What is hidradenitis suppurativa

Hidradenitis suppurativa also known as acne inversa or Verneuil’s disease, is a chronic (long-term) painful inflammatory disease of the apocrine sweat glands in your armpits, groin, under the breasts and/or genitals and anal regions of the body, although other sites may be involved, that causes deep scarring and impacts quality of life ¹, ², ³. People who have hidradenitis suppurativa develop painful red bumps or sores in places where they grow hair and where the skin rubs together, such as the armpits, groin, buttocks and breasts ⁴. Hidradenitis suppurativa is characterized by persistent or recurrent boil-like lumps and abscesses (swollen area within body tissue containing a pocket of pus) that culminate in a purulent discharge, unnels under the skin (sinuses), and scarring. Hidradenitis suppurativa can persist for many years and worsen over time, with serious effects on your daily life and emotional well-being. Hidradenitis suppurativa can cause a significant psychological impact, and many patients suffer from anxiety, depression, and impairment of body image ⁵.

Hidradenitis suppurativa is primarily considered a severe form of acne (an acne-like follicular occlusion disease) where apocrine glands (sweat glands) only become involved in the context of peri-follicular inflammation – it is not a primary disease of apocrine glands (sweat glands).

In hidradenitis suppurativa, the sweat glands (apocrine glands) become clogged due to a variety of reasons, leading to enlargement (dilatation) of the ducts behind them. This dilatation predisposes the area to inflammation and infection by a variety of bacteria. Those with hidradenitis suppurativa typically have multiple large, recurrent boil-like nodules (red bumps) and abscesses on the buttocks, breasts, groin, and armpits. The bumps gradually get larger and drain pus. After multiple bouts of this cycle of plugging, enlargement, drainage and difficult-to-heal open wounds (sinuses), there may be scarring.

Hidradenitis suppurativa tends to start after puberty and generally occurs in young adulthood to middle adulthood, most common between 18 to 39 years of age ⁶. Onset before puberty is uncommon, but does correlate with a greater severity later in life and a positive family history ⁷. Females and blacks are more than twice as likely to be affected ³. Additional risk factors include family history, smoking, and obesity ³. Hidradenitis suppurativa is associated with several comorbidities, including diabetes mellitus and Crohn disease ³.

The prevalence of hidradenitis suppurativa in the United States is approximately 0.1%, with increasing incidence over the past 10 years ⁸, ⁶.

Potential complications of hidradenitis suppurativa include keloid scars, fistulas, lymphedema, squamous cell carcinoma (SCC), anemia of chronic disease, amyloid of the skin and/or kidney with the development of nephrotic syndrome, scarring, and limb contractures ⁹. Cancer, in particular squamous cell carcinoma (SCC) may rarely occur ¹⁰. Patients may die. The typical patient is one with long term, severe disease who develops a very painful nodule or lesion, often in the perianal or perineal area.

At the present time, there is no cure for hidradenitis suppurativa, but you can work with your doctor to treat existing lesions and prevent new ones.

Clinical management of hidradenitis suppurativa is often complex and includes medical and surgical treatments, which are often combined, especially in moderate-to-severe disease ¹¹. The reduction of symptoms and inflammation activity as well as prevention of formation of chronic hidradenitis suppurativa lesions and scarring represent key therapeutic goals ¹.

Hidradenitis suppurativa treatment options:

• Weight loss
• Smoking cessation
• Topical or oral antibiotics
• Intralesional steroids
• Low-dose prednisone
• 1064 nm nd:YAG Laser
• Laser hair removal
• Adalimumab
• Diabetic agents (e.g. metformin)
• Surgery

In current hidradenitis suppurativa treatment guidelines, an individualized patient-oriented approach, based on the individual subjective impact and objective disease severity, is recommended ¹². Treatment includes wearing loose-fitting clothes, losing weight if overweight, and smoking cessation ³. Topical clindamycin alone can be effective for patients with mild disease. Patients with moderate disease can be treated with oral antibiotics, such as tetracyclines, in addition to topical clindamycin. Adalimumab, a tumor necrosis factor alpha inhibitor, is effective for patients with moderate to severe hidradenitis suppurativa. Surgical procedures are often necessary for definitive treatment and include local procedures, such as punch debridement and unroofing/deroofing. Wide excision is indicated for patients with severe, extensive disease and scarring ³.

Figure 1. Hidradenitis suppurativa armpit

Figure 2. Hidradenitis suppurativa groin

[Source ¹³ ]

Figure 3. Axillary hidradenitis suppurativa

Footnotes: Axillary hidradenitis suppurativa showing inflammatory nodules (black arrows), multiheaded open comedones (white arrows), and scarring.

[Source ³ ]

Figure 4. Hidradenitis suppurativa

Footnotes: Typical appearance of an open double “tomb stone” comedone in a patient with hidradenitis suppurativa. Multiheaded comedones are an end-stage result of inflammatory destruction of the folliculopilosebaceous unit.

[Source ³ ]

Is hidradenitis suppurativa contagious?

No. Hidradenitis suppurativa is non-contagious and you cannot spread hidradenitis suppurativa to another person through contact.

What are apocrine sweat glands?

Sweating prevents overheating of your body, because sweat cools your skin as it evaporates. Only mammals have sweat glands (sudoriferous glands). Humans have more than 2.5 million sweat glands distributed over the entire skin surface, except on the nipples and parts of the external genitalia. Humans normally produce about 500 ml of sweat per day, but this amount can increase to 12 liters (over 3 gallons) on hot days during vigorous exercise. Hair interferes with the evaporation of sweat and the ability to cool the body, so the need for increased temperature regulation through sweating led to a reduction of hairiness in humans.

There are two types of sweat glands, both of which increase their secretion in response to stress as well as to heat: eccrine and apocrine glands.

Eccrine glands (“secreting”) are by far the more numerous type (Figure 3). They are most abundant on the palms, soles, and forehead. Each is a coiled version of a simple tubular gland. The coiled, secretory base lies in the deep dermis and hypodermis, and the duct runs superficially to open at the skin surface through a funnel-shaped pore. (Although most pores on the skin surface are sweat pores, the “pores” seen on the face are openings of hair follicles.)

Apocrine glands are mostly confined to the armpits, anal, and genital areas. They are larger than eccrine glands, and their ducts open into hair follicles. Apocrine glands produce a special kind of sweat consisting of fatty substances and proteins, in addition to the components of true sweat. For this reason, apocrine sweat is viscous and sometimes has a milky or yellow color. This product is odorless when first secreted, but as its organic molecules are decomposed by bacteria on the skin, it takes on a musky smell. This is the source of body odor.

Apocrine glands start to function at puberty under the influence of androgens (a group of sex hormones that help start puberty and play a role in reproductive health and body development). Testosterone is the most common androgen. Apocrine glands activity is increased by sexual foreplay, and they enlarge and recede with the phases of a woman’s menstrual cycle. The secretions from the apocrine glands were identified as true human pheromones (chemical signals that convey information to a member of the same species) in the late 1990s when it was shown that they are responsible for the synchrony of the menstrual cycle that occurs in females who live together.

Apocrine glands are involved with sexual signaling and appear to function in attractiveness and mate selection. The genes that encode for the immune system, the major histocompatibility complex (MHC), also influence secretions from apocrine glands. Each person has a unique set of these genes. In experiments, the body odor scents that women selected as “sexy” or “attractive” came from men who had immune system genes most different from their own. Mates with complementary immune system genes provide their offspring with greater disease protection and decreased likelihood of recessive disorders.

Figure 5. Skin and apocrine sweat glands

Who’s at risk of hidradenitis suppurativa?

Hidradenitis suppurativa usually starts soon after puberty and continues into adult life. Hidradenitis suppurativa is most active between the ages of 20 and 40 years. Hidradenitis suppurativa is three times more common in females than in males and and in women, it can resolve at menopause. Hidradenitis suppurativa is also common in African Americans. Hair removal from shaving or using depilatories, deodorants, and irritation from anything rubbing against the affected area can worsen the condition. Hidradenitis suppurativa is often associated with smoking, obesity, and increased hormones. Additionally, it often runs in families.

Risk factors for developing hidradenitis suppurativa include ¹⁴, ¹⁵, ¹⁶, ¹⁷, ¹⁸, ¹⁹, ²⁰, ²¹, ¹², ²², ²³:

• Other family members with hidradenitis suppurativa
• Obesity and insulin resistance (metabolic syndrome)
• Cigarette smoking
• Follicular occlusion disorders: acne conglobata, dissecting cellulitis, pilonidal sinus
• Other skin disorders: psoriasis, acne, hirsutism
• Inflammatory bowel disease (Crohn’s disease)
• Comorbidities: hypertension, diabetes mellitus, dyslipidaemia, thyroid disorders, spondyloarthritis, polycystic ovary syndrome (PCOS), adverse cardiovascular outcomes
• Drugs: lithium, sirolimus, biologics
• Rare autoinflammatory syndromes associated with abnormalities of PSTPIP1 gene.
  • PAPA syndrome (pyogenic arthritis, pyoderma gangrenosum and acne),
  • PASH syndrome (pyoderma gangrenosum, acne, suppurative hidradenitis)
  • PAPASH syndrome (pyogenic arthritis, pyoderma gangrenosum, acne, suppurative hidradenitis).

