Hidradenitis suppurativa

What are the causes?

Hidradenitis suppurativa (HS) is a skin condition caused by blocked hair follicles associated with an abnormal proliferation of commensal bacteria in the dermis (where they are not normally found), leading the host to develop chronic inflammation in an unsuccessful attempt by the body to eliminate the bacteria. This inappropriate response by the skin to its flora could be a form of immunodeficiency which remains localized to the skin, since patients with HS are generally not immunodeficient in the blood or the bone marrow.

The exact mechanisms underlying the disease have not yet been fully elucidated.

It is thought that several factors contribute to its development:

• Genetics: family predisposition to the condition is observed in at least 30% of cases. But individuals who have a parent with HS will not necessarily develop the disease. Certain other conditions are also often observed among family members, such as pilonidal sinus disease, severe acne, and also inflammatory digestive disorders (Crohn's disease, ulcerative colitis), inflammatory rheumatic disorders (spondyloarthritis, SAPHO syndrome, polyarthritis), Behçet's disease, familial Mediterranean fever and sarcoidosis.
• Lifestyle factors: smoking and excess weight
• Hormonal imbalances, especially diabetes
• Deregulation of the immune system, whether congenital (genetic) or acquired (especially following medical treatment that reduces immunity)
• An abnormal proliferation of bacteria in the deep layers of the skin and in certain mucosa (commensal flora) was demonstrated in lesions in a patient by a Pasteur-Necker team for the first time anywhere in the world in 2007 (Professor Join-Lambert, Dr. Maïa Delage, Dr. A. Nassif, Professor Lortholary, Professor Hovnanian) and subsequently confirmed by several other international teams^1,2. This discovery revealed that the flora found in HS lesions differed depending on the severity of the condition^2,3.

The current hypothesis put forward by the Pasteur-Necker team is that HS is a form of immune deficiency localized in the skin, since these patients have no systemic infections. This theory seems to be supported by the presence of mutations in immunodeficiency genes:

• Mutations in some patients in the Institut Pasteur's HS patient cohort (more than 1,600 HS patients monitored since 2007), identified by Professor Hovnanian (Imagine)⁴.
• Mutations also found in patients in the medical literature⁵.

This research enabled the Pasteur-Necker team to develop a targeted treatment strategy (see below) depending on the bacteria isolated and the severity of the condition, which are correlated.

It is important to note that, contrary to popular belief, poor body hygiene is not a cause of hidradenitis suppurativa.

How does the disease spread?

Hidradenitis suppurativa is not a contagious disease (patients are infected with their own commensal flora and not that of their close contacts) and it cannot be spread from one person to another via airborne or sexual transmission.

But the condition can be passed down genetically in around 30% of cases.

What are the symptoms?

The symptoms of hidradenitis suppurativa vary in intensity and frequency from one individual to the next. The most common symptoms are:

• The appearance of painful, swollen red nodules in skin folds (the armpits, groin, buttocks and under the breasts). The neck, face, back and the area behind the ears can also be affected.
• The formation of abscesses which can burst and seep a smelly pus.
• The development of fistulas, tunnels under the skin linking the lesions.
• The presence of scars and induration (hardening and thickening of the skin) in the affected areas.
• Intense pain, especially during inflammatory flare-ups.
• Chronic fatigue and a general feeling of malaise (feeling unwell)
• Itchiness and a burning sensation in the affected areas.

Symptoms occur in cycles or flare-ups, with periods of relative remission depending on the severity of the condition – which may vary considerably, ranging from a mild form to a severe, debilitating form.

The condition can be divided into three stages depending on the severity of symptoms:

• Stage I: One or multiple abscesses without fistulas (tunnels) (70% of patients)
• Stage II: Recurring abscesses with fistulas and scars (25% of patients)
• Stage III: Multiple diffuse abscesses that are interconnected (5% of patients), with no healthy skin in the affected areas

NB: in the absence of aggravating factors, these stages are not progressive (a patient in stage I will theoretically stay in stage I throughout their lifetime). Stage III starts early in life and soon reaches stage III (within a few months/years).

The condition generally starts around age 22-23 or earlier for stages II and III.

How is hidradenitis suppurativa diagnosed?

Early diagnosis is crucial for effective treatment and to stop the condition from spreading. Unfortunately, because HS is not well known by healthcare professionals and the general population, diagnosis often takes several years from the onset of the first symptoms (six to eight years on average).

Diagnosis of hidradenitis suppurativa is mainly based on a clinical examination and symptom history. A dermatologist or experienced physician can generally diagnose HS by observing the characteristic lesions and their location.

