[upbeat intro music]
[Dr. Handy] Hi, welcome to Harrison's PodClass, where we discuss important concepts in internal medicine. I'm Cathy Handy. [Dr. Wiener] And I'm Charlie Wiener, and we're coming to you from the Johns Hopkins School of Medicine. Welcome to episode 89, a 66-year-old woman with elevated blood pressure. - Hey, Cathy. - [Dr. Handy] Hey, Charlie. [Dr. Wiener] So, today's patient is a 66-year-old woman who presents to the emergency room with malaise, confusion, and a headache.
At triage, her blood pressure is found to be 220/105. [Dr. Handy] Stop right there. So, the combination right off the bat of a very high blood pressure and neurologic findings is already consistent with hypertensive emergency. You should already be thinking about treatment and of course a complete physical exam. [Dr. Wiener] Right, so you're saying that the difference between hypertensive urgency and emergency is the presence of end organ damage in emergency?
[Dr. Handy] Yes. [Dr. Wiener] So I assume that can be neurologic changes, as in this patient, or also chest pain, new hematuria, proteinuria, or other signs of vascular insufficiency? [Dr. Handy] Yeah, and some require a systolic blood pressure of over 180 or a diastolic blood pressure over 110, but the point is that it's an uncontrolled elevated blood pressure with end organ damage, and if it's not treated, it may become irreversible. So, let's go back to the patient.
[Dr. Wiener] Okay, so on physical exam, she has no neurologic asymmetry but she's definitely somnolent and only oriented to person and city. Her family says this is radically different from her baseline and it's been going on for about one to two days. Her lungs are clear and her cardiac examination is only notable for a loud S4. Additional physical findings that you notice are skin thickening of her arms and legs, facial telangiectasias, and a decreased oral aperture.
[Dr. Handy] Well, the physical exam findings that you mentioned of the skin thickening, the facial telangiectasias and the decreased oral aperture are characteristic of scleroderma. Can you tell me more about her initial laboratory studies, as there can be organ involvement as well, which may be contributing to her current presentation?
[Dr. Wiener] Well, she has a creatinine of 3.5 mg/dL, a hemoglobin of 7 g/dL, platelets are 75,000, LDH is elevated at 700, and these are all different from her baseline, which was previously normal. [Dr. Handy] Okay, so those labs that you just mentioned, it sounds like she has acute kidney injury, anemia, thrombocytopenia, and a very elevated LDH. What does the question ask? [Dr. Wiener] So the question asks, what is the appropriate initial treatment for her current presentation?
And the options are, amlodipine; option B. is captopril; option C. is eculizumab; option D. is heparin; and option E. is plasmapheresis. [Dr. Handy] Well, the key to the answer in this case is to recognize that this is scleroderma renal crisis. [Dr. Wiener] Tell me more about that. [Dr. Handy] Scleroderma renal crisis may occur in 10% to 15% of patients with diffuse systemic sclerosis, but it's much less common in only about 2% of those who have limited systemic sclerosis.
The physical description that you gave, with the diffuse skin changes, telangiectasias, and limited oral orifice are all consistent with diffuse systemic scleroderma. [Dr. Wiener] Okay, let's discuss scleroderma renal crisis specifically. [Dr. Handy] Well, it's the most severe manifestation of renal involvement and it typically presents within the first four years of diagnosis.
It's characterized by accelerated hypertension, a rapid decline in renal function, nephrotic range proteinuria, and hematuria. Retinopathy and encephalopathy may accompany the hypertension. Salt and water retention with microvascular injury can lead to pulmonary edema. And cardiac manifestations, like myocarditis, pericarditis, and arrhythmias, denote an especially poor prognosis.
In very severe cases, the patient may develop posterior reversal encephalopathy, or PRES, which, frankly, I'm concerned about in this patient. [Dr. Wiener] This patient seems to have had a fall in her hemoglobin and her platelets, and she has an elevated LDH. Is that part of the crisis also? [Dr. Handy] Yeah. Sorry for not mentioning that before. So microangiopathic hemolytic anemia, or MAHA, is presented in more than half of patients, however, true coagulopathy is rare.
