Report

Calciphylaxis: a case series and the role of radiology in

diagnosis
Jonathan G. Bonchak1, MD, Kelly K. Park2, MD, MSL, Talentshia Vethanayagamony3, MD,
M. Mukarram Sheikh3, MD, and Laura S. Winterfield2, MD, MPH

1
Division of Dermatology, The Ohio State
Wexner Medical Center, Columbus, OH,
USA, 2Division of Dermatology, and
3
Department of Radiology, Loyola
University Medical Center, Maywood, IL,
USA
Correspondence
Jonathan G. Bonchak, MD
Division of Dermatology
The Ohio State Wexner Medical Center
540 Officecenter Place
Columbus, OH 43230
USA
E-mail: jonathan.bonchak@osumc.edu
Funding: None.
Conflicts of interest: None.
Abstract
Background Calciphylaxis is a syndrome of vascular calcification most commonly affecting
patients with end-stage renal disease (ESRD) on hemodialysis. Because of its high
mortality rate, early diagnosis and treatment are necessary. Although diagnosis is usually
based on skin biopsy, histopathology is often nonspecific. As the role of imaging in
calciphylaxis has not been studied extensively, we examined the utility of radiology in the
diagnosis of this disease.
Methods A thorough review of electronic medical records for 2005–2013 at Loyola
University Medical Center yielded 10 patients with biopsy-proven calciphylaxis. Using the
radiological picture archiving and communication system (PACS), all imaging studies of the
affected body part obtained within 6 months of diagnosis were analyzed and tabulated.
Results All 10 patients had undergone imaging (computed tomography, ultrasound, plain
radiography, and/or mammography) of the affected anatomy prior to diagnosis by skin
biopsy. Nine of these patients were noted to have moderate-to-severe soft tissue vascular
calcification in the area of skin biopsy.
Conclusions This case series supports the suggestion that findings of superficial vascular
calcifications on imaging studies are sensitive for the diagnosis of calciphylaxis. Used in
conjunction with histopathological, clinical, and laboratory data, radiology can serve an
important role in the diagnosis of calciphylaxis.

plaques, or purpura. Later, ulcerations and skin necrosis

Introduction
Calciphylaxis is a disease of dermal and subcutaneous
small- and medium-sized vessels most commonly seen in
patients with chronic kidney disease on hemodialysis.1 It
involves calcification of the tunica media and prolifera-
tion of the intimal layer of endothelial cells and is charac-
terized by luminal narrowing, inflammatory changes, and
thrombosis.2–4 The histopathological changes are similar
to those found in M€onckeberg’s arteriosclerosis and are
also seen in coronary artery and peripheral vascular dis-
ease.5
Calciphylaxis is associated with high rates of morbidity
and mortality (nearly 50% of patients die within 1 year6),
and thus prompt diagnosis and treatment initiation are
crucial. However, given the comorbidities common in the
at-risk population and its often ambiguous clinical and
histopathological presentations, calciphylaxis can be diffi-
cult to detect in early stages. Early lesions can be painful
and appear similar to those of thrombophlebitis, cellulitis,
or livedo reticularis, with erythema, subcutaneous
may develop and can lead to amputation, sepsis, or
death.7,8 On histopathology, small and medium vessel
calcification, dermal and subcutaneous inflammation, and
collagenous degeneration are frequently present in early
stages.2 Peripheral vascular disease, antiphospholipid syn-
drome, livedoid vasculitis, calcifying panniculitides, and
various thrombotic diseases have similar histopathological
presentations, which limits diagnostic specificity.2,9 This
highlights the importance of exploring other tools to sup-
port or exclude the diagnosis.
The role of radiology in calciphylaxis is not well estab-
lished. The ability to detect small vascular calcifications
in subcutaneous tissues may be diagnostically useful to
the clinician. Some imaging studies may reveal calcifica-
tion of soft tissue structures before ulceration is apparent
on clinical examination. As histologically similar calcifica-
tions are seen in M€ onckeberg’s arteriosclerosis,5,9,10 it fol-
lows that a modality capable of detecting vascular
changes in calciphylaxis may serve a purpose similar to
that of radiological studies of cardiovascular calcifications e275

