A Deadly Product: A Deadly Product: CalcificCalcific Uremic Uremic ArteriolopathyArteriolopathyMisdiagnosed as Misdiagnosed as CellulitisCellulitis

KaumakaKaumaka ShimatsuShimatsu, MD, , MD, ShubhaShubha AnanthakrishnanAnanthakrishnan MD, MD, AnkurAnkur Sharma, MDSharma, MD

University of California, Davis Medical Center; Sacramento, CAUniversity of California, Davis Medical Center; Sacramento, CA

Figure 1. Nonulcerative calcific uremic arteriolopathy of the breast

demonstrating erythema with violaceous and reticulated skin.

Image obtained from Google images

Figure 2. Biopsy showing subepidermal cleavage plane secondary to

ischemia, blood vessels filled with erythrocytes, and extravasated

erythrocytes suggestive of early thrombosis

Learning Objectives•Calcific uremic arteriolopathy (CUA) is a

calcification of vessels in the dermis and

subcutaneous fat, leading to ischemia and tissue

necrosis

•CUA causes painful skin lesions that can mimic

cellulitis in dialysis patients with elevated

calcium-phosphate product and can result in high

mortality

•Clinicians in both outpatient and inpatient

settings should be highly suspicious of painful

skin lesions in these patients in order to make an

early diagnosis and initiate treatment of CUA

Learning Objectives

Case presentation•71 yr old male with type 2 DM, Stage 5 CKD on

hemodialysis, systolic CHF, and history of PE,

previously on Coumadin presented to his PCP

with painful erythema over his left thigh

•He was diagnosed with cellulitis and treated with

one dose of IM ceftriaxone and started on a

course of keflex.

•He returned seven days later with extension of

the erythema, warmth & tenderness, now

doubled in size so he was admitted for

management of cellulitis after failed outpatient

treatment.

•He was afebrile and dermatologic exam was

notable for a 7”X8” exquisitely tender, indurated

plaque on an erythematous background over his

left medial thigh

•Labs showed no leukocytosis but were notable

for an elevated phosphorus of 9.5 mg/dL,

calcium of 9.4 mg/dL and PTH of 643 pg/mL.

•Lower extremity CT showed skin thickening and

subcutaneous edema extending to the

intermuscular fascia without subcutaneous

emphysema or abscess.

•He was admitted with a diagnosis of cellulitis

and was started on vancomycin and ceftriaxone

Case Presentation

Hospital course

•Nephrology was consulted for routine dialysis on hospital day

2 and suggested the diagnosis of CUA

•Bone scan showed moderately intense increased uptake in the

medial left thigh consistent with CUA, biopsy (Figure 2) was

supportive of CUA

• His dialysis was intensified and he was started on sodium

thiosulphate

•He developed new lesions on his right thigh, calf and left

ankle. His lesions enlarged, developed bullae, then ulcers.

•His phosphorus level eventually normalized and his skin

lesions improved

Hospital Course

Discussion• Prevalence: ~1% of CKD patients and 4.1% dialysis patients.

• Risk factors: hyperphosphatemia, elevated Ca2+ X PO4

product, calcium and vit D supplements, hypoalbuminemia,

female gender, warfarin use, obesity1

• Pathogenesis: vascular smooth muscle cells dedifferentiate

into "osteoblast"-like cells that produce bone matrix proteins2

• Lesions occur in vascular regions with thick adipose tissue like

breast, abdomen and thighs. They are exquisitely painful and

violaceous, forming plaques or nodules with skin mottling,

then bullae and ulcers, progressing to gangrene and sepsis.

• Six month mortality ~ 33% in plaques but > 80 % ulcers1

• Diagnosis is clinical, supported by bone scan. Tissue biopsy is

diagnostic but risks increased lesions and secondary infection1

• Management is supportive with intensified hemodialysis,

aggressive wound care and sodium thiosulfate (based on

success in case reports), duration usually 12 months

• Sodium thiosulfate may increase solubility of ca-phos deposits

• Prevention: goal Ca2+ × PO4 product < 55 mg2/dL2, PO4 < 5.5

mg/dL, Ca2+ < 9.6 mg/dL4

Discussion

References1. Fine A, Zacharias J. Calciphylaxis is usually non-ulcerating: risk factors, outcome and therapy. Kidney Int 2002; 61:2210.

2. Rivet J, Lebbe C, Urena P, Cordoliani F, Martinez F, Baglin AC, et al: Cutaneous calcification in patients with end-stage

renal disease: a regulated process associated with in situ osteopontin expression. Arch Dermatol 2006; 142: 900-906.

3. Goldsmith DJ: Calcifying panniculitis or ‘simple’ inflammation? Biopsy is better than a bone scan. Nephrol Dial

Transplant 1997; 12: 2463 – 2464

4. Block GA, Port FK: Re-evaluation of the risks associated with hyperphosphatemia and hyperparathyroidism in dialysis

patients: recommendations for a change in management. Am J Kidney Dis 2000; 35: 1226 – 1237.

Authors would like to acknowledge Dr. Maxwell A. Fung, Pathology Dept, UCDMC for pathology images

References