Hidradenitis suppurativa (HS) is caused by hair follicles becoming blocked, swelling, and eventually rupturing beneath the skin, triggering a powerful inflammatory response. About 2.5% of the global population is affected. The condition is not caused by poor hygiene, and it is not contagious. Instead, it results from a combination of genetic predisposition, immune system overactivity, hormonal influences, and lifestyle factors that interact in ways researchers are still untangling.
How HS Develops in the Skin
The process starts in the hair follicle. Cells lining the follicle overproduce keratin, a structural protein, which plugs the opening. The blocked follicle swells with trapped material. At the same time, immune cells begin infiltrating the area, and the inflammatory chemicals they release weaken the follicle wall by breaking down surrounding tissue.
Eventually the follicle ruptures. Keratin, bacteria, and cellular debris spill into the surrounding skin, and the immune system responds aggressively. Neutrophils and lymphocytes flood the area, forming the painful abscesses characteristic of HS. This destruction doesn’t stop at the original follicle. It can spread to nearby hair follicles and sweat glands, creating the tunnels and scarring that define more advanced disease. Crucially, bacteria don’t cause the initial blockage. The process begins with structural and immune changes in the follicle itself, and bacteria become involved after the rupture.
Genetics and Family History
More than one-third of people with HS have a family history of the condition. Researchers have identified 57 mutations across three genes that encode parts of an enzyme complex called gamma-secretase, which helps regulate how skin cells develop and communicate. The most commonly mutated gene is NCSTN, accounting for 39 of those mutations. Two other genes, PSENEN and PSEN1, make up the rest.
These mutations disrupt a signaling pathway that controls how keratinocytes (the cells that line hair follicles) mature and shed. When this signaling breaks down, the follicle is more prone to the blockage that sets the disease in motion. Not everyone with HS carries one of these mutations, and not everyone with a mutation develops severe disease. But the genetic component helps explain why HS runs in families and why it behaves differently from person to person.
An Immune System That Overreacts
HS is fundamentally an inflammatory disease. Several immune signaling molecules are elevated in HS skin, and they create a self-reinforcing cycle of inflammation that makes lesions persist and recur.
One of the most active is IL-1β, an inflammatory signal that recruits immune cells, activates tissue-degrading enzymes, and stimulates fibroblasts involved in scarring. Even skin that appears normal in HS patients overexpresses IL-1β compared to healthy skin, suggesting that the inflammatory tendency is body-wide, not just local to lesions.
IL-17 is another key player. It activates neutrophils and triggers keratinocytes to produce antimicrobial proteins that, in excess, fuel further inflammation. This creates a feedback loop: IL-17 draws neutrophils to the area, neutrophils amplify the inflammatory response, and pus forms. IL-23 sits upstream of this process, stimulating specialized immune cells to produce IL-17 in the first place. The IL-23/IL-17 pathway is also central to other chronic inflammatory conditions like Crohn’s disease and psoriasis, which frequently co-occur with HS.
TNF-alpha, a broad inflammatory signal, is also elevated in HS lesions and contributes to tissue damage and abscess formation. The fact that multiple overlapping immune pathways are involved explains why HS is so persistent and why treatments targeting a single pathway don’t always provide complete relief.
Hormonal Influences
HS typically first appears around puberty, and hormonal fluctuations clearly affect its course. Between 43% and 77% of women with HS report their symptoms worsen around their menstrual period. In one international survey of 279 women, over three-quarters experienced perimenstrual flares, while barely 1% noticed improvement.
Androgens appear to play a role, particularly in women. Studies have found that women with HS tend to have higher testosterone levels and a higher free androgen index than healthy controls. HS skin shows increased androgen receptor activity, even in the tunnels that form beneath the surface. In three documented cases, transgender patients receiving testosterone therapy experienced new onset or worsening of HS.
Women with HS also have a 2.64-fold higher risk of having polycystic ovary syndrome (PCOS), a condition characterized by excess androgens. This doesn’t mean androgens cause HS on their own, but in a subset of patients, particularly women, they appear to be an important contributing factor.
The Role of Bacteria
For years, HS was treated primarily as an infection. That understanding has shifted. The medical consensus now holds that HS is not infectious in origin. However, bacteria do play a supporting role.
The skin’s microbial balance is disrupted in HS-affected areas. Anaerobic bacteria, which thrive in low-oxygen environments like plugged follicles, tend to multiply in these conditions. When the follicle ruptures, those bacteria activate pattern-recognition receptors on immune cells, triggering further release of inflammatory signals like IL-1β and TNF-alpha. So while bacteria don’t start the disease, they amplify the inflammatory cascade once it’s underway. This is why antibiotics can help manage HS flares even though the condition isn’t truly an infection.
Smoking and Nicotine
Smoking is one of the strongest modifiable risk factors for HS. Nicotine and other chemicals in tobacco smoke promote the same inflammatory signals found in HS lesions. They also activate receptors on skin cells that further suppress the Notch signaling pathway, the same pathway disrupted by the genetic mutations linked to HS. In effect, smoking mimics or compounds the genetic vulnerability that drives follicular blockage.
Smokers with HS tend to have more severe disease, and quitting doesn’t always produce immediate improvement, which suggests that smoking causes lasting changes to skin biology. Still, it remains one of the few risk factors patients can directly address.
Obesity and Mechanical Friction
HS overwhelmingly affects skin folds: the armpits, groin, under the breasts, and between the buttocks. These are areas subject to constant friction, pressure, and shearing forces. A “two-hit” model has been proposed to explain this pattern. The first hit is a general susceptibility, often related to obesity and the chronic low-grade inflammation it produces. The second hit is the local mechanical stress in skin folds, which damages already-vulnerable follicles.
This model also helps explain why some patients develop lesions in unusual locations. When excess weight creates new areas of skin-on-skin contact, those sites can become affected too. Weight loss doesn’t cure HS, but reducing mechanical stress on the skin can lower the frequency and severity of flares in many patients.
Metabolic and Cardiovascular Risks
HS is consistently linked to metabolic syndrome, a cluster of conditions that includes diabetes, obesity, high blood pressure, and abnormal cholesterol levels. This association holds even in younger patients and those with mild disease, which suggests it isn’t simply a consequence of longstanding illness or medication side effects. The chronic systemic inflammation that drives HS likely contributes to cardiovascular risk as well, making metabolic screening an important part of long-term management.