Case Presentation: An 18 year old male with Diabetes Mellitus 1 was admitted for management of painful foot ulcerations after having submerged his feet daily in 20 hour ice baths for relief of chronic foot pain. On exam, there were numerous symmetric, foul-smelling, tender, shallow ulcers with overlying crusting and purulent drainage on bilateral dorsal feet with sharp demarcation at the ankles. Pulses were intact. Laboratory workup was significant for neutrophilic leukocytosis, elevated inflammatory markers and negative initial vasculitis workup including cryoglobulin. Skin biopsy showed necrotic skin and acute inflammation and was unable to rule out vascular targeted process. Cultures grew several gram positive organisms. A diagnosis of cold-induced trauma with superimposed multi-bacterial wound infection was made with suspected erythromelalgia as the cause of his chronic foot pain. After discharge, repeat cryoglobulins were positive and the patient developed palpable purpura in the regions of previously noted ulcerations. He was diagnosed with cryoglobulinemia and work-up for underlying cause is pending. He continues to improve with wound care.

Discussion: Cryoglobulinemia involves immunoglobulins that undergo precipitation at low temperatures and re-dissolve when warmed. Precipitation often results in vasculitis manifesting as petechiae and palpable purpura. Given his history of autoimmune disease, our patient was at increased risk for cryoglobulinema and his ice baths may have further promoted precipitation of underlying circulating immunoglobulins. Further, his skin trauma and associated ulcerations likely disguised the usual exam findings until the ulcers began to resolve. However, this diagnosis was thought to be ruled out when his first cryoglobulin screen was found to be negative. Testing is especially difficult for cryoglobulins due to the absences of reference range and collection standards along with the rigidity required to preserve testing temperature settings. For a reliable collection, blood should be kept warmed at 37 degrees celsius for up to seven days to avoid precipitation. With these obstacles to a reliable result in mind and our lab without a standardized method for collection and handling, it is likely that our patient’s initial negative testing was a false negative and improper testing protocol delayed his true diagnosis.

Conclusions: As demonstrated in this case, patient care is highly dependent on accurate laboratory collection and handling, with treatment and management contingent upon reliable results. Standardization is necessary for laboratory cryoglobulin detection. Until then, when cryoglobulinemia is clinically suspected, a single negative laboratory test does not exclude cryoglobulin-mediated disease and a repeat sample should be drawn with ensured appropriate temperature, transport and separation.