Rom J Morphol Embryol 2016, 57(2 Suppl):865869 [613854]

Rom J Morphol Embryol 2016, 57(2 Suppl):865–869
ISSN (print) 1220–0522 ISSN (online) 2066–8279 CCAASSEE RREEPPOORRTT
A case of a generalized symptomatic calcinosis in
systemic sclerosis
CRISTIAN RADU JECAN1,2), ȘTEFAN -IULIAN BEDEREAG3), RUXANDRA -DIANA SINESCU1,4),
VALENTIN -TITUS GRIGOREAN1,5), CRISTINA -NICOLETA COZMA2), ANCA BORDIANU1,6),
IOAN-PETRE FLORESCU1,6)
1)Department of Plastic and Reconstructive Microsurgery, “Carol Davila” University of Medicine and Pharmacy,
Bucharest, Romania
2)Department of Plastic and Reconstructive Microsurgery, “P rof. Dr. Agrippa Ionescu” Emergency Clinical Hospital,
Bucharest, Romania
3)Laboratory of Pathological Anatomy, “Bagdasar–Arseni” Emergency Clinical Hospital, Bucharest, Romania
4)Department of Plastic Surgery and Reconstructive Microsur gery, “Elias” Emergency Univer sity Hospital, Bucharest,
Romania
5)Department of General Surgery, “Bagdasar–Arseni” Emergency Clinical Hospit al, Bucharest, Romania
6)Department of Plastic and Reconstructive Microsurgery, “B agdasar–Arseni” Emergency Clinical Hospital, Bucharest,
Romania
Abstract
Calcinosis consists of abnormal calcium deposition in soft tissues, which appears often in patients with limited systemic scler osis, being one of
the criteria of CREST (calcinosis cutis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia) syndrom e. With
a long evolution, the aim of the treatment is to control the symptoms and prevent complications. In this article, we present th e challenging
management of a profuse lesion of calcinosis in a patient with systemic sclerosis. We describe the case of a 52-year-old woman with
systemic sclerosis and CREST syndrome who was admitted in our Depa rtment with multiple painful and disabling tumoral masses, si tuated
in nearly all joints. The interscapular vertebral tumoral mass was excised and the defect was closed. Histopathological examina tion revealed
cutaneous calcinosis, probably associated with CREST syndrome, a type of scleroderma. Postoperative results were favorable and no local
complications were encountered. Six months follow-up revealed no evidence of recurrence. Despite the size and the invasion of t he tumor
in the muscle, complete resection was possible with an adequate reconstruction; the postoperative result being acceptable. With a lower
response to medication, surgical treatment is considered the only option for treating symptomatic lesions of calcinosis in orde r to improve
quality of life.
Keywords : calcinosis, CREST syndrome, system ic sclerosis, autoimmune disease.
 Introduction
Systemic sclerosis is a rare, autoimmune disease with
a progressive evolution, a ffecting the connective tissue
of the skin and internal organs, through inflammation,
fibrosis and vasculopathy [1]. The disease is more common among women than men (4/1), with an onset age of 30–50 years [2].
The clinical forms of systemic sclerosis are limited
and diffuse. The limited syst emic sclerosis affects 60%
of the patients [3], a part of them developing in time
CREST syndrome, an acronym that describes calcinosis cutis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly and telangiectasia [4].
The pathology of the disease is not totally understood,
several cell lines being involved: fibroblasts, endothelial
cells and lymphocytes (B- and T-) [5, 6]. These cells
initiate an early vascular phase that is followed by an inflammatory infiltrate and fibrosis [2]. Genetic factors have been also incriminated, especially genes of the immune system and connective tissue which induce an activation
of the immune and vascular response [1, 7]. Collagen
and other extracellular matrix proteins are overproduced and accumulated in almost all tissues producing fibrosis
of the affected organs [8].
The cutaneous manifestations appear due to deposition
of compact collagen fibbers and others proteins in the reticular dermis that produce at rophy of dermal appendages
with skin fibrosis, calcinosis and cutaneous ulcers [9]. This increased accumulation of proteins determines an
extent of the hypoxic state with inflammation and further
depositions [1]. Clinical manifestations depend on the involved sites; usually the initial symptoms are vascular with appearance of a Raynaud’s syndrome of the fingers. Other symptoms include peripheral microvascular vaso-constriction, tightening of th e skin, fingers swelling and
contractures, polyarthralgia and dysphagia [9].
Even though the major impact of the health is due to
vascular involvement and progressive fibrosis of the internal organs, skin manifestations are almost always present, their extension being associated with a poor prognosis [9, 10].
Aim
We describe the case of a middle-aged female patient
with limited systemic sclerosis and generalized calcinosis
R J M E
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Cristian Radu Jecan et al.
866
discussing the challenging management of a profuse
calcified lesion.
 Case presentation
A 52-year-old woman was referred to our Department
of Plastic Surgery by the Department of Rheumatology,
with multiple tumoral masses situated bilaterally in the interscapulovertebral region. The tumors appeared five years ago and increased in size, being associated with pain at passive and active movements of the shoulders. Local ethical agreement and informed consent of the
patient were obtained.
The patient’s past medical history revealed that she was
diagnosed five years previous ly with systemic sclerosis
with a limited cutaneous involvement for which she had recurrent hospital admissions. Her cutaneous and vascular manifestations included sclerodactyly, digital ischemia,
ulcers and Raynaud phenomenon. She had musculo-
skeletal involvement with arthralgia, myositis and teno-synovitis and joints contractures due to severe calcinosis. The gastrointestinal tract and pulmonary system were also affected, the patient being diagnosed with gastro-esophageal reflux and interstitial lung disease. She had
also some cardiac problems as moderate mitral insuffi-
ciency and multiple episodes of paroxysmal supraven-tricular tachycardia for which a catheter ablation of the slow pathway was performed. The patient had osteoporosis and a discopathy of the cervi cal and lumbar spine at L5,
having total hysterectomy eight years ago. She was under
treatment with an immunosuppressive drug (Methotrexate),
folic acid, calcium channel blocker, beta-blockers, peri-pheral vasodilators, antiacids and pain medication.
Upon clinical examination, we found a normal weight
patient with a characteristic facies of “Byzantine icon”
including thin lips, small mouth, thin nose and perioral
wrinkles. She presented diffuse body hyperpigmentation
with no skin thickening (Rodnan score 0/51). In the right hand, in the index and middle finger, were present scars of the fingertips associated with fingers acro-osteolysis
(Figure 1).

