HS-TIME: A Modified TIME Concept in Hidradenitis Suppurativa Topical Management

Wound bed preparation (WBP) has gained international recognition as a concept that can provide practitioners with a structured approach when assessing and managing patients with wounds. To assist the concept of WBP, the TIME acronym was introduced to summarize the 4 main components of WBP: devitalized tissue management (T), control of infection and inflammation (I), moisture imbalance (M), and advancement of the epithelial edge of the wound (E). The TIME framework is a useful, practical tool based on identification and removal of barriers to healing.¹ 

Hidradenitis suppurativa 
Hidradenitis suppurativa (HS) is a chronic inflammatory disorder of the terminal follicular epithelium in the apocrine gland-bearing skin, due to a primary keratin plugging followed by inflammation of apocrine glands. It is characterized by recurrent, tender, and deep-seated nodules, abscesses, fistulas, sinus tracts, and scarring in those regions of the body with a higher density of apocrine glands, such as the axillary, inguinal, gluteal, and inframammary areas.² Epidemiological studies of HS have shown a range of prevalence from 0.053% to 4%.³ The female-to-male ratio of HS is about 3:1, and people aged 18 to 44 years are affected more frequently.^4,5 Smoking and elevated body mass index are associated factors⁶ and abnormal levels of hormones, such as androgens, also may be detected.⁷ Concomitant and secondary diseases such as obesity, metabolic syndrome, inflammatory bowel diseases, pyoderma gangrenosum, spondyloarthropathy, and SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome have been described.² The diagnosis is made upon the presence of HS lesions in common areas with at least 2 recurrences in the past 6 months. Several clinical scores have been used to evaluate the severity of the disease: Hurley, modified Sartorius score, HS Severity Index, HS Physician Global Assessment, Acne Inversa Severity Index, and Dermatology Life Quality Index.^2,8 The Hurley staging system is the most widely used HS severity scale in clinical practice. This staging system classifies HS patients into 3 stages: stage 1, abscesses without sinus tracts and scarring; stage 2, widely separated abscesses with tract formation and scarring; and stage 3, diffuse/near-diffuse involvement or abscesses and multiple interconnected tracts across the entire area (Figure 1).² 

The main differential diagnoses of HS are staphylococcal infections, cutaneous Crohn’s disease, simple abscesses, neoplasms, lymphogranuloma venereum, cutaneous actinomycosis, and cutaneous tuberculosis (scrofuloderma type).² Lesions may severely impair patient quality of life⁹ due to pain, malodorous lesions, and complications, such as reduction of limb mobility due to scarring, lymphedema, and depression.¹⁰ This condition is associated with embarrassment and social stigma with a strong negative impact on interpersonal relationships, education, and work.¹¹ Moreover, squamous cell carcinoma (SCC) may arise on chronic HS lesions and be lethal.¹² Treatment for HS includes topical and systemic antibiotics as well as anti-inflammatory and biologic drugs. Local wound care includes the use of antiseptics, topical antibiotics, and steroids to control infection and inflammation. Absorbent dressings also are employed for moisture control.¹³ In the case of long-term disease, hypergranulation tissue may develop and, in select cases, a skin biopsy is recommended to rule out the presence of SCC. In a mild to severe case, laser treatment and surgical excision of the affected tissue may provide a rapid and satisfying result, but recurrence of HS is reported frequently.^14,15 The type of surgical procedure depends mainly on the size and location of the affected tissue. Therefore, postsurgical HS wound care may include the removal of necrotic tissue, inflammation reduction, bacterial load management, moisture balance, and granulation tissue promotion.^1,13

TIME concept in wound healing
In 2000, Falanga¹⁶ described critical targets and ways to achieve optimal WBP, including necrotic tissue removal, edema and exudate control, bacterial balance, and vascularization promotion.In the same year, Sibbald et al¹⁷ defined WBP as a “changing paradigm that links treatment to the cause and focuses on three components of local wound care: debridement, wound-friendly moist interactive dressings, and bacterial balance.”

The addition of another component – the epidermal edge – led to the TIME acronym, a clinical tool for the management of chronic wounds that was developed in June 2002 by a group of experts in the field of wound care and management. These 4 components were first published in 2003 in the form of a table that linked clinical observation to the proposed underlying pathology and highlighted the clinical outcomes for each of the 4 aspects.¹

The aim of this study is to describe a modified concept of TIME useful for the management of HS: HS-TIME. In particular, the authors propose to modify the TIME concept in order to correctly address 2 distinct groups of HS lesions: typical HS lesions and postsurgical wounds. 

