Fever as a Presentation of Tumoral Calcinosis: A Case Report

Abstract

Tumoral calcinosis (TC) is a rare condition in which there is periarticular calcium deposition in the soft tissue forming a mass. The most common locations of TC are the larger joints such as the hip, shoulder, and knee, as well as the hands and wrists. Patients will often present with localized swelling, pain, and reduced joint mobility. We will discuss a 48-year-old male on hemodialysis who presented with a fever of unknown source and diffuse joint pain. He was found to have progressive, multiple tumor-like swellings on his shoulders, hands, and knees. He was diagnosed with TC and managed with a high dose phosphate binder with resolution of his fever and improvement in his pain.

Full text

INTERNATIONAL
JOURNAL
OF BIOMEDICINE
CASE REPORT
http://dx.doi.org/10.21103/Article8(1)_CR3
International Journal of Biomedicine 8(1) (2018) 75-78
Fever as a Presentation of Tumoral Calcinosis: A Case Report
Nga V. Nguyen, MD*; Edgardo J. Guzman MD;
Christopher J. Mesa, MD; Shante A. Hinson, MD
Lincoln Medical and Mental Health Center
Bronx, NY, USA
Abstract
Tumoral calcinosis (TC) is a rare condition in which there is periarticular calcium deposition in the soft tissue forming
a mass. The most common locations of TC are the larger joints such as the hip, shoulder, and knee, as well as the hands and
wrists. Patients will often present with localized swelling, pain, and reduced joint mobility. We will discuss a 48-year-old male on
hemodialysis who presented with a fever of unknown source and diffuse joint pain. He was found to have progressive, multiple
tumor-like swellings on his shoulders, hands, and knees. He was diagnosed with TC and managed with a high dose phosphate
binder with resolution of his fever and improvement in his pain.(International Journal of Biomedicine. 2018;8(1):75-78.)
Key Words: tumoral calcinosis • seronegative spondyloarthritis • hemodialysis • renal insufciency
Introduction
Tumoral calcinosis (TC) is a rare condition and a
complication of hemodialysis therapy.(1) The lesions formed
are described as a subcutaneous, periarticular, densely calcied
mass conned to the soft tissue, generally at the extensor
surface of the joint in the anatomic distribution of a bursa.
The formation of the calcications has been attributed to high
calcium and phosphorus levels in the blood. The most common
locations of TC are the larger joints such as the hip, shoulder,
and knee, however, hands, wrists, and feet have been involved.
(2) Plain radiographs reveal periarticular calcications, sparing
the underlying joint.(2) If resected, the lesions have been
described as cystic with a white to pale yellow chalky material,
identied as calcium hydroxyapatite crystals with amorphous
calcium carbonate and calcium phosphate. We report here a
case of severe TC in a febrile patient.
Case Presentation
A 48-year-old male with a past medical history of
human immunodeciency virus on treatment, end stage
renal disease on hemodialysis via permacath, hypertension,
and chronic reactive arthritis/seronegative spondyloarthritis
presented to the emergency department (ED) with complaint
of fever, chills, malaise, and joint pain. The patient stated he
had multiple joint pains, including his hands, shoulders and
knees with his right knee being more prominent. In addition,
he noticed “lumps” in several parts of his body growing in
the past several months, causing discomfort and interfering
with his activities of daily living. On review of systems, he
denied any rashes, myalgia, sore throat, coughing, nausea,
diarrhea, or genital discharge. Medications were consistent
with his medical conditions. On examination, he was febrile
at 101.5°F, tachycardic with HR of 110bpm, blood pressure
was 100/60mmHg, and pain was 10/10 in severity. He was
in mild distress with examination notable for tenderness and
swelling on multiple joints including the knees and shoulders
with the right knee being more prominent. His shoulders and
knees had limited range of motion in all directions. In the ED,
there was concern for septic arthritis, for which the patient had
an arthrocentesis of his right knee. He was started empirically
on cefepime and vancomycin. Of note, the patient had been
admitted to an outside hospital two weeks prior for similar
complaints and was treated with vancomycin at that time.
Patient was advised to discontinue his Humira and prednisone.
He was admitted to the hospital for further management of
sepsis, likely secondary to septic arthritis.
During admission, blood tests: CD4 count of 277cells/
mm³, WBC - 12.4×109/L, Hb - 8.7g/dL, ESR - 143mm/hr,
C-reactive protein - 28.89mg/dL, blood urea nitrogen - 62mg/
dL, creatinine - 10.3mg/dL, calcium - 9.2mg/dL, phosphate
*Corresponding author: Nga V. Nguyen, MD. Department
of Internal Medicine, Lincoln Medical and Mental Health Center,
Bronx, NY, USA. E-mail: ngavnguyen@gmail.com

