Hidradenitis Suppurativa: Clinical Guidelines

List of Abbreviations

IL – interleukin

TNF-α – tumor necrosis factor-α

Th-lymphocytes – T-helper lymphocytes

HS-PGA – Hidradenitis Suppurativa Physician’s Global Assessment

HSSI – Hidradenitis Suppurativa Severity Index

Terms and Definitions

Hidradenitis suppurativa is a chronic recurrent inflammatory skin disease that develops after puberty and is characterized by the appearance in areas of the skin rich in apocrine sweat glands (most commonly in the axillary, inguinal, and anogenital regions) of recurrent painful nodules, abscesses, and the formation of fistulous tracts and scars.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Hidradenitis suppurativa (syn.: suppurative hidradenitis) is a chronic recurrent inflammatory skin disease that develops after puberty and is characterized by the appearance in areas of the skin rich in apocrine sweat glands (most commonly in the axillary, inguinal, and anogenital regions) of recurrent painful nodules, abscesses, and the formation of fistulous tracts and scars.

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

The development of hidradenitis suppurativa is associated with pathological changes in the upper parts of the hair follicle. Follicular hyperkeratosis in the area of the isthmus and infundibulum leads to occlusion of the sebaceous gland ducts [1, 2]. Currently, it is being debated whether follicular hyperkeratosis is a primary event in the pathogenesis of hidradenitis suppurativa or if it develops as a result of an inflammatory response; from this perspective, hidradenitis suppurativa is considered an autoinflammatory disease [3].

The consequence of follicular hyperkeratosis and sebaceous gland occlusion is the accumulation of follicular contents and dilation of the hair follicle. Rupture of the dilated hair follicle followed by the release of follicular contents—keratin fragments, cellular detritus—into the surrounding dermis and subcutaneous tissue, as well as secondary bacterial invasion, significantly amplifies the inflammatory response. Further development and spread of inflammation in the skin are accompanied by the involvement of apocrine sweat glands and the formation of abscesses and fistulas [2, 4–7].

The skin microbiota plays a certain role in the pathogenesis of hidradenitis suppurativa, but bacteria are not the primary etiological factor in the development of the disease. The bacterial microflora colonizing the skin surface and hair follicles acts as an additional factor stimulating the enhancement of the immune-inflammatory response [8]. Higher temperatures and humidity in skin folds promote the active proliferation of microflora [9].

Several specific features must be emphasized in the development of the inflammatory process in hidradenitis suppurativa [10–18]:

1) Hidradenitis suppurativa is not a primary infectious disease; bacterial colonization of hair follicles and surrounding tissues is secondary.

2) Patients exhibit skin dysbiosis with a decrease in the number and species diversity of commensals, as well as a shift toward anaerobic microflora.

3) Biofilm formation is observed on the skin surface.

4) The results of studies on the bacterial composition of the skin show high variability and low reproducibility.

Bacteria and cellular detritus entering the dermis and subcutaneous tissue after hair follicle rupture activate macrophages, dendritic cells, and fibroblasts, stimulating the secretion of pro-inflammatory cytokines—IL-1β and tumor necrosis factor (TNF)-α, the levels of which are significantly elevated in the skin of patients with hidradenitis suppurativa [19-25]. IL-1β and TNF-α stimulate keratinocytes to produce a number of chemokines that attract neutrophil granulocytes, T lymphocytes, and monocytes to the lesion sites [6]. Furthermore, TNF-α increases adhesion molecule expression by endothelial cells and increases the ratio of Th17 lymphocytes to regulatory T lymphocytes, which is accompanied by increased cytokine production by Th17 lymphocytes [24, 25].

In the lesion sites, the number of Th17 lymphocytes is increased, and the expression level of the IL-17 they produce is elevated, which correlates with disease severity [25-28]. IL-17 increases macrophage production of IL-1β and TNF-α and promotes the further development of inflammation through the influx of neutrophils, dendritic cells, and T lymphocytes into the lesion sites [1, 22, 29, 30].

The cytokine IFN-γ induces the secretion of CXCL10 and other chemokines that attract Th1 lymphocytes to the lesion sites [21, 25, 31]. It stimulates the migration of immune cells from the systemic circulation to the site of inflammation, the differentiation of macrophages into antigen-presenting cells, and the activation of T lymphocytes in the lesion sites [32].

The development of inflammation in the dermis and subcutaneous tissue leads to the formation of nodules and their suppuration [20, 22, 33]. Matrix metalloproteinases degrade the extracellular matrix, promote the rupture of dilated hair follicles, and cause destruction of the dermis. In hidradenitis suppurativa, irreversible tissue destruction is observed, accompanied by the formation of fistulous tracts and coarse skin scars [20].

Fistulous tracts in hidradenitis suppurativa are unique structures consisting of stratified squamous epithelium, identical to the overlying epidermis and producing active inflammatory mediators [3, 34, 35]. It is hypothesized that they form as a result of hair follicle destruction and the release of stem cells, whose aberrant proliferation and differentiation lead to the formation of epithelial strands [36].

The involvement of sex hormones in the development of hidradenitis suppurativa is confirmed by the worsening of the disease during systemic hormonal therapy with androgen-like effects [37–39].

The presence of a genetic predisposition to the development of hidradenitis suppurativa is confirmed by the high frequency of the disease (34–42%) among close relatives of patients [6, 40]. Hereditary predisposition to hidradenitis suppurativa may be associated with genetically determined disorders in the differentiation of hair follicle keratinocytes or specific features of immune system activation during the inflammatory response in the dermis [41–45].

Predisposing factors for hidradenitis suppurativa include tobacco smoking and obesity. Nicotine induces epidermal hyperplasia, contributing to follicular hyperkeratosis, occlusion, and follicle rupture [46–48]. It also stimulates macrophage production of IL-1β and TNF-α, promotes the release of TNF-α by keratinocytes and Th17 lymphocytes, and increases the expression of matrix metalloproteinases [22]. In addition, nicotine promotes the adhesion of microorganisms on the skin surface and in hair follicles, which facilitates bacterial proliferation and the formation of bacterial biofilms [49, 50]. The significance of obesity as a factor that can contribute to the development and exacerbation of hidradenitis suppurativa lies in the formation of pronounced skin folds [51]. Mechanical friction of contacting skin surfaces in the folds contributes to the induction of follicular hyperkeratosis, while the moist, warm environment of the skin folds leads to excessive bacterial proliferation.

1.3 Epidemiology of the Disease or Condition

The prevalence of hidradenitis suppurativa is unknown; data vary widely from 0.1% to 4.1%. Among the European population, this figure is 0.7–1.2%. Women develop hidradenitis suppurativa twice as often as men. In women, skin lesions are more frequently observed in the submammary and inguinal-femoral folds, whereas in men, eruptions are more commonly localized in the perineal, perianal, and gluteal regions. The peak incidence occurs between the ages of 20 and 39 years. In individuals of African descent, the disease occurs 3 times more frequently than in Caucasians. According to major international studies, the delay between the onset of hidradenitis suppurativa and diagnosis averages 7–10 years. During this time, 2/3 of patients manage to make an average of six visits to a doctor. Diagnostic delay, misdiagnoses, and inadequate treatment methods contribute to the progression of hidradenitis suppurativa [52–54].

There is a direct correlation between body mass index and the risk of developing hidradenitis suppurativa, as well as disease severity. Patients with severe obesity more frequently experience active and severe hidradenitis suppurativa [94].

An association of hidradenitis suppurativa with inflammatory joint and bowel diseases (Crohn's disease, ulcerative colitis) has been identified [62, 64, 65, 72, 75]. The association of hidradenitis suppurativa with various diseases has made it possible to distinguish a number of autoinflammatory syndromes that include hidradenitis suppurativa [221]. These include PASH (pyoderma gangrenosum, acne, hidradenitis suppurativa), PAPASH (pyogenic arthritis, pyoderma gangrenosum, acne, hidradenitis suppurativa), PASS (pyoderma gangrenosum, acne, hidradenitis suppurativa, ankylosing spondylitis), PsAPSASH (pustular psoriasis, arthritis, pyoderma gangrenosum, synovitis, acne, hidradenitis suppurativa), and SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndromes [221].

