A big step forward in the treatment of atopic dermatitis was the appearance of topical calcineurin inhibitors — Elidel (cream 1%) and Protopic (ointment 0.1% or 0.03%).
The term «topical» means «local, local». An inhibitor is a kind of substance that suppresses or retards the course of certain physiological and physicochemical processes. Calcineurin is a key regulator of the immune system, a molecule required to initiate transcription of a gene that determines cytokine synthesis. Cytokines are small informational molecules that transmit a signal from one cell to another, triggering further reactions (including inflammatory ones).
Thus, if the above is generalized, it turns out that topical calcineurin inhibitors (including Elidel) are anti-inflammatory drugs applied to the skin, the principle of action of which is based on suppressing calcineurin, which leads to a blockade of the synthesis and release of pro-inflammatory cytokines (interleukins 2, 4 , 10, interferon — gamma). As a result, despite the fact that the cell receives a signal for the development of allergic inflammation, the response to this signal in the form of activation of mast cells and T cells necessary to trigger and maintain inflammation does not develop. These drugs are similar in effectiveness to topical steroids, but do not contain hormones, and therefore they can be used in cases where steroids did not fit or their further use is impossible.
Elidel cream is the most popular among topical calcineurin inhibitors, so this article will focus on it. I believe Elidel’s popularity is due to the fact that he is resolved from 3 months of life (and after all, atopic dermatitis most often manifests itself in the first year of life), and Protopic — from 2 years. The principle of action of these drugs is the same, but the active ingredient is different: Elidel has pimecrolimus, Protopic has tacrolimus. Another difference is that Elidel is used for mild to moderate atopic dermatitis, and Protopic is used for the treatment of moderate and severe dermatitis.
Elidel cream was developed specifically for the treatment of atopic dermatitis. Currently, there is a sufficient amount of information obtained from placebo-controlled, double-blind studies that this drug effectively fulfills the tasks for which it was created, namely: it allows you to quickly achieve stable clinical remission with moderate exacerbation of the disease as in adult patients and in children (including young children, which is very important, because the possibilities of using traditional anti-inflammatory therapy in relation to such patients are very limited).
As a result of a multicenter (41 pediatric centers from 8 countries of Europe, Africa and North America), randomized, double-blind study of the efficacy of Elidel cream in the treatment of atopic dermatitis in 251 children aged 3 to 23 months, it was found that the use of Elidel, started at the first signs or symptoms of atopic dermatitis significantly improved the course of the disease: the frequency of exacerbations decreased, the severity of objective symptoms of the disease, as well as itching, decreased. The effect of therapy was noted, as a rule, starting from the end of the first week of treatment and persisted for one year. At the same time, treatment with Elidel cream was safe and well tolerated without causing the side effects characteristic of local hormonal drugs.
The data of the conducted studies also show that the use of Elidel cream allows you to maintain long-term remission without the need for the use of external steroids and other anti-inflammatory drugs.
In terms of the effectiveness of blocking inflammatory reactions, Elidel cream is comparable to the highly active corticosteroids clobetasol-17-propionate and fluticasone. It effectively reduces skin inflammation (erythema, excoriation, infiltration and lichenification) and pruritus, and also provides long-term control over the disease when used at the beginning of the period of exacerbation of atopic dermatitis.
At the same time, Elidel does not contain hormones, and therefore is devoid of their inherent side effects (such as skin atrophy, formation of telangiectasias, increased hair growth, etc.), practically does not affect the frequency of skin infection (as confirmed by relevant studies).
The uniqueness of the mechanism of action of the cream consists in the combination of selective (targeted, selective) anti-inflammatory action on the skin with a slight effect on the systemic immune response. By preventing the release of pro-inflammatory cytokines and inflammatory mediators from mast cells, Elidel does not inhibit the synthesis of elastin and collagen fibers. In addition, Elidel is distributed mainly in the skin and practically does not penetrate through it into the systemic circulation (in contrast to local hormonal drugs and Protopic).
Moreover, according to the results of the studies, the concentration of pimecrolimus in the blood remained at a consistently low level, regardless of the area of skin lesions, as well as the duration of therapy (58 children aged from 3 months to 14 years old with atopic dermatitis with a lesion of 10-92 % of body surface area treated with Elidel cream 2 times a day for 3 weeks (five of them — for 1 year as needed)).