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e276 Report Radiology in diagnosis of calciphylaxis
and peripheral vascular disease. Given the presenting
symptoms of this disease, imaging studies may already be
available to support a diagnosis when patients first
develop symptoms of calciphylaxis or when the clinical
presentation is unclear. An extensive review of the Eng-
lish-language medical literature revealed few case reports
that referred to radiological images and only one study
that examined the sensitivity and specificity of plain
radiographs for the diagnosis of the disease. In that multi-
center retrospective study of 29 patients with calciphylax-
is, Shmidt et al.11 concluded that the presence of vascular
calcification on plain radiography was highly sensitive,
and a net-like pattern of calcification was highly specific
for calciphylaxis.
Multiple modalities are able to detect vascular calcifica-
tions in subcutaneous tissue. On ultrasound, these appear
hyperechoic, or bright, and may show posterior shadow-
ing, which is seen as dark areas posterior to calcium
deposits. Ultrasound is relatively inexpensive, portable,
does not emit harmful radiation, and can be performed
with relative ease. Furthermore, the deep tissues subjacent
to the area of skin change can be assessed directly with
this examination. Ultrasound is routinely used to assess
for lower extremity deep vein thrombosis, which can
present with initial symptoms similar to those of calciphy-
laxis. In the proper clinical setting, a lower extremity
Doppler examination showing soft tissue vascular calcifi-
cations could raise concern for calciphylaxis.
Vascular calcifications are easily seen on computed
tomography (CT) and appear as bright, linear, branching
structures. Severe vascular calcifications will have Houns-
field units (i.e. radiodensity or brightness) similar to that
of radiocontrast, even in non-contrasted examination.
The precise location and extent of disease can be deter-
mined, showing that the subcutis and deeper tissues are
involved. Disadvantages of CT include high radiation
exposure and non-portability of equipment, especially in
comparison with ultrasound. Plain radiography offers the
benefits of extremely high resolution, portability, speed,
and cost-effectiveness, and is able to detect small calcifica-
tions. It is rather ubiquitous and similar to CT in that
ionizing radiation is emitted, although to a much lesser
extent. Multiple views may be necessary to determine the
exact location of vascular calcification. Plain radiographs
were shown to be 89% sensitive in the diagnosis of calci-
phylaxis.11
Materials and Methods
A combined list of 19 patients diagnosed with calciphylaxis from
2005 to 2013 was provided by the Division of Dermatology and
Department of Nephrology at Loyola University Medical Center
(Maywood, IL, USA). The electronic medical record (EMR) was
International Journal of Dermatology 2016, 55, e275–e279
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Bonchak et al.
queried, and final pathology reports documenting biopsy-proven
calciphylaxis were found to be available for 10 of these
patients. Patient demographics, site of biopsy, date of
diagnosis, body mass index (BMI), and history of end-stage
renal disease (ESRD), hyperparathyroidism, cancer, organ
transplant, and peritoneal dialysis were recorded from the EMR.
Illuminate Version 3.0 (Softek Solutions, Inc., Prairie Village,
KS, USA), which aggregates patients’ radiology, pathology, and
laboratory data, was used in conjunction with InteleViewerTM X.X
(InteleRad Medical Systems, Inc., Montreal, QC, Canada) to
document the availability of imaging studies (within 6 months of
diagnosis) and location and extent of soft tissue vascular
calcification. Data were tabulated and analyzed with Microsoft
Excel Version X.X (Microsoft Corp., Redmond, WA, USA).
Results
A search of the Loyola University Medical Center EMR
identified 19 patients with a documented history of calci-
phylaxis diagnosed between 2005 and 2013. Of these
patients, accessible histopathology reports confirming cal-
ciphylaxis in biopsies performed at this institution were
available for 10. Coincidentally, all 10 patients had
undergone plain radiography, mammography, CT, or
ultrasound studies of the area biopsied in the imaging
database within 6 months of diagnosis.
Patients were predominantly female (n = 8) and had an
average age of 56 years at diagnosis (range: 28–77 years)
and an average BMI of 36.8 kg/m2. All patients had
ESRD requiring hemodialysis (Table 1). These demo-
graphics are consistent with the known risk factors for
calciphylaxis.1,12 The lower extremities were most com-
monly affected (n = 7), followed by the breasts (n = 3)
and abdominal wall (n = 2). Of these 10 patients, half
were documented as deceased in the EMR. Patients died
at 7–502 days after tissue diagnosis (median: 22 days).
Of our 10 patients, seven had calciphylaxis affecting a
lower extremity. Patient 6 had a non-contrast CT of the
proximal lower extremity that was completed approxi-
mately 1 week prior to the diagnosis of calciphylaxis and
revealed extensive vascular calcifications in the soft tissues
near the site of skin biopsy. A plain radiograph of the
right hip, performed 2 weeks before histological diagno-
sis, showed similar findings in that area. Interestingly,
vascular calcifications seen on CT of the pelvis performed
at 3 months before hospital admission were less extensive
and less severe, suggesting an acute component to this
disease. All patients with involvement of a lower extrem-
ity had moderate or severe calcification of the superficial
vasculature (Fig. 1).
There were no significant calcifications on the CT or
ultrasound studies performed in Patient 2. This was the
only exception in the records studied. The case is also
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 13654632, 2016, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/ijd.13043 by Ohiolink, Wiley Online Library on [31/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Bonchak et al. Radiology in diagnosis of calciphylaxis Report e277