1.4 Features of Coding the Disease or Condition

ICD-10

L73 – Other follicular disorders

L73.2 – Hidradenitis suppurativa

ICD-11

ED92 – Diseases of apocrine sweat glands

ED92.0 – Hidradenitis suppurativa

1.5 Classification of the disease or condition

There is no universally accepted clinical classification.

1.6 Clinical presentation of the disease or condition

One of the most characteristic features of hidradenitis suppurativa is the localization of eruptions, which are typically situated in skin folds rich in apocrine sweat glands. The eruptions are often symmetrical, localized predominantly in the inguinal (in 90% of cases), axillary (69%), perianal and perineal (37%), gluteal (27%) regions, and beneath the breasts (18%); they may also occur in the inguinal-femoral fold, the pubic region, and less commonly on the face, chest, retroauricular region, scalp, eyelids, and back [94–97]. Initially, the axillary or anogenital region is most frequently affected, but as the disease progresses, other body areas become involved, and approximately 90% of patients have more than one area affected [98, 99]. The presence of apocrine glands, usually found in skin folds, is not considered a significant factor for lesion development, as eruptions can also appear where they are absent, such as in skin folds formed around a hernia [100].

Involvement of the inguinal-femoral folds is more common in women, whereas anogenital involvement is more frequent in men. There are specific features of skin lesion localization in patients with hidradenitis suppurativa and comorbid metabolic syndrome, in whom rashes are located on the abdomen and waist area more often than in non-obese patients [101]. Perianal localization of hidradenitis suppurativa rashes is characteristic of the association of this skin disease with inflammatory bowel diseases, although in ulcerative colitis, skin involvement in this area typically develops after colectomy in the setting of ileoanal pouch inflammation [102].

Rashes in hidradenitis suppurativa are polymorphic [103, 104]. Primary lesions may present as deep-seated, painful, firm, bright red dermal nodules less than 1 cm in diameter, or nodes that can merge to form cord-like skin elevations [105]. Nodules and nodes may spontaneously regress, persist for a long time, or form abscesses [106]. The resulting abscesses can merge deep within the dermis and spontaneously rupture to the surface [107]. Their rupture is accompanied by purulent and/or serosanguineous discharge [107].

While inflammatory lesions are initially transient and spontaneously regress, over time they become persistent. Large, widespread, bluish-red nodes develop, the surface of which ulcerates in a honeycomb pattern, along with abscesses and fistulous tracts (draining sinuses) [108]. Fibrotic processes, pronounced in the areas of inflammation, lead to the formation of hypertrophic bridging scars [107, 108].

Periodic exacerbations characterized by the appearance of new inflammatory nodes, alternating with periods of remission, are typical [107].

The appearance of rashes is usually accompanied by pain; pruritus is possible [109–111]. Many patients experience prodromal pain symptoms prior to the appearance of new elements [107].

Complications of hidradenitis suppurativa may develop. With pronounced manifestations of the disease or its prolonged course, infectious complications (erysipelas, soft tissue phlegmon followed by sepsis), impaired lymph drainage (lymphedema and elephantiasis, especially with genital involvement), and malignant transformation of lesions with the development of cutaneous squamous cell carcinoma may occur.

Scars can lead to restricted mobility, which is particularly significant when the axillary regions are affected. Involvement of the anogenital region may result in urethral, anal, and rectal strictures, as well as the development of perirectal and perourethral fistulas. A prolonged disease course is frequently associated with anemia, hypoproteinemia, and amyloidosis.

Among patients with hidradenitis suppurativa, there is a high prevalence of mental disorders: the incidence of depression is 36–43%, suicidal ideation or attempts are reported in 9–12% of patients, and the rate of completed suicides is higher in women [53, 82, 112, 113].

Several staging systems can be used to assess severity. The Hurley staging system is considered the simplest severity assessment system, according to which three stages of the disease are distinguished (Appendix G1) [114].

The severity of skin lesions in patients can be assessed using the Hidradenitis Suppurativa Physician's Global Assessment (HS-PGA) scale (Appendix G2). The HS-PGA scale is relatively simple to use and is frequently employed for clinical assessment of the degree of improvement in a patient's skin condition in clinical trials [115]. However, a major limitation of the HS-PGA scale is that patients may experience a clinically meaningful improvement that is not reflected by the HS-PGA, especially when evaluating patients with the most severe hidradenitis suppurativa.

Another system for assessing the severity of hidradenitis suppurativa is the Hidradenitis Suppurativa Severity Index (HSSI) (Appendix G3) [116, 117]. The use of HSSI requires the evaluation of qualitative objective and qualitative subjective indicators.

In addition, the Sartorius system is used in clinical trials; it is a universal, detailed, and dynamic scale that detects changes in disease severity over time and in response to treatment [118]. However, it is difficult to use in clinical practice due to its labor-intensiveness [6].

2. Diagnostics, medical indications and contraindications for diagnostic methods

The diagnosis of hidradenitis suppurativa is established clinically by examination and palpation of the skin, taking into account anamnestic data [107, 119]. If necessary, probing of the fistulas is performed. Initially, the course of the disease may be such that isolated hidradenitis suppurativa lesions arise and spontaneously regress over several years, clinically resembling furuncles. This can be one of the reasons for the frequently noted significant delay in diagnosis following the appearance of the first hidradenitis suppurativa rashes (on average about 7–10 years) [120]. Therefore, most patients have more than one lesion at the time of diagnosis [96]. In such cases, attention should be paid to the localization of rashes typical of hidradenitis suppurativa.

The main criteria for establishing the diagnosis are [121]:

1. characteristic skin lesions (double open pseudocomedones, nodes, abscesses, fistulous tracts, scars);

2. tendency for rashes to localize in skin folds in the axillary regions, perineum and inguinal region, submammary region, and breast areas;

3. chronic course of the disease, which can be persistent (presence of rashes for at least 6 months) and recurrent (more than 2 lesions that arose for the first time or appeared as a relapse within the last 6 months).

Additional (secondary) criteria for establishing the diagnosis are:

1. family history of the disease;

2. sterile discharge from fistulous tracts or the presence of commensal microflora upon bacteriological examination;

3. presence of a pilonidal sinus.

To provide the patient with recommendations on potential lifestyle modifications that can enhance therapeutic efficacy, data on tobacco use and body mass index should also be obtained.

Given that hidradenitis suppurativa can be one of the manifestations of PASH, PAPASH, PASS, PsAPASH, and SAPHO syndromes, skin examination should include checking for the possible presence of pyoderma gangrenosum, acne (including conglobate acne), and ruling out joint syndrome.

Laboratory and instrumental diagnostic methods, as well as histological examination of skin biopsy material, are not used for diagnosing hidradenitis suppurativa, but may be required to determine the activity of the pathological process (laboratory methods), assess its depth and extent (instrumental methods), or for differential diagnosis (histological examination of skin biopsy material) [6, 122].

2.1 Complaints and Anamnesis

Complaints and anamnesis are described in section 1.6. "Clinical picture".

Due to the potential association of hidradenitis suppurativa with inflammatory joint and bowel diseases, patients should be questioned about complaints indicating joint and bowel involvement, such as joint pain or stiffness, restricted joint mobility, abdominal pain, and stool disorders. If there are complaints pointing to potential joint and bowel diseases, the patient should be referred for a consultation with a general practitioner and/or a rheumatologist and/or a gastroenterologist.

2.2 Physical Examination

Physical examination data are described in section 1.6. "Clinical picture".

During the physical examination, one should consider the possible association of hidradenitis suppurativa with other skin diseases, such as pyoderma gangrenosum, pustular psoriasis, and acne [221].

