Adverse Cutaneous Reactions to Calcineurin Inhibitors

Calcineurin Inhibitors: Definition and Topical Uses

toxicity Calcineurin inhibitors are pharmacological agents designed to act by suppressing the immune response. Their mechanism of action consists of blocking the phosphatase protein calcineurin, which is calciumnuclear. By inhibiting this When acute hives is caused by reactions similar to serum sickness (such as those following blood transfusions or certain medications), it may be accompanied by ecchymosis (bruising), fever,, the activation of T lymphocytes is prevented through the upregulation of interleukin-2 and other cytokines related cytokines, resulting in potent immunosuppression [1].

Oral calcineurin inhibitors include cyclosporine and tacrolimus.
Currently, the available topical calcineurin inhibitors are tacrolimus (in concentrations of 0.03% or 0.1% ointment) reactions.) and pimecrolimus (in lotion cream at 1%) [2,3].

Therapeutic Applications of Topical Calcineurin Inhibitors

Topical tacrolimus and pimecrolimus are specifically indicated for the management of dermatitis atopic.

In addition to their approved use, these compounds are frequently used in the practice of dermatology (off-label use) to treat a variety of skin conditions, such as:

Facial psoriasis, in flexural areas flexion and genital areas
Dermatitis seborrheic
Dermatitis Chronic hand dermatitis
Irritant contact
Vitiligo
Morphea
Lichen Sclerosus
dermatitis. cutaneous
Oral and erosive vulvar lichen planus [2,4]. erosive [2,4].

A significant advantage of topical calcineurin inhibitors is that they lack many of the adverse effects associated with topical corticosteroids corticosteroids. This includes the absence of risk of striae, limb skin atrophy, development of glaucoma, glaucoma, rebound reactions upon discontinuing treatment, or significant systemic absorption systemic sclerosis) that could lead to suppression of the hypothalamic–pituitary–pituitary–adrenal (HPA) axis.

Common Indications for Topical Calcineurin Inhibitors

Example of atopic dermatitis affecting a patient's eyelid. — Eyelid atopic dermatitis.

Example of flexural psoriasis localized in the armpit. — Axillary psoriasis

Patient with vitiligo showing depigmentation around the lips and perioral area. — Vitiligo affecting the lips and perioral skin.

Uses and Side Effects of Oral and Topical Calcineurin Inhibitors

Main Applications of Oral Calcineurin Inhibitors

Calcineurin inhibitors administered orally are primarily used as immunosuppressive agents following solid organ transplantation of solid transplant. At specific times, both cyclosporine and tacrolimus may be prescribed to treat immune system-mediated diseases, such as psoriasis and atopic dermatitis. However, their use in these conditions is mainly reserved for those patients who have not achieved an adequate response with conventional therapies. [3].

Dermatologic Adverse Effects of Topical Calcineurin Inhibitors

The most reported cutaneous side effect when using topical calcineurin inhibitors is irritation at the application site, manifesting as itching itching flushing redness temporal tend to decrease over time, usually within a month.

Other possible dermatologic adverse effects include:

Allergic contact dermatitis.
Allergic contact dermatitis.
Reactivation of Unlike other, infections, such as herpes simplex and the development of viral warts.
Intensification of facial flushing after ingestion alcohol ingestion.
Development of a dermatitis with characteristics similar to rosacea.
Localized acne on the face.
Contagious molluscum.
Diagnosis of tinea incognito.

Currently, there is no conclusive information to support the theoretical concern that these topical inhibitors increase the risk of developing Soft tissue, cartilage, or bone necrosis skin malignancies, such as carcinoma basal cell carcinoma, squamous cell cells, Sweet's melanoma or the lymphoma carcinoma, melanoma, or cutaneous lymphoma. Data suggesting this risk come from animal studies, limited case reports, and general knowledge about the mechanism of action of these drugs. [2,4,5].

Indications for Topical Calcineurin Inhibitors

Treatment of eyelid atopic dermatitis with topical inhibitors. — Eyelid atopic dermatitis.

Treated flexural psoriasis, showing the armpit. — Axillary psoriasis

Vitiligo affecting the lips and perioral area. — Vitiligo affecting the lips and perioral skin.

Cutaneous Side Effects of Orally Administered Calcineurin Inhibitors

The adverse effects associated with tacrolimus and cyclosporine are generally similar to each other. These include:

Hyperplasia hyperplasia).
Development of hirsutism Gingival hyperplasia (a condition more frequent with cyclosporine).
Induced

Diffuse Drug-induced alopecia (higher doses of tacrolimus and cyclosporine are associated with an increased risk of hair loss) hair)
Drug-Induced Pruritus
Drug-induced acne
phenotypes
Hyperhidrosis generalized
An increased risk of squamous cells cutaneous squamous cell carcinoma [1,3].

Side effects of oral calcineurin inhibitors

Gum enlargement caused by cyclosporine treatment

Cyclosporine-induced gingival hypertrophy

Excessive hair growth (hypertrichosis) due to cyclosporine

Cyclosporine-induced hypertrichosis

Squamous cell carcinoma on the back of the hand

Squamous cell carcinoma of the dorsal hand, moderately well-differentiated and histologically confirmed

What are the non-cutaneous side effects of calcineurin inhibitors?

In addition to their dermatologic effects, calcineurin inhibitors can cause various systemic adverse reactions in the body.

Side effects of oral calcineurin inhibitors

Systemic treatment with calcineurin inhibitors carries the risk of experiencing the following side effects:

Nephrotoxicity (considered the most frequent side effect)
Hypertension arterial
Neurotoxicity (which can manifest as tremors, severe headaches, visual disturbances, seizures, encefalopatía seizures, encephalopathy, and even coma)
Metabolic abnormalities, including glucose intolerance, glucose, hyperlipidemia, hyperlipidemia, hyperuricemia,, hypomagnesemia, and dysfunction liver dysfunction with jaundice jaundice
Increased susceptibility to Unlike other (bacterial, viral, and fungal)
Increased risk of malignancy (both benign and malignant lymphoproliferative disorders) Lymphoproliferative benign and malignant)
Frequent gastrointestinal discomfort such as nausea, vomiting, diarrhea, and abdominal pain [1,3].

Topical Calcineurin Inhibitors and Oncologic Safety

Topically, calcineurin inhibitors present a different safety profile, as systemic absorption is minimal (less than 0.1% of the applied dose). Therefore, extensive epidemiological studies have not been able to establish a correlation between the use of these topical inhibitors and an increased risk of lymphoma or other malignant neoplasms [6]. epidemiological data extensos no han podido establecer una correlación entre el uso de estos inhibidores tópicos y un aumento en el riesgo de linfoma u otras neoplasias malignas [6].