Hidradenitis suppurativa

Hidradenitis suppurativa
Classification and external resources
Specialty	Dermatology
ICD-10	L73.2
ICD-9-CM	705.83
DiseasesDB	5892
eMedicine	emerg/259 med/2717 derm/892
Patient UK	Hidradenitis suppurativa
MeSH	D017497

Hidradenitis suppurativa (HS) is a common (though rarely diagnosed), chronic skin disease characterized by clusters of abscesses or subcutaneous boil-like "infections" (oftentimes free of actual bacteria) that most commonly affects apocrine sweat gland bearing areas, such as the underarms, under the breasts, inner thighs, groin and buttocks. The disease is not contagious. There are indications that it is hereditary among certain ethnic groups and autoimmune in nature. Onset is most common in the late teens and early 20's.

HS outbreaks are painful in tender areas and may persist for years with interspersed periods of inflammation, often culminating in sudden drainage of pus. This process often forms open wounds that will not heal and frequently leads to significant scarring. For unknown reasons, people with HS develop plugging of their apocrine glands. Incision and drainage procedures may provide symptomatic relief. HS flares may be triggered by emotional/erotic stress, sweating, hormonal changes, heat and humidity, and the condition is exacerbated by friction from clothing.

Persistent lesions may lead to 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 is variable, with some experiencing remission for months to years at a time, while others may worsen and require multiple surgeries. Bacterial infections and cellulitis (deep tissue inflammation) are other common complications of HS. Depression and physical pain are often seen with HS and can be difficult to manage. HS often goes undiagnosed for years due to embarrassment causing delay in seeking treatment. Due to the "invisible" nature of it, it is frequently misdiagnosed. There is currently no known cure nor any consistently effective treatment.

Carbon dioxide laser surgery has been shown as an effective treatment providing quality of life improvement, with peer reviewed articles showing an 80% chance of non recurrence in the surgically removed site. Lukewarm Sitz baths can provide great relief, gentle antiseptic skin cleansers and hydrogen peroxide assist in keeping affected areas free of bacteria. HS is an orphan disease due to lack of publicity and sparse research efforts. The incidence of HS is not well established, but has been estimated as being between 1:24 (4.1%) and 1:600 (0.2%).

Causes

The cause of HS remains unknown and experts disagree over proposed causes.

Lesions occur in any body areas with hair follicle although intertriginous areas such as the axilla, groin, and perianal region are more commonly involved. This theory includes most of the following potentials indicators:

• Post-pubescent individuals are more likely to exhibit HS.
• Plugged apocrine (sweat) gland or hair follicle
• Excessive sweating
• Sometimes linked with other autoimmune conditions
• Androgen dysfunction
• Genetic disorders that alter cell structure
• 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 suggests dysfunctional apocrine glands or dysfunctional hair follicles, possibly triggered by a blocked gland, create inflammation, pain, and a swollen lesion.

Triggering factors

There are several triggering factors that should be taken into consideration.

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

Predisposing factors

• Genetic factors: an autosomal dominant inheritance pattern has been proposed.
• Endocrine factors: sex hormones, especially an excess of androgens, are thought to be involved, although the apocrine glands are not sensitive to these hormones. Women often have outbreaks before their menstrual period and after pregnancy; HS severity usually decreases during pregnancy and after menopause.

Stages

HS 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

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:

Stage	Characteristics
I	Solitary or multiple isolated abscess formation without scarring or sinus tracts. (A few minor sites with rare inflammation; may be mistaken for acne.)
II	Recurrent abscesses, single or multiple widely separated lesions, with sinus tract formation. (Frequent inflammation restrict movement and may require minor surgery such as incision and drainage.)
III	Diffuse or broad involvement across a regional area with multiple interconnected sinus tracts and abscesses. (Inflammation of sites to the size of golf balls, or sometimes baseballs; scarring develops, including subcutaneous tracts of infection – see fistula. Obviously, patients at this stage may be unable to function.)

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 the following:

• 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(actually sinuses), 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 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.

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 unclear, and patients should discuss all options with their physician or dermatologist. Nearly a quarter of patients state that nothing relieves their symptoms. Possible treatments include the following:

Lifestyle

• Changes in diet avoiding inflammatory foods.
• Warm compresses with distilled vinegar water, and taking hot baths with distilled white vinegar in the water hydrotherapy, balneotherapy.
• Icing the inflamed area daily until pain reduction is noticed.

