Hidradenitis Suppurativa Perineal and Perianal

Abstract

Hidradenitis suppurativa (HS) is a chronic inflammatory, recurrent, and a debilitating skin disorder that affects the follicular epithelium, specifically of apocrine-gland-bearing regions (such as axillae, inframammary folds, groin, perineal, and/or perigenital). HS prevalence is around 1–4%, and the perineal disease is more common in males. HS is initially characterized by perifollicular lymphocytic infiltrate, which causes glands’ duct occlusion, dilation, rupture of the follicle, and increased inflammation. The result is the formation of tunnels (fistulas) connecting the glands to the skin’s surface. Secondary bacterial infections may occur. The etiological factors are obesity, smoking, and hormones, with a genetic predisposition of up to 40% of patients. HS usually occurs in early adulthood, with inflamed skin nodules, abscesses, pus discharge tunnels, and scarring developed in axillary, inguinal, gluteal, and perineal body sites. The diagnosis is made clinically based on typical lesions, affected regions, and progression (chronicity, persistent lesions, and recurrence). The therapy for HS must be individualized and guided by severity. They range from topical and systemic antibiotics, retinoids, immunosuppressive drugs, local therapies such as laser, phototherapy, hyperbaric, and even regulated and extensive surgical resections, which may be associated with skin grafts.

1. Introduction

Hidradenitis suppurativa (HS) is characterized as a chronic inflammatory, recurrent, and debilitating skin disorder that affects the follicular epithelium, specifically of apocrine-gland-bearing regions such as axillae, inframammary folds, groin, perineal, and/or perigenital [1, 2, 3]. Even though HS is almost three times more common in women, the perineal disease is particularly seen more often in males, and it is related to higher morbidity compared to other regions [1, 2].

HS often presents with very painful, inflamed skin nodules, abscesses, pus-discharging tunnels (known as sinus tracts and fistulas), and scarring. The diagnosis is made clinically and based on typical lesions, affected regions, and progression (chronicity, persistent lesions, and recurrence) [3, 4]. HS is a difficult disease to diagnose, given its multiple differential diagnoses that can lead to erroneous conclusions, with a diagnostic delay that can reach 12 years, leading to disease recurrence and progression [1, 3, 4].

Owing to its diversified presentation, with intense chronic pain, continuous purulent secretion, and bad smell, HS has a profound negative influence on patients’ private and professional lives, affecting their economic condition and quality of life. Thus, the topic deserves to be highlighted, since HS is a chronic disease with high morbidity and a negative impact on health systems and society [4].

2. Historical context

The term hidradenitis suppurativa is derived from the Greek words “hidros” (sweat) and “aden” (glands). Also known as reverse acne, it was first described by Velpeau, a French physician, in 1839, as superficial abscesses of a peculiar location, affecting the armpits, breasts, and perianal region [4, 5]. In 1854, the French surgeon Verneuil suggested some association based on clinical data with sweat glands and named the disease after him. In 1893, Pollitzer and Dubreuilh established a clear etiopathogenesis associated with apocrine sweat glands [5]. Despite these discoveries, there were not enough studies to understand HS as a disease until 1939, when Brunsting published a complete work on the subject [4, 5, 6].

3. Epidemiology

HS is a disease with few epidemiological data described in the literature, with a large part of North American and European studies. It was considered a rare condition, mainly due to diagnostic errors and underreporting existing cases [5, 7]. In young European population, its prevalence is around 1–4% globally [8, 9]. In the United States, a study in Minnesota estimated a prevalence value of 0.13%, which is lower than that presented in Europe [10]. Regarding the age group, the disease is common between puberty and 40 years of age, being more frequent between 21 and 29 years of age, tending to decrease and disappear in women after menopause [5, 7]. The occurrence in females is higher, with a ratio of three females to one male. Perineal and perianal disease is more prevalent in males and is also more severe and associated with an increased risk of degeneration to squamous cell carcinoma [7, 11]. A Dutch study shows that disease severity is closely linked to disease, body mass index, male gender, and smoking [12]. There is evidence that the higher the body mass index, the greater the severity of the disease. HS was 10 times more prevalent in the morbidly obese compared to the general population [12, 13]. The relationship between smoking and HS was related in 60–70% of patients, but not associated with disease severity. There is no pattern of racial or even ethnic predilection today [13, 14].

