Livedoid vasculopathy, calciphylaxis, and Martorell's hypertensive ulcer: update on ischemic ulcers due to impaired microcirculation of the lower limbs

Abstract

Ischemic ulcers due to compromised microcirculation of the lower limbs cause painful ulcers that represent a challenge for the correct diagnosis and treatment. Livedoid vasculopathy, calciphylaxis, and Martorell's hypertensive ischemic ulcer are part of this group and present some similarities due to microvascular occlusive impairment. They are often misdiagnosed as inflammatory ulcers such as pyoderma gangrenosum and vasculitis. This review discusses the pathophysiology, risk factors, clinical aspects, differential diagnoses, histopathology, and presents a therapeutic update of livedoid vasculopathy, calciphylaxis, and Martorell's ulcer. Although they are less frequent causes of chronic ulcers, a correct diagnosis is essential to reduce the chance of erroneous therapies that may impact morbidity and mortality related to these conditions.

Keywords: Calcific uremic arteriolopathy; Calciphylaxis; Hypertension; Livedoid vasculopathy.

Fig. 1

Livedoid vasculopathy. (A) Active lesions characterized by small ulcers with crusts and erythematous-purpuric edges located on the medial side of the legs and feet. Livedo racemosa is also noted on the dorsum of the feet; (B) Lesions in remission on the lateral side of the leg and foot with brownish scars and ivory-white stellate scars characterizing Millian's white atrophy.

Fig. 2

Histopathology of livedoid vasculopathy. Vessel proliferation in the superficial and deep dermis, with vessel wall thickening. Small foci of necrosis and small thrombi in the superficial vessels (Hematoxylin & eosin, ×1000).

Fig. 3

Flowchart of the sequence of events related to the pathophysiology of calciphylaxis: calcification of arterioles, endothelial lesion and consequent thrombotic occlusion of these vessels. These alterations cause ischemia and necrosis of the subcutaneous tissue, with the appearance of necrotic ulcers in the most advanced stages. PTH, Parathyroid hormone.

Fig. 4

Calciphylaxis: (A) Retiform purpura and advanced stage of necrotic ulcers in the classical reticulated format in the lower limbs. (B) Close-up of the necrotic ulcer (patient of Ref. 39).

Fig. 5

Histopathology of calciphylaxis lesion. Necrosis of subcutaneous fat, with significant calcium deposition on the vessel wall and intima proliferation (Hematoxylin & eosin, ×400).

Fig. 6

Hypertensive ischemic ulcers. (A) Ulcer with necrotic bed and purpuric edges on the lateral side of the leg and another smaller ulcer located on the lateral malleolus with good bed granulation tissue. (B) Extensive ulcer on the posterior region of the leg and calcaneus, with a devitalized bed and the ‘red lipstick sign’ (arrow) in the internal edge and erythematous-purpuric external edge.

Fig. 7

Histopathology of hypertensive ischemic ulcer. Concentric hypertrophy of the tunica media of an arteriole in the deep dermis (Hematoxylin & eosin, ×400).