The Mysterious Calciphylaxis: Wounds with Eschar ‚Äî To Debride or Not to Debride?
Calciphylaxis (CPX) is a potentially fatal complication of end-stage renal disease.1 Many authors have called calciphylaxis a rare phenomenon, a potentially fatal condition, and a syndrome that leads to ischemic ulcerations. Throughout the years, this mysterious disease has been described in the literature by a variety of names such as uremic gangrene syndrome,1,2 calcifying panniculitis, and calcific uremic arteriolopathy.3,4 According to Bliss and others,1,5 the most functional term may be the most recent: vascular calcification-cutaneous necrosis syndrome.
The pathogenesis of CPX is uncertain.1 Just as perplexing is wound care treatment, which is limited to aggressive surgical debridement of necrotic tissue. Srikureja6 states that debridement and regular wound care are necessary to promote healing and prevent serious complications from overwhelming secondary infection. Hadler7 recommends topical wound care products to facilitate debridement. Acknowledging the fact that these ischemic ulcerations of the skin are due to metastatic calcification of subcutaneous tissue and small arteries,8 debridement of ischemic wounds with stable eschar is contraindicated until perfusion status is determined.9 Furthermore, preventing wound infection is critical because sepsis related to wound infection is the leading cause of death for patients with CPX.10
According to Nunley,11 the obscure pathogenesis of CPX is likely the result of a multiplicity of comorbid factors or events. It is believed that patients develop this condition as a result of a hypersensitivity reaction to sensitizers such as increased parathyroid hormone (PTH), hypercalcemia, and hyperphosphatemia.3,12,13 According to Ledbetter,3 underlying vascular damage is present within the small vessels that may be related to the cause of renal failure; this predisposes patients to metastatic calcification in the setting of an elevated PTH level with an elevated calcium and phosphate product. Yet some patients with CPX have normal calcium, phosphate, and PTH concentrations.14 Also, the exact role of parathyroid hormone is uncertain because CPX may occur after total parathyroidectomy in the absence of measurable PTH levels.11
Exposure to challenging agents such as blood transfusions, albumin administration, corticosteroids, immunosuppressive agents, and local trauma are also thought to be responsible for the precipitating events of CPX.8,15 This belief is based on the experimental studies performed on rats by Selye16 that included exposing the subjects to challengers such as blood products, metals salts, and trauma. Functional protein C abnormality or protein S deficiency could be likely causes of thrombotic events, representing the cause of ischemia in clients who are susceptible to developing CPX.1,3,17
What is known about this mysterious disease is that it is a potentially fatal complication of ESRD caused by progressive calcification of small and medium cutaneous blood vessels leading to necrosis of the skin and internal organs.1,3,13,15 Calcium phosphate metabolism alterations seem to be its most prominent characteristic.1,18 According to Hahler,19 phosphate excretion disappears in ESRD, causing significant hyperphosphatemia that leads to calcium release from the bone matrix. Calcium settles along the irregular lining of the arteriole intima, creating a build-up that narrows the lumen and restricts oxygenated blood. Chemical reactions accompany the decrease in blood flow, leading to tissue ischemia, necrosis, and gangrene. Unlike other arterial insufficiency conditions, no large vessel involvement occurs; therefore, peripheral pulses are present.19,20 Soft tissue calcium deposition primarily affects the trunk or lower extremities, causing infarction of the skin and underlying structures.1,21
In the past decade, according to Nunley,11 CPX has affected up to 4% of the population with ESRD internationally. Calciphylaxis is not uncommon and should no longer be considered rare.14 The overall mortality rates of CPX have ranged from 60% to 80%, mainly from uncontrolled sepsis from wound infection.8,22 Early recognition of signs and symptoms and prompt treatment are crucial for symptom relief, wound healing, and prevention of sepsis and death.1,17 Risk factors that predispose ESRD patients to CPX include: Caucasian, female, insulin-dependent diabetes mellitus due to extensive vascular calcification, warfarin therapy, prolonged dialysis, and peripheral vascular disease, among others.1,22,23 Obesity has recently been established as a risk factor, primarily due to large deposits of adipose tissue that may be associated with a reduction of local blood flow.8,24
