Hidradenitis suppurativa

Hidradenitis suppurativa is a skin disease that most commonly affects areas bearing apocrine sweat glands or sebaceous glands, such as the underarms, breasts, inner thighs, groin and buttocks.^[1]:710

Overview

The non-contagious disease manifests as clusters of chronic abscesses, epidermoid cysts, sebaceous cysts, pilonidal cyst or multilocalised infections, which can be as large as baseballs or as small as a pea, that are extremely painful to the touch and may persist for years with occasional to frequent periods of inflammation, culminating in incision and drainage of pus, often leaving open wounds that will not heal. For unknown reasons, people with hidradenitis develop plugging or clogging of their apocrine glands. It causes chronic scarring and pus formation of the underarms (axilla) and groin/inner thigh areas. The simple procedure of incision and drainage provides some relief from severe, often debilitating, pressure pain. Flare-ups may be triggered by perspiration, hormonal changes (such as monthly cycles in women), humidity and heat, and clothing friction. Persistent lesions may lead to scarring and the formation of sinus tracts, or tunnels connecting the abscesses or infections under the skin. At this stage, complete healing is usually not possible, and progression varies from person to person, with some experiencing remission anywhere from months to years at a time, while others may worsen and require multiple surgeries in order to live comfortably. Wound dehiscence, a premature "bursting" open of a wound, often complicates the healing process. Occurrences of bacterial infections and cellulitis (deep tissue inflammation) may occur at these sites. HS pain and depression can be difficult to manage.^[2]

HS often goes undiagnosed for years because patients are too ashamed to speak with anyone.^[2] When they do see a doctor or medical practitioner, the disease is frequently misdiagnosed or prescribed treatments are ineffective, temporary and sometimes even harmful. There is no known cure nor any consistently effective treatment. Carbon dioxide laser surgery is currently considered the last resort for those who have advanced to its highest stage, where the affected areas are excised, and the skin is grafted. Surgery does not always alleviate the condition, however, and can be very expensive.

Several articles and clinics consider this disease as widely misdiagnosed, due to the misunderstanding of the causes and progression of the disease.^[3] HS is neither the biblical stigmata, leprosy nor caused by poor hygiene. HS is often called an 'orphan illness', due to little research being conducted on the disease at this time. Because HS is considered a rare disease, its incidence rate is not well known, but has been estimated as being between 1:24 (4.1%) and 1:600 (0.2%).^[4]

Areas of involvement with hidradenitis suppurativa

• Note that for the study involved in the table hereinbefore was a personal series of 164 patients. Of the 164 patients with HS, 76% were in Hurley's stage I, 20% were in Hurley's stage II, and 4% were in the final phase of the disease, Hurley's stage III.

Other names for HS

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.^[2]

• Acne conglobata – not really a synonym – this is a similar process but in classic acne areas of chest and back
• Acne Inversa (AI) – a proposed new term^[5][6] which has not gained widespread favour.^[7]
• Apocrine Acne – a misnomer, out-dated, based on the disproven concept that apocrine glands are primarily involved. Though many do suffer with apocrine gland infection, so thought should be given to using HS with subtext re: glands involved.
• Apocrinitis – another misnomer, out-dated, based on the disproven concept that apocrine glands are primarily involved
• Fox-den disease – a catchy term not used in medical literature, based on the deep fox den / burrow – like sinuses
• Hidradenitis Supportiva – a misspelling
• Pyodermia fistulans sinifica – an older term, considered archaic now
• Velpeau's disease – commemorating the French surgeon who first described the disease in 1833
• Verneuil's disease – recognizing the French surgeon whose name is most often associated with the disorder as a result of his 1854–1865 studies^[8]

Historical overview of hidradenitis suppurativa

• In 1839, Velpeau identified and described hidradenitis suppurativa.^[9]
• In 1854, Verneuil described hidradenitis suppurativa as "Hidrosadénite Phlegmoneuse". This is how HS obtained its alternate name "Verneuil's disease".^[10]
• In 1922, Schiefferdecker hypothesized a pathogenic link between "Acne inversa" and human apocrine sweat glands.^[11]
• In 1956, Pillsbury wrote and published a medical journal article discussing hidradenitis suppurativa, describing the disease's main characteristics, dubbing them the "Acne triad: hidradenitis suppurativa,perifolliculitis capitis abscendens et suffodiens".^[12] Pillsbury's research study was one of the first peer-reviewed journal articles to appear publicly with many details of hidradenitis suppurativa, which are still used and relied on today in the medical realm of research on this disease.
• In 1975, Plewig and Kligman, following Pillsbury's research path, modified the "Acne triad", replacing it with the "Acne tetrad: acne triad, plus pilonidal sinus".^[13] Plewig and Kligman's research follows in Pillsbury's footsteps, offering explanations of the symptoms associated with hidradenitis suppurativa.
• Finally in 1989, Plewig and Steger's research led them to rename hidradenitis suppurativa, calling it "Acne Inversa" – which not still used today in medical terminology; although some individuals still use this outdated term.^[14]

A surgeon from Paris, Velpeau described an unusual inflammatory process with formation of superficial axillary, sub-mammary and perianal abscesses in 1839. One of his colleagues also located in Paris, named Verneuil, coined the term “hidrosadénite phlegmoneuse” approximately 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".

