Severe hidradenitis suppurativa treatment using platelet‐rich plasma gel and Hyalomatrix

Abstract

Hidradenitis suppurativa (HS) can be a debilitating chronic disease. The underlying cause of the disease is still not clear. HS may be managed through numerous different medical or surgical procedures. Surgical treatment may consist of local excisions and reconstruction using a variety of methods: perforator flaps, skin grafts, local flaps, primary closure or secondary wound healing with vacuum and other devices. This report describes our experience with surgical excision and closure using platelet‐rich plasma (PRP) gel and Hyalomatrix PA (HPA) in a patient with severe HS involving most of the body surface. We treated the patient with resection of severe HS of the nuchae and closure with PRP gel prepared with the RegenKit ^® to promote neovascularisation and HPA, a delivery system for hyaluronic acid, to induce a neodermis at the wound bed and to stimulate regeneration in a humid and protected environment. Complete wound healing was achieved after 2 months. The obtained result proved the efficacy of this treatment without complications. No recurrence was observed during the 1 year after the surgical procedure. Severe HS can be safely and effectively managed with wide excision, PRP gel and Hyalomatrix to achieve a successful outcome.

Introduction

Hidradenitis suppurativa (HS) is a chronic, suppurative and recurrent disease of unknown aetiology that causes considerable morbidity in affected patients. It is considered that the aetiology of HS is most likely multifactorial and heterogeneous. Revuz hypothesised on aberrant excretion of antimicrobial peptides. Jemec supposed it to be caused by special biomechanical conditions in the affected follicles; Kurokawa argued that fistula formation is an early event in HS pathogenesis as a result of epidermal invagination. Giamarellos‐Bouboulis and Nagy hypothesised on aberrant pattern recognition receptor pathways and aberrant tumour necrosis factor‐alpha (TNF‐a) release. Bechara and Altmeyer argued on the existence of multiple HS phenotypes, and Kurzen provided a review on possible pathogenic mechanisms of smoking as causing HS 1. Immunosuppressive system plays an important role in the pathogenesis of HS, and a reduction in the percentage of natural killer cells was reported in patients with HS and a lower monocyte response to triggering by bacterial components as well 1, 2. HS may be associated with other follicular diseases as well as acne conglobata, dissecting folliculitis of the scalp, pilonidal sinus and often correlated with autoinflammatory syndromes such as ‘PASH’ (pyoderma gangrenosum, acne and suppurative hidradenitis) 2.

The clinical criteria and characteristics of skin lesions are quite distinctive in HS. The disease is characterised by the development of tender, erythematous lesions, specifically deep‐seated painful nodules: ‘blind boils’ in early lesions; abscesses, fistulas, draining sinus, hypertrophic ‘rope‐like’ bridged scars and ‘tombstone’ open comedones in secondary lesions. Rupture of these lesions results in suppuration, formation of sinus tracts and extensive scarring. Another feature is the typical topography, especially, axillae, groin, perineal and perianal regions, buttocks, inframammary and intermammary folds, and chronicity as well as recurrences 3. Atypical locations have been reported: retro‐auricular folds, external auditory meatus, eyelids, nape of the neck, waist, hip, thighs and periumbilical region 4. HS may be managed through numerous different procedures: topical antibacterial or antiseptic lotions, retinoids, corticosteroids and antibiotics 5, 6. Hormonal therapy has limited or temporary results 7, but more recently TNF‐a inhibitors have shown promising results 1, 8, 9, but for severe cases of infection surgery is preferred 4. Surgery may be used as monotherapy after medical control of the disease or combined with medical therapy to achieve a better disease control and depends on the configuration of the lesion 4, 10. Surgical treatment may consist of local excisions and reconstruction using a variety of methods: perforator flaps, skin grafts, local flaps, primary closure or secondary wound healing 3, 10, 11, 12. Local or free flaps and skin grafting are often not reliable because lesions involve most of the body surface and local flaps frequently cannot encompass the entire area of resection and perforator flaps may be too bulky in many areas 13.

Furthermore, contracture development and limitation of movement are frequently seen in secondary healing, primary suturing and skin grafting; however, they are less frequent with flap reconstruction 10, 11, 12, 13.