Calciphylaxis typically involves the distal extremities and has been reported to affect the buttocks, lower abdomen, and thighs.7,14,25 Skin lesions are often the presenting sign1,5 (see Figure 1). Calciphylaxis generally manifests with tender, violet-colored or erythematous, mottled skin lesions, known as livedo reticularis.1,7,13 Vesicles often appear at the periphery of the ulcers12,18 (see Figure 2). These lesions usually progress rapidly over several days to weeks to painful indurated plaques and nodules in the skin and subcutaneous tissues, resulting in ulcers and thick dark eschars with underlying tissue necrosis associated with considerable pain1,21 (see Figures 3 and 4). Most patients report not only pain at the site of the ulcer but also an extreme burning sensation.6 Multiple lesions of variable age may be present following the path of the vasculature.11 Depth of tissue injury is most commonly limited to the subcutaneous and dermal layers.19,26 Why the cutaneous organ and the cutaneous vessels appear to be most involved in CPX is unclear.6
The diagnosis of CPX is not always obvious. No diagnostic laboratory test is available for CPX.22 Diagnosis can be inferred by clinical history and cutaneous examination. A skin biopsy that illustrates widespread calcification and fibrinous thrombi occluding vessel lumina plus the absence of inflammation confirms the diagnosis.1,27,28 According to Worth,10 the mere presence of calcification on biopsy does not prove CPX. Calcification is also found in calcinosis and calcergy. The diagnosis sometimes can be suggested radiologically by vessel and or soft tissue calcification,22 but often this is nonspecific and found in many patients with ESRD.7,27 According to Mathur,8 xeroradiography is the best technique to study soft tissue calcification.
Differential diagnosis. In diagnosing calciphylaxis, clinicians need to exclude other conditions that might seem similar.10 Differential diagnosis should always include disorders that can result in distal extremity ischemia and tissue necrosis, such as arteriosclerosis, diabetes, microembolization, disseminated intravascular clotting, peripheral vascular disease, and autoimmune vasculitis.1,2,7 Purpura and livedo reticularis are the cutaneous manifestations that differentiate the clinical diagnosis.1,7,27
Treatment Focused on Wound Care
Treatment of CPX is challenging and offers limited success. Early recognition and treatment are essential; failure often results in a delay in diagnosis and treatment, leading to the death of the patient.14 Treatment is primarily supportive with emphasis on controlling and eliminating the sensitizers and challengers.22 A combination of nonhealing ulcers and a weakened immune system secondary to multiple medical problems predisposes these patients to sepsis.14,29 Superinfection is the primary cause of the high mortality rate associated with the condition. Wound debridement may be necessary for patients exhibiting extensive wounds that are infected. Bacteria can proliferate in wounds with eschar that is hydrated, softens, and becomes moist slough, overwhelming the patient’s immune system.30 Lesions frequently do not heal or heal very slowly.1,18 With time, potential complications often occur, including digital gangrene, necessitating amputation.1,31
Management includes debridement and regular wound care to promote healing and prevent serious complication secondary to infection.1,3,6 However, the role of wound debridement is controversial for patients with CPX.8,32 The decision to debride a wound, as well as which method to use, depends on a complete patient and wound assessment. The appropriateness of wound debridement is determined by the patient’s condition and the goal of care. For example, if the goal of patient care is comfort instead of healing, potentially painful debridement methods may not be suitable. Similarly, debridement may not be advisable if a patient presents with seriously compromised peripheral perfusion and dry eschar on the lower extremities.33
