Year : 2010 | Volume
: 21 | Issue : 2 | Page : 323--327
Catastrophic calciphylaxis in a patient with lupus nephritis and recent onset of end-stage renal disease
Fatma I Al Beladi
Department of Internal Medicine, Nephrology Division, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
Fatma I Al Beladi
Department of Internal Medicine, Nephrology Division, King Abdulaziz University Hospital, Jeddah
Painful violaceous skin lesions that progress to non-healing ulceration and gangrene characterize calciphylaxis. These lesions are associated with secondary hyperparathyroidism and generally occur in patients on dialysis for more than one year. Hyperphosphatemia and hypoalbuminemia are the major risk factors for calciphylaxis. It is usually resistant to medical treatment although parathyroidectomy can help in controlling the disease. The mortality rate of calciphylaxis is very high due to uncontrollable sepsis. In our case, a young female with systemic lupus erythematosus (SLE) developed calciphylaxis within a short period after the onset of hemodialysis; she had a short period of hyperphosphatemia prior to dialysis. The serum phosphate was 4.24 mmol/L, calcium was 1.66 mmol/L, parathormone was 38 and calcium-phosphate was 7.0 mmol/L. It is likely that SLE provoked the development of calciphylaxis. The patient was treated medically but unfortunately died secondary to sepsis.
|How to cite this article:|
Al Beladi FI. Catastrophic calciphylaxis in a patient with lupus nephritis and recent onset of end-stage renal disease.Saudi J Kidney Dis Transpl 2010;21:323-327
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Al Beladi FI. Catastrophic calciphylaxis in a patient with lupus nephritis and recent onset of end-stage renal disease. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2020 Jul 10 ];21:323-327
Available from: http://www.sjkdt.org/text.asp?2010/21/2/323/60204
Calciphylaxis is a pathophysiological change that is caused by the deposition of calcium which leads to painful skin lesions and often cutaneous necrosis.  Calciphylaxis is an uncommon condition that occurs in patients with chronic kidney failure in association with secondary hyperparathyroidism. When kidney function is normal, calciphylaxis may be associated with breast cancer, , primary hyperparathyroidism, , short bowel syndrome, Crohn's disease,  protein S deficiency, rheumatoid arthritis,  and acute renal failure in alcoholic cirrhosis. 
Several risk factors for calciphylaxis have been identified. These include obesity, diabetes, Caucasian race, female gender, hypoalbuminemia, and a calcium-phosphate product (a-p) of 70 or more.  Clinical history and physical examination can be sufficient to diagnose calciphylxis. A biopsy of the ulcerated wound is the most accurate method to confirm the diagnosis. Histological examination shows medial calcification, and intimal fibrous hyperplasia of arterioles, capillaries, and venules.
Calciphylaxis is associated with high morbidity and mortality. To prevent calciphylaxis, aggressive management of calcium, phosphate, and parathyroid hormone levels are critical. If skin lesions occur, oral corticosteriod is effective in addition to aggressive local surgical care, and parathyriodectomy. In this paper, a case of calciphylaxis secondary to systemic lupus erythematosus (SLE) is reported.
In late 2004, a 23-year-old female patient, who presented with polyarthralgia, mouth ulcers, and alopecia, was diagnosed to have SLE complicated by class IV nephritis, in another hospital. Antinuclear antibody (ANA) and double stranded DNA antibody (dsANA) were positive. At that time, renal function was normal. Liver function was normal except low serum albumin, 12 gm/L (NR 34-40). She was treated with methylprednisolone (1g i.v.) for three days followed by oral prednisolone (60 mg) in a tapering dose. The total duration of treatment was not very clear. Since 2004, the patient had frequent relapses of disease activity and each time she was treated with pulse steroids followed by a tapering dose of prednisolone.
In March 2006, the woman was admitted to the King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia with dyspnea, lower-limb edema, decreased urine output and polyarthralgia. On clinical examination, the following findings were noted: body temperature, 37.1°C; blood pressure, 149/90 mmHg; heart rate, 84 beats/min; elevated jugular venous pressure (JVP); body weight, 90 kg and lower limb edema. Chest examination revealed bilateral basal crepitations. The remainder of the examination was unremarkable. Laboratory tests revealed high creatinine level of 402 mmol/L (NR 53-115), active urine sediment, high phosphate of 3.3 mmol/L (NR 0.81-1.58), calcium of 2.42 mmol/L (2.12-2.52), albumin of 19 gm/L and alkaline phosphatase of 63 IU/L (NR 53-115). Repeat renal biopsy showed diffuse proliferative glomerulonephritis with crescents, consistent with class IV lupus nephritis. She was treated with pulse methylprednisolone (1 gm i.v.) for three days followed by oral prednisolone (60 mg daily) for one month, to be slowly tapered. At the same time, treatment was started with mycophenolate mofetil, 1 gm twice daily. The patient responded to hemodialysis and began to produce urine in the range of 1.5-2 liters/day. The calcium and phosphorus homeostasis was wellmaintained and she came out of dialysis after one month almost totally symptom free and with no pulmonary or lower-limb edema.