[Dr. Wiener] What's the pathology of this disorder? [Dr. Handy] On renal biopsy during a crisis, you'll find arcuate artery intima and medial proliferation with luminal narrowing. This lesion is described as onion skinning and it can be accompanied by glomerular collapse due to reduced blood flow. Histologically, scleroderma renal crisis is indistinguishable from malignant hypertension, with which it can coexist. And fibrinoid necrosis and thrombosis are also common.
[Dr. Wiener] Okay, so in this case, you did go back to the family, and the family did confirm that the patient had a diagnosis of scleroderma made about two years ago. And the question's specifically asking about treatment. Which of the medications is the answer? [Dr. Handy] Yeah. So the answer is B. captopril. Now, before the availability of angiotensin-converting enzyme, or ACE inhibitors, the mortality rate for scleroderma renal crisis was over 90% at one month.
Introduction of renin-angiotensin system blockade has lowered the mortality rate to 30% at three years. Nearly two thirds of patients with scleroderma renal crisis may require dialysis support, but recovery of renal function does happen in about 50% of people, and the median time that that takes is about a year.
Treatment with ACE inhibition is the first-line therapy unless contraindicated, and the goal of therapy is to reduce systolic and diastolic blood pressure by 20 mmHg and 10 mmHg, respectively. And you want to do that every 24 hours until the blood pressure is normal. [Dr. Wiener] I assume you chose captopril because it is the most short-acting and the easiest to up-titrate. What about angiotensin II receptor antagonists?
[Dr. Handy] Yes, so initially captopril is easiest to manage in these patients who can have very volatile blood pressures but both ACE inhibitors and ARBs, or angiotensin II receptor antagonists, are effective, although data suggests that treatment with ACE inhibitors is superior. Now, ACE inhibition alone does not prevent scleroderma renal crisis but it does reduce the impact of the hypertension.
[Dr. Wiener] Why target that pathway and not use one of the other drugs like amlodipine, which is mentioned in this case to manage the blood pressure? [Dr. Handy] Like I mentioned before, the pathogenesis involves obliterative vasculopathy and luminal narrowing of the renal arcuate and interlobar arteries. So that's consistent with intravascular hemolysis, along with evidence of activation of the complement pathways.
Now, progressive reduction in renal blood flow aggravated by vasospasm, also leads to juxtaglomerular renin secretion and activation of angiotensin II. That results in further renal vasoconstriction, resulting in a vicious cycle that culminates in the accelerated hypertension. So, the ACE inhibition really works directly on the pathophysiology of the disease. [Dr. Wiener] Can you use additional anti-hypertensive agents? The question mentioned amlodipine.
[Dr. Handy] Yes, additional anti-hypertensive therapy, such as calcium-channel blockers, like amlodipine or nicardipine, may be given once the dose of drug for ACE inhibition is maximized. The things to mention, though, potentially nephrotoxic drugs should definitely be avoided, and in patients with persistent hypertension, you can add on ARBs or other calcium channel blockers. [Dr. Wiener] Okay, how about you run through the other options quickly just to finish off the discussion?
[Dr. Handy] Yeah, so eculizumab is a monoclonal antibody that binds a terminal component of complement 5. It's used in atypical hemolytic uremic syndrome and paroxysmal nocturnal hematuria, but that's not what's happening to this patient. And there's also no role for heparin to treat scleroderma renal crisis.
[Dr. Wiener] Great, so the teaching points of this case are that in a patient with scleroderma, renal crisis will often present with findings consistent with hypertensive emergency, or PRES. It is vital to treat early by interfering with the renin-angiotensin axis, preferably with an ACE inhibitor. [Dr. Handy] And you can read more about this in Harrison's chapter on vascular injury to the kidney and scleroderma. [upbeat outro music] [Mr. Shanahan] This is Jim Shanahan, publisher at McGraw Hill.
Harrison's PodClass is brought to you by McGraw Hill's AccessMedicine, the online medical resource that delivers the latest trusted content from the best minds in medicine. Go to accessmedicine.com to learn more.