Diagnostic criteria include:

• The presence of typical lesions: nodules (stage I lesions), abscesses (stage I lesions), fistulas (stage II lesions), connecting tunnels with no healthy skin in the affected areas (stage III lesions).
• Lesions located in the preferred HS areas: armpits, skin folds in the groin, buttocks and anus, and/or breasts and neck.
• The recurrence of lesions over a period of at least six months.
• The exclusion of other similar skin conditions.

Additional tests are not necessary for diagnosis but may be useful to provide a diagnostic workup:

• Blood or stool tests to assess inflammation and rule out or diagnose other conditions that may be associated with HS, such as diabetes, ankylosing spondylitis or Crohn's disease.
• Depending on the appearance and location of the lesions (severe forms on the buttocks), and whether or not there is also an inflammatory bowel condition, an MRI of the pelvis may be recommended to evaluate the extent of subcutaneous lesions.

What treatments are available?

General measures to limit development of the condition and prevent inflammatory flare-ups include:

• Weight loss in the event of excess weight;
• Management of diabetes if relevant;
• Discontinuation of anti-inflammatory drugs and medication that lowers immunity (corticosteroids, immunosuppressants);
• Holistic treatment for stress, pain and depression;
• Quitting smoking.

There are treatments to manage flare-ups and/or achieve remission (see below). Given that the microbiology differs depending on the severity of the condition, treatments are adapted as appropriate. The aim is to control inflammation and prevent relapses to improve the patient's quality of life. Therapeutic options include:

1. Local treatments:

• Antiseptics and antibiotics, which are moderately effective

1. Systemic treatments:

• Oral antibiotics during flare-ups to achieve remission or in the event of a relapse, then long-term, low-dose antibiotic therapy as a maintenance treatment to prevent relapse and the emergence of new lesions
• Biologic immunomodulators (such as adalimumab and secukinumab) for moderate to severe forms to reduce flare-ups by 50% in 50% of patients

1. Surgical treatments:

• Incision and drainage of abscesses for rapid relief
• Local or wide excision of the affected areas in severe cases to clear regions containing biofilms (persistent dormant bacteria in scars, which may represent a constant cause of relapse)
• Surgical treatment is only effective if combined with medical treatment, both before surgery to optimize the procedure and after surgery to prevent relapses once biofilms have been removed

1. Other approaches:

• Laser surgery for certain lesions
• Psychological support to manage the emotional impact of the condition
• Monitoring by a diabetes specialist, gastroenterologist, rheumatologist and/or internal medicine physician for any associated conditions

A multidisciplinary approach involving dermatologists, surgeons and specialists is often needed to optimize treatment.

Possible remission in certain cases with targeted treatment

The Pasteur-Necker team has hypothesized that HS is caused by immune deficiency localized in the skin, since patients have no systemic infections (see above). The species of commensal bacteria isolated in HS lesions vary depending on the severity of the condition.

With a targeted treatment strategy based on bacterial isolates and severity, cases of full remission have been observed, but they have been followed by relapse in the absence of maintenance treatment^6,7,8.

Maintenance treatment therefore seems necessary in most moderate and severe patients. Moreover, in 2015⁹, in patients under maintenance treatment, the Pasteur-Necker team observed relapses that only occurred on old scars, suggesting the persistence of dormant bacteria (also known as biofilms) in lesions; this was subsequently confirmed by several research teams¹⁰.

The presence of biofilms, for which there is currently no effective medical treatment, justified the combination of targeted antibiotic strategies with surgery to avoid the risk of resistance developing and enable long-term remission with maintenance treatment.

A therapeutic trial for the antibiotic strategy used for the past 15 years at Pasteur-Necker to treat Hurley stage II patients will soon be launched at the Institut Pasteur.

How can hidradenitis suppurativa be prevented?

There is no effective prevention for hidradenitis suppurativa.

Some measures may help limit the development of the disease and prevent inflammatory flare-ups:

• Losing excess weight, which is a well-known aggravating factor.
• Avoiding taking anti-inflammatories and drugs that reduce immunity, especially in children of HS patients, from the onset of the very first symptoms, especially for genetic forms.
• Avoiding irritants: opting for loose-fitting clothes made from natural fibers to reduce rubbing and sweating.
• Seeing a dermatologist as soon as possible in the event of suspected symptoms, so that the condition can be diagnosed and treated early.

Who is affected?

