- Definition of Acne vulgaris
- Clinical features
Is a common chronic skin condition that affects both males and females in adolescence. For some, it can also continue into adulthood and it can affect women during pregnancy or during their menstrual cycle. Acne results in the development of pimples or pustules from blocked hair follicles and increased secretions in the sebaceous glands. Sebaceous glands produce sebum which is a mixture of oils and waxes. This sebum lubricates the skin and prevents water loss. Acne commonly appears on the face, upper back and upper arms and chest, as this is where there is the highest concentration of sebaceous glands.
a)Elevated Sebum Excretion
The main determinant of sebum excretion is hormonal,accounting for the onset in the teenage years. Androgens are principal sebotrophic hormonal, but progestogens also increase sebum excretion, whilst oestrogen reduce it. Majority of patient with acne have a normal endocrine profile.
b)Infection with Propiobacterium acnes
This bacteria colonises the pilosebaceous duct and acts on lipids to produce several pro-inflammatory factors and the pilosebaceous unit becomes occluded
Diet is another contributing factor, certain foods can trigger or aggravate acne. The exact food trigger depend on a person’s unique constitution. Diet high in chocolate, fatty foods or fast food tend to increase acne flare-up. Daily products and high-glyceamic index foods have influence on hormonal and inflammatory factors.Alcohol us may exacerbate.
Hygiene; the primary concern is there is pattern of over-washing or repetitive rubbing of the skin. This behavior weaken the integrity of the skin’s surface making a person more susceptible.
When a person is engaged in a high degree of activities such as sports, acne is worsen in areas that sweat a lot such as chest and upper back. It is important to clean the skin thoroughly after each activity and before bed. Intense activity associated with acidic sweat can contribute to acne, especially on the back.
Prolonged or severe stress is not typically the cause, but is often an aggravating factor. Acne can cause or aggravate emotional stress and can impact social interactions and relationships. Acne often affects individuals when they are the most vulnerable – in adolescence
Medical prescription that alters hormone levels can worsen(aggravate) acne. This include medication such as;corticosteroids, halogens and long-term use of antibiotics.Using inhaled corticosteroid drugs (as with COPD) may be implicated in acne and other skin manifestations.
Lesion are usually limited to the face, shoulders, upper chest and back but may extend to the battocks. Seborrhoea (greasy skin) is often obvious. Open comedone (blackheads) due to plugging by keratin and sebum of the pilosebaceous orifice,or closed comedone (whitehead) due to accretion of sebum and keratin deeper in the pilosebaceous duct, are usually evident.It is thought that the combination of keratin breakdown and bacterial products gives rise to the black colour seen in blackheads. Inflammatory papules, nodule and ‘cyst’ occur, with one or two types of lesion predominating. Scarring may follow.
A number of descriptive terms are applied to clinical variants of acne.
- Conglobate acne is characterised by comedones, nodules, abscesses and sinus tracks, often accompanied by keloidal scarring. True cysts are rare in the acute phases and are more likely to reflect inflamed nodules. Epidermoid cysts are common later on in acne.
- Acne fulminans is severe acne accompanied by fever, joint pains and markers of systemic inflammation such as a raised ESR. Develops in males between the ages of 13 to 22,it is a rare condition.
- Acne excoriée refers to the effects of scratching or picking, principally on the face of teenage girls with acne. It is thought to be associated with underlying depression, anxiety, or emotional problems.
A mild form of acne dominated by the presence of comedones may be due to exogenous substances such as tars, chlorinated hydrocarbons or oily cosmetics. A primarily pustular rash may also be seen in those being treated with corticosteroids, lithium, oral contraceptives and anticonvulsants, but these forms are usually clinically distinct from the usual variety developing in adolescence.
Individuals with moderate or even severe acne very rarely have any other systemic disorder. However, those with polycystic ovary syndrome are more likely to have severe acne, and menstrual irregularities require investigation. If there is associated cutaneous virilism or other features of an androgen-secreting tumour, further endocrine investigation and assessment are warranted.
Investigations are rarely required. It is important to enquire about the details of previous treatments and their duration; for example, antibiotics are commonly prescribed for too short a period of time or without the appropriate advice that most tetracyclines need to be taken separately from dairy products. It is also important to establish the patient’s expectations
Topical therapy is useful in mild and moderate acne, as monotherapy or in combination and also as maintenance therapy.
It is an effective topical agent and is available in different formulations; lotions, creams, and gels and in different concentrations.
The stability is very dependent on its vehicle. Gels are generally more stable and active and water-based gel being less irritant is more preferred over creams and lotions. Benzoyl peroxide is a broad spectrum bactericidal agent which is effective due to its oxidizing activity.
