Albany Medical Review - January 2002

Case Report-
A 41-year-old dialysis patient with mysterious skin lesions

Lorilyn Cooley, MD

This patient is a 41-year-old Caucasian female admitted with three painful leg ulcers. The first leg lesion began to appear 3 months ago as nodule on her lateral right calf. Over time the central area broke down and a violaceous ulcer developed within an erythematous base. Two additional lesions formed with similar yet asynchronous progressions. The lesions were extremely painful; described as both stabbing and burning in quality. The pain was partially relieved while standing and with large doses of narcotics. There was no history of recent trauma, fevers, drainage, claudication, vascular insufficiency, hypoesthesias, myalgias, arthralgias, rashes or exposure to arthropods.

Her past medical history includes chronic renal failure secondary to poorly controlled hypertension. She was initially treated with peritoneal dialysis which began in February 1995. After multiple complications the CAPD catheter was removed in March 1996. Hemodialysis was subsequently started requiring multiple permacaths and arteriovenous fistulas. In October 2000 she developed MRSA catheter line sepsis. Further the patient had ischemic cardiomyopathy and congestive heart failure after a myocardial infarct, atrial fibrillation and mitral regurgitation.

She had peptic ulcer disease and iron deficiency anemia. She had a history of anxiety disorder and occasional migraine headaches. Other diagnoses included uncomplicated herpes zoster and a reactive tuberculin test in 1996 treated with Isoniazid for 5 months. There is no history of rheumatic heart disease or diabetes mellitus. Her surgical history includes secondary hyperparathyroidism treated with a subtotal (3/4) parathyroidectomy. She underwent pinning of a femoral neck fracture in 1997. She has never abused alcohol, tobacco or illicit drugs.

Her medications on admission were digoxin 0.125mg TIW, metoprolol 100mg BID, amiodarone 200mg BID, carvedilol 3.125mg BID, quinapril 10mg BID, alprazolam 0.25mg QD, warfarin 5mg QD, lansoprazole 30mg QD, cisapride 10mg QID, multivitamin with iron QD, renagal 1 tablet TID, vitamin D and calcitrol combination 0.5mcg TIW, fentanyl transdermal 50mcg/hour Q3 days, aspirin 325mg QD and hydrocodone/acetaminophen q6h PRN for pain.

Upon entering the room, the patient was found standing, leaning on a chair and appeared to be in significant pain. The standing blood pressure was 115/56, heart rate 82, respiratory rate 18 and temperature 98o F. The head and neck was normal including a normal thyroid and lymphatic exam. The chest revealed a quiet precordium, normal first and second heart sounds and a typical mitral regurgitation murmur (2/6). The abdomen was normal. On examination of the skin one small ecchymosis was found on the right forehead and a few small ecchymoses on the right chest. There was livedo reticularis covering both legs. Her lower extremities had multiple ulcerations of varying sizes and depths with erythema along the borders and central necrosis. The lesions were not particularly warm and there was no obvious drainage. They were extremely tender to palpation. Her joints were non-tender and had full range of motion. There was no cyanosis, clubbing or edema of uninvolved areas. The peripheral pulses were normal in all four extremities. The neurological exam was normal. The electrocardiogram showed left ventricular hypertrophy and a PA and lateral chest radiograph showed cardiomegaly and mild bilateral pleural effusions. Laboratory data showed a WBC of 10.9 (neutrophils 75%, lymphocytes 15%, monocytes 10%), Hgb 8.8 g/dl, BUN 45 mg/dl, Cr 5.8 mg/dl Ca 8.8 mg/dl, Alb 3.1 g/dl, Phos 6.4 mg/dl. The serum PTH level was 212 pg/ml.

Two views of a characteristic lesion. (click photo for close-up view)

Discussion:

Painful necrotic skin nodules complicate several diseases with various pathophysiologies. One subset of differential diagnoses is vascular entities including vasculitis (of various forms), venous insufficiency, antiphospholipid syndrome, coumadin necrosis and cholesterol emboli. Systemic conditions that affect the subcutaneous tissue are also known to cause this type of skin lesion. These include pancreatic panniculitis, erythema nodosum and weber-christian syndrome. Infectious causes of necrotic skin lesions include bacterial endocarditis and cellulitis. Dialysis patients can develop this type of skin lesion because of their unique propensity for progressive acral gangrene of dialysis and calciphylaxis. This case is an example of calciphylaxis.

