Acneiform Eruptions

Question 1

Clinical summary of acne (vulgaris)

Answer 1

-A common disorder of the pilosebaceous unit (hair follicle) which is most common in adolescence and early adult life.
-It is characterised by comedones, inflammatory papules, pustules and scars.
-The typical distribution over the face and upper torso, reflects the distribution and size of sebaceous glands

Question 2

Pathogenic factors of acne

Answer 2

1. Abnormal keratinisation of the follicular epithelium
2. Increased sebum excretion (and possible changes in sebum composition)
3. Infection with the the Gram-positive rod Propionibacterium acnes (P. acnes)

Question 3

Describe abnormal keratinisation of the infundibulum

Answer 3

-Formation of microcomedones
=keratinocytes die, separate from each other in the process of desquamation
=In acne, in the follicle, this process is deranged, with the result that the cells stick together, along with sebum forming a plug towards the top of the follicle
=Plug gets larger= visible.
=Plug greatly distends the follicle, ruptures and bursts into the surrounding skin.
=Inflammatory response

Question 4

Difference between open and closed comedones

Answer 4

-Closed comedones (whiteheads)
=skin coloured small~1mm papules, that look like grains of rice beneath the skin’s surface, and have no obvious opening

-Open comedones (blackheads)
=papules with a dilated opening filled with dead cells and sebum
=Blackheads are black from melanin: albinos do not get blackheads.

Question 5

Describe the role of sebum

Answer 5

-Produced by cell death of sebocytes in the sebaceous glands, with release of the lipid cell contents into the lumen of the follicle.
-The distribution of acne mirrors sebaceous activity (i.e sebum production).

Question 6

What are sebaceous glands?

Answer 6

-Androgen end organs sensitive to circulating androgens and to the production and metabolism of androgen precursors within and around the gland

Question 7

Effect of androgens in sebaceous glands (sebogenesis)

Answer 7

-Act so as to increase sebum production, and the severity of acne correlates with sebum production.

=Within the teenage population acne severity positively correlates with resting sebum excretion
=Disorders characterised by increased androgen levels are associated with worsening of acne (PCOS, androgen secreting tumours, exogenous androgens (‘bodybuilders acne’).-
=Prepubertal eunuchs produce little sebum and do not develop acne
=oestrogens and progestogens, also affect sebum production

Question 8

Describe infection with Propionibacterium acnes (P. acnes)

Answer 8

-P. acnes is on everybody’s skin, but numbers are greater in those with acne with heavy colonisation of the follicular epithelium.
=Acne: have different types / strains of P.acnes?

-P. acnes use sebum as a substrate and the break down products include free fatty acids.
=More sebum, the more P. acnes
=Some fatty acids are powerfully chemotactic for polymorphonucleocytes(PMN), and also cause abnormalities of the follicular keratinisation process.
=P. acnes appear to stimulate the innate immunity system, with the induction of inflammatory mediators from the surrounding keratinocytes

Question 9

Describe the inflammatory process of acne

Answer 9

-The direct release of P. acnes lipases, chemotactic factors and enzymes leads to comedone
rupture
=Exudation of keratin, sebum, P. acnes and cellular and vellus hair material into the surrounding dermis
=Inflammatory cascade with neutrophil infiltration which, in turn, release reactive oxygen species and lysosomal enzymes, followed by a T cell infiltrate

Question 10

Clinical signs of acne

Answer 10

-Open and closed comedones
=Pustules and inflammatory papules.
=Larger inflammatory nodules with sinus formation
=Genuine cysts (i.e. cavities lined with an epithelium)
=Pseudocysts (large inflammatory masses / nodules).
=Nodulocystic acne: multiple inflammatory nodules, whether there are true cysts or not. The end result is usually is scarring

Question 11

Describe acne scarring in different people

Answer 11

-The worse the inflammation, the greater the risk of scarring, but different people scar to different degrees.
-The same objective degree of acne may cause scarring in one person, but not in another.
-Individuals with darker skin tones may develop hyperpigmented scarring

Question 12

Types of scarring

Answer 12

-Icepick scars: narrow and deep, as though an icepick had been struck into firm snow or ice= punch excision, laser, chemical peel
-Keloids: large unsightly scars, also seen after surgery or trauma in some people without acne= intra-lesional corticosteroids, micro abrasion
-Shallow irregularity of the skin’s normally smooth surface.
-Hypopigmented or hyperpigmented areas may develop, with the former often being permanent

Question 13

Epidemiology of acne

Answer 13

-Teenage years: increase in androgens leads to a large increase in sebum excretion.
=What is still unexplained is why acne usually subsides after a decade or so or less, even though sebum excretion rates remain high until the 6th and 7th decades.
=Acne persists in some people, especially women, into their fourth and fifth decades

