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 Table of Contents  
CASE REPORT
Year : 2013  |  Volume : 3  |  Issue : 4  |  Page : 109-111

Acral gangrene as a presentation of non-uremic calciphylaxis


Department of Internal Medicine, Cleveland Clinic, Cleveland, Ohio, United States

Date of Web Publication25-Oct-2013

Correspondence Address:
Prashant Sharma
Cleveland Clinic Main Campus, 9500 Euclid Avenue, Cleveland, OH 44195
United States
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2231-0770.120504

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   Abstract 

We are describing a case of 55-year-old obese female with significant history of uncontrolled rheumatoid arthritis, who recently had decreased her immune-suppression medications. She presented with extensive acral gangrene involving multiple fingers and toes. Clinical picture and laboratory findings were suggestive of vasculitis; however, skin biopsy established diagnosis of calciphylaxis, in settings of normal kidney function. Patient was treated with sodium thiosulfate with gradual improvement in her skin lesions.

Keywords: Acral gangrene, calciphylaxis, non uremic, sodium thiosulfate, vasculitis


How to cite this article:
Hammadah M, Chaturvedi S, Jue J, Buletko AB, Qintar M, Eid Madmani M, Sharma P. Acral gangrene as a presentation of non-uremic calciphylaxis. Avicenna J Med 2013;3:109-11

How to cite this URL:
Hammadah M, Chaturvedi S, Jue J, Buletko AB, Qintar M, Eid Madmani M, Sharma P. Acral gangrene as a presentation of non-uremic calciphylaxis. Avicenna J Med [serial online] 2013 [cited 2019 Sep 23];3:109-11. Available from: http://www.avicennajmed.com/text.asp?2013/3/4/109/120504


   Clinical Presentation Top


A 55-year-old, morbidly-obese Caucasian woman with a history of severe rheumatoid arthritis (RA) presented with a 3-week history of painful, black lesions on the tips of fingers and toes.

The patient's medical course during the preceding six months had been extensive. She first developed a severe abdominal wall infection, which necessitated stopping her disease-modifying anti-rheumatic drug and biological agent (methotrexate and etanercept). Two months later, she was diagnosed with mononeuritis multiplex with right wrist drop attributed to rheumatoid vasculitis. The patient then suffered a left MCA territory ischemic stroke, from which she was recovering at the time of her presentation. Physical exam was remarkable for dry gangrene of multiple fingertips, toes, and the left forefoot with complete anesthesia of the gangrenous areas [Figure 1]. All peripheral pulses were palpable.
Figure 1: Dry gangrene secondary to non-uremic calciphylaxis involving finger and toe tips. Skin biopsy showing focal calcium deposit within a subcutaneous blood vessel with absence of vasculitis

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The acral distribution of the lesions suggested an arterial etiology-either embolic or secondary to vasculitis, especially considering her history of RA and the recent discontinuation of immunosuppressive medications. Initial work-up revealed an elevated Rheumatoid-Factor, CRP, ESR, and antibodies against cyclic-citrullinated-peptide [Table 1]. Arterial pulse volume recordings were normal, and a transesophageal-echocardiogram revealed no potential source of emboli. Pending biopsy results, patient was started on high-dose methylprednisolone and received a single dose of rituximab for a presumptive diagnosis of rheumatoid vasculitis. Three days later, the skin biopsy results showed significant calcium deposits in the media of the subcutaneous arterioles, confirming the diagnosis of calciphylaxis with no evidence of vasculitis. Interestingly, our patient had normal renal function and calcium-phosphorus product. She was started on treatment with sodium-thiosulfate with noted improvement of necrotic skin lesions.
Table 1: Admission laboratory results

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   Discussion Top


Calciphylaxis is a rare disorder that primarily affects patients with ESRD. [1],[2],[3] A few cases of non-uremic calciphylaxis (NUC) have been reported [4],[5],[6] and have been attributed to diverse etiologies such as hyperparathyroidism, malignancies, [5] connective tissue disease, [7],[8],[9],[10] warfarin-induced protein C and S deficiency, [11] chronic steroid use, and rapid weight loss. [4] The pathogenesis of NUC is not completely known, but disruption in the calcium-phosphate-byproduct has been implicated. Patients with disturbances in calcium and vitamin D metabolism such as hyperparathyroidism [12] or lymphoma can be affected by NUC. [4] A recent study suggested that calcium deposits in the arterial media in calciphylaxis are caused by dysregulation of the factors that regulate calcium deposition and removal from arterial walls. [13] These deposits cause vascular occlusion leading to ischemic necrosis of the skin and subcutaneous tissue. [4],[14] Intractable lower extremity pain and cutaneous ulcers are the most common presentations, but indurated nodules, violaceous skin lesions, and livedo-reticularis may also occur. Extra-cutaneous manifestations of calciphylaxis include myopathy, cardiomyopathy, and mesenteric ischemia. [4] A skin biopsy is essential for diagnosis, especially in patients with normal kidney function. NUC usually has poor prognosis with mortality up to 50%, mostly secondary to sepsis. [4],[15] Medical treatment aims to normalize mineral metabolism to reduce the serum concentration of calcium-phosphate-byproduct and thus prevent precipitation and calcification. Bisphosphonates, phosphate-binders, cinacalcet, and sodium-thiosulfate have been used with variable success. [6],[16]

Several cases of NUC in settings of connective tissue disease have been reported. [7],[8],[9],[10] Chronic immune suppressive therapy, rather than underlying skin injury because of vasculitis, was found to be the most important trigger of calcium deposition in these patients. [7],[8],[9],[10] Obtaining skin biopsy, in our patient before starting immune-suppressive medications, makes the possibility of calcium deposition in setting of resolving vasculitis to be less likely.