Hidradenitis suppurativa stages

The severity and extent of hidradenitis suppurativa should be recorded at assessment and when determining the impact of a treatment. Two scoring systems are in common use: Hurley Stages and Sartorius Hidradenitis Suppurativa Score. However, a standardized and internationally accepted score is still missing, resulting in the utilization of different classification tools in clinical studies for the evaluation of treatments ¹.

The Hurley staging system describes hidradenitis suppurativa into three distinct clinical stages ²⁴ and due to its simplicity is the most widely used classification system for hidradenitis suppurativa in routine clinical practice. The Hurley staging classifies hidradenitis suppurativa into three stages, mainly based on the presence of sinus tracts and scarring, allows medical professionals a fast and simple clinical based evaluation. However, the Hurley staging system is not applicable for monitoring of hidradenitis suppurativa, as it represents a static and non-quantitative tool and inflammation activity is not captured ²⁵. A revised Hurley staging system, that takes account of inflammation activity and subcategorizes Hurley stages 1 and 2 into mild, moderate and severe disease, has been described recently; however, clinical application is limited ²⁶.

Hidradenitis suppurativa stage 1

Solitary or multiple, isolated abscess formation without scarring and sinus tracts.

Hidradenitis suppurativa stage 2

Recurrent abscesses, single or multiple widely separated lesions, with sinus tract formation.

Hidradenitis suppurativa stage 3

Diffuse or broad involvement, with multiple interconnected sinus tracts and abscesses.

Severe hidradenitis (Hurley Stage 3) has been associated with:

• Male gender
• Armpit and perianal involvement
• Obesity
• Smoking
• Disease duration.

Sartorius Hidradenitis Suppurativa Score

The Sartorius Hidradenitis Suppurativa Score is made by counting involved regions, nodules and sinus tracts ²⁷:

• Anatomic region involved (axilla, groin, genital, gluteal, or other inflammatory region left and/or right): 3 points per region involved
• Number and scores of lesions (abscesses, nodules, fistulas, scars): 2 points for each nodule, 4 points for each fistula, 1 point for each scar, 1 point each for “other”
• Longest distance between 2 relevant lesions (ie, nodules and fistulas, in each region, or size if only 1 lesion): Less than 5 cm, 2 points; less than 10 cm, 4 points; more than 10 cm, 8 points
• Lesions clearly separated by normal skin in each region: If yes, 0 points; if no, 6 points.

Although the Sartorius Hidradenitis Suppurativa Score is a dynamic system, suitable for treatment monitoring, due to its complexity its use is often time-consuming and especially in severe cases difficult to apply ²⁷.

Hidradenitis suppurativa physician global assessment (HS-PGA) score

The hidradenitis suppurativa physician global assessment (HS-PGA) score is a frequently used tool to assess disease severity. HS is classified into six severity grades by counting the numbers of inflammatory nodules, abscesses and sinus tracts ²⁸. As a dynamic scoring tool hidradenitis suppurativa physician global assessment (HS-PGA) can be used for treatment evaluation, although especially in cases of extensive disease with multiple lesions the clinical correlation is limited ²⁹.

Hidradenitis suppurativa clinical response (HiSCR)

The Hidradenitis Suppurativa Clinical Response (HiSCR) is defined as a ≥ 50% reduction in inflammatory lesion count (abscesses + inflammatory nodules), and no increase in abscesses or draining fistulas when compared with baseline ³⁰. The Hidradenitis Suppurativa Clinical Response (HiSCR) is commonly used as a primary endpoint for treatment evaluation in recent studies and has been shown to be more responsive than hidradenitis suppurativa physician global assessment (HS-PGA) ³¹. It has been recently used to assess the effectiveness of treatment with biologics ³¹. According to the psoriasis area and severity index (PASI), HiSCR75- and HiSCR90- rates are further developed outcome parameters, assessed in current studies ³².

Severity assessment of hidradenitis suppurativa (SAHS) score

The severity assessment of hidradenitis suppurativa (SAHS) score was developed by Hessam et al. ³³ and is another clinical based scoring tool, that considers the number of affected body regions, fistulas and other inflammatory lesions as well as hidradenitis suppurativa-related pain and the number of new or flared boils in the last four weeks. The severity assessment of hidradenitis suppurativa (SAHS) score enables a dynamic evaluation of hidradenitis suppurativa severity and can also be used for treatment evaluation in clinical practice and studies ³⁴.

Cardiff Dermatology Life Quality Index (DLQI)

The Cardiff Dermatology Life Quality Index (DLQI) or DLQI questionnaire is often used to assess the degree of pain, the number of flares, and the impact on daily life in hidradenitis suppurativa.

International hidradenitis suppurativa severity score system (IHS4)

The international hidradenitis suppurativa severity score system (IHS4) represents a dynamic and easy-to-use scoring tool, and assesses disease severity by counting of inflammatory HS lesions (nodules 1 point, abscesses 2 points, sinus tracts 4 points) ³⁵. A total score of 3 or less signifies mild, 4–10 signifies moderate, and 11 or higher signifies severe disease ³⁵. Recently, a modified and dichotomous IHS4-55 score has been developed as a potential parameter for the measurement of treatment outcomes ³⁶.

Hidradenitis Suppurativa Burden of Disease (HSBOD)

A Hidradenitis Suppurativa Burden of Disease (HSBOD) tool has been described but is not fully validated ³⁷.

Hidradenitis suppurativa symptoms

Hidradenitis can affect a single or multiple areas in the armpits, neck, under the breasts, and inner thighs. Anogenital involvement most commonly affects the groin, mons pubis, vulva (in females), sides of the scrotum (in males), perineum, buttocks and perianal folds.

Some people with hidradenitis suppurativa experience only mild symptoms. The course of the disease is highly variable. Excess weight and being a smoker are associated with worse symptoms, but even people who are thin and don’t smoke can experience severe disease.

Signs of hidradenitis suppurativa include:

• Open double-headed comedones (also known as blackheads). Blackheads appear in small pitted areas of skin, often appearing in pairs.
• Painful firm papules and nodules (lumps). Hidradenitis suppurativa usually starts with a single, painful lump under the skin that persists for weeks or months. More bumps may form later, usually in areas where you have more sweat and oil glands or where the skin rubs together, such as the armpits, groin, buttocks and breasts.
• Pustules, fluctuant pseudocysts, and abscesses
• Leaking bumps or sores. Some bumps or sores get bigger, break open and drain pus with an odor.
• Tunnels draining sinuses linking inflammatory lesions. Over time, tunnels might form under the skin, connecting the lumps. These wounds heal very slowly, if at all, and drain blood and pus.
• Hypertrophic and atrophic scars.

Many patients with hidradenitis suppurativa also suffer from other skin disorders, including acne, hirsutism and psoriasis.

The severity and extent of hidradenitis suppurativa is recorded at assessment and when determining the impact of a treatment.

Table 1. Clinical phenotypes of hidradenitis suppurativa

Phenotype	Clinical features
Regular hidradenitis suppurativa	Most common form Recurrent inflammatory lesions in typical locations for at least 6 months
Frictional furuncle	Regular hidradenitis suppurativa plus multiple deep nodules and abscesses on sites exposed to enhanced friction (abdomen, thighs, buttocks)
Scarring folliculitis	Regular hidradenitis suppurativa plus pustules, cysts, superficial nodules, depressed cribriform scarring, and double-headed comedones Significant scarring
Conglobata	Cyst formation and acne conglobata lesions on the back and face
Syndromic	hidradenitis suppurativa in conjunction with syndromic features (PAPA, PASH, PAPASH)

[Source ⁵ ]

Hidradenitis suppurativa causes

The cause of hidradenitis suppurativa is unknown. It is thought that there is an exaggerated inflammatory response to the presence of bacteria trapped in obstructed hair follicles in the skin. Hidradenitis suppurativa isn’t exactly an “autoimmune disease,” but it is caused by over-activity of the immune system, which causes inflammation. Inflammation in the skin causes the mix of redness, swelling, itching, pain, sores, and drainage. People with hidradenitis suppurativa also have systemic inflammation that can cause joint pain or fatigue.

In some cases there does seem to be a genetic component. Bacteria seem to play some role, which is why antibiotics may be used in treatment. However, bacteria are not the primary cause of hidradenitis suppurativa. Other factors such as obesity, smoking and stress also play a role.

Contributing factors include:

• Friction from clothing and body folds
• Aberrant immune response to commensal bacteria
• Abnormal cutaneous or follicular microbiome
• Follicular occlusion
• Release of pro-inflammatory cytokines
• Inflammation causing rupture of the follicular wall and destroying apocrine glands and ducts
• Secondary bacterial infection
• Certain drugs.

Follicular Occlusion

Hidradenitis suppurativa was originally thought to be caused by a defect of the sweat gland, but this view has changed and it is now widely accepted to be a problem with the hair follicle. Build-up of keratin (a type of protein) within the hair follicle eventually plugs the hair follicle, causing further build up, and eventually the hair follicle ruptures and releases this material into the surrounding skin resulting in an intense inflammatory response ³⁸.

