Amniotic membrane dressings: an effective therapy for SSc-related wounds

Rheumatology key message

• Ulcerations cause morbidity in SSc and amniotic membrane dressings are effective for wound healing.

Sir, SSc is an autoimmune disease reffered to rheumatologists with profound morbidity and mortality. Ninety per cent of patients with SSc will experience RP; the sequellae include variable levels of ischaemia-induced ulceration leading to significant tissue loss. SSc-related digital ulcers (DUs), which occur in ∼50% of patients and reoccur in up to 70% of these patients, are a devastating complication of this disease that influence all aspects of self-care [1]. Lower extremity and elbow ulcerations are also a major source of morbidity and have limited treatment options [2].

Accepted therapies to heal and/or prevent DUs are often secondarily assessed in RP clinical trials. Consequently, the effectiveness of wound therapy for DUs is often difficult to assess and inconclusive, limited by small sample sizes, lack of randomization, blinding and inconsistent measurements. It is recognized that SSc disease features influence the natural history of DU formation, yet the impact of local DU wound care is unknown. The goal of this study was to evaluate our standard wound care practice using regenerative tissue applied directly to digital and extremity ulceration with digital photography to assess time to healing.

Patients were diagnosed with SSc by 2013 classification criteria [3], were enrolled in the University of Utah SSc registry and were receiving wound care. Initial images of the ulceration were obtained and cleansing was performed as previously described by our group [4]. After the wound was cleaned, application of amniotic membrane directly to the ulceration was applied. Triple antimicrobial ointment was placed over the amniotic membrane and xeroform wrap to prevent desiccation of amniotic membrane (Fig. 1A–D). The dressing was removed every 2–3 days and the wound was evaluated every week in an SSc wound clinic until complete healing was observed (Fig. 1E–G). The institutional review board (38705) of the University of Utah and Salt Lake City VAMC, which serves as the ethics committee, approved all procedures.

Fig. 1.

Amnion membrane dressing for SSc-related ulcers

(A) Amnion membrane. (B) Digital ulcers post-cleaning. (C) Triple antimicrobial ointment placed over the amniotic membrane and xeroform wrap to prevent desiccation of amniotic membrane. (D) Kerlix gauze wrapped around the digital dressing. (E) Lower extremity wound pre-amnion. (F) Eight weeks post-amnion. (G) Twenty-one weeks post-amnion membrane dressing.

Six SSc patients (four females, age 28–50, all SSc-specific antibody positive) received amniotic membrane dressings over a 6-month period for three DU, two elbow and one shin ulcer. All patients were on a calcium channel blocker. One patient was on a phosphodiesterase inhibitor. No patients were on endothelin receptor antagonists or prostacyclin analogues. No patients had pulmonary arterial hypertension. One patient had a history of a scleroderma renal crisis. Two patients were on immunosuppression. Two patients had previously failed hyperbaric oxygen treatment. All patients had the ulceration present for >12 weeks. With treatment, all patients had complete healing of their ulcerations: 1–3 weeks for DU, 7–9 weeks for elbow and 21 weeks for shin. While all patients had complete healing of their ulcerations, one patient required a repeat application for a reoccurrence after 2 months. There were no complications observed. All patients reported pain relief with dressing; however, this was not captured using a formal rating scale.

Our study demonstrates the role of amniotic membrane dressings for treatment of SSc-related ulcerations. Amniotic membrane was first described in 1910 as a split thickness graft to treat burn injury [5]. Amniotic membrane consists of an innermost layer and an outer chorion layer [5]. The foetal side or inner layer of amnion is a single layer of epithelial cells attached to a thin avascular membrane that contains collagen types III, IV, V and VII along with fibronectin and laminin. Proteins identified in the amniotic membrane dressing that are important in wound healing and remodelling include hyaluronic acid (anti-inflammatory), epidermal growth factor (regulates fibroblasts and angiogenesis), vascular endothelial growth factor (supports angiogenesis), insulin growth factor (cell–cell and cell–matrix communication and growth), transforming growth factors α and β (support proliferation), and other cytokines and chemokines that support cell movement and proliferation. Amniotic membrane is classified as immune privileged as it lacks expression of HLA-A, -B, -C, -DR and -β2 micro-globulin [6]. Typically, the amniotic membrane layer is obtained after the placenta is collected at elective caesarean section. The amnion/chorion membrane is separated from the placenta and the chorion is dissected away for the amnion layer. This amnion layer is processed, sterilized and cryopreserved by the Cell Therapy and Regenerative Medicine Facility at the University of Utah to create a dressing (Fig. 1A). While prior clinical studies of amnion membrane dressings demonstrate reduction in inflammation and scarring, modulation of vascular growth and promotion of epithelialization [6], our study is the first to examine this wound dressing in SSc-related ulcerations.

Our study is not without limitations. This was a single-centre; unblinded study with a limited number of participants and inadequate patient-reported outcome measures. Nonetheless, complete healing was demonstrated in all subjects suggesting that this dressing type may be considered effective for SSc-related DUs. Our data support those of other clinical studies [6, 7] that demonstrate reduction in inflammation and scarring, modulation of vascular growth and promotion of epithelialization with amniotic dressings, and suggest that this wound dressing should be used in wound care clinics treating SSc patients. Further studies are warranted to better understand the mechanism of action.

Acknowledgements

The investigators would like to thank the University of Utah Cell Therapy and Regenerative Medicine Center for donation of the products used in this study.

Funding: This work was supported by awards from the National Institutes of Health (K23AR067889) and the U.S. Department of Veterans Affairs (I01 CX001183). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Disclosure statement: The authors have declared no conflicts of interest.