Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic inflammatory skin disease that causes painful, deep-seated lumps, nodules, and abscesses. These lesions occur primarily in areas where skin rubs together and contains a high concentration of sweat glands and hair follicles, such as the armpits, groin, inner thighs, and under the breasts. The condition often leads to persistent drainage, the formation of tunnels under the skin called sinus tracts, and significant scarring. While the exact cause of HS is not fully understood, research points toward a complex interplay of genetic predisposition and external factors.
Understanding the Genetic Link
The evidence for a genetic component in hidradenitis suppurativa is substantial, with a significant percentage of patients reporting a family history of the disease. Studies indicate that between 30% and 40% of individuals with HS have a first-degree relative, such as a parent or sibling, who is also affected. This clustering within families strongly suggests that inheriting certain genetic factors increases the likelihood of developing the condition.
HS is not typically a simple single-gene disorder following classic inheritance patterns. Instead, it is considered a complex disease with polygenic inheritance, meaning multiple genes contribute to susceptibility. Twin studies support this, estimating the heritability of HS to be as high as 77%, suggesting a strong underlying genetic basis.
For a small percentage of cases (typically less than 7% of familial HS), specific gene mutations have been identified that follow an often autosomal dominant inheritance pattern. These mutations often involve genes responsible for the \(\gamma\)-secretase protein complex, such as NCSTN, PSEN1, and PSENEN. This complex is responsible for cleaving proteins, including those involved in the Notch signaling pathway, which regulates skin cells and hair follicles.
When these gene components are mutated, the Notch signaling pathway can become impaired, affecting hair follicle development and increasing the risk of follicular blockage and rupture. Individuals with these specific \(\gamma\)-secretase mutations often present with earlier onset and more severe forms of the disease. The concept of incomplete penetrance is also important; a person may inherit one of these genetic mutations but never develop the disease.
Non-Inherited Risk Factors and Triggers
While a genetic predisposition is common, environmental and lifestyle factors play a major role in triggering the onset and influencing the severity of HS. The disease is ultimately the result of this interaction between genetic susceptibility and external influences. These non-inherited factors accelerate its development in susceptible individuals.
Cigarette smoking is recognized as one of the strongest independent risk factors for HS, with a high percentage of patients being current or former smokers. Nicotine and other toxins in smoke promote inflammation and contribute to the follicular blockage that characterizes the early stages of the disease. Quitting smoking is a primary recommendation for managing the condition and reducing flare-ups.
Obesity is another significant non-inherited factor that correlates with both the development and increased severity of HS. Excess body fat increases mechanical friction in skin folds, where HS lesions commonly occur. Adipose tissue is metabolically active and produces inflammatory chemicals that can worsen the body’s overall inflammatory state.
Hormonal fluctuations also act as a trigger, explaining why HS typically begins after puberty and why women are more frequently affected than men. The disease often fluctuates with the menstrual cycle or during pregnancy, suggesting that sex hormones influence the follicular unit and the inflammatory response. This leads to the physical blockage of hair follicles, rupture, and the subsequent inflammatory cascade that defines HS.
Assessing Family Risk and Counseling
The high rate of familial clustering makes risk assessment a common concern for individuals with HS and their relatives. The risk for first-degree relatives (parents, siblings, and children) is significantly higher than for the general population. Siblings and offspring of an affected individual may have a risk of developing the condition ranging from approximately 14% to 20%.
Early identification is important, as recognizing symptoms early can lead to timely diagnosis and intervention, which may slow disease progression. Genetic testing for HS is not a routine part of clinical care for most patients. However, it may be considered in families with aggressive, early-onset, or syndromic forms where a specific \(\gamma\)-secretase mutation is suspected.
Genetic counseling focuses on discussing risk probability and the multifactorial nature of the disease, rather than providing a definitive prediction. Counselors explain that inheriting a genetic predisposition does not guarantee the disease will manifest. They emphasize that lifestyle modifications, such as maintaining a healthy weight and avoiding smoking, are actionable steps that can mitigate the genetic risk.