Wound Management and Surgery for Calcific Uremic Arteriolopathy (Calciphylaxis): A Retrospective Observational Cohort Study

ABSTRACT

Wound care in calciphylaxis remains poorly defined without evidence‐based consensus on timing and technique of surgical intervention. We demonstrate that surgical debridement and subsequent wound closure are safe and effective in calciphylaxis and describe a systematic multidisciplinary approach to intervention. We retrospectively reviewed a cohort of patients with calciphylaxis at our institution. Those who underwent surgical debridement and wound closure were analysed with emphasis on wound healing, progression to amputation and mortality. Sixty‐two patients with calciphylaxis underwent surgical debridement. Twenty patients had wound closure by skin grafting, five were excised with primary wound closure, and 37 were debrided and allowed to heal by secondary intention. There were excellent rates of healing in all groups, and no patients demonstrated wound progression or new lesions following operative intervention. Surgical debridement and wound closure are safe and effective in treating wounds related to calciphylaxis.

Key Points

• Surgical debridement and wound closure are safe and effective in treating wounds related to calciphylaxis

1. Introduction

Calciphylaxis is a disorder that manifests clinically as painful skin ischemia and necrosis. Histologically, it is characterised by extensive calcification of small‐ to medium‐sized arterioles within the dermis and subcutaneous adipose tissue, often accompanied by thrombosis [1]. As an entity, it portends a poor prognosis with a 6‐month survival rate of only 50% in many studies [2, 3]. Calciphylaxis is a phenomenon predominantly seen in patients with advanced chronic kidney disease on kidney replacement therapy but may also occur in patients who have received a kidney transplant and in those without any kidney disease [4] In patients without kidney disease, the entity is known as nonuremic calciphylaxis.

The pathogenesis of the disease remains incompletely understood. Alterations in the regulation of vascular calcification, along with a chronic inflammatory state are thought to contribute to the histological features that define the phenotype of this disease [1, 5, 6]. An association with warfarin has also been well reported over the years in the literature, likely due to vitamin K‐dependent calcification inhibition mediated by the actions of various proteins such as matrix Gla associated with the use of this drug [7, 8, 9]. Vascular calcification and thrombosis cause ischemic tissue injury. In the case of adipose tissue, ischemia results in cellular injury, inflammation, changes in adipocyte function, fibrosis, infarction and necrosis.

The index symptom of calciphylaxis is pain, which is frequently out of proportion to initial physical examination findings. This often starts before overt skin changes are noted. The regions that are most often affected include the distal lower extremities (55%), proximal lower extremities (39%), trunk (31%), distal upper extremities (7%) and proximal upper extremities (3%) [10].

The macroscopic appearance of the lesions of calciphylaxis is dependent on the degree of tissue injury. In the early stages of disease, patients may present with extremely painful subcutaneous induration or nodules in the absence of overlying skin changes. These lesions are the result of the ischemic, inflammatory process within the adipose tissue incited by vascular calcification and thrombosis. As the disease progresses, early overlying skin changes may appear erythematous, violaceous, mottled and remain indurated and extremely tender to palpation. Retiform purpura (violaceus skin discoloration in a net‐like pattern) is a classic skin finding, mirroring arteriolar compromise, and indicates ongoing disease activity. As the ischemic process evolves, frank skin necrosis ensues and characteristic eschars appear which may ulcerate. Superinfection of this nonviable tissue is common, and the high mortality associated with calciphylaxis is most often due to sepsis from bacterial infection [11].

