Diffuse Calcification and a Draining Wound FREE

A 46-year-old man receiving chronic hemodialysis for polycystic kidney disease is admitted to the hospital with new-onset dyspnea and altered sensorium. He is noted to have “milky” secretions draining from a spontaneous eruption on his left thigh (Figure 1A). His thigh is swollen; radiographs show bulky, extra-articular calcifications (Figure 1B). A 3.4 × 2.3-cm mass involving the posterior mitral leaflet associated with moderate regurgitation is found with transesophageal echocardiography.

Mental confusion is readily apparent on physical examination. There is no fever or hemodynamic instability. He has jugular venous distension and an apical 5/6 holosystolic murmur. He also has bilateral inspiratory crackles, lower extremity edema, and bilateral shoulder and hip swelling.

Initial laboratory evaluation shows leukocytosis (16.5 × 10⁹ cells/L [reference range, 3.5-10.5]); increased levels of blood urea nitrogen (121 mg/dL [8-24]), creatinine (7.1 mg/dL [0.8-1.3]), potassium (5.8 mmol/L [3.6-5.2]), and phosphorus (8.9 mg/dL [2.5-4.5]); and decreased levels of calcium (7.6 mg/dL [8.9-10.1]) and albumin (2.4 g/dL [3.5-5.0]).

Computed tomography of the head is unrevealing. A presumptive diagnosis of endocarditis is made, blood cultures are drawn, and broad-spectrum antibiotics are initiated.

See www.jama.com for online Clinical Challenge.

Uremic tumoral calcinosis (UTC) with mitral valve calcification

C. Initiate immediate hemodialysis with phosphate binders

Key Clinical Feature: Combined with the radiographic findings, a product of the serum concentrations of calcium and phosphate elevated to 79 mg²/dL² is diagnostic of UTC. Hemodialysis must be initiated with phosphate binders (non-calcium–based) to control the uremia, volume status, calcium, and phosphate levels.

UTC is characterized by large, extra-articular soft tissue calcifications that mainly involve the hips, shoulders, and elbows.¹ The lesions are lobulated, firm, slow-growing, nontender, and may have draining ulcerations. These masses originate from the bursa and may compress nearby neurovascular structures.¹ UTC occurs in up to approximately 7% of patients receiving hemodialysis.^2- 3

Up to 50% of patients with end-stage renal disease will develop mitral valve calcification (Figure 2).⁴ Large, polypoid calcific deposits occur at the anterior and posterior leaflet bases, sparing the free edges and chordae tendinae; this differs from senile degenerative mitral valve calcification, which usually demonstrates smaller nodules or ridges posteriorly and rarely affects the anterior leaflet. With UTC, mitral annular calcification may also develop, resulting in clinically significant stenosis or regurgitation.⁵ The differential diagnosis of soft tissue calcification includes myositis ossificans, heterotopic ossification, scleroderma, sarcoidosis, and sarcomas involving bone, cartilage, or synovium.⁶ Radiography of affected joints demonstrates extraosseous, densely calcific masses. In this patient the left hip joint was draining “milky” material. In patients with UTC, this drainage is usually composed of calcium hydroxyapatite, along with calcium carbonate, calcium phosphate, and even calcium oxalate. Similar presentations can be seen with abscesses, crystalline arthropathies, or acute infectious arthritis. Aspiration and microscopy of the involved sites is mandatory. UTC will demonstrate whitish-yellow, pasty material that under light microscopy is amorphous and may contain psammoma body–like masses that are variably birefringent⁶; staining with alizarin S red may help identify these calcific bodies.

The pathogenesis of UTC has not been fully elucidated. When the product of the serum concentrations of calcium and phosphate (CPP) exceeds 65 to 75 mg²/dL², calcium salts precipitate.⁷ Secondary hyperparathyroidism and abnormal vitamin D metabolism are thought to be the predominant mechanisms in end-stage renal disease and result in an increase in both calcium and phosphate release from the bone into the blood, along with a decrease in urinary phosphate excretion.³

Medical management of UTC includes reduction of CPP with low-calcium dialysate, non-calcium–containing phosphate binders (sevelamer/lanthanum), calcimimetics, vitamin D analogues, and bisphosphonates.⁸ If the parathyroid hormone level is elevated, parathyroidectomy may be indicated. Renal transplantation may be required for renal failure. Surgical debulking of calcific masses causing neurovascular impingement may be necessary.⁹ Intravenous glucocorticoids can be used for tophaceous gout concurrent with dialysis. Diagnostic joint aspiration should precede treatment for gout to rule out other diseases such as infectious arthritis or abscess.

This patient required multiple dialysis treatments using low-calcium dialysis with sevelamer, lanthanum, and vitamin D analogues. Blood cultures grew methicillin-resistant Staphylococcus epidermidis. Parathyroid hormone level was significantly elevated (3001 pg/mL [reference range, 15-65]). This patient steadily deteriorated and developed both venous and arterial thromboses, thrombocytopenia, gastrointestinal bleeding, and progressively worsening mental status. The family opted for a conservative approach and requested transfer to their local medical facility.