Topical glucocorticoids are the topical forms of glucocorticoids. Topical glucocorticoids are used in the treatment of many skin conditions. They provide anti-inflammatory,

antimitotic A mitotic inhibitor is a drug that inhibits mitosis, or cell division. These drugs disrupt microtubules, which are structures that pull the chromosomes apart when a cell divides. Mitotic inhibitors are used in cancer treatment, because cancer cel ...

, and immune-system suppressing actions through various mechanisms. Tube of hydrocortisone cream

Medical Uses

Topical glucocorticoids are indicated for the treatment of a variety of

skin conditions Many skin conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle and glands. The major function of this system is as a barrier agains ...

: * Eczema *

Atopic dermatitis Atopic dermatitis (AD), also known as atopic eczema, is a long-term type of inflammation of the skin (dermatitis). It results in puritis, itchy, red, swollen, and cracked skin. Clear fluid may come from the affected areas, which often thickens o ...

* Psoriasis * Vitiligo * Phimosis * Acute radiation dermatitis * Lichen sclerosus

Formulations

Topical glucocorticoids are available in different formulations. If an inappropriate formulation is administered, the therapeutic effect of the treatment may be delayed and rendered insufficient. The condition will even be worsened in some cases. For instance, usage of a topical glucocorticoid

gel A gel is a semi-solid that can have properties ranging from soft and weak to hard and tough. Gels are defined as a substantially dilute cross-linked system, which exhibits no flow when in the steady-state, although the liquid phase may still di ...

on fissured hand eczema intensifies the pain as well as stinging because of the

alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

present in the gel. If an

ointment A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...

is applied on a moist skin injury, it might lead to follicle infection due to the occlusive features of the ointment.

Ointments

Ointments A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...

are formed with water suspended in oil. Ointments are effective

lubricant A lubricant (sometimes shortened to lube) is a substance that helps to reduce friction between surfaces in mutual contact, which ultimately reduces the heat generated when the surfaces move. It may also have the function of transmitting forces, t ...

s that can retain heat, lower the loss of water from the skin and provide better absorption of medication. Ointments are also semi-occlusive. Ointments are usually the most effective formulations for topical glucocorticoids because of their occlusive effect. However, acceptance and compliance of patients to the pharmacological treatment may be relatively low as they are oily, tacky, and usually cannot be applied to large or hairy areas.

Creams

Creams Cream is a dairy product composed of the higher-fat layer skimmed from the top of milk before homogenization. In un-homogenized milk, the fat, which is less dense, eventually rises to the top. In the industrial production of cream, this process ...

are

semi-solid Quasi-solid, Falsely-solid, or semisolid is the physical term for something whose states of matter, state lies between a solid and a liquid. While similar to solids in some respects, such as having the ability to support their own weight and hold ...

emulsions consisting of oil suspended in water. They are of pleasant appearance and can be rinsed away by water. Regarding the same topical glucocorticoid, creams are generally more potent than lotions but less effective than ointments. Creams are especially useful in acute inflammation with exudates due to their drying effects. Creams can also be applied to intertriginous areas that are inappropriate for the application of ointments.

Lotions

Lotions refer to

suspensions In chemistry, a suspension is a heterogeneous mixture of a fluid that contains solid particles sufficiently large for sedimentation. The particles may be visible to the naked eye, usually must be larger than one micrometer, and will eventually ...

solution Solution may refer to: * Solution (chemistry), a mixture where one substance is dissolved in another * Solution (equation), in mathematics ** Numerical solution, in numerical analysis, approximate solutions within specified error bounds * Soluti ...

s of drugs in water, alcohol, or other types of solvent. Therefore, the container should be shaked adequately to ensure the drug is mixed well with the solvent before each dosage to achieve the best therapeutic effect. Lotions are especially effective in hairy areas and also in situations where the medication has to be applied in large areas on the body. Lotions exert a cooling and drying effect as they dry, making them to be effective in moist skin lesions and/or in itching.

Gels

Gel A gel is a semi-solid that can have properties ranging from soft and weak to hard and tough. Gels are defined as a substantially dilute cross-linked system, which exhibits no flow when in the steady-state, although the liquid phase may still di ...

s are emulsions with oil suspended in water containing alcohol in the base. Gels have a jelly-like property and dry in a thin and watery film. Gel formulations have therapeutic effects as good as ointments and appearance as cosmetically appealing as creams, resulting in a high patient acceptance. Gels are absorbed readily and are appropriate for distributing topical glucocorticoids to hairy areas. Gels are especially effective for inflammation with exudates.