4. Etiology

Although the etiology of HS has not been fully elucidated, there is a genetic predisposition, as up to 40% of patients with HS have a positive family history. Some other factors not so well described may also be associated, such as hormonal changes and hyperandrogenic states, use of oral contraceptives, lithium, chemical irritants such as antiperspirants and deodorants, metabolic syndrome, inflammatory bowel disease, diabetes, and spondyloarthropathy that can lead to an increase in morbidity and mortality [15, 16].

Smoking and obesity are possible secondary causes of the disease and factors of worse prognosis. Some studies suggest that nicotine acts by stimulating and leading to dysfunctional glandular secretion, further altering neutrophil chemotaxis, leading to more severe diseases [13, 14]. Some studies have proven the association between smoking and perianal HS in 70% of patients; thus, one of the pillars of treatment is discouraging smoking [14, 15, 16].

Obesity can aggravate HS by retaining sweat and breaking the follicular and glandular ostia [15].

Bacterial colonization in HS is uncertain, being more associated as a secondary cause of the pathology. It can exacerbate the disease, but it is not a primary etiologic factor; there is no bacterial growth in more than half of the initial cases [15]. Bacterial infection occurs secondary to follicular occlusion. The most common bacteria are Staphylococcus aureus and Staphylococcus epidermidis. Chlamydia trachomatis and some anaerobes such as Peptostreptococcus, Bacteroides, and Fusobacterium can also be found. Escherichia coli, Klebsiella, and Proteus are more common in perineal HS [15, 16].

5. Pathogenesis

HS is initially characterized by perifollicular lymphocytic infiltrate, which causes glands’ duct occlusion, dilation, and rupture of the follicle. The result is an increased inflammation that leads to the formation of tunnels connected to the surface of the skin and filled with debris (Figure 1) [14, 15].

Figure 1.

Steps of hidradenitis suppurativa pathology.

Histologically, the skin is formed by three main layers: epidermis, dermis, and subcutaneous tissue. The invagination of the epidermis develops the skin appendages: hair follicles, apocrine glands, and eccrine glands. The sebaceous glands are located in the mid-dermis and are connected to the hair follicle. They can be unilobular or multilobular holocrine glands that secrete sebum to the skin surface. This oily substance is important to protect the skin from water loss and traumas and to provide antibacterial activity. Eccrine and apocrine glands are the two main types of human sweat glands. The eccrine glands have a straight eccrine duct and secretory coiled portion and are responsible for thermoregulation. The apocrine glands are larger and mainly located at the axillary and anogenital area, areolae, and eyelids [14, 15, 16].

These skin appendages are considered a peripheral endocrine organ, expressing receptors and synthesizing various hormones, especially the androgenic ones. During adolescence, the gonadal cells in the ovary and testis secrete estrogen and testosterone, leading to the development of secondary sexual characteristics, including pubic hairs and axillary hairs. In addition, the apocrine glands grow, and the sebum secretion increases. The body odor is mainly from the axillary apocrine sweat glands, related to the bacterial catabolism of apocrine sweat [14, 15, 16].

The HS affects these glands. Histopathological patterns of HS include hyperkeratosis of the terminal follicle openings, hyperplasia of follicular epithelium, and perifolliculitis. The disease is believed to begin with occlusion and dilation or elongation of the infundibular follicles. The infundibulum of the hair follicles then ruptures, followed by dermal suppurative inflammation with subsequent sinus tract formation and dermal fibrosis. This occlusion cause is not well understood. The local microbiota may play a role in the innate immune system dysregulation [14, 17, 18].

