Hidradenitis suppurativa (HS) starts with a problem deep inside hair follicles: chronic inflammation triggers the follicle walls to thicken and clog, trapping debris beneath the skin. But that initial follicular blockage is only the first domino. HS is now understood as an autoinflammatory condition, meaning the immune system itself drives the disease rather than any single external cause. Genetics, hormones, weight, smoking, and skin bacteria all feed into the process, which is why pinpointing one clear cause has been so difficult.
How the Disease Begins Inside Hair Follicles
For years, the leading explanation was straightforward: a hair follicle gets plugged with a protein called keratin, the plug stretches the follicle until it bursts, and the contents spill into surrounding tissue, provoking an immune response. That sequence does happen, but newer evidence shows inflammation actually comes first. Subclinical inflammation, meaning inflammation you can’t yet see or feel, appears in the skin before any visible plugging occurs. Skin cells lining the follicle release inflammatory signals that cause the follicle walls to overproduce keratin. The clogging is a consequence of inflammation, not the other way around.
Once a follicle is inflamed and clogged, what happens next is more accurately described as “follicular disassembly” than a simple rupture. Inflammatory cells release enzymes that dissolve the structural framework holding the follicle together. The cells lining the follicle wall begin transforming into a different cell type through a process called epithelial-mesenchymal transition, essentially losing their identity as skin cells. The follicle wall breaks down, replaced by dense clusters of immune cells and scar-like tissue. This is how the tunnels and tracts characteristic of HS form beneath the skin, connecting one lesion to another.
The Inflammatory Feedback Loop
HS lesions are flooded with inflammatory signaling molecules at levels far beyond what healthy skin produces. Studies measuring gene activity in HS lesions have found that one key inflammatory signal, IL-17A, is expressed at 30 to 149 times the level seen in healthy skin. Another, IL-1β, has been measured at 115 times normal levels. These aren’t minor elevations. They reflect an immune system locked in overdrive.
What makes HS particularly stubborn is a built-in feedback loop. Inflammatory signals from immune cells stimulate skin cells to produce their own inflammatory molecules, which in turn activate more immune cells and amplify the original signal. Skin cells produce a compound called IL-17C in response to bacterial triggers and other inflammatory signals. IL-17C then stimulates even more production of the same molecules that triggered it, creating a self-sustaining cycle of inflammation. This is why HS lesions persist for weeks or months and why the disease tends to worsen over time without treatment.
Genetics and Family History
HS runs in families. Researchers have identified mutations in a group of genes responsible for producing a cellular enzyme complex called gamma-secretase. Three genes in particular (NCSTN, PSENEN, and PSEN1) have been linked to rare familial forms of the disease. Gamma-secretase plays a role in a signaling pathway that helps regulate how hair follicle cells develop and differentiate. When this pathway is disrupted, follicles are more prone to the abnormal keratinization that sets HS in motion.
These specific gene mutations account for only a small fraction of all HS cases. Most people with HS don’t carry them. But the broader pattern of familial clustering is well established, and pertinent family history is one of the features dermatologists look for when making a diagnosis. The genetic picture is likely polygenic, meaning many genes each contribute a small amount of risk rather than one gene causing the disease outright.
Smoking and Nicotine
Smoking is one of the strongest modifiable risk factors for HS, and the connection goes beyond general health effects. Tobacco smoke contains chemicals that directly promote the same inflammatory molecules found at elevated levels in HS lesions. Nicotine activates specific receptors on skin cells (nicotinic acetylcholine receptors), while other compounds in cigarette smoke activate a separate receptor system called aryl hydrocarbon receptors. Both pathways amplify inflammation in the skin. On top of that, smoking suppresses the same Notch signaling pathway that the gamma-secretase gene mutations disrupt, meaning smoking mimics a genetic predisposition to HS at the molecular level.
This doesn’t mean every smoker develops HS or that quitting will cure existing disease. But for someone who is already genetically susceptible, smoking adds fuel to every stage of the process.
Obesity, Friction, and Metabolic Inflammation
HS and obesity share a common foundation of chronic, low-grade systemic inflammation. Fat tissue isn’t passive storage. It actively produces inflammatory signals and disrupts the balance of hormones that regulate metabolism. This creates a baseline inflammatory state throughout the body that primes skin follicles for the kind of immune overreaction seen in HS.
The mechanical component matters too. HS almost exclusively affects intertriginous areas, the spots where skin folds against itself: armpits, groin, inner thighs, under the breasts, and the buttocks. Higher body weight increases skin-on-skin friction and creates warmer, more occluded environments in these areas, both of which can aggravate already-vulnerable follicles. The combination of systemic metabolic inflammation and local mechanical stress helps explain why weight loss often improves HS symptoms, even when it doesn’t eliminate them entirely.
Obesity is also linked to insulin resistance, which connects HS to a broader metabolic picture. The chronic inflammatory state disrupts insulin signaling in tissues throughout the body, contributing to a feedback loop between metabolic dysfunction and skin inflammation.
Hormonal Factors
Several features of HS point toward a hormonal influence. The disease almost always appears after puberty, with about 79% of cases beginning in the mid-to-late teen years and a second, smaller peak around the mid-40s. It’s more common in women. Many women report flares in the days before their period and improvement during pregnancy. All of this suggests sex hormones play a role in triggering or modulating the disease.
The exact hormonal mechanism remains unclear. Some studies have found associations between HS and elevated levels of androgens (sometimes called “male” hormones, though everyone produces them), and some patients improve on anti-androgen therapy. But results across studies have been inconsistent, and not all HS patients show hormonal abnormalities on blood tests. The hormonal connection is real but likely acts as a modifier of disease activity rather than a standalone cause.
The Role of Skin Bacteria
HS is not an infection, and that distinction matters. It was once treated primarily with antibiotics under the assumption that bacteria were driving the disease. Bacteria do play a role, but as contributors to an inflammatory process rather than the root cause.
People with HS have an altered skin microbiome even on unaffected skin, compared to people without the condition. This is significant because it suggests the microbial imbalance comes before lesions form, not after. Whether that imbalance actively drives inflammation or is itself a consequence of the underlying immune dysfunction is still an open question. What’s clear is that bacteria can worsen existing lesions. Once a follicle ruptures or a tunnel forms, bacteria colonize the damaged tissue and form biofilms, structured bacterial communities that are difficult for the immune system to clear. This secondary colonization intensifies the inflammatory response and contributes to the chronic, relapsing nature of the disease.
Where HS Appears and How It’s Recognized
HS is diagnosed clinically, without any blood test or biopsy required in most cases. Dermatologists look for three things: characteristic lesions (deep nodules, tunnels, and scars), location in skin-fold areas, and a pattern of recurrence over time. The axilla is the single most common site. Other frequent locations include the groin, inner thighs, perianal area, under the breasts, and the buttocks.
The nodules are typically 0.5 to 2 centimeters, seated deep in the skin, and persist for days to months. Unlike ordinary boils, they recur in the same areas, connect to each other through tunnels beneath the surface, and tend to drain intermittently. A biopsy is occasionally used to rule out other conditions, including skin cancer in long-standing lesions, but the diagnosis is primarily based on what a clinician can see and what a patient describes about their history.