Bacteria

Sometimes bacteria can be isolated from hidradenitis suppurativa lesions, while other times cultures from hidradenitis suppurativa lesions are sterile (no bacteria found) ³⁹. Those affected by hidradenitis suppurativa frequently experience the characteristic symptoms of an infection, such as pain, tenderness, warmth, and purulent drainage. It may be reasonable to assume that since symptoms tend to improve after antibiotics, that hidradenitis suppurativa is caused primarily by bacteria, however this is not the case.

Biofilms

Recently, hidradenitis suppurativa has been described as a biofilm disease. When numerous bacteria secrete a sticky material known as a polysaccharide matrix and bind to a surface they now exist in what is known as a biofilm. When bacteria exist in a biofilm they become highly resistant to antibiotics. A recent study looking at biopsy samples (pieces of skin) from patients with hidradenitis suppurativa, demonstrated that biofilms were associated with chronic hidradenitis suppurativa ⁴⁰. Although, biofilms likely don’t form primarily, this may be the reason that hidradenitis suppurativa become very resistant to medical management as it becomes more severe.

Aberrant Immunity

Several markers of inflammation exist in the blood and skin and can be used to assess the inflammatory state of the body. Abnormal levels of these markers have been implicated in the development of several diseases and similarly found to be abnormal in hidradenitis suppurativa. Additional research is needed to determine the implications of these abnormal levels, but these findings have led to the use of biologic medications, such as adalimumab and infliximab for the treatment of hidradenitis suppurativa.

Diet

Nutrition is an understudied and notoriously difficult topic to research in medicine. The majority of evidence is based on individual experience with few published articles in the literature, but the impact of diet on hidradenitis suppurativa infiltrates through social media and online message boards with reports of improvement that ranges from minimal or no effect to complete resolution. In one survey study involving 47 patients who followed dairy free diets, no patients experienced disease progression and 83% improved to various degrees ⁴¹. In another study, 12 subjects underwent surgical excision followed by diet modification with no wheat or brewers yeast consumption with immediate disease stabilization during a 12 month period of follow up ⁴².

Additional research is needed in order to allow for comprehensive diet counseling. Some patients have reported improvement after exclusion of nightshades, simple carbohydrates, and dairy, but the impact of diet modification appears to be highly individual and should be discussed with your physician or nutritionist. Dieticians can provide individualized meal plans to make sure that you are getting all of the required nutrients.

Other Factors

Several other factors have been implicated in the development of hidradenitis suppurativa. Smoking is more common among people with hidradenitis suppurativa than among the general population, and the components of smoke are known to promote hyperkeratosis (causing follicular occlusion) and also increases inflammation potentially worsening hidradenitis suppurativa ⁴³. Mechanical factors caused by skin to skin contact and obesity may also contribute to the overall inflammatory state of hidradenitis suppurativa and the development or progression of hidradenitis suppurativa.

Lastly, hormones are potentially implicated in hidradenitis suppurativa. It is known that more women are affected by hidradenitis suppurativa than men and therefore a hormonal component has been hypothesized. Androgens, a type of hormone, can increase proliferation of the keratinocytes (skin cells), however the hormonal profile of patients with hidradenitis suppurativa is usually found to be normal ⁴³.

With numerous factors implicated in the development of hidradenitis suppurativa, it is clear that additional research is needed and the trigger for one patient may not be consistent across the entire population.

Hidradenitis suppurativa pathophysiology

The pathologic process of hidradenitis suppurativa begins when a defective hair follicle becomes occluded and ruptures, spilling its contents, including keratin and bacteria, into the surrounding dermis ⁴⁴. A chemotactic inflammatory response by surrounding neutrophils and lymphocytes can lead to abscess formation and subsequent destruction of the pilosebaceous unit and other adjacent structures ⁴⁴. Other possible contributors to pathology include abnormal antimicrobial peptides, abnormal secretion of apocrine glands, abnormal invaginations of the epidermis leading to tract formation, and deficient numbers of sebaceous glands ⁴⁵.

Immunological abnormalities have also been observed. The inflammatory cascade in hidradenitis suppurativa involves tumor necrosis factor (TNF)-α, interleukin (IL)-17 and interleukin-1β ⁴⁶. Recognizing hidradenitis suppurativa as an autoinflammatory disease, and not a result of infection, has important clinical implications including the need to address comorbidities such as visceral adiposity, insulin resistance and hormonal factors that can activate or exacerbate the underlying inflammatory mechanisms. About one-third of patients have a family history of hidradenitis suppurativa, and at least 23 potentially pathogenic gene sequence variants have been identified ⁴⁷. The microbiome in hidradenitis suppurativa differs significantly from healthy controls in both affected and non-affected skin ⁴⁸. Bacterial infection, when it does occur, is likely to be secondary to skin damage and underlying inflammation rather than a primary contributor to pathogenesis. Aspirate from an unruptured lesion typically yields a sterile culture. However, bacterial infection and colonization during the process can secondarily worsen hidradenitis suppurativa ⁴⁹.

Hidradenitis suppurativa prevention

It is difficult to prevent hidradenitis suppurativa or flare-ups caused by the disease. However, obesity and smoking are related to this condition. Quitting smoking and healthy eating and exercise may help to prevent the likelihood of hidradenitis suppurativa and limit flare-ups in those that have it. Try to lose weight if you are overweight. Also work to stay healthy by exercising and getting enough sleep.

Quit smoking

The link between tobacco smoking and hidradenitis suppurativa has been suggested in several studies. In a retrospective study, 92.2% of hidradenitis suppurativa patients were smokers and clinical remission was more often reported among non-smoking patients ⁵⁰. Moreover, Sartorius et al. ⁵¹ found lower disease severities, evaluated by the Sartorius Hidradenitis Suppurativa Score, in non-smokers compared to active smokers. At a molecular level, components of cigarette smoke have been demonstrated to further promote inflammation in hidradenitis suppurativa via inhibition of the already compromised Notch signaling, induction of proinflammatory cytokine expression and causing infundibular epithelia hyperplasia and hypercornification ⁵², ⁵³. Although clear evidence of tobacco as a trigger of hidradenitis suppurativa has not been found yet, patients should be encouraged to quit smoking ¹².

Weight reduction

Overweight and obesity are considered as frequent comorbidities of hidradenitis suppurativa. In two case–control studies an increment of the likelihood of hidradenitis suppurativa with every body mass index (BMI) unit increase was reported ⁵⁴. In another retrospective study ⁵⁵, the point prevalence of hidradenitis suppurativa was much higher in an obese study population compared to the general population. This may be explained by changes of the skin microbiome and increased friction of skin folds in obese patients ⁵⁶, ⁵⁷. However, evidence for improvement of hidradenitis suppurativa after body weight reduction is limited. A retrospective study reported a significant reduction of inflammatory activity in hidradenitis suppurativa patients undergoing bariatric surgery ⁵⁵, ⁵⁸. Moreover, obese hidradenitis suppurativa patients reported lower remission rates than non-obese hidradenitis suppurativa patients ⁵⁰.

Obese patients should be motivated to reduce their body weight by initiating physical activity and dietary changes ⁵⁹. In cases of severe obesity, bariatric surgery (weight-loss surgery) may be an option ⁶⁰.

Consider altering your diet. Hidradenitis symptoms might be worsened by diets that include dairy, red meat and foods with a high glycemic index. If your diet includes these foods, talk with a dietitian about the benefits of eliminating them.

Hidradenitis suppurativa complications

Persistent and severe hidradenitis suppurativa can cause complications, including:

• Infection. The affected area is susceptible to secondary infection, but the presence of pus is common in hidradenitis suppurativa and doesn’t necessarily mean infection.
• Scars and skin changes. The wounds may heal but leave ropelike scars or pitted skin.
• Restricted movement. Sores and scar tissue can cause limited or painful movement, especially when the disease affects the armpits or thighs.
• Skin cancer. Squamous cell carcinoma (SCC) has been reported with long-term hidradenitis suppurativa, particularly in people whose condition involves the perianal area.
• Swelling in the arms, legs or genitals (lymphedema). The most common sites for hidradenitis suppurativa also contain many lymph nodes. Scar tissue can interfere with the lymph drainage system, which can result in swelling in the arms, legs or genitals.
• Pyogenic granuloma. Pyogenic granulomas are small, raised, and red bumps on the skin. The bumps have a smooth surface and may be moist. They bleed easily because of the high number of blood vessels at the site. It is a benign (noncancerous) growth.
  • Granuloma is a histological term for a chronic inflammatory pattern characterized by the localized aggregation of histiocytes with or without other inflammatory cells, with or without necrosis, with or without vasculitis, with or without calcification, with or without foreign bodies. A granuloma may be due to infection, chronic inflammatory disease, or reaction to foreign material.
• Anemia of chronic disease.
• Psychological effects and social isolation. The location, drainage and odor of the sores can cause embarrassment and reluctance to go out in public, leading to anxiety or depression.

