The Novel Use of Cryopreserved Human Allograft in Extensive Hurley Stage III Hidradenitis Suppurativa

HS is a chronic and recurring skin condition that is characterized by abscesses and fistulous tracts that affect the apocrine gland–bearing tissues, most commonly in the axilla, groin, inner thigh, buttock, perineum, and breast.^1,2 The chronic inflammation, odor, and pain can have significant detrimental effects on an individual’s QOL. Often, the condition is misdiagnosed and poorly managed. Recent studies implicate possible autoinflammatory and genetic components of the disease, as it has been recently described as part of an emerging triad of clinical conditions demonstrating neutrophilic abundance in the dermis without the presence of autoantibodies. In addition to HS, this triad includes PASH (pyoderma gangrenosum and acne) and may be genetically linked. Other similar autoinflammatory diseases do exist, namely PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne), which also carries a genetic component that gives weight to this theory.^3,4

Various methods for the management of HS have been described in the literature, including sitz baths, topical cleansing agents, and antibiotics.^1,2,5-7 First-line treatment generally consists of monotherapy or combination therapy with antibiotics. In minor cases of HS, monotherapy with topical clindamycin or a systemic tetracycline (ie, doxycycline) have been shown to reduce the extent of the disease, whereas combination therapy (ie, rifampin-clindamycin) or broad-spectrum antibiotics have been beneficial in more extensive cases. Targeted corticosteroid therapy has also been shown to be effective.^5-7 While surgical intervention is an option for severe cases, recent advancements in the understanding of the pathogenesis of HS have led to the development of biologic agents that target specific pathways in the disease process and may be used before surgical intervention is considered.^6,7 Although promising, management should be tailored on an individual basis depending on the extent of the disease.

For severe, extensive disease, surgical treatment remains a mainstay and can be curative in some instances. Reconstruction of these extensive wounds remains complex due to size and anatomic areas, including joint creases. For such extensive cases, the “TIME” pneumonic has been adapted to aid with wound bed preparation for proper healing as an important adjunct to the management above. This includes removing necrotic and infected Tissue, Inflammatory control, Moisture and bacterial load balance, and ensuring Epithelialization of wound bed edges.⁸ Reconstructive options following such optimization include NPWT, skin grafts, and locoregional flaps. NPWT is very useful and helps promote granulation tissue formation and wound contracture. However, patient adherence and obtaining an appropriate seal around joint creases and perineal areas remains challenging. Skin grafts are most useful for extensive wounds but are limited by donor site availability. Locoregional flaps are indicated over joint surfaces to prevent contracture. In patients with poor healing capacity or lack of autologous donor sites, skin substitute grafts may be used to aid in wound healing or as a bridge to skin grafting by minimizing donor site surface area needed.

The authors propose the use of cryopreserved human allograft in the management of severe cases in which autologous skin grafting is limited based on the extent of disease (Figure 1). TheraSkin (Bioventus) is a cryopreserved, biologically active, human allograft containing all native growth factors, cytokines, and collagen matrices. It is a split-thickness, meshed graft available in multiple sizes at a reasonable cost. After 2 weeks, the epidermis sloughs off and the dermal matrix becomes incorporated into the tissue. The dermal scaffold promotes wound contraction and skin edge epithelization, which helps to reduce the surface area needed in second-stage autologous skin grafting. As such, there is decreased dependence on initial skin grafting for larger wounds.^9,10 Therefore, because of these factors, cryopreserved human allograft should
be given further consideration in the management of HS involving extensive surface areas.¹¹

The authors present the case of a 37-year-old Black man with a history of extensive HS. The patient resided in a nursing home due to impaired QOL and need for constant wound care given the extent of his disease. His condition was being managed with local wound care consisting of topical antibiotic ointment, nonstick gauze, and abdominal gauze pads. Every 3 days, nursing staff applied collagen dressings to these wounds as well. Dermatology was monitoring his care and use of adalimumab was discussed but deferred because of persistent leukocytosis.

The patient presented to the emergency department for increasing pain to his groin, buttocks, and thighs secondary to worsening disease, preventing him from carrying out activities of daily living (Figures 2, 3). He underwent simple incision and drainage of his bilateral thigh and buttocks due to numerous actively draining tracts. A plastic surgeon recommended wide local excision of the bilateral posterior thighs due to the extent of the disease.