The damaged skin in HS expresses more keratin 16 at the interfollicular epidermis and infundibulum. Therefore, it is believed that a genetic propensity must be related to the epidermal cell differentiation and innate immunity in HS, leading to ill skin. Infiltrating CD4 + T cells secreting interleukin 17 (IL-17) and interferon-gamma (IFN-γ) are increased in perilesional and lesional skin of patients with HS. In these cases, the keratinocytes also produce significantly more IL-6, IL-8, tumor necrosis factor-alpha (TNF-α), interferon-gamma-induced protein 10, and C-C motif chemokine ligand 5 [16, 17, 18].

There are also morphological changes of the apocrine glands in HS, but it is still controversial whether the apocrine glands initiate or participate in the development of HS. The apocrine glands are full of secretory cell-like materials [18, 19]. The basal membrane zone gets thick and inflamed, and secondary bacterial Zcolonization contributes to the diffuse dense inflammatory aggregated in the dermis with dilated vessels, fibrotic changes, and diminished or absent appendageal structures, including apocrine glands. Besides, the number of eccrine sweat glands is reduced, and the sebaceous glands have a smaller volume and less number of sebaceous glands in the axilla and/or groin. The effect of decreased sebaceous glands is a drop in antimicrobial peptides and impaired innate immunity. Expression of integrin α6β4 in sick sebaceous glands may be associated with a bacterial infection [17, 18, 19].

6. Differential diagnoses

The diagnosis of HS is delayed in most cases due to the numerous possible differential diagnoses, which generates a negative impact on the course of the disease. The differential diagnosis includes a range of possibilities such as anthrax, dermoid cyst, furunculosis, fistulas, abscesses, pilonidal cyst, cutaneous tuberculosis, and inflammatory bowel disease, among others shown in Table 1 [20, 21].

Differential diagnosis of hidradenitis suppurativa
Noduloulcerative syphilis	Blastomycosis	Lymphogranuloma venereum
Cutaneous Crohn disease	Scrofuloderma – Tuberculosis	Donovanosis
Carbuncle	Neoplasms	Cutaneous actinomycosis
Epidermoid cyst	Erysipelas	Intergluteal pilonidal disease
Simple abscesses	Furuncle	Cat scratch disease

Table 1.

Differential diagnosis of hidradenitis suppurativa.

Adaptad from Zouboulis et al. [21].

The most important differential diagnosis of perianal and genital disease is subcutaneous tunneling diseases (e.g., pilonidal disease, Crohn’ disease (CD), benign anal fistula, and granuloma inguinale). A biopsy may be performed to elucidate the case. What differentiates pilonidal disease from HS is the absence of midline pits over the sacrum. The absence of involvement of the anal canal distinguishes HS from CD and benign anal fistula. About 50% of CD patients develop perianal lesions very similar to HS [20, 21, 22].

7. Associated conditions

HS is a chronic inflammatory systemic disease. It may be associated with several other pathologies (Table 2) [21]. Metabolic syndrome affects at least 50% of patients with HS, with an increased cardiovascular risk [20, 23].

Associated disease to hidradenitis suppurative
Follicular occlusive diseases
Acnevulgaris
Acne conglobate
Dissecting cellulitis
Intergluteal pilonidal diseases
Pigmentary disorders
Dowling - Degos disease
Kitamura disease
Rheumatologic diseases
Arthritis
Synovitis
Amyloidosis
SAPHO
Endocrinologic and hormonal diseases
Grave's disease
Hashimoto's thyroiditis
Hyperandrogenism
Miscellaneous
Fox-Fordyce disease
Steatocystoma multiplex
Pityriasis rubra pilaris
Pyoderma gangrenosum

Table 2.

Associated disease to hidradenitis suppurativa.

Adapted from Zouboulis et al. [21].

