Calcinosis cutis: a complication of intravenous administration of calcium glucanate

Calcinosis cutis, the deposition of calcium in the dermis, can be dystrophic, metastatic, iatrogenic, or idiopathic. Here, we describe a case of iatrogenic calcinosis cutis secondary to extravasation of an intravenous calcium-containing solution in a child. We also review the literature regarding the pathogenic mechanisms involved in the development of calcinosis cutis after extravasation injuries. While iatrogenic calcinosis cutis is generally a benign entity, it is important to recognize its unique clinical and histopathologic presentation to avoid complications from misdiagnosis.     

A dystrophic calcinosis cutis case treated with CO2 laser

Abstract

Calcinosis cutis is the deposition of insoluble calcium salts within cutaneous tissue. It may be divided into four major subtypes: dystrophic, metastatic, idiopathic, and iatrogenic. The most common subtype is dystrophic calcinosis cutis. It can occur as a result of local tissue injury. We herein present a child with dystrophic calcinosis cutis developed following trauma and successfully treated with CO₂ laser.     

Lack of response to intravenous sodium thiosulfate in three cases of extensive connective tissue disease‐associated calcinosis cutis

Dystrophic calcinosis cutis is a debilitating condition of calcium salt deposition in the skin often occurring in association with connective tissue disease (CTD). Available treatments for calcinosis cutis are unsatisfactory, but given the recent use of topical and intralesional sodium thiosulfate (STS) to treat calcifying disorders, we sought to describe the use of intravenous (IV) STS for CTD‐associated dystrophic calcinosis cutis. We report three patients with long‐standing and extensive CTD‐associated calcinosis cutis treated with IV STS after having failed multiple prior therapies. All three patients experienced fatigue and nausea with STS infusions, and none of the patients had notable clinical or symptomatic improvement of calcinosis. It remains to be seen whether the administration of IV STS earlier in the onset of calcinosis might be of benefit given that these patients all had long‐standing and refractory CTD‐associated calcinosis. Given the small number of patients in this series, further investigation into the use of IV STS in calcinosis cutis is warranted.     

Two cases of dystrophic calcinosis cutis in burn scars

Dystrophic calcinosis cutis is defined as the abnormal deposition of insoluble calcium salts in dead or degenerated cutaneous tissues in the absence of abnormal serum calcium or phosphate concentrations. Although dystrophic calcification can occur in various diseases, its occurrence on a burn scar has rarely been reported in the dermatologic literature. Herein we describe two patients who presented with a solitary non-healing ulcer in a postburn scar, with histopathologic evidence of calcium deposition in the dermis.     

Self-healing dystrophic calcinosis following trauma with transepidermal elimination

An unusual case of dystrophic calcinosis that occurred following trauma is presented. Calcinosis cutis is the deposition of calcium phosphate into the skin. It is classified as dystrophic if calcium and phosphorous levels are normal and tissue damage is present, idiopathic if calcium and phosphorous levels are normal and no tissue damage is present, or metastatic if there is hypercalcemia or hyperphosphatemia. The numerous causes of underlying tissue damage associated with dystrophic calcinosis are discussed.     

Calcinosis cutis: part I. Diagnostic pathway

Calcinosis cutis is characterized by the deposition of insoluble calcium salts in the skin and subcutaneous tissue. The syndrome is separated into five subtypes: dystrophic calcification, metastatic calcification, idiopathic calcification, iatrogenic calcification, and calciphylaxis. Dystrophic calcification appears as a result of local tissue damage with normal calcium and phosphate levels in serum. Metastatic calcification is characterized by an abnormal calcium and/or phosphate metabolism, leading to the precipitation of calcium in cutaneous and subcutaneous tissue. Idiopathic calcification occurs without any underlying tissue damage or metabolic disorder. Skin calcification in iatrogenic calcinosis cutis is a side effect of therapy. Calciphylaxis presents with small vessel calcification mainly affecting blood vessels of the dermis or subcutaneous fat. Disturbances in calcium and phosphate metabolism and hyperparathyroidism can be observed.     

Case of dystrophic calcinosis cutis in epidermal cyst arising from verrucous epidermal nevus

Dystrophic calcinosis cutis is diagnosed when calcium is deposited into previously damaged tissue by connective tissue disease, panniculitis, pseudoxanthoma elasticum or trauma. We report a case of dystrophic calcinosis cutis arising from the lesion of an epidermal cyst on the verrucous epidermal nevus. A 20‐year‐old woman presented with a polypoid pinkish tumor on a brownish, verrucous plaque. Histopathological findings of the pinkish tumor showed calcium deposits as amorphous, basophilic material lining the true epidermis in the upper dermis, which were compatible with dystrophic calcinosis cutis and the plaque was diagnosed as a verrucous epidermal nevus.     

Dystrophic calcinosis cutis in subacute lupus

Dystrophic calcinosis cutis is known to be associated with various connective tissue disorders but to the best of our knowledge has never been reported in subacute cutaneous lupus erythematosus (SCLE), a distinctive cutaneous subset in the spectrum of lupus erythematosus. It occurs without calcium and phosphorus metabolic abnormalities and may be localized or generalized. We report a patient with SCLE who developed calcinosis cutis and had normal serum calcium and phosphorus levels and, interestingly, a normal concentration of blood ionized calcium. This latter, which represents the active form in the total amount of blood calcium, is a parameter only rarely assessed in patients with dystrophic calcinosis cutis. Thus, other pathogenic factors should be investigated to clarify the pathophysiology of the dystrophic type of calcification.     

Congenital calcinosis cutis of the foot

Calcinosis cutis is a rare disease characterized by deposition of insoluble calcium salts in the skin. Subepidermal calcified nodule is a form of idiopathic calcinosis cutis that commonly affects children but rarely presents at birth. Herein we describe a healthy 10-month-old boy who had a solitary hard nodule on the left foot since birth. Surgical excision of the nodule was done and histopathology confirmed the diagnosis of subepidermal calcified nodule.     

A unique presentation of calcinosis cutis in a patient with cystic fibrosis after double lung transplants

Calcinosis cutis is the deposition of insoluble calcium salts in the skin and subcutaneous tissue. We report the case of a 28-year-old Caucasian woman with cystic fibrosis in whom strikingly symmetrical and reticulate calcinosis cutis developed on the lower extremities, which was noted on histology to spare the eccrine glands. Careful review of the literature fails to reveal any previous report with these remarkable cutaneous and histologic manifestations.     

Calcinosis cutis

A 22-year-old male patient presented with multiple swellings over elbows and knees and a sinus over the right elbow discharging chalky white material. Skin biopsy of the swelling demonstrated calcium deposition in dermis and subcutis. There was no evidence of connective tissue disorder or abnormal mineral metabolism. Hence it was concluded as idiopathic calcinosis cutis and is reported for its interesting presentation.     

Diffuse calcinosis cutis in a patient with congenital leukemia and leukemia cutis

We report an unusual case of congenital leukemia with leukemia cutis (LC) and diffuse calcinosis cutis. A newborn girl presented with widespread dusky red and yellowish cutaneous nodules and papules. Bone marrow morphology was consistent with the diagnosis of acute monocytic leukemia of the FAB M5 type. Skin biopsy specimens confirmed the presence of a leukemic infiltrate and revealed calcium salt deposition in the papillary and reticular dermis. Calcinosis was diffuse in the whole skin but spared other organs. Vascular calcification was not present. Serum calcium levels oscillated between 2.5 and 2.86 mmol/l, and phosphorus, parathyroid hormone and 25-hydroxyvitamin D(3) levels were normal. There were diffuse osteoporosis and spontaneous fractures of small tubular bones. The patient responded to chemotherapy but, following consolidation treatment, developed sepsis and died at 120 days of age. Congenital leukemia is rare and LC is uncommon. Hypercalcemia may be a complication of leukemia, which leads to multiorgan metastatic calcification. Despite the absence of frank hypercalcemia, the presence of bone lesions suggests that the patient's calcinosis cutis was of the metastatic type. However, the cutaneous leukemic infiltrate may also represent a triggering factor for calcium deposition in the skin.     

