Introduction

Most adolescents in developed countries suffer from acne leading many to conclude that acne is a 'normal'. However, the significant morbidity associated with it means it frequently has a negative impact on people's lives. Acne, from the Greek word 'acme' meaning 'prime of life', suggests a disorder mainly during adolescence; however, this is somewhat misleading as acne can affect young infants through to individuals in their 40s and 50s. Indeed, over the past two decades the number of individuals who suffer from acne in later life has been increasing. Estimates show that 5% of the population over the age of 45 years still suffers from acne. Acne can have a significant psychological impact on patients regardless of its severity. Nonetheless, severe acne may, in addition, also be very painful, may cause irreversible scarring and may be associated with systemic symptoms including fever, joint pains, and malaise.

What is acne?

Acne lesions develop from the sebaceous glands associated with hair follicles: face, back, chest, and ano-genital area (Figure 12-1). (Sebaceous glands are also found on the eyelids and mucosa, prepuce, and cervix; however, they are not associated with hair follicles.) The sebaceous gland contains holocrine cells that secrete triglycerides, fatty acids, wax esters and sterols as 'sebum'. The main changes in acne include:

• thickening of the keratin lining and subsequent obstruction of the sebaceous duct resulting in closed comedones ('whiteheads') (Figure 12-2) or open comedones ('blackheads' whose colour is due to melanin, not dirt) (Figure 12-3). Acne cannot be diagnosed without the presence of comedones (there are no comedones seen in rosacea)
• an increase in sebum secretion
• an increase in P. acnes bacteria within the duct
• inflammation around the sebaceous gland.

Underlying causes

There are various underlying causes of these changes (Box 12-1).

Hormones

Androgenic hormones increase the size of sebaceous glands and the amount of sebum in both male and female adolescents. Although androgen levels may be normal there is thought to be an increased sensitivity of the glands to androgen hormones. In some women with acne, there is a lowered sex hormone-binding globulin concentration with a consequent increase in free testosterone levels. These imbalances in hormone profile may be seen in females with polycystic ovarian syndrome (PCOS) who present with persistent/treatment resistant acne with irregular menses and possibly hirsutism (they have cysts in their ovaries seen in ultrasound scan). PCOS can lead to fertility issues and an increased risk in later life of metabolic syndrome and possibly endometrial carcinoma. Oral contraceptives containing more than 50 μg ethinyloestradiol can exacerbate acne. Progesterone-only contraceptive pills ('mini pill') increase sebum production and therefore exacerbate acne in those women who are predisposed. Fifteen per cent of women having the Mirena® coil (contains levonorgestrel, a synthetic form of progestin) inserted will experience worsening/new onset of acne.

Infantile acne occurs in the first few months of life. It can rarely be caused by congenital adrenal hyperplasia or virilising tumours; but is most commonly due to transplacental stimulation of the adrenal gland by maternal hormones causing increased adrenal androgens.

Fluid retention

Premenstrual exacerbation of acne is thought to be due to fluid retention, leading to increased hydration and swelling of the sebaceous duct. Sweating also makes acne worse, possibly by the same mechanism.

Stress

It has long been observed by patients that stress leads to a worsening of their acne. Now there is evidence to back up the clinical observation. Stress induces inflammation in the pilosebaceous unit, leading to acne or acne exacerbation. There is evidence that within sebocytes is a complete corticotrophin-releasing hormone system that leads to increased lipid and steroid synthesis and an interaction with testosterone and growth hormone.

Diet

Many patients believe their acne is exacerbated by eating certain foods. Most commonly implicated foods include dairy products, chocolate, nuts, coffee, and fizzy drinks. Some epidemiological studies have suggested that a Westernised diet with high levels of refined sugars and starch may explain striking differences in the prevalence of acne among different populations that are not thought to be explained by genetic factors or weight differences. Several small studies have shown when Westerners are given a low glycaemic index diet, both their BMI and their acne lesion count reduce. Other small studies have shown a weak potential link between acne and cow's milk and possibly even cocoa. The best advice to patients would be to eat a normal diet. However, if there are certain foods that they feel exacerbate their acne, then they should avoid eating those foods.

Seasons

Acne often improves with natural sunlight. Phototherapy with artificial light sources using visible blue light alone or in combination with red light has been shown in several clinical trials to be an effective treatment for acne in a proportion of patients. Heat and sweat can make acne worse.

