| ACNE VULGARIS
1.1 Definition
A disorder of the pilosebaceous apparatus characterized by papules, comedones and pustules.
1.2 Aetiology and Pathogenesis
Acne results from an overactivity of the sebaceous gland and a blockage in its duct by hypercornification. The mechanisms behind ductal hypercornification remains unclear. The gland produces sebum which is a mixture of lipids and may be converted into comedogenic and irritant free fatty acids by the microorganisms in the gland.
1.2.1 Sebaceous Gland and Sebum
Sebaceous glands are usually not active until puberty and are under the control of the sex hormones. Sebum is formed from the sebaceous gland via a holocrine process by which the cells of the gland disintegrate into lipids-glycerides, free fatty acids, wax esters, squalene and cholesterol. Although excessive sebum secretion, i.e. seborrhoea, is a feature of acne subjects, increase sebum secretion is not necessarily associated with acne.
1.2.2 Hormonal Factors
Possible underlying abnormalities in androgen metabolism in acne patients include: (1) target organ overactivity, such that there is increased conversion of testosterone to the more potent dihydrotestosterone by the enzyme 5-alpha-reductase in the sebaceous gland (2) increase production of testosterone (3) reduction in sex hormone binding globulin.
Oestrogens reduce the size of the sebaceous gland. However, high doses such as 50 ug of ethinyloestradiol daily are required in order to produce a therapeutic effect.
Progesterone causes water retention with consequent swelling of the pilosebaceous ducts. This is probably the mechanism behind premenstrual flare in many female patients.
1.2.3 Ductal Hypercornification
The comedones represents a blockage of the pilosebaceous duct by a keratin plug. This is caused by a failure of the epidermis lining the duct to keratinize properly so that the keratin is not shed normally. The possible stimuli to hypercornification include androgens and the free fatty acid in the gland. If the blockage is superficial, red papules and pustules result. If it is deeper, larger painful papules, cysts and scarring occur.
1.2.4 Microorganisms
The pilosebaceous apparatus is colonized by microorganisms-Propionibacterium acnes, Staphylococcus epidermidis and the yeast, Pityrosporum ovale. They may be responsible for the conversion of sebum into irritant and comedogenic free fatty acids.
Therapeutic agents aim at
(i) Reduction of the P acnes population e.g. benzoyl peroxides, systemic and topical antibiotics.
(ii) Decrease sebum production e.g. antiandrogen and hormonal therapy, retinoids.
(iii) Reduction of ductal hypercornification e.g. topical retinoids, azelaic acid.
1.3 Clinical Features
Acne vulgaris usually starts in adolescence but onset at twenties or thirties is by no means rare. The face is the commonest site involved. Shoulders, nape of neck and the upper trunk can also be affected. It is not uncommon for acne vulgaris to localize in one particular area. The physical signs of acne vulgaris are blackheads (open comedone), white heads (closed comedone), papules, pustules, abcesses and cysts. Seborrhoea is a frequent association.
Scarring occurs to some degree in almost every patient. Scars may show increased collagen (hypertrophic scars and keloid) or be associated with loss of collagen (i.e. ice-pick scars, depressed fibrotic scars, superficial and deep, soft scar and macular atrophy).
The following are variants of acne vulgaris
(i) Acne conglobata - characterized by deep and painful papules and nodules with cystic lesions. Grouped, multiple blackheads and extensive scarring are also present.
(ii) Acne fulminans - a rare variant seen almost exclusively in adolescent boys. The patient suddenly develops acute inflammatory lesions which may become necrotic with haemorrhagic crustings. There is associated fever, myalgia, arthralgia and even frank arthritis. The condition is immunologically mediated and requires treatment with systemic steroid.
(iii) Acne excoriée - this is a facial disorder secondary to an obsessional and neurotic tendency to interfere with the skin. Acne lesions may be mild or even absent and the physical signs are mainly unsightly excoriations and scarrings.
1.4 Management
Apart from general measures, topical treatment alone is usually adequate for patients with mild acne. For more severe acne, combination of a topical agent with an antibiotic, or with hormonal therapy for female patient, is indicated. It is better to combine agents having different mode of actions - for example a keratolytic with an antimicrobial. For acne conglobata, isotretinoin is the treatment of choice.
1.4.1 General Measures
Educating the patient on the nature of the disease and daily skin care is important. The latter should be in the form of cleansing the face with ordinary soap and water twice daily. Expensive soap or strong detergent are not necessary. 'Facial' treatment (facial sauna, heat and massage) is not only useless but may also worsen the condition by precipitating the development of inflamed lesions. Oily cosmetics and hair greases are comedogenic and causes pomade acne and should not be used. Squeezing lesions and excessive cleansing should also be avoided. The psychological aspect must not be overlooked especially for patients with acne excoriee.
1.4.2 Topical Therapy
(i) Benzoyl peroxide
It is an effective antibacterial and mild anti-inflammatory topical agent. Various strengths (2.5%,5% and 10%) are available. Since it can cause irritation of the skin patients should be warned and advised to start with the weakest strength. The frequency and duration of exposure could then be stepped up gradually.