The drug has an anti-inflammatory, keratolytic, and comedolytic activities, and is indicated in mild-to-moderate acne vulgaris. Clinicians must make a balance among desired concentration, the vehicle base, and the risk of adverse effects, as higher concentration is not always better and more efficacious.
The main limitation of benzoyl peroxide is concentration dependent cutaneous irritation or dryness and bleaching of clothes, hair, and bed linen. It can induce irritant dermatitis with symptoms of burning, erythema, peeling, and dryness.This occurs within few days of therapy and mostly subsides with continued use.
b) Tropical retinoids
Retinoids have been in use for many years. Topical retinoids target the microcomedo–precursor lesion of acne. It is preferred topical agent be used as the first-line therapy, alone or in combination, for mild-to-moderate inflammatory acne and is also a preferred agent for maintenance therapy.
Its effectiveness is well documented, as it targets the abnormal follicular epithelial hyperproliferation.Reduces follicular plugging and reduces microcomedones and both noninflammatory and inflammatory acne lesions.Their biological effects are mediated through nuclear hormone receptors (retinoic acid receptor RAR and retinoids X receptor RXR with three subtypes α, β, and γ) and cytosolic binding proteins.
Tretinoin, adapalene, tazarotene, isotretinoin, metretinide, retinaldehyde, and β-retinoyl glucuronide are currently available topical retinoids.The most studied topical retinoid for acne treatment worldwide are tretinoin and adapalene. There is no consensus about relative efficacy of currently available topical retinoids (tretinoin, adapalene, tazarotene, and isotretinoin). The concentration and/or vehicle of any particular retinoid may impact tolerability. Adapalene is generally better tolerated than all other retinoids. Tretinoin has recently become available in formulations with novel delivery systems which improves tolerability. One such product Retin-A Micro (0.1% gel) contains tretinoin trapped within porous copolymer microspheres. Avita, the tretinoin is incorporated within a polyoylprepolymer (PP-2). Each of the theses formulations releases tretinoin slowly within the follicle and onto the skin surface, which in turn reduces irritancy with the same efficacy.
Common side effects of Retinoid
The main adverse effects with topical retinoid is primary irritant dermatitis, which can present as erythema, scaling, burning sensation and can vary depending on skin type, sensitivity, and formulations.
c) Topical Antibiotics
Many topical antibiotics formulations are available, either alone or in combination. They inhibit the growth of Propiobacterium acne and reduce inflammation. Topical antibiotics such as erythromycin and clindamycin are the most popular in the management of acne and available in a variety of vehicles and packaging.
Side effects though minor includes erythema, peeling, itching, dryness, and burning, pseudomembranous colitis which is rare, but has been reported with clindamycin. A most important side effect of topical antibiotics is the development of bacterial resistance and cross resistance; therefore, it should not be used as monotherapy.
d) Other topical/new agents
Salicylic acid: It has been used for many years in acne as a comedolytic agent, but is less potent than topical retinoid.
Azelaic acid:It is available as 10–20% topical cream which has been shown to be effective in inflammatory and comedonal acne.
Lactic acid/Lactate lotion: It is found to be helpful in preventing and reduction of acne lesion counts.
Tea tree oil 5%; Initial clinical response with this preparation is inevitably slower compared to other treatment modalities.
Picolinic acid gel 10%;
It is an intermediate metabolite of the amino acid, tryptophan. It has antiviral, antibacterial, and immunomodulatory properties. When applied twice daily for 12 weeks found to be effective in both type of acne lesions.
Dapsone gel 5%;
It is a sulfone with anti-inflammatory and antimicrobial properties. The trials have confirmed that topical dapsone gel 5% is effective and safe as monotherapy and in combination with other topical agents in mild-to-moderate acne vulgaris
Benzoyl peroxide has the advantage to prevent and eliminate the development of Priopiobacterium acne resistance. Therefore it is being more preferred as combination therapy. Its efficacy and tolerability are enhanced when combined with topical erythromycin or clindamycin, confirmed on various trials. Benzoyl peroxide can be combined with tretinoin and found to be superior to monotherapy. Both the molecules should not be applied simultaneously as benzoyl peroxide may oxidize tretinoin. A combination of topical retinoid and topical antimicrobial is more effective in reducing both inflammatory and noninflammatory acne lesions than either agent used alone. Topical clindamycin and benzoyl peroxide applied once daily and fixed clindamycin phosphate 1.2% and tretinoin 0.025% in aqueous-based gel formulation used once daily are both found to be effective treatment for acne. Addition of zinc acetate to clindamycin and erythromycin gel showed equivalent efficacy but probably reduces the development of microbial resistance.
