Auto-inflammatory and Hair Follicle Involvement in HS
Second International HS Research Symposium Abstracts
The term “hidradenitis suppurativa” is firmly entrenched in the dermatological literature although it refers to a false pathogenetic concept. The term was historically coined based merely on the characteristic distribution of the apocrine glands and the anatomical coincidence with the disease process. The herein reported histopathological analysis of specimens of “hidradenitis suppurativa” from patients found at the center stage of the disease not a suppurative inflammation of the apocrine sweat glands but an occlusion of the hair follicles, comparable to acne vulgaris. The disease process starts with follicular hyperkeratosis and dilatation of the follicular infundibula evolving into comedones, comparable to the ones observed in acne vulgaris.
At this time, the apocrine glands are not involved. Eventually the dilated follicular infundibulum ruptures and the content spills into the surrounding dermis, evoking an acute inflammatory response in the immediate vicinity of the rupture site. Again, the apocrine glands do not show any signs of involvement nor an indication that they are the anatomical starting point of the sequence of events. If the inflammation remains confined to the immediate vicinity of the hair follicle, over time the initially neutrophilic infiltrate subsides and is gradually replaced by a granulomatous one, often with the addition of multinucleated foreign body giant cells. If, however, the acute inflammatory response following rupture is more florid, a large abscess develops which may extend into the subcutaneous tissue. Apocrine glands near the abscess but not involved by it, are unremarkable. Only by extension of the inflammatory process, apocrinitis evolves and apocrine glands are destroyed. Apocrine glands located further away from the extending abscess are morphologically unremarkable. When extensive tissue destruction has ensued, naked hair shafts, surrounded by an inflammatory infiltrate, are often the only indication that the process started from the hair follicle. In an attempt of the tissue to confine the inflammatory reaction and to prevent further spread, remnants of the hair follicle epithelium proliferate and sinus tracts form, often surrounded by fibrosis. The sinus tracts communicate with the surface. Upon bacterial superinfection, they rupture and the process becomes self maintaining and enters into a vicious cycle. Sinus tract formation is the main reason for the chronicity of the disease and why radical surgery is the only therapeutic option capable of achieving long lasting cure.
Thus, “hidradenitis suppurativa” is a disorder that shares histopathological and clinical aspects with acne vulgaris modified under the special circumstances of anatomical regions rich in apocrine glands. It is acne inversa because in contrast to acne vulgaris the disease involves intertriginous localizations and not the regions classically affected by acne.
Auto-inflammatory Mechanisms in the Pathogenesis of HS
Evangelos J. GiamarellosBourboulis, MD, PhD 4th Department of Internal Medicine, University of Athens, Medical School, Greece.
There is accumulating body of evidence suggesting that patients with HS have severe derangements of their innate immune system. This evidence is based on monocyte stimulation assays and on the favorable clinical responses with biological therapies. Blood monocytes were isolated from patients and stimulated with lipopolysacchraride (LPS) of Escherichia coli O144:H4 (1). Defective monocyte responses characterized by reduced production of tumor necrosis factoralpha (TNF_) and interleukin6 (IL6) were found. In the same study, it was shown that NK cells of patients were increased. These findings pointing towards serious derangements of the innate immune responses in the event of HS, led to a prospective, openlabel, one arm clinical trial of the administration of etanercept in patients with HS. Etanercept was administered at a dose of 50 mg sc once weekly for 12 weeks. Efficacy of treatment was evaluated by the Sartorius score and by the disease activity index. A more than 50% decrease of both scores compared with baseline was found in seven patients. All patients reported decreased pain by week 4 whereas the number of fistulas was significantly decreased. Treatment was well tolerated. Relapse was noted within 48 weeks after cessation of therapy.
The above findings implicate derangements of the innate immune system as part of the mechanism of pathogenesis of HS.
1. GiamarellosBourboulis EJ, Antonopoulou A, Petropoulou C, et al. Altered innate immune response in patients with hidradenitis suppurativea. Br J Dermatol: 2007; 156: 5156. 2. GiamarellosBourboulis EJ, Pelekanou E, Antonopoulou A, et al. An open label phase II study of the safety and efficacy of etanercept for the therapy of hidradenitis suppurativa. Br J Dermatol 2008; 158: 567572.