Historical view of hidradenitis suppurativa

Dermatohistological view of hidradenitis suppurativa

Stages

HS presents itself in three stages.^[2][17] Due to the large spectrum of clinical severity, to severe repercussions on quality of life and to the variety of available, a reliable method for evaluating HS severity is required. It should take into account the number, type and size of lesions, evolution, pain and repercussions for the quality of life of the patient. Such a comprehensive instrument does not yet exist, but there have been two successful attempts proposed to classify patients with HS according to the severity of their disease.

Hurley's staging system

This is historically the first classification system proposed, and is still in use for the classification of patients with skin/dermatologic 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 as follows:^[18]

Sartorious staging system

The Sartorious staging system is more sophisticated than Hurley's, and is likely to supplant it as a means for conducting clinical trials during research. Sartorius et al. have suggested that the Hurley system is not sophisticated enough to assess treatment effects in clinical trials. The need for uniform outcome variables when reporting treatment effects has led to the proposition of a score by Sartorious and colleagues. This classification allows for better dynamic monitoring of the disease severity in individual patients and therefore forms a complimentary system to the Hurley classification. They suggest a system that incorporates several of the involved areas of consideration:^[19]

• Anatomic regions involved (axilla, groin gluteal or other region or infra-mammary region left or right)
• Number and types of lesions involved (abscesses, nodules, fistulas, scars, points for lesions of all regions involved)
• The distance between lesions, in particular the longest distance between two relevant lesions (i.e. nodules and fistulas in each region or size if only one lesion present)
• The presence of normal skin in between lesions (i.e. are all lesions clearly separated by normal skin?)

Points are accumulated in each of the mentioned categories hereinbefore, 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.^[20] This system will likely be the basis of most future clinical trials and research studies.

Causes

As this disease is poorly studied, the causes are controversial and experts disagree.

Hydradenitis suppurativa occurs when apocrine glands become plugged. Lesions occur in areas of the body with numerous apocrine glands such as the axilla, groin, and perianal region. This theory includes most of the following potentials indicators:^[21]

• Post-pubescent individuals are more likely to exhibit HS.
• Females are more likely than males.
• Genetic predisposition among families of Sephardic Jewish, Italian, Greek, Middle Eastern and Northern African ancestry.
• Research is assessing possible relations with Hashimoto's thyroiditis, Crohn's disease, rheumatoid arthritis, and squamous cell carcinoma.
• Plugged apocrine (sweat) gland or hair follicle.
• Excessive sweating.
• Bacterial infection.
• Sometimes linked with other auto-immune conditions.^[22][23]
• Androgen dysfunction.
• Genetic disorders that alter cell structure.
• Being overweight makes it worse, however this condition is not caused by obesity and weight loss will improve but not cure it. Patients with more advanced cases may find exercise intolerably painful, which may increase the rate of obesity among sufferers.

The historical understanding of the disease is that there are dysfunctional apocrine glands^[17] or dysfunctional hair follicles,^[24] possibly triggered by a blocked gland, creating inflammation, pain, and a swollen lesion. More recent studies imply there is an autoimmune component.

HS is not caused by any bacterial elements.

Triggering factors

There are a number of triggering factors that should be taken into consideration, as it is advisable to avoid such triggers.

• Obesity^[25] is an exacerbating rather than a triggering factor,^[26] through mechanical irritation, occlusion, and maceration.
• Tight clothing,^[25] and clothing made of heavy, non-breathable materials.
• Smoking^[27] tobacco products.
• Deodorants, depilation products, shaving of the affected area – their association with hidradenitis suppurativa is still an ongoing debate amongst researchers.^[28]
• Drugs, in particular oral contraceptives^[29] (i.e. oral hormonal birth control; "the pill") and lithium.^[30]
• Hot and especially humid climates ^[31] (dry/arid climates often cause remission).

Predisposing factors

• Genetic factors:^[26] an autosomal dominant inheritance pattern has been postulated.^[32]
• Endocrine factors: sex hormones, principally an excess of androgens, are thought to be involved, although the apocrine glands are not sensitive to these hormones.^[33] Women often have outbreaks before menstruation and post-pregnancy, and the disease usually remits during pregnancy and after menopause.