Tissue trauma in a patient with calciphylaxis may result in a new calciphylaxis lesion at the site. The Koebner phenomenon, or ‘Koebnerization’, the appearance of new, isomorphic lesions on otherwise healthy appearing skin secondary to local tissue trauma has been proposed as a possible explanation for this in retrospective studies [12]. We postulate that the Koebner phenomenon may be a pseudo‐phenomenon in calciphylaxis, as secondary lesions only form in areas of ischemic tissue, which may be subclinically affected by the systemic, vascular calcific process and not in healthy skin and subcutis spared from this process. Observational prospective evidence to support this comes from patients with calciphylaxis on haemodialysis with arterio‐venous fistulae, who, despite frequent venipuncture at this site, do not develop lesions despite retrospective data suggesting that finger sticks for blood glucose measurement and subcutaneous injection sites progress to calciphylaxis lesions [12].

This long‐held association may have originated with skin biopsies that failed to heal and subsequently ulcerated and developed into chronic wounds because such biopsies are typically obtained from areas of retiform purpura or induration, which reflects compromised tissue. Nevertheless, this has led to a more thoughtful approach to biopsy and debridement due to fears of causing disease progression or new areas of ulceration, despite some data demonstrating increased survival with surgical debridement [13, 14].

Surgical debridement of calciphylaxis‐related lesions has not been well documented or described in the literature, partly due to the rarity of the disease, variability in lesion size, as well as patient‐related factors that make surgery less favourable. Also, dry, noninfected wounds covered in eschar are often managed non operatively, due to the belief that this temporary ‘biologic envelope’ is resistant to super‐infection despite data showing that subeschar cultures frequently yield pathogenic bacteria [15, 16, 17].

Our clinical practice as part of a multidisciplinary approach to calciphylaxis has been to selectively debride these lesions and surgically close the resultant wounds when feasible once their evolution, size and morphology suggest that the calciphylaxis lesion has stabilised and a clinical benefit is attainable. The decision to pursue debridement and surgical wound closure, however, is dependent on several patient and wound‐related factors which will be discussed in this feature.

This study retrospectively reviews our data on the surgical management of calciphylaxis to highlight the safety and importance of surgical debridement as a component of the therapeutic paradigm. We then propose an algorithm for the management of these wounds and compare outcomes of a matched cohort who did not have an operative management strategy.

2. Methods

Under Institutional Review Board approval, we performed a retrospective observational cohort study of our calciphylaxis registry, which was created at our institution in 2017 [18]. This registry contains 240 patients, all of whom had a confirmed clinical diagnosis of calciphylaxis. Not all patients required a histologic diagnosis to be included in the registry, and those with pathognomonic lesions in the appropriate clinical context did not proceed to early biopsy unless there was diagnostic uncertainty.

A cohort of patients from the registry who underwent operative surgical debridement (n = 62) was then selected. Operative surgical debridement was defined as excision of necrotic or infected tissue in the operating room under general or regional anaesthesia. The nonoperative cohort consisted of all remaining patients in the registry (n = 178). These patients were managed with nonsurgical wound care. There was no cross‐over between cohorts in our retrospective analysis. Both cohorts received medical management of calciphylaxis as described in the literature [19].

The decision to perform an operative debridement was made clinically, on a case‐by‐case basis, using patient and lesion‐specific variables.

Patient‐specific variables included nutritional status, glycemic control, the presence and severity of peripheral vascular disease, quality of life measures including pain and the feasibility of longitudinal wound care. Lesion‐specific characteristics included the stage and trajectory of disease, the size (greater than 3–5 cm) and location of the wounds, the extent of infection, whether surgery was necessary to achieve source control of infection, as well as the ability to close or cover the resultant wound. Analyses were stratified by dialysis status, location of lesion (peripheral [acral, distal extremities], central [abdomen, proximal extremities], mixed [concurrent peripheral and central lesions]), number of debridements performed, type of wound closure, need for amputation and mortality at 24 weeks and 2 years.

Descriptive statistics were performed to summarise the demographic and clinical characteristics of the patient population. Frequencies and percentages were used for categorical variables. This approach allowed for a comprehensive overview of the cohort and provided insights into the distribution of key variables and potential associations between these factors and outcomes such as amputation and mortality.

