Retroperitoneal Fibrosis

Retroperitoneal fibrosis is a chronic fibroinflammatory process that forms a plaque of fibrous tissue around the abdominal aorta and iliac arteries and may encase the ureters, causing obstruction. It is rare, with peak onset in middle age and a male predominance.

Classification

• Idiopathic disease accounts for most cases. A substantial proportion falls within the spectrum of IgG4-related disease or chronic periaortitis.
• Secondary causes include ergot derivatives and other drugs, malignancy, tuberculosis and other infections, retroperitoneal surgery, haemorrhage, radiotherapy, inflammatory aortic aneurysm and systemic autoimmune disease.

IgG4-related disease can show storiform fibrosis, obliterative phlebitis and increased IgG4-positive plasma cells on histology.

The plaque usually begins below the renal arteries around L4 to L5 and can spread to the ureters, renal hila, mesenteric root, inferior vena cava and pelvis.

Complications

• Hydronephrosis and acute or chronic kidney injury.
• Venous thrombosis, lower limb oedema and lymphatic obstruction.
• Hypertension, arterial narrowing, bowel obstruction and recurrent disease after treatment.

• Dull constant flank, back or abdominal pain, often poorly localised.
• Constitutional symptoms including malaise, fever, weight loss, anorexia and nausea.
• Obstructive features such as oliguria, anuria and uraemic symptoms.
• Lower limb oedema, deep vein thrombosis, scrotal swelling, varicocele or hydrocele from venous and lymphatic compression.
• Constipation or small bowel obstruction if bowel or mesenteric structures are involved.
• Hypertension and renal impairment.

Features of systemic IgG4-related disease may include autoimmune pancreatitis, sclerosing cholangitis, salivary gland disease, orbital pseudotumour, thyroid disease and mediastinal fibrosis.

Differential diagnosis includes lymphoma, metastatic carcinoma, sarcoma, aortic aneurysm, tuberculosis, ureteric stricture, inflammatory bowel disease and other retroperitoneal masses.

Features raising concern for malignancy include older age, rapid weight loss, an asymmetric or atypically located mass, lateral displacement of the ureters, abnormal lymph nodes and failure to respond to corticosteroids.

Laboratory tests

• Creatinine and eGFR, electrolytes, urinalysis, CBC, ESR, CRP, LDH and liver tests.
• Serum IgG4 and IgG subclasses when IgG4-related disease is suspected.
• ANA, ANCA, rheumatoid factor and complement according to context.
• Selective tumour markers, serum protein electrophoresis and tuberculosis testing when clinically indicated.

Imaging

• Contrast CT may show a periaortic soft tissue plaque encasing the aorta, iliac vessels and ureters, with medial ureteric deviation and hydronephrosis.
• MRI helps assess inflammatory activity and fibrosis and can be used for follow-up.
• FDG PET CT can demonstrate disease activity, identify other affected organs and guide biopsy.
• Ultrasound assesses hydronephrosis, while retrograde or antegrade pyelography demonstrates ureteric narrowing and deviation.
• Renography can estimate split renal function.

Biopsy

• CT-guided core biopsy is advised when malignancy must be excluded, IgG4-related disease requires confirmation, or the presentation is atypical.
• Laparoscopic or open biopsy is used when percutaneous biopsy is inconclusive.

Assess for associated aortic aneurysm and other manifestations of systemic IgG4-related disease.

The priorities are relief of urinary obstruction, suppression of inflammation, prevention of relapse and preservation of renal function.

Relief of obstruction

• Bilateral hydronephrosis with renal impairment requires ureteric stenting or percutaneous nephrostomy, particularly when infection or severe renal failure is present.
• Monitor for post-obstructive diuresis and replace fluid and electrolyte losses appropriately.
• Stents or nephrostomies can often be removed when the inflammatory mass regresses.

Idiopathic and IgG4-related disease

• Prednisolone about 0.6 to 1 mg/kg/day, commonly 40 to 60 mg daily, for 4 to 6 weeks, followed by gradual taper over 6 to 12 months or longer according to symptoms, inflammatory markers and imaging.
• Severe renal impairment or extensive vascular disease may be treated initially with IV methylprednisolone.
• Steroid-sparing treatment for relapse, steroid toxicity or high-risk disease includes methotrexate 15 to 25 mg weekly, azathioprine 1.5 to 2 mg/kg/day, mycophenolate mofetil 1 to 1.5 g twice daily, or rituximab in IgG4-related or refractory disease.
• Provide bone, gastric and infection prophylaxis appropriate to the intensity and duration of immunosuppression.

Secondary disease

• Stop causative drugs and treat the underlying infection, malignancy or systemic inflammatory disorder.

Surgery

• Ureterolysis with lateral transposition, intraperitonealisation or omental wrapping is reserved for failure of medical therapy, inability to use immunosuppression or persistent obstruction that cannot be managed by stenting.
• Ureteric reconstruction or autotransplantation may be required in difficult cases.
• Malignant fibrosis is treated according to the primary cancer, with decompression of the urinary tract when needed.

Monitoring

• Review within 2 to 4 weeks after starting treatment with symptoms, creatinine, ESR and CRP.
• Repeat CT, MRI or PET CT at about 3 to 6 months and again according to response.
• Relapse is treated by increasing anti-inflammatory therapy and adding a steroid-sparing agent when appropriate.
• Long-term monitoring includes renal function, blood pressure and ultrasound for recurrent hydronephrosis.