Steve Dong, MD
Leonard G. Gomella, MD, FACS
BASICS
DESCRIPTION
• Retroperitoneal fibrosis (RPF) also refered to as Ormond disease, is characterized by sclerotic tissue from inflammatory processes causing encasement of the retroperitoneal structures including the ureters, aorta, and inferior vena cava. The main manifestation is obstructive uropathy.
• Exhibits a perivascular distribution, typically including the periaortic, pericaval, and peri-iliac retroperitoneum.
• Generally classified as either primary (idiopathic) or secondary RPF.
• Hallmark is medial deviation of the ureters on imaging with or without hydronephrosis.
EPIDEMIOLOGY
Incidence
• In Finland, incidence is 0.1:100,000/yr
• Unknown, but estimated at 1:200,000–1:500,000/yr
Prevalence
1–38 per 100,000
RISK FACTORS
• Asbestos exposure
• Associated with autoimmune disorders
• Abdominal aortic aneurysm
• Male > Female (2–3:1)
• RPF most common in the 5th–6th decades, but can occur at any age
• Use of implicated medications (see below)
• Malignancy
Genetics
• Evidence suggests an immunogenetic role with certain HLA haplotypes:
– HLA-DRB1*03 and HLA-B*08
PATHOPHYSIOLOGY
• Idiopathic RPF recently identified as a immunoglobulin G4-related disease (IgG4-RD) and is a multisystem, fibroinflammatory condition (1)
• Most commonly, the retroperitoneal thickening is located between L5 and S1, close to the aortic bifurcation
• Mechanical obstruction of the ureters is usual presentation; may also cause venous or arterial occlusion
• Primary RPF:
– 70% of cases are idiopathic, and the exact pathogenesis is unclear
• Mitchinson and Parums classify idiopathic RPF in a range of diseases collectively termed chronic periaortitis
– Immune-mediated reaction to antigens (ceroid and low-density lipoprotein) within atherosclerotic plaques
– Often have autoantibodies, and thus overlap with many autoimmune disorders
– IgG4-bearing plasma cells may also be involved in the pathogenesis of RPF
• Secondary RPF: 30% of patients with RPF have an identifiable cause of their RPF:
– Medications:
Prolonged therapy with ergot alkaloids such as methylsergide (Sansert, once widely used for migraine headaches)
Others include LSD, methyldopa, phenacetin, β-blockers, amphetamines, hydralazine, and analgesics
– Malignancy:
Lymphoma (most common), multiple myeloma, carcinoid, pancreatic tumors, prostate cancer, testicular cancer, and sarcoma
– Radiotherapy for malignancies such as seminoma, colon, or pancreatic cancer
– Infections: Tuberculosis, actinomycosis, histoplasmosis
– Others: Trauma (hemorrhage, urinary extravasation), surgical injury, Crohn disease, inflammatory bowel disease, asbestos exposure, fat necrosis, collagen vascular disease, perianeurysmal inflammation
ASSOCIATED CONDITIONS
• Atherosclerotic disease (abdominal aortic aneurysm)
• Autoimmune diseases: Ankylosing spondylitis and Wegener granulomatosis
• Membranous glomerulonephritis
• Multifocal fibrosclerosis: RPF may present as part of a systemic sclerosis
– Presentation may include sclerosing mediastinitis, sclerosing cholangitis, orbital pseudotumor, and Riedel thyroiditis
GENERAL PREVENTION
Avoid medication implicated in RPF (see above)
DIAGNOSIS
HISTORY
• Constitutional symptoms (fatigue, weight loss, anorexia, low-grade fever)
• Pain (back, flank, abdominal) and duration
• Signs of vascular obstruction:
– Testicular pain, varicocele, hydrocele, leg edema, deep vein thrombosis, claudication
• GI symptoms such as weight loss, nausea, anorexia, constipation, or vomiting
• Urinary symptoms, including frequency, and dysuria, also oliguria if severe
• Medication history especially ergot alkaloids
• History of malignancies, other autoimmune or collagen vascular diseases, fibrotic processes, inflammatory bowel diseases, asbestos exposure, radiation exposure
• Surgical history:
– Abdominal, vascular, or endoscopic procedures
PHYSICAL EXAM
• Patient can appear pale, ill, and has malaise if significant azotemia is present
• Low-grade fevers and hypertension
• Abdominal exam: Mass, abdominal bruit, costovertebral angle tenderness
• Testicular masses
• Lower-extremity edema, varicosities
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• No tests are diagnostic
• Metabolic profile: Electrolyte abnormalities will depend upon the degree of ureteral obstruction