2.3 Laboratory Diagnostics

Laboratory tests are not required to diagnose hidradenitis suppurativa, but they may be necessary to detect its complications and to monitor the safety of systemic therapy.

Comments: in patients with high activity of the pathological process in hidradenitis suppurativa, the erythrocyte sedimentation rate increases [128]. Anemia is one of the complications of long-standing hidradenitis suppurativa [98]. Safety monitoring of therapy with #dapsone**, #cyclosporine**, psoriasis retinoids, #isotretinoin, adalimumab**, #infliximab** is necessary due to the possibility of their adverse effect on hematopoiesis [123–127, 129–132].

Comments: hypoproteinemia is one of the complications of long-standing hidradenitis suppurativa [98]. Safety monitoring of therapy with #dapsone**, #ciclosporin**, psoriatic retinoids, #isotretinoin, adalimumab**, #infliximab** is necessary due to their potential impact on liver function, lipid metabolism, and water-electrolyte balance [123–127, 131, 133–139].

Comments: in case of high inflammatory activity in patients with hidradenitis suppurativa, the serum level of C-reactive protein increases [95, 123]

Comments: therapy with #ciclosporin**, adalimumab**, #infliximab**, which possess immunosuppressive effects, predisposes patients to the development of renal and urinary tract infections [126, 135, 136].

Comments: microbiological (culture) testing in hidradenitis suppurativa is indicated when clinical manifestations (e.g., fever) indicate activation of the infectious process or secondary infection [6]. The sample for testing should be obtained not only from the skin surface, but also from deep affected tissue areas.

2.4 Instrumental Diagnostics

Instrumental diagnostic methods make it possible to assess the extent and depth of lesions in the dermis that are not visually identifiable in hidradenitis suppurativa.

Comments: Ultrasound is not required for the diagnosis of hidradenitis suppurativa, but it allows the detection of visually imperceptible dermal changes, especially in obese patients [6]. The main objectives of ultrasound are: identification of early morphological elements, differentiation of abscesses and subcutaneous fistulous tracts, more accurate disease staging using the ultrasound scoring system (SOS-HS), preoperative mapping, postoperative control, and monitoring during glucocorticoid administration [142–144]

Comments: magnetic resonance imaging in patients with hidradenitis suppurativa can reveal marked skin thickening, tissue induration, and multiple abscess formation [145]. Visualization of fistulous tracts is possible. Therefore, magnetic resonance imaging may be required when preparing a patient for surgery to determine the location and extent of fistulous tracts deep within the dermis, and when lesions are located in the anogenital region, to detect fistulas communicating with the rectum or anal canal [6].

Comments: fistulography allows for the evaluation of the location and extent of fistulous tracts [148]

2.5 Other Procedures

Comments: pathomorphological examination of skin biopsy specimens is most often required for the differential diagnosis of hidradenitis suppurativa with cutaneous lymphomas, pyoderma gangrenosum, as well as scrofuloderma and actinomycosis [6, 122]. Early morphological changes in hidradenitis suppurativa include follicular hyperkeratosis [98]. Psoriasiform epidermal hyperplasia and perifollicular and diffuse inflammatory infiltrates may also be observed [149]. Perifolliculitis, active folliculitis, abscesses, granulomas, cysts, epithelium-lined sinuses, and horizontal fibrosis are observed [150]. Fibrosis, fat necrosis, and inflammation can be found in the subcutaneous tissue [98]. The inflammatory infiltrate in the lesions is mixed, consisting of lymphocytes, histiocytes, foreign body giant cells, plasma cells, and neutrophil granulocytes. The severity of changes may vary depending on the degree of inflammation [98].

Squamous cell carcinoma of the skin may develop within long-standing lesions of hidradenitis suppurativa, especially in the perianal region, for the diagnosis of which a pathomorphological examination of skin biopsy specimens is necessary. Signs of developing cutaneous squamous cell carcinoma may include changes in the appearance of a long-standing lesion (formation of an erosive-ulcerative defect in the scar area, an increase in the size and depth of the existing skin defect, formation of pronounced granulation tissue at the base of the skin defect) or changes in the patient's subjective sensations (increased pain or the appearance of any new sensations in the lesion area).

Comments: surgical intervention in patients with mild hidradenitis suppurativa may reduce the severity of symptoms; when fluctuating abscesses form, incision and drainage may be required. In severe hidradenitis suppurativa, wide excision of lesions containing fistulas is one of the treatment methods [146].

Comments: during therapy with tumor necrosis factor alpha (TNF-alpha) inhibitors, activation of Mycobacterium tuberculosis infection with the development of pulmonary and/or extrapulmonary tuberculosis is possible, which requires appropriate monitoring by a phthisiatrician. Screening of patients for whom tumor necrosis factor alpha (TNF-alpha) inhibitor therapy is planned is performed before starting treatment and once every 6 months.

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

Therapy for patients with hidradenitis suppurativa is carried out taking into account the severity of skin lesions and the efficacy of previously administered therapy.

Topical treatment aims to prevent follicular occlusion, reduce bacterial colonization and associated inflammation (topical antiseptics, disinfectants, and antibiotics), and reduce pain and inflammation in isolated lesions (intralesional administration of systemic corticosteroids) [155].

Systemic therapy is performed for mild hidradenitis suppurativa (no more than 4 inflammatory papules, nodules, or abscesses according to the Hidradenitis Suppurativa Physician Global Assessment [HS-PGA] severity scale) with widespread rashes, and for moderate-to-severe hidradenitis suppurativa when there are 5 or more inflammatory papules, nodules, or abscesses. Systemic antibacterial drugs, systemic retinoids for psoriasis or topical retinoids for acne, and #dapsone** are used for the systemic therapy of patients with moderate-to-severe hidradenitis suppurativa.

The administration of systemic antibacterial drugs is considered the primary treatment method for hidradenitis suppurativa. Systemic antibacterial drugs not only inhibit bacterial activity but also possess anti-inflammatory effects. In addition to a broad spectrum of antibacterial activity, tetracyclines inhibit chemotaxis and the activity of metalloproteinases, leading to a reduction in the inflammatory process. Tetracyclines are prescribed to patients with Hurley stage I and II hidradenitis suppurativa, with a treatment duration of 3–6 months.

In cases where the aforementioned drugs are ineffective, immunosuppressants are prescribed: #ciclosporin**, systemic corticosteroids, tumor necrosis factor alpha (TNF-alpha) inhibitors, and interleukin inhibitors (secukinumab**). When choosing a medication between tumor necrosis factor alpha (TNF-alpha) inhibitors and secukinumab**, the potential association of hidradenitis suppurativa with inflammatory bowel disease should be considered. Secukinumab**, which blocks IL-17A, may trigger an exacerbation of inflammatory bowel disease [222]. Therefore, in patients with hidradenitis suppurativa associated with inflammatory bowel disease, when choosing between tumor necrosis factor alpha (TNF-alpha) inhibitors and secukinumab, preference should be given to tumor necrosis factor alpha (TNF-alpha) inhibitors.

Surgical treatment methods may be used: fenestration (incision), drainage, excision of single lesions, deroofing, CO₂ and Nd:YAG laser therapy, cryosurgery, and radical (wide) excision of inflammatory lesions.

3.1 Conservative Treatment

Comments: in pediatric practice, chlorhexidine** solution for local and topical application should be used with caution.

• or

  povidone-iodine** 7.5%, 10% solution for local and topical application for skin and mucosal treatment is used undiluted for swabbing, washing, or as a wet compress [150].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: a contraindication to the prescription of povidone-iodine** solution for local and topical application is the neonatal period. A contraindication to the prescription of povidone-iodine** 10% solution for topical application is childhood under 2 years of age.