Hidradenitis suppurativa diagnosis

Hidradenitis suppurativa can be mistaken for an infection, an ingrown hair or other conditions. Many people live with undiagnosed hidradenitis suppurativa for years before receiving a correct diagnosis.

Your doctor will base a diagnosis on your signs and symptoms, skin appearance and medical history. You might be referred to a doctor who specializes in skin conditions (dermatologist), as hidradenitis suppurativa can be difficult to diagnose and requires specialized care.

No laboratory test is available to diagnose hidradenitis suppurativa. But if pus or drainage is present, your doctor might take a sample for testing in a lab.

Skin biopsy can help differentiate hidradenitis suppurativa from other diagnoses, such as cutaneous Crohn disease in those with perianal involvement.

The British Association of Dermatologists guidelines state that a triad of “typical lesions, in characteristic locations, with a recurrent pattern” is required for diagnosis ⁶¹:

• specifically, two typical lesions (defined as inflamed nodules or abscesses) in typical locations (armpits, submammary, abdominal fold, groin, genital, neck, or perianal areas) over six months or a history of at least five such lesions over a lifetime.

Hidradenitis suppurativa differential diagnoses

Differential diagnoses for hidradenitis suppurativa can include the following conditions.

• Staphylococcal skin infections, including abscesses, carbuncles, and furuncles.
• Cysts, like Bartholin cyst or epidermoid cyst.
• Cutaneous Crohn disease.
• Anogenital Crohn disease.
• Acne conglobata: Severe nodular acne on the back, chest, face and neck; predominantly affects men.
• Granuloma inguinale: Genital ulcerations and subcutaneous granulomas.
• Lymphogranuloma venerum: Unilateral groin adenopathy; proctocolitis in men who have sex with men.
• Pilonidal cyst: Sacrococcygeal cyst or abscess; occurs more often in men.

Hidradenitis suppurativa treatment

There is no cure for hidradenitis suppurativa and treatments aren’t one-size-fits-all ⁶². The overall goals of treatment is to treat existing lesions to minimize pain and drainage, decreasing the frequency of recurrence, and preventing disease progression. Since limited studies compare treatment regimens, most treatment algorithms are based on expert opinion and consensus ⁴⁴.

The type of treatment you receive depends on how severe your condition is. Treatment with medications, surgery or both can help control symptoms and prevent complications of hidradenitis suppurativa. Expect to have regular follow-up visits with your dermatologist. Some people might need the comprehensive care provided by a multidisciplinary health care team.

For mild cases, apply a warm compress to the affected area. Wash the area with anti-bacterial soap. Non-steroidal anti-inflammatory drugs (NSAIDs) can help reduce swelling and relieve pain.

More severe cases may require antibiotics. These can be topical (applied to your skin) or oral (taken by mouth). Antibiotics help prevent or treat infection. For some people, hidradenitis suppurativa gets worse over time. Scarring can occur in the affected area. These people may need surgery to remove the sores and scars. People who have surgery to remove hidradenitis suppurativa may get it again.

Talk with your doctor about the risks and benefits of the treatment options and how to develop an approach tailored to you.

Hidradenitis suppurativa management principles are outlined below:

In early uncomplicated HS diseases, topical antibiotics are the first-line treatment. Topical clindamycin has been the most effective ⁶³. Intralesional corticosteroids can reduce local inflammation, and partial de-roofing (punch debridement) of individual lesions can facilitate healing.

Treatment for Hurley Stage 2 and resistant Hurley Stage 1 involves oral antibiotics. Antibiotics in the tetracycline family have been the most effective ⁶⁴. If treatment failure persists, combination therapy with oral clindamycin plus rifampin is recommended ⁶⁵. Anti-androgenic hormonal therapy can also be helpful, including cyproterone acetate, oral contraceptives, spironolactone, and finasteride ⁶⁶. Oral retinoids have shown mixed responsiveness. While isotretinoin is most effective in acne, acitretin appears more effective in hidradenitis suppurativa ⁶⁷, ⁶⁸. Systemic steroids are effective for some individuals.

For Hurley stage 3 and resistant lower stages, tumor necrosis factor-alpha inhibitors are indicated. Adalimumab is the only FDA-approved medication to treat hidradenitis suppurativa ⁶⁹, ⁷⁰.

Surgery is often needed for Hurley stage 3 and involves a wide excision to include the lesions, tracts, and scars of an entire affected area. A combination of medical treatment and surgical excision is often the preferred approach. Other therapeutic options may include localized laser and pulsed light therapy, which help to disrupt the inflammatory process ⁷¹, ⁷², ⁷³.

Pain management is also critical. The pain of hidradenitis suppurativa is both inflammatory and non-inflammatory. Sources of pain can include scarring (causing tensile pain), keloids, abscesses, open ulcerations, sinus tracts, frictional pain, lymphedema, anal fissures, and arthritis. Depending on disease severity and type of pain, topical agents (lidocaine and anti-inflammatories), systemic nonsteroidal anti-inflammatories, acetaminophen, atypical anticonvulsants, including gabapentin or pregabalin, and serotonin-norepinephrine reuptake inhibitors may be beneficial. Duloxetine is especially helpful if there is comorbid depression ⁷⁴, ⁷⁵.

Regardless of the stage of the HS disease, treatment should include the management of comorbidities that contribute to the development of or worsening of the disease process. Individuals who are above ideal weight or who smoke have more severe disease progression, so counseling and help with weight loss and smoking cessation are important components of treatment ⁵³.

Treatment also involves avoidance of skin trauma. Eliminating tight and synthetic clothing, avoiding harsh products or cleaning tools (loofahs, washcloths, brushes), and avoiding adhesive dressings can be beneficial. Soft dressings with clear petroleum jelly or non-occlusive dressings can be used to prevent further irritation to draining lesions ⁷⁶.

A critically important but often overlooked aspect of treatment involves the psychosocial aspect of the disease. Quality of life is diminished in individuals with this condition because of the associated pain, drainage, odor, and sensitive affected areas. Patients may become socially isolated, have employment difficulties because of missed days of work when flares occur, and may have increased sexual or relationship dysfunction. Assurance that this condition is not contagious or the result of poor hygiene can be helpful. Counseling and support groups are often beneficial additions to treatment plans ⁷⁷.

Figure 6. Hidradenitis suppurativa treatment algorithm

Footnote: This treatment algorithm is used in the Henry Ford Dermatology Clinic, which provides care to more than 1,000 patients with HS. The algorithm is based on a combination of evidence-based research and provider experience.

Abbreivations: HS = hidradenitis suppurativa; BID = bis in die (twice daily); I/L = intralesional; IV = intravenously; Nd:YAG = neodymium-doped yttrium aluminum garnet; QD = quaque die (once daily)

[Source ⁷⁸]

General measures

Friction and moisture in the affected areas should be reduced as much as possible. Weight loss can greatly improve the condition if the patient is overweight ⁷⁹. Topical clindamycin may be helpful (or benzoyl peroxide 10% wash). Bleach baths and Hibiclens may have some benefit. Patients who smoke are twice as likely to develop hidradenitis suppurativa compared with nonsmokers, and smoking is associated with decreased response to treatment ⁸⁰, ⁸¹. Smokers should stop. Bacterial cultures may occasionally be done to rule out other causes or secondary infection.

Not smoking is associated with a better response to treatment ⁸¹ and a 15% weight reduction in obese patients improves disease severity ⁷⁹.

• Weight loss; follow an anti-inflammatory, low-sugar, low-grain, low-dairy diet (mainly plants). Not being at a healthy weight can worsen the symptoms of hidradenitis suppurativa. Talk with your doctor or a dietitian to develop a plan. Try to find activities that don’t irritate your skin.
• Smoking cessation: this can lead to improvement within a few months
• Wearing loose-fitting clothes to prevent friction, although evidence for this is limited
• Daily unfragranced antiperspirants
• If prone to secondary infection, wash with antiseptics or take bleach baths
• Daily skin care routine. Gently wash your body with a nonsoap cleanser. It can sometimes be helpful to use an antiseptic wash such as chlorhexidine 4% or benzoyl peroxide wash when showering. First try it once a week, then increase usage up to once a day if your skin tolerates it well. Pat dry. When washing, avoid using washcloths, loofahs or other such items on affected areas, as they can irritate skin. Don’t squeeze pimples and sores. And avoid shaving or using depilatory creams.
• Apply hydrogen peroxide solution or medical grade honey to reduce malodour
• Use peeling agents such as resorcinol 15% cream to de-roof nodules
• Apply simple dressings to draining sinuses
• Analgesics, such as paracetamol (acetaminophen), for pain control
• Seek help to manage anxiety and depression.

Medications for hidradenitis suppurativa

Medical management of hidradenitis suppurativa is difficult. Treatment is required long term. Effective options are listed below.

