Fig. 26.1
Regional variation in the percutaneous penetration of hydrocortisone in men. Adapted from Feldman and Maibach
The duration of application of the TCS also contributes significantly to the occurrence of side effects. The frequency of side effects is minimized when the duration of treatment is limited to a few days to a few weeks or via the use of intermittent therapy rather than continuous therapy when prolonged treatment is indicated.
The most important factor that is linked directly to the occurrence of cutaneous side effects however is the potency of the TCS, which is derived at after subjecting it to the vasoconstrictor assay, designed by McKenzie and Stoughton [6]. Most of the classifications of TCS, including the American classification into seven classes, and the British National Formulary classification are based on the assessment of the compound using the vasoconstrictor assay. In this assay, the TCS is applied to the skin of normal human volunteers. It then penetrates the stratum corneum and causes pallor of the skin as a result of its capacity to constrict the dermal blood vessels. The degree of vasoconstriction is then evaluated instrumentally as well as objectively using a visual grading scale and the compound classified. Characteristically, pallor secondary to the TCS reaches a maximal intensity around 9–12 h after application and fades initially rapidly over the next 10 h and slowly thereafter [7].
Cutaneous side effects of TCS are commoner than systemic side effects of TCS [5]. They can be classified into atrophy and related changes, pigmentary changes, follicular changes, vascular changes, infections and miscellaneous (Table 26.1). The side effects listed are usually confined to the sites of application of the TCS.
Table 26.1
Topical side effects of topical corticosteroids
Cutaneous adverse effects of topical corticosteroids |
|---|
Atrophy and related changes |
• Steroid atrophy |
• Striae |
• Easy bruising |
• Ulceration |
• Telangiectasia |
• Purpura |
• Stellate pseudoscars |
Pigmentary changes |
• Hypopigmentation |
• Hyperpigmentation |
Follicular changes |
• Hypertrichosis |
• Acneiform eruption |
Vascular effects |
• Rosacea |
• Rebound phenomenon |
• Facial erythema |
• Red scrotum syndrome |
Infections and Infestations |
• Bacterial infections: folliculitis, furuncles |
• Viral infections: herpes |
• Fungal infections: |
– Tinea incognito |
– Majocchi granuloma |
– Candidiasis |
– Granuloma gluteale infantum |
• Infestations: scabies incognito |
Miscellaneous |
• Perioral dermatitis |
• Contact sensitization |
• Delayed wound healing |
26.3 Atrophy and Related Changes
Steroid atrophy is the most common cutaneous side effect of TCS [5]. Atrophy is also an irreversible side effect particularly when the TCS has been applied for a prolonged period. Steroid atrophy is most likely to occur at sites where the skin is inherently thinner such as the face especially the eyelids and flexures. Both fluorinated and non-fluorinated TCS can cause cutaneous atrophy. All atrophic changes secondary to application of TCS are reminiscent of actinically damaged skin and the ageing skin. Cutaneous atrophy secondary to TCS is classified into epidermal atrophy and dermal atrophy. Subcutaneous atrophy can rarely occur.
26.3.1 Epidermal Atrophy
In the first few days after commencing therapy with TCS, the metabolic activity of the keratinocyte is reduced [8]. Following protracted or rigorous exposure to the compound, the overall thickness of the epidermis decreases, as evidenced by thinning of the stratum corneum and almost complete loss of the underlying stratum granulosum. Ultrastructurally these changes occur as a result of decreased synthesis of keratohyalin granules, stratum corneum lipids and corneodesmosomes that are vital for the integrity of the stratum corneum [9].
Epidermal atrophy is clinically evident as fine ‘cigarette paper’ wrinkling of the skin at the site of application of the TCS.