• or

  povidone-iodine 0.5% spray for local and topical application is applied to the skin surface by spraying 1–2 times a day; the number of presses depends on the area of the affected skin, the course of treatment with the 0.5% spray for local and topical application is as needed, for no more than 7–10 days [150]

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: the use of povidone-iodine 0.5% spray for local and topical application is contraindicated in children under 8 years of age.

• or

  povidone-iodine 10% ointment for topical application is applied in a thin layer to the affected skin surface 2–3 times a day and can be used under occlusive dressings [150].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: The use of povidone-iodine 10% ointment for topical application is contraindicated in premature infants, newborns, and children under 6 months of age.

• or

  hydrogen peroxide** 3% solution for local and topical application: damaged areas of the skin and mucous membranes are treated with a cotton or gauze swab moistened with the drug solution; jet irrigation of the wound surface is also possible [150]

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)

Comments: The use of hydrogen peroxide** during pregnancy and breastfeeding is possible if the expected benefit to the mother outweighs the potential risk to the fetus and child.

• or

  hydrogen peroxide 3% spray for topical application: damaged skin areas are irrigated by pressing the spray nozzle in an amount sufficient to thoroughly moisten them [150]

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)

Comments: The use of hydrogen peroxide** during pregnancy and breastfeeding is possible if the expected benefit to the mother outweighs the potential risk to the fetus and child.

• or

  #benzoyl peroxide 2.5%, 5%, 10% gel for topical application: apply a thin layer of the gel to the affected skin areas 1 or 2 times a day [151, 152]

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)

Comments: contraindication to the prescription of #benzoyl peroxide 2.5%, 5%, 10% topical gel is children under 12 years of age

• or

  silver sulfadiazine 1% cream for topical application: after wound cleaning, the damaged surface is smeared with a 2 mm thick layer of cream 2 times a day; large damaged skin surfaces are covered with a sterile dressing changed 2 times a day, or up to 4 times in severe cases [152]

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: before each re-application, the previous layer of the drug must be removed with a stream of water or antiseptics and disinfectants. A contraindication for the prescription of silver sulfadiazine 1% cream for topical application is childhood under 2 years of age.

Comments: the efficacy of #zinc pyrithione in hidradenitis suppurativa is attributed to its anti-inflammatory, antiproliferative, and anti-androgenic effects [152].

Comments: #clindamycin has bacteriostatic and, at high concentrations, bactericidal effects against anaerobic bacteria, streptococci, and staphylococci. It has low efficacy for nodules and deep abscesses. Prolonged use (>3 months) may lead to the development of resistance [154, 155]. A contraindication to the prescription of #clindamycin 1% solution for topical application is childhood under 12 years of age.

A double-blind, randomized study involving 27 patients with hidradenitis suppurativa demonstrated that topical therapy with #clindamycin was 4.5 times more effective than placebo [154]. After 2 and 3 months of topical therapy with #clindamycin, the number of superficial skin lesions—folliculitis, papules, and pustules—decreased significantly; however, topical therapy with #clindamycin had no noticeable effect on deeper lesions, such as nodules and abscesses [154].

Comments: perilesional infiltration of individual nodules with systemic corticosteroids is indicated for relapses of hidradenitis suppurativa as monotherapy or in combination with systemic drugs. Injections of #triamcinolone lead to rapid pain relief, reduction of hyperemia and tissue edema, and a decrease in nodular suppuration. Pain intensity decreases within 24 hours after intralesional administration of #triamcinolone, and lesion severity decreases within 7 days [199]. #Triamcinolone in the form of a suspension for injection is contraindicated in children under 12 years of age. Systemic corticosteroids are contraindicated in the event of a developing bacterial infection.

Comments: It is believed that the efficacy of doxycycline** in hidradenitis suppurativa may be due to its antimicrobial as well as anti-inflammatory properties [156]. Doxycycline** is contraindicated in pregnant women and children under 8 years of age due to the negative impact of tetracyclines on skeletal development and the potential development of dental enamel and dentin hypoplasia resulting from the formation of insoluble calcium complexes in bone tissue [156].

• or

  combination of clindamycin** orally 300 mg twice daily and #rifampicin** for adults and children over 12 years of age orally 300 mg twice daily or 600 mg once daily, treatment course duration is 10–12 weeks [110, 156, 200–202]

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: The combination of clindamycin** and #rifampicin** is used in case of resistance development to tetracyclines. Clindamycin** is active against streptococci, staphylococci, and many anaerobes, whereas #rifampicin** effectively suppresses the growth of gram-positive and intracellular bacteria. The combination of clindamycin**+#rifampicin** is indicated for patients with Hurley stage I and II hidradenitis suppurativa as monotherapy or combination treatment [110, 156]. A contraindication for prescribing clindamycin** is age under 12 years. A contraindication for prescribing #rifampicin** is age under 3 years.

Comments: prior to initiating treatment with #dapsone**, glucose-6-phosphate dehydrogenase enzyme deficiency must be ruled out, as long-term use of #dapsone** in such patients may lead to hemolytic anemia. During therapy with #dapsone**, improvement in individual patients with hidradenitis suppurativa developed as early as week 2 of therapy, but most commonly the treatment became effective after 2–3 months of taking the drug [163, 164]. Improvement was noted in 38% of patients, whereas in 62% of patients no improvement was observed during #dapsone** treatment [164]. The effect of #dapsone** is associated with its antibacterial and anti-inflammatory action [164].

Due to the fact that therapy with #dapsone** may be accompanied by the development of adverse events, including hemolytic anemia, methemoglobinemia, eosinophilia, agranulocytosis, albuminuria without proteinuria, nephrotic syndrome, regular dynamic blood monitoring is required (complete blood count weekly at the start of therapy, and monthly after a few months). In case of a significant decrease in leukocyte, platelet, or hematopoietic levels, treatment with #dapsone** should be interrupted [124, 125, 128]. Before initiating therapy with #dapsone**, a general clinical biochemical blood test should also be performed to monitor liver function by measuring aspartate aminotransferase and alanine aminotransferase activity in the blood, along with a urinalysis [128]. A general clinical biochemical blood test should subsequently be performed once every 3 months; if aspartate aminotransferase and alanine aminotransferase activity exceeds the upper limit of normal by 4 times, #dapsone** therapy is discontinued [125]. A contraindication for prescribing #dapsone** is age under 18 years.

Comments: #Ertapenem** has a broad spectrum of activity against gram-positive, gram-negative, and anaerobic bacteria. Recommended by the Hidradenitis Suppurativa Foundation and the US and Canadian Hidradenitis Suppurativa Foundation for preparing a patient with Hurley stage II and III hidradenitis suppurativa for surgical intervention [151, 205–207].

Comments: It is essential to keep in mind the teratogenic effect of retinoids for the treatment of psoriasis and the long half-life (up to 2 years) of retinoids for the treatment of psoriasis and their metabolites (etretinate). Therefore, screening and regular testing during treatment, as well as the use of reliable contraception methods, are mandatory [56, 151, 208, 209].

Before prescribing retinoids for the treatment of psoriasis and during therapy with retinoids for the treatment of psoriasis, patients must be monitored to identify contraindications to prescribing the drug and due to the potential development of adverse events during treatment with retinoids for the treatment of psoriasis—hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, liver function impairment, impaired glucose tolerance, manifestation of its pronounced teratogenic effect, impaired night vision [118, 119]. Liver function should be monitored before starting treatment with retinoids for the treatment of psoriasis, every 1–2 weeks during the first month after treatment initiation, and then every 3 months. If test results indicate pathology, monitoring should be performed weekly. If liver function does not normalize or worsens, the drug should be discontinued. In this case, it is recommended to continue monitoring liver function for at least 3 months. Blood triglyceride and cholesterol levels must be monitored. In patients with diabetes mellitus, retinoids for the treatment of psoriasis may impair glucose tolerance, so blood glucose levels should be tested more frequently than usual in the early stages of treatment. Due to the possibility of impaired night vision, careful monitoring of visual impairment is necessary. Because of the high teratogenicity of retinoids for the treatment of psoriasis, a negative pregnancy test result (e.g., a negative urine human chorionic gonadotropin test) must be obtained 2 weeks before treatment initiation. During treatment, additional pregnancy tests are recommended at least once a month. It is absolutely essential that every woman of childbearing potential uses at least 1, preferably 2, effective methods of contraception, including a barrier method, without interruption for 4 weeks before treatment initiation, during treatment, and for two years after completing treatment with retinoids for the treatment of psoriasis. Retinoids for the treatment of psoriasis must not be prescribed to nursing mothers. When prescribing retinoids for the treatment of psoriasis to children, bone growth and development parameters must be closely monitored.