76 Nga V. Nguyen et al. / International Journal of Biomedicine 8(1) (2018) 75-78
- 8.4mg/dL, parathyroid hormone - 389.5pg/mL, vitamin D
- 31.5. Arthrocentesis of the right knee joint had uid with a
red/bloody appearance; decreased viscosity; WBC-0.9K/uL,
97% segmented neutrophils; RBC/WBC clumps; negative for
crystals. A right knee X-ray showed calcication on the medial
and lateral collateral ligaments with no bony erosions (Fig.1).
Given his persistent fever, there was an extensive
investigation. Three blood cultures were negative along with a
negative blood culture drawn from the permacath; fungal blood
culture, urine culture, inuenza swab, and chlamydia/gonorrhea
urethral culture were also negative. During that time, he
complained of a left shoulder mass which was causing discomfort.
The impression was that the fever may be related to ongoing
inammation from joint pain. Recommendations were to obtain
an echocardiogram to rule out culture-negative endocarditis and
imaging of left shoulder, and to continue antibiotics as fever was
trending downward, until a complete work-up was obtained.
Rheumatology was consulted for a complaint of bilateral knee
pain and bilateral hand pain, more on the right than the left. On
examination at that time, the right hand had diffuse soft tissue
swelling and tenderness over the second and third ngers, nodules
on the left forearm, and a palpable mobile soft tissue mass on the
left shoulder. There was also tenderness of the medial and lateral
aspect of the right knee and tenderness of the lateral aspect of
the left knee. The impression was TC, possibly due to secondary
hyperparathyroidism in the setting of a hemodialysis patient.
The recommendation was to obtain imaging of the left knee, left
shoulder, and bilateral hands. It was also recommended to have
a discussion with renal services to determine if the patient would
benet from a low calcium dialysate. Echocardiogram did not
show vegetations, ruling out endocarditis. The left knee X-ray
showed soft tissue calcications over the lateral femoral condyle
and in the anterolateral aspect of the knee joint. Hand X-rays
showed multifocal calcications in the hands and wrists (Fig. 2).
Shoulder X-rays showed calcication in the left shoulder
joint greater than the right with no marginal erosions in the
humeral heads (Fig. 3-4). After a multidisciplinary discussion,
the patient was started on a phosphate binder, sevelamer
2400mg three times a day, a phosphate restricted diet, and
low calcium dialysate during hemodialysis. He completed two
weeks of cefepime and one week of vancomycin. As the patient
was feeling well and fevers resolved, he was discharged to a
short-term skilled nursing facility.
One month after his discharge from the hospital, the
patient followed up in the rheumatology clinic. His symptoms
improved; however, he was found to have an elevated
calcium level of 12.5mg/dL with improving phosphate levels.
Given case reports of resolved calcium deposition with
parathyroidectomy, he was referred to the endocrinology clinic,
where it was discovered the patient was receiving calcitriol
from his dialysis center. After calcitriol was discontinued, his
calcium levels normalized. Three months after his discharge
from the hospital, repeat X-ray imaging of his shoulders
showed improving calcications (Fig. 5-6).
Fig. 1. Right knee X-ray on admission.
Fig. 2. Right hand X-ray during admission.

