feeling that subsides as the skin starts to heal.

Eczema Treatment Options

Eczema is traditionally treated with hydration of the skin (moisturizers), topical steroids for inflammation, oral antihistamines for control of itch, and antibiotics when there is infection.  Eczema is difficult to treat because the condition is recurring, or chronic.  Because of the recurrence of outbreaks, traditional treatments do not cure the condition and often have to be used for a prolonged period.  Many of the treatments, including topical steroid treatments, produce various side effects, such as thinning of the skin and a change in skin pigmentation.

The newest class of treatments for eczema, called Topical Calcineurin Inhibitors or TCIs, stops the immune system from generating a ‘flare up’ response to irritants that cause eczema outbreaks.  TCIs are chemically unrelated to steroidal treatments now in use, and are the first steroid-free treatment for eczema in forty years.

Sunlight, sun lamps, tanning salons and phototherapy treatment with UVA or UVB light should be avoided while using TCIs. If you are going outside after using TCIs, wear clothing that protects the treated area from the sun.

Safety Information

Concerns about product safety should be raised with your dermatologist.  In Canada, Topical Calcineurin Inhibitor medications are available as either Protopic® ointment or Elidel® cream.  These topical agents can be used alone or in conjunction with other medication as prescribed by your doctor. In April 2005, Health Canada issued an advisory about these products.

  • Use Elidel® and Protopic® only when other treatments have been shown to be ineffective or unsuitable.
  • Use a thin layer of Elidel® or Protopic® to control symptoms and only for short periods of time as the long-term safety is unknown.
  • Avoid using Elidel® and Protopic® in children younger than two years of age as the effect on the developing immune system is unknown.
  • Elidel® or Protopic® should not be used in children and adults with weakened immune systems.
  • Patients are advised to consult their physician should they have any concerns.

To view the Health Canada advisory visit www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2005/2005_31-eng.php

The Canadian Dermatology Association (CDA) notes that in clinical studies involving 38,000 people, including 14,000 children under the age of 17, only two cases of non-lymphoma cancer were discovered. There were no cases in children. Scientists usually expect to find three lymphomas among such a large group.
http://www.dermatology.ca/media/position_statement/TIMs-factsheet_e.pdf

In North America, nearly seven million patients are using Elidel® or Protopic® products. In the spontaneous reporting program (which means that companies making medications and other treatments must report to the regulatory agency if there is an adverse effect in people taking their products), there were 25 cases of malignancy, four of them in children 2-16 years old, out of nearly seven million patients on these medications (13 lymphomas).  In a group of this size, one would typically expect approximately 61 cases of lymphoma.

Comparative Chart: TCIs vs Topical Steroid Creams

Side Effect TCIs Steroids
Mild-moderate burning sensation x  
Thinning of the skin   x
Stretch marks   x
Fragile skin   x
Increased fine hair growth   x
Skin discolouration   x
Blood vessel formation   x
Necessary to avoid sunlight/artificial light x  
Lack of effectiveness with long-term use   x

11 Canadian Dermatology Association. Fact Sheet: Topical Calcineurin Inhibitors. 2008
12 Cork MJ. The importance of skin barrier function. Journal of Dermatological Treatment (1997) 8;S7-S13

  • Eczema

    Eczema

    is referred to as “chronic” because there is no cure and symptoms can reappear or ‘flare up’ at any time

  • Dermatology

    Dermatology

    is the science that is concerned with the diagnosis and treatment of diseases affecting skin, hair and nails

  • A Dermatologist

    A Dermatologist

    is the medical expert you should consult if you have any significant problems with your skin 
  • Ease Program
    Ease Program
  • For Kids
    For Kids