• or

  #isotretinoin orally at a daily dose of 0.8–1.2 mg/kg. Duration of treatment is 6–12 months [56, 151, 160–162, 208, 209].

GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)

Comments: The efficacy of #isotretinoin in the treatment of hidradenitis suppurativa is low. #Isotretinoin suppresses sebaceous gland activity, reduces their size, and suppresses sebum production. Skin areas rich in apocrine sweat glands where hidradenitis suppurativa develops contain a relatively small number of sebaceous glands [56, 151, 208, 209]. The use of #isotretinoin is considered as a reserve drug for the treatment of patients with hidradenitis suppurativa who have concomitant moderate-to-severe acne. #Isotretinoin is preferred over retinoids for the treatment of psoriasis in refractory hidradenitis suppurativa in women of childbearing potential [210].

When prescribing #isotretinoin, it is necessary to evaluate liver function and determine blood levels of aspartate aminotransferase and alanine aminotransferase before treatment, 1 month after initiation, and every 3 months thereafter or as clinically indicated. If liver transaminase levels exceed the normal range, the dose must be reduced or the drug discontinued. Fasting blood triglycerides and cholesterol levels should also be measured before treatment, 1 month after initiation, and every 3 months thereafter or as clinically indicated. Clinically significant increases in triglyceride concentrations must be monitored, as levels exceeding 800 mg/dL or 9 mmol/l may be complicated by acute pancreatitis, potentially with a fatal outcome. In cases of persistent hypertriglyceridemia, #isotretinoin should be discontinued. High-risk patients (with diabetes mellitus, obesity, chronic alcoholism, or lipid metabolism disorders) receiving #isotretinoin therapy may require more frequent laboratory monitoring, including blood glucose, triglyceride, and cholesterol levels. Due to the potential for decreased visual acuity, keratitis, and conjunctival dryness associated with #isotretinoin intake, patients presenting with visual complaints should be referred to an ophthalmologist and the discontinuation of the drug should be considered. Pregnancy is an absolute contraindication for #isotretinoin therapy. Female patients must have a negative result on a reliable pregnancy test within 11 days prior to starting the medication. A urine human chorionic gonadotropin test should be performed monthly as a pregnancy test during treatment and for 5 weeks after treatment discontinuation. Female patients must use at least 1, preferably 2, effective methods of contraception, including a barrier method, without interruption for 1 month before starting treatment, during treatment, and for 1 month after completing #isotretinoin therapy.

Comments: #Cyclosporine** acts selectively and reversibly on T-lymphocytes. It suppresses T-cell activation and the release of inflammatory mediators. Improvement in patients with hidradenitis suppurativa receiving #cyclosporine** therapy develops 1 month or later after its initiation [166].

Because #cyclosporine** therapy may be accompanied by adverse events including leukopenia, anemia, thrombocytopenia, increased plasma creatinine and urea concentrations, hyperlipidemia, hyperuricemia, hyperkalemia, hypomagnesemia, hyperglycemia, increased plasma bilirubin concentrations and liver enzyme activity, development of cholestasis, jaundice, hepatitis and hepatic failure, nephrotoxicity, and infectious complications of the kidneys and urinary tract, the patient's condition must be monitored before and during #cyclosporine** therapy. For this purpose, regular general (clinical) blood counts, standard general biochemical blood tests, and general (clinical) urinalysis must be performed [126]. Regular blood creatinine testing is required—an elevation may indicate a nephrotoxic effect and necessitate a dose reduction: by 25% if the creatinine level increases by more than 30% from baseline, and by 50% if it doubles. If reducing the dose for 4 weeks does not lead to a decrease in creatinine levels, #cyclosporine** is discontinued. Patient monitoring also includes testing blood levels of potassium, uric acid, free and conjugated bilirubin, and determining the activity of aspartate aminotransferase and alanine aminotransferase in the blood. To monitor the lipid profile, blood triglycerides and cholesterol levels should be measured.

• or

  add systemic corticosteroids to the treatment regimen for patients with hidradenitis suppurativa when ongoing systemic therapy is insufficiently effective [177]:

  #prednisolone** for adult patients orally at 2.5–10 mg per day.

GPP CLOE 4Strength of Recommendation C (Level of Evidence – 4)

Comments: It is hypothesized that low-dose systemic corticosteroids may enhance the efficacy of systemic therapy in patients with hidradenitis suppurativa, for example, by preventing the formation of antibodies against tumor necrosis factor-alpha (TNF-alpha) inhibitors [177].

Comments: Systemic corticosteroids are used in hidradenitis suppurativa in short courses to manage severe disease relapses. Long-term systemic corticosteroid therapy in patients with hidradenitis suppurativa is undesirable; if an exacerbation occurs during corticosteroid dose reduction, another anti-inflammatory agent should be prescribed [53].

Comments: #Spironolactone** is an aldosterone antagonist with antiandrogen properties. The drug may be effective in women suffering from Hurley stage I and II hidradenitis suppurativa in whom systemic antibacterial drugs are ineffective.

Comments: #Finasteride** is a testosterone 5-alpha-reductase inhibitor that blocks the peripheral conversion of testosterone to dihydrotestosterone.

Comments: #Metformin** increases peripheral tissue receptor sensitivity to insulin, accelerates cellular glucose uptake, and suppresses free fatty acid production and fat oxidation [151, 209–212].

Comments: If an adequate clinical response is not achieved with the 40 mg every 2 weeks maintenance dose, a dose escalation to 40 mg weekly or 80 mg every 2 weeks should be considered. The necessity of continuing adalimumab** therapy should be carefully evaluated if no response is observed within 12 weeks.

• or

  adalimumab** for adult patients subcutaneously once weekly according to the following schedule: week 0 – 160 mg, week 2 – 80 mg, with subsequent subcutaneous injections starting at week 4 of 80 mg every 2 weeks or 40 mg weekly [all GCP] [111, 143, 169–173, 194]

GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)

• or

  #infliximab** for adult patients at 5 mg/kg of body weight intravenously, followed by the same dose administered 2 weeks and 6 weeks after the first infusion, and every 8 weeks thereafter [110, 171, 174–176].

GCR BLEL 3Grade of Recommendation B (Level of Evidence – 3)

Comments: A contraindication for prescribing adalimumab** in patients with hidradenitis suppurativa is age under 12 years; a contraindication for #infliximab** is age under 18 years (except for Crohn's disease and ulcerative colitis, for which #infliximab** is contraindicated under 6 years of age).