Figure 1 – “Byzantine icon” facies and fingers acro-
osteolysis.
Local examination of the pos terior thorax revealed
multiple nodular tumoral masses of 2/2 cm and 5/4 cm dimensions, situated bilateral in the interscapulovertebral
region, well circumscribed with a firm, elastic consistency.
Evaluation of the right acromioclavicular joint showed another tumoral mass of 2/2 cm with the same charac-
teristics that limits the abduction of the right shoulder at 40
0. The elbows had on the lateral epicondyles tumoral
masses of 2/1 cm dimensions, with defined borders and
solid consistency (Figure 2). There were also present some
nodules on the volar surface of the radiocarpal joints and
also on the dorsal surface of the left radiocarpal joint with
an elastic consistency, which produced pain on active
and passive movements.
Paraclinical examinations were performed using imaging
techniques and laboratory tests. Radiographs of the thorax revealed multiple radiopaque masses in the soft tissue, in the interscapulovertebral region with a slightly evolution from the anterior evaluation. Radiographies of the elbow joints exposed multiple lobulated calcifications separated
from the associated bone (Figure 3). Right shoulder radio-
graphy revealed multiple soft tissue periarticular calcifi-cations associated with diffuse bone demineralization. The hand radiography showed amputation of the distal phalanges bilateral (without the right fourth finger) and multiple soft tissue calcifications on the radiocarpal joints,
thumb bilateral and the right three and five fingers with
the left fourth finger; no erosions were present.
To evaluate the structure of the tumoral masses situated
in the elbow joints an echography was performed which
displayed multiple nodular subcutaneous tumors, with a
well defined border, which are spread in the left elbow over 10 cm length and have a minimum wall-echo-
shadow. Echocardiography of the left radiocarpal joint
showed a distension of the flexors tendons with a minimum peritendinous fluid.
Evaluation of the Raynaud syndrome was realized
using a nailfold capillaroscopy that showed lower cutaneous transparency with structural alterations and disorganiza-
tion of the capillary architecture, absent giant capillaries
and presence of small hemorrhages.
Laboratory tests revealed moderate normocytic, normo-
chromic anemia (hemoglobin 11.3 g/dL), elevated erythro-
cyte sedimentation rate (49 mm/h) and elevated C-reactive protein (43.67 mg/L). Antinuclear antibodies (ANA) and
anti-Scl 70 antibodies were positive with negative anti-
U1RNP antibodies and negative rheumatoid factor.
After the preoperative investigations, surgical treatment
was decided. The operative time, under general anesthesia
consisted in excision of a large, solid tumoral mass with a whitish necrotic aspect with numerous calcified nodules
involving the deep structures including the muscle
(Figure 4). Full hemostasis was achieved using a bipolar electrocautery. The wound was closed in layers and a
drainage tube was placed.
Histopathological examination revealed morphological
changes of the dermis and hypodermis. The epidermis had a normal histology in comparison with the superficial dermis where is observed significant accumulation of
collagen forming thick bundles, homogeneous, with
pronounced eosinophilia, tending to compaction (Figure 5). A reduced fibroblastic component and a perivascular chronic infiltrate of lymphocyt es are present (Figure 6).
The structures of the pilosebaceous apparatus and of the sweat glands are under-represented.
Between deep dermis and adipose tissue of hypodermis
there are present some calcium deposits in different stages of maturation. Distribution of these amorphous
deposits is usually nodular (Figure 7) and less diffuse.
The presence of the calcium deposits induces a mixed