Calciphylaxis presenting with dry gangrene of multiple fingers and toes is exceedingly rare, and to our knowledge, has not been reported in the literature. Our patient's presentation with acral lesions, high inflammatory and rheumatoid markers, and recent discontinuation of immuno-modulatory therapy all suggested a vasculitic disorder but was not consistent with the skin biopsy. While our patient did not have renal impairment, or an elevated calcium phosphate product, her longstanding rheumatoid arthritis, chronic glucocorticoid therapy, obesity, and rapid weight loss are risk factors that may have predisposed her to develop calciphylaxis. [13]

 
   References Top

1.Hayashi M, Takamatsu I, Kanno Y, Yoshida T, Abe T, Sato Y; Japanese Calciphylaxis Study Group. A case-control study of calciphylaxis in Japanese end-stage renal disease patients. Nephrol Dial Transplant 2012;27:1580-4.  Back to cited text no. 1
    
2.Coates T, Kirkland GS, Dymock RB, Murphy BF, Brealey JK, Mathew TH, et al. Cutaneous necrosis from calcific uremic arteriolopathy. Am J Kidney Dis 1998;32:384-91.  Back to cited text no. 2
    
3.Verdalles U, Cueva Pde L, Verde E, Vinuesa SG, Goicoechea M, Mosse A, et al. Calciphylaxis: A severe complication of the cardiometabolic syndrome in patients receiving hemodialysis. J Cardiometab Syndr 2008;3:63-7.  Back to cited text no. 3
    
4.Nigwekar SU, Wolf M, Sterns RH, Hix JK. Calciphylaxis from Nonuremic Causes: A Systematic Review. Clin J Am Soc Nephrol 2008;3:1139-43.  Back to cited text no. 4
    
5.Sibai H, Ishak RS, Halawi R, Otrock ZK, Salman S, Abu-Alfa A, et al. Non-uremic calcific arteriolopathy (calciphylaxis) in relapsed/refractory Hodgkin's lymphoma: A previously unreported association. J Clin Oncol 2012;30:e88-90.  Back to cited text no. 5
    
6.Smith VM, Oliphant T, Shareef M, Merchant W, Wilkinson SM. Calciphylaxis with normal renal function: Treated with intravenous sodium thiosulfate. Clin Exp Dermatol 2012;37:874-78.  Back to cited text no. 6
    
7.Brouns K, Verbeken E, Degreef H, Bobbaers H, Blockmans D. Fatal calciphylaxis in two patients with giant cell arteritis. Clin Rheumatol 2007;26:836-40.  Back to cited text no. 7
    
8.Korkmaz C, Dundar E, Zubaroglu I. Calciphylaxis in a patient with rheumatoid arthritis without renal failure and hyperparathyroidism: The possible role of long-term steroid use and protein S deficiency. Clin Rheumatol 2002;21:66-9.  Back to cited text no. 8
    
9.Ozbalkan Z, Calguneri M, Onat AM, Ozturk MA. Development of calciphylaxis after long-term steroid and methotroxate use in a patient with rheumatoid arthritis. Intern Med 2005;44:1178-81.  Back to cited text no. 9
    
10.Lee JL, Naguwa SM, Cheema G, Gershwin ME. Recognizing calcific uremic arteriolopathy in autoimmune disease: an emerging mimicker of vasculitis. Autoimmun Rev 2008;7:638-43.  Back to cited text no. 10
    
11.Banerjee C, Woller SC, Holm JR, Stevens SM, Lahey MJ. Atypical calciphylaxis in a patient receiving warfarin then resolving with cessation of warfarin and application of hyperbaric oxygen therapy. Clin Appl Thromb Hemost 2010;16:345-50.  Back to cited text no. 11
    
12.Biller P, Marot L, Lambert M, Lefebvre C. Calciphylaxis: An uncommon manifestation of primary hyperparathyroidism. A case report. Acta Clin Belg 2012;67:442-4.  Back to cited text no. 12
    
13.Weenig RH. Pathogenesis of calciphylaxis: Hans Selye to nuclear factor kappa-B. J Am Acad Dermatol 2008;58:458-71.  Back to cited text no. 13
    
14.Brinster NK, Vincent L, Diwan AH, McKee PH. Dermatopathology: High-Yield Pathology. Vol. 293-294. 2011.  Back to cited text no. 14
    
15.Yalin AS, Altiparmak MR, Trabulus S, Yalin SF, Yalin GY, Melikoglu M. Calciphylaxis: A Report of Six Cases and Review of Literature. Ren Fail 2013;35:163-9.  Back to cited text no. 15
    
16.Wollina U. [Cutaneous calciphylaxis]. Hautarzt 2010;61:1063-71; quiz 1072.  Back to cited text no. 16
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1]


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