Foams

Foams spread efficiently and are easier to be applied than other preparations, especially for skin inflammation and scalp conditions. Foams can be applied and spread readily, especially in hairy areas. The compliance for foam formulations is usually high. However, due to the difficulty in designing appropriate vehicles, foam formulations are generally higher in price than other formulations.

Pharmacology

Mechanism of action

Topical glucocorticoids alter the functions of epidermal and dermal

cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...

as well as that of the

white blood cell White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...

s involved in proliferative and inflammatory skin diseases. Topical glucocorticoids act as

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

s for the cytoplasmic glucocorticoid receptor. After binding to the receptor, the complex is then transported into the

nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucle ...

. Within the nucleus, the complex binds to the

glucocorticoid response elements Response elements are short sequences of DNA within a gene promoter or enhancer region that are able to bind specific transcription factors and regulate transcription of genes. Under conditions of stress, a transcription activator protein binds ...

in the promoter region of target genes. This results in the

regulation of gene expression Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are wide ...

through altering the rate of

transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...

of certain mRNA. As mRNA acts as a template for

protein synthesis Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the product ...

, topical glucocorticoids can either enhance or suppress the synthesis of specific proteins. This series of events lead to numerous effects. Transcription factors that are responsible for the synthesis of inflammation mediators including

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...

s, eosinophils, lymphocytes, mast cells and

dendritic cell Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. ...

s are inhibited, anti-inflammatory proteins such as lipocortin are released and cell division of

epidermal cells The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water relea ...

and

dermal fibroblast Dermal fibroblasts are Cell (biology), cells within the dermis layer of skin which are responsible for generating connective tissue and allowing the skin to recover from injury. Using organelles (particularly the rough endoplasmic reticulum), derma ...

s is inhibited.

Pharmacokinetics

There are many factors determining the extent of

absorption Absorption may refer to: Chemistry and biology * Absorption (biology), digestion **Absorption (small intestine) *Absorption (chemistry), diffusion of particles of gas or liquid into liquid or solid materials *Absorption (skin), a route by which ...

of topical glucocorticoids, including: * Body area of application; body regions with thin skin are significantly more permeable to topical glucocorticoid than areas with thick skin. * Condition of the skin; topical glucocorticoids are absorbed for a larger extent through areas of inflammation or in peeled areas when compared to normal skin * Age of the patient; infants and young kids who have much thinner skin than that of adults absorb topical glucocorticoids more easily *Presence of urea, dimethylsulphoxide, or other agents (e.g.

salicylic acid Salicylic acid is an organic compound with the formula HOC6H4CO2H. A colorless, bitter-tasting solid, it is a precursor to and a metabolite of aspirin (acetylsalicylic acid). It is a plant hormone, and has been listed by the EPA Toxic Substance ...

) in vehicle that will raise the absorption rate * Placement of

occlusive dressing An occlusive dressing is an air- and water-tight trauma medical dressing used in first aid. These dressings are generally made with a waxy coating so as to provide a total seal, and as a result do not have the absorbent properties of gauze pads. Th ...

on the body area, that will raise the absorption rate The differences in extent of percutaneous absorption in different parts of the body (percent of the total dose absorbed into the body through the skin) are as follows: * Sole – 0.05% * Palm – 0.1% * Forearm – 1% * Scalp – 3.5% * Face – 7% * Eyelids and genitalia – 30%

Adverse Effects

Topical glucocorticoids are generally safer than systemic glucocorticoids. However, cutaneous and systemic adverse effects may happen, especially with the use of superpotent and potent topical glucocorticoids or excessive use of lower-potency agents.

Cutaneous

Withdrawal syndrome Drug withdrawal, drug withdrawal syndrome, or substance withdrawal syndrome, is the group of symptoms that occur upon the abrupt discontinuation or decrease in the intake of pharmaceutical or recreational drugs. In order for the symptoms of wit ...

: Withdrawal of topical glucocorticoids after long-term use, particularly on the face or genitals, may bring about different kinds of signs and symptoms including redness of the skin, burning or stinging sensation, itching, pain, and hot flashes on the face. These symptoms could persist for days to weeks after glucocorticoids withdrawal. Allergic reaction: The vehicles (solvent containing the drug) or preservatives are usually the agents causing sensitivity, although allergy due to the contact with glucocorticoids merely is possible. Contact allergy caused by topical glucocorticoid should be suspected in patients with chronic skin conditions that do not seem to improve but instead, is worsened by the treatment. Other: Other cutaneous adverse effect of topical glucocorticoid consist of appearance of purpura (red discoloured spots) on the skin, changes in pigmentation, and abnormal hair growth.