Tumor necrosis factor alpha (TNF-alpha) inhibitor therapy is associated with the development of adverse events, some of which require laboratory monitoring: urinary tract infections (including pyelonephritis), leukopenia or leukocytosis, anemia, thrombocytopenia, elevated lipid levels, hypokalemia, elevated uric acid levels, abnormal blood sodium levels, hypocalcemia, hyperglycemia, hypophosphatemia, elevated liver enzymes, elevated bilirubin, coagulation disorders, and hemorrhagic disorders. Activation of chronic infections, including tuberculosis and viral hepatitis, is possible [127, 129–136, 148, 149]. Therefore, patients should be carefully monitored for the appearance of infections, including tuberculosis, before starting treatment, during treatment, and after the completion of treatment with adalimumab**, including for 4 months after the last injection of the drug. Appropriate screening tests (tuberculin skin test and targeted chest radiography) must be performed in all patients (local guidelines may be applied). An initial consultation with a phthisiatrician may be required. Consequently, prior to initiating therapy with tumor necrosis factor alpha (TNF-alpha) the following examinations must be performed:

1. Complete blood count (CBC) with differential leukocyte count and platelet count;

2. General biochemical blood test, including creatinine, urea, free and conjugated bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase activity;

3. Urinalysis;

4. Targeted chest radiography in 2 projections, intradermal tuberculosis allergen test, initial consultation with a phthisiatrician to rule out tuberculosis infection;

5. Determination of hepatitis B virus surface antigen (HbsAg) in the blood.

6. Determination of human immunodeficiency virus HIV-1 antibodies (IgM, IgG) in the blood.

7. Determination of human immunodeficiency virus HIV-2 antibodies (IgM, IgG) in the blood.

8. Determination of hepatitis C virus antigen in the blood

9. Urinary human chorionic gonadotropin (hCG) test.

Tumor necrosis factor alpha (TNF-alpha) inhibitor therapy must not be administered during pregnancy. Therefore, before initiating therapy with tumor necrosis factor alpha (TNF-alpha), women of childbearing potential must obtain a negative pregnancy test result. During therapy with tumor necrosis factor alpha (TNF-alpha) and for at least 6 months after its completion, women of childbearing potential must use reliable methods of contraception.

During therapy with tumor necrosis factor-alpha (TNF-alpha), adverse events are monitored and laboratory parameters are controlled:

1. Clinical evaluation of the patient's condition – every 3–6 months;

2. Initial consultation with a neurologist every 3–6 months to detect signs of neurological diseases, including demyelinating conditions;

3. Initial consultation with a cardiologist every 3–6 months to detect signs of heart failure;

4. Initial consultation with a phthisiatrician 2 times a year to rule out the development of tuberculosis;

5. Complete blood count (CBC) every 3–6 months (for #infliximab** – before each intravenous infusion);

6. General biochemical blood test (creatinine, urea, free and conjugated bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase activity) every 3–6 months (for #infliximab** – before each intravenous infusion);

7. Urinalysis every 3–6 months (for infliximab** – before each intravenous infusion);

8. Determination of hepatitis B virus surface antigen (HbsAg) in the blood – every 6 months.

9. Determination of human immunodeficiency virus HIV-1 antibodies (IgM, IgG) in the blood – every 6 months.

10. Determination of human immunodeficiency virus HIV-2 antibodies (IgM, IgG) in the blood – every 6 months.

11. Determination of hepatitis C virus antigen in the blood – every 6 months;

12. Urinary human chorionic gonadotropin (hCG) test (for #infliximab** – before each intravenous infusion), as well as if pregnancy is suspected;

13. Targeted chest radiography 2 times a year;

Ultrasound examination of the abdominal organs (complex), pelvic organs (complex), and prostate gland as clinically indicated

• or

  secukinumab** in adult patients 300 mg subcutaneously once a week for 5 weeks, then once every 4 weeks [216–220]

GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)

Comments: A contraindication for prescribing secukinumab** to patients with hidradenitis suppurativa is pediatric age under 18 years. Secukinumab** may cause exacerbation of inflammatory bowel disease [222]. This should be taken into account when choosing therapy for patients with hidradenitis suppurativa associated with inflammatory bowel disease.

3.2 Surgical Treatment

Surgical treatment may be required for severe pain in the lesions, as well as in patients with fluctuating abscesses and in the presence of fistulas. Surgical treatment should not be performed in patients with high inflammatory activity of hidradenitis suppurativa. In such cases, patient preparation is required, during which systemic drug therapy is administered.

Comments: A CO₂ laser (carbon dioxide laser) is used for laser destruction of skin tissue. Active skin lesions accompanied by discharge, inflammation, infiltration, or suspected abscess are selected for treatment. Areas that have been asymptomatic for more than 2 years and show no current inflammation, although previously showing signs of activity (e.g., scars with post-inflammatory hyperpigmentation, sometimes with dry pseudocomedones), are usually not treated with laser radiation. The affected skin is examined macroscopically for scars, tissue deformation and discoloration, dry sinuses or sinuses with purulent discharge, macropseudocomedones, and other manifestations. The examination is completed by palpating the lesions to detect volumetric indurations and small, hard subcutaneous nodules or fluctuating purulent tissue. The affected area is outlined with ink. Local anesthesia with a 1% lidocaine** solution may be used. Excision is performed down to the level of the skin located directly beneath the identified fistulas, scars, or loose tissue, most frequently at the level of the deep reticular dermis or upper subcutaneous tissue [181]. After removing the masses contained within the fistulas, it becomes possible to assess the condition of the wound base and edges with a small probe and identify additional fistulas. These areas can also be removed using a laser after local anesthesia.

Comments: After opening, curettage of the cavity and identified fistulas is necessary.

Comments: Wide excision of the affected skin and, potentially, underlying tissues is preferred, as partial excision of lesions is associated with a higher recurrence rate [56, 189].

Comments: Split-thickness skin transplantation is performed on an open area either immediately or in a delayed manner after 10–14 days. Following 367 operations in 138 patients, the recurrence rate was 33% [190].

• or

  reconstructive plastic surgery with transposition of tissue complexes (skin, muscles, tendons) [192, 193]

LeRR CLoE 4Level of recommendation confidence C (level of evidence – 4)

Comments: The use of myocutaneous flaps for reconstructive surgery in hidradenitis suppurativa is preferable in case of disease recurrence. It is believed that the closure of skin defects with fasciocutaneous and myocutaneous flaps can be achieved with an acceptable recurrence rate (efficacy in 81.25% of cases across 50 operations in 35 patients) [192]. These interventions often require the use of a bowel management system or the formation of a colostomy in perineal/perianal lesions [192].

3.3 Other Treatment

Patients with hidradenitis suppurativa may require symptomatic therapy aimed at pain reduction.

Comments: Contraindication for prescribing #diclofenac 1% topical gel is childhood under 6 years of age.

• or

  #lidocaine** 2% topical gel [195]

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: Contraindication for prescribing #lidocaine** 2% topical gel is childhood under 12 years of age.

• or

  #ibuprofen** 400 mg orally 3 times daily [195]

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: Contraindication for prescribing #ibuprofen** at a dose of 200 mg is childhood under 6 years of age, and for #ibuprofen** at a dose of 400 mg is childhood under 12 years of age. The maximum daily dose for adults is 1200 mg, and for children aged 6–18 years, it is 800 mg.

Adverse events that may occur during treatment with #ibuprofen** include peptic ulcer, gastrointestinal bleeding and gastric perforation, anemia, leukopenia, thrombocytopenia, agranulocytosis, liver dysfunction, increased "hepatic" transaminase activity, hepatitis, and jaundice; very rarely, renal damage may develop (acute renal failure, nephritis syndrome, nephrotic syndrome).

During prolonged treatment, monitoring of the peripheral blood picture and the functional state of the liver and kidneys is required. If symptoms of gastropathy appear, careful monitoring is indicated, including esophagogastroduodenoscopy, a general (clinical) blood test (determination of total hemoglobin level in the blood), and a fecal occult blood test.

• or

  celecoxib 200–400 mg daily orally, swallowed whole with water, regardless of food intake [195].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: Contraindication tocelecoxib therapy is age under 18 years.

• or

  naproxen tablets should be taken whole, washed down with liquid, and can be taken with meals: if disease severity is Hurley stage S1, start naproxen at 250 mg twice daily and increase to 500 mg twice daily; if disease severity is S2 or S3, take 500 mg twice daily [195]

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: Contraindication to therapy with 250 mg naproxen tablets is childhood under 6 years of age.

• or

  #indometacin 50 mg 2–4 times daily or 75 mg twice daily [195]

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)

Comments: Contraindication to therapy with indometacin tablets is childhood under 14 years of age. The maximum daily dose is 200 mg. For long-term treatment, the daily dose should not exceed 75 mg.

