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BY-NC-ND 4.0 license Open Access Published by De Gruyter Open Access May 9, 2018

Penile calciphylaxis in a patient with end-stage renal disease: a case report and review of the literature

Ti-Yuan Yang, Tao-Yeuan Wang, Marcelo Chen, Fang-Ju Sun, Allen W. Chiu and Yu-Hsin Chen
From the journal Open Medicine

Abstract

Penile calciphylaxis is a rare cause of penile gangrene that presents in patients with end-stage renal disease. The rates of comorbidity and mortality of penile calciphylaxis are extremely high. Unlike other penile gangrene, such as Fournier’s gangrene, the benefit of aggressive surgical therapy is controversial. Here we present a case of penile calciphylaxis in a 43-year-old man with end-stage renal disease on hemodialysis. He received total penectomy but died due to multisystem complications 2 weeks after surgery. We review the literature on the management options and outcomes in patients with penile calciphylaxis.

1 Introduction

Calciphylaxis is a serious systemic disorder of smaller arteries, arterioles and capillaries seen in 1% to 4% of patients with end-stage renal disease on hemodialysis and is usually associated with elevated calcium-phosphate product [1]. It is a clinical condition with mortality rate higher than 60% [2]. Penile calciphylaxis is rare because of its rich vascular network and the prognosis is also poor, with a reported overall mortality rate of 64% and mean time to death of 2.5 months [1,3]. The benefit of penectomy is still under debate. Herein, we present a hemodialysis-dependent diabetic patient who presented with subacute distal penile dry gangrene due to penile calciphylaxis, and review the pertinent medical literature.

2 Case report

A 43-year-old man presented with fever, chills and a purulent sternotomy wound. He had a history of end-stage renal disease for which he had been treated with hemodialysis for 6 years, poorly controlled type II diabetes mellitus, hypertension, and double vessel coronary artery disease. He had undergone coronary artery bypass graft surgery 2 months before this presentation, and received debridement for a sternotomy wound infection and pectoralis major myocutaneous flap rotation 1 month before this presentation. One month after admission, he presented with dry gangrene of the distal third of the penis, including the glans and part of the shaft for 7 days (Figure 1). Dry gangrene was also present in both feet, the right ankle and thigh. Serum phosphate was 6.7 mg/dL (2.7-4.5 mg/dL), calcium was 9.8 mg/dL (8.9-10.3 mg/dL), calcium-phosphate product was 65.7 mg2/dl2 (20.6-52.5 mg2/dl2), albumin was 2.4g/dL (3.5-5.0 g/dL), HbA1c was 9.0%, and BMI was 24.8kg/m2. He did not take any anticoagulant medication, such as Warfarin. Computed tomography of his abdomen showed severe diffuse vascular calcifications, including in the branches of bilateral internal iliac arteries (Figure 2). Due to penile pain and progression of necrosis of the distal penis, penectomy was performed. The intraoperative findings after penile degloving showed extensive ischemic damage, and the spongiosal and cavernosal tissues of the pendulous part of the penis showed no signs of vitality. After incision of the cavernous bodies, only blood clots were drained, and therefore we performed total penectomy and perineal urethrostomy. Plastic surgeon consultation suggested not to resect other extragenital gangrene due to patient’s poor condition. The pathological report showed microcalcifications in the stroma and vascular wall consistent with calciphylaxis (Figure 3). Dyspnea and conscious disturbances occurred after three days antibiotics usage for post-operative fever. His overall condition deteriorated and died of respiratory failure and sepsis 2 weeks later.

Figure 1 Gangrenous penis.

Figure 1

Gangrenous penis.

Figure 2 Internal pudendal (large arrow) and penile artery (small arrow) calcification seen on computed tomography.

Figure 2

Internal pudendal (large arrow) and penile artery (small arrow) calcification seen on computed tomography.

Figure 3 Calcifications in the vascular wall within the gangrenous penile shaft.

Figure 3

Calcifications in the vascular wall within the gangrenous penile shaft.

Ethical approval: Research has been complied with all the relevant national regulations, institutional policies and in accordance the tenets of the Helsinki Declaration.

