BY HABIR MANDAIR; KEYUR KURANI; & KHALID MALIK, MD
A 62-year-old obese woman with end-stage renal disease (ESRD) who was on hemodialysis, hypertension, diabetes mellitus, and chronically elevated serum calcium levels presented to the ED with altered mental status. Nursing home staff stated that she was unable to answer questions coherently and seemed confused.
Her vitals were within normal limits except for a body temperature of 99.9°F. Several necrotic lesions of various sizes were found on her left and right buttocks and the medial aspects of both thighs. The patient also had severe necrosis of the third finger on her left hand and the second on her right hand. Calciphylaxis was suspected because of her history and the unique characteristics of the lesions.
Lab results showed a serum calcium level of 13.6 mg/dL, a PTH of 102.2 pg/mL, and elevated vitamin D levels. The patient was admitted and treated by wound care, nephrology, and endocrinology. Medications and dialysis regimen were also adjusted to achieve adequate serum calcium control.
Recognition and Risk Factors
Calcific uremic arteriopathy (CUA), the more accurate name for calciphylaxis, is a rare disorder resulting from impaired calcium and phosphate homeostasis most often found in ESRD patients. Metastatic calcification of blood vessels isn't uncommon in ESRD patients, but CUA is distinctly different because it selectively targets dermal and subcutaneous arterioles in areas of high adiposity, as seen in the thighs and buttocks of our patient. This results in painful violaceous mottling and fixed livedo reticularis that progress to retiform purpura, followed by black eschar and ulceration.
The areas most commonly affected are the thighs, buttocks, and abdomen, but CUA can also affect the digits, which is a sign of more advanced disease. (UpToDate. May 18, 2018; https://bit.ly/2IF7PLg.) Early recognition of this disorder is extremely important because CUA has a high mortality rate with a six-month survival rate of less than 50 percent and even worse prognosis for patients on long-term hemodialysis. (UpToDate. May 18, 2018; https://bit.ly/2IF7PLg.)
CUA lesions are the result of decreased blood flow in dermal and subcutaneous arterioles. Progression of the disease is related to factors that increase serum calcium X phosphate product such as hyperparathyroidism, ESRD, and mineral bone disease. The disease's predilection for areas of high adipose tissue suggests that adipocytes may also play a role in its pathogenesis. Our patient had chronically high calcium levels due to a multitude of co-morbidities, including obesity, which made achieving adequate serum calcium levels necessary for survival.
ESRD patients can have risk factors for CUA related to hyperphosphatemia; medications such as warfarin, calcium-based binders, vitamin D analogs, and systemic glucocorticoids; being female; obesity; hypercoagulable states such as protein C and S deficiency and antiphospholipid syndrome; hypoalbuminemia; diabetes; longer dialysis vintage; inflammatory and autoimmune conditions; and recurrent skin trauma. (Am J Nephrol. 2013;37:325; http://bit.ly/2HYc6Y9.)
Physical findings of painful, non-healing, non-ulcerating lesions in areas of high adiposity, with or without necrosis, should be evaluated for CUA. Lab values that point to increased calcium and phosphate in the serum may increase the index of suspicion, as was the case with our patient, including hyperparathyroidism. Warfarin use prior to onset of lesions has been observed in studies as well. Histologic findings of skin lesions show dermal and pannicular arteriolar calcification, subintimal fibrosis, and thrombotic occlusion.
Calcification most commonly involves the medial layer of small arteries and arterioles, but it can also involve the intimal layer and interstitial subcutaneous adipose tissue. A skin biopsy may be performed to rule out other disorders that mimic CUA, though it is contraindicated in patients with infected lesions. Differential diagnosis of CUA includes atherosclerosis, cholesterol embolization, warfarin necrosis, endarteritis obliterans, vasculitis, cellulitis, purpura fulminans, oxalate vasculopathy, and antiphospholipid antibody syndrome. (UpToDate. May 18, 2018; https://bit.ly/2IF7PLg.)
The optimal treatment for CUA has yet to be established, but it involves a multidisciplinary approach that addresses wound care as well as endocrine- and dialysis-related care. The administration of sodium thiosulfate has been shown to reduce pain in as little as two weeks after the first dose and completely resolve early lesions in many cases. (UpToDate. May 18, 2018; https://bit.ly/2IF7PLg.)
Our patient had advanced-stage lesions, making wound care the primary therapy and critical to recovery, as is pain management. This means selecting proper dressings, chemical debridement agents, and negative-pressure wound therapy. Surgical debridement is reserved for patients with infected wounds and chemical debridement for patients with wounds that are not infected. Opioids are often required for pain control, especially immediately following wound care debridement procedures. All patients suffering from CUA should avoid repetitive local tissue trauma. Most importantly, abnormalities of calcium, phosphorus, and PTH must be treated to reduce the calcium X phosphorus product levels. (UpToDate. May 18, 2018; https://bit.ly/2IF7PLg.)
CUA is a painful disorder with a poor prognosis. Patients with isolated digital ischemia has a somewhat better prognosis than those with proximal lesion disease, but both carry a high mortality rate. Infection is the primary cause of mortality. (UpToDate. May 18, 2018; https://bit.ly/2IF7PLg.) The incidence of CUA is rising in the United States and is thought to be the result of increased awareness and recognition. Early intervention can have a profound effect on patients' quality of life and survival. Treatment strategies are variable and dependent on the stage at which patients present.
Mr. Mandair is a fourth-year medical student at Xavier University School of Medicine who is currently rotating at Weiss Memorial Hospital ED. Mr. Kurani is a fourth-year medical student at the University of Medical and Health Sciences in St. Kitts, also rotating at Weiss ED. Dr. Malik is the chief of emergency medicine at Weiss Memorial Hospital in Chicago.