A case of a generalized symptomatic calcinosis in systemic sclerosis
867
inflammatory response formed of macrophages, lympho-
cytes and foreign body-type multinucleated giant cells (Figure 8). The presence of these degenerative calcium
lesions supports the diagnosis of an advanced type of
scleroderma, associated with CREST syndrome.
The inflammatory component is disposed in the
periphery of the calcium deposits, being included in a
mass of dense connective tissue that appears to act as a barrier between the dystrophic calcium lesions and the
surrounding tissues. Probably, the conjunctive barrier
originated in the fibrous septa of the subcutaneous tissue. At this level, there are also present capillary vessels with
pronounced hyperemia (Figure 9). Striated muscle tissue contains no calcification (on the studied material), their
presence is noticeable to th e epimysium (Figure 10).
To exclude Sjögren’s syndrome, a condition relatively
frequent associated with scleroderma, we analyzed biopsy
fragments from the mouth mucosa, containing minor salivary glands. Histopathological study has not revealed
the presence of lymphocytic aggregates, invalidating thus a
possible association with Sjögren’s syndrome (Figure 11).
The patient made a good postoperative recovery with
no local complications. Satisfactory functional and cosmetic
results were achieved and six months follow up revealed no recurrence.

Figure 2 – Tumoral masses on the
left elbow. Figure 3 – Radiographic aspect of
the left elbow with lobulated calci-
fications.Figure 4 – Excision of the lesion
involving the deep structures.

Figure 5 – Compacted aspect of the superficial dermis.
HE staining, ×40. Figure 6 – Perivascular inflammatory infiltrate in dermis.
HE staining, ×100.

Figure 7 – Nodular distribution of calcium deposits
within deep dermis and hy podermis. HE staining, ×40. Figure 8 – Mixed inflammatory infiltrate in the inter-
face between calcium depos its and hypodermis. HE
staining, ×200.

Cristian Radu Jecan et al.
868

Figure 9 – Hyperemic capillary vessels in fibrous septa
of the subcutaneous tissue. HE staining, ×200. Figure 10 – No calcification in striated muscle. HE
staining, ×200.

