Thank you, Hailen, for presenting a case of an older woman with ESRD on PD who presented with a week of progressive pain in her bilateral calves, found to have very tender subcutaneous nodules on exam, a calcium-phosphorus product of ~75, and imaging findings of calcium deposition in the arteries and subcutaneous tissue – putting it all together, concerning for calcemic uremic arteriopathy!
- The differential diagnosis for subcutaneous nodules is extensive! Starting with a framework to break down categories of disease can be useful, such as primary inflammatory causes, infectious causes (both direct infection and via distant immunephenomena), benign causes, and malignant causes.
- Calciphylaxis, now called calcemic uremic arteriopathy is a rare disorder associated with ESRD patients that leads to skin ischemia and necrosis. See more below!
Calcemic Uremic Arteriopathy – check out this 2014 review for more details
- Thought to develop due to disruption of balance between factors favoring calcification and those preventing pathologic calcification
- Likely a combination of passive mineralization in setting of high calcium-phosphorus product, as well as abnormal active cellular processes
Hallmarks of Disease:
- Vasculopathy with extensive medial calcification
- HIGH risk of cardiovascular mortality
Risk Factors: #1 CKD/ESRD
- Demographics: Female sex, white race
- Comorbidities: Diabetes mellitus, Obesity, Secondary hyperparathyroidism
- Labs: Calcium-phosphate product > 70, Low serum albumin, Elevated AlkPhos, Protein C and/or S deficiency
- Time on HD
- Medications: Vitamin D supplementation, Calcium-based phosphate binders, warfarin, corticosteroids, iron dextran, erythropoietin,
- Often initially present as excruciatingly painful subcutaneous nodules with violaceous mottling, similar to livedo reticularis. Lesions generally progress to forming ulcers and eschars as a result of ischemic necrosis.
- Main body areas affected are those with higher fat concentrations: breast, abdomen, thighs, hips.
- Secondary infection VERY common
- Often made clinically, though histopathology is considered the gold standard.
- Medial calcification of small arteries and arterioles with intimal hyperplasia, inflammation, endovascular fibrosis, thrombosis and tissue necrosis. Panniculitis can also be present.
- However, biopsy does raise concern for initiating a new ulcer that may not heal!
- Take home: biopsy when clinical picture is not clear in order to rule out other diagnoses such as warfarin-induced skin necrosis, vasculitis, cholesterol embolism syndrome, nephrogenic systemic fibrosis
- Other diagnostic modalities include:
- Bone scintography – sensitivity of 97% in detecting abnormal calcifications
Treatment (from the 2014 review by Yerram and Chaudhary linked above):