Malignant hypertension (MH) is recognized clinically by elevated blood pressure together with retinal haemorrhages or exudates with or without papilloedema (grades III or IV hypertensive retinopathy); and may constitute a hypertensive emergency or crisis when complicated by evidence of end-organ damage including microangiopathic haemolysis, encephalopathy, left ventricular failure, and renal failure. Though reversible, it remains a significant cause of end-stage renal failure, and of cardiovascular and cerebrovascular morbidity and mortality in developing countries.MH can complicate pre-existing hypertension arising from diverse aetiologies, but most commonly develops from essential hypertension. The absolute level of blood pressure appears not to be critical to the development of MH, but the rate of rise of blood pressure may well be relevant in the pathogenesis. The pathogenesis of this transformation remains unclear.The pathological hallmark of MH is the presence of fibrinoid necrosis (medial vascular smooth muscle cell necrosis and fibrin deposition within the intima) involving the resistance arterioles in many organs. Fibrinoid necrosis is not specific to MH and this appearance is seen in other conditions causing a thrombotic microangiopathy such as haemolytic uraemic syndrome, scleroderma renal crisis, antiphospholipid syndrome, and acute vascular rejection post transplant. MH can both cause a thrombotic microangiopathy (TMA) but can also complicate underlying conditions associated with TMA.The pathophysiological factors that interact to generate and sustain this condition remain poorly understood. Risk factors include Afro-Caribbean race, smoking history, younger age of onset of hypertension, previous pregnancy, and untreated hypertension associated with non-compliance or cessation of antihypertensive therapy.Evidence from clinical studies and animal models point to a central role for the intrarenal renin–angiotensin system (RAS) in MH; there is good evidence for renal vasoconstriction and activation of the renal paracrine RAS potentiating MH once established; however, there may also be a role in the predisposition of MH suggested by presence of increased risk conferred by an ACE gene polymorphism in humans and polymorphisms for both ACE and AT1 receptor in an animal model of spontaneous MH. Other vasoactive mediators such as the endothelin and the inflammatory response may be important contributing to and increasing endothelial damage. There have been no randomized controlled trials to define the best treatment approach, but progressive lowering of pressures over days is considered safest unless made more urgent by critical clinical state. It seems logical to introduce ACE inhibition cautiously and early, but in view of the risk of rapid pressure lowering some recommend delay.
Acute renal failure, systemic lupus erythematosus and thrombotic microangiopathy following treatment with beta-interferon for multiple sclerosis: case report and review of the literature
