Acne vulgaris

Acne vulgaris is the common skin eruption that occurs with blockage and inflammation of the pilosebaceous unit followed by the formation of comedones (non-inflammatory), papules, pustules, nodules and cysts (inflammatory). It peaks in adolescence but may occur in any age group.

🏘️ Epidemiology

Acne is is very common worldwide. Around 95% of adolescents are affected during puberty to some extent. It is more common in males during adolescence but more common in women in adulthood. Males are more likely to develop more severe forms of acne too.

🔢 Classification

Acne can be classified by its type as well as by its severity.

Let’s discuss the different types of acne first:

• Non-inflammatory acne (comedonal acne) - comedones are papules (solid, raised lesion <0.5cm in diameter) that form when the pilosebaceous ducts are blocked and debris of keratin and sebum accumulate. They may be closed (whiteheads), open (blackheads), or clinically invisible (microcomedones).
• Inflammatory acne (papular/pustular or nodulocystic acne) - pustules are pus-containing blisters (<1cm in diameter). Nodules are solid, raised lesions that are >0.5cm in diameter and are a little deeper and firmer. Inflammatory forms of acne have a higher risk of scarring.
• Acne conglobata - this is is a rare, and severe form of nodulocystic acne that most commonly occurs in men. It presents with extensive inflammatory papules, cysts and pus-filled nodules that join to form larger sinuses.
• Acne fulminans - this is a sudden and severe inflammatory reaction that causes deep ulcerations and erosions as well as systemic symptoms. It most commonly occurs as a severe reaction to isotretinoin.
• Neonatal acne - it may present at birth or before the child reaches 6 weeks old. It presents with papules and pustules on the forehead, cheeks or nose and resolves spontaneously. It is also known as neonatal cephalic pustulosis.

Let’s now discuss the severity of acne:

Acne can be classified from mild - very severe:

🦴 Anatomy

There are 3 layers of the skin - the epidermis, the dermis and the hypodermis.

Let’s look at these 3 layers in more detail:

• Epidermis

“Epi“ means above. As such the name denotes that the epidermis lies above the dermis. It is the most superficial layer of skin and is made up of layers of keratinocytes that have undergone differing levels of maturation. With each level of maturation there is increased keratinisation and migration towards the surface. This process is known as cornification (the process in which skin, as well as nails and hair, become dry and hard). There are 5 distinct layers of the epidermis:

1. Stratum corneum - as the name implies, this is the layer in which cornification is most prominent. The cells here have lost their nucleus and all other organelles and are highly keratinised. They are known as corneocytes - the terminally differentiated epidermal cell. The corneum layer is made up of 10-30 corneocytes stacked on top of each other. Th
2. Stratum lucidum - this is the “clear layer”. It is a thin, clear layer of cells containing eleidin. Eleidin is a clear intracellular protein that tightens the connection between cells and improves the protection of the skin.
3. Stratum granulosoum - this layer consists of 3-5 layers of flattened cell layers that produce keratohyaline granules which gives it a granular appearance. These granules are used for cross-linking of keratin filaments. They also secrete lipids and other waterproofing molecules.
4. Stratum spinosum - these keratinocytes are held together by desmosomes. The stratum spinosum also contains Langerhans cells which are tissue-specific macrophages that help with immune function.
5. Stratum basale - this is the deepest epidermal layer. It has dividing and non-dividing keratinocytes that are attached to the basement membrane by hemidesmosomes. Here the cells are dividing rapidly and the daughter cells migrate upwards. Melanocytes are present here and they are responsible for melanin production. Langerhans cells are also found here and they are sensory mechanoreceptors that are sensitive to touch.

• Dermis

The dermis has 2 layers which are not as clearly defined. These are the papillary layer (superficial) and the reticular layer (deep). The reticular layer is thicker and has bundles of collagen fibres that provide rigidity and durability.

There are numerous structures present in the dermis:

1. Blood vessels
2. Cutaneous nerves
3. Fibroblasts - these produce the extracellular matrix, predominantly made up of collagen and elastin.
4. Mast cells - these are innate immune cells containing histamine granules.
5. Skin appendages - this includes hair follicles, sebaceous glands, sweat glands, nails. These structures actually derive from the epidermis and descend into the epidermis during development.
6. The pilosebaceous unit refers to the hair follicle, the hair shaft, and the sebaceous gland. The sebaceous gland releases sebum through the process of holocrine secretion (the contents are produced in the cytoplasm of the cell and released into the gland through rupture of the plasma membrane). Sebum contains lipids and fatty acids that lock in moisture and make the skin soft. However, it also may predispose the skin to acne in some instances. The hair follicle has an associated arrector pili muscle which contracts to pull the hair follicle upright. It is involved in thermoregulation and emotional response. It also puts pressure on the sebaceous gland which aids in directing sebum to the hair shaft.
7. Sweat glands present in the dermis are both eccrine and apocrine sweat glands. Eccrine sweat glands are involved in thermoregulation and they release a clear, odourless substance to help cool the skin. Apocrine sweat glands are larger. They are located in the axillary and genital regions. It’s contents may be broken down by microbes on the skin which is what produces body odour.
• Hypodermis

The hypodermis is another name for the subcutaneous tissue that lies deep to the dermis. It functions to store adipose tissue.