On 1 April 2006, the woman was discharged with creatinine of 330 mmol/L and phosphorus of 1.4 mmol/L to be assessed once each week. On 2 July 2006, she was re-admitted to KAUH with skin lesions that started in the gluteal region. The lesions were diagnosed at the other hospital as gluteal abscess. Since the lesions were drained at the other hospital, their precise characteristics were not clear.
On re-admission to our hospital, the lesions typically were violaceous, painful, plaque-like, and involved the dermis and subcutaneous fat on back, buttocks, thighs, and breast [Figure 1]. Subsequently, the lesions progressed to ischemic/necrotic ulcers [Figure 2].
The patient denied a history of fever or trauma. On clinical examination, the following findings were noted: body temperature, 37°C; blood pressure, 140/80 mmHg; jugular venous pressure was not elevated and there was no lower limb edema. Laboratory tests showed creatinine of 763 mmol/L, alkaline phosphatase of 149 IU/L, calcium of 1.66 mmol/L, phosphate of 4.24 mmol/L, calcium × phosphate product of 7.0 mmol/L, parathyroid hormone of 38, ANA 1:320 g/L, dsDNA 52 iu/mL, C3 0.87 g/L, C4 0.33 g/L, CRP 130 mg/L with normal protein C, proteins, anticardiolipin and cryoglobin levels.
The patient was evaluated by dermatology and rheumatology and the lesion was biopsied. Histology examination revealed vasculitis and paniculitis consistent with lupus profundus. The patient was treated with daily dialysis and oral prednisolone (0.5 mg/1 kg on alternate days) and phosphate binders. Unfortunately, the condition of the patient progressively deteriorated. The skin lesions continued to expand [Figure 3]. Consequently, the patient underwent surgical debridement of necrotic tissue of the back [Figure 4]. Staphylococcus aureus was isolated from the skin lesions and treatment with a broad spectrum antibiotic was started. However, the patient developed septic shock and was transferred to ICU for intubation. Based on a second skin biopsy report, calciphylaxis was diagnosed. Repeat parathyroid hormone level after one month of this treatment was 5.3, calcium was 2.2 mmol/L, phosphate was 1.4 mmol/ L. However, despite all efforts, the patient died due to sepsis.
Calciphylaxis is a disease, which occurs as a result of deposition of calcium resulting in painful skin lesions leading to advanced non-healing ulcers and skin necrosis. Calciphylaxis in hemodialysis patients was first described in 1962. It is usually seen in patients with chronic kidney disease with most of them being on dialysis. These patients usually are characterized by the presence of hypercalcemia, hyperphosphatemia, and hyperparathyroidism. The syndrome described above has also been reported in patients with normal kidney function as in malignancy, , inflammatory bowel disease,  and primary hyperparathyroidism in association with protein C and protein S deficiency. ,
Our patient developed calciphylaxis two months after starting dialysis, with only a short duration of hyperphosphatemia, hypercalcemia, and high calcium-phosphate product. However, it is known that a long duration of hyperparathyroidism and hyperphosphatemia is crucial for the development of calciphylaxis. Mazhar et al  demonstrated a three-fold increase in the likelihood of developing calciphylaxis for each 1 mg/dL increment in serum phosphate over 12-months period prior to the diagnosis. Initially, calciphylaxis was described in older dialysis patients although recent reports suggest that younger patients also can be at high-risk and a few pediatric cases have also been described.  The syndrome is common among females as in our case.
On reviewing other reports, a majority of patients who developed calciphylaxis were patients who had received dialysis for more than one year, and most of them were on hemodialysis.  There was an occasional report of calciphylaxis occurring in a patient on peritoneal dialysis. We found no studies in which the incidence of calciphylaxis was compared among patients who received hemodialysis or peritoneal dialysis. A recent report described two patients with SLE who developed calciphylaxis after they received peritoneal dialysis for endstage renal disease. In one of these patients, cutaneous lesions developed two days after ultraviolet phototherapy for pruritus. The second patient was a young woman who developed calciphylaxis four years after being on peritoneal dialysis.  In our case, calciphylaxis developed almost simultaneously with the onset of hemodialysis after only a short period of kidney failure, apparently without other causes of calciphylaxis. The patient in our case was obese (BMI 37.5) and had hypoalbuminemia, both of which are strongly associated with calciphylaxis.  Bleyer et al  reported a 17-fold increase in the risk of developing calciphylaxis with each 1 g/L reduction in serum albumin. In addition, they suggested that for an increase in BMI of 1 kg/m 2 , the odds ratio for developing calciphylaxis was 6.29 (95% confidence interval 3.7-10.7). 
The mechanisms of vasculopathy in calciphy laxis are unclear but established risk factors include disturbance of calcium-phosphate and parathyroid hormone homeostasis. However, we found no reports on the underlying mechanisms for the development of calciphylaxis.
Based on this case study, it is proposed that vasculitis may be an underlying cause of calciphylaxis. To our knowledge, this is the only case of calciphylaxis with SLE that developed at the beginning of dialysis after only a short period of impaired calcium-phosphate homeostasis. The patient had profound hypoalbuminemia and she was obese which are well known risk factors for calciphylaxis. However, the possibility of vasculitis as an additional risk factor should be considered.
Calciphylaxis is a lethal disease that carries a high rate of morbidity and mortality. Our patient died shortly after the diagnosis of calciphylaxis.
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