Cryofibrinogenemia-Induced Cutaneous Ulcers: A Review and Diagnostic Criteria

Abstract

Chronic skin ulcers are frequently encountered in clinical practice and are often due to very heterogeneous etiologies. Cryofibrinogenemia is an unusual cause of non-healing skin ulcers. It is a small-vessel occlusive vascular disorder that results from the precipitation of cryofibrinogens in plasma. The lack of definitive diagnostic criteria means cryofibrinogenemia remains an under-diagnosed entity that causes significant morbidity. One of the most common manifestations of cryofibrinogenemia is skin ulceration. The presence of non-healing ulcers in otherwise healthy patients with no evidence of large-vessel disease should raise the suspicion of essential cryofibrinogenemia. An important clinical feature is the presence of microlivedo, which represents short hyperpigmented linear streaks around the ulcer or even distally about the foot. Histopathologic findings are microthrombi in the dermis and not confined exclusively to the ulcerated area. Cryofibrinogenemia can be secondary to an underlying disorder, so careful investigation to exclude other etiologies is always necessary.

Chilblains

“…Blue toe syndrome, due to distal embolism, is caused by ischemia of the toe. In cryofibrinogenemia, the skin lesions are different from those of pernio with purpura or skin necrosis in acral areas [44]. The clinical presentation of Cold Agglutinin Disease is variable and nonspecific.…”

Inflammatory skin diseases and wounds

“…The diagnosis of cryofibrinogenaemia is made by the typical clinical features in conjunction with a skin biopsy. Here, intravascular thrombi from an eosinophilic amorphous material are found without surrounding inflammation and the presence of cryofibrinogens in the plasma 43 . Cholesterol emboli syndrome is diagnosed when there is a history of surgical procedures or anticoagulation therapy and a skin biopsy shows needle‐shaped clefts in small vessels 44 .…”

“…Here, intravascular thrombi from an eosinophilic British Journal of Dermatology (2022) 187, pp167-177 amorphous material are found without surrounding inflammation and the presence of cryofibrinogens in the plasma. 43 Cholesterol emboli syndrome is diagnosed when there is a history of surgical procedures or anticoagulation therapy and a skin biopsy shows needle-shaped clefts in small vessels. 44 Even though the histopathological findings are not specific, a skin biopsy can be very helpful in differentiating the PG lesion from other differential diagnoses.…”

Pernio — the least severe local cold injury (scientific literature review)

“…Гістопатологічні дані вказують на мікротромби в дермі і не обмежуються виключно ділянкою виразки. Кріофібриногенемія може бути вторинною щодо основного захворювання, тому завжди необхідно ретельне обстеження для виключення іншої етіології [31].…”

“…Хронічні виразки шкіри часто зустрічаються у клінічній практиці і здебільшого мають гетерогенну етіологію. До озноблення потрібно ставитися дуже серйозно, оскільки воно може прогресувати до імерсійної стопи [31,39].…”