Informed consent: Informed consent has been obtained from all individuals included in this study.

3 Discussion

Calciphylaxis is characterized by medial calcification and intimal fibrosis of medium and small arteries. Mottling of the skin and induration in a livedo reticularis pattern is a characteristic clinical presentation of calciphylaxis, which generally affects the distal extremities, buttocks, and thighs, and sometimes the penis. Penile calciphylaxis has an extremely poor prognosis, with a reported overall mortality rate of 64% and mean time to death of 2.5 months [3]. Cimmino et al. recommend penile biopsy is unnecessary for diagnosis of penile calciphylaxis [4].

A total of 50 cases of penile calciphylaxis have been reported in the English literature (Table 1) [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41]. The average age was 54.5 years (range 32 to 81). Including our case, all patients had end stage renal disease, 42 patients received hemodialysis, 7 patients received peritoneal dialysis and 2 patients were in the pre-dialysis stage. Forty-one patients had diabetes mellitus. Average calcium level was 9.2 mg/dl, average phosphate level was 8.0 mg/dl and average calcium-phosphate product was 72.8 mg2/dl2. The overall mortality rate was 56.5%. Three-month mortality rate was 47.8%. Mean time to death was 97 days and median time to death was a month. There was no correlation between mortality rate and age, diabetes mellitus, calcium level, phosphate level and calcium-phosphate product level.

Table 1

Review of reported cases of penile calciphylaxis with end-stage renal disease.

AuthorsAgeCaPCaPPTHextragenital gangrenepenectomyparathyroidectomy3-month prognosis
(mg/dl)(mg/dl)(mg2/dl2)(pg/mL)
MMH439.86.765.7no datayesyesnodeath
Ivker RA[5]439.25.651.5375yesnoyesalive
Ivker RA[5]587.96.450.689yesyesyesalive
Melikoglu M[6]487.41181.4no datayesyesnodeath
Wood JC[7]568.9980.11280yesyesyesalive
Jhaveri FM[8]629.39.588.474yesnonodeath
Jhaveri FM[8]4410.57.679.81450yesnoyesalive
Jhaveri FM[8]441010.2102405yesnoyesloss
Jhaveri FM[8]4110.67.175.3746yesnonodeath
Jhaveri FM[8]5910.37.476.289yesnoyesdeath
Siami GA[9]447.98.667.9no datayesyesnodeath
Boccaletti VP[10]7210.57.891.9881nononodeath
Rich A[11]34no datano datano datano datayesyesnodeath
Jacobsohn HA[12]609.7987430yesyesnodeath
Karpman E[3]597.99.675.8379yesyesnodeath
Barthelmes L[13]48no datano datano datano datanoyesnodeath
Oikawa S[14]32no datano datano data63yesnoyes[*]death
Rifkin BS[15]61no datano datano datano datayesno datano dataloss
Woods M[16]358.47.462.238noyesnodeath
Halachmi S[17]578.58.576.5375yesnonodeath
Agarwal MM[18]528.57.563.8no datayesnonodeath
Sorensen MD[19]658.5no datano data121noyesnoalive
Ohta A[20]419.85.25118yesyesnoalive
Rizvi T[21]727.47.354315nononoalive
Bhatty TA[22]39no data7.1no data344.7yesnonoalive
Sandhu G[23]5810.210.3105.182nononoalive
Bappa A[24]729.67.370.1315.2yesnonoloss
Shah MA[25]727.96.652.1164yesnonodeath
Prematilleke I[26]6610.45.961.430.8noyesnodeath
Prematilleke I[26]389.97.776.248noyesnoalive
O’Neil B[27]728.9544.51462noyesyesalive
O’Neil B[27]59no datano datano data816yesyesyesalive
O’Neil B[27]6488.164.8516noyesyesalive
Akai A[28]36no datano data56no datayesnonoalive
Kumar V[29]738.811.8103.8633nononoalive
Barbera V[30]5012.88.6110.1615noyesnoalive
Yecies T[31]33no datano datano datano datanoyesnoalive
Cimmino CB[4]6298.475.6no datanononoalive
Cimmino CB[4]388.7no datano datano datayesnonoloss
Cimmino CB[4]497.49.671799.8nononoloss
Haider I[32]61no datano datano data260yesnonodeath
Morrison M[33]60no datano datano datano datayesnonoalive
Hanna RM[34]64913.5121.5612yesyesnoalive
Sarkis E[2]54no datano datano data94yesnonodeath
Malthouse T[35]619.18.475.9155yesnonodeath
Shiraki T[36]76no datano data42127yesnonoalive
Endly D[37]5894.139.8410yesnonodeath
Bashir SO[38]469.57.470.3600nonoyesalive
Maselli G[39]64no datano datano datano datanononoalive
Campbell RA[40]4610.7664.21096noyesnoalive
Olaoye OA[41]819.88.482.31131nononodeath