For these reasons, we chose to treat a patient undergoing resection of HS and closure with platelet‐rich plasma (PRP) gel prepared with the RegenKit^® (RegenLab, Le Mont‐sur‐Lausanne, Switzerland) to promote neovascularisation 14 and Hyalomatrix PA^® [(HPA), Anika Therapeutics S.r.l., Abano Terme, Padova, Italy], a delivery system for hyaluronic acid (HA), to induce a neodermis at the wound bed and to stimulate regeneration in a humid and protected environment 15. The role of platelets in wound healing is well described. Numerous proteins are contained within the alpha‐granules of platelets that strongly influence wound healing, including platelet‐derived growth factor, transforming growth factor‐beta, vascular endothelial growth factor and epidermal growth factor 16, 17, 18. These factors are released from the alpha‐granules in response to platelet activation with platelet aggregation inducers. HA is one of the primary extracellular matrix (ECM) components. Its physiological functions derive from the structural role in ECM and its ability to interact with cell‐surface receptors. The structural role is exerted through the hygroscopic and rheological properties that allow hydration and modulation of the cellular microenvironment. The influence on cell signalling pathways is ensured by cell‐surface receptor bindings that induce cell–cell adhesions, cell–substrate adhesions, proliferations and cell migrations 19, 20, 21, 22. HA binds with PRP forming a temporary wound matrix 19. This matrix provides a scaffold for contact guidance and cell migration analogous to its morphogenic role 20. HA combined with PRP stimulate angiogenesis and endothelial cell proliferation 14, 15, 21, 22.

This report describes our experience with surgical excision and closure with PRP gel and HPA in a patient with severe HS involving most of the body surface.

Materials and methods

We report a case treated in the Department of Plastic and Reconstructive Surgery, ‘Tor Vergata’ University of Rome. A 31‐year‐old Caucasian man (170 cm, 72 kg) presented with severe cystic acne lesions on his face and back, which he had suffered from since adolescence. A skin examination showed clusters of chronic and repeatedly draining sinuses, fistulas, abscesses and hypertrophic scars in the nape of the neck, both axillae, groin and gluteal region. On his trunk, upper and lower extremities, several multiple inflammatory and raised plaques with open multiporous comedones were observed. Some epidermal cysts, sometimes inflamed, were found scattered over the entire body surface. The face showed multiple depressed and hypertrophic ‘rope‐like’ bridged scars resulting from acne conglobata (Figure 1). His medical history and family history were unremarkable. He had a 30‐pack‐year smoking history. Laboratory tests showed a slight increase of thrombocytes, leucocytes, C‐reactive protein and gamma‐glutamyl transferase as shown in Table 1.

Figure 1.

Characteristic facial scars of hidradenitis suppurativa (HS).

Table 1.

Clinical data of the patient

Description	Result	Units	Normal values
WBC	12·4	x103/µl	4·0–11·0
RBC	4·98	x106/µl	4·0–6·0
HCT	43·6	%	35–55
PLT	422	x103/µl	150–440
PDW	13	%	8·0–18·0
MPV	8·7	fl	6·0–10·0
NEUT#	8·43	x103/μ	2·0–8·0
LYMPH #	2·59	x103/µl	1·0–5·0
MONO #	0·58	x103/µl	0·10–0·80
EO #	0·72	x103/µl	0·0–0·4
BAS #	0·06	x103/µl	0·0–0·2
C‐RP	36·7	mg/l	0–5·0
ESR	42	mm	0–20
GGT	53	U/l	8–61

WBC, white blood cell; RBC, red blood cell; HCT, hematocrit; PLT, platelet; PDW, platelet distribution width; MPV, mean platelet volume; NEUT#, neutrophils; LYMPH#, lymphocytes; MONO#, monocytes; EO#, eosinophils; BAS#, basophils; C‐RP, C‐reactive protein; ESR, erythro sedimentation rate; GGT, gamma‐glutamyl transferase.

Five years earlier he was treated for severe acne with Roaccutane (Roche Pharmaceuticals, Basilea, Switzerland) isotretinoin, a form of vitamin A, but without positive effect and his disease recurred. During young adulthood, he received numerous oral antibiotics, which helped control his disease initially; however, further intervention was now required to try to improve his condition.

On the basis of all these data and clinical presentation at the initial examination, we made diagnosis of HS with acne conglobata. According to Hurley's criteria, we classified nuchae and gluteal region as stage III axillae and groin region as stage II 16. Surgical options were then discussed with him. He was informed about the possible risks related to surgical procedures of non‐sterile lesions, including the risk of infection, recurrence, dehiscence and unsightly scars. With the patient's consent, we decided to start removing the nuchae lesion that caused malodorous discharge, soiling of clothes, movement restrictions, and increased distress with a significant impairment of quality of life (Figures 1 and 2). Declaration of Helsinki protocols was followed and the patient gave his written, informed consent.

