Year : 2008 | Volume
: 19 | Issue : 1 | Page : 82--86
Calciphylaxis of both Proximal and Distal Distribution
Abdulla K Al-Hwiesh
King Fahd University Hospital, Al Khobar, Saudi Arabia
Abdulla K Al-Hwiesh
Department of Nephrology, King Fahd Hospital of University, PO Box 40246, Al Khobar 31952
Calciphylaxis is a dreaded complication of chronic renal failure characterized by nodular subcutaneous calcification and pain. Full tissue necrosis often leads to ulceration, secondary infection and high mortality rate. We herewith present a 65-year-old Saudi gentleman who presented with multiple necrotic skin lesions of both proximal and distal distribution. Skin biopsy confirmed the diagnosis of calciphylaxis. Patient was started on sevelamer hydrochloride and low calcium dialysate to which he responded dramatically without the need for parathyroidectomy. To our knowledge, this is the first reported case of calciphylaxis with both proximal and distal distribution.
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Al-Hwiesh AK. Calciphylaxis of both Proximal and Distal Distribution.Saudi J Kidney Dis Transpl 2008;19:82-86
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Al-Hwiesh AK. Calciphylaxis of both Proximal and Distal Distribution. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2019 Aug 23 ];19:82-86
Available from: http://www.sjkdt.org/text.asp?2008/19/1/82/37440
The co-existence of proximal and distal calciphylaxis in the same patient has not been reported previously. We herewith describe a 65-year-old Saudi gentleman who presented to our hemodialysis (HD) unit with combined proximal and distal necrotic painful skin lesions which was confirmed by skin biopsy to be calciphylaxis. To our knowledge, this is the first case report in the literature of such an association.
A 65-year-old Saudi male, a known case of chronic renal failure secondary to diabetic nephropathy who also had associated hypertension, hypertensive heart disease, congestive heart failure class IV and hyperlipidemia was started on HD through a right perm catheter, four months prior to presentation. He received dialysis three times per week. The patient presented to us with painful necrotic skin ulcers involving the proximal upper and distal lower limbs in symmetrical distribution [Figure 1],[Figure 2],[Figure 3] that progressively increased to involve the scrotum and penis [Figure 4] as well as the abdomen over the next two-months. There was no history of receiving any blood transfusions nor there was history suggestive of chronic liver disease. The patient was not maintained on any anticoagulant except heparin, which was given during HD. Also, there was no history suggestive of connective tissue disease. Examination revealed an elderly male without pallor, jaundice or cyanosis. His BP was 110/60 mmHg, pulse 85/min regular, respiratory rate 18/min; he was febrile and had an oxygen saturation of 97% at room air. There was no jugular venous distention. There was moderate peripheral edema. Systemic examination was normal. There were scattered necrotic, painful, violacious skin ulcers of symmetrical distribution involving both upper proximal and lower distal limbs, bilaterally [Figure 1],[Figure 2],[Figure 3]. The lesions involved the scrotum and the penis showed necrosis and gangrenous features [Figure 4].
Investigations revealed the following: Hemoglobin 9 gm/dl with normochromic normocytic picture, platelet count 406/mm 3 , white blood cell within normal limits, serum sodium 140 mmol/L, potassium 4.5 mmol/L, chloride 111 mmol/L, bicarbonate 22 mmol/L, blood urea nitrogen 35 mg/dl, serum creatinine 5 mg/dl, phosphate 8 mg/dl, calcium 9 mg/dl, calcium x phosphate product 72, alkaline phosphate 400 u/l, parathyroid hormone 1900, total protein 7.2 g/dl, serum albumin 2.5 g/dl with normal liver enzyme levels. The serum complement C3 and C4 levels, ANA, Anti-DNA, rheumatoid factor and cryoglobulin levels were all within normal limits. Virology studies including cytomegalovirus (CMV), Epstein barr virus (EBV), herpes, human immunodeficiency virus (HIV) and markers for syphilis were all negative. Skin biopsy [Figure 5] showed diffuse calcification of the blood vessel.
The patient was started on low calcium dialysate and high dose of sevelamer hydrochloride (Renogel) as well as increase in frequency of HD to five times per week. Additionally, both calcitriol and calcium carbonate were discontinued. After two months of this treatment, the patient showed dramatic improvement of his skin lesions [Figure 6]. Parathyroidectomy was not done on the patient due to his poor general condition.
Calciphylaxis is a poorly understood and highly morbid syndrome of vascular calcification and skin necrosis. Bryant and White first reported it in association with uremia in 1898.  However, the significance of this relationship became more certain when vascular calcification was subsequently shown to be prevalent in uremia; yet the syndrome of vascular calcification with cutaneous necrosis remained rare.  Interestingly, the clinical importance of this syndrome was not recognized until the report of Gipstein et al was published in 1976. Since then, a multitude of case reports of calciphylaxis have been documented outlining its morbidity and therapeutic dilemmas, as well as a quest to better understand its etiology and pathogenesis. Unfortunately, these aspects still remain obscure and are likely the result of a multiplicity of co-morbid factors or events.  Disorders that are most often implicated in the pathogenesis of calciphylaxis include chronic renal failure, hypercalcemia, hyperphosphatemia, an elevated calcium x phosphate product, and secondary hyperparathyroidism. Yet, although these abnormalities are extremely common in patients with end-stage renal disease (ESRD), calciphylaxis is relatively rare and affects 14% of the population with ESRD. , The incidence has increased during the last decade because of a number of possible factors, including more widespread use of parenteral vitamin D and iron dextran. The mortality rate of calciphylaxis is reported to be as high as 60-80%. , The leading cause of death is sepsis cation and skin necrosis. Bryant and White first reported it in association with uremia in 1898.  However, the significance of this relationship became more certain when vascular calcification was subsequently shown from infected, necrotic skin lesions, although death due to internal organ failure has been reported. The mortality rate is higher in patients with proximal disease than in those with only distal disease. A two-fold increase in mortality is seen in those with ulcerative disease. The overall one-and five-year survival rates have recently been reported to be 45% and 35%, respectively.
Calciphylaxis appears to be more prevalent in whites and females with a female-to-male ratio of approximately 3:1. Calciphylaxis has been reported in individuals ranging in age from six months to 83 years. Most patients with calciphylaxis have a long-standing history of chronic renal failure and renal replacement therapy. On rare occasions, calciphylaxis may occur in a patient with chronic renal failure prior to the initiation of replacement therapy. Very rarely, it may occur in an individual without a history of chronic renal failure. Frequently, patients have been non-compliant with dietary, medical, and/or dialysis prescriptions prior to the onset of calciphylaxis.
The lesions of calciphylaxis typically develop suddenly and progress rapidly. Lesions may be singular or numerous, and they generally occur on the lower extremities [Figure 2]; however, lesions may also develop on the hands and torso. Intense pain is a constant finding. The patient's history may reveal an event that is a suspected trigger or risk factor for the development of calciphylaxis. ,,, These triggers include long-term HD, obesity, recent and sudden weight loss, infusion of medications such as iron dextran, remote and/ or recent use of immunosuppressive agents, especially corticosteroids and concurrent use of warfarin anti-coagulation: Current data suggest that warfarin therapy may lower protein C concentrations leading to a procoagulant condition in the calcified vessel. It is sometimes difficult to differentiate calciphylaxis from cryoglobulinemia, cryofibrinogenemia, coumarin necrosis, protein C deficiency, protein S deficiency, antiphospholipid syndrome, polyarteritis nodosa, atherosclerotic peripheral vascular disease and panniculitis.
Treatment of calciphylaxis is mainly supportive. ,,,, Aggravating conditions should be addressed, and triggering factors should be eliminated. This may mean the discontinuation of parenteral iron therapy, calcium, and vitamin D supplementation. Recent studies suggest that some patients may benefit early on from systemic glucocorticoids, unless ulcerated lesions are present. Serum calcium and phosphate concentrations must be brought to low-normal levels as quickly and safely as possible. Conservative therapy should be tried first, with dietary alteration, use of noncalcium, phosphate binders and low-calcium bath dialysis. Some benefit may be achieved with increasing the frequency of dialysis sessions. Although only speculative, calcimimetics such as cinacalcet hydrochloride may be beneficial in cases of hyperparathyroidism. Parathyroidectomy should be considered if conservative management fails. Marked improvement of calciphylaxis has now been reported with the use of intravenous sodium thiosulfate. Sodium thiosulfate increases the solubility of calcium deposits. Judicious use of antibiotics may be advantageous. In some cases, hyperbaric oxygen may be beneficial. The role of anticoagulation in all cases of calciphylaxis is controversial. Random prophylactic use of warfarin or heparin is probably not indicated because precipitation of calciphylaxis has occurred with indiscriminate use.
Our patient showed dramatic improvement with control of his calcium and phosphate levels as well as calcium x phosphate product and high doses of sevalemir hydrochloride. Parathyroidectomy was not done on the patient because of his poor general condition. A Medline literature search by the author did not disclose any prior case report of coexistence of proximal and distal calciphylaxis in the same patient.
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