Hidradenitis suppurativa mainly affects young adults, with the highest incidence between the ages of 20 and 40. There are certain notable demographic characteristics:

• Sex: women are three times more likely to be affected than men (the opposite is true in Korea and Japan).
• Age: the condition generally begins after puberty, on average around age 22 to 23, but often earlier for severe forms; it is rare after the age of 50 and in this case aggravating factors should be sought (significant weight gain, diabetes, medical treatment that reduces immunity).
• Genetic predisposition: around 30-40% of patients have a family history of the condition.
• Comorbidities: Since nearly 80% of HS patients are overweight, the condition is often associated with a metabolic syndrome (characterized by high waist circumference, high blood pressure, hyperglycemia and an abnormal cholesterol level). Hidradenitis suppurativa has also been linked to some other conditions: chronic inflammatory bowel disease or inflammatory rheumatic disorders that are sometimes already in the family (see above).

It is important to note that the condition may affect people of all backgrounds, regardless of hygiene or socio-economics status.

The exact prevalence of hidradenitis suppurativa is hard to determine because it is often underdiagnosed. But recent estimates are as follows:

• Global prevalence is estimated at between 1 and 4% of the adult population.
• In France, it is thought that around 1% of the population is affected, or roughly 670,000 individuals.
• In the United States, estimates range between 1 and 2% of the population.
• The incidence seems to be on the rise, possibly because the condition is more easily recognized but also because of an increase in risk factors such as obesity.

It is worth noting that these figures may vary from one study to the next and depending on the diagnostic criteria used. Efforts are under way to improve the epidemiological data on the condition, which remains poorly known.

FAQ

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Scientific publications:

1. Guet-Revillet et al. Bacterial pathogens are associated with Hidradenitis suppurativa. Emerg Infect Dis. 2014 Dec ; 20(12):1990-8.
2. Guet-Revillet H et al. The microbiological landscape of anaerobic infections in Hidradenitis Suppurativa: a prospective metagenomic study. Clin Infect Dis 2017 Apr 1.
3. Naik B et al. Skin Microbiota Perturbations Are Distinct and Disease Severity-Dependent in Hidradenitis Suppurativa. .J Invest Dermatol. 2020 Apr;140(4):922-925.e3.
4. Miskinyte S et al Inborn Errors of Immunity in Hidradenitis Suppurativa: a New Lead for HS Genetics? J Clin Immunol. 2023 Dec 22;44(1):7.
5. Colvin A et al. Inborn Errors of Immunity in Hidradenitis Suppurativa Pathogenesis and Disease Burden. J Clin Immunol. 2023 Aug;43(6):1040-1051.
6. Join-Lambert O et al. Efficacy of rifampin-moxifloxacin-metronidazole combination therapy in hidradenitis suppurativa. Dermatology. 2011;222(1):49-58.
7. Join-Lambert O et al. Efficacy of ertapenem in severe Hidradenitis Suppurativa: a pilot study in a cohort of 30 consecutive patients. J Antimicrob Chemother 2016 Feb : 71(2) :513-20.
8. Delage M et al. Rifampin-moxifloxacin-metronidazole combination therapy for severe Hurley Stage 1 Hidradenitis Suppurativa: prospective short-term trial and one-year follow-up in 28 consecutive patients. J Am Acad Dermatol. 2020 Jan 10. pii: S0190-9622(20)30049-9.
9. O. Join-Lambert et al. Remission of refractory PASH syndrome by targeted antibiotherapy in 4 patients. J Am Acad Dermatol. 2015 Nov;73(5 Suppl 1): S66-9.
10. Ring HC et al. Bacterial biofilm in chronic lesions of hidradenitis suppurativa. Br J Dermatol. 2017 Apr;176(4):993-1000.

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La Maladie de Verneuil, ou Hidrosadénite Suppurée, Hidradénite Suppurée, Acné Inversée... | Association Française pour la Recherche sur l'Hidrosadénite | Marie-France Bru-Daprés (afrh.fr) (in French)

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La Maladie de Verneuil » SNFCP (in French)

Maladie de Verneuil : Définition, symptômes et traitements | ElsanMaladie de Verneuil — Définition, symptômes et traitements | Elsan | Elsan (in French)

Hidradenitis Suppurativa - StatPearls - NCBI Bookshelf (nih.gov)

Hidradenitis suppurativa (HS) - NHS (www.nhs.uk)

Hidradenitis suppurativa: Overview (aad.org)

Hidradenitis Suppurativa | Acne Inversa | MedlinePlus

Hidradenitis suppurativa - Symptoms and causes - Mayo Clinic

 Zouboulis et al HS Europ guidelines JEADV, 2015

Stades (in French)

Population concernée | Vaincre Verneuil (in French)