Table 1 Characteristics of 10 patients with calciphylaxis diagnosed according to biopsies performed at the study institution, in
whom imaging of the site biopsied was performed within 180 days of diagnosis

Age at Age at
diagnosis, death, BMI,
Patient Sex years years Site DPRE Plain CT US MAM kg/m2 ESRD HPT CA T PD

1 F 77 78 Right leg 67 Moderate NP Moderate NP 28.7 Yes

2 F 28 28 Both/left 0 NP Clear Clear NP 62.9 Yes Yes
breasts,
both/left
legs
3 F 40 42 Both/left 66 NP Moderate Moderate Severe 30.0 Yes
breasts
4 F 57 57 Abdomen 1 NP Moderate NP NP 34.9 Yes
5 F 53 53 Abdomen, 140 Moderate Moderate NP Severe 35.2 Yes Yes Yes
right
breast
6 F 73 73 Right leg 13 Moderate Severe NP NP 27.8 Yes Yes Yes Yes
7 F 65 Right leg 2 NP Severe NP NP NA Yes Yes
8 M 64 Right leg 14 Severe NP Moderate NP 29.0 Yes Yes Yes
9 F 43 Left leg 1 NP Moderate NP NP 44.5 Yes Yes
10 M 63 Left foot 131 Severe Mild NP NP 45.1 Yes Yes Yes Yes

BMI, body mass index; CA, history of cancer; CT, computed tomography; DPRE, number of days prior to biopsy that radio-
logical evidence of vascular calcification was apparent; ESRD, history of end-stage renal disease on hemodialysis; F, female;
HPT, history of hyperthyroidism; M, male; MAM, mammography; NA, not available; NP, not performed within 180 days of
biopsy; PD, history of peritoneal dialysis; T, history of organ transplant; US, ultrasound.

(a) (b)

(c) (d)

Figure 1 Imaging of regions biopsied days or weeks prior to histopathological diagnosis of calciphylaxis in the lower
extremities. (a) Patient 6 had dense subcutaneous vascular calcifications on computed tomography (CT) just superior to the
area of skin changes. (b) Similar changes are seen in Patient 7 on CT at the level of the distal thigh. (c) A plain radiograph
shows a cluster of superficial calcified vessels in Patient 10. (d) Calcified vessels on ultrasound have a hyperechoic wall (solid
arrows) and show posterior shadowing (hollow arrow) as seen in the Doppler examination in Patient 8