3. Results

Patient demographics are shown in Table 1. The registry consists of 240 patients with calciphylaxis, the majority of whom were female (67%) and white (78%). As would be expected, most patients were on dialysis (68%); however, approximately one third of patients in the registry were not on dialysis at presentation. Sixty‐two (26%) patients in the registry underwent operative debridement. The topographic distribution of their lesions is illustrated in Figure 1.

TABLE 1.

Demographic data for patients in the calciphylaxis registry.

	Operative debridement	Nonoperative
Total number of patients	62 (26%)	178 (74%)
Male	14	65
Female	48	113
Race or ethnic group
Black	16	18
White	42	144
Hispanic	4	0
Other/not specified	0	16
Dialysis status
On haemodialysis	45	117
Not on haemodialysis	17	61

FIGURE 1.

Topographic location of calciphylaxis lesions in patients undergoing operative debridement.

3.1. Wound Closure

Among the operative cohort, 20 patients underwent wound closure by skin grafting, five underwent excision with primary wound closure, and 37 underwent operative debridement and were allowed to heal by secondary intention. Overall, 24 (39%) of the patients had one operative procedure, while 38 (61%) patients required more than one operative procedure. Multiple operative procedures typically consisted of serial debridement.

Our standard practice for wounds that were not overtly infected after debridement was to use negative pressure wound therapy (NPWT) to facilitate contracture and wound bed preparation.

Figure 2 illustrates the outcomes of the 42 patients managed operatively without autografting. Of the patients surgically debrided with intention to heal secondarily, 18 (43%) had healed or were in the process of closing at follow up, either in the hospital or at 4–6 weeks in the outpatient clinic; 15 (36%) patients had their goals of care changed to comfort measures only (CMO) with palliative wound care due to progressive and overwhelming wound‐related infection, intolerable pain due to extensive wounds, or acute decompensation due to another co‐existent diagnosis rendering further debridement futile (Figures 3 and 4). Three patients (7%) were healing well after excision and closure by primary intention, and three (7%) were lost to follow‐up. One patient developed a joint space infection and required a below‐knee amputation, one had a combination of amputation of the fingers and delayed primary closure at another site, and one had a delayed primary closure after debridement.

FIGURE 2.

Outcomes of the operatively managed cohort without autografting.

FIGURE 3.

Example of a patient with a large total body surface area involvement with extensive wounds complicated by overwhelming infection where the decision was made to proceed with palliation after the index debridement due to futility.

FIGURE 4.

Contralateral cutaneous involvement of the same patient in Figure 3.

Figure 5 illustrates the outcomes of the 20 patients managed operatively with autografting. Fourteen patients (70%) had satisfactory incorporation of the skin graft at the 4 week follow up defined as greater than 80% epithelialization of the surface area of the original wound. Two of these patients required repeated autografting due to graft loss. An example of graft loss can be seen in Figure 6. Five patients (25%) ultimately developed infections of the ipsilateral limb necessitating amputation: two of which had severe peripheral arterial vascular disease, one developed a joint space infection of the ankle due to the depth of the original wound over the joint, and two had distal calcaneal tendon and calcaneal bone involvement. One patient died of aspiration pneumonia before the skin graft was fully healed. All patients who were autografted had the donor site back‐grafted with 4:1 or 6:1 meshed split‐thickness autograft to ensure and expedite closure of the donor site. There were no donor site complications including infection or the appearance of isomorphic lesions.

FIGURE 5.

Outcomes of the operatively managed cohort with autografting.

FIGURE 6.

Lower extremity autograft on post op Day 5 (A) when primary dressing was removed. Same autograft on post op Day 13 (B) demonstrating significant graft loss. Repeat autografting may be considered.

3.2. Death

As stated, among the nonautografted operative cohort, 15 (36%) were transitioned to comfort measures only after the index debridement or during the process of serial debridement; among the autografted operative cohort, one patient died prior to adequate assessment of graft incorporation.