Question 14

Prevalence/ incidence of acne

Answer 14

-What is ‘normal spots’ and ‘disease’?
-50% of teenagers would benefit from active treatment for their disease, with about 85% of young people showing some degree of acne
-Severe acne is more severe in males than females but more females consult for acne

Question 15

Genetics of acne

Answer 15

-Sebum excretion rates appear under some degree of genetic control.
-Clinically, parents with extensive scarring from acne, or a history of bad acne in early adulthood, often ‘push’ to ensure appropriate treatment for their children (now that we have highly effective treatments that would have spared the parents their disease)

Question 16

Types of acne

Answer 16

-Comedonal: comedones predominate
-Papulopustular: inflammatory lesions predominate
-Acne fulminans
-Acne conglobata
-Acne excoriee: minimal but patient picking to excessive degree
-Infantile
-Mechanical: frictional occlusion (headbands, hands)
-Chloracne: severe comedonal, secondary to dioxin
-Cosmetic: oil based, aromatic hydrocarbons, tar derivatives
-Post adolescent acne in women (pre-menstrual flares, jaw and mouth)
-Endocrine causes

Question 17

Describe acne fulminans

Answer 17

-Severe variant of acne with the abrupt onset of nodular suppurating lesions often following a deterioration of pre-existing acne in teenage boys. Systemically unwell
-Lesions may ulcerate and result in severe scarring.
-Systemic features such as joint pains, pyrexia, hepatosplenomegaly, and osteolytic lesions, with a high ESR, leucocytosis, proteinuria and anaemia.
-Management is an emergency

Question 18

Describe acne conglobata

Answer 18

-Severe form of nodulocystic acne, with multiple painful abscesses and scarring- systemically well
-Possible extensive involvement of the chest, back and face, and even widespread involvement of the arms, scalp and buttocks.
-Unlike acne fulminans, there are no systemic manifestations.
-May occur with acne inversa

Question 19

Describe infantile acne

Answer 19

-Reflects androgen activity seen in infants of both sexes (but boys more frequently) under one year of age.
=In males, elevated LH leads to testicular androgen production, and in both sexes, raised DHEA produced by the adrenals, may be the explanation.
=You may see comedones, pustules and scarring.
=This is ‘true’ acne.
=This androgen activity physiologically fades after one year, and re-starts prior to puberty

Question 20

Describe endocrine causes of acne

Answer 20

-Consider if acne is severe, or the age of onset is unusual (childhood or middle age).
-Features of hyperandrogenism in women include hirsutism, changes in the voice and body build, androgenic alopecia and cliteromegaly
-A normal menstrual cycle is strong evidence against any systemic endocrine abnormality
-Evaluation should include total and free testosterone, DHEAS and 17- hydroxyprogesterone.
-You usually need to think about ovarian and adrenal steroid production
-Disorders to consider: PCOS; congenital adrenal hyperplasia; and androgen secreting tumours
-Do not forget the use of androgens in bodybuilders

Question 21

Main aims of acne treatment

Answer 21

-Reverse the keratinisation defect
-Inhibit sebum production
-Kill off the bacteria

Question 22

Main treatment modalities for acne

Answer 22

1.Topical retinoids or benzoyl peroxide (BPO)
2. Antibiotics, either systemically or topically
3. Hormonal methods in females
4. Systemic retinoids

Question 23

Describe topical retinoids

Answer 23

-Isotretinoin, tretinoin
-Vitamin A activity, topical or systemic
=Topical: do not decrease sebum excretion, but appear to work by normalising follicular keratinisation and reversing the excess adhesion of the dead corneocytes in the follicle.
=Promote a mild inflammatory reaction: slight toxic or irritant reaction like a mild sunburn (erythema, dryness and scaling, with or without a mild soreness of the skin)
=In a patient with predominant comedonal acne, retinoids are the best agent to start with.
=Used once a day or, if the inflammatory response is prominent, once every other day, gradually building up to once or twice daily
=Avoided during pregnancy because of the theoretical risks about teratogenicity from retinoid

Question 24

Describe Benzoyl Peroxide (BPO)

Answer 24

-Irritant, but effective in reducing the level of P. acnes within the follicle.
=Reduction in the pro-inflammatory free fatty acids and inflammatory activation
-Dose may need to be gradually increased and can be combined with topical retinoids, one used in the morning, the other in the evening.
-Retinoids and BPO can be used in the same patient, or combined with topical or systemic antibiotics

Question 25

Systemic antibiotics in acne

Answer 25

-Tetracyclines or erythromycin.
-Failure: inadequate dosing and /or inadequate duration of therapy.
=It is not possible to say that a drug is not working for acne unless the patient has been taking it for at least 2 months.
-Treat until the disease improves then withdraw the antibiotic (say at 3-6 months), but continue with a retinoid or BPO or both.
=Therapeutic holidays to try and minimise resistance.
-Tetracyclines should not be used in patients under the age of 12 years (they permanently stain teeth and are absorbed by bone), nor in pregnancy as they are teratogenic (effects on teeth and bone).
=Erythromycin is safe in pregnancy.

