Transcript Rheumatology Ground Round

Hooman Dehghan, MD
Rheumatology Fellow
Stanford University
Fibromuscular dysplasia of the renal
artery as a cause of secondary
hypertension
Case
• 45 yo male with PMHx of migraines, sinusitis and Sertoli-cell-only
syndrome (male sterility/azoospermia diagnosed with testicular biopsy in
2005).
• Patient was in his usual state of good health until late August 2013 when
he experienced acute onset of abdominal pain.
• He presented to the ED, found to have hypertensive urgency with a
systolic BP of 210/100. He was given nitroglycerin, started on IV
antihypertensive medication and admitted to the hospital for further
work-up.
• He had abd/pelvic CT which showed absence of enhancement involving a
segmental portion of the mid-to-lower pole of the right kidney with a
suggestion of a filling defect within one of the segmental branches of the
right renal artery concerning for renal artery thrombosis.
• He was in the hospital for 3 days, treated with IV heparin and
discharged with no definite diagnosis and with no anticoagulation
or antihypertensive medications.
• After discharging from hospital, he did not have any abdominal pain
but remained hypertensive and had to call his MD who prescribed
diltiazem for controlling his BP.
• Notably he reported extensive physical activities, including wind
surfing between July and August when he was in Hawaii for
vacation and had multiple non-serious trauma with some bruised
ribs.
• ROS: No history of HTN or thrombosis in the past. No fever/chills, rash,
joint or muscle pain, fatigue, decreased appetite or wt loss. No numbness
or tingling in extremities, diarrhea, dysuria, or hematuria. No palpitation
or chest pain.
• PMH: Migraines, sinusitis, Sertoli-cell-only syndrome.
• Surgery Hx: septal deviation surgery, testicular biopsy with diagnosis of
Sertoli-cell-only syndrome in 2005, L temporal artery biopsy in August.
• FH: no family history of hypercoagulable state/thrombosis or
rheumatologic disease. History of Renal ca in maternal grandmother and
uncle. Multiple family members with cholecystitis/cholecystectomy.
• SH: drinks alcohol socially. No smoking. Married and has one healthy
adopted child. He is an engineer and used to work in Russia where he had
his annual medical exam, last unremarkable exam about 2 years ago.
• Allergy: Ampicillin, Chlorpheniramine, Erythromycin
• Home Meds: Motrin , Imitrex , Maxalt, Diltiazem 240mg qday. Arimidex
(aromatase inh) for his Sertoli-cell-only syndrome (March-August); already
stopped before his current presentation.
P/E:
• BP: 146/99, PR: 65, RR: 14, Temp: 97 °F, Ht: 1.88 m (6' 2"), Wt: 183 lbs
• General Appearance: NAD
• HEENT: EOMI, PERRL, Nose: without ulcers. Mouth: moist, no ulcers. No
Sinuse tenderness. Well healed site of L temporal artery biopsy.
• Neck: Thyroid not palpable, no LAP, no JVD or carotid bruits
• Chest: Clear, No rales/wheezing
• CV: RRR with nl S1 & S2, no M/G/R
• Abd: soft, non tender, no mass or organomegaly, +BS , no bruits
• Ext: without cyanosis, clubbing or edema, 2+ DP pulses
• Neuro: A&Ox3, CN II-XII intact, +5/5 strength BUE and BLE, DTR 2/4,
Sensation to light touch grossly intact. Gait nl.
• Skin: nails and nail beds wnl, no color changes in digits, no digital puffiness
or sclerodactyly. No nodules or skin rashes.
• MSK: no joint tenderness, swelling, synovitis or deformity, full ROM
Labs:
ESR 6
CRP <0.2
PR3 <0.2
MPO <0.2
ACA IgG/IgM, Beta-2 GP, LAC: Negative
HBS Ag/HCV Ab: neg
Blood Cx: neg
UA: SG 1.013, trace blood, neg Pr, 0-3 RBC, 0-2 WBC
Retic 1.2
JAK2 mutation: Negative
Flow cytometry for PNH: Negative
Initial Work-Up:
• Kidney US
3.3 x 2.4 x 2.9 cm focal area of heterogeneous echogenicity within the
lateral aspect of the lower pole of right kidney which has absent
cortical perfusion. Renal infarction is favored given the absence of
vascular flow.
