During dialysis rounds, 64-year-old Mrs. V complained of a painful sore on her left breast. Mrs. V was a thin, white woman who had been on hemodialysis for four years. She noted not only the tenderness and extreme pain in her breast, but also complained that this was accompanied by a significant amount of pain in her thighs.
Mrs. V denied any recent trauma and reported no new exercise routines or changes in medication. A review of her chart showed an episode of atrial fibrillation two months earlier that was treated with warfarin (Coumadin, Jantoven), but otherwise her medical history for the past year was unremarkable.
1. Examination and Laboratory Tests
Examination of the left breast showed a black area with a red circumference without any drainage (Figure 1). The breast area was exquisitely tender. There were no palpable lymph nodes, and the right breast was slightly lumpy without any open lesions.
Bilateral thighs had multiple moveable lumps, which were firm and approximately 3×4 cm each. The thigh masses were also hypersensitive to touch, but without accompanying skin lesions.
Mrs. V’s lungs were clear to auscultation. Her heart rate was regular without any murmur or ectopy. She dialyzed through an upper-left-arm arteriovenous fistula. The rest of the examination was noncontributory. Mrs. V’s hemoglobin level was 11.5 g/dL. (In adult women, the normal range is 12-16 g/dL.) Her calcium level was below normal at 7.8 mg/dL (baseline range 8.4-10.2 mg/dL), and her phosphorus level was significantly elevated at 7.6 mg/dL (3.5- 5.5 mg/dL is the typical target range for dialysis patients). Mrs. V’s intact parathyroid hormone (PTH) level was 1,251 pg/mL (normal is 14- 72 pg/mL), her albumin level was 2.5 g/dL (normal 3.5-5.2 g/dL) and her hemoglobin A1c was 5.9% (standard range 4.8%-5.9%).
2. Differential Diagnosis
The differential diagnosis includes cholesterol emboli, necrosis from warfarin, cellulitis, nephrogenic sclerosing fibrosis (NSF), vasculitis, calciphylaxis or gangrene.1
Cholesterol emboli and their close relatives (atherosclerosis and atheroemboli) can be excluded due to location of the lesion on the upper extremity as well as intact peripheral pulses. Gangrene is also excluded for this reason. Vasculitis is unlikely since the patient lacks the telltale signs — neuropathy and polyarteritis — plus, Mrs. V is older than the usual age group. NSF is also unlikely due to a lack of recent radiology tests.
Heparin-induced necrosis was considered, but Mrs. V’s platelet count came back in the normal range, which made this diagnosis less likely. Cellulitis and calciphylaxis are usually hard to distinguish from each other without a biopsy, but the lumpy lesions in the patient’s thighs made calciphylaxis the most likely diagnosis.
3. Treatment and Outcome
Calciphylaxis is an ischemic disease of the arterioles. Calcification of the vessels causes narrowing, decreased blood flow and hypoxia, leading to necrosis of the skin. Since calciphylaxis has an 80% death rate once ulceration occurs, all known treatments were initiated simultaneously.2 IV sodium thiosulfate was started (12.5 mg with the first dialysis, then increasing to 25 mg with each subsequent hemodialysis). It is unknown how sodium thiosulfate works in calciphylaxis, but it is thought to dissolve the calcification in the tissues and move the previously insoluble calcium into the bloodstream.3 Empiric reports of the effectiveness of sodium thiosulfate treatment were a clinical guide here, although no rigorous, controlled studies have been conducted.
Mrs. V was referred to a local wound center and a breast surgeon. Her warfarin was discontinued since it is a known factor in the development of calciphylaxis. Mrs. V was started on oral cinacalcet (Sensipar), a calcimimetic that increases the sensitivity of the parathyroid gland to calcium.4,5 However, she was unable to tolerate cinacalcet, so it was stopped.
Pain control was an extremely important and difficult problem due to severe nausea and vomiting, and a palliative-care consult was obtained. A combination of patches and short- and long-acting oral narcotics were required.
The wound center began hyperbaric oxygen (HBO) treatments and local care of the lesions. There are case reports that indicate that HBO helps wound healing by increasing oxygenation to the tissues affected by calciphylaxis.6 The breast surgeon was reluctant to operate due to the likelihood of poor wound closure and healing. He asked that we consider a parathyroidectomy prior to any breast surgery, unless the wound center was able to heal the lesions with conservative care.