Question 26

Topical antibiotics in acne

Answer 26

-Erythromycin, clindamycin and tetracyclines.
-Not suitable for patients with extensive back and chest involvement
-The exact clinical role bacterial resistance plays in therapy failure in acne is unknown, but resistance rates of over 50% have been reported in some studies.
=BPO is commonly used with topical antibiotics in an attempt to reduce resistance

Question 27

Describe azelaic acid

Answer 27

-Possesses antibacterial, anti-inflammatory and anti-comedonal effects.
-It may be used as an alternative topical preparation

Question 28

Hormonal methods in females

Answer 28

-Oestrogens decrease sebum secretion, whereas progestogens increase sebum excretion (magnitude less than androgens)
=Progestogens worsen acne or may produce acne flares,
=Oestrogens may improve acne.

-For combined contraceptives the exact effect may depend on the balance of hormones used and the exact steroids used (modern pills have better side effect profiles)
-Older oestrogen containing contraceptives contained larger doses of oestrogen, which have larger effects on sebum exertion and were therefore more effective in treating acne, (but of course had greater side-effects e.g. thromboembolism).
-Modern lower dose oestrogens likely have less effect on sebum excretion but, in the combined pill, act so as to inhibit ovulation which of itself inhibits ovarian androgen production.

Question 29

Use of systemic retinoids

Answer 29

-Potently reduces sebum excretion (temporary and reversible atrophy of sebaceous glands)
-Isotretinoin: treat acne that is either causing scars or has failed to respond to ‘conventional treatments’.
=4-month course, with the dose dependant on body weight, although longer courses at a lower dose are as effective.
=Perhaps 10-20% of patients will require a further course of treatment and very occasional patients may need to be left on the drug at a lower dose.
=Delay before any beneficial effect is seen (doesn’t affect current lesions). 2 months.
=May precipitate acne fulminans in some individuals (which will in turn require treatment with prednisolone to dampen down the immune response and the gradual re-introduction of the isotretinoin).
=Upon completion of the course, sebum excretion does not return to pre-treatment levels for several years.
=Consent form and 2 methods of contraception
=FBC, LFTs, pregnancy tests

Question 30

Side effects of systemic retinoids

Answer 30

-Tetra genic effects
-Increase triglycerides (perhaps even precipitating acute pancreatitis) and cholesterol, and produce abnormal liver function tests.
=Interferes with lipogenesis: cheilitis, dry eyes, a dry nose with nose bleeds, and inducing dry skin and eczema in some individuals.
-Temporary worsening of acne within the first few weeks of treatment.
-Acne fulminans like syndrome develops, which requires stopping of the isotretinoin with or without the addition of systemic steroids.
-Alter mood and precipitate depression? specialist psychiatric input
-Not safe to conceive for at least five weeks after the drug has been stopped

Question 31

Other treatments of acne

Answer 31

-Potent peels (α-hydroxy acids)
-Photodynamic therapy (blue light + topical porphyrins)
-Comedone extraction or electrocautery of comedones

Question 32

Treatments for scarring

Answer 32

-Dermabrasion (removal of the superficial layers of skin)
-Carbon dioxide laser resurfacing (vaporisation of the superficial layers of skin using a laser producing effects similar to dermabrasion)
-Excision (of small scars) or excision of cystic lesions, whether these are pseudocysts or real epidermal cysts that may occasionally occur in acne
-Punching (using a punch biopsy tool) out ice-pick scars, or grafting them
-Filling in depressions with fillers, or using potent peels (α-hydroxy acids).

Question 33

Describe drug induced acne

Answer 33

-Papulopustular eruption or folliculitis without comedones.
=Common drug causes of this ‘acneiform’ reaction include corticosteroids, anti-epileptic medication and lithium.
=Patients receiving antibiotics for their acne vulgaris may develop a widespread gram- negative folliculitis which, if the offending tetracyclines are stopped, will improve.
=Many of us have been caught out by ‘unexplained worsening of acne’ (sic) in a patient previously treated with tetracyclines.
=Taking anabolic steroids will induce or precipitate classical acne with comedones (‘bodybuilders acne’).
=EGF receptor inhibitors induce a widespread ‘acne like’ pustular eruption (no comedones, evident)

Question 34

What is acne inversa?

