Calcinosis of the cutis and subcutis: An unusual nonimmunologic adverse reaction to subcutaneous injections of low-molecular-weight calcium-containing heparins

Background: Local side effects at the injection sites of low-molecular-weight heparins are rare and can be of immunologic or nonimmunologic origin. Calcinosis cutis is a rare disorder and occurs in various circumstances. In patients with chronic renal failure the risk of pathologic calcifications is raised due to elevated calcium-phosphorus products. Objective: Five patients suffering from renal failure developed remarkable cutaneous and subcutaneous nodules or plaques following subcutaneous nadroparin-calcium injections. Our aim was to evaluate the morphology and precipitation factors of these calcifications and to discuss immunological and nonimmunological differential diagnoses. Methods: Histological examination, spectroscopic analysis, ultrasonography, allergy testing and reexposition testing including non-calcium heparins were performed. Results: Histology using the van Kossa staining technique revealed calcinosis of the dermis and subcutis. Ultrasonography showed focal subcutaneous calcifications. In all patients the calcium-phosphorus products were elevated. Conclusion: Clinicians should be aware that patients with renal failure and elevated calcium-phosphorus products may be at risk of developing calcinosis cutis at calcium-containing heparin injection sites. As a consequence, we propose the use of non-calcium heparins in these patients.