Diagnosing calciphylaxis: A better way?
By Warren R. Heymann, MDAug. 1, 2017
One of the most dramatic presentations on the dermatology consultation service is the patient with stellate purpura and necrosis, engendering a differential diagnosis of thrombotic disorders (including, but not limited to, vasculitis, septic vasculitis, purpura fulminans, cholesterol emboli, warfarin necrosis, and calciphylaxis). Last year I consulted on a patient with end-stage renal disease with presumed calciphylaxis causing penile necrosis. Both he and his nephrologist did not want a skin biopsy performed (I can’t say I blamed them). Would radiologic studies been of benefit in confirming a diagnosis of calciphylaxis?
Calciphylaxis (calcific uremic arteriolopathy), is characterized by skin ulceration and tissue necrosis, presumably resulting from vascular calcification with accompanied by intimal hypertrophy and small vessel thrombosis. Although most often associated with end-stage renal disease, it has also been seen in a number of other disorders (nonuremic calciphylaxis). Risk factors include female gender, diabetes mellitus, liver disease, obesity, and others. Clinically, it is characterized by painful skin ulceration and necrosis. Wounds are often secondarily infected, leading to death in up to 60% of patients within one year. (1)
The precise pathophysiology of calciphylaxis is unknown. Recent studies suggest that vitamin K deficiency mediated impairment in Matrix Gla Protein carboxylation may be one of the likely pathogenic mechanisms. Treatment should be multidisciplinary with specific plans tailored to the patient. Therapeutic options include intravenous sodium thiosulfate, intralesional sodium thiosulfate, bisphophonates, vitamin K, surgical debridement, dermal regenerative templates, hyperbaric oxygen, surgical parathyroidectomy, novel anticoagulants, renal transplantation, becaplermin (recombinant platelet-derived growth factor), and prostaglandins. Many of these recommendations are derived from retrospective cohort studies, case series, or case reports, necessitating the need further investigation .(2)
Securing the diagnosis of calciphylaxis is the first step in management. There have been a few recent articles in the dermatologic literature addressing radiologic diagnosis.
According to Bonchak et al, multiple modalities are able to detect vascular calcifications in subcutaneous tissue, including routine X-rays, ultrasound, and computed tomography (CT) scans. The authors retrospectively reviewed their imaging database, finding that 9 of 10 patients who had radiographic studies prior to their confirmatory skin biopsies, had radiological evidence of soft tissue vascular calcification. This underscored the capability to diagnose calciphylaxis prior to tissue diagnosis. Based on these findings, the authors recommended a thorough review of the patient’s recent CT, plain radiography, and ultrasound examinations should be performed when calciphylaxis is considered in the differential diagnosis. (3)
Paul et al performed a retrospective case-control study involving 49 patients undergoing bone scintigraphy, including 18 patients with clinically diagnosed calciphylaxis and 31 control patients with end stage renal disease without calciphylaxis; 10 in the control group had undergone renal transplantation. Bone scintigraphy was reported as positive for calciphylaxis based on increased heterogeneous radiotracer uptake within soft tissues throughout the body, with a predilection for areas corresponding to clinical findings in 16 of 18 calciphylaxis cases and in 1 of 31 control patients. Uptake was more intense in areas corresponding to plaques and nodules rather than ulcerations. In 2 patients with calciphylaxis, bone scintigraphy demonstrated an interval decrease in uptake following sodium thiosulfate therapy, corresponding to a clinical response to treatment. The authors concluded that bone scintigraphy may be a valuable modality in recognizing early onset calciphylaxis, and may also be useful in monitoring the therapeutic response. (4)
Halasz et al evaluated 7 patients with chronic renal disease and calciphylaxis by different radiographic techniques. Small-vessel calcification as fine as 0.1 to 0.3 mm was identified on plain films in 3 patients; 0.1 to 0.2 mm by mammography in 3 patients, and 0.1 to 0.2 mm by computed tomography imaging in 1 patient, nearly as fine a resolution as on histopathology. The authors stated that: “Mammography was particularly useful in visualizing calcification in 3 cases where the involved tissue site was thick, limiting the resolution of plain films. Plain films and CT imaging of thinner parts of the body (the heel, foot, or leg…areas not clinically involved with calciphylaxis) also visualized calcification of vessels less than 1 mm, most in the same 0.1- to 0.3-mm range.” (5)
As a dermatopathologist, I reflexively think that biopsies offer the gold standard of diagnosis. In patients with calciphylaxis where performing biopsies may be difficult, perhaps there are better ways to confirm the diagnosis — either by reviewing radiographic studies that were already performed or selectively ordering new ones.
1. Jeong HS, Dominguez AR. Calciphylaxis: Controversies in pathogenesis, diagnosis, and treatment. Am J Med Sci 2016; 351: 217-27.
2. Nigwekar SU. Calciphylaxis. Curr Opin Nephrol Hypertens 2017; 26: 276-81.
3. Bonchak JG, et al. Calciphylaxis: A case series and the role of radiology in diagnosis. Int J Dermatol 2016; 55: e275-9.
4. Paul S, et al. The role of bone scintigraphy in the diagnosis of calciphylaxis. JAMA Dermatology 2017; 153: 101-3.
5. Halasz CL, et al. Calciphylaxis: Comparison of radiologic imaging and histopathology. J Am Acad Dermatol 2017; 77: 241-6.
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