Calciphylaxis and Martorell Hypertensive Ischemic Leg Ulcer: Same Pattern - One Pathophysiology

Abstract

This review presents a closer look at four diseases which are probably closely related to one another pathophysiologically: (a) calciphylaxis (distal pattern); (b) calciphylaxis (proximal pattern); (c) Martorell hypertensive ischemic leg ulcer; (d) calciphylaxis with normal renal and parathyroid function (synonym: eutrophication). The four diseases have largely the same risk factors: (1) arterial hypertension, (2) diabetes mellitus (types 1 and 2), (3) secondary or tertiary hyperparathyroidism (in end-stage kidney disease) and (4) oral anticoagulation with vitamin K antagonists. They share the same clinical patterns: necrotizing livedo, skin infarctions at typical locations and acral gangrene in calciphylaxis. They also share the same histopathology: ischemic subcutaneous arteriolosclerosis and small-artery disease and ‘miniaturizing' Mönckeberg medial calcinosis. The treatment concept for the acute phase of the diseases is also broadly similar. In addition to an optimized control of the cardiovascular risk factors, a proactive wound approach (necrosectomy, negative pressure wound treatment with vacuum dressings, and early skin grafts supported by systemic antibiotic therapy) leads most rapidly and effectively to a reduction of the initially severe wound pain, and finally to complete healing of the wound. Oral anticoagulation with vitamin K antagonists should be stopped. In extensive cases, the use of intravenous sodium thiosulfate is recommended. All four diagnoses are little known in the medical schools of most countries. The need to improve familiarity with these four closely related disorders is therefore great. In particular, the risk of confusion with pyoderma gangrenosum is a major diagnostic problem which can lead to false and even damaging treatment.

<p>Martorell ulcer: chronic wound management and rehabilitation</p>

“…10 The shared pathophysiology of calciphylaxis, eutrophication, and HYTILU is a localized skin infarction leading to tissue necrosis. 8 Clinically, all share a similar pattern of skin infarctions and necrotizing livedo. On histopathology, all conditions have ischemia, subcutaneous arteriolosclerosis, hyperplasia of the arteriole wall musculature, and narrowed lumen diameter.…”

“…4 Both diseases present similarly as a central necrotic ulcer with an inflammatory, violaceous border; however, the wound margin is not pustular in Martorell HYTILU. 8 PG typically presents as liquefaction necrosis with a superficial moist appearance, whereas HYTILU presents as a black, dry infarction. A misdiagnosis of PG can occur due to an inadequate biopsy which may show dermal necrosis without subcutaneous arteriolosclerosis or medial calcification.…”

“…In terms of location, Martorell HYTILU only occurs on the dorsolateral shin or Achilles' tendon Martorell HYTILU shares a common histopathological and clinical picture to calciphylaxis and eutrophication, best described in a review paper by Hafner in 2016. 8 Calciphylaxis has a varied initial morphology but generally presents with an erythematous or violaceous plaque with livedo or retiform purpura. 10 In its late stages, it progresses to a necrotic ulcer with eschar or gangrene.…”

A persistent penile ulcer in end stage renal disease: It is not always calciphylaxis

“…In our patient, though parathormone and calcium‐phosphate product levels were raised, we could not demonstrate calcium deposits in skin biopsy, otherwise necessary to diagnose calciphylaxis . Importantly, microvascular compromise brought on by ESRD, DM and hypertension is essentially similar and involves hyaline subcutaneous arteriolosclerosis of small arterioles and capillaries in subcutaneous fat, which occurs at the expense of lumen . Many patients do not demonstrate calcification, and it has been suggested that the luminal compromise in absence of calcification may in fact be an early stage of calciphylaxis (calciphylaxis sine calcifications) …”

“…3 Importantly, microvascular compromise brought on by ESRD, DM and hypertension is essentially similar and involves hyaline subcutaneous arteriolosclerosis of small arterioles and capillaries in subcutaneous fat, which occurs at the expense of lumen. 4 Many patients do not demonstrate calcification, and it has been suggested that the luminal compromise in absence of calcification may in fact be an early stage of calciphylaxis (calciphylaxis sine calcifications). 5 To conclude, persistent penile ulceration can occur in setting of long-standing DM, hypertension and ESRD; and represents an atypical clinical manifestation of vascular compromise.…”