Your doctor might prescribe one or more of the following types of medications:

• Antibiotics applied to the skin. Mild symptoms might be managed with a topical antibiotic in liquid or gel form. For more-widespread disease, your doctor might prescribe antibiotic pills, such as doxycycline (Monodox), clindamycin (Cleocin), rifampin (Rimactane) or both. People with severe disease might need to take antibiotics for months.
• Steroid injections. Triamcinolone (Aristospan, Kenalog-10) injected into the sores might help reduce swelling and inflammation.
• Hormonal therapy. Hormone pills, such as estrogen-containing combined oral contraceptives (Estrace, Prefest), might be effective for people with mild hidradenitis suppurativa.
• Biologics. These drugs, usually administered by injection, alter the immune system in a way that disrupts the disease cycle and improves symptoms and signs of disease within weeks. Several of these drugs are approved for the treatment of moderate to severe hidradenitis suppurativa. Two of them are the tumor necrosis factor (TNF) inhibitors adalimumab (Humira) and infliximab (Remicade). Many other biologics are in clinical trials for hidradenitis suppurativa.
• Retinoids. Oral retinoids might be an option for some people with acnelike (acneiform) disease. These drugs are not recommended when you’re pregnant or breastfeeding or if you intend to become pregnant.
• Pain medication. If over-the-counter pain relievers don’t help, your doctor might prescribe a stronger pain medication or refer you to a pain clinic.

Antibiotics

• Topical clindamycin, with benzoyl peroxide to reduce bacterial resistance
• Short course of oral antibiotics for acute staphylococcal abscesses, eg flucloxacillin
• Oral antibiotics can be very helpful. A current study assessed the duration of antibiotic treatments in HS patients and showed that in the majority of oral antibiotic courses the duration of treatment was less than 12 weeks ⁸². Prolonged courses (minimum 3 months) of tetracycline, metronidazole, trimethoprim + sulphamethoxazole, fluoroquinolones, ertapenem or dapsone for their anti-inflammatory action.
  • Doxycycline 100 mg oral twice daily ongoing can be beneficial.
  • Dapsone, 5-200 mg/day, may be helpful.
• 6–12 week courses of the combination of clindamycin (or doxycycline) and rifampicin for severe disease.
  • Several experts recommend treatment for more severe, unstable hidradenitis suppurativa, with the combination of clindamycin 300 mg and rifampicin 300 mg both twice daily for 10 weeks. On the plus side, rifampicin acts against Clostridium difficule infections, decreasing the risk of colitis. On the down side, rifampicin can inactivate birth control pills. Also, it can turn bodily secretions orange, e.g. tears, sweat and urine.
  • Other options include amoxicillin with clavulanic acid or fluoroquinolones (e.g., ciprofloxacin). Trimethoprim with sulfamethoxazole may also be beneficial. One study showed Staphylococcus epidermidis, Proteus mirabilis, and Staphylococcus aureus to be the most common isolates ⁸³.

Recent guideline recommendations recognize tetracyclines as the first-line treatment for more widely spread hidradenitis suppurativa in Hurley stage 1 or 2 ¹². Established tetracycline antibiotics include tetracycline, doxycycline and minocycline ⁸⁴. A prospective study comparing the efficacy of the different tetracycline antibiotics tetracycline, doxycycline and lymecycline showed a reduction of hidradenitis suppurativa in all treatment groups with greatest response in the tetracycline group. Moreover, a reduction of pain, formation of new inflammatory lesions and an improvement of quality of life was observed in all treatment groups ⁸⁵.

An antibiotic combination therapy with clindamycin and rifampicin is recommended as first-line therapy for patients with Hurley stage 2 and moderate-to-severe disease and as second-line therapy for patients who do not respond on oral tetracycline treatment ¹², ⁸⁶. In an open-label prospective study with 56 patients, the combination of clindamycin and rifampicin showed an overall clinical response with reduction of hidradenitis suppurativa in 79.6% ⁸⁷. HSS50 (50% remission) was 37% and complete remission (HSS100) was observed in 13%. Side effects were observed in 55.6% of patients with diarrhea, abdominal pain and nausea being the most commonly reported ⁸⁷. This data is strengthened by several retrospective trials, which came to similar results; however, the majority of patients with initial complete remission relapsed after discontinuation of treatment ⁸⁸, ⁸⁹, ⁹⁰. However, due to the role of rifampicin as a potent inductor of the hepatic CYP system, metabolization of clindamycin is intensified within the combination therapy ⁹¹. In one study clindamycin blood levels were decreased by around 90% within two weeks after treatment initiation, raising the question of whether the observed response rates under combination antibiotic therapy may be traced to rifampicin alone ⁹². More research with prospective randomized controlled trials is needed to address this topic.

For more extensive disease with severe inflammation and widespread distribution of inflammatory lesions some intensified antibiotic treatment regimens have been described; however, up to now evidence is based on case report and retrospective analyses, and these therapies have not been evaluated in prospective trials.

Join-Lambert et al. ⁹³ described a broad-spectrum antibiotic combination therapy consisting of rifampicin, moxifloxacin and metronidazole leading to high rates of complete remissions, defined as clearance of all inflammatory lesions, especially in Hurley stage 1 or 2 patients.

Ertapenem, another broad-spectrum antibiotic, showed rapid improvement in treatment-refractory cases of hidradenitis suppurativa as a rescue therapy ⁹⁴. In a retrospective pilot study with 30 patients, a 6 week course of ertapenem led to a significant and sustained improvement of disease severity, assessed with the Sartorius score ⁹⁵. Through its rapid clinical improvement, ertapenem may be initiated in severe hidradenitis suppurativa as neoadjuvant therapy for bridging to surgery or other maintenance therapies ⁹⁴, ⁹⁶, ⁹⁷.

Antiandrogens

Clinical observations in female hidradenitis suppurativa patients with premenstrual flares and cyclic alterations of inflammation activity led to the suggestion that hormonal alterations may influence the course of hidradenitis suppurativa ⁹⁸. Moreover, hidradenitis suppurativa is associated with endocrine disorders such as polycystic ovary syndrome (PCOS) and metabolic syndrome ⁹⁹, ¹⁰⁰. However, the role of hormonal influences on the pathogenesis of hidradenitis suppurativa is still unclear ¹⁰¹. Most data regarding antiandrogenic treatment approaches for hidradenitis suppurativa are based on retrospective analyses, and case reports and prospective trials are rare.

• Long-term oral contraceptive pill; antiandrogenic progesterones drospirenone or cyproterone acetate (CPA) may be more effective than standard combined pills. These are more suitable than progesterone-only pills or devices. Successful disease control with an antiandrogenic therapy containing ethinylestradiol and cyproteronacetate has been described in a case series ¹⁰². In a double-blind controlled cross-over trial comparing two contraceptive regimens containing ethinylestradiol and norgestrel or cyproterone acetate, both treatments produced substantial improvement of disease activity; however, there was no significant difference ¹⁰³. In a retrospective study, Kraft et al. ¹⁰⁴ compared an antiandrogen treatment approach with antibiotic therapies in 66 female hidradenitis suppurativa patients and found significantly superior response rates, 55% vs. 26%, suggesting that antiandrogen therapy should be considered for all women presenting with hidradenitis suppurativa. Moreover, the authors concluded that female hidradenitis suppurativa patients should be investigated for underlying PCOS and insulin resistance ¹⁰⁴.
• Spironolactone. Spironolactone is a potassium-sparing diuretic with antiandrogen properties due to the inhibition of mineralocorticoid receptors ¹⁰⁵. Some women experience a premenstrual flare. For them, antiandrogen therapy (e.g., spironolactone) may be helpful. In several retrospective analyses of female hidradenitis suppurativa patients, spironolactone treatment led to a significant reduction of pain and inflammatory lesions, and improved quality of life ¹⁰⁶, ¹⁰⁷, ¹⁰⁸.
• The antidiabetic agent metformin reduces insulin resistance by improving peripheral insulin sensitivity and may have some antiandrogen properties ⁹⁷. In several retrospective trials and case reports, metformin showed promising clinical response rates and thus may contribute to disease control in hidradenitis suppurativa as an adjunctive treatment option ¹⁰⁹, ¹¹⁰, ¹¹¹.
• Finasteride has been used in children with hidradenitis suppurativa with success ¹¹², ¹¹³. Three female patients, ages six, seven, and 15 who had failed standard therapy including isotretinoin, were treated with finasteride 1.25-10 mg/day for up to six years. Adjunctive birth control pills were given if the patient was a menstruating female. Treatment resulted in decreased frequency and severity of disease flares with no significant adverse effects.
• Response takes 6 months or longer.

