Calciphylaxis, also referred to as calcific uremic arteriolopathy (CUA), is a rare, highly morbid pathological syndrome of vascular calcification and tissue necrosis. Primary lesions appear as painful violaceous skin lesions that develop secondary to extensive small vessel calcification.6 Clinically, patients may present with areas of tissue necrosis and nonhealing wounds.7 Vascular calcification of the dermis is a consistent finding in cases of calciphylaxis, but calcifications of the muscle, brain, lungs, intestine, and mesentery also have been reported.8-12 Although the disease process in humans has been documented in the medical literature since 1898,13,14 the condition is still poorly understood and continues to be a treatment challenge for clinicians.
Definitive diagnosis of calciphylaxis requires a tissue biopsy. Histologic findings typically consist of calcification within the media and intima of both the small and medium arterioles with considerable hyperplasia, fibrosis, and inflammatory infiltrate.15,16 Subcutaneous calcium deposits, fat necrosis, and vascular microthrombi are also common.15,16 Pathologic examination may reveal tissue calcification and ischemic epidermolysis, while radiographic studies often reveal calcification of median and small vessels.7,17
Calciphylaxis is predominantly seen in patients with ESRD on chronic dialysis. Between 1% to 4% of patients with ESRD may show signs of calciphylaxis.7,18 The overall prognosis is bleak—complications such as amputation, infection, or death occur in 60% to 80% of patients affected, and the disease has a 1-year mortality rate of 45% to 80%.18-20 Patients with ulcerated lesions have a greater mortality rate than those with nonulcerated lesions, with sepsis being the leading cause of death.13,19,20 The majority of calciphylaxis lesions occur on the lower extremity.13,20
Additional implicated risk factors for calciphylaxis include hyperphosphatemia, hypercalcemia, diabetes mellitus, secondary hyperparathyroidism, elevated calcium-phosphorus product, female sex, warfarin use, corticosteroid use, protein C or S deficiency, malnutrition, liver disease, hypokalemia, and vitamin D therapy.18,20-24 Thus, in patients with suspected CUA, it is essential to conduct laboratory evaluations of renal function, mineral bone parameters, liver function, infection, coagulation, inflammation, autoimmune disease, and malignancy.25
There is no set standard of care for the treatment of calciphylaxis. A comprehensive treatment plan requires a multidisciplinary approach. In 2010, Sowers and Hayden suggested various therapeutic approaches to treat and prevent CUA24; among these were the attempt to normalize metabolic parameters via medication and dialysis, adjust calcium and phosphorus ratios by replacing all calcium phosphate binders with noncalcium phosphate binders, use the antioxidant STS, improve wound hypoxia, and provide proper wound care.
With the present patient, nephrology adjusted dialysis and medication, but improving wound hypoxia and providing proper wound care fell to the primary author and her team. Given the restrictions imposed by COVID-19, this challenge was even greater than usual. With the need to “think outside the hospital” in order to provide care in the lowest-risk environment possible to a high-risk patient while minimizing the use of resources, the primary author determined that at-home treatment was the best course of action.
With no consensus on effective wound care management for CUA, and limited data regarding successful therapies, the use of adjunctive wound therapies and dressings often varies widely based on the clinician’s experience. Although the etiology of chronic wounds is multifactorial, hypoxia is a common component in a vast majority of cases. However, oxygen is essential for wound healing; numerous biochemical and cellular processes requisite for wound healing are highly dependent on a sufficient supply of oxygen.26-28 Thus, supplementing oxygen to chronic wounds may help promote healing.26,29
Hyperbaric oxygen therapy (HBOT) has been proposed as a treatment modality in calciphylaxis with some success.24,30-33 While HBOT has been used therapeutically since the 1600s, it was not until the 1960s that this modality was used for wound healing.34 Around the same time, topical oxygen therapy (TOT) also was introduced for the treatment of chronic wounds, but it was only in more recent decades that TOT has truly garnered interest in the wound care space.27,31 Growing evidence shows TOT has a positive effect on chronic wound healing outcomes by facilitating the oxidative killing of bacteria, regulating growth factors, aiding in collagen synthesis and deposition, influencing angiogenesis, and decreasing wound infection rates.26,29,35,36
Topical oxygen therapy has shown promising results with treating arterial, diabetic, venous stasis, and other chronic ulcerations. In a 2015 article, Dissemond et al reviewed the effectiveness of TOTs for wound healing. They concluded that although no single TOT approach is widely used universally throughout the wound healing community, there is increasing evidence that suggests its effectiveness as an adjunctive therapy to speed wound healing outcomes.26 In 2019, Nataraj et al conducted a systematic review of the use of TOT in healing diabetic foot ulcers, concluding that TOT may be an important adjunct modality in the management of chronic ulcers as it facilitates chronic wound healing, particularly in lower grade ulcers.37
A recent study by Hunter et al demonstrated potential antibiotic properties for TOT as the microbiome of healed wounds shifted to a predominantly aerobic population vs the microbiome of the 1 unhealed wound that retained anaerobic flora.38 Both Hayes and Silvestrini observed autolytic debridement properties of TOT within days of initial placement in which the wounds began to appear healthier, with decreased signs of infection and increased signs of granulation.5,29
When formulating the treatment plan for this patient, the primary author recalled an article by Ng and Peng, which stated that combination therapy is more effective than single-agent therapy if the therapies act synergistically.16 In their report, Ng and Peng16 referenced work by Rogers and Coates,30 which recommended using HBOT as an adjunctive with STS in the treatment of CUA. Considering the high-risk status of the patient, shelter-in-place order, potential for cross contamination, limitations in medical personnel staffing, restricted clinic hours, and personal protection equipment shortages, the primary author determined that HBOT was not a viable treatment option. At this point, the primary author’s thoughts shifted toward cTOT with TOT paired with telemedicine.
As discussed previously, the use of innovative remote therapies is essential during a pandemic. For this patient, TOT permitted at-home treatment, was easy to use, was portable, and had minimal risks of complications. This patient was well-suited for self-application of TOT as she was fully independent, accustomed to self-procedures such as PD, and compliant with her medical care.