Pathophysiology

Acne vulgaris is a multifactorial disorder that primarily affects the pilosebaceous units (hair follicles and sebaceous glands). Its pathogenesis involves a complex interplay of factors, including increased sebum production, hyperkeratinization, colonization by Cutibacterium acnes (formerly Propionibacterium acnes), as well as inflammation.

• Increased sebum production

Sebum is the oily substance produced by sebaceous glands, which are abundant in areas like the face, chest, and back. During puberty, androgens (particularly testosterone and dihydrotestosterone (DHT)) stimulate the sebaceous glands to produce more sebum. Excessive sebum production creates an environment conducive to acne development.

• Follicular hyperkeratinisation

Hyperkeratinisation is the abnormal shedding and proliferation of keratinocytes within the hair follicle. In acne, keratinocytes become sticky and fail to shed normally, leading to the formation of a microcomedo, the initial lesion of acne. The accumulation of keratin and sebum in the follicle causes it to become clogged, forming comedones (blackheads and whiteheads).

• Colonization by Cutibacterium acnes

Cutibacterium acnes is a gram-positive, anaerobic bacterium that is part of the normal skin flora. In acne-prone individuals, the increased sebum production provides a nutrient-rich environment for C. acnes, leading to its overgrowth. C. acnes releases lipases that break down sebum into free fatty acids, which are pro-inflammatory. The bacteria also stimulate toll-like receptors (TLRs) on keratinocytes and immune cells, enhancing the inflammatory response.

• Inflammation

The inflammatory component of acne is crucial in its pathogenesis. The presence of C. acnes and free fatty acids within the follicle triggers an immune response. This involves the activation of TLRs and the release of pro-inflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), and interleukin-8 (IL-8). Neutrophils and other immune cells are recruited to the site, leading to the formation of inflammatory lesions like papules, pustules, nodules, and cysts.

As such we can summarise the development of acne as such:

Microcomedones form due to increased sebum production and hyperkeratinisation which clogs the follicle → these microcomedones grow to form blackheads (open comedones) and whiteheads (closed comedones) → proliferation of C. acnes and the immune response results in the formation of inflammatory lesions such as papules and pustules → inflammation increases in severity and ruptures the follicular wall which releases the contents into the surrounding dermis and forms painful nodules and cysts.

Other factors that play an important role in the development of acne include:

• Androgens - androgenic hormones increase sebum production and influencing keratinocyte proliferation. Conditions such as polycystic ovary syndrome (PCOS) and androgen-secreting tumors can exacerbate acne due to elevated androgen levels.
• Genetics - genetic predisposition influences sebaceous gland activity, keratinocyte behavior, and immune response, making some individuals more prone to acne.
• Diet and lifestyle - certain dietary factors (e.g., high glycemic index foods, dairy products) and lifestyle factors (e.g., stress) can influence acne severity by affecting hormone levels and inflammatory pathways.

😷 Presentation

As mentioned previously, acne varies in severity. Let’s look at the different manifestations of acne from comedones to cysts:

• Comedones - blackheads and whiteheads.




• Papules and pustules




• Nodules and cysts




• Scarring

🚨

Acne conglobata

Acne conglobata is a rare and severe form of acne in which interconnecting nodules and cysts coalesce to form sinuses which can become infected causing pain and malodour. It heals slowly and leaves scars.

🚨

Acne fulminans

Acne fulminans is a severe form of acne that is associated with systemic symptoms. It almost always affects adolescent males and is associated with isotretinoin use.

😷 Presentation

• Acute onset
• Large, painful nodules, plaques and ulcer with haemorrhagic crusts
• Most commonly is located on the trunk
• Systemic symptoms may include:
• Fever
• Myalgia
• Arthralgia
• Loss of appetite and weight loss
• Hepatosplenomegaly

🔍 Investigations

• CRP and ESR - raised.
• FBC - shows leukocytosis, thrombocytosis, anaemia.
• LFTs - elevated liver enzymes.

🧰 Management

• Urgent referral to dermatology - the patient needs to be seen within 24 hours.
• Discontinue isotretinoin
• Systemic corticosteroids - for 2-4 weeks.
• Once lesions have improved, continue steroids + initiate low-dose isotretinoin.
• Second-line options include ciclosporin, dapsone and biological agents.

🔍 Investigations

The diagnosis of acne vulgaris is a clinical diagnosis.

We may rarely need to test for hyperandrogenism if an underlying pathology or alternative diagnosis is suspected:

• Total testosterone - elevated.
• DHEA-S (dehydroepiandrosterone sulfate) - elevated.
• Luteinising hormone - elevated.
• Follicle stimulating hormone - elevated.

🧰 Management

✍️ Referral

• Refer people to a consultant dermatologist-led team if:
• There is diagnostic uncertainty.
• They have acne conglobata.
• They have nodulo-cystic acne.
• Consider referring the patient to dermatology if:
• Mild to moderate acne has not responded to two completed courses of treatment.
• Moderate to severe acne has not responded to previous treatment that includes an oral antibiotic.
• Acne with scarring.
• Acne with persistent pigmentary changes.
• Acne is causing or contributing to persistent psychological distress or a mental health disorder.
• Refer urgently to hospital (within 24 hours) if acne fulminans is suspected
• Consider referral to mental health services if a person with acne experiences significant psychological distress or a mental health disorder, including those with a current or past history of:
• Suicidal ideation or self-harm.
• Severe depressive or anxiety disorder.
• Body dysmorphic disorder.