Some rheumatologic pathologies may also be related, such as pyogenic arthritis, spondyloarthritis, gangrenosum pyoderma, amyloidosis, and synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome [20, 21].

Owing to chronic inflammation, patients with HS have an increased risk for malignancy, and squamous cell carcinoma is the worst complication [22].

Psychiatric pathologies, such as depression, panic syndrome, and suicidal ideation, are also reported [21, 23].

8. Diagnosis and classification

The absence of a pathognomonic test to identify HS may delay the diagnosis [21]. Three clinical diagnostic criteria are used: the presence of typical lesions, typically affected regions, and chronicity [24, 25].

The typical lesions are painful nodules, abscesses, suppurative sinus tracts, coalescing scars, and complex comedones. Pruritus, fetid smell, pain, and burning sensation are the most common symptoms. Affected regions must include at least one of the following: axillary, infra- and intermammary, inguinal, perineal, perianal, and gluteal regions. Chronicity is characterized by persisting lesions over 3 months or two recurrences within the period of 6 months. Secondary bacterial infection may also cause chronicity [21, 23, 24, 25].

Familiar HS history must be considered and a full skin examination performed to assess the severity and exclude other diagnoses [21, 26].

The skin biopsy may be useful and should be performed if there is suspicion of squamous cell carcinoma. A firm, nonfluctuant, nondraining, superficially eroded, or ulcerated mass are strong evidence of malignancy [22].

If there is a primary infectious disease or clinical evidence of secondary cellulitis, a culture may help [21, 25, 26].

High-frequency ultrasound and magnetic resonance are used to detect dermal and subcutaneous involvement, discriminating differential diagnosis, such as fistula [21, 27].

HS severity is classified by the Hurley classification, which defines three stages according to the number, chronicity, and coalescence of the lesions as shown in Table 3 [21].

Hurley staging—severity score	Clinical features
Stage l-Mild	Single or multiple abscesses without sinus tracts and scarring
Stage II-Moderate	Recurrent abscesses with sinus tracts and scarring
Stage III-Severe	Diffuse or multiple interconnected sinus tracts and abscesses across the entire area

Table 3.

Hurley staging severity score.

Adaptad from Zouboulis et al. [21].

Sartorius scoring system and international hidradenitis suppurativa severity score system (IHS4), most appropriate to assess disease severity and grade of inflammation, was later proposed (Tables 4 and 5) [21, 24].

Sartorious score
I—Anatomical region involved (axilla, groin, gluteal or other region or inframammary region left and/or right: 3 points per region).
II—Number and scores of lesions (abscesses, nodules, fistulas, scars: points per lesion of all regions involved: nodules 2, fistulas 4, scars 1, others 1).
III—The longest distance between two relevant lesions, i.e. nodules and fistulas, in each region, or size if only one lesion (<5 cm, 2 points; $<10\mathit{cm},4$ points; $>10\mathit{cm},8$ points).
IV—Are all lesions clearly separated by normal skin? In each region (yes $0/$no 6).

Table 4.

Sartorious score.

Adapted from Sartorius et al. [24].

International hidradenitis suppurativa severity score system (IHS4)
Number of nodules multiplied by 1
Number of abscesses multiplied by 2
Number of draining tunnels (fistulas/sinuses) multiplied by 4
A score of more than 3 = mild; 4-10 = moderate ;11 or more = severe

Table 5.

International Hidradenitis Suppurativa Severity Score System (IHS4).

Adapted from Zouboulis et al. [21].

Three clinical subtypes of HS have been described: axillary-mammary, follicular, and gluteal. According to another classification by van der [26], there are six phenotypes of HS: (I) regular type; (II) frictional furuncle type; (III) scarring folliculitis type; (IV) conglobata type; (V) syndromic type; and (VI) ectopic type. Recently, it has been suggested to distinguish between a follicular subtype and an inflammatory phenotype, which is usually associated with a worse course of the disease [21, 26, 27].

