calciphylaxis is a rare disease entity first described by bryant and white in 1898 to characterize a syndrome exemplified by vascular calcifications with cutaneous necrosis .
attempts to shed light on its pathophysiology was undertaken by selye et al . in 1962 using a rat model to induce calcinosis through a series of experimental steps [ 2 , 3 ] .
the condition was reproduced in nephrectomized rats as well as those challenged with sensitizers such as parathyroid hormone ( pth ) and vitamin d [ 2 , 3 ] .
a series of sensitization events appears necessary to alter the calcium homeostasis prior to the induction of systemic calcinosis with another challenger agent [ 2 , 3 ] .
therefore , patients can develop calciphylaxis even after renal transplantation or in the absence of end - stage renal disease such as hyperparathyroidism [ 46 ] . as the disease is multifactorial , many predisposing conditions contribute to the development of this serious disease , including morbid obesity , diabetes mellitus , malnutrition , liver disease , misuse of vitamin d and calcium - based phosphate binders , or coumadin intake [ 47 ] .   
the disease first gained notoriety after gipstein et al . reported a series of 11 patients with calciphylaxis with concurrent end - stage renal disease .
since his description , the incidence appears to be increasing within the last decade , afflicting 1%4% of patients with end - stage renal disease [ 4 , 6 ] .
attempts to characterize this patient population seem to concentrate on caucasians with a female to male ratio of 3 to 1 [ 4 , 6 ] . although end - stage renal disease ( esrd ) is the most likely culprit to result in disorders of calcium homeostasis , other conditions such as secondary hypercalcemia , hyperparathyroidism , sarcoidosis , or underlying connective tissue disease can also be potential etiologies to this disease entity .  
the typical cutaneous manifestations of calciphylaxis , also seen in calcinosis cutis , comprise exquisitely tender and firm lesions with ninety percent located in the lower extremities .
the skin lesions of stellate purpura and livedo reticularis seen as a result of this disease arise from microthrombus formation within the small vessels [ 9 , 10 ] .
both proximal and distal lesions can occur although the proximal lesions are usually located on the thighs and the lower abdomen .
the proximal location helps to distinguish this disease from vascular causes of lower extremity skin necrosis .
this is the case of a 56-year - old caucasian woman with extensive medical problems who initially presented with bilateral firm thigh lesions that are extremely painful and tender to touch ( figure 1 ) .
her past medical history is complicated by type ii diabetes , morbid obesity ( bmi > 35 ) , and medically managed chronic renal insufficiency with a baseline creatinine level of 3.0  mg / dl .
interestingly , the patient had a history of poor wound healing following a hysterectomy in the past .
initial management consisted of a skin biopsy of these thigh lesions which led to the confirmation of calciphylaxis .
histologically , there were extensive calcifications within the subcutaneous tissue and small blood vessels ( figures 2 and 3 ) .
surveillance chemistries revealed a preoperative intact pth level of 737  pg / ml , with concurrent calcium level of 9.7  mg / dl , chloride level of 107  mmol / l , and phosphate level of 8.4  mg / dl .
preoperative vitamin d levels were examined and showed a normal total 25 hydroxy - vitamin d levels of 39  ng / ml .
intraoperatively , the patient was found to have an enlarged nodular goiter as well as a 1.3-cm papillary carcinoma of the thyroid .
surprisingly , the patient was also found   to have four normal parathyroids but an aberrantly located adenoma within the thymic tissue of the mediastinum , weighing 0.62 grams ( figure 4 ) .
intraoperative pth level remained elevated ( > 300  pg / ml ) after excisional biopsy of three normally appearing parathyroid glands .
finally , the levels fell to 79  pg / ml after the removal of the enlarged adenoma , with a postoperative repeat value of 57  pg / ml .
postoperatively , the patient 's thigh wound started to granulate with immediate improvement in her thigh pain .
historically , the first reported case of calciphylaxis from hyperparathyroidism was described by ellis and barr in 1951 .
the authors reported findings of a 29-year - old female with metastatic recurrent parathyroid carcinoma who had classic lesions of calciphylaxis during autopsy findings .
the recognition of this disease entity follows the early descriptions of selye et al . in laboratory models of calciphylaxis [ 2 , 3 ] .