• or

  ketorolac** 10 mg tablets orally for patients aged 17–64 years: single dose 20 mg orally, for repeated doses take 10 mg up to 4 times daily as needed, but not exceeding 40 mg/day; patients aged 65 years and older or with renal impairment and/or weight <50 kg: single dose 10 mg orally once, for repeated doses take 10 mg up to 4 times daily as needed, but not exceeding 40 mg/day [195]

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: Contraindication to therapy with ketorolac** tablets is childhood under 16 years of age. The duration of therapy with ketorolac** should not exceed 5 days.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Not applicable.

5. Prevention and Dispensary Observation

Primary prevention of hidradenitis suppurativa, aimed at preventing the development of the disease, has not been developed.

Secondary prevention measures aimed at preventing flare-ups of hidradenitis suppurativa in patients include diet, weight loss, and smoking cessation. Limiting exposure to skin-irritating factors, including avoiding shaving and using laser hair removal, is considered useful for preventing flare-ups of hidradenitis suppurativa [196].

There is evidence that the condition of patients with hidradenitis suppurativa can be improved by a diet restricting dairy products and excluding brewer's yeast [197, 198]. Disease remission is considered achievable after significant weight loss [198]. However, it should be borne in mind that active exercising for weight loss may be accompanied by friction of opposing skin fold surfaces during movement, making it painful for a patient with hidradenitis suppurativa, thus hindering workouts. Furthermore, intensive weight loss can lead to the formation of skin folds, increasing friction and potentially promoting hidradenitis suppurativa flare-ups. Therefore, such patients may require reconstructive plastic surgery and, accordingly, an initial consultation (examination, consultation) with a plastic surgeon [6].

There is evidence that smoking cessation can improve the course of hidradenitis suppurativa [92]. However, patients often find it extremely difficult to quit smoking, and tobacco cessation may be accompanied by weight gain, which can worsen the course of hidradenitis suppurativa. Additionally, choosing underwear with appropriate styles and fabrics capable of influencing friction, humidity, temperature, and microbial colonization in the lesions can improve the course of hidradenitis suppurativa and thereby affect lesion status [6].

6. Organization of Medical Care

Medical care for patients with hidradenitis suppurativa is provided in the following forms:

- primary health care;

- specialized, including high-tech, medical care.

Medical care for patients with hidradenitis suppurativa may be provided in the following settings:

- out-patiently (in settings not requiring round-the-clock medical observation and treatment);

- in a day hospital (in settings providing medical observation and treatment during daytime hours, not requiring round-the-clock medical observation and treatment);

- inpatiently (in settings providing round-the-clock medical observation and treatment).

Primary health care includes measures for prevention, diagnosis, treatment of patients with hidradenitis suppurativa, medical rehabilitation, and the promotion of a healthy lifestyle.

Primary health care includes:

- primary general medical care;

- primary specialized health care.

Primary general medical care is provided in medical organizations by a district general practitioner, district pediatrician, or general practitioner (family physician) in outpatient settings.

As part of primary general medical care, district general practitioners, district pediatricians, and general practitioners (family physicians) refer patients with hidradenitis suppurativa to a medical organization for primary specialized health care and also provide medical care in accordance with the recommendations of a dermatovenereology medical organization in the absence of medical indications for referral.

Primary specialized health care for patients is provided by dermatovenereologists or surgeons.

If medical care cannot be provided in outpatient settings and medical indications are present, a patient with hidradenitis suppurativa is referred to a medical organization providing inpatient medical care.

Specialized medical care for patients with hidradenitis suppurativa is provided by dermatovenereologists or surgeons and includes prevention, diagnosis, treatment using special methods and complex medical technologies, and medical rehabilitation.

When medical indications are present, the treatment of patients with hidradenitis suppurativa is carried out with the involvement of medical specialists in accordance with the Nomenclature of Specialties of Specialists with Higher and Postgraduate Medical and Pharmaceutical Education in Healthcare of the Russian Federation, approved by Order of the Russian Ministry of Health No. 700n dated October 7, 2015 (registered by the Ministry of Justice of the Russian Federation on November 12, 2015, registration No. 39696), as amended by Orders of the Russian Ministry of Health No. 771n dated October 11, 2016 (registered by the Ministry of Justice of the Russian Federation on December 26, 2016, registration No. 44926) and No. 996n dated December 9, 2019 (registered by the Ministry of Justice of the Russian Federation on December 30, 2019, registration No. 57070).

The provision of specialized (excluding high-tech) medical care to patients with hidradenitis suppurativa in federal state medical organizations subordinate to the Russian Ministry of Health is carried out when it is necessary to establish a definitive diagnosis due to the atypical course of the disease, lack of effect from ongoing therapy and/or repeated treatment courses with potential efficacy of other treatment methods, high risk of surgical treatment due to a complicated course of the underlying disease or comorbid conditions, the need for additional examination in diagnostically complex cases, and/or comprehensive preoperative preparation in patients with complicated forms of the disease and comorbidities, or when repeated hospitalization is necessary upon the recommendation of the said federal state medical organizations in accordance with the Procedure for referring patients to medical organizations and other organizations subordinate to federal executive authorities for the provision of specialized (excluding high-tech) medical care, given in the Appendix to the Regulation on the organization of specialized, including high-tech, medical care, approved by Order of the Ministry of Health of the Russian Federation No. 796n dated December 2, 2014 (registered by the Ministry of Justice of the Russian Federation on February 2, 2015, registration No. 35821), as well as in the presence of medical indications in the patient—in federal state medical organizations providing specialized medical care, in accordance with the Procedure for referring citizens by executive authorities of the constituent entities of the Russian Federation in the field of healthcare to the place of treatment in the presence of medical indications, approved by Order of the Ministry of Health and Social Development of the Russian Federation No. 617 dated October 5, 2005 (registered by the Ministry of Justice of the Russian Federation on October 27, 2005, registration No. 7115).

If there are indications for surgical treatment in a surgical inpatient setting, patients with hidradenitis suppurativa are referred by a general practitioner, district pediatrician, general practitioner (family physician), or dermatovenerologist for a consultation with a surgeon.

Indications for planned hospitalization in a dermatovenereological medical organization:

1) Indications for providing medical care in a day hospital setting:

- insufficient efficacy of outpatient treatment;

2) Indications for inpatient medical care;

- insufficient efficacy of outpatient treatment in patients with moderate to severe hidradenitis suppurativa.

Indications for planned hospitalization in a surgical medical organization:

1) Indications for inpatient medical care;

- Presence of fluctuating abscesses requiring incision;

- Presence of fistulous tracts requiring excision;

Indications for patient discharge from a medical organization:

- Partial or complete regression of rashes.

7. Additional Information

The course of hidradenitis suppurativa may worsen with weight gain and in tobacco smokers [6]

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Alexey A. Kubanov – Director of the State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, Academician of the RAS, Doctor of Medical Sciences, Professor, President of the Russian Society of Dermatovenerologists and Cosmetologists. No conflict of interest.

2. Margarita R. Rakhmatulina – Deputy Director for Organizational and Analytical Work, State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, Doctor of Medical Sciences, Professor, Chairman of the Executive Committee of the Russian Society of Dermatovenerologists and Cosmetologists. No conflict of interest.

3. Sofia A. Burova – Head of the Center for Deep Mycoses, Head of the Department of Opportunistic Mycoses at the Institute of Allergology and Clinical Immunology, Doctor of Medical Sciences, Professor, Member of the Russian Society of Dermatovenerologists and Cosmetologists. No conflict of interest.

4. Lyudmila F. Znamenskaya – Leading Researcher, Department of Dermatology, State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, Doctor of Medical Sciences, Member of the Russian Society of Dermatovenerologists and Cosmetologists. No conflict of interest

5. Arfenya E. Karamova – Head of the Department of Dermatology, State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, Candidate of Medical Sciences, Associate Professor, Member of the Russian Society of Dermatovenerologists and Cosmetologists. No conflict of interest.