• CT abd/pelvis
absence of enhancement involving a segmental portion of the mid-tolower pole of the right kidney. A filling defect with one of the
segmental branches of the right renal artery which may reflect renal
artery thrombosis. Also luminal narrowing of portions of the superior
mesenteric artery involving the ileal branches.
• Temporal artery biopsy: Negative
Further Work-Up:
- Bilat Carotid/Vertebral artery US:
No ICA stenosis. Antegrade flow in the R/L vertebral artery. Normal
flow in the R/L subclavian artery.
- Echo: Normal LV/RV size and systolic function. Mild TR. RVSP 23 mmHg
CT Angio Abd/Pelvis
1. SEGMENTAL SCARRING OF THE RIGHT KIDNEY, CONSISTENT WITH HISTORY
OF PRIOR INFARCTION. ONGOING LARGE PERFUSION DEFECT OVER HALF
OF THE RIGHT RENAL PARENCHYMA. Normal left kidney.
2. MAIN RIGHT RENAL ARTERY, LEFT RENAL ARTERY, SMA BRANCH, AND
INTERNAL ILIAC BRANCH ARTERY ANEURYSMS.
3. No calcified and non-calcified atherosclerotic plaque in the abdominal
aorta. Abdominal aorta is not aneurysmal.
Multiple visceral artery aneurysms:
• 1.2 cm splenic artery aneurysm
• 1.0 cm R renal artery aneurysm
• 0.8 cm L renal artery aneurysm
• 0.4 cm R renal artery branch aneurysm
• 4 mm SMA branch aneurysm
• 5 mm obturator branch of the internal iliac artery aneurysm
Discussion
DDX:
• POLYARTERITIS NODOSA (PAN) ?
• FIBROMUSCULAR DYSPLASIA (FMD)?
Polyarteritis Nodosa (PAN)
• PAN is a small and medium–sized arteritis affecting multiple organs,
especially the skin, peripheral nerve, gut, kidney, and heart.
• Age of onset ranges from childhood to late adulthood but averages 40
years.
• Men are twice as likely to be affected than women.
• A minority of patients with PAN have an active hepatitis B infection.
• In the rest of the cases, the cause(s) is unknown (idiopathic).
Diagnosis:
• Confirming the diagnosis requires either biopsy specimen showing small–
or medium–sized arteries, or mesenteric arteriography showing
microaneurysms or alternating areas of stenosis and dilation.
• Because mesenteric angiography is 60% sensitive, it should be done when
there is not a symptomatic site to biopsy.
• Renal biopsy should be avoided unless angiography rules out
microaneurysms susceptible to rupture.
ACR Criteria for the Classification of Polyarteritis Nodosa (PAN)
Classified as PAN if at least 3 of the 10 criteria are present:
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Weight loss > 4 kg: since illness began, not related to dieting or other factors.
Livedo reticularis: over the skin of portions of the extremities or torso.
Testicular pain/tenderness: not due to infection, trauma or other causes.
Myalgias, weakness or leg tenderness: Diffuse myalgias (excluding shoulder or hip
girdle) or weakness of muscles or tenderness of leg muscles.
Mono- or polyneuropathy: mononeuropathy, multiple mononeuropathies or
polyneuropathy.
Diastolic BP >90 mmHg: hypertension with the diastolic BP higher than 90 mmHg.
Elevated BUN or creatinine: BUN >40 or Cr >1.5, not due to dehydration or
obstruction.
Hepatitis B virus: Presence of hepatitis B surface antigen or antibody in serum.
Arteriographic abnormality: Arteriogram showing aneurysms or occlusions of the
visceral arteries, not due to arteriosclerosis, fibromuscular dysplasia or other noninflammatory causes.
Biopsy of small or medium-sized artery containing polymorphonuclear cells: the
presence of granulocytes or granulocytes and mononuclear leucocytes in the
artery wall.
These criteria have a reported sensitivity of 82.2% and a reported specificity of 86.6%
for the classification of polyarteritis nodosa compared with other vasculitides.
Treatment:
• Without treatment, almost all affected patients die within 2 to 5 years.