Immunomodulatory treatments for severe disease

• Intralesional corticosteroids into nodules (e.g., Triamcinolone 5-10 mg/mL) can give the patient great relief. In one study utilizing triamcinolone 10 mg/mL ¹¹⁴, pain was reduced after 1 day and signs of inflammation after 7 days.
• Systemic corticosteroids short-term for flares. In one report ¹¹⁵, 13 patients were treated initially with prednisone 10 mg/day (ultimate dose varied from 5-15 mg/day). This was given in addition to existing therapy when that was not sufficient for control (e.g., acitretin, adalimumab, dapsone, clindamycin, doxycycline). All patients received calcium (1200 mg/day) and vitamin D (1000 IU/day) and monthly glucose monitoring. Overall, 11/13 patients showed a clinical response with the addition of low-dose prednisone. Side effects were minor and included hyperglycemia, sleep disturbance, and mild psychomotor agitation.
• Methotrexate, cyclosporin, and azathioprine. A few case reports highlight the benefit of cyclosporin. One patient did well on long-term cyclosporin 5 mg/kg/day, then 3 mg/kg/day ¹¹⁶.
• If oral and topical antibiotics plus general measures are not sufficient, a biologic agent is often added. TNF-α inhibitors adalimumab and infliximab, used in higher dose than required for psoriasis, are the most successful treatments to date. Note that paradoxically, they may sometimes induce new-onset hidradenitis suppurativa
• Other biologics are under investigation, such as the IL-1β antagonist, canakinumab

Adalimumab

Adalimumab, a fully human IgG1 monoclonal antibody specific for TNFα, is FDA-approved for moderate to severe hidradenitis suppurativa in adults and adolescent patients ≥12 years that is resistant to conventional therapies, but the dosing is weekly (for psoriasis, it is every other week) ¹¹⁷. Adalimumab can be administered in subcutaneous injections in two treatment regimens with 40 mg every week or 80 mg every other week after an initial loading dose ¹². The therapy is usually well tolerated with injection side reactions being the most common side effects and large meta-analyses have shown non-significant safety issues compared to placebo ¹¹⁸
. In very rare cases malignancies (especially lymphomas) have been reported under therapy ¹¹⁹, ¹²⁰.

In one randomized double blind controlled trial, adalimumab weekly was superior to both adalimumab every other week and placebo ¹²¹.

Other biologic agents

In recent years, adalimumab biosimilars have become a frequently used alternative to the adalimumab originator agent and currently six adalimumab biosimilars are approved by the FDA and European Medicines Agency ¹²².

Infliximab is a chimeric mouse/human IgG1 monoclonal antibody with high affinity to soluble and transmembrane bound TNF⍺. A recent metanalysis calculated a pooled response rate for infliximab of 83% in patients with moderate-to-severe hidradenitis suppurativa and described a low toxicity with a rate of 2.9% for severe adverse events ¹²³. In a phase 2 placebo-controlled crossover study, 57% of patients under infliximab treatment reached a reduction of the Hidradenitis Suppurativa Severity index (HSSI) of >50% compared to 5% in the placebo group. Additionally, improvements in pain intensity and quality of life were observed with concomitant reduction in clinical markers of inflammation ¹²⁴. In another prospective trial, sustained treatment responses were observed in hidradenitis suppurativa patients after a single course of infliximab ¹²⁵. Overall, infliximab is a promising treatment option for hidradenitis suppurativa; however, larger prospective randomized trials are needed to investigate its efficacy compared to other biologic therapies ¹²³.

Etanercept, a fusion protein consisting of the extracellular ligand-binding domain of the 75 kDa TNF⍺ receptor and the Fc portion of human IgG1, inhibits TNF⍺ signaling through competitive binding of its ligand ¹²⁶. In a small prospective placebo-controlled phase 2 trial, etanercept showed no significant efficacy compared to placebo ¹²⁷.

In comparing all the biologic agents, one review put the percent responders at 89% infliximab, 79% adalimumab, and 56% for etanercept ¹²⁸. Other TNF⍺ inhibitors like golimumab and certolizumab pegol showed inconstant response rates, and evidence is limited on several case reports and small retrospective studies ¹²⁹, ¹³⁰, ¹³¹. Ustekinumab has also been used in a few patients.

Infliximab seems to be most effective but in one study 22% experienced serious adverse events, the most common being infusion reactions, and one patient died of pneumococcal sepsis. In one study ¹³² of 11 patients with severe hidradenitis suppurativa unresponsive to more than three prior therapies, infliximab 5 mg/kg every four weeks was given. Nine of the 11 patients remain well-controlled on this regimen.

Canakinumab is a human IgGk monoclonal antibody targeting IL-1B. It was beneficial in two patients with severe hidradenitis suppurativa ¹³³.

Interleukin-17

In recent years, interleukin 17 (IL-17) has emerged as a major player in various autoimmune and inflammatory skin disorders, and its proinflammatory isoforms IL-17A, IL-17C and IL-17F are presumed as key cytokines in hidradenitis suppurativa ¹³⁴, ¹³⁵. IL-17A and IL-17F are mainly produced by T-helper 17 cells (TH17) and play a major role in control of many fungal and bacterial infections, while IL-17C is released by epithelial cells like keratinocytes, and promotes further inflammation by mediation of the production of other inflammatory molecules and further enhancing the inflammation cascade through stimulation of IL-17A and IL-17F production in TH17-cells as a feed forward loop ¹³⁶.

The first evidence for the role of IL-17 in hidradenitis suppurativa was reported by Schlapbach et al. ¹³⁷, who found a 30-fold increased expression of IL-17A in hidradenitis suppurativa lesions compared to healthy skin. Another study confirmed these findings and identified a dysregulated cytokine milieu in perilesional skin, suggesting that subclinical inflammation may be present in hidradenitis suppurativa skin prior to the formation of active lesions ¹³⁸. Moreover, Navrazhina et al. ¹³⁹ found significantly increased expressions of the proinflammatory IL-17 isoforms A, C and F in lesional, perilesional and even unaffected skin of hidradenitis suppurativa patients compared to healthy individuals. Given these accumulating findings pointing toward a key role of IL-17 signaling in the pathogenesis of hidradenitis suppurativa, targeting the IL-17 pathway seems like a promising treatment approach. However, as hidradenitis suppurativa can be associated with inflammatory bowel disease, it should be kept in mind that paradoxical exacerbations of pre-existing inflammatory bowel disease have been reported under anti-IL17 treatment ¹⁰⁰, ¹⁴⁰.

Secukinumab is a recombinant human monoclonal IgG1κ antibody that selectively targets IL-17A and blocks its interaction with the IL-17 receptor ¹⁴¹. In an open-label pilot study with nine patients, 78% reached HiSCR after 24 weeks of treatment with secukinumab 300 mg every 4 weeks ¹⁴². Another open-label trial with 20 enrolled patients tested two dose levels of secukinumab (300 mg every 2 or 4 weeks after an initial loading dose) and observed pooled hidradenitis suppurativa clinical response (HiSCR) rates of 70%. Interestingly, clinical responses were also observed in patients with failure to prior anti-TNF⍺ treatment ¹⁴³.

Recently, the first results of two randomized, placebo-controlled, multicenter phase 3 trials ¹⁴⁴ evaluating the efficacy of secukinumab in two dose regimens (every 2 weeks or every 4 weeks) have been presented. After 16 weeks, the primary endpoint was reached in both studies for the every 2 weeks regimen and in one for the every 4 weeks regimen, demonstrating the superiority of secukinumab over placebo in patients with moderate-to-severe hidradenitis suppurativa (HiSCR rates: 45% vs. 33.7% (study 1) and 42.3% vs. 31.2% (study 2) for secukinumab 300 mg every 2 weeks, and 41.8% vs. 33.7% (study 1) and 46.1% vs. 31.2% (study 2) for secukinumab every 4 weeks). In both treatment groups secukinumab significantly reduced inflammatory lesions and pain, and improved patients’ quality of life ¹⁴⁴, ¹⁴⁵.

Bimekizumab is another humanized IgG1κ monoclonal antibody, targeting IL-17A and IL-17F. In a recent double-blind, placebo-controlled, phase 2 clinical trial ¹⁴⁶ 90 patients were randomized to receive bimekizumab (640 mg at week 0, 320 mg every 2 weeks), adalimumab (160 mg at week 0, 80 mg at week 2 and 40 mg every week for weeks 4–10) or placebo. Hidradenitis suppurativa clinical response (HiSCR) was reached in 57.3% of the bimekizumab group compared to 26.1% in the placebo arm. Moreover, 46% of the patients under bimekizumab achieved HiSCR75 and 32% achieved HiSCR90, compared to 10% and 0% in the placebo group, respectively ³². These promising results led to the initiation of three placebo-controlled phase 3 studies, which are currently ongoing  – NCT04901195 ¹⁴⁷, NCT04242498 ¹⁴⁸ and NCT04242446 ¹⁴⁹.

Nanobodies represent a novel innovative class of antibody-derived targeted therapies. Consisting of one or more domains based on the small antigen binding variable regions of heavy chain antibodies, they are much smaller compared to conventional monoclonal antibodies, facilitating their tissue penetration ¹⁵⁰. Moreover, several nanobodies can be linked to obtain multi-specific molecules ¹⁵¹. Sonelokimab is a trivalent nanobody containing three domains with specificity for IL-17A, IL-17F and human serum albumin, and has already showed clinical efficacy in the treatment of plaque psoriasis in a recent phase 2 study ¹⁵². An ongoing randomized placebo-controlled trial evaluates the efficacy of sonelokimab in patients with moderate-to-severe hidradenitis suppurativa (ClinicalTrials.gov NCT05322473) ¹⁵³.

Izokibep, another small, molecular, antibody-mimetic IL-17A inhibitor has recently shown significant clinical responses in patients with psoriatic arthritis and is currently in a placebo-controlled phase 2 trial in hidradenitis suppurativa ¹⁵⁴.