External factors

Oils, whether vegetable oils in the case of cooks in hot kitchens or mineral oils in engineering, can cause 'oil folliculitis', leading to acne-like lesions through contact with the skin. Other acnegenic substances include coal tar, dicophane (DDT), cutting oils, and halogenated hydrocarbons. Cosmetic acne is seen in adult women who have used cosmetics containing comedogenic oils over many years. Individuals who use rich oils in the scalp can suffer from 'pomade acne', which occurs close to the hairline.

Iatrogenic factors

Corticosteroids, both topical and systemic, can cause increased keratinisation of the pilosebaceous duct resulting in acne. Androgens, gonadotrophins, and corticotrophin can induce acne in adolescence. OCPs of the combined type/progesterone-only pill (mini pill) and antiepileptic drugs may also cause acne. However, an OCP with a high oestrogen combined with low androgen can actually be used to treat acne in women. Some patients develop perioral dermatitis (Figure 12-4) after application of topical steroids to the face, which is characterised by papules and pustules around the mouth and eyes that may mimic acne but there are no comedones. The topical steroid should be stopped and the patient treated with oral tetracycline or erythromycin for six weeks.

Types of acne

Acne vulgaris

Acne vulgaris, the common type of acne, occurs during puberty and affects the comedogenic areas of the face, back, and chest. There may be a familial tendency to acne. Acne vulgaris is more common in boys, 30-40% of whom develop acne between the ages of 18 and 19 (Figure 12-5). In girls, the peak incidence is between 16 and 18 years. Adult acne is a variant affecting 3% of men and 5% of women over the age of 40. Acne keloidalis is a type of scarring acne seen particularly on the neck in men (Figure 12-6; Box 12-2).

Patients with acne often complain of excessive greasiness of the skin, with 'spots', 'blackheads', or 'pimples'. These may be associated with inflammatory papules and pustules developing into larger cysts and nodules. Resolving lesions leave post-inflammatory pigment changes and scarring. Scars (Figure 12-7) may be atrophic and pitted, deep, ('ice-pick') (Figure 12-8), rolling, and boxcar or they may be more hypertrophic or even keloid (Figure 12-9). Scars may also be hyper/hypopigmented and erythematous.

Treatment of acne scarring does depend on the severity and scar type. Generally, more superficial procedures are used to improve the appearance of shallow acne scars (chemical peel, dermabrasion, and fillers) whereas deeper scars may require more aggressive therapy (dermaroller, punch excision, spot fractional resurfacing, fraxel, and intense pulsed light).

Acne excoriée

In this variant of acne, the patient picks at the skin producing disfiguring erosions (Figure 12-10). The acne itself is usually mild but tends to be persistent as it is often very difficult to help the patient break this habit.

Infantile acne

Localised acne lesions occur on the face in the first few months of life. Infantile acne may require topical or systemic therapy as although it will resolve spontaneously it may last up to five years and can cause scarring. There is an association with severe adolescent acne.

Acne conglobata/fulminans

This is a severe form of acne, more common in boys and in tropical climates. There is extensive, nodulocystic acne, and abscess formation affecting particularly the trunk, face, and limbs (Figure 12-11). Acne fulminans is similarly severe but is associated with systemic symptoms of malaise, fever, and joint pains (Figure 12-12). It appears to be associated with a hypersensitivity to P. acnes. Another variant is pyoderma faciale, which produces erythematous and necrotic lesions and occurs mainly in adult women.

Treatment of acne

Although acne can be very painful and may result in pigment change and scarring, it is the psychological impact of the condition that is often the most debilitating for those affected. In the past some medical practitioners have underestimated the effect acne has on patients' lives and consequently patients were often dismissed with no treatment on the assumption they would 'grow out of it'. Although most acne will settle with time, early intervention for those seeking medical advice results in a significant improvement in their quality of life scores as determined by DLQI (dermatology life quality index, which is a validated questionnaire to assess the impact of skin disease on quality of life). DLQI scores for acne are similar to those for psoriasis. Early intervention can also help reduce the likelihood of permanent scars and post-inflammatory pigment changes (Table 12-1).

When choosing a topical formulation to prescribe for a patient with acne it is worth bearing in mind the patient's skin type: for dry/sensitive skin, prescribe creams; for oily skin, use solutions or gels; and for combination skin and hair-bearing sites, lotions are well tolerated.

When treating patients with acne it is important to advise them that they may not see any improvement in their acne for several months and that treatment may need to continue for months or years.

