4.1.1 Acne

One can distinguish between physiological acne (60%) as a mild variant from clinical acne (40%) that needs medical care. It starts at the age of 8-9 years at beginning of releasing growth factors and other puberty associated hormonal factors (androgens) continuing into late adolescents time and decreases in clinical activity by around 20 years of age. Highest prevalence in 14-18 years old adolescents with a prevalence of up to 94%. Specific forms may also occur in newborn, infants and children and adults up to the 5th life decade as well.

Acne has a complex aetio-pathogenesis. A specific gene mutation directly linked to acne does not exist, however, there is a tendency for more severe courses of acne in families having such history. In homozygotic twins the clinical course shows > 80% homology. Genes that have established roles in controlling the development, morphology and activity of hair follicles are WNT10A, LGR6, TP63 and LAMC2.

The 4 main pathogenetic factors are:

1. Seborrhoea as a result of increased proliferation and modification of sebocyte differentiation caused by androgens and insulin growth factor followed by an increased production of sebum.

2. Proliferation of follicular keratinocytes (response to androgen and growth signals) resulting in follicular retention hyperkeratosis with keratin- and integrin-pattern disturbance.

3. Dysbiosis. Low oxygen saturation and sebum components in the infra-infundibulum ideal for proliferation of Cutibacterium acnes (C. acnes). Specific C. acnes strains drive the inflammation. Increased expression of TLR-2 and 4 and other danger signals are upregulated. IL-1α and C. acnes mediators are involved.

4. Inflammation driven by IL-1α and C. acnes mediators. The innate immune system reacts strongly. CD4 and CD17 T-cells accumulate and invade the follicular wall. Neutrophils do not play a primary role. Later macrophages come into the surrounding perifollicular area and micro-scarring takes place.

Furthermore, nutritional factors can play a role: increased carbohydrate load with stimulation of IGF- receptor-1 and stimulation of androgens via nuclear factors (FoxO1). Endogenous cannabinoids and corticotropin-releasing hormone are also involved (stress reactions).

Precursor lesion is a microcomedo, which is invisible for the naked eye.

Primary lesions are: closed comedones (whiteheads), open comedones (blackheads), papules, pustules, nodules <1cm, nodes >1cm.

Secondary lesions are: macules, abscesses, fistules, hemorrhagic crusts, atrophic and hypertrophic scars and keloids. There is often a marked emotional reaction reaching up to an increased risk for suicidal intention. Social phobias are very common.

Typical forms:

• Comedonal acne: primarily comedones.

• Papulo-pustular acne: primarily papules and pustules.

• Severe papulo-pustular acne: with nodules (<1cm).

• Acne conglobata: nodes (>1cm), scars, abscesses, fistules, typical localisation (mid-face, shoulders, chest, upper back).

Special forms:

• Acne neonatorum (common and temporary, relative hyperplasia of the adrenals in newborn)

• Infantile acne after 1 year of age, uncommon, LH/FSH-induced raise in testosterone and other androgens, deficiency of isoenzymes of steroid metabolism, genetic background possible. Primary manifestation of adrenogenital syndrome

• Late onset acne (persisting or relapsing or first onset). Most prominent in females. Often mild endocrinological dysfunction. Sometimes evident with polycystic ovary syndrome (PCOS) and androgenic signs.

• Late type of androgenital syndrome (LTAGS): late onset of changes in androgen and cortisol metabolism in adolescent when malfunction or deficiency of 11-, 17- or 21 OH- dehydrogenase is present. Full spectrum disease is usually detected after birth and in childhood.

• Acne fulminans: severe acne with fever, leukocytosis, arthralgias, immune- mediated vasculitis, sterile abscesses of bone, elevated CRP.

• Cosmetic acne: overuse of washing and cleansers followed by microbial dysbiosis, occlusive cosmetics, lipid rich ointments.

• Acne venenata: induction, maintenance or aggravation of acne by medications (for example corticosteroids, anabolic steroids), chlorinated organic compounds (Agent Orange), iodine, oil, tar. High humidity i.e. in washing salons. Friction.

• Acne excoriée des jeunes filles (skin picking disorder): artefactual disorder with excoriations and squeezing of papules around the mouth and chin, often marked emotional component. Belongs to obsessive compulsive disorders.

• The special acneiform type acne inversa/hidradenitis suppurativa as a disease of the terminal hair follicle is discussed under the diagnosis “4.1.4. Hidradenitis suppurativa”. It shows marked inflammation of terminal hair follicles in intertriginous regions rich in apocrine glands.

• Acne tetrade = acne conglobata, foliculitis et perfolliculitis capitis absedens et suffodiens, pilonidal sinus and acne inversa. Specific syndromes, such as PAPA: see diagnosis 2.2.2.

In therapy-refractory acne, compliance / adherence has to be checked. Causes of elevated androgen levels (isoenzyme deficiency of steroid metabolism, hormone-producing tumours, adrenogenital syndrome, polycystic ovarian syndrome, exercise induced androgen increase) should be excluded.

Late onset of therapy leads to scars in 20% of patients (atrophic, hypertrophic, keloids), fistules, and pigmentary changes. Disturbed self-esteem. Long-term psychosomatic/psychiatric problems may develop. Suicidal ideation may occur.

Clinical findings and case history.

Prevention: no obligatory prevention possible, however, avoidance of provoking factors for lowering course of severity.

Therapy:

Basic topical therapy:

• In comedonic acne are drugs of first choice retinoids (comedolytic, anticomedogenic, and anti- inflammatory) and azelaic acid (anticomedogenic, antimicrobial and anti-inflammatory. Topical sebum suppressing drugs such as clascosterone (synthetic antiandrogen) are now available and should be given acne as a part of a combination therapy in all types where the topical route is indicated.

• Papulo-pustular acne grades I or II: treat sequentially or better with combination preparation retinoids plus benzoyl peroxide (BPO) or azelaic acid or clascosterone. An antibiotic such as clindamycin can be combined with BPO or retinoid or azelaic acid. Never use topical antibiotics as monotherapy (development of resistance).

• Papulo-pustular acne with small nodules grades III-IV: treat always combined topically and systemically often oral tetracyclines such as doxycycline or minoycline, which have strong anti- inflammatory effect.

• Papulo-pustular acne with nodes: treat always topically and systemically (often oral tetracycline such as doxycycline or minocycline, which have strong anti-inflammatory effect). Consider isotretinoin and in females oral contraceptives indicated for acne or anti-androgens (e.g. cyproterone acetate, drospirenone or dienogest alone or combined with estrogens).

• Acne conglobata: Isotretinoin is the first choice. Systemic tetracycline plus retinoids plus BPO or with azelaic acid. In women consider antiandrogens (e.g. cyproterone acetate, drospirenone or dienogest combined with estrogens).

Treatment of different types of scars: chemical peels, dermabrasion, microneedling, CO2 Laser, fillers, cryosurgery, surgical defect elevation for depressed scars.

Maintenance treatment to prevent relapses is essential. Above all, topical retinoids or azelaic acid for the prevention of the development of new microcomedones are indicated.