Key points

Introduction

Hidradenitis suppurativa (HS) is a chronic, painful, and inflammatory skin disorder of unknown origin, affecting inverse skin areas and associated with a high burden of disease. The diagnosis is made clinically, based on the patients’ history of recurrent typical lesions such as tender subcutaneous nodules or abscesses and tunnels (sinus tracts ) in the prototypical areas. HS was originally thought to be a disease of the apocrine sweat glands. However, more recent data indicate that HS is a disease originating from the hair follicles, following follicular occlusion by infundibular hyperkeratinization and dilatation of the follicle with subsequent rupture, which are thought to be the first events in HS.

There are conflicting reports about the influence of external physical or chemical factors on the development of HS. Patients claim that their condition deteriorates as a result of external factors, ranging from sweating to shaving. An association has been shown between shaving the affected areas before the onset of HS and earlier disease onset. However, a retrospective study showed that factors such as deodorants, depilatory products, and shaving did not influence HS in a negative manner. Hitherto, no experimental evidence has been shown in support of mechanical stress as a cause of HS. In contrast, in a questionnaire-based survey, it was shown that tight clothing or friction aggravated patients’ HS and that they obtained some relief when avoiding tight-fitting clothes. The role of mechanical stress is also supported by 3 case reports and 1 pathology study that suggested increased fragility of the dermoepidermal junction, which suggest that mechanical stress may contribute or be causative in the development of HS. Additional observations also suggest that an interplay may exist between mechanical stress on the epidermis and the development of HS lesions.

Introduction

Hidradenitis suppurativa (HS) is a chronic, painful, and inflammatory skin disorder of unknown origin, affecting inverse skin areas and associated with a high burden of disease. The diagnosis is made clinically, based on the patients’ history of recurrent typical lesions such as tender subcutaneous nodules or abscesses and tunnels (sinus tracts ) in the prototypical areas. HS was originally thought to be a disease of the apocrine sweat glands. However, more recent data indicate that HS is a disease originating from the hair follicles, following follicular occlusion by infundibular hyperkeratinization and dilatation of the follicle with subsequent rupture, which are thought to be the first events in HS.

There are conflicting reports about the influence of external physical or chemical factors on the development of HS. Patients claim that their condition deteriorates as a result of external factors, ranging from sweating to shaving. An association has been shown between shaving the affected areas before the onset of HS and earlier disease onset. However, a retrospective study showed that factors such as deodorants, depilatory products, and shaving did not influence HS in a negative manner. Hitherto, no experimental evidence has been shown in support of mechanical stress as a cause of HS. In contrast, in a questionnaire-based survey, it was shown that tight clothing or friction aggravated patients’ HS and that they obtained some relief when avoiding tight-fitting clothes. The role of mechanical stress is also supported by 3 case reports and 1 pathology study that suggested increased fragility of the dermoepidermal junction, which suggest that mechanical stress may contribute or be causative in the development of HS. Additional observations also suggest that an interplay may exist between mechanical stress on the epidermis and the development of HS lesions.

Mechanical stress of the skin

There are various kinds of mechanical stress: pressure, friction, shearing forces, stretching, rubbing, tension, pulling, pinching, and almost all other types of physical forces that act on the skin. Tribological (friction/rubbing science) studies have helped clinicians to understand the role of friction as a causative agent in various dermatologic events. Friction or frictional force, which may be defined as the resistance to motion in a direction relative to the common boundary of 2 surfaces, is a significant mechanical force that can cause tissue ischemia resulting in skin breakdown. There is a substantial difference between frictional forces and shear forces, or sheer stress, which is defined as force per unit area exerted parallel to the plane of interest. Sheer injury is not observed at the skin level because it occurs in deeper skin layers. A common example of shear force is when a person sitting in a wheelchair slides forward while the skin on the buttocks adheres to the surface of the seat cushion. This type of motion can result in pressure sores or decubitus ulcers, which are usually seen in persons confined to bed for long periods of time. In contrast, friction may occur on tight dressings, skin-to-skin contact (as seen in obese individuals), and continuous frictional skin contact with external material. Body areas at greatest risk for such frictional forces are largely the axillae, groins, buttocks, neck, and waistline. Table 1 lists the effects of the different kinds of mechanical stress.