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e278 Report Radiology in diagnosis of calciphylaxis
(a) (b)
Figure 2 Mammography is capable of detecting small
vascular calcifications in the breast. It is essential in
differentiating malignancy from calciphylaxis as their clinical
presentations are often identical. Severe vascular
calcifications involving the entire breast were seen in (a)
Patient 3 and (b) Patient 5
notable because this patient was the youngest (28 years
at diagnosis) and most corpulent (BMI of 62.9 kg/m2) of
the patients with biopsy-proven calciphylaxis. Although
no blood dyscrasias were documented, the patient was on
chronic anticoagulation (a risk factor for calciphylaxis8)
for multiple embolic events that were most probably initi-
ated by extended periods of immobility. The CT and
ultrasound images available were obtained approximately
5.5 months prior to diagnosis, which represents the lon-
gest period between imaging and diagnosis in any of the
patients. This may explain why no significant calcifica-
tions were apparent on imaging, especially in a case that
is likely to have had a significant acute component. The
patient died 29 days after diagnosis.
Patients 2, 3, and 5 had a chief complaint of pain at
the affected site. Peau d’orange was documented in
Patients 3 and 5, mimicking clinical signs of malignancy,
consistent with several other reports of breast calciphy-
laxis in the literature. Severe dystrophic calcifications
were evident on mammography (Fig. 2). None of the
patients underwent surgical intervention, and all were
managed medically. All patients with breast calciphylaxis
died within 2 years after diagnosis.
In Patients 1 and 8, CT was not performed around the
time of biopsy, but these patients were found to have sig-
nificant calcifications on other imaging modalities. In all
but one patient, at least one imaging study completed
days or weeks before histological diagnosis showed vascu-
lar calcification at the symptomatic site, supporting the
utility of imaging as a sensitive diagnostic tool in evaluat-
ing patients with suspected calciphylaxis. For those
patients, radiological signs of subcutaneous vascular calci-
International Journal of Dermatology 2016, 55, e275–e279
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Bonchak et al.
fication were evident in the affected anatomic site an
average of 48 days (range: 1–140 days) prior to diagnosis
by biopsy.
Discussion
This case series supports the suggestion that multiple
imaging modalities are capable of detecting subcutaneous
small vessel calcification in patients with calciphylaxis
prior to histopathological diagnosis. In evaluating a
patient with suspected calciphylaxis, careful attention
should be paid to imaging studies of the symptomatic
region. Imaging may clinch the diagnosis in this disease,
which can present with ambiguous symptoms and often
has histological features similar to those of other condi-
tions.
Shmidt et al.11 previously reported that the presence of
vascular calcification on plain films is sensitive and that a
net-like pattern of calcification is specific to the diagnosis
of calciphylaxis. The present small series supports these
authors’ first conclusion because all patients with plain
radiographs of the affected site showed moderate or
severe small vessel calcification. It does not necessarily
support the latter conclusion because this pattern of calci-
fication was not seen on all radiographs. Further studies
exploring imaging in calciphylaxis, with controls for age,
gender, hemoglobin A1c, and duration of hemodialysis
(important risk factors for the development of peripheral
vascular calcification13), are needed to further define the
utility of radiological studies.
Given that calciphylaxis mostly affects the lower
extremities, Doppler ultrasound studies for deep vein
thrombosis or ankle–brachial index and plain radiographs
and CT studies of the pelvis and lower extremities may
already be available and can aid in clinical decision mak-
ing. For those patients in whom studies are not already
available, the anatomical site of suspicion dictates which
imaging modality is selected. Based on this case series, we
recommend CT without contrast for the proximal lower
extremity, plain radiography for the distal lower extrem-
ity, and mammography for suspected breast calciphylaxis.
Depending on the overall clinical picture, the absence of
calcification on imaging examinations can exclude dis-
ease. However, treatment may be indicated in a patient
with equivocal skin biopsy findings but extensive small
vessel calcifications on CT or plain film in the area of
painful skin changes.
Conclusions
Calciphylaxis is associated with high rates of morbidity
and mortality, and given its clinical and histological simi-
larities with other less fatal diseases, a multifaceted diag-
ª 2015 The International Society of Dermatology

Bonchak et al.
nostic approach is useful for early detection and treatment
initiation. A retrospective review of our imaging database
revealed that nine of 10 patients with biopsy-proven calci-
phylaxis had radiological evidence of soft tissue vascular
calcification, which highlights the pathogenesis of this dis-
ease prior to tissue diagnosis. Based on these findings,
when calciphylaxis is included in the differential diagnosis,
a multidisciplinary approach conducted with the radiology
service and a thorough review of the patient’s recent CT,
plain radiography, and ultrasound examinations is recom-
mended in order to facilitate diagnosis.
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