Oral antibiotics are indicated in mainly moderate-to-severe inflammatory acne. Tetracyclines and derivatives still remain the first choice. Macrolides, co-trimoxazole, and trimethoprim are other alternatives for acne.The following agents should not be used in acne due to lack of efficacy and safety consideration such as cephalosporins, sulphonamide, and gyrase inhibitors.
Tetracycline (500 mg–1 g/day), doxycycline (50–200 mg/day), minocycline (50–200 mg/day), lymecycline (150–300 mg/day), erythromycin (500 mg–1 g/day), co-trimoxazole, trimethoprim, and recently azithromycin (500 mg thrice weekly) are being used successfully in acne. Minocycline and doxycycline are more effective than tetracycline and erythromycin.
Common side effects
Gastrointestinal upset and vaginal candidiasis are most common side effects. Doxycycline can be associated with photosensitivity. Minocycline may produce pigment deposition in the skin, mucous membrane, and teeth. Autoimmune hepatitis, systemic lupus erythematosus-like syndrome, and serum sickness-like reactions occur rarely with minocycline.
Long term use of antibiotic is associated with resistance to Propiobacterium acnes. To avoid resistance the following are recommendation;
- Antibiotic monotherapy should be avoided and combination with topical retinoid or benzoyl peroxide to be used as per need.
- Wherever possible the duration of therapy should be limited. The usual minimum duration of therapy is 6–8 weeks but can be given up to 12–18 weeks and more.
- It is advisable to use the same antibiotic if retreatment is necessary and use benzoyl peroxide for a minimum of 5–7 days between antibiotic courses to reduce resistant organism.
- Concomitant use of oral and topical therapy with chemically dissimilar antibiotics is to be avoided.
The main approach of hormonal therapy in acne is to prevent the effects of androgens on the sebaceous gland and probably follicular keratinocytes as well. It is wiser to take consultation with gynecologist before starting therapy.
Estrogen is commonly combined with progestin to avoid the risk of endometrial cancer. Anti-acne effect of oral contraceptive governed by decreasing level of circulatory androgens through inhibition of luteinizing hormones (LH) and follicle stimulating hormone (FSH). The currently FDA approved agents include norgestimate with ethinyl estradiol, and norethindrone acetate with ethinyl estradiol.
They functions primarily as a steroidal androgen receptor blocker. It may cause hyperkalemia (when higher doses are prescribed or when there is cardiac or renal compromise), menstrual irregularities.
It is the first androgen receptor blocking agent to be well studied and found to effective in acne in females. Higher doses have been found to be more effective than lower dose. It is also combined (2 mg) with ethinyl estradiol (35 or 50 μg) as an oral contraceptive formulation to treat acne.
It is useful in acne when given in females with hirsutism.
Oral retinoid is indicated in severe, moderate-to-severe acne or lesser degree of acne producing physical or psychological scarring, unresponsive to adequate conventional therapy. It is the only drug that affects all four pathogenic factors implicated in the etiology of acne.
Although there are many studies, but very large evidence-based study is lacking to confirm the dosing schedule. The approved dose is 0.5–2 mg/kg/day, given for 20 weeks.
Alternatively, lower dose is given for longer period, with a total cumulative dose of 120 mg/kg. New developments and future trends are low-dose long-term isotretinoin regimens and new isotretinoin formulations (micronized isotretinoin) to be used.
Common side effects of oral isotretonoin
Side-effects, especially drying of the skin and mucous membranes, are common but well tolerated. This relate to the drug’s effects on the function of modified sebaceous glands on the lips, and on lipid biosynthesis in the interfollicular epidermis. Rarely, abnormalities of liver function occur and limit treatment. Isotretinoin may increase serum triglycerides; levels should be checked before therapy and monitored during it. Depression and suicide have been reported, although it is difficult to disentangle the role of the drug from that of the underlying disease and age groups at risk; it is currently under investigation. Brief psychiatric history and screening for depressive symptoms should be recorded before prescribing it. Like all systemic retinoids, isotretinoin is highly teratogenic. Females must have a negative pregnancy test before treatment and must be checked regularly and following cessation of therapy.
Inflamed nodules can be incised and drained under local anaesthetic, and ‘cysts‘ excised. Intralesional injections of triamcinolone acetonide (0.1-0.2 mL of a 10 mg/mL solution) hasten the resolution of stubborn inflamed nodules. Scarring following acne is uncommon if patients receive adequate care. Small deep acne scars can be excised and other forms of more extensive but shallower scars can be treated by carbon dioxide laser.