Many assays using laboratory animals and human volunteers have been used to estimate the clinical efficacy of the topical corticosteroids. Cell cultures, laboratory animals and tests using human volunteers are also used to assess atrophogenic potential of the molecules, as skin atrophy is a common adverse drug reaction reported with the use of topical corticosteroids.

Human vasoconstriction assay, developed by McKenzie and Stoughton, is a commonly used method to estimate the potency of topical corticosteroids. Different dilutions of the drug are applied to the skin and the degree of skin blanching is observed [10]. Some studies have shown a co-relation between the vasoconstriction activity and anti-inflammatory activity in clinical use [11, 12]. Vasoconstriction may not always co-relate with therapeutic assay [13]. A study which compared four ranking systems (vasoconstriction, clinical outcome, therapeutic index and efficacy/safety/cost) found that vasoconstriction assay co-related with clinical efficacy in 62% of agents studied [14]. Currently, however, vasoconstriction property forms the basis for classification of topical corticosteroids.

As the vasoconstriction assay is based on subjective assessment, efforts have been made to make the assessment more objective by laser Doppler velocimetry, capillaroscopy or transepidermal water loss.

Recently, Humbert and Guichard questioned the rationale of using vasoconstrictor effect, which is one of the many possible actions of corticosteroids, as a measure of their anti-inflammatory effect and therapeutic efficacy. They proposed a new classification of topical corticosteroids based on the condition for which it is to be used and measuring the relative effects of the different molecules [15].

The small plaque psoriasis bioassay proposed by Dumas and Scholtz is a modification of the vasoconstrictor assay. In this assay, the corticosteroid formulation is directly tested on psoriatic plaques, rather than on the normal skin, and its anti-inflammatory effect measured [16]. Rat thymus involution assay and anti-granuloma assay have also been used to measure the anti-inflammatory effect of topical corticosteroids. Fibroblast assay measures the atrophogenicity property of topical corticosteroids [6].

The WHO classification divides the topical corticosteroids into seven classes/groups, with group 1 being the most potent and group 7 being the least potent. In this system, potency is based on activity of topical corticosteroid molecule, its concentration and nature of vehicle. The same drug can be placed into different classes with the use of different vehicles [17]. In this classification, the seven classes of corticosteroids are categorized into four groups, wherein class I is considered as ultrahigh-potency, classes II and III as high-potency, classes IV and V as moderate-potency and classes VI and VII as low-potency corticosteroids.

The British National Formulary classification divides the topical corticosteroids into four classes and does not take into consideration the vehicle [18]. Class I is considered to be very potent, while class IV includes drugs with low potency.

The high-potency formulations are recommended for short-term use only and are required for areas like palms and soles and also for chronic or hyperkeratotic lesions. Low- to medium-potency topical corticosteroids are useful for acute inflammatory lesions on the face and intertriginous areas and can be used for a longer term (Table 2.1).

Corticosteroids have anti-inflammatory, immunosuppressive, anti-proliferative and vasoconstrictor actions. Many of these actions are mediated by the nuclear glucocorticoid receptor which modulates transcription of proteins. This is considered to be the genomic mechanism and mediates many of the actions produced by the corticosteroids. Additionally, non-genomic mechanisms have been proposed to explain some of the immediate effects which cannot be explained by the classic glucocorticoid-receptor mechanism [19].

The corticosteroid receptor can be present in several isoforms. Corticosteroids produce their effects through the α-isoform, while relatively high levels of β-isoform may cause the resistance to glucocorticoids [2]. The glucocorticoid receptors are found in most of the cells of the body, which accounts for their widespread systemic effects. In the skin, glucocorticoid receptors have been located in keratinocytes and fibroblasts within the epidermis and dermis [20, 21].

When the receptors are unoccupied by the corticosteroid molecule, they are usually present in the cytoplasm. The inactive receptor is bound to proteins like heat-shock proteins (Hsp) like Hsp90, Hsp70 and immunophilins. The glucocorticoid molecule, being lipophilic, enters the cell by passive diffusion. Within the cell, it binds to the receptor, the heat-shock proteins and immunophilins dissociate from the receptor and the corticosteroid-receptor complex then translocates to the nucleus [2].

Within the nucleus, this receptor-corticosteroid dimer complex then binds to a specific sequence of DNA, known as the glucocorticoid-response element. This interaction induces synthesis of anti-inflammatory proteins and regulator proteins involved in metabolic processes. This process is known as transactivation. The metabolic effects and some of the adverse drug reactions may occur through this process [22].

When the corticosteroid molecule directly/indirectly interacts with regulation of pro-inflammatory genes for transcription factors, such as activator protein 1 (AP1), nuclear factor κ B (NFκB) or interferon regulatory factor-3 (IRF-3), this process is termed as ‘transrepression’. This negative regulation brings about anti-inflammatory and immunosuppressive effects [23].

The following non-genomic mechanisms for corticosteroids have been proposed to explain some of their rapid actions:

Corticosteroids are useful in varied dermatological conditions due to their anti-inflammatory, immunosuppressant, vasoconstrictive and anti-proliferative effects (Fig. 2.2).