Hidradenitis suppurativa (HS), sometimes known as acne inversa or Verneuil's disease, is a long-term dermatological condition characterized by the occurrence of inflamed and swollen lumps. These are typically painful and break open, releasing fluid or pus. The areas most commonly affected are the underarms, under the breasts, perineum, buttocks, and the groin. Scar tissue remains after healing. HS may significantly limit many everyday activities, for instance, walking, hugging, moving, and sitting down. Sitting disability may occur in patients with lesions in sacral, gluteal, perineal, femoral, groin or genital regions; and prolonged periods of sitting down can also worsen the condition of the skin of these patients. The exact cause is usually unclear, but believed to involve a combination of genetic and environmental factors. About a third of people with the disease have an affected family member. Other risk factors include obesity and smoking. The condition is not caused by an infection, poor hygiene, or the use of deodorant. Instead, it is believed to be caused by hair follicles being obstructed, with the nearby apocrine sweat glands being strongly implicated in this obstruction. The sweat glands themselves may or may not be inflamed. Diagnosis is based on the symptoms. No cure is known, though surgical excision with wet-to-dry dressings, proper wound care, and warm baths or showering with a pulse-jet shower may be used in those with mild disease. Cutting open the lesions to allow them to drain does not result in significant benefit. While antibiotics are commonly used, evidence for their use is poor. Immunosuppressive medication may also be tried. In those with more severe disease, laser therapy or surgery to remove the affected skin may be viable. Rarely, a skin lesion may develop into skin cancer. If mild cases of HS are included, then the estimate of its frequency is from 1–4% of the population. Women are three times more likely to be diagnosed with it than men. Onset is typically in young adulthood and may become less common after 50 years old. It was first described between 1833 and 1839 by French anatomist Alfred Velpeau.

Terminology

Although hidradenitis suppurativa is often referred to as acne inversa, it is not a form of acne, and lacks the core defining features of acne such as the presence of closed comedones and increased sebum production.

Causes

The exact cause of hidradenitis suppurativa remains unknown, and there has, in the recent past, been notable disagreement among experts in this regard. The condition, however, likely stems from both genetic and environmental causes. Specifically, an immune-mediated pathology has been proposed, although environmental factors have not been ruled out. Lesions will occur in any body areas with hair follicles, and/or sweat glands, although areas such as the axilla, groin, and perineal region are more commonly involved. This theory includes most of these potential indicators: The historical understanding of the disease suggests dysfunctional apocrine glands or dysfunctional hair follicles, possibly triggered by a blocked gland, which creates inflammation, pain, and a swollen lesion.

Triggering factors

Several triggering factors should be taken into consideration:

Predisposing factors

Some cases have been found to result from mutations in the NCSTN, PSEN1, or PSENEN genes. The genes produce proteins that are all components of a complex called gamma- (γ-) secretase. This complex cuts apart (cleaves) many different proteins, which is an important step in several chemical signaling pathways. One of these pathways, known as notch signaling, is essential for the normal maturation and division of hair follicle cells and other types of skin cells. Notch signaling is also involved in normal immune system function. Studies suggest that mutations in the NCSTN, PSEN1, or PSENEN gene impair notch signaling in hair follicles. Although little is known about the mechanism, abnormal notch signaling appears to promote the development of nodules and to lead to inflammation in the skin. In addition, the composition of the intestinal microflora and as a consequence dietary patterns appear to play a role. Although dysbiosis of the cutaneous microbiome apparent in HS is not observed, the concurrent existence of inflammatory gut and skin diseases has led to the postulation of a gut-skin axis in which gut microbiota is implicated. Indeed, analysis of bacterial taxa in fecal samples from HS patients support the possibility of a role for intestinal microbial alterations in this chronic inflammatory skin disease. Precocious puberty is more common among children and adolescents with hidradenitis suppurativa (HS) compared to those without the condition, according to a recent case-control study. An analysis of the Explorys database revealed that pediatric patients with precocious puberty have double the risk of developing HS, even after adjusting for factors like demographic characteristics and body mass index (BMI).

Diagnosis

Early diagnosis is essential in avoiding tissue damage. However HS is often misdiagnosed or diagnosed late due to healthcare professionals not being aware of the condition or people not consulting with a physician. Globally, the diagnosis is delayed more than 7 years in average after symptoms appear. This is much longer than with other skin conditions.

Stages

Hidradenitis suppurativa presents itself in three stages. Due to the large spectrum of clinical severity and the severe impact on quality of life, a reliable method for evaluating HS severity is needed.

Hurley's staging system

Hurley's staging system was the first classification system proposed, and is still in use for the classification of patients with skin diseases (i.e., psoriasis, HS, acne). Hurley separated patients into three groups based largely on the presence and extent of cicatrization and sinuses. It has been used as a basis for clinical trials in the past and is a useful basis to approach therapy for patients. These three stages are based on Hurley's staging system, which is simple and relies on the subjective extent of the diseased tissue the patient has. Hurley's three stages of hidradenitis suppurativa are:

Sartorius staging system

The Sartorius staging system is more sophisticated than Hurley's. Sartorius et al. suggested that the Hurley system is not sophisticated enough to assess treatment effects in clinical trials during research. This classification allows for better dynamic monitoring of the disease severity in individual patients. The elements of this staging system are: Points are accumulated in each of the above categories, and added to give both a regional and total score. In addition, the authors recommend adding a visual analog scale for pain or using the dermatology life quality index (DLQI, or the 'skindex') when assessing HS.