Hidradenitis suppurativa lesions were classified into 2 categories: typical HS lesions (nodules, abscesses, fistulous tracts, sinus tracts, and scars) and postsurgical wounds. The authors applied the TIME rules (devitalized tissue management, control of infection and inflammation, moisture imbalance, and advancement of the epithelial edge of the wound) to both categories, considering the standard approach for evaluating the postsurgical wounds and a modified approach for typical HS lesions (HS-TIME).

Typical HS lesions and TIME
The HS-TIME rules are summarized in the Table.

T: tissue. Devitalized tissue can be removed by deroofing technique with local anesthesia. The objective of deroofing is to remove damaged tissue from the affected skin regions, together with proinflammatory factors and biofilms, that contribute to the persistence, worsening, and spread of HS lesions.¹⁸ After physical examination identifies HS lesions to be deroofed, a blunt probe is used to locate sinus openings. The probe is held at different angles in search of connecting fistulas. The sinus roof is removed using electrosurgical dissection with a wire loop tip, with the epithelial bottom of the sinus tract left intact.¹⁹ The deroofing procedure is followed by secondary intention healing according to the standard TIME concept.

Simple incision and drainage of lesions may induce reduction of pain and tenderness but is not recommended because the relief is temporary and cannot be considered a definitive therapeutic approach.

I: inflammation/infection. Hidradenitis suppurativa is a systemic inflammatory disease with inflammatory lesions that may be treated with intralesional steroids or topical antibiotics with anti-inflammatory properties, such as clindamycin.²

The pathogenesis of HS lesions is referred to as an initially sterile process, but the biofilm aggregates constitute a possible immunological driver of the proinflammatory cytokines found in HS lesions, especially in sinus tracts.²⁰ The role of bacterial colonization as a trigger rather than the mere result of an altered innate immune response is unclear. Sartorius et al²¹ did not isolate any Staphylococcus aureus species from inflammatory nodules of HS, suggesting S aureus is involved in the late stages of the disease, probably as a superinfection.

The inflammation/infection can be managed with antiseptic products to avoid cytologic damage. Agents with low cytotoxicity, including sterile water and isotonic normal saline, should be employed to cleanse the lesion. Such procedures also may be important to suppress potential triggers of an aberrant immune response and prevent secondary infection.²² Topical antibacterial agents and antiseptics, such as polyhexamethylene biguanide (PHMB), silver, and iodine, proved beneficial in critically colonized lesions. Previously, PHMB has been shown to protect keratinocytes from damage by S aureus and provide a high antibacterial efficacy at a high pH in chronic wounds.²³ Silver is combined with calcium alginates, hydrofibers, foams, and hydrogels. In 2012, an international consensus concluded that silver dressings are able to reduce the bacterial burden in critically colonized wounds.²⁴ Cadexomer iodine showed superior efficacy compared with other topical antimicrobials used in wound dressings.²⁵ Honey has antibacterial and anti-inflammatory properties due to its acidic pH and high sugar concentration (osmolality), which creates a hostile environment for bacterial proliferation, but poor literature is available.²⁶

M: moisture imbalance. Hidradenitis suppurativa lesions can show a severe exudation, leading to impairment of the patient’s quality of life. Moisture imbalance can be controlled by using wound dressings such as polyurethane foams, hydrofibers, alginates, or negative pressure wound therapy (NPWT), which can control odor and discomfort, thus reducing the number of dressing changes over time. 

Considerations in dressing selection in HS includethe amount of exudate, the anatomical site, and the shape of the dressing. The selected dressing must remain in place to avoid friction and should conform to body area contours. In cases of cavities and tunneling sinuses, dressings should be adequate for bulk filling of cavities and fluid absorption. Patients with HS may learn to adapt and combine existing dressing materials to achieve optimal wound coverage. Atraumatic adhesives (eg, silicone and nonadherent wound contact layers) limit traumatic skin damage and minimize pain at dressing changes.²⁷

E: elevation. Regarding typical HS lesions, the authors propose E as elevation to stress the importance of preventing pathologic scarring and detecting neoplastic transformation. 