Figure 2.

Preoperative.

The patient underwent a wide surgical excision of the nuchae area (15 × 10 cm) under general anaesthesia. The entire diseased skin and subcutaneous fatty tissue down to the trapezius fascia were removed with a cold blade and electrocautery. The lesions were resected to a depth of 3–4 cm to ensure that the deep coils of the apocrine glands were excised.

The wound was left open to heal by secondary intention and the PRP gel and Hyalomatrix were used as topical treatments. A self‐contained disposable kit (RegenKit; RegenLab) was used to process 40 ml of venous peripheral blood. Blood was collected in five ATS (autologous thrombin serum) Regen tubes (8 ml each). All tubes were centrifuged at 1500 g (corresponding to 3100 rpm) for 15 minutes at room temperature using the universal centrifuge Regen Lab PRP‐Centri (Regen Lab SA, Le Mont‐sur‐Lausanne, Switzerland). After centrifugation, PRP activated by autologous thrombin becomes consolidated in the tube. Some of the PRP gel was not consolidated and the liquid was injected with a syringe into the perilesional wound areas (Figure 3). PRP has a concentration of platelets three to five times more than baseline, whose action consists of stimulating skin fibroblasts and favouring tissue growth by newly synthesised collagen. As a laboratory product, the platelet gel is easy and safe to use. It cannot be contaminated and lacks surface antigens responsible for potential allergic reactions 17, 18, 22, 23. Furthermore, it is easy to handle and was readily anchored with absorbable suture to the wound bed (Figure 4). Hyalomatrix is a non‐woven mesh dressing composed of 80% esterified HA fibres and beneath it includes a semi‐permeable silicone membrane supplied by Fidia Advanced Biopolymers (FAB, Abano Terme, Padova, Italy). Hyalomatrix was chosen to cover the PRP gel and the silicone membrane was sutured to the wound edges to allow neck movements and to ensure that the coverage material stayed in place. This approach provides a flexible coverage to the wound with good functional outcome. At the first dressing change after 15 days, the silicon membrane was removed. Successive dressing changes were performed every week thereafter for next 2 months using Hyalofill F (Fidia Advanced Biopolymers), an absorbent, soft and conformable fibrous dressing composed of ester of HA. Before each new application, the residues of esterified HA fibres and fibrin were carefully removed from the wounds using a sterile saline solution. The total expenditure for the treatment was about 1200 Euro, excluding hospital stay and operation theatre charges. The expenditure was totally covered by the Italian National Healthcare system.

Figure 3.

Platelet‐rich plasma (PRP) liquid was injected into the perilesional wound areas.

Figure 4.

Platelet‐rich plasma (PRP) gel and Hyalomatrix [esterified hyaluronic acid (HA) fibres] treatment.

Results

The patient tolerated the procedure well and was discharged from the hospital after 24 hours. The second week he was admitted into the outpatient ambulatory and the first dressing change was performed. At that time, the floor of the wound appeared to be covered with pink granulation tissue without any slough. During the subsequent dressings, the granulation tissue was observed to be more stable and was gradually getting covered with thin layer of skin over it. The patient achieved complete wound healing after 2 months (Figure 5). No recurrence, infection or wound dehiscence was observed 1 year following the surgical procedure. No scar contractures, itching, pain, irritation, hypertrophic scars or restriction of neck movements were observed or reported by him. After complete healing, he was kept in regular follow‐up for every 2 months during the first year.

Figure 5.

Postoperative at 2 months.

