Acne is polygenic and multi-factorial. Four main pathogenetic factors contribute to the disease:
Sebaceous gland hyperplasia and excess sebum production. Sebaceous follicle size and number of lobules per gland are increased in patients with acne.  Androgens stimulate sebaceous glands to enlarge and produce more sebum, which is most prevalent during puberty.
Abnormal follicular differentiation. In normal follicles, keratinocytes are shed as single cells into the lumen and then excreted. In acne, keratinocytes are retained and accumulate due to their increased cohesiveness. 
Propionibacterium acnes colonisation. These gram-positive, non-motile rods are found deep in follicles and stimulate the production of pro-inflammatory mediators and lipases. While there may be increased numbers of P acnes in acne, bacterial counts often do not correlate with acne severity. 
Inflammation and immune response. Inflammatory cells and mediators efflux into the disrupted follicle, leading to the development of papules, pustules, nodules, and cysts.
External factors occasionally contribute to acne, including mechanical trauma, cosmetics, topical corticosteroids, and oral medicines (corticosteroids, lithium, iodides, some antiepileptics). Endocrine disorders resulting in hyperandrogenism may also predispose patients to developing acne. Acne fulminans is a rare acne subtype that presents with variable systemic manifestations, including fever, arthralgias, myalgias, hepatosplenomegaly, and osteolytic bone lesions.
Given the high prevalence of the disease, isolating specific genetic factors is difficult. However, the concordance rate for the prevalence and severity of acne among identical twins is high.  One study concluded that 81% of variance in acne was attributable to genetics and only 19% to environmental factors.