Oil production in the sebaceous glands increases during puberty, causing comedones and acne to be common in adolescents. Acne is also found premenstrually and in women with polycystic ovarian syndrome. Smoking may worsen acne.

Oxidation rather than poor hygiene or dirt causes blackheads to be black. Washing or scrubbing the skin too much could make it worse, by irritating the skin. Touching and picking at comedones might cause irritation and spread infection. It is not clear what effect shaving has on the development of comedones or acne.

Some, but not all, skin products might increase comedones by blocking pores, and greasy hair products (like pomades) can worsen acne. Skin products that claim to not clog pores may be labeled noncomedogenic or non-acnegenic. Make-up and skin products that are oil-free and water-based may be less likely to cause acne. It is not known whether dietary factors or sun exposure make comedones better, worse or have no effect.

A hair that does not emerge normally can also block the pore and cause a bulge or lead to infection (causing inflammation and pus).

Genes may play a role in the chances of developing acne. Comedones may be more common in some ethnic groups. People of recent African descent may experience more inflammation in comedones, more comedonal acne, and earlier onset of inflammation.

Risk factors for the development of acne, other than genetics, have not been conclusively identified. Possible secondary contributors include hormones, infections, diet and stress. Studies investigating the impact of smoking on the incidence and severity of acne have been inconclusive. Sunlight and cleanliness are not associated with acne.

Comedones are associated with the pilosebaceous unit, which includes a hair follicle and sebaceous gland. These units are mostly on the face, neck, upper chest, shoulders and back. Excess keratin combined with sebum can plug the opening of the follicle. This small plug is called a microcomedo. Androgens increase sebum (oil) production. If sebum continues to build up behind the plug, it can enlarge and form a visible comedo.

A comedo may be open to the air ("blackhead") or closed by skin ("whitehead"). Being open to the air causes oxidization, which turns it black. "Propionibacterium acnes" is the suspected infectious agent in acne. It can proliferate in sebum and cause inflamed pustules (pimples) characteristic of acne. Nodules are inflamed, painful deep bumps under the skin.

Comedones that are 1 mm or larger are called macrocomedones. They are closed comedones and are more frequent on the face than neck.

Solar comedones (sometimes called senile comedones) are related to many years of exposure to the sun, usually on the cheeks, not to acne-related pathophysiology.

The predisposition to acne for specific individuals is likely explained by a genetic component, a theory which is supported by studies examining the rates of acne among twins and first-degree relatives. Severe acne may be associated with XYY syndrome. Acne susceptibility is likely due to the influence of multiple genes, as the disease does not follow a classic (Mendelian) inheritance pattern. Multiple gene candidates have been proposed including certain variations in tumor necrosis factor-alpha (TNF-alpha), IL-1 alpha, and CYP1A1 genes, among others. Increased risk is associated with the 308 G/A single nucleotide polymorphism variation in the gene for TNF.

Histomoniasis (or histomonosis), also known as blackhead disease, is a commercially important disease of poultry, particularly of chickens and turkeys, due to parasitic infection of a protozoan, "Histomonas meleagridis". The protozoan is transmitted to the bird by the nematode parasite "Heterakis gallinarum". "H. meleagridis" resides within the eggs of "H. gallinarum", so birds ingest the parasites along with contaminated soil or food. Earthworms can also act as a paratenic host.

"Histomonas meleagridis" specifically infects the cecum and liver. Symptoms of the infection include depression, reduced appetite, poor growth, increased thirst, sulphur-yellow diarrhoea, listlessness, and dry, ruffled feathers. The head may become cyanotic (bluish in colour), hence the common name of the disease, blackhead disease; thus the name 'blackhead' is in all possibility a misnomer for discoloration. The disease carries a high mortality rate, and is particularly highly fatal in poultry, and less in other birds. Currently, no prescription drug is available to treat this disease.

Poultry (especially free-ranging) and wild birds commonly harbor a number of parasitic worms with only mild health problems from them. Turkeys are much more susceptible to getting blackhead than are chickens. Thus, chickens can be infected carriers for a long time because they are not removed or medicated by their owners, and they do not die or stop eating/defecating. "H. gallinarum" eggs can remain infective in soil for four years, a high risk of transmitting blackhead to turkeys remains if they graze areas with chicken feces in this time frame.

Histomoniasis is characterized by blackhead in birds. "H. meleagridis" is released in the cecum where the eggs of the nematode undergo larval development. The parasite migrates to the mucosa and submucosa where they cause extensive and severe necrosis of the tissue. Necrosis is initiated by inflammation and gradual ulceration, causing thickening of the cecal wall. The lesions are sometimes exacerbated by other pathogens such as "Escherichia coli" and coccidia. Histomonads then gain entry into small veins of the blood stream from the cecal lesions and migrate to the liver, causing focal necrosis. Turkeys are noted to be most susceptible to the symptoms in terms of mortality, sometimes approaching 100% of a flock. Diagnosis can be easily performed by necropsy of the fresh or preserved carcass. Unusual lesions have been observed in other organs of turkey such as the bursa of Fabricius, lungs, and kidneys.

Symptoms appear within 7–12 days after infection and include depression, reduced appetite, poor growth, increased thirst, sulphur-yellow diarrhoea, listlessness, drooping wings, and unkempt feathers. Young birds have a more acute disease and die within a few days after signs appear. Older birds may be sick for some time and become emaciated before death. The symptoms are highly fatal to turkeys, but effect less damage in chickens. However, outbreaks in chickens may result in high morbidity, moderate mortality, and extensive culling, leading to overall poor flock performance. Concurrence of "Salmonella typhmurium" and "E. coli" was found to cause high mortality in broiler chickens.