(ii) Retinoic acid
It is a keratolytic, and can increase the basal cell mitosis and epithelial turnover. Various strength are available in the gel and cream base (Retin A gel 0.01% and 0.025%, and cream 0.05 and 0.1%) As it is also an irritant, the same principle of application like benzoyl peroxide is employed.
(iii) Azelaic acid
It is available as 20% azelaic acid in cream base. It act by both inhibition of the growth of the propionibacteria and decreases the ductal hypercornification and is indicated for comedonic and mild to moderately severe papulopustular acne. It is a safe topical agent and can be given to pregnant woman. The cream should be applied twice daily and minor degree of irritation is commonly seen.
(iv) Topical antibiotics
Although topical antibiotics are less effective than benzoyl peroxide in inhibiting P acnes, they offer the advantage of causing less irritation and being more convenient. Erythromycin and clindamycin appear to be both safe and effective for the topical treatment of mild to moderate inflammatory acne. However there is concern on the possible epidemiological consequences of transferred bacterial resistance resulting from the use of topical antibiotics.
(v) Other topical agents
Sulphur, salicylic acid and resorcinol are agents commonly used in commercial preparations, probably act as keratolytic and are useful in mild acne. Topical steroids are sometimes added into proprietary preparations. Although they are anti inflammatory and may help to reduce the inflammatory effects of keratolytics, long-term use is not advisable in acne patients (cf perioral dermatitis).
1.4.3 Systemic Therapy
(i) Antimicrobials
Antibiotics in acne act by inhibition of the follicular bacterium, Propionibacterium acnes. In addition to this tetracycline and erythromycin also have anti-inflammatory effects. Antimicrobials should be given for 6 months to exert its full effect, despite that noticeable improvement may be observed earlier. If the response to one antibiotic is not satisfactory another one can be tried. If successful, any of these drugs can safely be continued on a long-term basis. The patients should be made to understand that treatment is only suppressive and not curative, and relapse may follow withdrawal of the drug. A pustular folliculitis of the face due to Gram-negative superinfection is a rare complication of long-term antibiotic therapy and should be looked out for in case of 'resistance' to treatment. Culture of the pustules should be done in case of doubt.
(a) Tetracycline
This is still the drug of choice, being cheap and effective. It is a bacteriostatic agent which acts mainly by reducing the acne bacteria population on the skin. The usual dose is 1 gm/day in divided dosage and should be taken with an empty stomach. Milk and diary products should be avoided. Side effects include GI upset, drug eruption (especially fixed drug eruption). This group of antibiotic is absolutely contraindicated in pregnancy and extra caution should be taken in prescribing it to young female patients.
(b) Minocycline and doxycycline
Minocycline is more lipid soluble and penetrates the sebaceous glands better than tetracycline. It has a more persistent effect and bacteria resistance is less common. Both minocycline and doxycycline are probably more effective, but more expensive, than tetracycline. They have the advantage of causing less GI upset and can be given as a single daily dose (100 mg/day) or in a divided twice daily dosage. Their side effects are similar to tetracycline. Minocycline in addition can cause dizziness and induce various type of pigmentary change occasionally.
(c) Erythromycin
This is as effective as Tetracycline but resistance develops more rapidly. The drug is safe in pregnancy, and is preferred to tetracycline for married woman.
(d) Dapsone - previously very useful for treating cystic acne before isotretinoin is available. Dosage is 100 mg daily. This may cause haemolytic anemia in G6PD deficiency patients.
(e) Septrin - this has been proven effective for acne that does not respond to conventional therapy. The dosage is one to two tablet twice daily. Because it can produce severe allergic reactions such as erythema multiforme as well as blood dyscrasia, it is only recommended for use in refractory patients for relatively short periods (6 months or less).
(f) Ampicillin is used mainly for gram negative folliculitis.
(ii) Hormonal therapy
This is indicated for women with acne especially for those patients with features of androgen excess like hirsutism and androgenic alopecia. Possibilities of androgen excess secondary to diseases like polycystic ovarian disease should not be overlooked.
Diane 35 (Dianette) - is a combination drug of anti-androgen, cyproterone with an estrogen, ethinyl estradiol. It is indicated only for women and especially for those who would consider oral contraceptive pill for contraception. Cyproterone is teratogenic and the drug is contraindicated in pregnancy. It is also not used for patients with other risk factors like familial history of cardiovascular diseases or diabetes mellitus. Patients on long term Dianette should be followed up regularly for pap smear and blood pressure.
Others - Ketoconazole has antiandrogen activity but is limited by its serious side effects. Cimetidine is a mild antiandrogen and is not clinically useful. Administration of gonadotropin releasing hormone agonist as a form of medical castration should only be undertaken by endocrinologists or gynecologists.
