Hidradenitis suppurativa (HS), previously known as acne inversa is a chronic inflammatory skin disease that affects approximately 1% of the Irish Population. The condition causes boils, abscesses and scarring in the axillae, groin and inframammary areas of patients. HS is chronic, recurrent and debilitating and tends to be progressive. The disease causes significant pain and distress and has a huge impact on patients’ lives affecting their ability to work and intimate relationships.
Epidemiology of Hidradenitis Suppurativa:
HS may affect between 1-4% of the population, and a study from Irish dermatology departments indicated a prevalence of 1.4% amongst the patient population attending dermatology clinics1.
HS is three times more common in women and generally starts around puberty and ameliorates around menopause. One third of patients have a family history of the condition or a family history of pilonidal sinus.
HS begins as small pustules and boils under the arms and in the groin or buttock area, they may be predated by blackheads which are ope comedones, the presence of ‘double comedones’, two blackheads beside each other, is pathognomic of the condition. Because the disease begins in puberty it is often not recognized at its beginning. Pustules enlarge to become abscesses which are extremely painful and eventually discharge a mixture of pus and blood which is foul-smelling and the pain gradually resolves. As the disease progresses abscesses join up to form sinus tracts and eventually marked scarring. Thus patients suffer both pain and the embarrassment of foul-smelling discharge
The most commonly areas affected are the axillae, inguinal creases, buttocks, natal cleft and under the breasts or abdominal pannus, any site where skin touches off itself or at sites of friction. The diagnosis of HS is a clinical one and is the presence of:
1. Typical lesions: Primary lesions – painful deep-seated nodules (blind boils) Secondary lesions – abscesses, draining sinuses, bridged scars, “tombstone comedones”
2. Typical localization: Axillae and groin, genitals Under breasts, on buttocks and perineum
3. Chronicity and recurrences: Chronic recurrent lesions for more than six months
Despite this, diagnosis of HS may be delayed as the chronicity of lesions may not be appreciated and patients may present in different clinical settings, primary care, emergency departments, gynaecology and surgery. It has been estimated that patients may wait eight years for diagnosis, see five different specialities over on average 17 consultations. This delay in diagnosis leads to irreversible changes of scar, sinus tracts and fistula as the disease progresses, leading to scarring and disability.
Patients with HS may also have other cutaneous disorders such as severe acne and a pilonidal sinus where the spectrum is known as follicular triad, when patients have HS, severe acne, pilonidal sinus and folliculitis de calvens it is known as follicular tetrad.
Severity of HS is most commonly graded using the Hurley Staging
Stage 1 (Mild cases): Single or multiple abscesses
• Painful bumps, pustules and abscesses in the armpits, groin, under the breasts, in between the buttocks or inner thigh; • These bumps generally start as firm, pea-sized nodules.
Stage 2 (Moderate cases): Recurrent abscesses, sinus tract formation • Recurring spots, pustules and abscesses in multiple areas with scarring and skin tunnelling • Scarring can occur as a result of long-term or repeat occurrences in a single location
Stage 3 (Severe cases): Widespread involvement of area, with multiple interconnected tracts and abscesses • Widespread spots, pustules and abscesses with multiple interconnected skin holes and tunnels (sinus tracts)
• Abscesses can be painful and develop into deep sinus tracts under the skin. Areas of skin involved may split and produce an unpleasant odour.
Historically HS was thought to be a disease of apocrine glands it is now recognized as a follicular disorder. It is thought that the initial occlusion is caused by hyperkeratinisation of the pilosebaceous unit leading to occlusion of the follicle with swelling leading to rupture of the follicle and discharge of contents into the dermis (Fig 2A). There may also be abnormalities in the skin’s innate immune system as recent work has shown altered copy numbers of β-defensin, an antimicrobial peptide, was associated with HS. Keratinocytes from the follicles of patients with HS also display differing expression of antimicrobial peptides compared to controls. These follicular contents trigger an immune response leading to redness and inflammation.
Dysregulation of the innate and adaptive immune system has also been demonstrated based on clinical association with other immune-mediated disorders, its response to biologic therapy in the clinical arena, and from molecular research. Anti-TNF therapy is proving effective in HS and increased lesional expression of IL-17 and IL-23 suggest other pathways and cells may be involved it is clear that HS has a much more heterogeneous immune signature that involves B cells.
When two adjacent follicles rupture a sinus tract/tunnel under the skin (Fig 2B).
Microbial colonisation plays a role and recent work has shown the formation of biofilms in HS lesions and HS skin that is not clinically involved. Bacterial infection may serve a secondary role in the pathogenesis of HS by exacerbating local inflammation via a series of pathogen associated molecular pathways. As yet there are no definitive bacterial pathogens identified, but antibiotic treatment is a mainstay of HS treatment.
Risk Factors for developing HSSmoking
Smoking has been associated with a 5 to 12 fold increased risk of HS. In 2011, the specific term “smoker’s boils “for HS lesions in patients who are smokers . This stemmed from a previous randomized, matched-pair control group study showing that the percentage of active cigarette smokers among HS patients was 88.9%, with an odds ratio of 9.4 and the percentage of smokers in the matched-pair control group was 46%.
Nicotine causes release of tumour necrosis factor alpha causing inflammation, promotion of follicular occlusion and epidermal hyperplasia and contains polyaromatic carbohydrates, that may activate keratinocytes and cells of the immune system.
