Calciphylaxis and Anorexia Nervosa A Case Report and Review

Abstract

Calciphylaxis is a life threatening condition most commonly seen in end stage renal disease, a rapidly growing patient population. Its primary clinical manifestation is painful skin lesions, which are thought to be secondary to metastatic calcification and ischemic damage. Herein, we review the relevant literature and present an atypical case of calciphylaxis. Our patient is a 25-year-old female with a body mass index of 15.3 and a history of chronic renal insufficiency, though never having undergone dialysis. We report what appears to be the first case of calciphylaxis occurring in a patient with a long standing history of anorexia nervosa. This is an unexpected occurrence, as several studies have cited obesity as a major risk factor for the development of calciphylaxis.

Introduction

Calciphylaxis (CPX) is a rapidly progressing and life threatening condition. It manifests as painful, violaceous skin lesions classically described in end stage renal disease patients undergoing hemodialysis. ¹  Although the condition is rare, it is likely that the internist will be challenged with recognizing this condition sometime in his or her career as the number of patients on the road to renal replacement therapy continues to grow. In this report, we present what appears to be the first case of CPX occurring in a patient suffering from anorexia nervosa, with a body mass index (BMI) of approximately 15. This is a unexpected finding as obesity is commonly sited as a major risk factor for the development of CPX, with the average BMI reported as being greater than 30. ²  We also review the relevant literature regarding CPX to discuss other risk factors, clinical features, and how this condition can be managed.

Case Report

A 25-year-old Caucasian female presented with progressive, painful skin lesions and acute renal failure superimposed on chronic renal failure. Her co-morbid conditions included gout, purge and restriction type anorexia nervosa (for 7 years), depression, chronic interstitial nephritis (for 2 years), anemia, and secondary hyperparathyroidism. The patient’s chronic interstitial nephritis resulted from chronic hypokalemia and was likely the result of laxative and diuretic abuse. Her medications include calcitriol, calcium carbonate, ferrous sulfate, and a non-calcium phosphate binder, sevelamer (Renagel®).

Physical exam revealed a frail young woman in mild to moderate distress. Vital signs were recorded: blood pressure 135/65 mmHg, temperature 36.2°C , and heart rate 114 beats/min. Her BMI was calculated to be 15.3. No thyromegaly or neck mass was noted. Lower extremity exam revealed painful, diffusely mottled skin with purple indurated areas on both lateral thighs. Also noted was a black eschar with a purpuric border on the left calf (figure 1). Relevant findings from laboratory investigation included high normal serum calcium of 9.6 mg/dL, elevated serum phosphorous of 10.0 mg/dL, elevated intact parathyroid hormone level of 7704 pg/dL, and elevated blood urea nitrogen and serum creatinine of 141 mg/dL and 6.7 mg/dL, respectively.

CPX was suspected and steps were taken to provide appropriate wound care and to normalize the patient’s metabolic derangements: calcitriol was discontinued, the dosage of sevelamer was increased, and a calcimimetic, cinacalcet (Sensipar®) was initiated. Daily hemodialysis was also initiated to lower the calcium x phosphorous product and to optimize platelet function in anticipation of a possible parathyroidectomy. Over the course of the next 48 hours the patient’s skin lesions progressed (figure 2) and the patient underwent a 3 and 2/3 parathyroidectomy (leaving one-third of one gland functionally intact) following the third dialysis treatment. Pathological exam of the gland revealed diffuse hyperplasia without any adenoma. Postoperatively, intravenous and oral calcium was administered and the patient’s lesions began to stabilize. Vitamin D supplementation was provided only on a temporary basis until serum calcium was normalized.

Discussion

CPX, also known as calcific uremic arteriopathy, is a process of metastatic calcification localized primarily to the middle layer of systemic arterioles. ¹  It is a potentially fatal condition with a disease-specific one year survival rate of 45.8%. ³  Although isolated cases have been reported in patients with normal kidney function, CPX is primarily recognized as a complication of end stage renal disease with a prevalence of 4.1% in patients receiving hemodialysis. ⁴  Details of the pathogenesis have yet to be elucidated.

Clinical presentation is critical to understand as the confirmatory measure, incisional biopsy looking for medial calcification of small vessels, is avoided whenever possible because of poor wound healing and increased risk of infection associated with the procedure. ¹  Due to the ischemic damage that results from vascular calcification and local thrombus formation, painful skin lesions are the primary clinical manifestation. These lesions tend to progress rapidly and sequentially: from painful or purpuric plaques to symmetrical violaceous discolorations (livedo reticularis) to non-healing ulcers to necrosis with eschar formation. ^{1 2 5 6}  These lesions typically follow a symmetrical distribution that is proximal (abdomen, thigh, buttock) or distal (acral areas, calf, forearm, genitalia) in nature, with the former having a higher mortality rate. ¹  Biochemical factors that have been associated with CPX and that can help in supporting the diagnosis include serum phosphate > 5 mg/dL (68% of cases), parathyroid hormone > 2-3 times the upper limit (80% of cases), and uremic findings (azotemia, anemia, etc). ⁷

Management hinges on three aspects of care: 1) meticulous wound care. ⁸  This includes antibiotic therapy if an infection is suspected and surgical debridement if removal of devitalized tissue is needed. The importance of proper wound care cannot be overstated, as sepsis resulting from wound infection has a mortality rate of 60 – 80%. ⁹  2) rapid lowering of calcium and phosphorous. This can be tried with medical management initially (e.g. calcimimetic, non-calcium phosphate binder, discontinuation of calcitriol). ¹⁰  Many patients, including ours, with hypercalcemia, hyperparathyroidism, and skin lesions refractory to medical management have shown significant therapeutic benefit from parathyroidectomy. ^{6 11 12}  3) aggressive pain management, as over the counter strength medication is often insufficient. ¹³  Experimental treatment modalities that have shown favorable outcomes include hyperbaric oxygen therapy ¹⁴ and vacuum assisted closure. ¹⁵

CPX occurs most commonly in Caucasian women, patients undergoing dialysis for greater than one year, and presents at a median age of 48 years old. ^{1 6}  Modifiable risk factors include malnutrition, hyperparathyroidism, warfarin administration, systemic hypotension, and obesity. ¹⁶  Among the atypical features of our patient’s presentation, including her young age and having never undergone dialysis, the most striking is her co-morbid condition of anorexia nervosa as several studies have identified obesity as a significant risk factor. Bleyer et al ² reported nine patients with an average BMI of greater than 30, Janigan and Hirsch ¹⁷ reported 14 of 17 patients as being morbidly obese, and Wilmer et al ¹ reported 21 patients with an average weight of 94 kg. None of these studies or the case reports reviewed in the literature identified any of their patients as being anorexic. We report, to the best of our knowledge, the first case of CPX in a patient also suffering from anorexia nervosa. It is our hope that in reporting this case it will improve the likelihood of a timely diagnosis in those patients presenting with features that are atypical, but equally as dangerous.

Acknowledgement

We would like to thank Dr. Theodore A. Spevack for his critical reading of the manuscript.