Cleansers

Mild acne may respond well to simple measures such as cleansing the skin with proprietary keratolytics; these dissolve the keratin plug of the comedones. Cleansers need to be used with care as they can cause considerable dryness and scaling of the skin.

Topical treatments

Benzoyl peroxide has been available for the treatment of acne for many years; it has bacteriostatic effects against P. acnes and is mildly comedolytic. It is available with or without prescription at concentrations ranging from 1% to 10% in numerous formulations including lotions, creams, gels, and washes. Mild irritant dermatitis may result, particularly if the patient is using additional anti-acne treatments. Bleaching of clothing and bedding may occur.

Salicylic acid promotes desquamation of follicular epithelium and therefore inhibits the formation of comedones. It is available over the counter at concentrations between 0.5% and 2% in cream and lotion formulations to be used twice daily.

Azelaic acid appears to be effective through its antikeratinising and antibacterial effects. Twenty percent azelaic acid cream is available on prescription and can be used twice daily for up to six months. Mild skin irritation can result in approximately 5% of patients. Azelaic acid can cause depigmentation of the skin and therefore should be used with care.

Topical retinoids are vitamin A derivatives that are anti-inflammatory and comedolytic. Treatments currently available include tretinoin, adapalene, and tazarotene. Topical retinoids are available in cream and gel formulations and are usually applied once daily at night (as they can cause photosensitivity). The main side effect is skin irritation that results in erythema and desquamation; if this occurs patients may be able to tolerate alternate night applications. Tolerance to the irritation usually appears with continued use. Occasionally, an initial acne flare may occur with the use of topical retinoids; this is not, however, an indication to stop treatment as it usually heralds accelerated resolution of the acne.

Topical antibiotics are effective through their bactericidal activity against P. acnes and consequent anti-inflammatory effects. The most commonly prescribed antibiotics include erythromycin and clindamycin either alone or in combination with other agents such as zinc or benzoyl peroxide. Preparations are usually applied twice daily. Antibiotic resistance has been reported more commonly with antibiotics used alone than in combination. Also bear in mind that patients shouldn't be prescribed topical and oral antibiotics to treat their acne simultaneously.

Phototherapy with ultraviolet, visible light or even some laser combinations may be effective as alternative therapies in those unresponsive to or unable to tolerate conventional treatments. Photodynamic therapy has been shown to be superior to blue-red light treatment for mild to moderate acne. However, new hand-held blue-light devices (2 J/cm²/day and 29 J/cm²/day) are available for use at home, with reported reduction in acne lesions about 70% at eight weeks after daily treatment to the whole face.

Systemic treatments

Hormone therapies

These include certain types of OCPs that increase sex hormone-binding globulin and consequently reduce free testosterone levels. These are generally OCPs that have higher oestrogen and lower androgen potential (such as Yasmin®). Antiandrogen treatment alone can be teratogenic and therefore is given to women in the form of a contraceptive that contains cyproterone acetate with ethinyloestradiol (Dianette®). Long-term safety data are available up to five years. Dianette may also help diminish mild hirsutism.

Spironolactone (androgen receptor blocker) may be used in recalcitrant or recurrent acne usually in women over the age of 25 years with 'hormonal acne' (worse around their menstrual cycle and affecting the lower jawline), often given in conjunction with oral contraception. Hormone therapies need to be given for at least 3-6 months before benefits are seen. Spironolactone 50-150 (200) mg daily is frequently effective, the dose is usually started at 50 mg daily and built up slowly, once the acne is controlled then low-dose maintenance (25-50 mg daily) can be continued as necessary. There is a small risk of hyperkalaemia and patients should be advised not to consume excessive amounts of bananas/coconut water.

Oral antibiotics

Tetracyclines continue to be the mainstay of treatment in those over the age of 12 years (below this age, they may cause dental hypoplasia and staining of teeth). Once-daily preparations (lymecycline 408 mg, minocycline 100 mg (MR), and doxycycline 100 mg) are more convenient to use than twice-daily preparations (tetracycline and oxytetracycline) and are equally well tolerated. Tetracyclines should be avoided in pregnancy/breastfeeding and children 12 years. Erythromycin and trimethoprim are good alternatives. Treatment benefits may not be seen for the first six to eight weeks of therapy. An adequate treatment course should last approximately 6-12 months, depending on severity and response.

