|Other names||Acne inversa, acne conglobata, apocrine acne, Verneuil's disease, Velpeau’s disease|
|Hidradenitis suppurativa (stage II) in the left armpit.|
|Symptoms||Multiple inflamed and swollen skin lesions|
|Usual onset||Young adulthood|
|Types||Stage I, II, III|
|Diagnostic method||Based on symptoms|
|Differential diagnosis||Acne, acne conglobata, pilonidal cysts|
|Treatment||Warm baths, laser therapy, surgery|
|Medication||Antibiotics, immunosuppressive medication|
|Frequency||1–4% of people|
Hidradenitis suppurativa (HS), also known as acne inversa, is a long-term skin disease characterized by the occurrence of inflamed and swollen lumps. These are typically painful and break open, releasing fluid or pus. The areas most commonly affected are the underarms, under the breasts, and the groin. Scar tissue remains after healing. Self-consciousness or depression may result.
The exact cause is usually unclear but believed to involve a combination of genetic and environmental factors. About a third of people with the disease have an affected family member. Other risk factors include obesity and smoking. The condition is not infectious, related to hygiene, or the use of deodorant. The underlying mechanism is believed to involve either a dysfunction of apocrine sweat glands or hair follicles. Diagnosis is based on the symptoms.
There is no known cure. Warm baths may be tried in those with mild disease. Cutting open the lesions to allow them to drain does not result in significant benefit. While antibiotics are commonly used, evidence for their use is poor. Immunosuppressive medication may also be tried. In those with more severe disease, laser therapy or surgery to remove the affected skin may be carried out. Rarely, a skin lesion may develop into skin cancer.
It is estimated to affect between 1% and 4% of people. Women are three times more likely to be diagnosed than men. Onset is typically in young adulthood and may become less common after fifty years old. It was first described some time between 1833 and 1839 by French anatomist Alfred Velpeau.
Signs and symptoms
The disease is characterized by the occurrence of inflamed and swollen lumps. These are typically painful and break open, releasing fluid or pus. The areas most commonly affected are the underarms, under the breasts, and the groin. Scar tissue remains after healing. Self-consciousness or depression may result.
Lesions occur in any body areas with hair follicles, although areas such as the axilla, groin, and perianal region are more commonly involved. This theory includes most of the following potential indicators:
- Post-pubescent individuals
- Blocked hair follicles or blocked apocrine sweat glands
- Excessive sweating
- 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, which creates inflammation, pain, and a swollen lesion.
Several triggering factors should be taken into consideration:
- Obesity is an exacerbating rather than a triggering factor, through mechanical irritation, occlusion, and skin maceration.
- Tight clothing, and clothing made of heavy, non-breathable materials.
- Deodorants, depilation products, shaving of the affected area – their association with HS is still an ongoing debate amongst researchers.
- Drugs, in particular oral contraceptive pills and lithium.
- Hot and especially humid climates.
- 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.
Some cases have been found to result from mutations in the NCSTN, PSEN1 or PSENEN genes. The genes produce proteins that are all components of a complex called gamma- (γ-) secretase. This complex cuts apart (cleaves) many different proteins, which is an important step in several chemical signaling pathways. One of these pathways, known as Notch signaling, is essential for the normal maturation and division of hair follicle cells and other types of skin cells. Notch signaling is also involved in normal immune system function. Studies suggest that mutations in the NCSTN, PSEN1, or PSENEN gene impair Notch signaling in hair follicles. Although little is known about the mechanism, abnormal Notch signaling appears to promote the development of nodules and lead to inflammation in the skin.
Hidradenitis suppurativa 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.
The Hurley's staging system was the first classification system proposed, and is still in use for the classification of patients with skin 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:
|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.)|
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:
- Anatomic regions involved (axilla, groin gluteal, or other region or inframammary region left or right)
- Number and types of lesions involved (abscesses, nodules, fistulas or 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., if all lesions are 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.
Treatment depends upon presentation and severity of the disease. Due to the poorly studied nature of the disease, the effectiveness of the drugs and therapies listed below is unclear. Possible treatments include the following:
- Antibiotics: taken by mouth, 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. A few popular antibiotics include tetracycline, minocycline, and clindamycin. Topical clindamycin has been shown to have an effect in double-blind placebo controlled studies.
- 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.
- Antiandrogen therapy: hormonal therapy with antiandrogenic medications such as spironolactone, flutamide, cyproterone acetate, ethinylestradiol, finasteride, dutasteride, and metformin have been found to be effective in clinical studies. However, the quality of available evidence is low and does not presently allow for robust evidence-based recommendations.
- Intravenous or subcutaneous infusion of anti-inflammatory (TNF inhibitors; anti-TNF-alpha) drugs such as infliximab, and etanercept. This use of these drugs is not currently Food and Drug Administration (FDA) approved and is somewhat controversial, so may not be covered by insurance.
- TNF inhibitor: Studies have supported that various TNF inhibitors have a positive effect on HS lesions. Specifically adalimumab at weekly intervals is useful.
- 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.
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 or delayed application of a split-thickness skin graft is an option. Another option is covering the defect with a perforator flap. With this technique the (mostly totally excised) defect is covered with tissue from an area nearby. For example, the axilla with a fully excised defect of 15 × 7 cm can be covered with a TAP flap (thoracodorsal artery perforator flap)
Laser hair removal
In stage III disease, as classified by the Hurley's staging system, fistulae left undiscovered, undiagnosed, or untreated, can rarely lead to the development of squamous cell carcinoma 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 sepsis, but clinical data is still uncertain.
- Contractures and reduced mobility of the lower limbs and axillae due to fibrosis and scarring occur. Severe lymphedema may develop in the lower limbs.
- Local and systemic infections (meningitis, bronchitis, pneumonia, etc.), are seen, which may even progress to sepsis.
- Interstitial keratitis
- Anal, rectal, or urethral fistulae
- Normochromic or hypochromic anemia
- People with HS may be at increased risk for autoimmune disorders including ankylosing spondylitis, rheumatoid arthritis, and psoriatic arthritis.
- 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, and liver cancer.
- Hypoproteinemia and amyloidosis, which can lead to kidney failure and death
- Seronegative and usually asymmetric arthropathy: pauciarticular arthritis, polyarthritis/polyarthralgia syndrome
- From 1833 to 1839 in a series of three publications, Velpeau identified and described a disease we now know as 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 sweat glands.
- In 1956, Pillsbury et al. coined the term follicular occlusion triad for the common association of hidradenitis suppurativa, acne conglobata and dissecting cellulitis of the scalp. Modern clinical research still employs Pillsbury's terminology for these conditions' descriptions.
- 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, submammary, and perianal abscesses, in a series of three publications from 1833 to 1839. One of his colleagues also located in Paris, named Verneuil, coined the term hidrosadénite phlegmoneuse about 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".
|Velpeau||1839||First description of the hidradenitis suppurativa|
|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|
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 – 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 outdated term based on the same thesis
- Fox-den disease – a term not used in medical literature, based on the deep fox den–like sinuses
- Hidradenitis supportiva – a misspelling
- Pyodermia fistulans significa – now considered archaic
- Verneuil's disease – recognizing the surgeon whose name is most often associated with the disorder as a result of his 1854–1865 studies
|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.|
Although hidradenitis suppurativa is often referred to as acne inversa, it is not a form of acne and lacks the core defining features of acne such as the presence of closed comedones and increased sebum production.
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