Cutaneous necrosis by cold agglutinins associated with glomeruloid reactive angioendotheliomatosis

Abstract

The cold agglutinin syndrome is a haemolytic disorder that can cause skin lesions, mainly on the acral areas, with acrocyanosis being the most frequent manifestation. Cutaneous necrosis due to cold agglutinins is very rare. Reactive angioendotheliomatosis (RAE) is an uncommon condition that exclusively affects the skin, characterized by a hyperplasia of endothelial cells and pericytes that can result in the formation of glomeruloid structures. The association of cold agglutinin syndrome with glomeruloid RAE has not been previously described. We report a 70-year-old man diagnosed as having a B-cell low-grade non-Hodgkin's lymphoma. He had two episodes of cutaneous necrosis in acral areas which were related to exposure to cold and due to IgM anti-I(T) cold agglutinins. Biopsy specimens showed vessel proliferations composed of dilated vascular spaces in the dermis and subcutis. Some vessel lumina were partially occluded by eosinophilic thrombi of fibrin and erythrocytes. Numerous closely packed capillaries were observed within pre-existing dilated vessels. This intravascular proliferation of capillaries displayed a glomeruloid pattern. We emphasize the possible presence of a cold agglutinin syndrome in patients with skin necrosis and findings of RAE with a glomeruloid pattern. Cold agglutinaemia may cause these distinctive histological changes.

Increased Expression of VEGF in Glomeruloid Reactive Angioendotheliomatosis

“…Histology of lesional skin showed a glomeruloid picture of small vessels as described before by Wick and Rocamora [14], Porras-Luque et al [16]and Salama and Jenkin [22]. In the latter publication the patient suffered from MGUS and later went on to develop chronic B-cell leukemia.…”

“…RAE, on the other hand, has remained pathogenetically less well elucidated, although hypotheses have been proposed regarding RAE as a hypersensitivity reaction to foreign antigens suggested by its frequent association with infections [1, 2, 5, 12, 13, 14]. Moreover, an association with milk intolerance [13], luminal cryoprotein deposition [15], cold agglutinins [16], antiphospholipid syndrome [17]and severe atherosclerotic disease [18]has been described.…”

Cold Agglutinin Disease – The Importance of Cutaneous Signs

“…acrocyanosis, which can sometimes be painful, Raynaud’s phenomenon and livedo reticularis [10, 11, 12, 13]. Rare findings are cold urticaria, distal loss of sensitivity in the extremities and sometimes even hemorrhagic blisters and gangrene [14]. Hemolytic anemia is usually present but can be very mild in cases with a moderate titer of cold agglutinins.…”

Angioendotheliomatosis proliferans systematisata

“…Die RAE bleibt stets auf die Haut beschränkt.Als assoziierte Erkrankungen der reaktiven Angioendotheliomatose wurden die subakute bakterielle Endokarditis (häufigste Assoziation), Lungentuberkulose, Kuhmilchallergie, chronische lymphatische Leukämie,Kryoproteinämie, Leberzirrhose und periphere arterielle Verschlusskrankheit beschrieben, sodass ätiologisch möglicher-weise infektallergische Mechanismen, eine reaktive Endothelzellproliferation im Rahmen der intravasalen Ablagerung der Kälteproteine oder die Produktion von Angiogenesefaktoren eine Rolle spielen [5,11,12,15,16,18,19,22].Andererseits lässt sich bei einem Teil der Patienten keine assoziierte Erkrankung diagnostizieren [3,11].…”