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Nga V. Nguyen et al. / International Journal of Biomedicine 8(1) (2018) 75-78
Discussion
TC is a rare condition in which a calcied lesion is
deposited in the periarticular soft tissue, sparing the joint
capsule. It can be found as a complication in those with end
stage renal disease on hemodialysis due to high serum calcium
or phosphate. In 1899, the original condition was rst described
by Duret in siblings who had multiple calcications in the hips
and elbows.(2) In 1943, the term TC was rst described by Inclan,
who reported three separate cases with no familial relation.(3)
Initially, the condition was thought to be familial/hereditary
as it was seen in young, healthy individuals. However, it can
also be described as a secondary entity from chronic renal
insufciency, hyperparathyroidism, and hypervitaminosis.(4)
The
most common sites of tumoral calcinosis are the hip, shoulder,
elbow, and knee. The TC deposition leads to reduced mobility,
arthralgia, nerve compression, and pain. There are few reports
of TC with presenting signs of systemic inammation, such
as fever and constitutional symptoms mimicking infections,
as in this case.(5) Such a presentation could lead to a delay
in management, inappropriate antibiotic use and extensive
investigations. A multidisciplinary approach is often needed
for the correct diagnosis and effective management.
Management of TC is often difcult and can be
challenging. It involves dietary restriction of phosphate, non-
calcemic phosphate binders, dialysis treatment with low calcium
dialysate, parathyroidectomy in patients with high parathyroid
hormone levels (due to tertiary hyperparathyroidism), surgical
resection of the mass, or renal transplantation.(1) In this case,
dietary restriction of phosphate, a non-calcemic phosphate
binder, and low calcium dialysate was used to manage the
extensive TC. A few cases have provided immunohistochemical
and microscopic ndings from the resected soft tissue
calcications, indicating involvement of histiocytes and
osteoclast-like giant cells of histiocyte origin.(6) The fever and
systemic inammatory response from TC could be associated
with the release of cytokines and anti-inammatory markers
from these cells. A few reports have described bisphosphate use
to prevent a systemic inammatory response due to cytokine
release from osteoclastic activity.(5) Ultimately, the selection
Fig. 3. Right shoulder X-ray during admission.
Fig. 4. Left shoulder X-ray during admission.
Fig. 5. Right shoulder X-ray 4 months after admission.
Fig. 6. Left shoulder X-ray 4 months after admission.

78 Nga V. Nguyen et al. / International Journal of Biomedicine 8(1) (2018) 75-78
of treatment depends on the severity of the presentation and a
change in treatment if there is minimal or no response.
Conclusion
In our case, the patient presented with fever and pain
from the diffuse periarticular soft tissue calcications. Initially,
it was presumed he had septic arthritis; however, the joint
aspiration was not convincing. He continued to have fever
despite being on antibiotics. After a multidisciplinary approach
and extensive investigations, he was diagnosed with TC and
started on the appropriate treatment with resolution of his fever
and improvement in his symptoms. It is important to note that
TC could present with pyrexia and systemic inammatory
symptoms/markers, which could delay management or lead to
worsening complications if unrecognized.
Competing interests
The authors declare that they have no competing
interests.
References
1. Binnani P, Aggarwal V, Bahadur M, Fulara N. Tumoral
calcinosis (Teutschlander disease) in a dialysis patient. Indian
J Nephrol. 2008;18(3):122-4. doi: 10.4103/0971-4065.43692.
2. Hammert WC, Lindsay LR. Tumoral calcinosis --or is it?
A case report and review. Hand (NY). 2009; 4(2):119-22. doi:
10.1007/s11552-008-9132-0.
3. Inclan A. Tumoral calcinosis. JAMA. 1943;121:490-5.
4. Smack D, Norton SA, Fitzpatrick JE. Proposal for a
pathogenesis-based classication of tumoral calcinosis. Int J
Dermatol 1996;35(4):265-71.
5. Phanish MK, Kallarackal G, Ravanan R, Lawson TM,
Baboolal K. Tumoral calcinosis associated with pyrexia and
systemic inammatory response in hemodialysis patients:
successful treatment using intravenous pamidronate. Nephrol
Dial Transplant. 2000;15(10):1691-3.
6. McGregor DH, Mowry M, Cherian R, McAnaw M, Poole
E. Nonfamilial tumoral calcinosis associated with chronic
renal failure and secondary hyperparathyroidism: report of
two cases with clinicopathological, immunohistochemical,
and electron microscopic ndings. Hum Pathol. 1995;
26(6):607-13.