9. Treatment

HS is a complex and difficult-to-treat disease, with success rates depending on the stage of the disease. To efficiently control it, a multidisciplinary treatment should be offered with an early approach, involving clinical and preventive measures, psychological support, and surgery [21, 28].

Behaviors to mitigate the disease development are smoking cessation, weight management, avoiding mechanical friction, chemical and physical irritants such as shaving, and the use of deodorants [17, 21].

Drug therapy ranges from topical and systemic antibiotics, anti-inflammatory agents, retinoids, antiandrogens, fumarates, and biguanides to immunosuppressive therapy. Local therapies, such as laser, phototherapy, hyperbaric, surgical resections, and skin grafts, can be useful [28, 29].

Topical antibiotics such as clindamycin were found to reduce nodules, pustules, and abscesses and should be used in mild-to-moderate disease with limited extent [21, 28]. On the other hand, systemic antibiotics are necessary in advanced disease commonly used for a long period (10–12 weeks). There is evidence supporting that the prescription of rifampicin and clindamycin soften the pain and lessen lesions count and suppuration [28]. In a randomized controlled trial, the combination of oral antibiotics (rifampicin and clindamycin) and 20 sessions of hyperbaric oxygen therapy was significantly superior to antibiotics alone in improving HS symptoms [29, 30].

Intralesional injections of glucocorticoids also play a role in the treatment of mild HS with few nodules and have shown to be effective and alleviate pain rapidly [21, 31].

Immunosuppressive drugs, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-12/23 (IL-12/IL-23) inhibitors, are an option of treatment. Even though their effects were demonstrated mostly in small case series, there is strong evidence based on large randomized controlled trials supporting the use of adalimumab (anti-TNF). In one of these studies, patients received weekly dose of adalimumab and 58.9% of them achieved at least 50% of reduction in acute lesion count, with no increase in abscesses [31, 32, 33].

More effective treatment involves several therapeutic strategies together, considering the severity and distribution of the lesions. Clinical and social income conditions of the patient may be considered to guide the proper management [31, 32, 33].

Some studies indicated that the best perineal/perianal outcome with the lowest recurrence rate is the surgical removal of all apocrine tissue with ill glands and subsequent reconstruction [21, 28, 32].

As an adjuvant measure, the use of hyperbaric oxygen therapy has been satisfactory in cases of extensive surgical resections as well [29]. In addition, among patients undergoing postoperative reconstructions with the creation of flaps that evolve with complications, such as necrosis or infection, hyperbaric oxygen therapy presented excellent results, with a shorter healing time [28, 29, 33].

Treatment for HS is established according to the Hurley stage, which classifies it into three degrees of severity, as shown in Table 6.

Hidradenitis suppurativa treatment according to Hurley stage
Adjuvant treatment (all stages)	Weight loss and tobacco cessation Pain control Antimicrobial wash Appropriate dressings Psychosocial support measures Management of concomitant comorbidities
Hurley Stage 1; and II	Topical treatments	Topical antibiotics and keratolytic agents (e.g. clindamycin lotion 1% bid for 3 months; resorcinol 15% bid) Intralesional corticosteroids – triamcinolone
	Systemic treatments	Oral antibiotics (e.g. oral tetracycline 500 mg bid for 4 month; dapsone 25-200 mg daily) Systemic retinoids (e.g. acitretin 0.25 to 0.88 mg/kg daily; alitretinoin 10 mg daily) Antiandrogenic therapies (e.g. oral contraceptive pills; finasteride 5 mg daily; metformin 500-1500 mg daily)
	Surgical/Physical Treatments	Less invasive surgical approaches (e.g. local excision, curettage and electrocauterization, deroofing, punch debridement, cryoinsufflation) Laser and lights therapy (e.g.Nd:YAG, CO2 laser, PUVA)
Hurley Stage; II to III; (includes; Stage I to II; approaches)	Systemic treatments	Oral antibiotics (e.g. oral rifampin 600 mg daily + clindamycin 300 mg bid for 10 weeks) Systemic immunosuppressants (e.g. ciclosporin 2-6 mg/kg/day) Biological treatments (e.g. adalimumab 160 mg week 0,80 mg week 2 , then 40 mg weekly. Consider also, infliximab 5 mg/kg weeks 0,2 and 6; ustekinumab 45 or 90 mg at weeks 0,4,16 and 28)
	Surgical/Physical Treatments	More invasive surgical approaches (e.g. wide radical excision)

Table 6.