The possibility of long-term therapy is another advantage of Elidel over hormonal drugs, which can be used, as a rule, for no more than a month. As for the maximum duration of Elidel’s use, it has not been established (however, there is a note in the instructions for use of this drug that there is no data on the safety of long-term use of Elidel cream, since all studies were limited to 1 year), as well as restrictions on the daily dose of the applied drug …
As for the use in children, the undoubted «plus» of Elidel is the possibility of its use from 3 months (hormonal preparations — not earlier than 4 months (Advantan) and 6 months (Lokoid, Afloderm), and on all parts of the body, including the face, neck and skin folds, no restrictions on the area of application.
Indications of Elidel cream
In accordance with the instructions, the only indication for the use of Elidel cream is atopic dermatitis in adults, adolescents and children from 3 months (previously there was an age limit of 2 years).
Indeed, this drug was developed as an alternative to hormone therapy and is used in the following cases:
— when local corticosteroids do not work;
— when there are contraindications to the use of hormonal drugs;
— when there is a need for long-term treatment of atopic dermatitis in areas with thin delicate skin (including the face and neck area);
— when it is necessary to supplement local hormonal therapy (in particular, after the allowed time of using an external corticosteroid has expired, if remission has not yet been achieved);
— when the form of the disease is mild or moderate and does not require the use of corticosteroids. In this case, as a rule, Elidel is prescribed and only if there is no effect from its use within 5 days (or earlier, if there is a progressive deterioration of the skin condition), one should switch to the use of a hormonal drug. The exception is cases when an exacerbation arose against the background of the use of Elidel — a hormonal drug is immediately prescribed.
Contraindications cream Elidel
It should be remembered that in the event of a severe exacerbation of atopic dermatitis, Elidel cream is not used — local corticosteroids are prescribed immediately.
In the case of a viral, bacterial or fungal infection of the skin attached to dermatitis, Elidel is also not used. As a rule, in such a situation, corticosteroids are prescribed in conjunction with antibacterial / antifungal drugs or combination agents. And only after the secondary infection recedes, it is possible to treat dermatitis with Elidel.
Also, a contraindication to the use of Elidel cream is hypersensitivity to any components of the drug and children under 3 months of age (since the safety and efficacy of using the drug in children under the specified age has not been studied).
Elidel cream should be used with caution in patients with Netherton’s syndrome, as well as in severe forms of inflammation or skin lesions (including generalized erythroderma), since there are no data on the safety of the drug for these diseases, but there is a possibility of an increase in its systemic absorption (i.e. permeability of the drug into the blood).
Also, with caution, the drug should be used with weakened immunity, since its safety and efficacy in such patients has not been studied.
It should be remembered that there are no data on the safety of long-term use of Elidel cream. In particular, the effect of long-term use of the drug on the immune defense of the skin and the incidence of malignant neoplasms has not been studied, and therefore, the cream should not be applied to damaged areas of the skin with possible malignancy or dysplastic changes.
Rules for using Elidel cream
- Despite the fact that there are isolated reports of the positive experience of using Elidel cream for other dermatitis, the manufacturer recommends using it only for atopic dermatitis.
- The use of Elidel cream should be started at the first manifestations of the disease to prevent an exacerbation, as well as with an already existing mild or moderate stage of exacerbation.
- Elidel cream is not used for severe forms of atopic dermatitis.
- The drug is approved for use in adults, adolescents and children over 3 months of age (the safety and efficacy of the drug in children under the specified age has not been studied).
- The dosage form, concentration and frequency of use of the drug are not differentiated depending on the age of the patient, the stage of the disease, the nature and localization of skin lesions and the activity of dermatitis: Elidel cream 1% is applied to the affected areas of the skin 2 times a day and gently rubbed until completely absorbed. Even if the form of dermatitis is mild, the patient is an infant or the drug is used for prophylaxis — the drug is applied to the affected areas 2 times a day, since all the declared properties of the drug (including its effectiveness) are based on the results of its use 2 times a day.
- Elidel cream can be applied to the affected areas of the skin of any part of the body, including the head, face, neck, and also in the area of diaper rash.
- Due to the fact that the systemic absorption of Elidel cream is insignificant, it can be applied to large areas without limiting the total daily dosage.
