Hidradenitis suppurativa

Hidradenitis suppurativa, sometimes known as acne inversa or Verneuil's disease, is a long-term dermatological condition 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, perineum, buttocks, and the groin. Scar tissue remains after healing. HS may significantly limit many everyday activities, for instance, walking, hugging, moving, and sitting down. Sitting disability may occur in patients with lesions in the sacral, gluteal, perineal, femoral, groin or genital regions. Prolonged periods of sitting down can also worsen the condition of the skin of these patients.
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 caused by an infection, poor hygiene, or the use of deodorant. Instead, it is believed to be caused by hair follicles being obstructed, with the nearby apocrine sweat glands being strongly implicated in this obstruction. The sweat glands may or may not be inflamed. Diagnosis is based on the symptoms.
No cure is known, though surgical excision with wet-to-dry dressings, proper wound care, and warm baths or showering with a pulse-jet shower may be used 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 viable. Rarely, a skin lesion may develop into skin cancer.
If mild cases of HS are included, then the estimate of its frequency is from 1–4% of the population. Women are three times more likely to be diagnosed with it than men. Onset is typically in young adulthood and may become less common after 50 years old. It was first described between 1833 and 1839 by French anatomist Alfred Velpeau.

Terminology

Although hidradenitis suppurativa is often called acne inversa, it is not a form of acne. Hidradenitis suppurativa lacks the core defining features of acne, such as the presence of closed comedones and increased sebum production.

Causes

The exact cause of hidradenitis suppurativa remains unknown, and there has, in the recent past, been notable disagreement among experts in this regard. The condition, however, likely stems from both genetic and environmental causes. Specifically, an immune-mediated pathology has been proposed, although environmental factors have not been ruled out.
Lesions will occur in any body area with hair follicles, and/or sweat glands. Areas such as the axilla, groin, and perineal region are more commonly involved. This theory includes most of these potential indicators:

Post-pubescent individuals
Blocked hair follicles or blocked apocrine sweat glands
Excessive sweating
Androgen dysfunction
Genetic disorders that alter cell structure

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.

Triggering factors

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, nonbreathable materials
Deodorants, depilation products, shaving of the affected area – their association with HS is still an ongoing debate among researchers.
Drugs, in particular oral contraceptive pills, cigarette smoking, and lithium.
Hot and especially humid climates.
Stress
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.
* Diabetes mellitus is common in hidradenitis suppurativa and seems to be a risk factor.

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- secretase. This complex cuts apart many different proteins, which is a crucial 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 influences normal immune system function. Studies suggest mutations in the NCSTN, PSEN1, or PSENEN genes 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 skin inflammation. In addition, the composition of the intestinal microflora and as a consequence dietary patterns appear to play a role. Although dysbiosis of the cutaneous microbiome apparent in HS is not observed, the concurrent existence of inflammatory gut and skin diseases has led to the hypothesis of a gut-skin axis in which gut microbiota is implicated. Indeed, analysis of bacterial taxa in fecal samples from HS patients supports the possibility of a role for intestinal microbial alterations in this chronic inflammatory skin disease.
Precocious puberty is more common among children and adolescents with hidradenitis suppurativa compared to those without the condition, according to a recent case-control study. An analysis of the Explorys database revealed that pediatric patients with precocious puberty have double the risk of developing HS, even after adjusting for factors like demographic characteristics and body mass index.

Diagnosis

Early diagnosis is essential in avoiding tissue damage. However, HS is often misdiagnosed or diagnosed late due to healthcare professionals not being aware of the condition or people not consulting with a physician. Globally, the diagnosis is delayed more than 7 years in average after symptoms appear. This is much longer than with other skin conditions.

Stages

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.

Hurley's staging system

Hurley's staging system was the first classification system proposed and is still in use for the classification of patients with skin diseases. 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 to determine appropriate therapy for patients. These three stages are based on Hurley's staging system, which relies on the subjective extent of the diseased tissue. Hurley's three stages of hidradenitis suppurativa are:

Stage	Characteristics
I	Solitary or multiple isolated abscess formation without scarring or sinus tracts
II	Recurrent abscesses, single or multiple widely separated lesions, with sinus tract formation
III	Diffuse or broad involvement across a regional area with multiple interconnected sinus tracts and abscesses

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:

Anatomic regions involved
Number and types of lesions involved
The distance between lesions, in particular, the longest distance between two relevant lesions
The presence of normal skin in between lesions

Points are accumulated in the above categories and added to give a regional and total score. In addition, the authors recommend adding a visual analog scale for pain or using the dermatology life quality index when assessing HS.

Treatment

Treatment depends upon the presentation and severity of the disease. Due to the poorly studied nature of the disease, the effectiveness of medications and therapies was unclear. Clear and sensitive communication from health care professionals, and social and psychological interventions can help manage the emotional impact of the condition and aid necessary lifestyle changes. In May 2023, the European Commission approved Cosentyx for active moderate to severe hidradenitis suppurativa in adults.
Other possible treatments include the following:

Cryotherapy

has demonstrated efficacy against the disease, with 88% of persistent lesions resolving in a clinical trial of 23 patients.

Lifestyle

Warm baths may be tried in those with mild disease. Weight loss and smoking cessation are recommended.

Medication

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. Popular antibiotics also include tetracycline and minocycline. Topical clindamycin has been shown to have an effect in double-blind placebo-controlled studies. In a retrospective review and telephone survey, intravenous ertapenem therapy showed clinical improvement with 80.3% of subjects reporting medium to high satisfaction and 90.8% would recommend ertapenem to other patients.
Corticosteroid injections, also known as intralesional steroids, can be 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, are effective in clinical studies. However, the quality of available evidence is low and does not presently allow for robust evidence-based recommendations.
Intravenous infusion or subcutaneous injection of anti-inflammatory drugs such as infliximab, and etanercept This use of these drugs is not currently approved in the United States by the Food and Drug Administration and is somewhat controversial.
Biologics: Various biologics can improve HS lesions. Specifically adalimumab at weekly intervals is useful. Adalimumab and secukinumab are both approved by the FDA for the treatment of HS as of 2023.
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.
Zinc and nicotinamide, at doses of 90 mg and 30 mg respectively, have shown efficacy against mild to moderate hidradenitis suppurativa in a controlled retrospective clinical trial.