Moreover, the common detrimental lifestyle choices associated with patients with depression and HS also suggest the possibility of a collective genetic susceptibility. Patients with depression also report increased consumption of alcohol, tobacco, and illicit substances; sedentary lifestyle leading to obesity; and poor compliance with prescribed medical treatment.42 Smoking and obesity are known contributors to the pathogenesis of HS, and their modification also is known to positively impact the disease course. In a retrospective single-cohort study, 50% of obese HS patients (n=35) reported a substantial decrease in disease severity after a reduction of more than 15% in body mass index over 2 years following bariatric surgery (n=35).43 Patients with HS also have reported disease remission following extensive weight loss.44 In addition, evidence has supported smoking cessation in improving the disease course of HS.43 Because these detrimental lifestyle choices are prevalent in both patients with HS and those with depression, a co-genetic susceptibility also may exist.
Furthermore, depression is characterized by a persistent inflammatory state,13,45 similar to HS.46 Elevated levels of a variety of inflammatory markers, such as C-reactive protein (CRP), IL-6, and soluble intercellular adhesion molecule 1, have been reported in patients with depression compared with healthy controls.13,45 Further analysis found a positive correlation and a strong association between depression and these inflammatory markers.47 Moreover, adipokines regulate inflammatory responses, and adipokines play a role in the pathogenesis of HS. Adipokine levels such as elevated omentin-1 (a recently identified adipokine) were found to be altered in patients with HS compared with controls.48 Results from clinical studies and meta-analyses of patients with depression also have demonstrated that adipokines are dysregulated in this population,49,50 which may be another potential genetic link between depression and HS.
In addition, genetic susceptibility to depression and HS may be shared because the inflammatory markers that have a strong association with depression also have been found to play an important role in HS treatment and disease severity prediction. In a retrospective cohort study of 404 patients, CRP or IL-6 levels were found to be reliable predictors of HS disease severity, which may explain why anti–tumor necrosis factor antibody regimens such as adalimumab and infliximab have clinically ameliorated disease activity in several cases of HS.51 In a study evaluating these drugs, high baseline levels of high-sensitivity CRP and IL-6 were predictive of patient response to infliximab.52 In a meta-analysis evaluating 20,791 participants, an association was found between concurrent depression and CRP. Furthermore, inflammation measured by high levels of CRP or IL-6 was observed to predict future depression.53 If the same inflammatory markers—CRP and IL-6—both play a major role in the disease activity of depression and HS, then a concurrent genetic predisposition may exist.
Conclusion
Understanding the comorbidities, etiologies, and risk factors for the development and progression of HS is an important step toward improved disease management. Available studies on comorbid depression in HS largely involve White patients, and more studies are needed in patients with skin of color, particularly the Black population, who have the highest prevalence of HS.10 Given the evidence for an association between depression and HS, we suggest a large-scale investigation of this patient population that includes a complete medical history, onset of HS in comparison to the onset of depression, and specific measures of disease progress and lifetime management of depression, which may help to increase knowledge about the role of depression in HS and encourage more research in this area. If shared genetic susceptibility is established, aggressive management of depression in patients at risk for HS may reduce disease incidence and severity as well as the psychological burden on patients.