• Treatment with prednisone (1 mg/kg daily) and cyclophosphamide (2
mg/kg daily) appeared to revolutionize the outcome of polyarteritis
nodosa by achieving 70% 10–year survivals and established this
combination of agents as the standard therapy.
• Newer studies suggest that prednisone alone may achieve the same high
survival as prednisone and CYC, although flares were less frequent in
patients taking CYC.
• PAN associated with hepatitis B respond to treatment with prednisone
and CYC, but should be avoided as almost all survivors become chronic
carriers of hepatitis B and may die later of cirrhosis or variceal bleeding.
Fibromuscular Dysplasia (FMD)
• Non-atherosclerotic, non-inflammatory vascular disease that causes
abnormal growth within arterial walls.
• FMD has been found in nearly every arterial bed in the body.
However, the most common arteries affected are the renal and
carotid arteries.
• There are various types of FMD, with medial fibroplasia being the
most common. Intimal and adventitial are less common forms of
the disease.
• FMD predominantly affects middle-aged women (90%), but has
been found in men and people of all ages.
• Signs and symptoms that FMD patients present with is largely
dependent on the vascular bed(s) affected.
Renal FMD
• The main symptoms associated with renal FMD are
hypertension and bruits audible over the abdomen or flanks.
• Complications such as aneurysms, dissections, or occlusion of
the renal artery have been associated with renal artery FMD.
• Renal FMD accounts for ~ 70% of this disease process. In
adults it accounts for ~ 10% of renovascular hypertension.
FMD of the renal arteries is bilateral in ~ 40% of patients.
• Severe resistant hypertension, a sudden rise in BP, and
increased serum creatinine upon initiation of ACE inhibitors
are common presentations of FMD.
Diagnosis:
Time from a patient’s first signs or symptoms to diagnosis is commonly
5 years.
 Non-invasive testing:
– duplex ultrasonography
– magnetic resonance angiography (MRA)
– computed tomographic angiography (CTA)
 Invasive testing through angiography is the gold standard. However,
due to the higher risk of complications this is often is not done early
on.
• Duplex ultrasound is highly operator and center dependent, but can
suggest the diagnosis.
• MRA has a sensitivity of about 20% and is not as diagnostic for FMD.
• “Beading” is an important and common angiographic finding and is
present in >90% of cases.
Treatment:
• There is no known cure for FMD. Treatment options include both medical
therapy and revascularization.
• Blood pressure control is the primary concern when treating patients with
renal FMD.
• Conservative treatment involves adequate control of BP with
antihypertensive drugs, but stenosis may lead to renal dysfunction and loss
of renal parenchyma.
• Revascularization can cure hypertension in more than half of the cases and
can lower the BP in another 25% of the cases.
• Percutaneous balloon angioplasty has become the preferred method of
revascularization with a low complication rate and good results. Stents are
typically used only as a bailout (if there is dissection or disruption of the
renal artery).
• Patients with carotid or vertebral FMD should be medically managed to
reduce the risk of a stroke (Aspirin, Antiplatelets and anticoagulants).
References
1. Hundae A, Hebert C, MD, Schussler J. Fibromuscular dysplasia of the renal artery as a
cause of secondary hypertension. Proc (Bayl Univ Med Cent). 2013 October; 26(4):
405–406.
2. Olin JW, Pierce M. Contemporary management of fibromuscular dysplasia. Curr Opin
Cardiol. 2008;23(6):527–536.
3. Lüscher TF, Keller HM, Imhof HG, Greminger P, Kuhlmann U, Largiadèr F, Schneider
E, Schneider J, Vetter W. Fibromuscular hyperplasia: extension of the disease and
therapeutic outcome. Results of the University Hospital Zurich Cooperative Study on
Fibromuscular Hyperplasia. Nephron. 1986;44(Suppl 1):109–114.
4. Slovut DP, Olin JW. Fibromuscular dysplasia. N Engl J Med. 2004;350(18):1862–1871.
5. Alhadad A, Mattiasson I, Ivancev K, Gottsäter A, Lindblad B. Revascularisation of renal
artery stenosis caused by fibromuscular dysplasia: effects on blood pressure during
7-year follow-up are influenced by duration of hypertension and branch artery
stenosis. J Hum Hypertens. 2005;19(10):761–767.