Figure 7 illustrates the mortality rates in the operative and nonoperative groups at 24 weeks and 2 years. We chose these two time points to address the short‐term mortality associated with calciphylaxis and to detect a possible survival benefit after operative management that would not have been superseded by the natural history of the disease. There were no significant differences between the two cohorts with respect to mortality. We also evaluated mortality based on topographic location of lesions as seen in Figure 8 with a higher mortality rate observed for central (proximal) versus peripheral (distal) calciphylaxis demonstrated at 24 weeks, but not at 2 years.

FIGURE 7.

Mortality rates in the operative and nonoperative groups at 24 weeks and 2 years.

FIGURE 8.

Mortality at 24 weeks and 2 years in the operative group based on topographic location of lesions.

4. Discussion

Our data supports the established literature that describes the poor prognosis associated with calciphylaxis, with overall mortality approaching 25% by 24 weeks. By 2 years, nearly half of the operative group (47%) and over 40% of the nonoperative group (41%) had died—highlighting the critical unmet need for more effective therapeutic strategies. Despite this, we have demonstrated that with judicious patient selection, operative intervention results in a reasonable wound closure rate with 55% of patients in the debrided group and 70% of patients in the debridement plus autografting group demonstrating closed wounds in follow up. Furthermore, we did not identify any cases congruent with the Koebner phenomenon, particularly at the donor site in patients who had donor skin harvested for autografting. We did not observe any issues with healing or infection at the donor site, and all the back‐grafted donor sites demonstrated satisfactory skin graft incorporation in follow‐up.

The high rate of death (36%) in the operatively managed cohort without skin grafting may reflect their large disease burden, akin to a large total body surface area (TBSA) involvement in burn injury, and the need for more urgent surgery for source control of infection and lack of suitability of the resultant wound bed for interval closure. Due to the retrospective, observational nature of this review, patients were not randomised to an operative arm which would have introduced significant selection bias, a limitation which we acknowledge.

Autografting was shown to be a useful technique for wound closure but was only performed in 32% of all patients in the operative cohort due to wound and patient characteristics.

The high mortality rate at 24 weeks in the operative cohort may have also been affected by selection bias as these patients likely were sicker and had an operative intervention for source control of infection.

At 2 years, the 6% higher mortality with operative debridement may also reflect patients who needed debridement for source control.

Notably, patients in the nonoperative group had smaller lesions (less than 3–5 cm) with less overall infection and therefore did not meet criteria for upfront operative management.

Channelling bias was difficult to avoid here as large wounds requiring complex wound care and overtly infected wounds would trigger the involvement of a wound care team, staffed by a surgeon with expertise in operative management.

Concern related to tissue trauma invoking the Koebner phenomenon causes hesitation when considering debridement even though some data suggest a decrease in mortality in patients that have had surgical debridement [3, 10]. We did not observe the Koebner phenomenon in our cohort.

We suggest that macroscopically appearing intact skin adjacent to frank calciphylaxis lesions may demonstrate subclinical vasculopathy with attendant ischemia and inflammation, and this predisposes traumatised tissue (from biopsy or debridement) to poor wound healing. The resultant wounds are therefore not new calciphylaxis lesions but rather the clinical manifestation of this vulnerable substrate. Clinical studies have demonstrated low cutaneous oxygen tension in patients with calciphylaxis indicating that severe and diffuse skin ischemia exists, even in areas free of skin lesions. Furthermore, in many patients with calciphylaxis, cutaneous oxygen levels do not substantially improve after increasing the fraction of inspired oxygen to 100%, suggesting a fixed insufficiency of the dermal vasculature [20]. This lends support to the fact that dermal and subdermal tissues are susceptible to injury. Therefore, even when the overlying epidermis appears normal, the underlying dermal and subcutaneous tissue may be severely compromised. The lack of Koebnerization noted at all split‐thickness skin graft donor‐sites in this series and in other areas of trauma, for example, frequent needle sticks at arterio‐venous fistulae for haemodialysis access and other wounds related to distant operative sites further argues against Koebnerization. Regardless of the underlying cause, worsening of skin ulceration, the appearance of lesions at sites of tissue trauma, and poor wound healing at these sites is well demonstrated and must be carefully considered when deciding on tissue biopsy and debridement.