Recommendations for surgical treatment of hidradenitis supurativa according to Hurley Stage.

Adapted from Zouboulis et al. [21], and Ingram et al. [28].

CO2: carbon dioxide; Nd:YAG: long-pulsed neodymium:yttrium-aluminum-garnet laser; IPL: intense pulse light; PDT: photodynamic therapy; and PUVA: bath psoralen plus ultraviolet A

Punch debridement is recommended to treat acute inflammatory nodes. This is known as the “mini unroofing” procedure: a single follicle is evacuated by partially removing its roof. Surgical unroofing (deroofing management) can also be performed in Hurley stages II or III [31, 33].

A similar procedure referred as skin-tissue-saving excision with electrosurgical peeling (STEEP) is an alternative to wide excision. It may be performed on local or extensively affected tissue areas. It consists of careful unroofing and debridement of sinuses and inflamed tissue followed by scrubbing. This can be alternatively made with a carbon dioxide laser [31, 32, 33].

Incision and drainage alone lead to high recurrence levels and are, therefore, not recommended as a single treatment. However, it may be useful for pain relief [33, 34].

Sweeping excision is used to manage an extensive area of chronic HS (Hurley stage III), particularly when conservative measures fail. It is not curative but generally leads to long periods without recurrence. The entire affected area is removed until the normal-appearing subcutaneous fat is evident [28, 34].

Figures 2–5 demonstrate selected cases of HS and extensive lesion resections.

Figure 2.

Hidradenitis suppurativa lesions in the perianal and perineal region. (a) Preoperative and (b) immediate postoperative aspects.

Figure 3.

Extensive HS resections (a, b, c—immediate and d—late).

Figure 4.

Patient underwent modified radical vulvectomy. Preoperative (a), intraoperative (b), and reconstruction primary (c) image of the external genitalia marked scarring and fistulous tracts were evident in the pubis, vulva, and groin.

Figure 5.

Extensive resection in the gluteus and perineum of HS with closure by second intention. Preoperative (a) and postoperative (b) immediate.

In our experience, patients with mild/moderate HS confined to a small area tend to respond to clinical and simple pharmacological treatment (topical and/or oral antibiotics). In cases of refractoriness and high inflammatory activity, adalimumab associated with antibiotics should be a great option to control the symptoms and extension of HS.

Among patients presenting scars, tunnels, and contractures or chronic refractory lesions, surgery should be considered. Localized lesions allow small procedures such as deroofing; nevertheless, in severe and extensive injuries, the size of intervention associates inversely with recurrence rates.

10. Conclusions

HS is a chronic disease that causes significant weakness and suffering. Its onset in young adulthood leads to loss of productivity given the limiting nature of the disease. Treatment must be individualized, according to the extent, severity, and degree of interference in quality of life. Topical or oral antibiotic therapy may be effective to treat mild diseases in small areas. Biological agents can be applied to severe or widespread diseases. New treatment options are emerging to target inflammatory agents. Perianal, perineal, and refractory cases of HS should be vigorously treated. Best outcomes are achieved with large resections and reconstructive procedures.

Conflict of interest

The authors declare no conflict of interest.

Abbreviations

HS	hidradenitis suppurativa
CD	Crohn disease
IL	interleukin
TNF	tumor necrosis factor
SAPHO	pustulosis-hyperostosis syndrome
STEEP	skin-tissue-saving excision with electrosurgical peeling