Oral retinoids

Isotretinoin has revolutionised the treatment of severe acne, but it is usually reserved for moderately severe/resistant disease unresponsive to other oral therapies. This is because of its side effect profile including teratogenesis (90% risk of birth defects) and its ability to potentially cause a rise in liver enzymes and lipids. Blood testing may be required before and during therapy as indicated clinically. Female patients of child-bearing age (who are sexually active) will need to use a robust form of contraception while taking isotretinoin and for one month following its cessation. Pregnancy testing is usually undertaken before release of prescriptions for females.

All patients will experience some drying of the lips (Figure 12-13) and skin (Figure 12-14), and it is this side effect that may limit the dose of isotretinoin tolerated, at least initially. Mood change and depression have been suggested as a possible side effect of isotretinoin. However, a recent meta-analysis showed that there was no difference in low mood/depression between patients with moderately severe acne and patients with moderately severe acne taking oral isotretinoin. The conclusion at this time therefore is that moderately severe acne leads to low mood/depression. Nonetheless, most patients are advised that if they notice any adverse effects on their mood then they should stop the medication immediately.

A modern approach to isotretinoin dosing is for patients to start on a low dose for the first one to two months (20-40 mg daily) and then increase to 1 mg/kg/day to minimise initial xerosis. The cumulative target dosage for isotretinoin is 120-150 mg/kg based on studies showing that acne is likely to be 'cured' if a full treatment course is taken. Occasionally, patients require a second or even third course of isotretinoin treatment, and some patients (particularly males with very severe acne/seborrhoea) may require long-term treatment with very low doses such as 20 mg/week.

Residual lesions, keloid scars, cysts, and persistent nodules can be treated by injection with triamcinolone, topical retinoids, chemical dermabrasion, carbon dioxide laser resurfacing and collagen injections. For severe atrophic boxcar and 'ice-pick' scarring punch biopsies can be used to remove scars from the face and pinch grafts applied to the areas (harvested from behind the ear). When healing is complete dermabrasion can then be used for resurfacing with good cosmetic results. For milder scarring chemical peels or dermaroller treatments may be considered.

Rosacea

Rosacea is characterised by facial flushing, persistent erythema, telangiectasia, inflammatory papules, pustules, and oedema (Figure 12-15); in some patients the changes may be localised to one cheek or the nose (Figure 12-16). In chronic rosacea the nasal skin can become coarse in texture, eventually resulting in gross thickening and hypertrophy - known as rhinophyma (Figure 12-17) (from the Greek, 'rhis' nose, 'phyma' growth). Conjunctivitis, blepharitis (Figure 12-18), and eyelid oedema may be associated. Facial flushing and erythema are frequently exacerbated by heat, exercise, hot food/drinks, spicy food, emotion, alcohol, and sunlight. Eventually, facial erythema can become permanent due to multiple dilated blood vessels - telangiectasia.

Differential diagnosis of rosacea

• Acne, in which there are comedones, a wider distribution and improvement with sunlight. (Acne may, however, co-exist with rosacea - hence the older term 'acne rosacea'.)
• Seborrhoeic eczema, in which there are no pustules and eczematous changes are present, scalp flaking usually present. However, an overlap syndrome of seborrhoeic dermatitis/rosacea is recognised.
• Dermatomyositis, where there may be periorbital and upper eyelid swelling and erythema.
• Lupus erythematosus, which shows light sensitivity, erythema, and scarring, but no pustules.
• Perioral dermatitis, which occurs mainly in women with pustules and erythema around the mouth and chin (Figure 12-4). This may be precipitated by the use of potent topical steroids; some patients experience a premenstrual exacerbation. Treatment is to stop the topical steroids and prescribe oral tetracyclines.

Management

Trigger factors should be identified and ideally avoided. All patients should be encouraged to avoid using skin irritants such as soaps or astringent cleansers. There is evidence that regular use of a broad-spectrum sunscreen can be helpful.

Topical metronidazole has been the mainstay of treating mild disease for many years; however, benefits may not be apparent for several months. Gel and cream formulations of metronidazole 0.75-1% should be used twice daily to the affected skin. Topical 1% ivermectin cream (Soolantra®) has been shown on recent trials to be slightly superior to metronidazole. It is thought to reduce the numbers of demodex mites in the skin. Azelaic acid 15% in a gel formulation is now also available for the treatment of rosacea. Topical preparations seem to be more effective at treating the papules and pustules than the erythema and flushing. However, -adrenoreceptor agonists have recently been evaluated for treatment of diffuse facial erythema because of their ability to reversibly constrict peripheral vasculature with some promising results. Oxymetazoline/xylometazoline (0.05% solutions once daily), both 1-agonists, and brimonidine tartrate (0.5% gel once daily), 2-agonist, have been shown to reduce diffuse facial erythema for up to 12 hours; however, larger studies are ongoing and there is the theoretical risk of tachyphylaxis and rebound once the applications are stopped.

