Acne Conglobata and Rarer Forms of Acne

Acne vulgaris, in the form of "teenage spots" is a normal feature of adolescence but other forms of acne are not and they are far more disabling. Severe forms of acne can affect many aspects of a person's life, causing a great deal of embarrassment and stress. Severe acne may significantly limit social life and amorous intent and even interfere with opportunities for employment. It can be disfiguring and require years of treatment, so it is best referred to a dermatologist.

There are 4 types of severe acne:

• Acne conglobata
• Acne fulminans
• Gram negative folliculitis
• Nodulocystic acne

• Acne vulgaris affects almost every adolescent to some degree but acne conglobata is a much more severe and rare form of the disease.
• It tends to present between the ages of 18 and 30 but scars for life.
• Males are affected more often than females.
• Acne, even of such severity, can occur in infants and neonates.¹

• The primary cause of acne conglobata remains unknown.
• Changes in reactivity to Propionibacterium acnes may be important.
• Exposure to halogenated aromatic hydrocarbons such as dioxins or ingestion of halogens may trigger the disease in those who are predisposed. The world saw the effects of dioxin with the poisoning of Ukrainian President Viktor Yushchenko.²
• Androgen-producing tumours and anabolic steroids used for medical or other purposes may induce severe acne.
• It may appear after testosterone therapy has been stopped.
• There is a tendency for it to run in families and there is an association with certain HLA antigens.

Acne conglobata

This is a chronic and severe form of acne vulgaris showing:

• Deep abscesses
• Inflammation
• Severe damage to the skin
• Scarring
• Comedones (blackheads) are obvious and widespread, often occurring on the face, neck, trunk, upper arms and/or buttocks
• Inflammatory nodules form around multiple comedones and grow until they break down and discharge pus. Deep ulcers may form under the nodules, producing keloid-type scars, and crusts may form over deeply ulcerated nodules
• Abscesses can form deep, irregular scars
• Acne conglobata may be preceded by acne cysts, papules or pustules that do not heal, but instead rapidly deteriorate. Occasionally, it flares up in acne that had been dormant for many years.

Acne fulminans

There is a sudden onset of very destructive inflammation.

• Severe and often ulcerating acne
• Fever
• Inflammation and pain in joints, especially hips and knees. It is like a seronegative arthropathy but without the HLA-B27 association.³
• A person who develops acne fulminans may have had unsuccessful treatment for another form of severe acne
• Gram negative folliculitis is caused by bacterial infection that follows long-term antibiotic treatment.

Nodulocystic acne

This is severe acne with cysts. They may occur in isolation or be widespread over the face, neck, scalp, back, chest and shoulders. They can be painful.

• Acne cysts are nodules of inflammation.
• A cyst may be filled with thick, yellow pus-like fluid and is inflamed and infected.
• If a cyst is drained, it must be done under sterile conditions.

Acne rosacea. Look for features of hirsutism that may suggest a virilising process.

Ask about steroid use. This may include contraceptives in females. Ask about illicit steroid abuse. Check the hormonal profile in such severe acne, especially if it occurs at an unusual age. Remember the possibility of a steroid producing tumour.

• Total and free testosterone for polycystic ovarian syndrome or ovarian cancer. The androgen producing arrhenoblastoma is rare.
• Serum dehydroepiandrosterone (DHEAS) for adrenal tumour or congenital adrenal hyperplasia.
• Ratio of LH/FSH for polycystic ovarian syndrome.
• 17-hydroxyprogesterone for congenital adrenal hyperplasia.
• Prolactin in case of pituitary adenoma.
• 24 hour urinary free cortisol for Cushing's syndrome.
• If isotretinoin is considered, baseline blood tests such as LFTs and fasting lipids are required.

Non-drug

There is little evidence that a fatty diet increases the rate of sebum excretion. Regular face washing and the use of antiseptic gels may reduce the amount of P. acnes.

Along with vigorous medical therapy, emotional support is essential.

Drugs

• For such severe acne, topical therapy is inappropriate and systemic treatment is essential.⁴
• A severely inflamed cyst may rupture and cause a scar. Such cysts can be injected with dilute steroids and the cyst "melts" over 3 to 5 days.
• Oral antibiotics have been the main treatment for severe acne for many years. Like topical antibiotics, they reduce the P. acnes population, which decreases inflammation. Treatment usually begins with a high dose which is reduced as the acne resolves. The bacteria can become resistant to the antibiotic with time. Another antibiotic may work. The commonest used are doxycycline, erythromycin, minocycline and tetracycline.
• Dapsone may be valuable where antibiotics fail.
• Oral contraceptives reduce acne in women by suppressing over activity of sebaceous glands. The oestrogen tends to be beneficial and the progestogen adverse. Hence predominantly oestrogenic pills or those with the newer "cleaner" progestogens are preferred. Dianette is a combination of 35μg ethinyl oestrogen with cyproterone 2 mg that is an anti-androgen in place of a progestogen and so it is even more effective.⁵ Although this is an effective contraceptive it is not licensed as such and the patient should be warned that pregnancy whilst taking this can result in the cyproterone causing ambiguous genitalia in a male fetus.
• Isotretinoin is a potent drug reserved for treating severe cystic acne and acne that is resistant to other medications. Isotretinoin is a synthetic retinoid. The regime is once or twice a day for 16 to 20 weeks. In the UK it may be prescribed only under supervision of a consultant dermatologist.
• It is a most effective treatment because it works on all four factors that predispose to acne- excess oil production, clogged skin pores, P. acnes and inflammation. Remissions usually last from many months to many years. Often only one course is needed.
• It is highly teratogenic and so steps must be taken to avoid pregnancy during treatment and for some time after. It is a contraindication to breast feeding.
• Infliximab has been tried but not with good results.⁶

Other side effects of isotretinoin include:

• Severe pain in the chest or abdomen
• Dysphagia
• Severe headache, blurred vision or dizziness
• Bone and joint pain
• Nausea or vomiting
• Diarrhoea or rectal bleeding
• Depression and possibly even suicide
• Dryness of the skin, eyes and nose
• Thinning hair
• Increase in low density lipoproteins (monitor during treatment)
• Oral steroids are sometimes used for 2 to 4 weeks, especially if there are systemic symptoms.

Surgical

Some large cysts do not respond to medication and may require drainage and extraction. This must be done by an appropriately trained doctor. If the patient squeezes and bursts comedones himself it can cause infection and deterioration of the condition and aggravate scarring.

NICE recommends that (see page 7 of advice⁷):

• People who have a severe variant of acne including acne fulminans or Gram-negative folliculitis should be referred urgently to be seen within 2 weeks.
• People who have severe acne such as painful, deep nodules or cysts (nodulocystic acne), or other people who could benefit from oral isotretinoin should be referred as "soon".
• Milder cases with possible scarring or failure to get an adequate response require "routine" referral.

• The psychological effect of severe acne on the developing adolescent must not be underestimated.
• Renal amyloidosis has been reported.⁸
• Scars remain for life. This is probably true of psychological as well as physical scars.

The disease dies down after about 30 years of age but scars remain. Men often grow a beard to hide them.

There is nothing that can be done to prevent this disease but it needs to be treated energetically to minimise the psychological impact and to reduce scarring.