- The course of application of Elidel cream is individual — on average, about 4-6 weeks, but the doctor can prescribe either less or more, focusing on the data of visual control. At the same time, in accordance with the instructions, while maintaining the severity of symptoms after 6 weeks of using the drug, it is necessary to re-examine the patient to confirm the diagnosis of atopic dermatitis (however, if no improvement is observed within 5 days of using the drug or there are deterioration, it is necessary already at this time think about replacing the drug).
- Since, due to insignificant penetration into the bloodstream, Elidel cream can be used for a rather long time (in special studies, its use was even up to 1 year), treatment with the drug is carried out until the symptoms, including itching of the skin, disappear completely. After stopping treatment, in order to avoid subsequent exacerbations, at the first signs of a relapse of atopic dermatitis, therapy should be resumed.
- Elidel cream should not be mixed with other drugs, however, its use should be combined with the use of emollients , since the penetration of any topical drugs largely depends on the saturation of the stratum corneum with water, the amount and quality of unsaturated fatty acids and ceramides included in its composition. In accordance with the instructions for use, emollients can be applied immediately after applying Elidel to the skin. However, in accordance with the rules for bathing children with atopic dermatitis , the emollient is applied to wet skin within 3 minutes after the end of the water treatment. Thus, after water procedures, an emollient is first applied to the skin, and then Elidel cream.
- In case of contact of Elidel cream with eyes or mucous membranes, immediately remove the cream and rinse the eyes and mucous membranes with running water.
Like any other drug, Elidel Cream can cause some side effects. The most common of these is transient reactions at the site of application, such as a feeling of warmth and / or burning (≥1 / 10). Basically, such a reaction occurs at an early stage of treatment, it is mild to moderate and is of short duration. In case of significant severity of such reactions, you should consult a specialist. It is worth noting that Protopic also causes a burning sensation, but Elidel is better tolerated.
Quite often (≥1 / 100, <1/10), patients may experience local reactions such as itching, irritation, redness of the skin. When scratching or getting an infection, folliculitis and other signs of skin infection can occur. Given the mechanism of action of the drug, the possibility of local immunosuppression (suppression of immunity) cannot be ruled out, however, in patients receiving treatment with Elidel, the risk of developing secondary skin infections is much lower than in patients receiving topical corticosteroids.
Sometimes (≥1 / 1000, <1/100) during treatment with Elidel, side effects may develop such as worsening of the disease, suppuration, molluscum contagiosum, herpes simplex, herpetic eczema, as well as local reactions such as rash, dryness, peeling, swelling, pain , cutaneous papillomas, furuncles, paresthesias.
Less common are allergic (urticaria, rash, angioedema) and anaphylactic reactions, discoloration of the skin (hypo- and hyperpigmentation), alcohol intolerance (face redness, burning, itching, rash or swelling when used during treatment with Elidel).
In clinical studies with the use of Elidel in 0.9% of patients (14 out of 1544), an increase in the lymph nodes of the lymphatic system (lymphadenopathy) was also noted. Usually, this condition was due to infectious diseases and after a course of appropriate antibiotic therapy, the lymph nodes returned to their normal state. However, the manufacturer recommends discontinuing the drug if it is impossible to establish the etiology of lymphadenopathy or if the patient has acute mononuclear inflammation.
And perhaps the most frightening side effect: in rare cases, with the use of topical calcineurin inhibitors (including Elidel cream), the development of malignant neoplasms, including skin tumors, other types of lymphomas, and skin cancer, has been noted. A causal relationship between these adverse events and the use of the drug has not been established. However, the FDA (American Food and Drug Administration) published a warning back in 2005 for pimecrolimus (Elidel cream) and tacrolimus (Protopic cream), due to the lack of data on the safety of these drugs with long-term use (this was before as Elidel was allowed to use from 3 meat, and not from 2 years, however, many are still alarmed by such a coincidence).
Despite the unidentified causal relationship, the manufacturer made recommendations for the use of Elidel to minimize artificial or natural skin insolation (or better, complete exclusion of UV radiation). On sunny days, after applying the drug to the skin, it is also recommended to use sunscreens.
Thus, despite its benefits, Elidel cream is not perfect. Like any other immunomodulator (drug that regulates the immune system), it can cause extremely unpleasant consequences. In addition, in the instructions for the drug itself there are many «white spots»: unknown, not studied, etc., and therefore it is not worth using it for a long time without a good reason.
You may be interested in the following entries: