Pediatr Radiol (2005) 35: 539–542 DOI 10.1007/s00247-004-1363-9
Surasak Puvabanditsin Eugene Garrow Ruetima Titapiwatanakun Rahel Getachew Jigneshkumar B. Patel
Received: 8 August 2004 Revised: 5 September 2004 Accepted: 14 September 2004 Published online: 23 November 2004 Ó Springer-Verlag 2004
S. Puvabanditsin Department of Pediatrics, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA E. Garrow Department of Surgery, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA S. Puvabanditsin (&) Æ E. Garrow R. Titapiwatanakun Æ R. Getachew J. B. Patel Department of Pediatrics, Jersey City Medical Center, 50 Baldwin Ave., Jersey City, NJ 07304, USA E-mail:
[email protected] Tel.: +1-201-9152458
CASE REPORT
Severe calcinosis cutis in an infant
Abstract We report on an infant with severe asphyxia and persistent pulmonary hypertension as a newborn. The baby received prolonged intravenous calcium gluconate therapy for hypocalcemia. At 5 weeks of age, multiple firm, indurated areas (armor-like lesions) were palpable in the subcutaneous tissues of the trunk, arms, legs, and face, particularly in skin folds. Roentgenographic study showed generalized soft-tissue calcifications throughout the body, extremities, and face. Calcinosis cutis occurs through a variety of pathogenetic mechanisms. Case reports on calcinosis cutis in infants are uncommon, and the calcifications are mostly localized. In our patient, they are generalized.
Keywords Infant Æ Calcinosis cutis Æ Hypocalcemia Æ Asphyxia Æ Persistent pulmonary hypertension
Introduction
Case report
Calcinosis cutis, the cutaneous deposition of calcium salts in the dermis, is an uncommon disorder. It occurs through a variety of pathogenic mechanisms. Calcinosis cutis may be classified as metastatic, dystrophic, or idiopathic and has been described only rarely in the pediatric age group. We report calcinosis cutis in a term newborn who developed severe persistent pulmonary hypertension and received intravenous and oral calcium therapy for hypocalcemia.
A 4,240-g term female infant was born by repeat Cesarean section after an uneventful prenatal course. Apgar scores were 1 and 5 at 10 and 20 min, respectively. She was resuscitated and stabilized before transfer to our NICU. The postnatal course was complicated by severe persistent pulmonary hypertension, seizure, and refractory hypocalcemia. High doses of intravenous 10% calcium gluconate (500 mg/kg/day) were given during the first 2 weeks of life for treatment of persistent
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hypocalcemia. Serum calcium was in the range of 4– 7 mg/dl (normal: 8–11 mg/dl). Calcium gluconate was given by direct intravenous injection at a rate greater than 2 ml/min into the peripheral veins. Other values of serum electrolytes were within normal limits. On day 7 of her hospitalization, calcium gluconate extravasated into the surrounding tissue along the anterior aspect of the left forearm. During the next several days the discrete area of necrotic skin sloughed. This measured 0.5– 2.0 cm and was surrounded by yellow-white groups of papules. The skin around the sloughed skin was firm (Fig. 1). Subsequently, the patient received oral calcium (NeoCalglucon: calcium glubionate) supplements (500 mg/kg/day) during her 3rd and 4th weeks of life to maintain a normal serum calcium level. During her 5th week of life, after calcium supplement was discontinued, firm indurated areas were observed on her back. There were no erythematous areas noted. The following week, the areas of induration spread to her entire body, extremities, and face. Roentgenographic study showed extensive subcutaneous calcifications throughout the infant’s body (Figs. 2, 3, 4). There were no calcifications in her heart or kidneys on the radiographs of the chest and abdomen. Serum calcium and phosphorus were normal. The calcification of the cheek interfered with sucking initially. Subsequently, her sucking improved and she was fully fed orally before discharge at 6 weeks of age. At 7 months of age the generalized calcifications resolved. The wound on the left forearm healed completely with barely visible scars. The patient appeared well at follow-up visits.
Fig. 2 Radiograph shows extensive subcutaneous calcification of the left upper extremity. There is accentuated focal calcification at the forearm where extravasation of calcium occurred
Discussion Calcinosis cutis is characterized by abnormal deposits of calcium salts in the dermis and/or hypodermis.
