Metastatic calcinosis cutis in end-stage renal disease

Abstract

Alterations in calcium and phosphorus levels and joint pain are a common occurrence in end-stage renal disease patients. However, metastatic calcinosis cutis is a rare diagnosis that often combines these two findings, with extensive soft tissue calcification surrounding a large joint being the hallmark of this disease. The exact mechanism behind this clinical entity is unknown. The treatment and complications can be severe and disabling. Here, we discuss the case of a 26-year-old man presenting with unusually advanced skin and joint calcification of the shoulders, neck, hand, and penis.

Calcinosis cutis is an unusual disorder characterized by large calcium phosphate deposition into cutaneous and subcutaneous tissues. Five subtypes of calcinosis cutis exist: dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis. The shoulders, elbows, and hips are typically the joints affected by these lesions. However, cases have been reported in various other periarticular areas of the body (1). Patients present with symptoms such as pain, joint stiffness, nerve compression, inflammation, fistula formation, infection, and sometimes systemic symptoms such as fever (1, 2). Presenting skin findings may be nodules with extrusion of a chalky while substance. Here, we describe a patient who presented with advanced metastatic calcinosis cutis with multiple lesions of the large joints, neck, hands, and penis.

CASE REPORT

A 26-year-old man with a history of focal segmental glomerulosclerosis and a congenital solitary kidney presented with left hand pain and fatigue. He had been treated for presumed gout affecting the left hand 12 days prior to presentation at the emergency department without resolution of his symptoms. He appeared cachectic and ill, with multiple areas of calcium deposits on the left hand, left shoulder, right axilla (Figure 1), and penis. The left third digit was swollen with calcific deposits and nodules. The dorsal and left lateral penile shaft had hard, nontender nodules without swelling. Initial laboratory values were a calcium level of 9.7 mg/dL, phosphorus level of 10.6 mg/dL, parathyroid hormone level of 5646 pg/mL, creatinine of 7.60 mg/dL, blood urea nitrogen of 124 mg/dL, and estimated glomerular filtration rate of 8.8 mL/min/1.73 m². Computed tomography without intravenous contrast showed extensive, lobulated soft tissue calcifications in both shoulders and the left chest wall, extending into the neck (Figure 2). Findings were consistent with metastatic calcinosis cutis secondary to chronic kidney disease stage 5. Hemodialysis, cinacalcet, a renal diet, and phosphate binders were started. A calcium-phosphate product <50 was targeted. Sodium thiosulfate was given following dialysis, and a subtotal parathyroidectomy was ultimately performed to resolve tertiary hyperparathyroidism.

Figure 1.

Extensive ulcerated calcific deposits in (a) the left third digit and (b) the left axilla.

Figure 2.

CT scan showing extensive, lobulated soft tissue calcification about the left shoulder girdle and left chest wall in aggregate measuring up to 16.1 cm anteroposteriorly × 17.6 cm transversely × 11.5 cm in the craniocaudal dimension.

DISCUSSION

Hundreds of cases of calcinosis cutis have been reported, but only a small number have involved areas of the hand. The typical sites of involvement are the superior and lateral shoulder, posterior elbows, and lateral hip and gluteal regions (1). Other areas such as hands, feet, spine, temporomandibular joint, and knee have been observed. Our patient had extensive involvement of the usual shoulder regions, but also involvement of the digits, neck, and genitals.

Five subtypes of calcinosis cutis exist. Our patient presented with the subclass termed metastatic calcinosis cutis, which was likely secondary to end-stage renal disease. Though rare, calcinosis cutis is a severe complication of chronic kidney disease with an incidence of 0.5% to 3% (2). The subclass of calcinosis cutis that our patient presented with is characterized by abnormal phosphorus or calcium metabolism resulting in widespread deposition of calcium in the skin and soft tissues (3). Metastatic calcinosis cutis has been linked to other conditions such as sarcoidosis, Albright hereditary osteodystrophy, neoplasms, and hypervitaminosis D (3). The most common predisposing condition, however, is chronic kidney disease. A mechanism of pathogenesis of calcinosis cutis has been proposed. It is believed that repeated small trauma occurs, which creates hemorrhages in tissues surrounding the joints and initiates an inflammatory response (1, 4).

Metastatic calcinosis cutis usually presents with benign nodules at periarticular sites (3). However, symptoms such as pain, joint stiffness, nerve compression, inflammation, fistula formation, and infection may be present at the time of diagnosis (1, 2). Physical exam findings may be significant for decreased range of motion or pain at the affected site. Our patient presented with advanced disease with large, calcific ulcerated skin lesions. In metastatic calcinosis cutis, calcification is typically seen in blood vessels, kidneys, lungs, and gastric mucosa as well (3). Radiographic evidence of the disease is the primary modality of diagnosis, along with supporting laboratory data. The appearance on computed tomography (CT) is characterized as cystic loculi with fluid and calcium layering known as the sedimentation sign (1). CT is typically used to evaluate the disease burden for surgical planning. Another key feature is absence of erosion and destruction of nearby bone (1). Laboratory studies should be performed to rule out other disease processes before a definitive diagnosis of calcinosis cutis is made, as it is a diagnosis of exclusion (1, 4). If the diagnosis remains uncertain, biopsy can be performed (1).

Secondary calcinosis cutis is usually treated with medical management of the underlying cause. When medical therapy has failed, subtotal parathyroidectomy is indicated. Renal transplant is also an option in secondary hyperparathyroidism, as it resolves the underlying process (5), but may not be an option for tertiary hyperparathyroidism, as in our case. Surgical debridement of the lesions is indicated for recurrent infection, ulceration, and pain or impairment (1). Treatment includes restricting calcium and phosphorus intake (to <700 mg/day) in the diet and the use of phosphate binders (1, 2, 6, 7). Other medical therapies such as vinpocetine, sodium thiosulfate, and intravenous pamidronate have been used with variable success (1). In our patient, sodium thiosulfate was used. This drug was originally used to treat cyanide poisoning, but has shown efficacy in several cases of calcinosis cutis (2, 6).