Oral antibiotics including tetracycline, doxycycline, erythromycin, and minocycline have all been used to effectively treat rosacea. Patients should be advised that there may be no visible clinical improvement for several weeks, and treatment courses may need to continue for many months.

The use of low-dose oral isotretinoin for between three and nine months has been shown to be effective in those with refractory disease.

Laser ablation of dilated telangiectatic vessels with a pulsed dye laser can be undertaken once the inflammatory component has been treated. An average of three treatments six to eight weeks apart is usually required to achieve significant improvement. Intense pulsed light (IPL) can also be effective at reducing erythema, telangiectasia, and papules. One study delivered IPL every three weeks for an average of seven treatments, which led to 70% of patients reporting reduced flushing and improved skin texture. Carbon dioxide laser or shave removal with a scalpel blade of excess skin from the nose can significantly improve the appearance of rhinophyma.

Hidradenitis suppurativa (HS) is a chronic relapsing disease leading to occlusion of mainly follicular structures in the intertriginous skin of the axillae, groin, inner thighs, buttocks, perineal, and sub-mammary folds. This occlusion leads to follicular rupture and then an inflammatory response, which translates clinically into chronically inflamed and painful nodules/boils/abscesses and draining sinuses that eventually heal with scarring and then relapse at the same/adjacent sites (Figure 12-19). HS can be painful, distressing, and embarrassing and patients may suffer from depression as a result.

The prevalence is around 3% of the population in the developed world, with a female preponderance, more common in smokers, and presentation usually around age 20-30 years. There may be a family history of HS, especially in patients presenting at a younger age. Patients with HS are more likely to be overweight or obese compared to the general population and there seems to be a link with the severity of the HS and higher BMI. The role of bacteria in HS is uncertain but most physicians agree that secondary infection or colonisation of individual lesions leads to exacerbation of the HS and there is some evidence that the skin microbiome may be altered in diseased skin. HS is thought to be associated with acne, follicular occlusion triad, metabolic syndrome, cardiovascular disease, diabetes, and inflammatory bowel disease.

Clinical stages can be useful to determine the best management strategy for each patient. Hurley describes three stages:

• Stage I: single or multiple abscesses without sinus tracts or scarring
• Stage II: recurrent abscesses with sinus tracts and scarring at single and widely separated lesions
• Stage III: diffuse involvement with connecting sinus tracts and abscesses across an entire area.

Management of HS should include patient education, psychological support, and assessment of QoL. Patients should be encouraged to stop smoking and try to manage their weight and try to achieve their ideal BMI. Measures such avoiding friction to the skin of the affected area are also thought to be helpful, as is daily washing with 4% chlorhexidine (if tolerated). Topical 1% clindamycin solution used twice daily has been shown to be effective in mild (Hurley stage 1) disease. 10 mg/ml triamcinolone injections can be used to settle painful inflammatory nodules, punch de-roofing of new lesions can relieve pressure and allow active drainage. Chemical peels containing keratolytics have been shown in limited trials to help settle mild/moderate lesions more rapidly. However, there may be mild peeling of the surrounding skin. Dapsone 50-200 mg daily can be used to treat Hurley class I/II.

Oral tetracycline antibiotics are frequently used for Hurley class II/III, doxycycline 100 mg/200 mg daily can be taken, or tetracycline, lymecycline, or minocycline. For more severe disease combination rifampicin and clindamycin (300 mg twice daily) can be prescribed for 12 weeks. Other combinations include rifampicin, moxifloxacin plus metronidazole. Oral retinoids can be used (acitretin, isotretinoin) but these medications are teratogenic, which may limit the numbers of patients who are suitable to take them. Oral antiandrogens have also been shown to be of some benefit to women suffering from HS, including cyproterone acetate, spironolactone, and finasteride. Metformin may also be helpful.

Biological agents including infliximab, adalimumab, and ustekinumab have been used with some success in patients with Hurley stage III.

Surgical treatment with punch de-roofing can be used for individual stubborn lesions or sinus tracts has been shown to be beneficial however for more extensive disease wide local excision (possibly with grafting) may be the only option to give the patient long-lasting symptomatic relief.