Hidradenitis Suppurativa - Current research and findings

Hidradenitis suppurativa (HS) is a chronic dermatological condition that results in painful bumps under the skin and in the hair roots near sweat glands.  It is also commonly known as acne inversa.  The early stages of Hidradenitis suppurativa are often misdiagnosed, due to the beginning stages often just looking like an ingrown hair or a minor skin infection.  

Hidradenitis Suppurativa is an inflammatory disease that is characterized by the formation of nodules.  These recurrent lesions can occur in the armpits, the groin, between the buttocks, palms of the hands, and under the breasts. The nodules may spontaneously rupture with a foul-smelling discharge, or they may coalesce, forming painful, deep dermal abscesses. In extreme cases, scarring and sinus tracts can form. 

 Hidradenitis suppurativa is graded on a system called the Hurley Grading System.   

Stage 1 
The first stage of HS is usually solitary or multiple lesions (boil-like or abscesses).  These are typically located in the armpit, groin, thighs, buttocks, and under the breasts.  At this stage, the lesions are usually small bumps, which can become swollen and sore.  They will often burst and drain but often recur in the same location.  The recurrence of the lesions is a strong indicator of HS. This stage is often misdiagnosed and mistaken for a boil, ingrown hair, or just a skin infection.  There are no scarring or sinus tracts present in Stage 1. 

Stage 2 
In Stage 2 the abscesses are recurring with sinus tract formation, scarring, and tunneling.  The recurring lesions occur where the old lesions have been and subsequently healed over.  As the lesions heal, they can scar.  The repeated scarring results in tunneling or sinus tracts occurring in the skin.  The sinus tracts form under the skin.  The tunnel contains a lot of pus and drains constantly, leading to a foul smell. 

At this stage, Hidradenitis Suppurativa can be diagnosed by a medical professional.  Due to the scars and tunneling, doctors are able to recognise the condition. 

Stage 3 
This stage is severe and is characterised by diffuse or near-diffuse involvement of multiple interconnected tracts and abscesses across an entire area.  The abscesses are occurring in multiple sites and there are sinus tracts from repeated scarring, which are interconnected.  There is no healthy skin between the lesions.  It is painful and the wounds don’t heal and stay open. 
 
There is currently no cure and the etiology of how it forms is not fully elucidated.  The medical treatment of the condition includes long-term antibiotics and antiandrogens.  Surgery is sometimes performed to remove the sinuses and drain the lesions, but it only partially successful at controlling the symptoms. 
 
Women are more likely to have this condition than men, and young African-American women and biracial individuals are at the greatest risk, with a two to threefold higher prevalence.   The age group with the highest number of sufferers is 30-39 years of age.  Early diagnosis is usually missed, with many taking 7 years to get a diagnosis of their condition.   

Smoking has been shown to worsen the condition and research has shown that those with hidradenitis suppurativa tend to have a higher rate of smoking than the general population.  The condition is a condition of hyperkeratosis, and smoking is known to aggravate and cause further hyperkeratosis and follicular occlusion. 

Originally Hidradenitis Suppurativa was thought to be caused by a defect of the sweat gland, but it is now recognised that it is a problem with the hair follicle itself.  The hair follicle develops a buildup of keratin within it, which eventually plugs the hair follicle, causing the cells to build up and eventually the rupture of the hair follicle, causing an inflammatory response and infection.   

Despite the use of antibiotics as a treatment, bacterial involvement is not always a component of the condition, with bacterial swabs and cultures showing no bacteria in some lesions and other lesions containing anaerobic bacteria, staphylococcus aureus, and coagulase-negative staphylococci. 

The discovery of biofilms being involved in the condition a new discovery. Biofilms are a polysaccharide that is secreted by bacteria that is sticky and bind to the surface of the skin.  Bacteria when enclosed in a biofilm become resistant to antibiotic treatment.  Chronic lesions of hidradenitis suppurativa (HS) exhibit several characteristics, which are compatible with well-known biofilm infections. 

Studies have shown that biofilms were seen in 67% of the samples of chronic lesions and in 75% of the perilesional samples. The larger biofilms were found in sinus tracts (63%) and in the infundibulum (37%). The majority of the sinus tract samples (73%) contained active bacterial cells, which were associated with inflammation. 
 
Immune dysregulation has been implicated in HS, with a range of associated cytokines identified, including interleukin (IL)-1β and tumor necrosis factor (TNF)-α and anti-inflammatory cytokine IL-10 in lesional and perilesional skin.  The increase in cytokines is directly correlated to the severity of the disease. 

In another study, enhanced expression of cytokines IL-17, IL1β, IL-18, and TNF-α were found in lesional HS skin. In normal and perilesional skin, there was enhanced expression of IL-17A and IL-1β, suggesting the presence of subclinical inflammation preceding the formation of active HS lesions.  T helper (Th) type 17 cells also appear to play a role in the pathogenesis of HS, as the presence of elevated levels of them have been established.  Additionally, the role of other pro-inflammatory cytokines such as IL-36 and IL-32 continues to be defined. In a study comparing the cytokine profiles of skin specimens from healthy donors, patients with HS, and patients with psoriasis, there was increased expression of IL-36β, IL-36γ, and slightly increased expression of IL-36α and IL-36RA in lesional HS skin. 