4.1. General Considerations and Diagnosis

Calciphylaxis is best managed by a multidisciplinary team comprised of nephrologists, general or plastic surgeons, dermatologists, pathologists, nutritionists and pain specialists. If the diagnosis is not obvious from the clinical history and physical examination, and the differential remains broad, histologic evaluation is recommended via a tissue biopsy to rule out the conditions that mimic calciphylaxis [21].

The differential diagnosis includes primary thrombotic skin disease such as warfarin‐induced skin necrosis, atherosclerosis, vasculitis, cellulitis, necrotizing infections and Monckeberg's medial calcific sclerosis [22]. The decision to obtain a tissue biopsy must be considered carefully given that the ischemic tissue at the biopsy site may demonstrate poor or delayed wound healing and may become secondarily infected [19].

A skin punch biopsy, 4–5 mm deep, taken from an area of retiform purpura at the wound edge, or a deep incisional wedge biopsy of the same depth are likely to have the best yield [23]. It is our practice to perform a punch biopsy given the smaller resulting wound. In patients who meet criteria for debridement in the absence of a prior biopsy, we routinely send discarded tissue from the operating room for histopathologic study, ensuring that our sample includes the interface between grossly normal and grossly abnormal tissue to increase diagnostic yield. Biopsies consisting solely of necrotic eschar are of low diagnostic yield and should be avoided. Histopathologic features of calciphylaxis include finely stippled calcium deposits involving subcutaneous small and medium‐sized vessels, possibly with intravascular thrombosis and fibrointimal hyperplasia [22]. Extravascular, coarse calcium deposits may be seen but are nonspecific and can be identified in patients with chronic kidney disease in the absence of calciphylaxis [21]. Diagnostic accuracy is improved by adequate biopsy sampling to include ample subcutaneous adipose tissue for light microscopic evaluation, histochemical staining for the detection of calcium in tissue sections using specialised staining methods such as the von Kossa special stain, and having the samples reviewed by a pathologist with subspecialty training in dermatopathology (Figure 9) [22].

FIGURE 9.

Calciphylaxis skin biopsy specimen. Histologic sections display the presence of coarse concentric medial calcification of medium‐sized vessels (arrows) and subcutaneous fat necrosis (asterisk) at the deep biopsy edge (A, H&E stain, 200× original magnification). Presence of subtle finely stippled calcium deposits (arrowheads) involving small vessel walls is identified by von Kossa stain (B, von Kossa, 200× original magnification).

4.2. Initial Management and Stabilisation

As soon as the diagnosis is established, medical therapy can be instituted using current, evidence‐based practice. This includes cessation of culprit medications including vitamin D analogues, calcium‐containing phosphorus binders, warfarin and intravenous iron. Hyperparathyroidism is treated, targeting parathyroid hormone (PTH) levels of 150–300 pg/mL using a calcimimetic agent like cinacalcet in patients on dialysis. Surgical parathyroidectomy is only considered if the PTH level is refractory to medical management. Bisphosphonates are used if calciphylaxis is associated with hypercalcemia. The dialysis prescription is optimised to ensure the patient is receiving National Kidney Foundation‐Kidney Disease Outcomes Quality Initiative (NKF‐KDOQI) guided therapy. The prescription is only changed if the patient has refractory hyperphosphatemia despite dietary and medical management. The use of sodium thiosulfate (STS) as an off‐label treatment for calciphylaxis is recommended despite its uncertain efficacy. Evidence in support of its use from retrospective studies and case series has not yet been validated in meta‐analysis [24, 25, 26]. Despite this, given our anecdotal evidence, we continue to use it as an important part of therapy. It is preferably used via the intravenous route, but intraperitoneal and intralesional therapy has also been described [27, 28]. Multimodal control of nociceptive and neuropathic pain is also a critical component of initial management.