One aspect of wound management that is different for the ischemic wound is the recommended approach for a dry, noninfected necrotic wound. Although necrotic tissue presents the potential for bacterial growth, a dry intact eschar also can serve as a bacterial barrier. A closed wound surface is advantageous when managing a poorly perfused wound in which any bacterial invasion is likely to result in clinical infection and limb loss.34 Dry eschars often act as “Nature’s biologic dressing”; in this case, surgical debridement is not necessary.35 Dry, desiccated eschar is not a medium for bacterial growth. Most clinicians would agree that when blood supply to an ulcerated area covered with eschar is compromised, the most appropriate management often consists of painting the eschar with povidone iodine to reduce the bacterial bioburden on the surface and leaving it open to air or applying a dry dressing as needed.30
When eschar covers a stable noninfected wound on an ischemic extremity, debridement is contraindicated until an overall plan of management in terms of revascularization has been decided.9 Freidman36 reported that only four cases of lower extremity revascularization of patients with CPX appear in the literature and all four patients were reported to have 100% mortality within 2 months of lower extremity revascularization. In all patients, worsening gangrene was noted and wound healing complications occurred despite a patent bypass. Revascularization may not be an option for patients with CPX. A more conservative and less invasive measure of care may be the priority for these patients. At the present time, it appears that treatment goals for patients diagnosed with CPX presenting with wounds are to control pain and sepsis.7
Ms. D, a 51-year-old Hispanic woman with a history of lupus, diabetes mellitus, hypertension, and obesity, underwent peritoneal dialysis (PD) after exhibiting signs of renal failure. After several months, she experienced PD failure and started on hemodialysis. Approximately 1 month later, the patient complained of a lingering bruised area on her right calf. Shortly after, she noticed a blister. The blister opened and the area dried into an eschar. She reported that more blisters appeared, opened, and turned black.
On examination, Ms. D had an eschar measuring 15 cm x 10 cm with irregular borders. The area appeared without signs and symptoms of infection. The surrounding skin had a mottled appearance resembling livedo reticularis and indurated nodules tender to the touch. Both legs were sclerotic on palpation with multiple smaller necrotic lesions. The patient’s pain became unbearable and she was unable to lie down. She reported that the pain was more tolerable standing or walking and for a few minutes sitting. She could not sleep due to the pain and a constant burning sensation. Her primary physician provided pain management.
More and more nodules appeared along the vasculature. Ms. D was sent for a hyperbaric oxygenation (HBO) evaluation and was found to be a poor candidate. Transcutaneous oxygen pressure measurement was 25 mm Hg with minimal improvement on oxygen challenge. Results between 20 and 40 mm Hg are considered equivocal in terms of wound healing.34 She was instructed to keep the necrotic lesions dry and clean.
Unable to sleep due to the pain, Ms. D went to the emergency department complaining of severe pain, inability to sleep, and increased eschar formation with erythema on both lower extremities and was admitted for further evaluation. A skin biopsy showed many features of CPX as confirmed by the clinical picture. Deep vein thrombosis was ruled out. Intravenous antibiotics were administered and pain management was initiated. Laboratory tests were negative for systemic infection. Parathyroid scan and PTH levels were within normal limits; parathyroidectomy was not performed. At this time, clinicians felt that removing stable eschar would increase the patient’s risk for infection. The patient was sent home with eschars intact and instructions on pain management (see Figures 5, 6, and 7).
Calciphylaxis should no longer be considered a rare disease. It is a potentially fatal condition with a high mortality rate that affects arteriole microvasculature, leading to cutaneous ischemia and necrosis. Usually, the expected outcome or goal for wound care is healing. Unfortunately, for the ESRD patient with CPX, maintenance and prevention of infection of wounds is the most achievable goal. To debride or not to debride is dependent on accurate assessment of the wound and patient condition. Patients with comorbidities are at higher risk for infection, complications, and loss of limb. Early recognition and treatment are vital to prevent unnecessary suffering and increase patient’s quality of life.