Systemic

Some topical glucocorticoids can cause hypothalamic-pituitary axis (HPA) suppression. Reasons that lead to suppression of the HPA include the use of high-potency glucocorticoids, long-term use, application to highly permeable areas, treatment of large areas, occlusion, changed skin barrier and young age. Regular use of even mild glucocorticoids in young kids can lead to HPA suppression. Rarely, long-term application of high-potency topical glucocorticoids around the eyes may induce glaucoma or cataracts. The incorrect use of topical glucocorticoids can worsen or cover the typical clinical signs of the appearance of

fungal skin infections A skin infection is an infection of the skin in humans and other animals, that can also affect the associated soft tissues such as loose connective tissue and mucous membranes. They comprise a category of infections termed skin and skin structure ...

Cautions

Use in children

To reduce the risk of adverse events, high-potency glucocorticoid should not be applied on the face, intertriginous areas, areas with thin layers of skin (e.g. the perineum, armpit) in children. Moreover, high-potency glucocorticoid should be applied to skin only once a day and should not be used for more than fourteen days. Even low-potency topical glucocorticoids are able to cause adverse effects in children when used for prolonged periods of time. Generally, a smaller dose of topical glucocorticoid is required by children for a given condition than adults, as children have relatively smaller body surface area compared to adults.

Use during pregnancy or lactation

Based on the evidence that are currently available, the use of low- to medium-potency topical glucocorticoid is not found to raise the risk of adverse effects for the mother and the baby, such as

preterm delivery Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is between 2 ...

, birth defects, and low birth weight. However, since the correlation between long-term use of potent topical glucocorticoid in pregnant women and low birth weight cannot be neglected, pregnant women who require topical glucocorticoids should be administered with low- or medium-potency agents instead of potent or superpotent ones. If potent or superpotent topical glucocorticids are necessary in pregnant women, they should only be administered for a short period of time, the dose used should also be minimised, and growth of the baby should be closely monitored.

Classifications

USA Classification System

Topical glucocorticoid causes cutaneous vasoconstriction in proportion with their

potency Potency may refer to: * Potency (pharmacology), a measure of the activity of a drug in a biological system * Virility * Cell potency, a measure of the differentiation potential of stem cells * In homeopathic dilutions, potency is a measure of how ...

. With reference to the United States classification system, topical glucocorticoid can be classified into seven groups, with group 1 being the most potent and group 7 the least potent.

Super-high potency (Group 1)

Betamethasone dipropionate Betamethasone dipropionate is a glucocorticoid steroid with anti-inflammatory and immunosuppressive abilities. It is applied as a topical cream, ointment, lotion or gel (Diprolene) to treat itching and other skin conditions such as eczema. Minor ...

, augmented 0.05% *

Clobetasol propionate Clobetasol propionate is a corticosteroid used to treat skin conditions such as eczema, contact dermatitis, seborrheic dermatitis, and psoriasis. It is applied to the skin as a cream, ointment, or shampoo. Use should be short term and only if ot ...

0.05% *

Diflucortolone valerate Diflucortolone valerate (also Nerisone cream/oily cream/ointment, Neriderm ointment, Japanese is a corticosteroid rated Class 2 "potent" (100-150 times) in the New Zealand topical steroid system. It is a white to creamy white crystalline powder. ...

0.3% (not available in the US) * Fluocinonide 0.1% * Flurandrenolide 4 mcg/cm² * Halobetasol propionate 0.05%

High potency (Group 2)

Amcinonide Amcinonide (trade name Cyclocort) is a topical glucocorticoid used to treat itching, redness and swelling associated with several dermatologic conditions such as atopic dermatitis and allergic contact dermatitis. Amcinonide can also be classifi ...

0.1% *

0.05% *

0.025% *

Desoximetasone Desoximetasone is a medication belonging to the family of medications known as topical corticosteroids. It is used for the relief of various skin conditions, including rashes. It helps to reduce redness, itching, and irritation. Desoximetasone i ...

0.25% * Diflorasone diacetate 0.05% * Fluocinonide 0.05% *

Halcinonide Halcinonide is a high potency corticosteroid, in group II (second most potent group) under US classification. It is used topical A topical medication is a medication that is applied to a particular place on or in the body. Most often topic ...

0.1% * Halobetasol propionate 0.01%

Higher-mid potency (Group 3)

0.1% *

0.05% *

Betamethasone valerate Betamethasone valerate is a synthetic glucocorticoid ester. It is the 17-valerate ester of betamethasone. Betamethasone valerate is often used to treat mild eczema with good efficacy and lower incidence of steroid induced adverse effects due to ...