Etiopathophysiology

The primary events in HS are follicular plugging (infundibulo)folliculitis, and dilatation of the follicle. In predisposed subjects, such a folliculitis can develop to the more serious and extended HS stages, classically in the inverse skin areas, a hallmark of HS. The question arises: why does this involvement happen in the regions with this typical topography? Pathohistologic studies have shown that within these affected regions the follicles are always involved. Moreover, the inflammation starts deep in the follicle around the bulbus, and continuous laterally. Furthermore, investigations using ultrasonography to visualize HS lesions showed abnormalities in the hair follicles of the axillae and groins. A consistent finding was the widened hair follicles in the affected areas, indicating enlargement and distortion of the base of the hair follicle in early stages. In more advanced stages, dermal and subcutaneous tracts were found, commonly connected to the base of the hair follicles. The widening of the follicles seems to represent an anatomic predisposition rather than a reactive pattern to existing disease. A child was recently described who developed HS-like lesions in an inguinal nevus comedonicus following increased mechanical stress on the region. The patient had a biopsy-verified congenital skin abnormality characterized by dilated hair follicles grouped in the inguinal fold. It had also been speculated that mechanical stress applied to follicles of a given size or width may provoke HS. However, in a later study, Kamp and colleagues failed to find any indication of increased follicular diameter in HS samples.

The biomechanical circumstances of the inverse or concave skin areas are different from those of convex skin regions. The anatomy and properties of the skin show differences. It has been observed, by means of sonographic investigations, that an abnormal dermal thickening is present in the axillary and genitofemoral regions, while the axillary skin is thinner than in the genitofemoral region. It was postulated that the increased dermal thickness, resulting in alterations of the mechanical conditions of the inverse skin areas, could be the physical factor in the development of HS. However, it remains to be shown whether the skin thickening is a primary manifestation in HS or the result of chronic inflammation. The special biomechanical circumstances are also supported by histologic findings of the normal axillary skin, which showed a ruffled surface as opposed to convex body sites such as the face. Moreover, the epidermal surface of the axillary skin affected by HS is thrown into folds. It has been postulated that constant mechanical forces, such as friction in the axillae and groins, contributes to microcomedo formation, considered an early step in the cascade of development of HS, which may lead to infrafollicular hyperkeratinization, dilatation of the follicle, and eventually microtears and rupture of the follicle wall with ensuing abscesses. This process is enhanced by obesity (discussed later). It has also been suggested that microtears of the hair follicle of predisposed subjects may even be the primary event. It has been postulated that HS may be caused by defective follicular support. The sebofollicular junction in HS skin was found to be a thinning of the periodic acid schiff (PAS)-positive material along the basement membrane zone, which may explain the apparent fragility of this junction. It may be hypothesized that, in individuals with such a predisposition, exposure to mechanical stress easily leads to damaged and subsequently ruptured follicles. These biomechanical mechanisms in the affected areas are stimulated in particular in the obese. It is widely accepted that obesity is a risk factor for HS and it is indicated that there is a dose-response effect with a positive correlation between disease severity and degree of body mass index. Moreover, it has been found that weight loss can ameliorate disease symptoms. There are several explanations why obesity may aggravate or contribute to the development of HS. The skin-to-skin contact is intensified in the intertriginous locations, especially in the deep skin folds. These folds could be the abdominal folds but also the axillae of obese patients, in whom the axillae are between the enlarged lateral thoracic walls and the upper arms, resulting in overlapping skin folds and subsequently an increase of maceration and friction. Mechanical stress in such obese patients contributes to the retention of the hair follicle material (ie, corneocytes, hair shafts, sweat, and sebaceous products), leading to plugging of the follicle opening, follicle dilation, and the whole cascade of the development of HS. Moreover, in these skin folds, a warm, humid, occlusive microclimate develops, favoring microbial growth. Furthermore, the fat mass by itself is associated with a low-grade systemic inflammatory state, capable of producing adipokines, cytokines, and chemokines. Recently, an obese patient with classic HS was described who developed HS lesions in the abdominal skin folds as well as on the upper abdomen, at the height of the waistband. This finding suggests that not only the low-grade inflammatory state of the fat mass but also the mechanical stress may be a contributing factor in the development of HS. In that case, unspecific factors such as mechanical stress or friction might initiate the inflammation. It would be useful to know whether mechanical stretching or friction of the skin has an effect on the keratinocytes, and, if so, how this event is translated by the epidermal keratinocytes. Mechanical stress induces the proliferation of epidermal keratinocytes under influence of calcium signaling. Moreover, this induction is further increased by the presence of ATP. Mechanical stress also strongly increases the release of the proinflammatory enzyme matrix metalloproteinase 9 in human keratinocytes. Furthermore, mechanical stress is also responsible for the thickening of the epidermis (hyperplasia) and hyperkeratosis through an increase of keratinocyte differentiation and proliferation after the mechanical stimuli. Recent studies of wound repair models show that fibroblast but not keratinocytes secrete the epidermal growth factor responsible for keratinocyte migration in wound healing.

Some genes related to wound healing are downregulated in keratinocytes as a response to mechanical stress. The downregulation is on a messenger RNA level and has been shown in skin grown from human embryonic stem cells. The genes are connexin 43, laminin α5, interleukin α, endothelin 1, and keratinocyte growth factor. The fact that mechanical stress may induce cell proliferation, while suppressing genes related to wound healing, underlines that keratinocyte responses to mechanical forces are still poorly understood.