Several studies have confirmed that patients with HS have a higher Body Mass Index (BMI) compared to the general population and this ranges from 12% to 88%, depending on the type of population. In a large retrospective, matched case-control study the association between obesity and HS was high with 17.3-fold higher odds of being obese when also afflicted with HS. Overweight individuals tend to have larger and increased skin folds, leading to subsequent increased mechanical friction and maceration of the overlying skin. In addition, a warm, humid and occlusive environment in these areas favours microbial growth and colonization. In addition obesity is considered to be a state of systemic, low-grade inflammation which contributes to the inflammation in the skin.
Approximately a third of patients have a family history of the disease and early onset HS is associated with a stronger genetic predisposition ( 55% vs 34 %) and more widespread disease. . This pattern probably represents autosomal dominant inheritance with incomplete penetrance. No definitive genes have been identified apart from rare mutations in gamma secretase gene mutation which leads to a particularly severe clinical presentation.
Given that HS is three times more common in women and that some women report premenstrual flare HS can resolve after the menopause, hormonal influences play a role. This has yet to be fully elucidated and hormonal treatments such as anti-androgens have not proved particularly useful. High rates of Polycystic Ovarian Syndrome among patients with HS also corroborate the likelihood that hormones play a role in pathogenesis.
Co-morbidity in Hidradenitis suppurativa
In a similar paradigm to psoriasis, it is now apparent that HS carries a substantial comorbidity burden, these include obesity, metabolic and cardiovascular disease, inflammatory bowel disease, inflammatory joint dIsease and psychological distress.
Obesity, Metabolic Syndrome and Cardiovascular Disease
Unsurprisingly the increased rates of obesity in HS result in increased rates of metabolic syndrome and also the individual components of metabolic syndrome, including dyslipidemia, hypertension and diabetes, this in turn increases cardiovascular risk. One of the first studies to evaluate CVD risk in HS patients using a validated risk assessment tool, the Framingham Risk Score (FRS) was an Irish study by Hughes et al. In this study patients were mainly in their thirties yet showed an increased cardiovascular risk than controls.
Inflammatory Bowel Disease
An association between IBD and HS has been reported as early as in 1991. Of 1,076 patients with HS, 3.3% had IBD, with a prevalence of 2.5% for CD and 0.8% for CD. Using the estimated prevalence of IBD in the general it was indicated that the prevalence of IBD is 4-8 times higher in the included HS cohort than in the general population. HS and CD share several similar clinical and pathogenic features. Both conditions are chronic diseases of epithelia which are inhabited by commensal flora and both have demonstrated a clinical response to anti-TNF α therapy. They share a number of predisposing factors including genetic predisposition and smoking association
In a French study the estimated prevalence of spondyloarthropathy was 3.7% which far exceeded that of the populationn, 0.3%. In a retrospective, case-control study of 1,730 HS patients in Massachusetts General Hospital, it was found that 908 patients had spondyloarthritis compared to only 52 in those who did not have HS (52.5% vs. 3.0% p< 0.0001). The pathogenesis underlying the development of SpA in HS patients is unclear. The shared features of dysregulated innate immune response and the role of microbial factors have been hypothesized.
HS patients suffer significant pain and foul-smelling suppuration from abscesses or sinuses in affected areas during flares which leads to disruption of activities of daily living as well as work and embarrassment contributing to high levels of psychological distress. Multiple studies have demonstrated high levels of depression and anxiety in patients with HS. These findings support several other studies in the literature proposing a possible link between chronic inflammation and depression.
Treatment of Hidradenitis suppurativa
The publication of the European S1 Guideline for the treatment of hidradenitis suppurativa in 2015 has provided some clarity on how to manage patients at different Hurley Stage (Fig 3). It clearly suggests a triple-track approach to the management of patients of all stages, i.e. a surgical approach, a medical approach and adjuvant management of pain, suppuration and co-morbidities. The evidence supporting this Guideline was reviewed in an evidence based way and a more complex algorithm generated . This was the first attempt to provide an algorithm for the treatment of patients.
Surgical treatment consists of either lesional treatment: such as de-roofing and carbon dioxide laser ablation, or regional treatment where wide areas of hair-bearing skin are excised and the defect repaired by skin grafting or healing by secondary intention.
Medical treatments consist of topical clindamycin for mild disease, oral tetracyclines for a prolonged period of up to four months. The combination of rifampicin and clindamycin, both 300mg twice daily for a 10- week period, has proved highly efficacious, though patients must be warned about the risk of developing C. difficile. Adalimumab (Humira®) is recommended as a first-line treatment option in patients with moderate-to-severe HS who were unresponsive or intolerant to oral antibiotics. It should be administered as 160mg at week zero, 80mg at week two and 40mg each week thereafter, starting from week four and has received a licence for the treatment of HS. Second-line agents for severe disease include infiximab 5mg/ kg, and ustekinumab. The area of biological treatment is being intensely investigated, largely using biologics licensed for other indications.
The third track of treatment includes treating patients’ symptoms of pain, appropriate wound care and identifying and treating superinfections.
Smoking cessation is important, as research has shown that 92 per cent of patients smoke and smoking is associated with less self-reported remission. The severity of HS was associated with pack years in 846 Dutch patients. Encouraging weight loss is also desired, as weight loss of more than 15 per cent is associated with a significant reduction of disease severity. Clearly treating HS patients requires a multidisciplinary approach involving a dermatologist, a surgeon, nursing support, smoking cessation advice and weight loss programmes.
Although there has been considerable advances in the treatment of HS the disease however remains one for which a definitive treatment have been produced.
Written by Professor Anne Marie Tobin, Consultant Dermatologist Tallaght University Hospital, Clinical Associate Professor Trinity College Dublin, Clinical Lead in Dermatology Health Service Executive
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