Discussion

HS is a disease involving skin areas where apocrine sweat glands are present. However, recent data indicate that HS is a disease arising from the hair follicles 2, 3, 4, 16. More specifically, von Laffert et al. 24 found that follicular occlusion by infundibular hyperkeratinisation and dilatation are considered to be the early events in HS. For this reason, HS is not an unusual finding in different locations and in several body parts. Furthermore, most of the patients are referred to a plastic surgeon when conservative management has failed, as well as when local incisions and drainage or incision and primary closure fail 13. Therefore, HS represents a challenge for the management of the wound and for the choice of treatment. In addition to drug therapy, surgery is frequently performed to control severe HS. Several kinds of surgery have been described including smaller excisions that carry a higher rate of recurrence than wider excisions 25. Parks and Parks 26 recommend that wide excision should be performed by removing all of the apocrine glands from all hair‐bearing skin to the deep underlying fascia. Büyükaşik et al. 27 also suggest wide excision for prevention of future recurrence and to achieve good cosmetic results. The various methods of wound closure include secondary healing, primary suturing, skin graft and flap reconstruction. Mandal and Watson 28 identified that 69% of patients with HS who underwent excision and primary closure needed to be reoperated on, at least once. The authors also stated that no recurrence or serious complications such as infections or dehiscence were observed in patients who had a flap and graft repair. Other authors recommend closure of wound using a split‐thickness graft because of low recurrence rates, but using graft repair for lesions in the perineal and perianal region because of axillary bacterial contamination may lead to graft loss 12. Furthermore, as reported by Haynes et al. 11, skin grafts leave a significant contour deformity and in some areas develop contractures and limit movements. Secondary closure may be performed using the vacuum‐assisted closure (VAC) therapy 13; however, the management of wounds in several areas (groin, perineal and perianal region, axillae and neck) is difficult for many reasons. It is hard to obtain a seal in these areas, because usually the disease is bilateral, and avoidance of shearing forces on the grafts is problematic as is the management of urinary and faecal output 8. In our experience, application and maintenance of VAC across the joints and areas of great mobility is not easy. In the neck region, the presence of hair, neck movements, bulkiness of dressing, its accessories and difficulty in wearing clothes makes application of VAC uncomfortable and cumbersome to the patients. Venturi et al. 29 described some complications in patients treated with VAC. These include pain, skin irritation or maceration, tissue necrosis, bleeding and infection. In a recent Cochrane review, Webster et al. 30 concluded that the evidence for the effectiveness of negative pressure wound therapy in complete healing of acute wounds remains unclear.

Existing evidence suggests that the use of Hyalomatrix provides a flexible covering for the wound surface, and adds increased tear strength to the device 15. When Hyalomatrix is applied on the wound bed, the esterified HA fibres provide a three‐dimensional scaffold for cellular invasion and capillary growth 19, 20, 21. PRP offers the significant additional hypothetical benefit of accelerated postoperative wound healing, which is bestowed by the presence of high concentrations of growth factors and cytokines present in the platelets 22.

The objective of this study was to describe an innovative application of PRP gel supported by a three‐dimensional matrix of HA in the treatment of a complex wound. Several clinical studies showed the application of PRP to soft‐tissue wounds and found encouraging results. Martinez‐Zapata et al. presented a meta‐analysis of 20 clinical studies on PRP 31. With regard to skin ulcers, they provide inconclusive data, but selected applications in oromaxillofacial surgery show advantageous results. Kazakos et al. investigated PRP gel in the management of acute wounds, including friction burns. They found that PRP was an effective aid in the management of acute wounds 32. Pallua et al. purposed the use of PRP in burn patients to decrease the inflammation and to accelerate the reepithelialisation, as it is known that prolonged inflammation induces hypertrophic scarring and wound contractures 33.

The clinical observation established that the use of a three‐dimensional matrix of HA applied on the PRP gel can enhance tissue proliferation and promote wound healing by decreasing the pain, the risk of infection, contractures and hypertrophic scars. In addition, the procedure required minimal downtime and hospitalisation.

Bacterial infection contributes to pathogenesis of HS 1, 2. However, it is likely to be a secondary phenomenon, as cultures from lesions are frequently sterile and antibiotics are not curative. Usually, no bacteria are found in the initial stages of the disease. Lapins et al. 34 found that in severe HS, various pathogens can be present, including coagulase‐negative Staphylococcus, Staphylococcus aureus, Propionibacterium, Streptococcus milleri and Chlamydia trachomatis, and high rate of infections are reported after treatment 3, 4, 5, 6, 7, 29. In this sense, PRP is also useful in the prevention of infections because it contains abundant concentrated leucocytes, neutrophils, monocytes and lymphocytes 25. Recently, Burnouf et al. described the antimicrobial activity of PRP 35. In our case, the use of HPA to cover the wound allowed the controlled release of growth factors at the site of action over an extended period and provided an additional barrier against external elements.

Conclusion

Severe HS can be managed safely and effectively with wide excision. Application of PRP gel with Hyalomatrix is a new concept in the management of HS. Its application is easy, compatible and provides excellent results without additional morbidity. This case study presents an alternative technique for the successful management of a complex clinical challenge and the authors would encourage plastic surgeons and dermatologists to consider it as a treatment for these patients.