Severe complications

In disease stage III, fistulas left undiscovered, undiagnosed, or untreated, can lead to the development of squamous cell carcinoma, a rare cancer, in the anus or other affected areas.^[34][35] Other stage III chronic sequelae may also include anemia, multilocalised infections, amyloidosis, and arthropathy. Stage III complications have been known to lead to death, but clinical data is still uncertain.

Potential complications

• Contractures and reduced mobility of the lower limbs and axillae due to fibrosis and scarring. Severe lymphedema may develop in the lower limbs.
• Local and systemic infections (meningitis, bronchitis, pneumonia, etc.), which may even progress to sepsis.
• Interstitial keratitis.
• Anal, rectal, or urethral fistulas in anogenital hidradenitis suppurativa.^[36]
• Normochromic or hypochromic anemia.^[37]
• Squamous cell carcinoma: this has been found on rare occasions in chronic hidradenitis suppurativa of the anogenital region.^[38] The mean time to the onset of this type of lesion is 10 years or more and the tumors are usually highly aggressive.
• Tumors of the lung and oral cavity, probably related to the high level of smoking among these patients, and liver cancer.^[39]
• Hypoproteinemia and amyloidosis, which can lead to renal failure and death.^[40]
• Seronegative and usually asymmetric arthropathy: pauciarticular arthritis, polyarthritis/polyarthralgia syndrome.^[41]

Treatments

Treatments may vary depending upon presentation and severity of the disease. Due to the poorly studied nature of this disease, the effectiveness of the drugs and therapies listed below is not yet clear, and patients should discuss all options with their doctor or dermatologist. Nearly a quarter of patients state that nothing relieves their symptoms.^[42] A list of treatments that are possible treatments for some patients is as follows.

• Lifestyle
  • Changes in diet avoiding inflammatory foods, foods high in refined carbohydrates.
  • Warm compresses,^[43] hydrotherapy, balneotherapy.
  • Icing the inflamed area daily until pain reduction is noticed.
  • Weight loss in overweight and obese patients, as well as smoking cessation can improve or even alleviate many symptoms of Hidradenitis suppurativa: Obese and overweight patients should be helped to lose weight^[26] in all cases of HS regardless of which stage patient may be in.

• Medication
  • Antibiotics Taken orally, these are used for their anti-inflammatory properties rather than to treat infection. The most effective is a combination of Rifampicin [300 mg twice a day] and Clindamycin [300 mg twice a day] given concurrently for 2–3 months. This brings about remission in around three quarters of cases.^[44] A few popular antibiotics used to treat HS include tetracycline, minocycline, and clindamycin.
  • Corticosteroid injections. Also known as intralesional steroids: can be particularly useful for localized disease, if the drug can be prevented from escaping via the sinuses.
  • Vitamin A supplementation
  • Anti-androgen therapy: hormonal therapy with cyproterone acetate and ethinyloestadiol proved effective in randomized control trials. It is of note that dosages reported have been very high.^[45]
  • IV or subcutaneous infusion of anti-inflammatory (anti-TNF-alpha) drugs such as infliximab (Remicade), etanercept (Enbrel),^[46] and adalimumab.^[47] This use of the drugs is not currently Food and Drug Administration (FDA) approved and is somewhat controversial, and therefore may not be covered by insurance.
  • Zinc gluconate taken orally has been shown to induce remission. Recommended dose is at least 30 mg taken 3 times daily (90 mg/day). Toxicity is known to occur at doses exceeding 1000 mg/day.^[48]
  • Chlorhexidine (Hibiclens) plus an antibiotic soap for cleansing the skin surface. Hexachlorophene shower with liquid soap like Phisohex, covering sores with Metrolotion after medicated showers. These are considered to be general measures, and are the foundation of any good medical treatment and management plans for HS.
  • Turmeric capsules orally or through topical application. The active ingredient in the tumeric spice is curcumin.
  • Infliximab: a chimeric monoclonal anti-TNF antibody has demonstrated efficacy in treating HS.^[43]
  • Topical clindamycin has been shown to have an effect in double-blind placebo controlled studies.^[49]

• Surgical therapy

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 application of a split thickness skin graft is more appropriate.^[21]

• Radiation

Electron beam radiotherapy has been a successful treatment of hidradenitis, especially in Europe; it is not a common treatment option in most of the United States, as radiation oncologists generally refuse to treat patients with non-malignant diseases because of the potential for secondary radiation-induced tumors in the long term.

References

External links

• Medline: What is Hidradenitis Suppurativa?
• The Doctor's Doctor
• Hidradenitis Suppurativa (2004) Prof J. Revuz
• Hidradenitis Suppurativa Links
• Hidradenitis Suppurativa Foundation A Foundation site for sufferers of Hidradenitis Suppurativa
• HS-USA HS-USA is a nonprofit public 501c3 charity incorporated in the State of Michigan, USA.