ABSTRACT
This case report describes a rare differential diagnosis of soft-tissue infection in a neonate. Fever, pain, inflammation, and acute tenderness in the limb of a neonate signify acute infection or osteomyelitis unless proved otherwise. Iatrogenic calcinosis cutis presents with similar symptoms and signs; its diagnosis may be easily confused with an infective condition by an unwary orthopaedic surgeon. This report aimed to raise doctors' awareness on the presentation, aetiopathogenesis, and course of the relatively rare iatrogenic calcinosis cutis.
Key words: calcification, physiologic; calcinosis; infant, newborn; soft tissue infections
CASE REPORT
A 20-day-old female infant was referred to the orthopaedic department of Guru Teg Bahadur Hospital in Delhi, India in May 2001. The patient had had symptoms of rapidly increasing swelling and erythema of the left leg for 10 days. A local practitioner had been treating her for convulsive disorder. Four days prior to the appearance of erythematous indurations, the practitioner had given a 10% calcium gluconate intravenous infusion through the great saphenous vein of the same leg for the management of convulsions. The infant was reluctant to move her left lower limb. The practitioner made a diagnosis of cellulitis of the left leg and started intravenous antibiotics.
The child weighed 3000 g and was well nourished and well developed. She was febrile with a temperature of 38.4°C, but was not irritated. Local examination revealed swelling and erythematous induration involving the whole left leg (Fig. 1). The swelling was warm and tender; there were no signs of fluctuation; and the regional lymph nodes were not enlarged. The white blood cell count was raised to 12×10^sup 9^/l and differential counts revealed an increase in polymorph counts to 80%. Aspirate from the site revealed no pus. Smear from this aspirate did not show any microorganism. The aspirate was also subjected to culture at the same time.
Radiographs of the left leg showed extensive extraosseous calcification extending from the ankle region almost to the proximal third of the leg (Fig. 2). The serum calcium level was 91 mg/1, the serum phosphorus level was 55 mg/1, and serum electrolytes were within normal limits. Blood urea was 280 mg/1 and serum creatinine was 8 mg/1. Cultures from the aspirate were later reported to be sterile.
A diagnosis of iatrogenic calcinosis cutis was made. The child was treated symptomatically and intravenous antibiotics were stopped. Inflammation settled down following symptomatic treatment over 4 weeks.
DISCUSSION
The clinicoradiological diagnosis of this case is iatrogenic calcinosis cutis following intravenous infusion of calcium solution for the management of convulsions.1 Although iatrogenic calcinosis cutis has references in the paediatric and dermatology literature, the majority of orthopaedic surgeons are unaware of this disease.
The disease is commonly described in neonate but no age is exempt.2,3 Calcinosis cutis is classically categorised into 3 types: dystrophic, metastatic, and iatrogenic. The dystrophic variety occurs in damaged or traumatised tissues and the serum calcium/phosphorus ratio is found to be normal.4 The metastatic variety occurs in normal tissues in the presence of a disturbed calcium and/or phosphorus balance.4 The rarest variety is iatrogenic calcinosis cutis. Some of these lesions are observed in lowbirth-weight babies subjected to multiple heel pricks in intensive care units.1 Other cases of iatrogenic calcinosis cutis are due to intravenous administration of calcium- or phosphate-containing infusions such as calcium gluconate or calcium chloride.1
Intravenous infusion as the iatrogenic cause is comparatively easy to corroborate when extravasation is massive, leading to early signs of inflammation. When extravasation is small, this corroboration may be difficult, as inflammatory signs may then be less marked and calcification delayed.5 In the present case, the local practitioner infused 10% calcium gluconate for management of convulsions through the great saphenous vein, which extravasated into the soft tissue, leading to the iatrogenic variety of calcinosis cutis.
Clinically, signs of inflammation usually appear several days after administration of a calcium solution. The mean period reported between infusion and appearance of a clinical lesion is 13 days (range, 2 hours to 24 days).4 The lesion appeared in the present case over a duration of 4 days. On clinical examination, these lesions may be firm, diffusely erythematous, consisting of white to brown papules or nodules or bullous.1,4 The lesion can be tender, warm, and fluctuant. If massive extravasation has occurred, the lesion may cause sloughing of the overlying skin and secondary infection.1
Calcium solutions used therapeutically are radiolucent. The initial radiographie finding following extravasation of calcium gluconate is soft-tissue swelling with no evidence of calcium density. Radiographs taken at 4 or 5 days to 3 weeks after infusion show calcification in the soft tissues, which is maximum at about 2 weeks.1 The soft-tissue calcification may show certain distinctive patterns or a combination of these patterns.5 This may vary from an amorphous mass localised to the site of injection to extensive areas of calcification, vascular or perivascular calcifications, and the rare annular variety.4,5
The diagnosis is frequently mistaken for cellulitis, osteomyelitis, arthritis, abscess, periostitis, myositis ossificans, and thrombophlebitis.4 These patients were subjected to frank incision and drainage with a mistaken diagnosis of abscess.2
The pathogenesis of iatrogenic calcinosis cutis has been explained by several mechanisms (Table6-11). Rodriguez-Cano et al.1 recapitulated various mechanisms and concluded that iatrogenic calcinosis cutis may have multifactorial pathogenesis. Temporary elevated levels of serum and/or tissue calcium, localtissue damage resulting from phlebitis, repeated attempts to insert a peripheral line, and extravasation of solution into the surrounding tissue may act as initiating factors. Free fatty acids released after fat cell necrosis caused by trauma may further contribute secondarily to the process. The raised local tissue pH level causes calcium salts to precipitate. Other agents that may favour precipitation of calcium salts when given along with calcium solutions are: quinine, vasopressin tannate, epinephrine (by initiating local tissue damage), prednisolone sodium phosphate, prochlorperazine maleate, streptomycin sulphate, amphotericin, and sodium bicarbonate (by formation of calcium precipitates).1,12 The exact mechanism remains unresolved. Soft-tissue calcification may occur even in the absence of extravasation if the patient is receiving phosphorous in high doses or has hyperphosphatemia.5
The development of radiological pattern is determined by the extent of extravasation and the course by which the extravasated solution follows, i.e. whether along the blood vessel sheaths or in fascial planes.5
There is no specific treatment available for this condition. Fortunately, further course of calcinosis cutis is benign and treatment remains supportive therapy. Treatment of hypercalcaemia or calcification of the tissues by sodium sulphate or cellulose phosphate has been proposed.13,14 However, these methods are not suitable for use in infants.15 In experimental situations, injection of intralesional triamcinolone acetonide has been shown to reduce local signs.16 In most reported cases, progressive clearing of calcification starts occurring without any special treatment at about 8 weeks after the onset. At about 6 months, there is no evidence of tissue calcification.2,6 Areas of skin necrosis, if present, require debridement and local tissue care. Some of these cases might require subsequent skin grafting.10 Several authors have recommended against the use of intravenous infusion of calcium gluconate in newborn infants to prevent complication of calcinosis cutis.2,5,6 They prefer oral calcium therapy whenever feasible.
It is apparent in this case report that active surgical intervention is clearly not indicated in this condition. When fluctuation is present, needle aspiration may be performed to differentiate the diagnosis from a pyogenic cause. The diagnosis of iatrogenic calcinosis cutis rests on elucidation of the history of intravenous calcium solution along with radiological evidence of soft-tissue calcification, which is usually present when the local pathological signs are noticed. We highlight the importance of identification of this rare but innocent disease and the avoidance of unnecessary use of antibiotics and surgical procedures. One should, however, still attend the patient with a high index of suspicion for superimposing infection.
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A Arora, A Agarwal, S Kumar, SK Gupta
Department of Orthopaedics, University College of Medical Sciences, Guru Teg Bahadur Hospital, Shahdara, Delhi, India
Address correspondence and reprint requests to: Dr Anil Arora, F-4/9, First Floor, Mandir Marg, Krishna Nagar, New Delhi 110051, India. E-mail: anilarora101@rediffmail.com
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