as the understanding of calciphylaxis became more widespread , reported cases of unusual causes of calciphylaxis also became more frequent [ 4 , 5 ] .
a search into the available data in the english literature identified a total of 15 other cases of patients with calciphylaxis secondary to primary hyperparathyroidism , with half of them being reported in the last decade [ 9 , 1122 ] ( table 1 ) .
the majority of patients succumbed to their disease due to the progressive nature of the disease .
however , a few patients did benefit from early parathyroidectomy and medical optimization [ 9 , 1218 ] .  
initial reports of calciphylaxis secondary to nonrenal - related causes were usually a result of autopsy findings [ 11 , 19 , 20 ] .
bogdonoff and colleagues associated two autopsy findings of calciphylaxis with parathyroid adenomas in those patients in 1956 .
subsequently , anderson et al . and winkelman et al . also found parathyroid adenomas on autopsy findings of two sixty - two year old females and a sixty year old female in 1968 and 1970 , respectively [ 9 , 20 ] . with better understanding of the physiology of hyperparathyroidism and its effects on calcium homeostasis
, surgeons are taking a more active role in treating this disease to decrease serum calcium levels in the hope of controlling the systemic manifestations associated with hypercalcemia .
winkelman et al . introduced parathyroidectomy as a management option in these patients and reported the first patient recovering from calciphylaxis caused by hyperparathyroidism in 1970 .
the second published report of a patient surviving after parathyroidectomy for hyperparathyroidism causing calciphylaxis was by khafif et al . in 1989 , on a 71-year - old female .
despite the more aggressive approach undertaken recently , patients with calciphylaxis still have a guarded prognosis , with 80% succumbing to their disease secondary to recurrent skin infections [ 10 , 23 ] .
hafner et al . reported a survival advantage for patients who underwent parathyroidectomy in comparison to those who did not .
reported in their series that parathyroidectomy was not associated with a survival advantage in patients with end - stage renal disease [ 10 , 24 ] .  
calciphylaxis is not always a disease secondary to unopposed parathyroid hormone production from an aberrant gland .
presented an interesting case of a patient with hypercalcemia that was successfully managed with steroids and immunosuppression alone [ 4 , 13 ] .
there are also cases of calciphylaxis without association with renal failure or hyperparathyroidism reported in the literature .
this also correlates with the finding that patients with end - stage renal failure can have progressive calciphylaxis following renal transplantation and normalization of their parathyroid levels .
it appears that once the disease process initiates following sensitization with hyperparathyroidism , there is difficulty in resetting the calcium homeostatic switch
. however , parathyroidectomy may be the only option in these difficult cases especially with documented hyperparathyroidism , as evidenced by favorable results with early intervention recently .  
this patient illustrates the various etiologies that can lead to calciphylaxis as well as the difficulty in managing this disease entity . her disease presented with calciphylaxis secondary to primary hyperparathyroidism that improved with the use of parathyroidectomy . however , her chronic renal insufficiency and dysregulation of electrolyte balances initially suggested secondary hyperparathyroidism as the culprit for her calciphylaxis . only during the surgery
vitamin d , though replete in this patient , can sometimes be a contributor to the development of hyperparathyroidism when deficient . in patients with calciphylaxis ,
early parathyroidectomy may still play a role in improving their cutaneous disease , especially in cases of hyperparathyroidism .
 calciphylaxis , or calcific uremic arteriolopathy , commonly affects people with end - stage renal disease and carries with it a high rate of morbidity and mortality . here 
 , we present the unusual case of a 56-year - old woman , with extensive medical problems , who developed calciphylaxis in the presence of primary hyperparathyroidism .   
 our patient initially presented with bilateral , exquisitely tender thigh lesions .   
 the diagnosis of calciphylaxis was rendered histologically by extensive calcification of the subcutaneous blood vessels . 
 subsequent parathyroidectomy identified the presence of a hyperactive mediastinal parathyroid adenoma , weighing 0.62 grams .   
 postoperatively , the patient had normalization of hypercalcemia and parathyroid hormone levels , with subsequent healing of her thigh wounds . 
 currently , there have been sixteen cases described in the english literature , with only nine being offered a potentially therapeutic parathyroidectomy .   
 it is contingent upon the vigilant physician to diagnose and properly manage this difficult yet treatable condition . 
1. Introduction
2. Case Report
3. Discussion
 Author Contributions