Calciphylaxis is a serious skin condition in patients with secondary hyperparathyroidism and ESRD. In essence, it is metastatic calcification of the skin. It affects approximately 1% of patients with ESRD per year of dialysis and is more common in Caucasian women at the forth to fifth decades of life.¹ It usually begins as livedo reticularis then progresses to plaques or nodules and finally culminates as painful skin ulcerations. This disease predominately affects the lower extremities. Involvement of the trunk or proximal extremities is associated with a poorer prognosis.² The onset of calciphylaxis in ESRD is quite variable, occurring from one month to a decade after the initiation of hemodialysis.¹ The etiology is unknown. One theory postulates that calciphylaxis is caused by a calcium:phosphate imbalance and increased PTH levels.^1,3 This results in precipitation and deposition of a calcium:phosphate product in vessel walls. The resulting inflammation and fibrosis leads to thrombi and arterial insufficiency.⁴ An alternative theory, proposed by Mehta et. al., suggests that protein c deficiency leads to calciphylaxis in renal failure patients by causing a hypercoagulable state. This theory also postulates thrombotic occlusion of the arterial supply.⁵ Diagnosis is established by skin biopsy. Biopsy of a lesion shows calcification in the media of small and medium sized vessels.³ Untreated ulcerations continue to expand in width and depth. Larger lesions are associated with serious local and disseminated infections. Mortality rates are higher than 80%.¹ Management is aimed at treating hyperparathyroidism. Aluminum based antacids can be used to normalize phosphate levels.⁵ Common practice is subtotal or total parathyroidectomy. This treatment has never been shown to significantly improve outcome.^2,6 Meticulous wound care is essential.⁶ Skin grafting is sometimes needed with large nonhealing wounds.¹ Pain control is one of the most challenging management issues. Calciphylaxis is a seriously debilitating illness that remains incurable.

HOSPITAL COURSE:

Once admitted, the patient was placed on vancomycin and tobramycin for suspected secondary infection. Her pain was treated with fentanyl and acetominophen/oxycodone 325/5mg. A diagnostic skin biopsy confirmed calciphylaxis. She required surgical wound debribement and skin grafting of the large ulcers. Intensive hemodialysis and completion parathyroidectomy were performed for the calciphylaxis because her serum PTH levels were elevated. Postoperatively, her serum calcium and PTH levels stayed within normal limits. Despite vigorous treatment over several months she continued to suffer from severe lower extremity pain and skin ulcerations.

Acknowledgments:

I would like to thank Dr. K Mok for the photographs. Permission was granted by patient for educational use.

References:

1. Budisavljevic MN, Cheek D, Ploth DW Calciphylaxis in chronic renal failure. J Am Soc Nephrol. 7(7): 978-982, 1996.

2. Chan YL, Mahony JF, Turner JJ, et al. The vascular lesions associated with skin necrosis in renal disease. Br J Dermatol 109: 85-95, 1983.

3. Kalagji AN, Douglass MC, Chaffins M, Lowe L. Calciphlaxis: a cause of necrotic ulcers in renal failure. J cutan med and surg. 2 (4): 242-244, 1998.

4. Hafner J, Keusch G, Wahl C, et al. Uremic small artery disease with medial calcification and intimal hyperplasia (so-called calciphylaxis): a complication of chronic renal failure and benefit from parathyroidectomy. J Am Acad dermatology. 33: 954-962, 1995.

5. Mehta RL, Scott G, Sloand JA, et al. Skin necrosis associated with aquired protien c deficiency in patients with renal failure and calciphylaxis. Am J Med 88: 252-257, 1990.

6. Worth RL Calciphylaxis: Pathogenesis and therapy. Journal of cutan med and surg. 2 (4): 245-247, 1998.

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30.01.2002

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