26.3.2 Dermal Atrophy
This occurs as a result of diminution in the synthesis of dermal collagen via inhibition of the enzyme hyaluronan synthase 2 in the dermis [10]. In addition, the size of dermal fibroblasts as well as the number of mast cells is also significantly reduced [11, 12]. Research using capillaroscopic studies has demonstrated prolonged ischemia as another factor leading to dermal atrophy [13, 14]. These effects are heightened when the TCS is applied under occlusion. Collagen synthesis was found to be decreased as early as the third day of application of a potent TCS like betamethasone valerate and persisted for more than 2 weeks after discontinuation of the compound [12].
26.3.3 Striae
Striae are visible linear scars which form in areas of dermal damage. Striae occurring due to TCS application occur as a result of cutaneous atrophy and are observed at the site of prolonged TCS application. Histologically they are characterized by thinning of the epidermis and arrangement of the dermal collagen in fine thin lines parallel to the surface of the skin. Striae initially have an inflammatory phase in which they may be elevated and tender. Subsequently they flatten and become violaceous and smooth [15].
26.3.4 Purpura and Easy Bruisability
Secondary to TCS-induced loss of glycosaminoglycans in the dermis, the dermal blood vessels lose their supportive framework and hence rupture when subjected to even trivial trauma, leading to easy bruisability and subsequent purpura formation [16]. Frank cutaneous ulceration has also been rarely documented [17].
26.3.5 Telangiectasia
Telangiectasia refers to chronically dilated capillaries or venules. The word is derived from Latin, tel = end; Greek, angos = vessel; and Greek, ectasis = expansion. Due to loss of surrounding dermal substance and overall cutaneous atrophy, the blood vessels become more prominent and are visible to the naked eye [16]. Endothelial cell proliferation by TCS is also another mechanism which leads to formation of telangiectasia [18].
26.3.6 Stellate Pseudoscars
These are another consequence of TCS-induced cutaneous atrophy. They appear as hypopigmented star-shaped or linear scars with irregular margins [19]. They mostly occur on the skin of the extremities, sometimes at the sites of resolved purpura.
26.4 Pigmentary Changes
TCS inhibit melanin synthesis by hindering normal function of melanocytes [20]. This is pronounced when the TCS is applied under occlusion and results in hypopigmentation. This effect is reversible and normal pigmentation is restored within a few weeks after discontinuation of the TCS application [21].
26.5 Follicular Changes
26.5.1 Hypertrichosis
Hypertrichosis is defined as increase in the growth of hair which is thicker, denser and longer for the age, sex and race of the individual at a particular site. It has to be differentiated from hirsutism in which there is increase in terminal hair in the androgen-dependant areas of the body in women. TCS are iatrogenic causes of localized hypertrichosis; they stimulate growth of the vellus hair after prolonged application [22]. The hair persists as long as the TCS is continued. Upon stopping, the hair will be shed only after the anagen stage is over, an average of 2–3 years [5].
26.5.2 Acneiform Eruption
Acneiform eruption is an inflammatory follicular reaction characterized by erythematous monomorphic papules and pustules. Unlike acne vulgaris, the lesions here are monomorphic and lack comedones and cysts. The commonest cause is steroids, both systemic and topical, although various other drugs can also cause it [23]. The most common sites affected include the face, chest and upper back. Histopathologically a steroid-induced acneiform eruption demonstrates focal necrosis in the follicular infundibulum with extrusion of the follicular contents into the surrounding dermis and neutrophilic infiltrate in the perifollicular and intrafollicular areas [24]. A drug-induced acneiform eruption should be suspected when there is a sudden occurrence of the lesions in a patient who has never had acne before, abrupt flare of acne in a patient with pre-existing acne, or late-onset of acne [25]. The treatment of acneiform eruption is similar to acne vulgaris.
26.6 Vascular Side Effects
They include steroid-induced rosacea, perioral dermatitis, red scrotum syndrome and rebound phenomenon. They occur more commonly with the use of fluorinated TCS [26].