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are usually elevated
• Ferritin and other acute phase reactants are often high
• Polyclonal hypergammaglobulinemia
• ANA is positive in 60% of patients along with other autoantibodies including antismooth muscle antibodies and rheumatoid factor
Imaging
• Excretory Urography (2):
– Medial deviation of the ureters with tapering of the middle 1/3 of the ureter beginning at the 3rd or 4th lumbar vertebra
– Varying degrees of hydronephrosis; may see a nonfunctioning kidney
– Encasement of ureters may prevent dilation of middle and distal ureteral segments
• Ultrasound (US)
– More useful for following the response to therapy
• Computed tomography (CT)
– Imaging modality of choice
– Typically shows a symmetric, geometrically shaped mass encasing the retroperitoneal structures
– Demonstrates the medial deviation of the ureters and extrinsic compression with hydronephrosis
– Mass is often isodense to muscle with contrast enhancement
• Magnetic resonance imaging (MRI)
– Hypodensity on T1 images but high intensity on T2-weighted images
• Positron emission tomography (PET):
– Investigational; may visualize other disease sites
– May reveal neoplastic or infectious processes to which the RPF may be secondary
Diagnostic Procedures/Surgery
• Retrograde pyelography may be indicated in patients with severe azotemia prohibiting the use of contrast-enhanced imaging. Usually shows medial deviation of ureters.
• CT-guided biopsy may be necessary to rule out a malignant process.
Pathologic Findings
• Gross findings secondary RPF:
– Smooth, flat, firm, grayish/tan-colored mass
– Extends from the origin of the renal vessels to the distal extent of the common iliac vessels
– May also involve the thoracic aorta and other atypical areas
• Microscopic findings
– Early findings: Collagen bundles with capillary proliferation and inflammatory cells
– Later acellular and avascular mass with sheets of hypocellular collagen
– Vasculitis of small retroperitoneal vessels with plasma cells staining for IgG4 (rarest IgG subclass)
DIFFERENTIAL DIAGNOSIS
• Medial deviation of the ureters
– Malignancies, aneurysms, bladder diverticulum, and prior surgery
– 20% of normal individuals have medial deviation of the ureters, especially on the right
• Retroperitoneal mass: See also Section I “Retroperitoneal masses, fluid, and cysts”
– Malignant processes; inflammatory myofibroblastic tumors
– Desmoid-type fibromatosis; associated with Gardner syndrome; presents as soft tissue mass with mass effect
TREATMENT
• Discontinue any offending medications
• Relieve urinary obstruction:
– Monitor for postobstructive diuresis after the urinary system is decompressed
• Biopsy to rule out malignancy
• Unclear if trial of steroids or immediate ureterolysis is optimal therapy
MEDICATION
First Line
• After ureteral obstruction has been relieved, 1st-line therapy is generally glucocorticoids (prednisone). No consensus as to duration of therapy:
– Prednisone 60 mg every other day for 2 mo, then tapered over 5 mo to 5 mg/d
– Alternate regimen: 60 mg/d for 6 wk, and tapered over the next 2–3 mo to 10 mg/d for a total of 1 yr
Second Line
• In patients with glucocorticoid-resistant RPF or who have recurrent disease, immunosuppressive agents may also be helpful:
– Prednisone in combination with cyclophosphamide or azathioprine for 6–12 mo
– Mycophenolate mofetil has also been used in combination with glucocorticoids
SURGERY/OTHER PROCEDURES
• Relief of ureteral obstruction:
– Ureteral stents may be helpful during subsequent ureterolysis
– Usually not difficult; often elect to stent both sides even if not bilaterally obstructed to prevent obstruction or provide guide for surgery
• Percutaneous nephrostomy undertaken only in acutely ill patients; rarely necessary
• Ureterolysis:
– May be performed via an open approach (transabdominal) or laparoscopically (hand-assisted or standard) (3)
– Ureters are often wrapped in omentum or intraperitonealized to prevent further fibrous entrapment
• Other procedures: May require ileal interposition graft, autotransplantation, nephrectomy, or urinary diversion in complicated or severe cases
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
• Observation:
– There may be a role in patients on methylsergide after discontinuation of the medication if normal renal function.