Fig. 1 Necrotic lesions and several yellow-white papules on the anterior aspect of the left forearm where extravasation of calcium occurred
Fig. 3 Radiograph shows extensive subcutaneous calcification of the right upper extremity
Calcinosis cutis is categorized into three types: metastatic, dystrophic, and idiopathic [1]. Metastatic calcinosis cutis occurs in normal tissue in the presence of abnormal serum calcium and phosphorus levels. Patients with hypervitaminosis D, hyperparathyroidism, milk– alkali syndrome, paraneoplastic hypercalcemia, sarcoidosis, destructive bone disease, and chronic renal failure may develop metastatic deposits of calcium. Dystrophic calcinosis cutis is the most common and occurs in damaged and traumatized tissues in the presence of normal serum calcium and phosphorus levels. Calcium deposits appear in previously inflamed, degenerated, or neoplastic tissues, and cutaneous involvement is a common feature. In the newborn, secondary cutaneous deposits may be observed after intrauterine herpes simplex infection or subcutaneous fat necrosis [1, 2]. Idiopathic calcinosis cutis occurs in apparently normal tissue in the presence of normal serum calcium and
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Fig. 4 Radiograph shows extensive subcutaneous calcifications of the lower extremities
phosphorus levels. Three distinctive disorders of childhood in this group are milia-like calcinosis cutis associated with Down syndrome, idiopathic calcinosis of the scrotum, and subepidermal calcified nodule of Winer (cutaneous calculus) [3]. Iatrogenic calcinosis cutis, a special subset of softtissue calcification, has various causes. They might include a complication of either intravenous calcium chloride or calcium gluconate therapy, as in our patient. Iatrogenic calcinosis cutis that occurs as a complication of intravenous calcium therapy can occur with or without extravasation of calcium solution. There are several theories to explain the pathogenesis of the calcification. These include tissue damage and transient elevation of the local calcium concentration. Local tissue injury increases cell membrane permeability, allowing cytosolic influx of calcium that exceeds the capacity of mitochondria to sequester calcium and phosphate. This leads to the precipitation of calcium phosphate in the cytoplasm [4]. Mast cells might play a significant part because histamine and serotonin have been found to induce local calcification. In calcinosis that is caused by extravasated calcium, the primary pathologic alterations described are collagen degeneration and soft-tissue necrosis. The lesions appear an average of 13 days after the extravasation of the calcium solution, with a
range of 2 h to 24 days [5, 6]. Radiological changes are seen as early as 4–5 days and maximal roentgenographic changes are present at about 2 weeks. Gradual resolution usually takes several months. Other extravasated medications predispose patients to tissue calcification either by tissue damage (quinine, vasopressin tannate, and epinephrine) or by the formation of calcium precipitates (prednisolone sodium phosphate, prochlorperazine maleate, streptomycin sulfate, amphotericin, and sodium bicarbonate) [7]. There are several recommendations for reducing the risk of iatrogenic calcinosis cutis. In hypocalcemia, oral calcium supplementation should be used when possible. The intramuscular and subcutaneous routes should be avoided because of the risk of tissue necrosis. Gluconate is preferred to chloride, because the calcium is less likely to precipitate. If calcium gluconate is required intravenously, a maximum of 2 ml/min should be administered, and its use with anions such as bicarbonate, phosphates, and sulfates should be avoided. Cannulation sites should be rotated regularly, and each cannula should be checked for a backflow of blood before the infusion of calcium. In our case, the patient was severely asphyxiated and developed persistent pulmonary hypertension. This may have caused generalized cutaneous tissue damage or degeneration. As previously reported, two asphyxiated newborns who underwent hypothermic treatment developed subcutaneous fat necrosis. Extensive calcifications were noted after 4–5 weeks of age. Our patient’s underlying condition and timing of the extensive calcifications are similar to those of the previous report [2]. Soon et al. [6] reported on two infants with calcinosis cutis as a complication of parenteral calcium gluconate therapy. Both cases involved cardiac surgery and intensive care. The lesions were noted several weeks after the infusion of the calcium. The pathogenesis of this condition is unknown and probably multifactorial [8]. It is thought to involve both transient elevation of the local concentration of calcium after infusion and tissue damage at the site of the extravasated calcium solution. However, extravasation is not a prerequisite for tissue calcification; transient local concentration of calcium after intravenous administration and local trauma or tissue damage can be sufficient [8]. Hypocalcemia in our patient was transient and probably caused by severe asphyxia and persistent pulmonary hypertension. The patient recovered and has had normal growth and development without endocrinologic problems. Acknowledgments We thank Judy Wilkinson, Librarian, Jersey City Medical Center, for her assistance. We also thank Sylvia Sutton-Thorpe for supporting this effort and preparing the manuscript.
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3. Schepsis C, Siragusa M, Palazzo R, et al (1994) Perforating milia-like idiopathic calcinosis cutis and periorbital syringomas in a girl with Down syndrome. Pediatr Dermatol 11:258–260 4. Anderson H (1980) Calcification processes. Pathol Annu 15:45–75 5. Goldminz D, Barnhill R, McGuire J, et al (1998) Calcinosis cutis following extravasation of calcium chloride. Arch Dermatol 124:922–925 6. Soon SL, Chen S, Warshaw E, et al (2001) Calcinosis cutis as a complication of parenteral calcium gluconate therapy. J Pediatr 138:778
7. Sahn EE, Smith DJ (1992) Annular dystrophic calcinosis cutis in an infant. J Am Acad Dermatol 26:1015–1017 8. Kagan MH, Bansal MG, Grossman M (2000) Calcinosis cutis following the administration of intravenous calcium therapy. Cutis 65:193–194