0.1% *

0.05% * Diflorasone diacetate 0.05% *

0.1% (not available in the US) * Fluocinonide 0.05% *

Fluticasone propionate Fluticasone propionate, sold under the brand names Flovent and Flonase among others, is a steroid medication. When inhaled it is used for the long term management of asthma and COPD. In the nose it is used for hay fever and nasal polyps. It ...

0.005% * Mometasone furoate 0.1% * Triamcinolone acetonide 0.5%

Medium potency (Group 4)

0.05% *

Clocortolone pivalate Clocortolone pivalate (brand names Cilder, Cloderm, Purantix), also known as clocortolone trimethylacetate, is a synthetic compound, synthetic glucocorticoid corticosteroid and corticosteroid ester which is marketed in the United States and Austr ...

0.1% * Fluocinolone acetonide 0.025% * Flurandrenolide 0.05% *

Hydrocortisone valerate Hydrocortisone valerate is a synthetic compound, synthetic glucocorticoid corticosteroid and a corticosteroid ester. References

Corticosteroid esters Glucocorticoids Valerate esters {{steroid-stub ...

0.2% * Mometasone furoate 0.1% * Triamcinolone acetonide 0.1%

Lower-mid potency (Group 5)

0.05% *

0.1% *

Desonide Desonide (INN) is a low-potency topical corticosteroid anti-inflammatory that has been available since the 1970s. It is primarily used to treat atopic dermatitis (eczema), seborrheic dermatitis, contact dermatitis and psoriasis Psoriasis is ...

0.05% * Fluocinolone acetonide 0.025% * Flurandrenolide 0.05% *

0.05% *

Hydrocortisone butyrate Hydrocortisone butyrate is a corticosteroid that comes in one of the following forms: * '' Hydrocortisone-17-butyrate'' — * '' Hydrocortisone-21-butyrate'' — It is a group IV corticosteroid under US classification. See also * Cortisol ...

0.1% * Hydrocortisone probutate 0.1% *

Hydrocortisone valerate Hydrocortisone valerate is a synthetic compound, synthetic glucocorticoid corticosteroid and a corticosteroid ester. References

Corticosteroid esters Glucocorticoids Valerate esters {{steroid-stub ...

0.2% * Prednicarbate 0.1% * Triamcinolone acetonide 0.1%

Low potency (Group 6)

* Alclometasone dipropionate 0.05% *

0.1% *

0.05% * Fluocinolone acetonide 0.01% * Triamcinolone acetonide 0.025%

Least potent (Group 7)

* Hydrocortisone (base, ≥2%) 2.5% * Hydrocortisone (base, <2%) 1% *

Hydrocortisone acetate Hydrocortisone acetate is a synthetic glucocorticoid corticosteroid and a corticosteroid ester Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these ...

2.5%

Society

Topical Glucocorticoid Phobia

Topical glucocorticoid phobia is a concern or fear about using topical glucocorticoids, which is commonly found among patients with

atopic dermatitis Atopic dermatitis (AD), also known as atopic eczema, is a long-term type of inflammation of the skin (dermatitis). It results in puritis, itchy, red, swollen, and cracked skin. Clear fluid may come from the affected areas, which often thickens o ...

and their caregivers. This phenomenon has been identified in more than 15 countries globally, including Canada, France,

Japan Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north ...

, the United Kingdom, and the United States. The most prevalent causes for topical glucocorticoid phobia were found to be the concern regarding skin thinning as well as that regarding systemic absorption that could possibly affect growth and development. This phenomenon may be associated with low adherence to topical glucocorticoid therapies.{{Cite journal, last1=Li, first1=Alvin W., last2=Yin, first2=Emily S., last3=Antaya, first3=Richard J., date=2017-10-01, title=Topical Corticosteroid Phobia in Atopic Dermatitis: A Systematic Review, url=http://archderm.jamanetwork.com/article.aspx?doi=10.1001/jamadermatol.2017.2437, journal=JAMA Dermatology, language=en, volume=153, issue=10, pages=1036–1042, doi=10.1001/jamadermatol.2017.2437, pmid=28724128, s2cid=25763417, issn=2168-6068 The extent of corticosteroid fears is independent of corticosteroid acceptability, but correlates with patients' quality of life. Desensitization of parental corticosteroid fears should be integral part of eczema education and therapeutics in order to improve therapeutic efficacy and patients' quality of life. Drugs Context. 2018;7:212547

References

Glucocorticoids Corticosteroids