Dystrophic calcinosis cutis in pseudoxanthoma elasticum

Pseudoxanthoma elasticum (PXE) is a genetic disorder in which elastic fibers become calcified with prominent cutaneous, ocular, and cardiovascular features. Calcinosis cutis is an acquired disorder of calcium deposition in cutaneous tissues that occurs as one of the following forms: dystrophic, metastatic, idiopathic, and iatrogenic. We report a case of a woman with PXE who developed widespread dystrophic calcinosis cutis in areas affected by PXE. Although tumoral calcification and nephrolithiasis have been reported in patients with PXE, only one other case in the English-language literature of PXE and calcinosis cutis has been reported and this case was characterized by small, milia-like papules on the front of the neck, without significant discomfort, whereas our patient had widespread involvement that was very painful and pruritic. On 6-month follow-up, this patient had only mild improvement after treatment with an anti-itch lotion and aluminum hydroxide, with which she was noncompliant.     

Dystrophic scrotal calcinosis originating from benign eccrine epithelial cysts

Scrotal calcinosis has been classified as a form of idiopathic calcinosis cutis. However, the pathogenesis of the calcified nodules has not been fully elucidated: it is still unclear whether the condition is truly idiopathic, or the result of breakdown of calcified epithelial cysts. We describe a 29-year-old Japanese patient with scrotal calcinosis originating from epithelial cysts. Light microscopy revealed a large epithelial cyst containing von Kossa-positive material and several small dilated ductal structures beside the cyst. The epithelia of the cyst and ductal structures were connected, showing similar eccrine duct differentiation on immunohistochemical staining and electron microscopy. In the cyst lumen, calcium was present as needle-shaped crystals. The pathogenetic mechanism of calcium deposition seemed to be due to excessive production and discharge of matrical debris and sulphated mucopolysaccharides, which derived from luminal cells, and their accumulation in the lumina.     

Utilization of Ultrasonography in Dermatology: Two Case Reports of Calcinosis Cutis

Development of newer generation of cost-effective ultrasonic devices in recent years has increased the use of ultrasonography in dermatology. Several lesions can be diagnosed and managed using ultrasonography. Calcinosis cutis involves the deposition of insoluble calcium salts in the cutaneous and subcutaneous tissues. On ultrasonography, it specifically presents as hyperechoic deposits with a posterior acoustic shadowing artifact due to the acoustic properties of calcium. A 62-year-old female patient presented with a solitary, skin-colored, palpable nodule on the inner side of the right lower leg. The lesion was beneath the intact skin and detectable only on palpation. However, ultrasonography demonstrated a clear delineation of the lesion, showing hyperechoic deposits with a posterior acoustic shadow (15 MHz, linear probe). Skin biopsy and curettage were performed, revealing histological features consistent with calcinosis cutis. Four weeks after the procedure, ultrasonography performed to evaluate the outcome of treatment, showed recurrence. Another 18-year-old female patient presented with a skin-colored deep-seated nodule on the left temple. On ultrasonography, linear hyperechoic deposits with a posterior acoustic shadow were visible. Skin biopsy was performed, and histopathologic features showed calcified material in the subcutaneous tissue. These two cases of calcinosis cutis highlight the diagnostic value of ultrasonography in dermatology.     

Cutaneous manifestations of tumoral calcinosis.

We have followed up a large family in which seven members have tumoral calcinosis. One girl had the skin lesions of localized calcinosis cutis apart from the typical subcutaneous deposits of calcium. Like most persons with tumoral calcinosis, our patient had normal serum calcium concentrations; however, the serum phosphorus levels were greatly elevated. The familial occurrence and elevated serum phosphorus levels suggest the possibility of some as yet undefined, heritable metabolic defect as the underlying cause. The occurrence of tumoral calcinosis with localized calcinosis cutis is a rare association, and there has been only one other reported case to our knowledge. This report describes our patient and offers a brief discussion of tumoral calcinosis. The therapeutic response to the phosphate depletion regimen and topical steroids was disappointing in our case.     