– These patients should be monitored for resolution of hydronephrosis. If the hydronephrosis does not resolve, then the standard combination of medical and surgical therapy should be administered.
• Tamoxifen has been used
• Low-protein, sodium-restricted diet for patients with renal insufficiency
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
Prognosis is excellent with combined medical and surgical therapy
COMPLICATIONS
• Recurrence of RPF: Typically in 1st yr; usually limited to those treated with medical therapy
• Ureteral injury, requiring further surgical management
• Vascular injury
• Postoperative adhesions due to intraperitoneal procedure
FOLLOW-UP
Patient Monitoring
• Patients can be monitored at regular intervals with symptom check, ESR/CRP levels, creatinine, and degree of hydronephrosis on US
• CT/MRI is usually performed 2–4 mo after the beginning of the steroid treatment (1)
• Patients treated with definitive surgical intervention require less frequent follow-up
Patient Resources
• Medline Plus: Retroperitoneal Fibrosis
http://www.nlm.nih.gov/medlineplus/ency/article/000463.htm
REFERENCES
1. Khosroshahi A, Carruthers MN, Stone JH, et al. Rethinking ormond’s disease: “Idiopathic” retroperitoneal fibrosis in the era of IgG4-related disease. Medicine (Baltimore). 2013;92(2):82–91.
2. Caiafa RO, Vinuesa AS, Izquierdo RS, et al. Retroperitoneal fibrosis: Role of imaging in diagnosis and follow-up. Radiographics. 2013;33(2):535–552.
3. Brown JA, Garlitz CJ, Hubosky SG, et al. Hand-assisted laparoscopic ureterolysis to treat ureteral obstruction secondary to idiopathic retroperitoneal fibrosis: Assessment of a novel technique and initial series. Urology. 2006;68(1):46–49.
ADDITIONAL READING
• Scheel PJ Jr, Feeley N. Retroperitoneal fibrosis. Rheum Dis Clin North Am. 2013;39(2):365–381.
• Vaglio A, Palmisano A, Corradi D, et al. Retroperitoneal fibrosis: Evolving concepts. Rheum Dis Clin N Am. 2007;33:803–817.
• Vaglio A, Salvarani C, Buzio C. Retroperitoneal fibrosis. Lancet. 2006;367:241–251.
See Also (Topic, Algorithm, Media)
• Hydronephrosis/Hydroureteronephrosis (Dilated Ureter/Renal Pelvis), Adult
• Retroperitoneal fibrosis (RPF, Ormond Disease) Image 
• Retroperitoneal Hematoma
• Retroperitoneal Masses, Fluids and Cysts
CODES
ICD9
• 590.80 Pyelonephritis, unspecified
• 593.4 Other ureteric obstruction
• 599.60 Urinary obstruction, unspecified
ICD10
• N13.5 Crossing vessel and stricture of ureter w/o hydronephrosis.
• N13.6 Pyonephrosis.
• N13.9 Obstructive and reflux uropathy, unspecified.
CLINICAL/SURGICAL PEARLS
• Although no tests are diagnostic of RPF, most will present with medial deviation of the ureters on imaging.
• CT is the image modality of choice.
• Stents are often placed for relief of obstruction.
• Patients who fail steroid treatment without evidence of malignancy should undergo ureterolysis.