A Possible Role For POCUS in the Diagnosis of Calciphylaxis

“Calciphylaxis is a life-threatening vasculopathy that results from the deposition of calcium in the arteriolar vasculature of the deep dermis and subcutaneous adipose tissue…”

Calciphylaxis is a life-threatening vasculopathy that results from the deposition of calcium in the arteriolar vasculature of the deep dermis and subcutaneous adipose tissue, which causes occlusion of the affected blood vessels and overlying tissues and skin. Often manifesting as extremely painful retiform purpura (branching, non-blanching purple patches or plaques) at times with necrotic ulcerations due to tissue ischemia in the lower extremities and pannus (although it can appear elsewhere, including in the breasts, penis, and areas of previous trauma such as insulin injection sites), calciphylaxis carries dramatic morbidity and mortality, with one-year mortality rates ranging from 45% to 80%. Although calciphylaxis is classically associated with end-stage kidney disease (ESKD), it may present in patients with acute kidney injury or no identifiable renal pathology.[1] There are several other well-documented risk factors for calciphylaxis which include female sex, obesity, diabetes mellitus, warfarin therapy, Vitamin D deficiency, Crohn's disease, malignancies, hyperparathyroidism, recurrent hypotension, and substantial weight loss.

Despite the dramatic signs and symptoms associated with calciphylaxis, making this diagnosis solely on clinical grounds can be challenging: retiform purpura is a cutaneous manifestation that commands a wide differential (including cryoglobulinemia, polyarteritis nodosa and other vasculitides, heparin-induced thrombocytopenia, to name a few) and therefore these lesions are not specific to calciphylaxis. While punch biopsy is often indicated in the initial management of patients with retiform purpura, they may fail to identify calciphylaxis if the obtained specimen does not harbor calcified vessels. Recent reports have suggested a possible role for point-of-care ultrasound (POCUS) in the diagnosis of calciphylaxis.[2]–[4] POCUS may be able to detect microvascular calcification in dermal structures deep to cutaneous lesions. One report presented a case of penile calciphylaxis that was successfully identified through POCUS after two negative punch biopsies were obtained, suggesting that POCUS may be an additional tool to confirm this condition in the setting of non-diagnostic punch biopsies.[4] Of note, plain radiography and other specialized imaging methods such as xeroradiography have also been used to assist in diagnosing calciphylaxis.[5]

One investigation that examined sonographic features of high frequency ultrasound in patients with inflammatory dermatosis secondary to calcium deposition identified the following three patterns, with pattern # 3 being the most common in biopsy-proven calciphylaxis:

1. Presence of thin hyperechoic bands parallel to the epidermal surface resulting in a strong posterior acoustic shadow.

2. Hyperechoic spots with a narrow acoustic window.

3. Linear hyperechoic bands parallel to the wall of blood vessels with a narrow acoustic window. [6]

Figure 1. Ultrasound image of calciphylaxis demonstrating subcutaneous tissue (yellow arrow), echogenic subcutaneous calcifications (blue arrow), and a posterior shadow (blue shadow). Obtained from Rosen et al., 2021. [3]

An important consideration for providers is that calciphylaxis lesions are extremely painful and therefore placing the transducer over the area of interest may not be tolerated by patients. Therefore, providers should consider pain control prior to initiating the ultrasound examination as well as using a generous amount of ultrasound gel. While randomized-controlled studies are needed to ascertain the utility of POCUS in the diagnosis of calciphylaxis and further characterization of the sonographic features that are sensitive and specific to this inflammatory dermatosis are needed, early reports suggest that this non-invasive imaging modality may be of diagnostic aid and therefore facilitate the early initiation of treatment.  

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Author: Benjamin Gallo Marin is a fourth-year medical student at The Warren Alpert Medical School of Brown University applying for dermatology residency.

Faculty Reviewer: Kristin Dwyer, MD, MPH is Assistant Professor of Emergency Medicine at Warren Alpert Medical School of Brown University and Emergency Ultrasound Fellowship Director

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References:

[1]   B. Gallo Marin, G. Aghagoli, S. L. Hu, C. M. Massoud, and L. Robinson-Bostom, “Calciphylaxis and Kidney Disease: A Review,” Am. J. Kidney Dis., Aug. 2022, doi: 10.1053/j.ajkd.2022.06.011.

[2]   N. Tobarran and M. Collin, “Point-of-care Ultrasound in the Diagnosis of Calciphylaxis,” Clin Pract Cases Emerg Med, vol. 4, no. 3, pp. 495–496, Aug. 2020.

[3]   R. J. Rosen, H. E. Fernandez, S. Shirazian, and A. A. Moses, “Ultrasound findings of calciphylaxis,” Kidney Int., vol. 100, no. 5, p. 1144, Nov. 2021.

[4]   W. Helmeczi, T. Pitre, E. Hudson, S. Mondhe, and K. Burns, “Isolated Penile Calciphylaxis Diagnosed by Ultrasound Imaging in a New Dialysis Patient: A Case Report,” Can J Kidney Health Dis, vol. 8, p. 20543581211025846, Jul. 2021.

[5]   K. M. Idris and M. E. Laing, “Xeroradiography as a Noninvasive Tool in Diagnosing Calciphylaxis,” JAMA Dermatol., vol. 158, no. 9, pp. 1080–1082, Sep. 2022.

[6]   M. Gamissans et al., “Multicentric Study on High-Frequency Ultrasound Characterization of Calcium Deposits in Dermal and Subcutaneous Calciphylaxis and Calcinosis,” J. Ultrasound Med., vol. 41, no. 8, pp. 1975–1979, Aug. 2022.