The primary event with hidradenitis suppurativa is follicular hyperkeratosis, which plugs and causes dilatation of the hair follicle.  This results in inflammation, abscess, and sinus tract formation.  Involvement of the sweat glands is a secondary factor resulting from the diffusion of inflammation into the deeper structures of the skin.  The apocrine glands empty their content into the follicular canal, just above the sebaceous gland duct. 

One of the factors that have been overlooked, however, is the fact that the skin produces antimicrobial peptides and these can have both an inflammatory and anti-inflammatory effect.  Antimicrobial peptides are part of the innate immune response of the skin and play a role in immune dysregulation in HS.  These peptides are produced by mature keratinocytes, as well as in the eccrine or sweat glands, which are the same areas that hidradenitis suppurativa ironically occurs.  The areas where sweating occurs.  One of the antimicrobial peptides psoriasin is produced in the sweat glands, and studies have shown that it is directly regulated by antibiotics, which would explain why antibiotics can be successful in treating hidradenitis suppurativa.  One study showed a nine-fold increase in the expression of S100A7 (psoriasin) expression in hidradenitis suppurativa and is directly correlated to the severity of it.  There was also a three-fold reduction in human β defensin-1, which is a molecule that protects against infection.  IL-32 has also been found to be present in higher amounts in inflamed lesional skin and has been shown to upregulate antimicrobial peptides and cathelicidins.  IL-32 in contrast is nearly absent in healthy skin.   

Studies have shown that HS lesional skin is also deficient in sphingolipids such as ceramides. These membrane lipids are present in the skin and appendages, acting as biologically active signaling molecules. In lesions of HS, ceramide synthases and enzymes that create ceramides de novo are downregulated, and enzymes that metabolize ceramide are upregulated.  A decrease in ceramides has been shown to cause sebum to solidify, leading to blockages of the hair duct.  

Is there a genetic component?  Initially, a genetic component was suspected due to the positive family history.  Up to 40% of patients have a positive history of HS with a first-degree relative.  It was not until 2006 when the first genetic locus thought to be responsible for HS was identified.  The gene responsible was mapped to chromosome 1p21.1–1q25.3.  

Nutrition plays a critical role in the management of inflammatory diseases, especially of the pilosebaceous duct.   Both acne vulgaris and hidradenitis suppurativa are affected by diet-modulating pathogenic pathways.  The Western diet influences hidradenitis suppurativa by increasing insulin and modulating the FOX01m/mTOR pathway.  This results in the overexpression of various keratins, and the hypercornification of the follicular wall.  Reduction in simple carbohydrates and sugar will be beneficial in reducing the incidence of hidradenitis suppurativa. 

Medical Treatment 
Antibiotics are the first-line therapy for mild to moderate HS.  the condition is not driven entirely by bacterial infection; however, the antibiotics have shown to reduce the inflammation associated with the condition.  Therefore, antibiotic efficacy is likely due to a combination of antibacterial and anti-inflammatory actions. Antibiotics have been the mainstay of treatment since early randomized controlled trials demonstrated that both topical and oral antibiotics are effective for HS lesions.  

In 1983, Clemmensen et al. discovered that topical clindamycin 1% solution significantly improved HS lesions compared to placebo. Then in 1998, Jemec et al. compared topical clindamycin 1% solution twice daily with oral tetracycline 500 mg twice daily. Both treatments were found to be effective against HS without significant differences between the topical and oral medications.  

Treatment of Stages 1 and II, the recommendation is topical clindamycin 1% solution and switch to an oral tetracycline antibiotic such as doxycycline 100 mg up to twice daily, minocycline 100 mg up to twice daily, or tetracycline up to 500 mg twice daily if there is no response.  

More extensive and complex cases of HS require the combination of clindamycin and rifampin.  A 2006 study with 14 HS patients treated with clindamycin 300 mg BID and rifampin 300 mg BID for 10 weeks found 8 patients achieved complete remission.  Rifampin is considered a good choice for HS because of its anti-inflammatory properties and its ability to penetrate bacterial biofilms. 

In extensive cases, surgery may be necessary.  Surgery involves excision, of the lesions.  Wide excision removes both affected skin and the tissue around it. The aim of wide excision is to prevent the disease from spreading. A person who undergoes wide excision may also need a skin graft to replace the tissue removed. Tissue-sparing excision removes only the affected tissue. And local excision removes individual lesions. 

An alternative to surgery is laser treatment. Recent studies have also investigated the efficacy of laser surgery on HS. Benefits of laser surgery include less invasive, less expensive procedures that produce well-healing lesions. Laser surgery is thought to be effective because it destroys the hair shaft and clears debris from the follicular unit. Options for laser surgery include carbon dioxide laser, IPL laser, and Nd: YAG laser.  

Other less invasive therapeutic measures that have been studied are the use of photodynamic therapy (PDT) with intralesional 5-aminolevulinic acid or methylene blue followed by 630–635 nm light treatment. Both of these methods produced high remission rates in small studies. Further, the combination of surgery followed by treatment with PDT may have added benefit, with advantages of faster healing and less extensive scarring. 

The treatment of hidradenitis suppurativa needs to be commenced from the earliest stage possible, to minimise the occurrence of the condition and scarring.  There are many options medically to manage the condition including dietary modification, antibiotics, and laser.  Skin therapists can encourage the conversation for conservative management, by being observant of any indications of potential disease in their clients.  Many clients are unaware that they have the condition, and just assume it is an ingrown hair in many instances.  The beauty therapist can encourage the client to get a medical diagnosis to rule out the condition.