4.3. Intralesional STS

The use of intralesional sodium thiosulfate (ILSTS) is patient‐dependent and is used as part of multimodality therapy. This may include the addition of ILSTS for patients who may not be responding or even progressing despite maximal medical therapy, including intravenous sodium thiosulfate (IVSTS). Alternatively, for patients with a limited TBSA of calciphylaxis, ILSTS may be a good option that can help avoid the adverse systemic effects seen with IVSTS.

To perform this procedure, patients are asked to apply a topical local anaesthetic agent an hour prior to injection. This can be done in both an ambulatory and hospital setting. Afterward, the borders of the lesion are cleaned with 70% isopropyl alcohol, and a 1:1 mixture of 1% lidocaine without epinephrine mixed with STS 12.5 mg/50 mL is injected into the active areas, clinically apparent by erythematous or violaceous skin changes. The goal is to inject the medication into the deep dermis and superficial subcutis, and 0.1 mL is injected at each site, separated by 1 cm between injection sites. Some patients prefer to have 1% lidocaine without epinephrine injected first and then the 1:1 mixture of STS and lidocaine without epinephrine injected afterward where they are already fully anesthetised. In our experience, a subset of patients is unable to tolerate this procedure, but the majority are.

Anecdotally, systemic toxicity from STS has not been seen in our experience with intralesional use. While some patients have received ILSTS multiple times a week, our usual practice is to administer ILSTS weekly in an ambulatory setting.

4.4. Local Wound Care

There is a scarcity of consensus in the literature on wound management for calciphylaxis lesions. We utilised our data and experience to inform a calciphylaxis wound management protocol to help standardise our approach to treatment and to allow for improved data collection to guide future decision making (Figure 10). Regular skin assessment by dermatology and care of the wounds that result from calciphylaxis are integral components of management. Prevention and control of infection are paramount; however, selection of local wound care options must consider the significant pain associated with the wound care strategy. A global assessment of the patient, including their goals of care, should be performed when the decision is being made to proceed with a wound management plan.

FIGURE 10.

Algorithm for the management of wounds associated with calciphylaxis.

Cleaning the wounds of devitalized tissue is the first step. Our approach is to consider whether the patient's calciphylaxis lesions are in an ‘active phase’ or a ‘dormant phase’ which clinically represents a distinction between ongoing ischemia, inflammation and infarction with overt necrosis (Figure 11). This is best differentiated based on the clinical appearance of the border of the ulcer. If there is a halo of erythematous, violaceous, dark‐red skin or retiform purpura (active phase), we err on the side of avoiding surgical debridement, as the lesion is in evolution and is likely to progress. In this case, autolytic and/or enzymatic debridement is pursued using emollients such as wound gel (with or without antimicrobials), medical grade honey, or collagenase. Minor, local infections can be treated with topical and/or systemic antibiotics. Once the lesions have entered clinical dormancy (stable eschar) with local wound care, in our opinion, it is safer to pursue more aggressive wound debridement, either at the bedside or in the operating room. Wounds that are infected or those with a heavy bioburden benefit from the use of topical bactericidal agents such as solutions of dilute sodium hypochlorite. (0.25%).

FIGURE 11.

Skin changes in the lower leg of a patient with active disease, note initial evaluation (left) with progression to necrotic lesion over 6 weeks (right), at which point surgical debridement, wound bed preparation and wound closure would be appropriate.

Once malodor and purulence have resolved, indicating reduction of the bioburden and removal of necrotic tissue, a wound gel or medical grade honey may be used on the wound and covered to promote autolytic debridement. If there is a small amount of exudate, then petroleum impregnated gauze or petroleum with bismuth impregnated gauze can be used for coverage, the gauze assisting with mechanical debridement.