Following radical excision of the skin and subcutaneous tissue from the right and left posterior thighs, cryopreserved human allograft was then used to provide 100% coverage over the wounds. NPWT was used as a bolster dressing but ultimately had to be removed due to loss of a seal. At 1 week postoperatively, there was 99% take of the graft over the wound beds with healthy granulating tissue noted (Figure 4).

The patient continued with local wound care with xeroform for 1 month, then a second application of cryopreserved human allograft was performed to further negate the surface area required for secondary skin grafting given the extent of the disease. Continued wound contracture, granulation tissue formation, and improved contour depth was noted. Once the wounds had significantly contracted in size, the patient was taken back to the operating room for autologous skin grafting. Two sheets of 3:1 meshed split-thickness grafts (1:1400 of an inch) were harvested from the right side of the patient’s back and applied to the remaining bilateral thigh wounds. Full 100% coverage was obtained, totaling 882 cm² (Figure 5). Sponge bolsters were used. The graft take was over 95% on postoperative day 7. Only minor areas of breakdown were noted, which were treated with local wound care and antibiotic ointment. The patient was followed for over 1 year following surgery, and the grafts were noted to be well incorporated with minimal contraction and no evidence of disease recurrence (Figure 6).

The severity of HS can be classified based on the widely used Hurley classification system, a staging system representing a straightforward and consistent way to guide treatment (Table). Stage I is classified as abscess formation (single or multiple) with no sinus tracts or scarring. Stage II is classified as recurrent abscesses with sinus tracts and scarring (single or multiple separated lesions). Stage III is classified as diffuse or almost diffuse involvement, or multiple interconnected sinus tracts and abscesses across the entire area. Patients with Hurley stage III HS that does not respond to biologics or other medical modalities often undergo surgical excision to remove existing sinus tracts and nodules.^1,2,6,7 Small surface areas can be treated with local excision and autologous skin grafting, which is the ideal scenario.  However, with extensive involvement of HS, it is important to have other options available for reconstruction of the wounds. This case illustrates the need for alternatives to immediate skin grafting following excision of a large surface area given donor site morbidity and extensive disease.

Multiple skin substitutes are currently available for use in such an extensive disease, all of which have different properties and characteristics. Skin matrices may be dermal, epidermal, or a combination, depending on their composition and the type of tissue they are to replace. They may be used temporarily as a bridge or as a permanent remedy. Additionally, they may be bioengineered or artificial and can exist as a multilayer product. Each of these may have different growth characteristics based on their individual cellular characteristics.

While other skin substitutes do exist, cryopreserved human allograft is a novel surgical treatment of extensive HS, and to the authors’ knowledge, it has not been previously used in the management of this condition. Other products are currently on the market, but few are derived from human skin.^10,12-14 In this case, the use of cryopreserved human allograft ultimately decreased the dependence on immediate skin grafting as it decreased the surface area required for secondary grafting through wound contracture after application, as well as providing contour improvement. Immediate skin grafting would require a larger surface area in the setting of a larger contour deformity and potential graft failure due to a higher risk of infection. Thus, cryopreserved human allograft leads to less overall morbidity. Extensive areas can also be difficult to manage with NPWT, further necessitating the need for alternative options. The cadaveric allograft described is the only epidermal and dermal substitute made solely from cadaveric human skin. It is a cryopreserved human allograft containing all necessary components of extracellular matrix, growth factors, and viable cells needed for regeneration and wound healing, and the amount and ratios of type I and III collagen and growth factors have been found to be comparable to those of human autografts.^11,14-16 Overall, cryopreserved human allograft has been shown to be as highly efficacious as other matrices, but it more easily adheres to exposed structures and is cost effective at approximately $23 per cm.^2,17

It is important to note that this is only representative of a single case of HS. Additional reports of the use of cryopreserved human allograft need to be described, especially in the use of other dermatologic conditions requiring skin excision and skin grafting.

HS is a debilitating condition that can greatly affect a patient’s QOL. For severe, refractory cases, radical resection may be necessary for local disease control. While autologous skin grafting is necessary for final wound closure, the use of cryopreserved human allograft provides biologic wound management that aids in wound contracture and granulation formation, improves contour deformity, and serves as a bridge to autologous skin grafting. Therefore, the authors advocate its use as a tissue scaffold in the management of severe, extensive HS, although further investigation of this product is warranted to further establish an algorithm for its use. In addition, cryopreserved human allograft may be applicable to other
extensive dermatologic and autoimmune skin diseases.