Treatment

Treatment depends upon presentation and severity of the disease. Due to the poorly studied nature of the disease, the effectiveness of drugs and therapies were unclear. Clear and sensitive communication from health care professionals, social and psychological interventions can help managing the emotional impact of the condition and aid necessary lifestyle changes. In May 2023, the European Commission (EC) approved Cosentyx (secukinumab) for active moderate to severe hidradenitis suppurativa in adults. Other possible treatments include the following:

Cryotherapy

Cryotherapy has demonstrated efficacy against the disease, with 88% of persistent lesions resolving in a clinical trial of 23 patients.

Lifestyle

Warm baths may be tried in those with mild disease. Weight loss and the cessation of smoking are also recommended.

Medication

Surgery

When the process becomes chronic, wide surgical excision is the procedure of choice. Wounds in the affected area do not heal by secondary intention, and immediate or delayed application of a split-thickness skin graft is an option. Another option is covering the defect with a perforator flap. With this technique, the (mostly totally excised) defect is covered with tissue from an area nearby. For example, the axilla with a fully excised defect of 15 × 7 cm can be covered with a thoracodorsal artery perforator flap.. A less invasive excision procedure called Skin-Tissue-sparing Excision with Electrosurgical Peeling or "STEEP" has also been developed for treating moderate to severe disease.

Laser hair removal

The 1064-nm wavelength laser for hair removal may aid in the treatment of HS. A randomized control study has shown improvement in HS lesions with the use of a YAG laser.

Botox injection

A 2022 study reported that administration of Botulinum toxin resulted in either clinical improvement or improved quality of life in 96.8% (n = 30/31) of HS patients. Level of evidence was moderate. It concluded that the treatment was a safe and potentially effective alternative for hidradenitis suppurativa patients resistant to standard of care therapies.

Prognosis

In stage III disease, as classified by the Hurley's staging system, fistulae left undiscovered, undiagnosed, or untreated, can rarely lead to the development of squamous cell carcinoma in the anus or other affected areas. Other stage III chronic sequelae may also include anemia, multilocalized infections, amyloidosis, and arthropathy. Stage III complications have been known to lead to sepsis, but clinical data are still uncertain.

Potential complications

Impact on mental health

HS is a painful and socially isolating condition which leads to a negative impact on mental health as well. A 2020 meta-analysis found that 21% of people with HS have depression and 12% have anxiety. A 2020 study found that people with HS have suicide rates more than double the rates in controls, and also have a higher risk of attempting suicide.

Epidemiology

Prevalence

Estimates of the prevalence of HS vary worldwide and there is no accepted generalization. In the USA, the prevalence is estimated to be 0.1% while in Europe it is thought to be 1% or more.

Gender

In North America and Europe, women are three times more likely to have HS. However, in South Korea, men are twice as likely to have HS.

Age

HS is the most prevalent in people in their 40s and 50s.

Comorbidities

Especially endocrine diseases are more common in HS. Diabetes mellitus may be both a causal factor contributing to the evolution and/or severity of HS and a consequence of inflammation in HS. Thyroid disorders are more common, too, in HS.

History

A surgeon from Paris, Velpeau described an unusual inflammatory process with formation of superficial axillary, submammary, and perianal abscesses, in a series of three publications from 1833 to 1839. One of his colleagues, also located in Paris, named Verneuil, coined the term hidrosadénite phlegmoneuse about 15 years later. This name for the disease reflects the former pathogenetic model of acne inversa, which is considered inflammation of sweat glands as the primary cause of hidradenitis suppurativa. In 1922, Schiefferdecker suspected a pathogenic association between acne inversa and apocrine sweat glands. In 1956, Pillsbury postulated follicular occlusion as the cause of acne inversa, which they grouped together with acne conglobata and perifolliculitis capitis abscendens et suffodiens ("dissecting cellulitis of the scalp") as the "acne triad". Plewig and Kligman added another element to their acne triad, pilonidal sinus. Plewig et al. noted that this new "acne tetrad" includes all the elements found in the original "acne triad", in addition to a fourth element, pilonidal sinus. In 1989, Plewig and Steger introduced the term "acne inversa", indicating a follicular source of the disease and replacing older terms such as "Verneuil disease".

Other names

Hidradenitis suppurativa has been referred to by multiple names in the literature, as well as in various cultures. Some of these are also used to describe different diseases, or specific instances of this disease.

Histology

Society and culture

Experiences of people with HS

HS can have a strong negative impact on people's lives, as well as physical and mental health. People with HS often feel stigmatised and embarrassed by their condition. Many try to hide the symptoms which can lead to impaired relationships and social isolation. A multidisciplinary approach by healthcare professionals, social support networks and psychological interventions can contribute to a better quality of life. Compared to other skin diseases, HS has one of the highest Dermatology Life Quality Index (DLQI) scores.