For larger wounds, once the wound bed is adequately prepared and devoid of overt infection, we have found NPWT with serial surgical debridement and dressing changes, typically performed in the operating room, to be a helpful adjunct. It should be noted, however, that the use of NPWT has been shown to have variable effects on tissue oxygenation and capillary blood flow in different parts of the wound, particularly in tissue with vascular compromise. This is due to the technique used to measure perfusion. It is likely that this variability in perfusion may accelerate wound healing and granulation tissue formation [29, 30, 31, 32].

4.5. Surgical Wound Management

The decision to debride the wound should be made on a case‐by‐case basis using well‐defined steps. The high mortality associated with calciphylaxis is often due to sepsis from the cellulitis caused by infected lesions superimposed on significant co‐morbidity [11]. In a patient with a suspect lesion and signs of systemic infection, surgical debridement for source control is paramount and may be lifesaving; therefore, the first question should be, ‘Is this lesion making the patient sick?’ If the lesion is not causing systemic illness, debridement should be undertaken only after specific questions have been answered regarding the characteristics of the patient and the lesion.

Patient characteristics to consider include nutritional status, the presence of peripheral vascular disease (especially if the lesions are on the distal lower extremities), glycemic control, pain and quality of life regarding wound care and general goals of care. Distal wounds in patients with severe arterial vasculopathy may be better served with upfront amputation given the poor results of re‐vascularization in this cohort but consultation with vascular surgery should be considered on a case‐by‐case basis as re‐vascularization may limit the extent of tissue loss [33].

Characteristics of the lesion that are important to consider include disease activity and extent, presence of infection, size, location and the ability to close or cover the wound. In the early phases of calciphylaxis, ischemia often causes the classic painful evolution of skin changes which represent the progression of tissue loss. The early findings are marked by erythematous or livedo‐like skin and a woody, nodular impression on palpation (Figure 12). This occurs before frank necrosis ensues ultimately resulting in the formation of relatively adynamic eschars that are commonly seen as the infarcted tissues declare their margin (Figure 13). Despite the obvious disease continuum, we think of this as a bipartite process and, as mentioned earlier, typically separate lesions into those that are ‘active’ and those that are ‘dormant’.

FIGURE 12.

Skin changes on the distal lower leg in a patient with active, evolving lesions. Note the retiform purpura with evolving eschar formation.

FIGURE 13.

Skin changes in the right breast of a patient with dormant disease marked by dense, well demarcated eschar and lack of surrounding retiform purpura.

Generally, our practice is to refrain from debridement until the lesion has become dormant, to avoid intervention on a lesion that has yet to declare a grossly infarcted margin (Figure 12). During the active phase, we recommend optimization of previously discussed medical therapy combined with local wound care to prevent infection, while maintaining a high index of suspicion for cellulitis given the significant associated mortality and the difficulty with distinguishing it from the early ischemic skin changes (Figure 14). Once tissue ischemia has progressed to infarction and necrosis and the demarcation is clear and stable, debridement should be considered. If the necrotic eschar and peripheral tissues become superinfected, debridement should focus on source control of infection while achieving healthy margins of surrounding skin and deep adipose tissue. If the infection is mild and the patient is not systemically affected, a closely monitored short course of broad‐spectrum antibiotics combined with local wound care can be trialed. In these cases, patients are typically admitted, given the need for dialysis and dose‐adjusted intravenous antimicrobials.

FIGURE 14.

Skin changes in active calciphylaxis, mimicking acute cellulitis.

In dormant lesions, before debridement, we consider the size, location, available tissue for closure or coverage and the quality of the surrounding subcutaneous adipose tissue. We also consider goals of care, general health status, pain, and the need for potentially painful dressing changes during wound bed preparation until the wound is ready for closure. We typically debride dormant, necrotic lesions greater than 3–5 cm. Any wound smaller than 3–5 cm without signs of infection, we have allowed to progress via autolytic debridement with twice monthly serial wound checks (Figure 15). These patients have frequent medical encounters because of dialysis and have their wounds evaluated regularly.