Calcinosis cutis following trauma

We report an 8-year-old boy who developed dystrophic calcinosis cutis that occurred following trauma. Multiple abrasions were observed in the inguinal folds after a soccer game. Subsequently, multiple papules with soft centers and white particles appeared in the same area. A biopsy specimen showed calcinosis cutis with transepidermal elimination of calcium. The causes of the underlying tissue damage associated with dystrophic calcinosis are discussed.     

Successful Treatment of Severe Iatrogenic Calcinosis Cutis with Intravenous Sodium Thiosulfate in a Child Affected by T-Acute Lymphoblastic Leukemia

Abstract:   Sodium thiosulfate has been successfully used to treat calcyphilaxis in adults and children, but its effect on iatrogenic calcinosis cutis secondary to extravasation of calcium solutions is less known. We describe a 5-year-old boy with acute lymphoblastic leukemia who developed severe calcinosis cutis in the right forearm and hand, and in the left leg and foot after extravasation of calcium gluconate during treatment for tumor-lysis-syndrome-related hypocalcaemia. Surgical debridement, local wound care, hyperbaric oxygen therapy, and sodium thiosulfate infusion achieved a complete healing of all lesions in an eight-month period with a short discontinuation of chemotherapy. No functional or sensitive impairment remained.     

Idiopathic Calcinosis Cutis Universalis Treated Successfully with Oral Diltiazem—A Case Report

Idiopathic calcinosis cutis is very rare and difficult to treat. Various medical modalities of treatment described with inconsistent results include chelating agents, colchicine, and probenecid. Calcium channel blockers are known to work by inhibiting intracellular entry of calcium. We successfully treated a case of idiopathic calcinosis cutis using oral diltiazem.     

PROPOSAL FOR A PATHOGENESIS-BASED CLASSIFICATION OF TUMORAL CALCINOSIS

Background. Deposition of calcium in skin is currently categorized into a group of disorders referred to as calcinosis cutis. Divisions between types and subtypes within this confusing classification are predominantly based on morphologic differences in the calcification and serve to obscure pathogenesis. This is especially evident in a subtype of calcinosis cutis, known as tumoral calcinosis. Calcifications in cases of tumoral calcinosis share the following characteristics, but without evidence of a common pathogenesis: large size, juxtaarticular location, progressive enlargement over time, a tendency to recur after surgical removal, and an ability to encase adjacent normal structures. The goal of this study was to formulate a pathogenesis-based classification for cases of tumoral calcinosis. Methods. In a literature review 121 cases of tumoral calcinosis were identified. These cases, along with a case evaluated in our clinic, were reviewed retrospectively, and their features compared. Results. Analysis suggests three pathogenetically distinct subtypes of tumoral calcinosis: (1) Primary normophosphatemic tumoral calcinosis: patients have normal serum phosphate, normal serum calcium, and no evidence of disorders previously associated with soft tissue calcification; (2) primary hyperphosphatemic tumoral calcinosis: patients have elevated serum phosphate, normal serum calcium, and no evidence of disorders previously associated with soft tissue calcification; and (3) secondary tumoral calcinosis: patients have a concurrent disease capable of causing soft tissue calcification. Justification for this classification is based on the presence or absence of disorders known to promote soft tissue calcification and statistically significant differences in family history, mean calcification number, mean serum phosphate level, and calcification recurrence after excision. Conclusions. A classification for tumoral calcinosis is devised that outlines potential pathogenetic mechanisms and predicts response to therapy and prognosis. Analysis of other forms of calcinosis cutis may reveal definable pathogenetic differences that suggest a coherent classification for all cutaneous calcinoses.