(iii) Retinoid
13 Cis-retinoic acid (Roaccutane) is a vitamin A derivative with a potent effect on sebaceous glands. The drug is the treatment of choice for nodulocystic acne, for acne that is unresponsive to adequate conventional therapy, and particularly for acne causing scarring. It is given in a dosage of 0.5-1 mg/kg/day orally. Studies have been shown that optimal long-term benefit can be achieved by using the higher dosage regime especially in younger patients and in patient with predominantly truncal disease. There is also evidence that when patients have received a total cumulative dose of more than 120 mg/kg, they have a better chance of achieving long-term remission. In practice the cure rate approaches 90% if given for 4 months with the 1 mg/kg dosage. Occasionally longer duration of therapy may be needed for resistant cases.
This drug is teratogenic and it is unwise to prescribe the drug to female patients without concomitant adequate contraception, and contraception should be continued for at least 1 month after cessation of therapy. Its side effects include dryness of the skin and lips, epistaxis, arthralgia and myalgia, and temporary hyperlipidaemia and abnormal liver function test. Headaches can occur , and benign intracranial hypertension has been reported.
1.4.4 Other Specific Therapy
(i) Surgery
Unsightly scars and persistent cysts, when they are no longer inflamed, may be excised. Dermabrasion may be of value for depressed scars and can be considered when the disease is inactive. Pigmentary changes after dermabrasion is a problem in colored race.
(ii) Treatment of comedones
Blackheads can be removed with a comedones extractor. The use of light cautery after the application of EMLA as a local anaesthetic has been shown to help patients with multiple macro-whiteheads.
(iii) Collagen injection of scars
Purified bovine dermal collagen injection can give good cosmetic results for some acne scars. This is an expensive procedure and injection need to be repeated to maintain the improvement. There is also a small risk of hypersensitivity reaction.
(iv) UVB irradiation - UVB irradiation to the face in sufficient doses to produce mild erythema and desquamation of the skin can improve acne in some patients, but response to treatment is variable.
(v) Systemic steroids-very useful in arresting the inflammatory lesions before isotretinoin is available. Now rarely used except for treatment of acne fulminans.
(vi) Intralesional Kenacort A - for individual cystic lesion, can reduce the inflammation quickly but there is a risk of leaving a pitted scar. Injection for keloidal acne is another indication.
(vii) Oral zinc therapy - was very popular before but failed to demonstrate significant benefit in many clinical trials. Dosage-Zinc gluconate 200 mg/day.
2. OTHER ACNEIFORM ERUPTIONS
2.1 Rosacea
Rosacea is a disease of unknown aetiology. It is seen in both sexes and is rare before the fourth decade. Patients usually complain of flushing attacks and erythema the face. Examination will reveal acneiform papule, pustules, telangiectasia and dilated venules on the face especially over the nose and cheeks. Its late onset and absence of comedones differentiate it from acne vulgaris. Rhinophyma is a known complication where there is a marked hyperplasia of the sebaceous glands of the nose. Other complications include conjunctivitis, blepharitis and keratitis. Treatment with low dose tetracycline is usually effective. Other antibiotics effective in acne vulgaris can also be used. Metronidazole either as a topical or a systemic therapy is also helpful. Topical steroids, especially potent ones, should be avoided because rebound vasodilatation may actually worsen the condition.
2.2 Perioral Dermatitis
Perioral dermatitis results from prolonged therapy with potent topical corticosteroid therapy. It affects predominantly young women and the clinical appearance is characteristic. There are red papules and pustules, often on a background of erythema and scaling, around the mouth. Discontinuing the topical steroids is the most important step in treating this condition. Oral tetracycline 250 mg two to three times daily for one month is usually successful.
2.3 Steroid Acne
Although a number of drugs can cause an acneiform eruption, by far the commonest cause of drug induced acne is systemic corticosteroid therapy. Steroidal acne usually appears as a monomorphic erythematous papular eruption on the face, upper chest and back of the patients on systemic steroid therapy. Withdrawal of therapy will usually lead to a remission.
2.4 Pityrosporum Folliculitis
Histologically, there is inflammation of the hair follicle with presence of spores of the pityrosporum yeast. Clinically there is a fairly monomorphic papular to pustular eruption on the upper back and chest. The face is not usually involved but association with acne vulgaris is common. Treatment with conventional antiacne therapy is usually futile. Systemic antifungal therapy with ketoconazole or itraconazole has to be used. Topical antifungals, like clotrimazole cream, have been reported to be useful.
2.5 Oil Acne and Chloracne
Industrial workers may develop acne when exposed to industrial oil and other chlorinated hydrocarbon. Oil acne is typically seen on the thighs and knees and appears as an acneiform eruption.
2.6 Gram-negative Folliculitis
Patients on long term antibiotics for inflammatory acne will occasionally complicate by crops of pustules or deep seated nodules around nose. Culture of these lesions reveals Enterobacter, Klebsiella or Proteus. Treatment with Roaccutane is very effective. Ampicillin is also effective to suppress the disease.
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