Retroperitoneal fibrosis

Retroperitoneal fibrosis (RPF, Ormond's disease) is a rare disease of unknown etiology, characterized by inflammation and fibrosis of the retroperitoneum resulting in compression and encasement of the ureter, and/or the retroperitoneal blood vessels. RPF may be primary/idiopathic (most common) or secondary (e.g., drug-induced, inflammatory, iatrogenic). Patients often present with nonspecific symptoms (e.g., fever, malaise, weight loss, flank pain, etc.). Bilateral ureteral obstruction, with subsequent hydronephrosis and obstructive nephropathy, is common. Diagnosis is often suspected in patients who present with bilateral hydronephrosis of unknown etiology. Contrast CT is the diagnostic test of choice and reveals a retroperitoneal mass encasing and obstructing the ureters and/or the aorta and IVC. Diagnosis is confirmed on CT-guided biopsy of the mass. High-dose glucocorticoids are the mainstay of treatment of primary RPF. Secondary RPF is managed by treating the underlying cause (stopping the offending drug, treating the infection, etc.). Symptomatic/severe obstruction of the retroperitoneal structures require treatment (ureteric stenting, ureterolysis, arterial stenting, etc.). Prognosis of non-malignancy-induced RPF is good, but recurrence rates are high (70%).

• Prevalence
  • Rare (1 per 200,000–500,000 of the general population) ^[1]
  • Primary/idiopathic RPF: most common (70% of the cases) ^[2]
• Peak age of incidence: 40–60 years ^[3]
• Sex: ♂ > ♀ (2:1) ^[1]

Epidemiological data refers to the US, unless otherwise specified.

Primary/idiopathic retroperitoneal fibrosis

• Immune reaction to antigens within aortic atherosclerotic plaques
• Systemic autoimmune disease: RPF may be a systemic autoimmune disease of large arteries → periaortic inflammation → inflammation and fibrosis in the periaortic region
• IgG4-related disease (immunoglobulin G4 related disease): characterized by an infiltration of various organs by IgG4-bearing plasma cells which cause inflammation and fibrosis ^[4]

Secondary retroperitoneal fibrosis

• Drugs: ergot alkaloids (methysergide, ergotamine) ; Dopamine agonists (pergolide, methyldopa), β-blockers, analgesics (phenacetin), hydralazine, etc. ^[4][5]
• Biological agents: infliximab, etanercept, etc. ^[4]
• Malignancies: primary retroperitoneal malignancies , Retroperitoneal metastases , neuroendocrine tumors (NETs)
• Infections: mycobacterium tuberculosis, actinomycosis, histoplasmosis
• Iatrogenic: surgery or radiation therapy to the retroperitoneum
• Trauma: retroperitoneal hemorrhage
• Tobacco use
• Exposure to asbestos

Malignancies and exposure to methysergide are the most common causes of secondary RPF.

• The etiological factors incite an immune response in the retroperitoneum. → inflammation of the retroperitoneal tissue → healing by fibrosis
• Fibrosis can entrap and obstruct retroperitoneal structures.

• Pain in the lower back/flanks (most common symptom)
• Constitutional symptoms: fever, anorexia, weight loss, nausea, etc.^[4]
• Specific symptoms
  • Ureters → upper urinary tract obstruction → hydronephrosis and features of chronic renal failure (obstructive nephropathy: uremia, hypertension, etc.) ^[6]
  • Infrarenal aorta/iliac arteries → chronic mesenteric ischemia, lower limb and gluteal claudication pain, etc. ^[7][8]
  • Inferior vena cava/iliac veins → deep vein thrombosis, renal vein thrombosis
  • Gonadal vessels → hydrocoele, varicocoele, testicular pain ^[4][9]
  • Lymphatic channels → lymphedema

In RPF, the ureters are the earliest and most commonly involved structures, and ureteral obstruction is often bilateral. ^[6]

• Laboratory tests ^[4]
  • Raised inflammatory markers: elevated CRP and ESR
  • Renal parameters: blood urea nitrogen, serum creatinine, and serum electrolyte levels
  • Autoantibodies: e.g., ANA (antinuclear antibody), ANCA (antineutrophilic cytoplasmic antibody) ^[10]
• Imaging
  • Contrast-enhanced CT scan
    • Investigation of choice to diagnose RPF
    • Findings: ^[6]
      • Para-aortic mass extending from the renal arteries to the common iliac arteries.
      • Encasement and/or compression of the ureters, IVC, and/or aorta ^[7]
      • May identify malignancies
    • CT-guided biopsy of the mass
  • MRI and MRA: useful in patients in whom contrast administration is contraindicated
  • Intravenous urography and retrograde pyelography ^[6]
  • Renal ultrasonography: useful in assessing response to therapy
• Biopsy: (confirmatory test)
  • CT-guided/laparoscopic biopsy of the retroperitoneal mass
  • Early stage: hypervascular tissue with perivascular lymphocytic infiltrate and lipid-laden macrophages
  • Late stage: avascular fibrous tissue which is devoid of cells

Medical therapy ^[4][9]

• Primary RPF
  • Oral high-dose glucocorticoids: first line therapy with high dose prednisone (1 mg/kg/day for the first month)
  • Tamoxifen: indicated as monotherapy in patients with contraindications to glucocorticoid therapy
  • Immunosuppressants : indicated in glucocorticoid-resistant disease
• Secondary RPF
  • Treatment of the underlying etiology: e.g., discontinue the causative drug, treat chronic infections, treatment of lymphoma, etc.
  • Oral high-dose glucocorticoids: Indicated in symptomatic/severe drug-induced cases of secondary RPF

Decompression of obstructed retroperitoneal structures ^[11]

• Kidneys and ureters: (see “Treatment” of “Upper urinary tract obstruction”)
  • Conservative therapy
    • Patients with mild hydronephrosis and normal renal parameters: respond well to medical therapy alone
    • Mild hydronephrosis with abnormal renal parameters: cystoscopy-guided ureteric stenting
    • Obstructive nephropathy: urgent decompression with percutaneous nephrostomy, followed by surgery
  • Surgical decompression: open/laparoscopic ureterolysis (release of the ureter from fibrotic tissue)
• Aorta or iliac arteries: see “Revascularization” in “Peripheral arterial disease.”
• IVC or iliac veins: see “Treatment” in “Deep vein thrombosis.”

• Prognosis of nonmalignancy induced RPF is good, with symptomatic and clinical improvement obvious within a few weeks of initiating therapy.
• High recurrence rates of idiopathic RPF (70%)
• Poor prognosis of malignancy-induced RPF (∼ 6 months) ^[12]