  1. Ca, calcium; P, phosphate; CaP, calcium-phosphate product; PTH, parathyroid hormone

Parathyroid hormone level was reported in 38 patients and average parathyroid hormone level was 458.9 pg/ml. Secondary hyperparathyroidism was found in 33 patients. One patient underwent parathyroidectomy before and 10 patients underwent parathyroidectomy after calciphylaxis developed. The 3-month mortality rates were 33.3% and 60% in patients undergoing parathyroidectomy after calciphylaxis and patients without parathyroidectomy, respectively (P=0.18). Mortality rate was not correlated with parathyroid hormone level and parathyroidectomy. This finding was different from that reported by Karpman et al., who suggested that parathyroidectomy may improve survival [3]. The possible reason for the difference was that they included patients without documented parathyroid hormone level in their statistics.

Extragenital gangrene was noted in 32 patients. The 3-month mortality rate was higher in patients with extragenital gangrene than in those without extragenital gangrene (60.7% vs. 27.8%, p=0.03). Extragenital gangrene involves more blood vessels and may result in worse prognosis.

Twenty-one patients received partial or total penectomy. The mortality rates were 42.9% and 52% in patients undergoing partial or total penectomy and patients who received local debridement and wound care, respectively (P=0.54). Karpman et al. also reported no statistically significant difference in survival between patients treated with penectomy and those treated with local debridement and wound care [3]. Since penectomy showed no survival benefit, we suggest that penectomy should be considered in the presence of severe pain refractory to analgesics or uncontrolled infection.

Akai A et al. reported a case of penile calciphylaxis who underwent femoral artery to deep dorsal penile vein bypass [28]. After revascularization surgery, pain subsided and the wound healed. Shiraki T et al. reported a case of penile calciphylaxis successfully treated with internal iliac artery balloon-expandable bare metal stent implantation [28]. Two cases were treated with hyperbaric oxygen therapy but both of them died within a month [12,14].

Three cases were treated with sodium thiosulfate, and 2 patients survived [2,23,33]. The possible mechanism of sodium thiosulfate is chelation of calcium ions, dissolution of insoluble calcium deposits and restoration of endothelium [2]. In a retrospective study of 27 patients with calciphylaxis in other locations, 52% resolved with sodium thiosulfate administration [2].

Penile calciphylaxis is a rare disease with poor prognosis because calciphylaxis involves smaller arteries, arterioles and capillaries systemically. Unlike other penile gangrene, such as Fournier’s gangrene, the benefit of aggressive surgical therapy is controversial. Patients with extragenital gangrene have higher rates of mortality. Due to its rarity, there is no consensus regarding the treatment of this disease. Conservative treatment, sodium thiosulfate, hyperbaric oxygen, internal iliac artery stent, revascularization surgery, penectomy and parathyroidectomy have all been described. Literature review showed that penectomy and parathyroidectomy had no significant survival benefit. However, since there is no definite curative treatment, physicians may attempt combining different treatment modalities.

  1. Conflict of interest

    Conflict of interest statement: Authors state no conflict of interest.

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Received: 2018-01-26
Accepted: 2018-03-19
Published Online: 2018-05-09

© 2018 Ti-Yuan Yang et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

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