to support the idea that acne and associated scarring negatively affect a person's psychological state, worsen mood, lower self-esteem, and are associated with a higher risk of anxiety disorders, depression, and suicidal thoughts. misperceptions about acne's causative and aggravating factors are common, and people with acne often blame themselves, and others often blame those with acne for their condition. such blame can worsen the affected person's sense of self-esteem. until the 20th century, even among dermatologists, the list of causes was believed to include excessive sexual thoughts and masturbation. dermatology's association with sexually transmitted infections, especially syphilis, contributed to the stigma. another psychological complication of acne vulgaris is acne excoriée, which occurs when a person persistently picks and scratches pimples, irrespective of the severity of their acne. this can lead to significant scarring, changes in the affected person's skin pigmentation, and a cyclic worsening of the affected person's anxiety about their appearance. epidemiology globally, acne affects approximately 650 million people, or about 9.4% of the population, as of 2010. it affects nearly 90% of people in western societies during their teenage years, but can occur before adolescence and may persist into adulthood. while acne that first develops between the ages of 21 and 25 is uncommon, it affects 54% of women and 40% of men older than 25 years of age and has a lifetime prevalence of 85%. about 20% of those affected have moderate or severe cases. it is slightly more common in females than males (9.8% versus 9.0%). in those over 40 years old, 1% of males and 5% of females still have problems. rates appear to be lower in rural societies. while some research has found it affects people of all ethnic groups, acne may not occur in the non-westernized peoples of papua new guinea and paraguay. acne affects 40–50 million people in the united states (16%) and approximately 3–5 million in australia (23%). severe acne tends to be more common in people of caucasian or amerindian descent than in people of african descent. history domolene ointment, a mid-1900s medication that was claimed to cure acne historical records indicate pharaohs had acne, which may be the earliest known reference to the disease. sulfur's usefulness as a topical remedy for acne dates back to at least the reign of cleopatra (69–30 bce). the sixth-century greek physician aëtius of amida reportedly coined the term "ionthos" (ίονθωξ,) or "acnae", which seems to be a reference to facial skin lesions that occur during "the 'acme' of life" (puberty). in the 16th century, the french physician and botanist françois boissier de sauvages de lacroix provided one of the earlier descriptions of acne. he used the term "psydracia achne" to describe small, red, and hard tubercles that altered a person's facial appearance during adolescence and were neither itchy nor painful. the recognition and characterization of acne progressed in 1776 when josef plenck (an austrian physician) published a book that proposed the novel concept of classifying skin diseases by their elementary (initial) lesions. in 1808 the english dermatologist robert willan refined plenck's work by providing the first detailed descriptions of several skin disorders using morphologic terminology that remains in use today. thomas bateman continued and expanded on robert willan's work as his student and provided the first descriptions and illustrations of acne accepted as accurate by modern dermatologists. erasmus wilson, in 1842, was the first to make the distinction between acne vulgaris and rosacea. the first professional medical monograph dedicated entirely to acne was written by lucius duncan bulkley and published in new york in 1885. scientists initially hypothesized that acne represented a disease of the skin's hair follicle, and occurred due to blockage of the pore by sebum. during the 1880s, they observed bacteria by microscopy in skin samples from people with acne. investigators believed the bacteria caused comedones, sebum production, and ultimately acne. during the mid-twentieth century, dermatologists realized that no single hypothesized factor (sebum, bacteria, or excess keratin) fully accounted for the disease in its entirety. this led to the current understanding that acne could be explained by a sequence of related events, beginning with blockage of the skin follicle by excessive dead skin cells, followed by bacterial invasion of the hair follicle pore, changes in sebum production, and inflammation. the approach to acne treatment underwent significant changes during the twentieth century. retinoids became a medical treatment for acne in 1943. benzoyl peroxide was first proposed as a treatment in 1958 and remains a staple of acne treatment. the introduction of oral tetracycline antibiotics (such as minocycline) modified acne treatment in the 1950s. these reinforced the idea amongst dermatologists that bacterial growth on the skin plays an important role in causing acne. subsequently, in the 1970s, tretinoin (original trade name retin a) was found to be an effective treatment. the development of oral isotretinoin (sold as accutane and roaccutane) followed in 1980. after its introduction in the united states, scientists identified isotretinoin as a medication highly likely to cause birth defects if taken during pregnancy. in the united states, more than 2,000 women became pregnant while taking isotretinoin between 1982 and 2003, with most pregnancies ending in abortion or miscarriage. approximately 160 babies were born with birth defects due to maternal use of isotretinoin during pregnancy. treatment of acne with topical crushed dry ice, known as cryoslush, was first described in 1907 but is no longer performed commonly. before 1960, the use of x-rays was also a common treatment. society and culture the costs and social impact of acne are substantial. in the united states, acne vulgaris is responsible for more than 5 million doctor visits and costs over us$2.5 billion each year in direct costs. similarly, acne vulgaris is responsible for 3.5 million doctor visits each year in the united kingdom. sales for the top ten leading acne treatment brands in the us in 2015 amounted to $352 million. acne vulgaris and its resultant scars are associated with significant social and academic difficulties that can last into adulthood. during the great depression, dermatologists discovered that young men with acne had difficulty obtaining jobs. until the 1930s, many people viewed acne as a trivial problem among middle-class girls because, unlike smallpox and tuberculosis, no one died from it, and a feminine problem, because boys were much less likely to seek medical assistance for it. during world war ii, some soldiers in tropical climates developed such severe and widespread tropical acne on their bodies that they were declared medically unfit for duty. research efforts to better understand the mechanisms of sebum production are underway. this research aims to develop medications that target and interfere with the hormones that are known to increase sebum production (e.g., igf-1 and alpha-melanocyte-stimulating hormone). other sebum-lowering medications such as topical antiandrogens, peroxisome proliferator-activated receptor modulators, and inhibitors of the stearoyl-coa desaturase-1 enzyme are also a focus of research efforts. particles that release nitric oxide into the skin to decrease skin inflammation caused by c. acnes and the immune system have shown promise for improving acne in early clinical trials. another avenue of early-stage research has focused on how to best use laser and light therapy to selectively destroy sebum-producing glands in the skin's hair follicles to reduce sebum production and improve acne appearance. the use of antimicrobial peptides against c. acnes is under investigation as a treatment for acne to overcoming antibiotic resistance. in 2007, scientists reported the first genome sequencing of a c. acnes bacteriophage (pa6). the authors proposed applying this research toward the development of bacteriophage therapy as an acne treatment to overcome the problems associated with long-term antibiotic use, such as bacterial resistance. oral and topical probiotics are under evaluation as treatments for acne. probiotics may have therapeutic effects for those affected by acne due to their ability to decrease skin inflammation and improve skin moisture by increasing the skin's ceramide content. as of 2014, knowledge of the effects of probiotics on acne in humans was limited. decreased levels of retinoic acid in the skin may contribute to comedo formation. researchers are investigating methods to increase the skin's production of retinoic acid to address this deficiency. a vaccine against inflammatory acne has shown promising results in mice and humans. some have voiced concerns about creating a vaccine designed to neutralize a stable community of normal skin bacteria that is known to protect the skin from colonization by more harmful microorganisms. other animals acne can occur on cats, dogs, and horses.