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Open Med. 2018; 13: 158-163
Case report
Ti-Yuan Yang, Tao-Yeuan Wang, Marcelo Chen, Fang-Ju Sun, Allen W. Chiu, Yu-Hsin Chen*
Penile calciphylaxis in a patient with end-stage
renal disease: a case report and review of the
literature
https://doi.org/10.1515/med-2018-0025
received January 26, 2018; accepted March 1 9, 2018
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 gan-
grene, such as Fournier’s gangrene, the benefit of aggres-
sive 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 man-
agement options and outcomes in patients with penile
calciphylaxis.
Keywords: Penile calciphylaxis; Penile gangrene; Penec-
tomy; End-stage renal disease; Microcalcification
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-phos-
phate product [1]. It is a clinical condition with mortal-
ity 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 puru-
lent sternotomy wound. He had a history of end-stage
renal disease for which he had been treated with hemo-
dialysis 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 pec-
toralis major myocutaneous flap rotation 1 month before
this presentation. One month after admission, he pre-
sented 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), calci-
um-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 anticoagu-
lant medication, such as Warfarin. Computed tomogra-
phy of his abdomen showed severe diffuse vascular cal-
*Corresponding author: Yu-Hsin Chen, Department of Urology,
Mackay Memorial Hospital, Taipei, Taiwan
Department of Medicine, Mackay Medical College, New Taipei City,
Taiwan, E-mail: walterchen0702@gmail.com
Ti-Yuan Yang, Marcelo Chen, Allen W. Chiu, Department of Urology,
Mackay Memorial Hospital, Taipei, Taiwan
Ti-Yuan Yang, Allen W. Chiu, Department of Medicine, Mackay Medi-
cal College, New Taipei City, Taiwan
Allen W. Chiu, School of Medicine, National Yang-Ming University,
Taipei, Taiwan
Tao-Yeuan Wang, Department of Pathology, Mackay Memorial Hos-
pital, Taipei, Taiwan
Marcelo Chen, Department of Cosmetic Applications and Manage-
ment, Mackay Junior College of Medicine, Nursing and Management,
Taipei, Taiwan
Open Access. © Ti-Yuan Yang et al., published by De Gruyter. This work is licensed under the Creative Commons Attribution-NonCom-
mercial-NoDerivatives . License.
Penile calciphylaxis in a patient with end-stage renal disease 159
cifications, including in the branches of bilateral internal
iliac arteries (Figure 2). Due to penile pain and progres-
sion of necrosis of the distal penis, penectomy was per-
formed. 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.
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 calciphy-
laxis 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) [2-41]. 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. For-
ty-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
Figure 1: Gangrenous penis.
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.
160Ti-Yuan Yang et al.
Table 1: Review of reported cases of penile calciphylaxis with end-stage renal disease.
Authors Age
Ca PCaP PTH extragenital
gangrene penectomy parathyroidec-
tomy
-month
prognosis
(mg/dl) (mg/dl) (mg/dl) (pg/mL)
MMH . . . no data yes yes no death
Ivker RA[] . . . yes no yes alive
Ivker RA[] . . . yes yes yes alive
Melikoglu M[] . . no data yes yes no death
Wood JC[] . . yes yes yes alive
Jhaveri FM[] . . . yes no no death
Jhaveri FM[] . . . yes no yes alive
Jhaveri FM[] . yes no yes loss
Jhaveri FM[] . . . yes no no death
Jhaveri FM[] . . . yes no yes death
Siami GA[] . . . no data yes yes no death
Boccaletti VP[] . . . no no no death
Rich A[] no data no data no data no data yes yes no death
Jacobsohn HA[] . yes yes no death
Karpman E[] . . . yes yes no death
Barthelmes L[] no data no data no data no data no yes no death
Oikawa S[] no data no data no data yes no yes* death
Rifkin BS[] no data no data no data no data yes no data no data loss
Woods M[] . . . no yes no death
Halachmi S[] . . . yes no no death
Agarwal MM[] . . . no data yes no no death
Sorensen MD[] . no data no data no yes no alive
Ohta A[] . . yes yes no alive
Rizvi T[] . . no no no alive
Bhatty TA[] no data . no data . yes no no alive
Sandhu G[] . . . no no no alive
Bappa A[] . . . . yes no no loss
Shah MA[] . . . yes no no death
Prematilleke I[] . . . . no yes no death
Prematilleke I[] . . . no yes no alive
O’Neil B[] . . no yes yes alive
O’Neil B[] no data no data no data yes yes yes alive
O’Neil B[] . . no yes yes alive
Akai A[] no data no data no data yes no no alive
Kumar V[] . . . no no no alive
Penile calciphylaxis in a patient with end-stage renal disease 161
correlation between mortality rate and age, diabetes mel-
litus, calcium level, phosphate level and calcium-phos-
phate product level.
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 calciphy-
laxis 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 parathy-
roid hormone level in their statistics.
Extragenital gangrene was noted in 32 patients. The
3-month mortality rate was higher in patients with extra-
genital gangrene than in those without extragenital gan-
grene (60.7% vs. 27.8%, p=0.03). Extragenital gangrene
involves more blood vessels and may result in worse prog-
nosis.
Twenty-one patients received partial or total penec-
tomy. 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 sig-
nificant 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 implan-
tation [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 mecha-
nism 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
Barbera V[] . . . no yes no alive
Yecies T[] no data no data no data no data no yes no alive
Cimmino CB[] . . no data no no no alive
Cimmino CB[] . no data no data no data yes no no loss
Cimmino CB[] . . . no no no loss
Haider I[] no data no data no data yes no no death
Morrison M[] no data no data no data no data yes no no alive
Hanna RM[] . . yes yes no alive
Sarkis E[] no data no data no data yes no no death
Malthouse T[] . . . yes no no death
Shiraki T[] no data no data yes no no alive
Endly D[] . . yes no no death
Bashir SO[] . . . no no yes alive
Maselli G[] no data no data no data no data no no no alive
Campbell RA[] . . no yes no alive
Olaoye OA[] . . . no no no death
Ca, calcium; P, phosphate; CaP, calcium-phosphate product; PTH, parathyroid hormone
* Calciphylaxis was developed after parathyroidectomy.
Table 1 continued: Review of reported cases of penile calciphylaxis with end-stage renal disease.
162Ti-Yuan Yang et al.
with calciphylaxis in other locations, 52% resolved with
sodium thiosulfate administration [2].
Penile calciphylaxis is a rare disease with poor prog-
nosis 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 thiosul-
fate, hyperbaric oxygen, internal iliac artery stent, revas-
cularization surgery, penectomy and parathyroidectomy
have all been described. Literature review showed that
penectomy and parathyroidectomy had no significant sur-
vival benefit. However, since there is no definite curative
treatment, physicians may attempt combining different
treatment modalities.
Conflict of interest statement: Authors state no conflict
of interest.
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