FIGURE 15.

Small lesion that we would not routinely debride based on size.

When we do choose to debride, we usually perform excisional debridement using sharp and blunt dissection to achieve healthy margins of skin and adipose tissue on gross visual inspection. Adipose tissue that is indurated and often more pale appearing is partially ischemic and unhealthy. It is more likely to desiccate after debridement and does not granulate well and therefore should be excised. Serial excision is often required. The tissue defects are then covered using NPWT therapy or antimicrobial dressings until the underlying tissue has granulated, and a healthy wound bed exists for delayed primary closure or autologous skin grafting. The resulting wounds can be large and painful, and patients may return to the operating room every 3–5 days for dressing changes and serial debridement until wound care can be transitioned to the bedside.

If tissue redundancy permits, and the entire wound with all affected adipose tissue inclusive of a clear margin of normal adipose tissue can be removed, wounds can be closed primarily or in a delayed primary fashion (Figure 16). If there is significant dead space, a fenestrated drain is left in situ to help manage the postoperative effluent and prevent seroma formation.

FIGURE 16.

Multifocal abdominal wall lesions (A and B) after debridement with primary closure over drains (C) with complete healing (D) at the 6 week follow up.

Given the impaired wound healing commonly seen in this co‐morbid population, as well as to decrease pain, when autologous skin grafting is used for closure (Figure 17), we frequently back‐graft the donor site with a widely meshed (4:1 or 6:1), thin, split‐thickness skin graft (Figure 18). This markedly hastens wound closure and decreases donor site pain [34]. For autologous coverage of larger wounds, the use of widely meshed grafts (3:1 or 4:1) combined with autologous cell suspension (Recell) can be a useful adjunct to further hasten closure and reduce donor site size [35].

FIGURE 17.

Evolution of a large lesion prior to debridement (A), after debridement with serial NPWT (B), 1 week after autografting (C) and 3 months after autografting (D).

FIGURE 18.

Example of donor site back‐grafted with 4:1 meshed STSG 5 days postgrafting (left) with excellent wound healing and complete epithelialization at 2 week follow up (right).

Our study has some important limitations requiring discussion. First, the retrospective nature introduces significant selection bias as patients who proceeded to operative intervention likely had an operative indication. Also, the mortality rates were not adjusted for any other study variable which may have enhanced the validity of the study. The single‐institution population also introduces bias as it limits the heterogeneity in the treatment paradigm. Furthermore, as the data was collected retrospectively, there was no standardisation in the photographic documentation of the lesions and our study could have been enhanced by having more intraoperative photographs.

Our goal is to decrease potentially life‐threatening wound infections, decrease pain, and improve quality of life for patients with wounds caused by calciphylaxis through selective debridement and appropriate wound closure. In line with our findings, early referral to a multidisciplinary team that includes a surgeon experienced in excisional debridement, longitudinal wound care and autologous skin grafting is recommended for all patients diagnosed with calciphylaxis to optimise outcomes and initiate comprehensive care early in the treatment course. Surgical debridement should not be considered contraindicated in appropriate patients with calciphylaxis.

Funding

The authors have nothing to report.

Conflicts of Interest

Sagar U. Nigwekar, MD received compensation from the American Society of Nephrology for his role as the Deputy Editor for the Clinical Journal of Society of Nephrology and from the National Kidney Foundation for his role as Associate Editor of the Advances in Kidney disease and Health, consulting fees and/funding from CSL Behring, Fresenius Medical Care, Inozyme Pharma, Epizon Pharma, Vera Therapeutics, Alexion, RubiconMD and Sanofi and royalty payments from UpToDate. The other authors declare no conflicts of interest.

Data Availability Statement

Data were obtained using the Institutional Review Board approved protocol #2016P002690.