Cold Agglutinin Disease – The Importance of Cutaneous Signs

Abstract

We present the case of a woman where the diagnosis of cold agglutinin disease could be made after we had noticed slight cutaneous manifestations during a routine examination. Leading symptoms were livedo reticularis of the thighs and a history of acrocyanosis and Raynaud’s phenomenon upon cold exposure. The current knowledge about the etiology, clinical presentation and treatment of the disease is briefly discussed.

Livedo reticularis: An update

“…32,33 Cold agglutinin disease is another cold-associated condition that may lead to cutaneous findings such as acrocyanosis and LR. 34,35 This disease is caused by monoclonal autoantibodies that agglutinate erythrocytes, causing intravascular sludging and compliment mediated hemolysis. 34,35 This condition is important to identify because some cases are associated with an underlying infection or lymphoproliferative disorder.…”

Cold agglutinin disease

“…[38][39][40][41][42][43][44][45] In addition to hemolysis, clinical manifestations include coldinduced circulatory symptoms; livedo reticularis, Raynaud disease, acrocyanosis and, rarely, cutaneous necrosis. 20,[46][47][48][49] Berentsen et al 5 reported cold-induced symptoms in more than 90% of patients. Splenomegaly is not prominent in CAD.…”

Low-Titer Cold Agglutinin Disease with Systemic Sclerosis

“…There are two types of cold agglutinins: monoclonal and polyclonal antibodies (2,10). Monoclonal antibodies are mostly found in patients with the "idiopathic" form or chronic CAD or with proliferative B-cell diseases.…”

“…Polyclonal antibodies are associated with the "secondary" form in the setting of an infectious disease, especially that caused by mycoplasma pneumoniae, or malignant non-Hodgkin lymphoma. These polyclonal forms are usually of a benign, transitory nature with low cold agglutinin titers (10).…”