JAK/STAT Inhibitors

The Janus kinase and signal transducers and activators of transcription (JAK/STAT) pathway represents a rapid membrane-to-nucleus cell signaling module, which regulates the expression of various critical mediators of cancer and inflammation ¹⁵⁵. Inhibitors of the JAK/STAT pathway are a potential approach for future treatment of hidradenitis suppurativa, as they enable the simultaneous modulation of expression of different cytokines that are involved in the complex inflammatory process of hidradenitis suppurativa ¹⁵⁶.

The efficacy of the JAK1 inhibitor INCB054707 was evaluated in two phase 2 studies (ClinicalTrials.gov NCT03569371, NCT03607487) in patients with moderate-to-severe hidradenitis suppurativa ¹⁵⁷. Janus Kinase 1 Inhibitor INCB054707 was well tolerated and clinical improvement of disease was observed; however, the effect was only significant in the high-dose group with 90 mg (HiSCR 88% vs. 57% placebo) ¹⁵⁷.

Upadacitinib is a second-generation JAK inhibitor with selectivity for JAK1. In a retrospective cohort study 75% and 100% of patients treated with upadacitinib reached hidradenitis suppurativa clinical response (HiSCR) after 4 and 12 weeks of treatment, respectively. HiSCR75 rates were 30% and 95% after 4 weeks and 12 weeks ¹⁵⁸. These promising observations led to the initiation of a phase II randomized controlled trial with results unpublished (ClinicalTrials.gov NCT04430855) [182].

A phase 2 trial for topical treatment of early-stage hidradenitis suppurativa lesions with the JAK1/JAK2 inhibitor ruxolitinib is currently ongoing (ClinicalTrials.gov NCT04414514) ¹⁵⁹.

Other medical treatments

• Metformin in patients with insulin resistance. Metformin ¹⁶⁰ and more recently with glucagon-like peptide-1 agonist liraglutide ¹⁶¹ have shown benefit in difficult to control hidradenitis suppurativa. In overweight or obese patients with recalcitrant disease, these agents may be beneficial.
• Acitretin (unsuitable for females of childbearing potential). Acitretin has been evaluated for the treatment of moderate-to-severe hidradenitis suppurativa in a small prospective trial with 17 patients and showed an overall response rate of 47%; however, another 47% of patients dropped out due to lack of efficacy or adverse events ¹⁶². Acitretin in a retrospective study of 12 patients, acitretin showed promising results with all treated patients achieving clinical remission and reduction of pain ⁶⁸. The average dose was 0.67 mg/kg/day. Nine patients achieved marked or complete remission after one course. The improvement generally started within two months and further improvement was achieved within the first six months of therapy. Another recent retrospective cohort study reported significant clinical responses under acitretin treatment and identified the follicular hidradenitis suppurativa phenotype, a history of follicular plugging diseases and a family history of hidradenitis suppurativa as potential predictive markers for treatment response ¹⁶³.
• Isotretinoin has only shown limited efficacy for treatment of hidradenitis suppurativa and several retrospective studies reported treatment response rates between 16.1% and 35.9% ¹⁶⁴, ¹⁶⁵, ¹⁶⁶. Clinical exacerbations and occurrence of new flares of hidradenitis suppurativa have been reported after initiation of isotretinoin in various cases, which could be explained by the further reduction of the size and action of sebaceous glands due to isotretinoin therapy ¹⁶⁷, ¹⁶⁸.
• Colchicine and minocycline. This prospective study or case series (n = 20) indicates that the combination of the anti-inflammatory actions of colchicine and minocycline is effective in disease control in hidradenitis suppurativa ¹⁶⁹.
• Zinc salts (zinc gluconate) show anti-inflammatory effects in hidradenitis suppurativa, probably through inhibition of chemotaxis of neutrophil granulocytes, modulation of cytokine expression and anti-androgen properties ¹⁷⁰. In hidradenitis suppurativa, a high-dose therapy with 90 mg zinc gluconate per day in gradual dose escalation can be considered as a maintenance therapy for limited disease ¹². In several small studies, zinc gluconate showed promising results in mild-to-moderate hidradenitis suppurativa ¹⁷¹, ¹⁷², ¹⁷³. As zinc competes with copper in gastrointestinal resorption, long-term use of high doses of zinc may cause hypocupremia and anemia; thus, routine monitoring of copper levels and hemoglobin is recommended ¹⁷⁴. Gastrointestinal discomfort is a frequent reported side effect.
• Anakinra (IL-1 receptor antagonist) showed benefit in a study of five patients ¹⁷⁵. Another study randomized 20 patients to receive either anakinra or placebo for 12 weeks. The disease activity score was decreased at the end of treatment in 20% (2 of 10) of the placebo arm compared with 67% (6 of 9) of the anakinra arm ¹⁷⁶. Several case reports described inconstant clinical responses with partial improvements and failure of anakinra treatment ¹⁷⁷, ¹⁷⁸, ¹⁷⁹, ¹⁸⁰, ¹⁸¹.
• Bermekimab (also known as MABp1) is a recombinant monoclonal antibody that neutralizes IL-1⍺. In a prospective randomized controlled phase 2 trial, patients with moderate-to-severe hidradenitis suppurativa, that were not eligible for or failed a prior anti-TNF⍺ treatment, showed significant clinical responses with hidradenitis suppurativa clinical response (HiSCR) rates of 60% compared to 10% in the placebo group after 12 weeks ¹⁸². Patients who were initially randomized to the placebo group were allowed to continue in an open-label extension study and 75% showed clinical response (HiSCR) after 12 weeks of bermekimab treatment ¹⁸³. In another phase 2 study with 42 patients with moderate-to-severe hidradenitis suppurativa who were naïve to or had failed prior anti-TNF⍺ therapy, significant clinical responses were observed in both groups with HiSCR rates of 63% in the TNF⍺-failure group and 61% in the TNF⍺-naïve group, respectively, qualifying bermekimab as potential alternative treatment option for non-responders to anti-TNF⍺ ¹⁸⁴. A randomized placebo and active-comparator-controlled phase IIa/b trial evaluating the efficacy of bermekimab compared to placebo and adalimumab is currently ongoing (ClinicalTrials.gov NCT04988308) ¹⁸⁵.
• Medical management of anxiety and depression
• Nd:YAG laser hair removal. For axillary involvement, laser hair removal can be quite helpful. In addition, the 1064 nm nd:YAG laser has been used ongoing with benefit in uncontrolled studies ¹⁸⁶.

Hidradenitis suppurativa surgery

If medical therapy is not successful and the patient desires a “cure,” a surgical approach may be considered ¹⁸⁷. This usually consists of excision of all diseased tissue in the area. Limited excisions usually result in recurrence adjacent to the scar. In one study, limited excision of diseased tissue had a 43% recurrence rate whereas radical excision had only a 27% recurrence rate ¹⁸⁸. With appropriate patient selection, patient satisfaction with surgery is high ¹⁸⁹.

There are both localized and extensive surgical interventions. Although there is no consensus on the best approach, procedures are carried out based on disease severity and location, with the overall goal of removing lesional tissue and sparing healthy skin to optimize outcomes.

