The Pathogenesis of Acne and What It Means for Drug Developers

Acne — specifically acne vulgaris — is the most common skin disorder in the United States, affecting up to 50 million Americans each year. While many cases are restricted to mild manifestations during one’s teenage years, acne is a highly visible condition that can have a major impact on a patient’s quality of life. It’s a disorder with the potential for significant physical and psychosocial morbidity due to the risk of causing permanent scarring, poor self-image, depression, and anxiety.

For these reasons, annual costs associated with acne treatment now exceed $3 billion. In other words? Novel acne treatments represent a significant opportunity for sponsors and drug developers.

Understanding Acne

The most effective and best-tolerated modern acne therapies target the condition’s underlying pathophysiology. Acne is a complex skin disorder of the pilosebaceous unit, which include the hair, hair follicle, sebaceous gland, and associated arrector pili muscles. In acne, the “pores” of the skin become clogged by sebum and cellular debris. This in turn leads to inflammation and the clinical presentation of comedones, papules, pustules, and nodules affecting the face, neck, chest, back, and upper extremities. Dermatologists classify acne based on lesion type and severity, from Grade 1 at the most mild to Grade 4 at the most severe.

Factors Contributing to Acne

The four major interrelated factors contributing to acne pathophysiology are:

  • Hyperkeratinization, usually caused by genetics, occurs when cells overproduce keratin. Excess keratin promotes clumping of cells and cellular debris.
  • Stimulation of sebaceous glands by androgens and retention of sebum. This is one reason why acne typically begins during puberty, often subsides by adulthood, and presents differently in males and females.
  • Obstruction of sebaceous follicles, specifically by accumulated sebum and dead cells, but can be exacerbated by external mechanical factors.
  • Microbial colonization by and overgrowth of Propionibacterium acnes, a species of bacteria that promotes perifollicular inflammation.

The Microbiology of Acne

While P. acnes is usually commensal and a normal part of healthy skin flora, it plays an important role in acne pathogenesis. This microbe grows on sebum and, consequently, excess sebum encourages bacterial overgrowth and an immunogenic response. Additionally, pathogenic strains of P. acnes may have the ability to manipulate the host environment by stimulating sebum production and promoting inflammation. Partly because a focus of traditional acne treatment was the control of this bacterium, antibiotic-resistant strains of P. acnes are becoming more common.

The follicles of patients with acne may be also be colonized by a number of other bacteria, including other normally commensal species and opportunistic pathogens. Of these, Staphylococcus epidermidis may be the most significant, with recent research suggesting it may play a role in disease pathogenesis.

How to Treat Acne

Some cases of mild, transient acne can be effectively treated at home through over-the-counter remedies. Further clinical treatment is common and based on type and severity. Unfortunately, few treatment options existed for severe, chronic acne until recently. Luckily, continuing advances in dermatology are changing that.

To find out more about acne treatments — including traditional, new, and emerging therapies — be sure to read our recent dermatology white paper, What’s New in Acne. And to join our mailing list for more news you can use, sign up here.

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