Answer 34

-Hidradenitis suppurativa (apocrine bearing areas of skin are affected)
=Acne inversa as centred around the follicles and sebaceous glands, occlusion of the follicular infundibulum and rupture of the follicle is central to its pathogenesis

-Rupture of the follicle with dispersion of its contents into the surrounding dermis, and secondary inflammation.
=initially to sterile abscess formation
=sinus tracts down as far as deep fascia, and extensive scarring.
-The most affected areas are: the axillae, groins, perineum and perianal areas.
=Malodorous discharge comprising blood, pus and serous exudate; pain and systemic malaise.
-In chronic lesions, squamous cell carcinoma may develop.
-Infection is not the primary problem but may contribute to its course.
-The condition is usually misdiagnosed as a bacterial abscess as the initial inflammatory lesions often resembles an abscess. It is more common in women, and young adults. It does not occur before puberty

Question 35

Treatment of acne inversa

Answer 35

-Courses of systemic antibiotic combinations are frequently used, as are courses of systemic retinoids.
-Systemic anti-androgens have been used.
-In acute flare ups systemic steroids are useful.
-Excision of the areas may be curative.
-TNFα inhibitors may improve some patients: if confirmed this will represent a major advance. Other biologics including IL12/23 inhibition or IL-1 receptor antagonists have been tried

Question 36

Differentials of acne vulgaris

Answer 36

-Folliculitis: erythematous papules and pustules follicular based, often affects trunk and extremities
-Rosacea: older people, background erythema and telangiectasias, inflammatory papules and pustules superimposed

Question 37

Clinical features of rosacea

Answer 37

-No comedones, not primarily follicular disorder
-Erythema, telangiectasia and flushing, starting early in its course, with possible sensory symptoms
-Oedema of the facial skin with papules and pustules
-Hyperplasia of the sebaceous glands with fibrotic overgrowth of the dermis, with the presence of a(rhino)phyma
-Ocular symptoms and signs
-Common on nose and cheeks
-Middle aged, worse in men

Question 38

Pathophysiology of rosacea

Answer 38

-Neurovascular: with transient erythema and flushing, leading to persistent erythema and telangiectasia. There are often sensory symptoms including stinging or burning of the skin. These vascular changes maybe reflected by mild oedema and vascular ectasia.
-Inflammatory: there is a marked perivascular and perifollicular lymphohistiocytic infiltrate, with sebaceous gland overgrowth and possible granuloma formation.
-Ocular rosacea: The mechanism is unknown, but rosacea can affect the eyes, with or without skin signs. Changes include blepharitis, keratitis, chalazia, scleritis, and uveitis. Untreated, ocular rosacea can lead to corneal scarring.
-Rhinophyma: In a minority of patients there is gross sebaceous gland hyperplasia together with an increase in the amount of the dermal fibrous tissue leading to tissue overgrowth. The follicular orifices becomes much more prominent (as they often do with age)= over-enlargement of the nose.

Question 39

Treatment of rosacea

Answer 39

-General skin care is advised, including avoiding irritants, soaps, UVR and many cosmetics.
-Alcohol and spicy food will tend to make the telangiectasia and flushing worse
-Topical brimonidine tartrate, a selective α1A-adrenergic agonist improves the erythema.
Lasers are useful in treating the telangiectasia
-In mild disease, there are a variety of topical agents that may be tried: topical antibiotics (most commonly, topical metronidazole); azeleic acid; and ivermectin.
-If topical agents fail (and they may actually make some cases worse) use systemic antibiotics such as tetracyclines or metronidazole.
=If these agents fail, then use isotretinoin systemically as in acne vulgaris
-Rhinophyma requires surgical treatment, including either dermabrasion or, more likely, surgical shaving of the skin.
-Never ever treat rosacea with topical corticosteroids.

Question 40

Differentials of rosaecea

Answer 40

-Acne vulgaris (comedones seen in acne vulgaris)
-Seborrheic dermatitis (scaly, look for nasolabial fold involvement, dandruff, central chest
-Perioral dermatitis (history of corticosteroid use?)

Question 41

Describe perioral dermatitis

Answer 41

Presentation: young women, papules, pustules and erythema with or without a small degree of scaling around the mouth, precipitated by the use of topical corticosteroids on the face (or the use of steroid inhalers).
-Sudden withdrawal of corticosteroids will make the rash worse. Continued use of the topical corticosteroids seems to produce temporary improvement

-Treatment: If it is not possible to gradually reduce the strength of the topical corticosteroids, then the patient
should be treated with systemic tetracyclines as cover for the gradual withdrawal of the topical corticosteroid.

Question 42

Describe juvenile excoria

Answer 42

Psychological intervention