6. Lyubov P. Kotrekhova – Associate Professor, Department of Dermatovenereology, Head of the Dermatological Department of the Mycological Clinic, North-Western State Medical University named after I.I. Mechnikov of the Russian Ministry of Health, Candidate of Medical Sciences, Associate Professor, Member of the Russian Society of Dermatovenerologists and Cosmetologists. No conflict of interest.

7. Muza M. Kokhan – Head of the Scientific Clinical Department of Dermatology, Ural Research Institute of Dermatovenereology and Immunopathology, Doctor of Medical Sciences, Professor, Member of the Russian Society of Dermatovenerologists and Cosmetologists. No conflict of interest.

8. Olga Yu. Olisova – Head of the V.A. Rakhmanov Department of Skin and Venereal Diseases, First Moscow State Medical University (Sechenov University) of the Russian Ministry of Health, Corresponding Member of the RAS, Doctor of Medical Sciences, Professor, Member of the Russian Society of Dermatovenerologists and Cosmetologists. No conflict of interest.

9. Anna S. Pirogova – Dermatovenerologist, Moscow Regional Clinical Dermatovenereological Dispensary, Member of the Russian Society of Dermatovenerologists and Cosmetologists. No conflict of interest.

10. Ksenia I. Plakhova – Scientific Secretary, State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, Doctor of Medical Sciences, Associate Professor, Member of the Russian Society of Dermatovenerologists and Cosmetologists. No conflict of interest.

11. Evgeny V. Sokolovsky – Head of the Department of Dermatovenereology with Clinic, Academician I.P. Pavlov First Saint Petersburg State Medical University, Doctor of Medical Sciences, Professor, Member of the Russian Society of Dermatovenerologists and Cosmetologists. No conflict of interest.

12. Vladislav R. Khayrutdinov – Professor, Department and Clinic of Skin and Venereal Diseases, S.M. Kirov Military Medical Academy of the Russian Ministry of Defense, Doctor of Medical Sciences, Associate Professor, Member of the Russian Society of Dermatovenerologists and Cosmetologists. No conflict of interest.

13. Vadim V. Chikin – Senior Researcher, Department of Dermatology, State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, Doctor of Medical Sciences, Member of the Russian Society of Dermatovenerologists and Cosmetologists. No conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Dermatovenereologists.

2. Surgeons.

3. Residents and trainees of continuing professional education programs in the specified specialties.

Table 1. Level of Evidence (LoE) grading scale for diagnostic methods (diagnostic interventions)

Table 2. Level of Evidence (LoE) grading scale for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 3. Grade of Recommendation (GoR) scale for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

These clinical guidelines have been developed taking into account the following regulatory and legal documents:

1. Procedure for providing medical care in the profile of "dermatovenereology", approved by Order of the Ministry of Health of the Russian Federation No. 924n of November 15, 2012.

2. Order of medical care profile "surgery", approved by Order of the Ministry of Health of the Russian Federation No. 922n of November 15, 2012.

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

Hidradenitis suppurativa is a chronic inflammatory skin disease often accompanied by pain in the skin lesions. Hidradenitis suppurativa may require prolonged therapy, which can lead to the resolution of inflammatory skin lesions. However, in the event of fistulas and scarring, complete regression of skin lesions is impossible, and surgical correction of visible aesthetic skin defects may be required.

Hidradenitis suppurativa is characterized by a more severe course in obese individuals and tobacco smokers. Therefore, smoking cessation and weight loss can contribute to a milder course of the skin disease.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1. Hurley Staging System

Russian title: Hurley staging system.

Original title (if any): Hurley Staging System.

Source (official developer website, validation publication):

Hurley H.J. Axillary hyperhidrosis, apocrine bromhidrosis, hidradenitis suppurativa, and familial benign pemphigus: surgical approach. In: Dermatologic Surgery: Principles and Practice (Roenigk R.K., Roenigk H.H., eds). New York: Marcel Dekker, 1989; 729–739.

Type (underline):

- rating scale

Purpose: Determination of the stage of hidradenitis suppurativa corresponding to the severity of the disease.

Content (template):

Table G1. Clinical classification of hidradenitis suppurativa according to Hurley (1989)

Key (interpretation): According to the Hurley staging system, there are 3 stages of hidradenitis suppurativa reflecting the severity of the disease.

Notes: The Hurley staging system is not quantitative, which prevents its use for assessing therapeutic efficacy.

Appendix G2. Hidradenitis Suppurativa Physician’s Global Assessment

Russian title: Hidradenitis Suppurativa Physician's Global Assessment

Original title (if any): HS-PGA (Hidradenitis Suppurativa Physician’s Global Assessment).

Source (official developer website, validation publication):

Kimball A.B., Kerdel F., Adams D. et al. Adalimumab for the treatment of moderate to severe hidradenitis suppurativa: a parallel randomized trial. Ann Intern Med. 2012; 157 (12): 846–855.

Type (underline):

- assessment scale

Purpose: Assessment of the severity of hidradenitis suppurativa.

Content (template):

Table G2. Assessment of the severity of hidradenitis suppurativa using HS-PGA

Key (interpretation): The severity of hidradenitis suppurativa using the HS-PGA scale is assessed by counting the number of abscesses, fistulas, inflammatory, and non-inflammatory nodules/nodes in all body areas. According to the HS-PGA scale, there are six stages of the disease, increasing in severity from 1 to 6 (from stage 1 (no inflammatory or non-inflammatory nodules/nodes) to stage 6: extremely severe manifestations, >5 abscesses or draining fistulas) [56, 110].

Notes: The HS-PGA scale is relatively simple to use and is frequently used for clinical assessment of the severity of patient skin improvement in clinical trials [110]. However, a major limitation of the HS-PGA scale is that patients may experience clinically significant improvement that is not reflected when using HS-PGA, especially when evaluating patients with extremely severe hidradenitis suppurativa.

Appendix G3. Hidradenitis Suppurativa Severity Index

Russian title: Hidradenitis Suppurativa Severity Index.

Original title (if any): HSSI (Hidradenitis Suppurativa Severity Index)

Source (official developer website, validation publication):

Amano M., Grant A., Kerdel F.A. A prospective open-label clinical trial of adalimumab for the treatment of hidradenitis suppurativa. Int J Dermatol. 2010; 49 (8): 950–955.

Grant A., Gonzalez T., Montgomery M.O. et al. Infliximab therapy for patients with moderate to severe hidradenitis suppurativa: a randomized, double-blind, placebo controlled crossover trial. J Am Acad Dermatol. 2010; 62 (2): 205–217.

Type (underline):

- index

Purpose: Assessment of the severity of hidradenitis suppurativa.

Content (template):

Table G3. Hidradenitis Suppurativa Severity Index (Hidradenitis Suppurativa Severity Index - HSSI)

VAS – Visual Analog Scale from 0 to 10.

* – palm area = 1% of body surface area

† – interferes with daily activities

Key (interpretation): Total score (0-19 points): mild severity (0-7 points), moderate severity (8-12 points), and severe severity (>13 points).

Notes: The use of HSSI involves the assessment of qualitative objective indicators and qualitative subjective indicators. The affected body surface area, number of skin lesions, pain intensity (determined using a visual analog scale), and drainage (determined by the number of dressings per work shift) are assessed. An HSSI score of ≥13 indicates severe disease, 8 to 12 points indicate moderate disease, and 0 to 7 points indicate mild disease.

Body areas considered: left axillary region, right axillary region, left side of the chest, right side of the chest, left side of the inguinal region, right side of the inguinal region, perianal region, sacral region, and perineum.

Calculation example: 3 affected areas (3 points) + 2% affected body surface area (2 points) + 4 lesions (3 points) + 1 dressing (2 points) + 4 VAS pain points = 14.