The term “elevation” refers to the tissue elevation on the surface of the lesions that could be related to hypertrophic scarring or SCC development. Squamous cell carcinoma arising from HS may be considered a type of Marjolin ulcer (MU), characterized by aggressiveness and ulceration. The incidence of MU arising from long-standing HS varies from 1% to 3.2%.²⁸ Transformation from HS to SCC may be explained by chronic irritation and possible infection, which both lead to proliferative epidermal changes and increased rate of spontaneous mutations.

Postsurgical wounds and TIME
Postsurgical wound care also plays a critical role in HS management, considering wide excision with secondary closure or skin grafting are often regarded as the best surgical approaches in severe cases.^29,30

The aim of postoperative wound care is to remove devitalized tissue, maintain a moist wound environment, and enhance bacterial balance, with the ultimate goal of the formation of good quality granulation tissue, which can lead to complete wound healing either spontaneously or through engineered skin products and grafting procedures.

T: tissue. There are several types of surgical and laser treatments, some of which may be highly invasive. The aim of these procedures is to remove nonviable tissues, particularly in the case of surgical tissue removal with secondary closure. Correct postsurgical wound care, with standardized debridement techniques, is mandatory to permit correct WBP. 

I: inflammation/infection. Inflammation/infection can be managed by antiseptics, such as silver, PHMB, honey, iodine, or a bacteria-binding dressing. In particular, the use of silver alginate dressings and honey showed good results in surgical HS wounds, with enhanced healing and improvement in the quality of life.^31,32

The use of topical antibiotics on surgical wounds generally is not recommended, considering such agents can cause delayed hypersensitivity reactions and promote superinfections especially by resistant pathogens.¹³

M: moisture imbalance. Specific postsurgical wound dressings are required for moisture balance in HS, such as hydrofiber, foam, and alginate, depending on the specific features of the wounds.¹³ Negative pressure wound therapy may be used with satisfactory results²⁹;  in some cases, an internal vacuum-assisted closure method was applied with good outcomes in terms of healing time and control of recurrences.³³ Negative pressure can be followed by a split-thickness skin graft or extracellular matrix in order to improve healing rates and reduce recurrences.³⁴ 

E: epithelial (edge) advancement. To improve edge proliferation in postsurgical lesions, bioactive products or tissue engineering devices, such as platelet-rich plasma gel and hyaluronic acid-based silicone membrane, can be used to finalize the healing process.³⁵ In order to obtain epidermal reepithelization, the wound bed needs to be prepared through the creation of an adequate microenvironment that will promote wound healing.

Notably, HS is characterized by significant morbidity and a severe psychological impact on affected patients. Related complications may impact patient quality of life and cause permanent consequences. Though rare, death may be a possible consequence of SCC development.^1,22 Often, HS requires systemic treatment, but the role of a correct topical approach is crucial to reduce daily dressing changes and costs and limit refractory scarring, which reduces limb mobility and is a risk factor for SCC.

Appropriate management of typical HS and postsurgical lesions is recommended (Figure 2), referring to the concepts of WBP summarized in the acronym TIME. The HS-TIME concept may help to give the right point of view to both clinicians who are experts on HS and vulnologists who are experts on wound healing.

The use of atraumatic adhesives is important to avoid skin damages and reduce pain at dressing changes. Moisture imbalance and odor may be managed using adequate moist wound dressings or NPWT. The antiseptic products are useful to avoid superinfections and to control the possible trigger action of the bacteria, considering the already discussed role of biofilm aggregates in HS lesions. Biofilm has been defined as a coherent cluster of bacterial cells embedded in a biopolymer matrix. The presence of biofilm causes an increased tolerance to topical and systemic antimicrobials and is involved in the progression of the lesion to a nonhealing wound. Complete elimination of biofilm is difficult to achieve, other than by mechanical or surgical means.³⁶ Bioactive products or tissue engineering devices can be used in postsurgical wounds to finalize the healing process. Before using these products, it is important to obtain a good WBP with a controlled bacterial load.

The HS-TIME concept is a proposed new tool that may improve the management of HS. Further studies with the involvement of a larger number of clinicians are necessary to confirm the real utility of this new tool in terms of better results in clinical practice and improved quality of life of HS patients. 

Considering the lack of strong evidence regarding wound care in HS, the authors propose a new concept of TIME, which differentiates between the typical HS lesion approach and postsurgical wound approach. As a new, easy-to-use, helpful tool, HS-TIME may assist physicians in identifying the best wound care approach to improve outcomes in patients with HS.