Medication

• Antibiotics- taken orally, these are used for their anti-inflammatory properties rather than to treat infection. Most effective is a combination of rifampicin and clindamycin given concurrently for 2–3 months. This brings about remission in around three quarters of cases. A few popular antibiotics used to treat hidradenitis suppurativa 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 ethinyl estradiol proved effective in randomized, controlled trials. Dosages reported have been very high.
• Intravenous or subcutaneous infusion of anti-inflammatory (anti-TNF-alpha) drugs such as infliximab (Remicade), and etanercept (Enbrel). This use of these drugs is not currently Food and Drug Administration (FDA) approved and is somewhat controversial, and therefore may not be covered by insurance.
• TNF inhibitor: Studies have supported that various TNF inhibitors have a positive effect on hidradenitis suppurativa lesions. There is a large efficacy and safety study of adalimumab registered with the FDA. It recruited 309 patients and is currently completed. The results have not yet been published. FDA cleared Adalimumab for the treatment for Hidradenitis suppurativa. Humira adalimumab is the first FDA approved drug for the treatment of HS.
• Zinc gluconate taken orally has been shown to induce remission.
• Chlorhexidine (Hibiclens) plus an antibiotic soap for cleansing the skin surface. 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 plan for hidradenitis suppurativa.
• Topical clindamycin has been shown to have an effect in double-blind placebo controlled studies.
• Topical resorcinol is a keratolytic agent that targets the follicular keratin plug and has been shown to have efficacy in several case series studies.
• Topical isotretinoin is usually ineffective in people with HS and is more commonly known as a medication for the treatment of acne vulgaris. Individuals affected by HS who responded to isotretinoin treatment tended to have milder cases of the condition.

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 are disinclined to treating patients with non-malignant diseases because of the potential for secondary radiation-induced tumors in the long term.

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 application of a split thickness skin graft is more appropriate.

Laser hair removal

The 1064 nanometer wavelength laser for hair removal aids in the treatment of HS. A randomized control study has shown improvement in HS lesions with the use of an Nd:YAG laser.

Prognosis

In stage III disease, 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. Other stage III chronic sequelae may also include anemia, multilocalized 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.
• Normochromic or hypochromic anemia.
• Squamous cell carcinoma: this has been found on rare occasions in chronic hidradenitis suppurativa of the anogenital region. 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.
• Hypoproteinemia and amyloidosis, which can lead to renal failure and death.
• Seronegative and usually asymmetric arthropathy: pauciarticular arthritis, polyarthritis/polyarthralgia syndrome.

History

• In 1839, Velpeau identified and described hidradenitis suppurativa.
• In 1854, Verneuil described hidradenitis suppurativa as "Hidrosadénite Phlegmoneuse". This is how HS obtained its alternate name "Verneuil's disease".
• In 1922, Schiefferdecker hypothesized a pathogenic link between "Acne inversa" and human apocrine sweat glands.
• 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 abscedens et suffodiens". 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". Plewig and Kligman's research follows in Pillsbury's footsteps, offering explanations of the symptoms associated with hidradenitis suppurativa.
• In 1989, Plewig and Steger's research led them to rename hidradenitis suppurativa, calling it "Acne Inversa" – which is not still used today in medical terminology; although some individuals still use this outdated term.

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 pathogenicassociation 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".

Author	Year	Findings
Velpeau	1839	First description of the hidradenitis suppurativa
Verneuil	1854	"Hidrosadénite phlegmoneuse"
Pillsbury	1956	Acne triad (hidradenitis suppurativa, perifolliculitis capitis abscendens et suffodiens, acne congoblata)
Plewig & Kligman	1975	Acne tetrad (acne triad + pilonidal sinus)
Plewig & Steger	1989	Acne inversa

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.

• 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 which has not gained widespread favor.
• Apocrine acne – an outdated term based on the disproven concept that apocrine glands are primarily involved, though many do suffer with apocrine gland infection
• Apocrinitis – another outdate term based on the same thesis
• Fox-den disease – a term not used in medical literature, based on the deep fox den / burrow – like sinuses
• Hidradenitis Supportiva – a misspelling
• Pyodermia fistulans significa – now considered archaic
• Velpeau's disease – commemorating the surgeon who first described the disease in 1833
• Verneuil's disease – recognizing the surgeon whose name is most often associated with the disorder as a result of his 1854–1865 studies

Histology

Author	Year	Major Features
Plewig & Steger	1989	Initial hyperkeratosis of the follicular infundibulum. Bacterial super-infection and follicle rupture. Granulomatous inflammatory reaction of the connective tissue. Apocrine and eccrine sweat glands secondarily involved.
Yu & Cook	1990	Cysts and sinus tracts lined with epithelium, in part with hair shafts. Inflammation of apocrine sweat glands only if eccrine sweat glands and hair follicles are also inflamed.
Boer & Weltevreden	1996	Primary inflammation of the follicular infundibulum. Apocrine sweat glands are secondarily involved.

External links

• The Hidradenitis Suppurativa Trust The HS Trust is a UK registered charity
• Medline: What is Hidradenitis Suppurativa?
• The Doctor's Doctor
• Hidradenitis Suppurativa (2004) Prof J. Revuz
• Hidradenitis Suppurativa Support Hidradenitis Suppurativa Support provides support and advice for sufferers