• Incision and drainage of acute abscesses. In acute cases with abscess formation, incision and drainage can be considered for acute pain relief, although this is only a symptom treatment with nearly 100% recurrence rates ¹⁹⁰. As deroofing can be performed approximately in the same amount of time, coming with higher recurrence-free rates, experts recommend deroofing over incision and drainage ¹¹.
• Deroofing. Deroofing describes a superficial removal of the skin covering an inflammatory nodule or a solitary sinus tract, exposing the partially epithelialized basis of the lesion with subsequently curettage of the gelatinous granulation tissue ¹⁹¹. The advantages of this procedure are its simplicity, cost-effectiveness and that it can be performed under local anesthesia, qualifying this method for treatment of inflammatory nodules, abscesses and solitary sinus tracts ¹⁹². In a small study with 44 patients undergoing deroofing of axillary or inguinal hidradenitis suppurativa lesions, 87% were recurrence-free in the follow-up interval of five years ¹⁹³.
• Skin-tissue-sparing excision with electrosurgical peeling (STEEP). The skin-tissue-sparing excision with electrosurgical peeling (STEEP) method represents a similar surgical approach and was first described by Blok et al. ¹⁹⁴. Here, successive tangential excisions are performed with an electrosurgical wire loop until the epithelialized bottom of the lesion is exposed, whilst saving as much healthy tissue as possible. Although this surgical technique is associated with a short time to wound healing and a low risk of wound contraction, no long-term outcomes are reported and evidence is limited on small case series ¹⁹⁵.
• Excision. Excision describes the complete removal of the affected tissue and represents a more invasive surgical approach in hidradenitis suppurativa. Depending on the extent of resection experts differentiate between limited, wide and radical excisions; however, there are no generally accepted definitions and distinctions between surgical interventions are blurred ¹⁹². Van Rappard et al. ¹⁹⁶ defined limited or localized excisions as the complete excision of the affected tissue, beyond the borders of activity, leaving clear margins. Limited excisions represent a low-invasive surgical approach, appropriate for the treatment of recurrent inflammatory nodules or abscesses and solitary sinus tracts in Hurley stage 1 or 2, and can be performed under local anesthesia in an outpatient setting ¹⁹⁶. Wide excisions are understood as the surgical removal of the affected tissue including the surrounding subcutaneous fat and perilesional skin with an additional resection margin ¹⁹⁷. In severe cases, radical excisions with the complete removal of the entire hair bearing area including the subcutaneous fat to the underlying fascia of an affected body region can be performed ¹². Nesmith et al. ¹⁹⁸ suggested an additional superficial lymphadenectomy for a further reduction of the risk of recurrence. Although there are no accepted definitions for surgical techniques and recurrence in hidradenitis suppurativa, it is generally considered that more extensive resections are associated with a lower risk of recurrence ¹⁹⁹.
  • In cases of extensive disease with multiple or confluent sinus tracts, preoperative MRI- or ultrasound-based imaging methods or an intraoperative use of dye mapping methods, such as methyl violet or iodine starch, can contribute to an improved visualization of the surgical site ²⁰⁰.
• Laser ablation of nodules, abscesses and sinuses. Various laser and light-based therapies have gained increasing attention as a possible treatment modality for hidradenitis suppurativa ²⁰¹.
  • Carbon dioxide (CO2) laser acts at a wavelength of 10,600 nm and can be used for tissue ablation in different modalities, namely vaporization and excision. CO2-laser vaporization represents a tissue-sparing treatment option, that aims on a focal destruction of chronic or inflammatory hidradenitis suppurativa lesions, and was first described by Dalrymple et al. for the treatment of sinus tracts ²⁰². In two case series, Lapins et al. ²⁰³, ²⁰⁴ reported low local recurrence rates and satisfactory postoperative outcomes after a stepwise horizontal CO2-laser evaporation of sinus tracts in Hurley stage 2 patients. Another retrospective study showed similar outcomes, but described local recurrence rates of 29% ²⁰⁵. A retrospective study evaluated the outcomes of 185 treated sites of 61 hidradenitis suppurativa patients after CO2-laser excision or marsupialization with secondary intention healing, and demonstrated fast healing rates and a local recurrence rate of 1% ²⁰⁶. Summarizing, CO2-laser interventions are tissue-sparing treatment options for hidradenitis suppurativa lesions with fast postoperative wound healing and low complication rates. As they can be performed under local anesthesia and wounds are generally allowed to heal by secondary intention, these treatments seem suitable for an outpatient setting ²⁰¹.
  • Neodymium-doped yttrium aluminum garnet (Nd:YAG) lasers act as non-ablative lasers at a wavelength of 1064 nm and enable a selective photothermolysis of hair follicles ²⁰⁷. Their efficacy has been demonstrated in several randomized controlled studies, leading to significant clinical improvements and prevention of new inflammatory lesions in the treated body areas of hidradenitis suppurativa patients ²⁰⁸, ²⁰⁹. In a histopathologic study, an initially increased perifollicular inflammation, observed after 1 week of treatment, was followed by a fibrotic tissue transformation after 4–8 weeks of treatment ²¹⁰. Axillary and inguinal areas have been shown to be more responsive to Nd:YAG-laser treatment compared to inframammary and gluteal regions ²⁰⁹. Moreover, combination treatments consisting of Nd:YAG-laser-mediated hair follicle destruction and CO2-laser ablation of hidradenitis suppurativa lesions have shown superior clinical responses ²¹¹.

Many approaches exist to manage hidradenitis suppurativa, including local destruction, incision and drainage, standard unroofing, and wide excision techniques ²¹². Local destruction is used to ablate hidradenitis suppurativa lesions and may be carried out with electrosurgery, cryotherapy, or laser removal. Incision and drainage may be used for decompression in acute episodes of unbearable pain. However, incision and drainage does not assist in the long-term resolution of disease, as the inflamed tissue remains and infection is almost certain to recur ²¹³. Unroofing techniques are effective for both small and large lesional units and are carried out by opening the surface of all connected abscesses and tracts within an hidradenitis suppurativa lesion. The contents are removed by curettage, often leaving the site open to heal by secondary intention ²¹⁴. Unroofing techniques are preferred for Hurley stage I/II, whereas skin-tissue-saving excision with electrosurgical peeling (STEEP) is preferred for Hurley stage II/III. Skin-tissue-saving excision with electrosurgical peeling (STEEP) similarly removes diseased, fibrotic tissue via electrosurgical loop while sparing healthy skin to decrease sequelae following the surgical procedure ²¹⁵. Lesions that cannot be unroofed may be excised, which includes the removal of the entire diseased area up to the margins of normal-appearing subcutaneous tissue ²¹².

The best surgical approach for long-term outcomes is controversial and is dependent on the patient’s disease severity and location of the lesions. A recent systematic review and meta-analysis assessed for recurrence rates with varying methods of surgical management. The lowest rates of recurrence occurred following wide excision therapy when compared to local excision and deroofing procedures. This study also indicated that recurrence rates were lowest with skin grafts and skin flaps compared to primary closure, although this was limited by retrospective analysis and lack of randomization of closures ²¹⁶. Wide excision followed by secondary intention healing was also shown to be functional and aesthetically acceptable to patients ²¹⁷. Bias may exist in the discrepancy between recurrence rates and type of closure owing to the fact that primary closure is possible only with smaller wound sizes compared to larger excisions that simply cannot be closed by primary intention. Although this has not been formally assessed, the size of the wound may play a role.

The use of lasers in hidradenitis suppurativa management has gained recent popularity. The 1064 nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser appears to be an effective, novel modality in hidradenitis suppurativa management. After a series of treatments, two trials reported decreases in hidradenitis suppurativa-associated inflammation, scarring, and fibrosis, indicating successful, selective photothermolysis to manage the disease ²¹⁸. It is best used in recalcitrant Hurley stage 1 and 2 patients.

Another type of laser used in the treatment of hidradenitis suppurativa is the carbon dioxide (CO2) laser, which is used to excise hidradenitis suppurativa lesions and ablate pathologic tissues. CO2 laser has been used since the late 1980s for hidradenitis suppurativa, although it is now increasing in popularity. Laser excision followed by marsupialization has been shown to be effective for the management of persistent or late-stage cases of hidradenitis suppurativa, with overall patient satisfaction in post-operative quality of life and pain measures ²¹⁹. Additionally, a retrospective study (n = 58) of CO 2 laser evaporation techniques reported a 29% recurrence rate of disease within 12.2 months of the procedure (noted around the borders of treated regions), while 95% of patients reported some or great improvement in disease status ²²⁰. A reported complication of CO2 excision is scar contracture, restricted range of motion, and delayed wound healing. Nicholson et al. determined that fractional CO 2 therapy could be a helpful adjunct in these cases ²²¹.

Psychological support

Due to its chronic recurrent course with painful lesions and purulent discharge, hidradenitis suppurativa has a pronounced impact on the patient’s life and professional support may be required. Esmann et al. ²²² described an increased risk of social isolation due to shame and fear of stigmatization. Quality of life can be severely affected by hidradenitis suppurativa and hidradenitis suppurativa has been observed as one of the most distressing conditions in dermatology ²²³, ²²⁴. Hidradenitis suppurativa is associated with an increased risk for distinct psychiatric disorders including depression, anxiety disorders and substance-related abuse ²²⁵. Moreover, a meta-analysis found a more than two-fold increased risk for suicide in hidradenitis suppurativa patients ²²⁵. For this reason, physicians treating hidradenitis suppurativa patients should perform a screening for psychiatric comorbidities and initiate psychiatric referral if necessary.

Hidradenitis suppurativa prognosis

The way hidradenitis suppurativa develops in individual people is not very well understood and there is no cure for this condition but is generally controllable with one or more of the above treatments. Hidradenitis suppurativa prognosis is variable and not all cases progress to the most severe form of the disease. However, the prognosis worsens if there is a delay in diagnosis and treatment during the early stages of the disease and if comorbid conditions of smoking and obesity (if present) are not addressed and improved ²²⁶.

Treatment and control of the inflammation is important to minimize HS skin disease from progressing and scarring.

Weight gain and smoking worsen hidradenitis suppurativa and should be avoided. Hidradenitis suppurativa is generally most active during teenage years and young adulthood. It often, but not always, improves as the person gets older.

Hidradenitis suppurativa complications include both physical and psychological conditions ²²⁷. Physically, recurrence of lesions leading to abscesses, tracts, and scarring can cause chronic pain, limb contractures, and impaired mobility. Lymphatic obstruction can lead to peripheral lymphedema. Long-term effects of chronic inflammation can also occur, including anemia, hyperproteinemia, and amyloidosis, as well as axial and peripheral arthropathy. In rare cases, a superimposed infection can lead to systemic illness of variable severity. Squamous cell carcinoma can occur in the setting of hidradenitis suppurativa, sometimes occurring up to 30 years after diagnosis. There is an associated increase in buccal and hepatocellular cancer based on observational data.

Hidradenitis suppurativa can have a psychological impact as well. Combining chronic pain with drainage, odor, and deformity of skin appearance can lead to depression, social isolation, decreased relationship satisfaction, sexual dysfunction, reduced work productivity, and even suicide in extreme cases ²²⁷.

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