26.6.1 Rosacea and Perioral Dermatitis
These side effects were first observed in 1957 after topical steroids were in use for 7 years. The terminology steroid rosacea has undergone numerous revisions; it was initially termed ‘light sensitive seborrheid’ by Frumess and Lewis as it resembled seborrhoeic dermatitis [27]. It was later named ‘perioral dermatitis’ by Mihan and Ayres [28]. Following this in 1969, Sneddon labelled it ‘rosacea-like dermatitis’ [29], and in 1974, the term ‘steroid rosacea’ was introduced by Leydon et al. [30]. Both the later terminologies are used in the current dermatology literature.
The time of onset of these varies greatly and can range between 2 months and 7 years but usually lies within 2–6 months [31]. TCS are used with or without prescription for a wide range of facial dermatoses. Following initial use, the patient notes dramatic improvement in the concerned dermatosis and continues using the TCS without consultation. After temporary discontinuation, flaring of the dermatosis results, and the TCS restarted by the patient. Hence, the vicious cycle continues before a patient lands at a dermatology OPD with full-blown steroid rosacea.
The symptoms include burning, stinging, facial flushing, skin dryness, persistent redness, photosensitivity and sometimes immense pruritus, similar to the symptoms of classical rosacea. On examination, telangiectasia, papules and pustules are seen on a background of erythema. Increased dermal populations of the commensal mite Demodex folliculorum are particularly noted in steroid rosacea and are postulated to cause blockage of the hair follicle leading to an inflammatory response [32].
The clinical picture is classified into three morphological types: perioral, centrofacial and diffuse [30].
The perioral form, also referred to as perioral dermatitis, is characterized by erythematous papulopustules in the perioral area with a rim of sparing immediately adjacent to the vermilion border of the lips. The centrofacial type affects the convexities of the face including the cheeks, chin and forehead with sparing of the perioral area. The diffuse type affects the entire face and is the severe form. Untreated, steroid rosacea can progress to fibrotic changes in the dermis and irreversible lymphedema secondary to prolonged inflammation.
The first step in the management of steroid rosacea is discontinuation of the offending agent, the TCS. In a patient who has been using a potent TCS for more than 2 months, tapering of the potency for the first few weeks followed by slow tapering of the low-potency steroid is initiated. In one who has been using a low-potency steroid for a prolonged duration, using it initially on alternate days, followed by twice weekly, once weekly and finally discontinuation, is advised. Tapering the TCS in the above manner is done to avoid the rebound phenomenon. In addition to this, low-dosed doxycycline at a dose of 40–100 mg daily for 3–4 months is prescribed. This is done to act against the increased populations of Propionibacterium acnes that are observed in a chronic steroid-exposed face [33]. The treatment regimen is changed after 3–4 months if adequate response is not achieved; low-dose isotretinoin at a dose of 5–20 mg is then introduced and continued for 3–4 months [31].
26.6.2 Red Scrotum Syndrome
This syndrome is analogous to rosacea and occurs due to repeated application of TCS on the scrotum [33]. It is characterized by chronic bright red erythema, itching, hyperalgesia and a burning sensation. A neuropsychiatric aetiology compounded by repeated application of TCS is implicated in the pathogenesis [34, 35]. Withdrawal of the TCS and response to tetracyclines favour the latter, whereas a response to gabapentin in a few patients favours the neuropsychiatric theory.
26.6.3 Rebound Phenomenon
This is characterized by the worsening of the dermatosis when the TCS is withdrawn. It is commoner in chronic dermatoses such as psoriasis and rosacea. On withdrawal of the TCS application on psoriatic plaques, pustulation can be precipitated, localized usually, but rarely generalized [36]. This phenomenon occurs with the use of potent TCS, application under occlusion, use of large quantities and sudden withdrawal. Mommers et al. demonstrated that an almost complete block of proliferation of basal cells occurs after use of clobetasol-17-propionate ointment, a superpotent TCS, under occlusion in psoriatic patients, and a rebound increased proliferation resulted after withdrawal [37].
26.7 Infections and Infestations
TCS decrease the overall immunity of the skin, both cell-mediated and humoral. Hence, bacterial, viral, fungal infections as well infestations can resurface or be aggravated.
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