Figure 11 – Salivary normal gland with normal histo-
logy. HE staining, ×100.
 Discussion
Calcinosis cutis often develops in patients with limited
systemic sclerosis being associated with CREST syndrome
[8]. It represents an abnormal calcium deposition in the
skin and subcutaneous tissues independent of the serum levels of calcium and phosphorous [9], due to tissue
hypoxia, mechanical stress or hypovascularity [11]. This
produces inflammation and macrophage activation with alteration in various mediators balance causing increased
influx of calcium to cells [8, 12]. Clinically is character-
ized by subcutaneous nodules or white papules of hard consistency, distributed symmetrically to the extremities
and rarely to the trunk [13]. The lesions may ulcerate
discharging a chalk-like mate rial formed of calcium
phosphate and calcium carb onate [14]. The remained
lesion has a slow healing evolution being associated with
numerous infections [13]. Calcinosis causes local pain,
inflammation, irritation, ulcera tion with infections, muscle
atrophy and joint contractures that leads to severe dis-ability and morbidity [15]. Diagnosis is usually made
clinically associated with plain radiographies, in some
cases being necessary also an echography or a computed
tomography [16]. Despite the symmetrical distribution of
the subcutaneous nodules in the extremities, our patient
had also a rarely distribution of a calcinotic mass to the posterior trunk. This dystrophic calcification might have
been appeared due to mechanical stress and tissue hypoxia. Pharmacological therapy usually has lower results [9],
as it had also with our patient who used Diltiazem and
Colchicine. Other local treatments used for smaller localized
lesions are extracorporeal shock wave lithotripsy and
carbon dioxide laser with reduced results [17, 18]. The only effective treatment is considered the surgical therapy,
which is used when other treatments failed or calcium
deposits continue to expand being associated with func-tional joint impairment, nerve compression, recurrent
infection and severe pain [12]. In some cases, the surgical
therapy is only palliative due to common recurrences. Surgical treatment has also disadvantages requiring
anesthesia and having the possibility of damaging the
healthy tissue and the vascular network producing further ischemia [9].
CREST syndrome is a form of limited systemic sclerosis
being associated with calci nosis, Raynaud phenomenon,
esophageal dysfunction, sclerodactyly (tapering deformity
of the fingers bones) and telangiectasia on the skin of the
face and fingers, or inside the mouth, the presence of two being sufficient for a diagnosis [17, 19]. Our patient meets
all the criteria of CREST syndrome with calcium deposits
in the skin (histopathological examination), Raynaud
syndrome (diagnosed using symptomatology and nailfold
capillaroscopy), gastroesophageal acid reflux, thickening and tightening of the skin of the fingers and dilation of
capillaries (teleangiectasias) on the face and hands [20, 21].
The patient has also osteoporosis, which was aggravated in the last two years despite the medical treatment. The
pathogenesis of calcinosis is not clearly understood, but
it has been shown that its seve rity is not related with the
severity of systemic sclerosis [3], although in our case
calcinosis could have a negative impact, being an aggra-
vating factor for osteoporosis [22, 23].
Although the concern of the disease is the progressive
involvement of the internal organs [24], the patient’s main complaint was the presence of calcium tumoral masses in the skin, especially the one in the interscapulovertebral region that was associated w ith pain and difficulty in
lying down.
Considering that no phar macological therapy has
demonstrated efficacy in the reduction of a large calcified

A case of a generalized symptomatic calcinosis in systemic sclerosis
869
mass [25] and that the patient’s tumor did not responded
to initial medical treatment, surgical treatment was decided
to be the option for removing the calcinotic mass in order to improve the patient’s quality of life.
 Conclusions
Even though there is a risk of recurrence and additional
calcification due to surgical trau ma, it is favorable to treat
tumoral calcinosis before it progresses and become a large, ulcerated and disabling mass. Optimal treatment of calcinosis cutis is a challenge because the pathogenesis is unclear, no treatment being completely effective due to the higher rate of recurrences. Consequently, the mana-gement of complications became essential in order to lower morbidity and improve the quality of life.
Conflict of interests
The authors declare that they have no conflict of
interests.
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Corresponding author
Cristina-Nicoleta Cozma, MD, Department of Plastic and Reconstructive Surgery, “Prof. Dr. Agrippa Ionescu”
Emergency Clinical Hospital, 7 Arhi tect Mincu Street, Sector 1, 0113 56 Bucharest, Romania; Phone +40730–
289 141, e-mail: cristina.cozma88@yahoo.com

Received: January 20, 2016
Accepted: August 31, 2016