Retroperitoneal fibrosis

Retroperitoneal fibrosis (RPF) is a relatively rare condition that is characterised by a chronic inflammatory and fibrotic process in the retroperitoneum that can lead to compression of structures within the retroperitoneum¹. This fibrotic process can often lead to encasement of the aorta, vena cava, ureters and psoas muscle. It may extend from the renal pedicle to below the pelvic brim.

• RPF is thought to be an autoimmune response to an insoluble lipid that has leaked through a thinned arterial wall from atheromatous plaques.

• The centre of the plaque is usually located at the level of the aortic bifurcation. The fibrous tissue may bifurcate and follow the common iliac arteries.

Epidemiology¹²

RPF is a rare disease. It most commonly affects patients between the ages of 40 and 60. There is a male predominance, with a male-to-female ratio estimated to be approximately 2:1 or 3:1. The true incidence is unknown but is estimated to be 1 per 200,000 to 500,000 per year.

Paediatric RPF is a very rare entity with fewer than 40 reported cases worldwide, the majority of which have known secondary causes³.

Aetiology

Approximately 75% of cases are idiopathic RPF². The recently advocated concept and diagnostic criteria of immunoglobulin G4 (IgG4)-related disease has led to widespread recognition of RPF associated with IgG4-related disease⁴.

Identified secondary causes include⁵⁶:

• Drugs: eg, methysergide, beta-blockers, methyldopa, amfetamines, phenacetin, pergolide and cocaine.

• Abdominal aortic aneurysm.

• Trauma to the renal tract.

• Infection.

• Retroperitoneal malignancy⁷.

• Post-irradiation therapy or chemotherapy.

RPF may also be associated with primary biliary cirrhosis, fibrosing mediastinitis, panhypopituitarism, glomerulonephritis, rheumatoid arthritis, systemic lupus erythematosus, polyarteritis nodosa, ankylosing spondylitis, hemilaminectomy, hypothyroidism, carcinoid tumour and Hashimoto's thyroiditis.

Presentation

Symptoms may occur such as low back pain, nonspecific systemic complaints, and lower limb oedema¹. The diagnosis is usually late when a patient is evaluated for renal insufficiency and obstructive uropathy.

• Most patients present with nonspecific symptoms, including dull abdominal pain, of less than 12 months in duration.

• Patients may present with the complications of RPF - see 'Complications' section below.

• Early clinical features depend on any underlying cause.

• Advanced disease causes obstructive uropathy. The patient may present with acute kidney injury or chronic kidney disease resulting from ureteric involvement.

• Reduced blood flow to the lower limbs may cause features of peripheral arterial disease.

• The most common presentation is pain, which may occur in the loin, back, scrotum or lower abdomen⁶.

• Fever, weight loss, nausea and vomiting, malaise and peripheral oedema may occur.

• Urinary features include polyuria, polydipsia, anorexia, nocturia, oliguria, urinary frequency and haematuria.

• Children may present with hip or gluteal pain.

Differential diagnosis⁷⁸

• Other conditions that can cause ureteric obstruction and either acute kidney injury or chronic kidney disease - eg, retroperitoneal abscess, periaortic haematoma, pelvic surgery, radiation therapy and amyloidosis.

• Similar radiological appearances may be caused by abdominal aortic aneurysm, lymphomas, sarcomas, pancreatic carcinoma and metastatic malignancies.
  

Investigations

There needs to be a high index of suspicion of a diagnosis of RPF when patients present with an elevated ESR and CRP and renal insufficiency from obstructive uropathy.

Biopsy remains the gold standard for diagnosis but radiological investigations may also be useful⁸.

• Blood and urine tests: findings may include renal function tests (renal dysfunction), FBC (anaemia, raised white cell count), raised ESR, and urinalysis and urine culture (pyuria).

• Plain X-ray: nonspecific but may show evidence of complications - eg, bowel obstruction, pulmonary oedema (acute kidney injury).

• Ultrasound: may help in identifying the retroperitoneal mass; can demonstrate the degree of obstruction to the ureters and kidneys.

• Barium follow-through and enema: bowel obstruction.

• Intravenous urography (IVU): shows dilated ureters with medial deviation of ureters. IVU may lead to contrast nephropathy; therefore, good hydration is essential and IVU should be used with caution in the elderly and those with renal impairment (always check renal function beforehand).

• Retrograde pyelography: for patients with severely impaired renal function.

• Aortography, venography, and lymphangiography help in assessing the level and extent of occlusion.

• CT and MRI scanning: delineation of the extent of the retroperitoneal fibrosis and help to exclude secondary causes.

• Isotope renography is useful in the serial assessment of renal function.

• Biopsy under CT guidance⁹: differentiate benign masses from malignant retroperitoneal masses; biopsy in RPF shows periaortic inflammation with lymphocyte and plasma cell infiltrate.

• The diagnosis may not be established until surgical exploration.

Management

• In drug-related RPF, stopping the offending drug may result in resolution of urinary tract obstruction and symptoms.

• Medical treatment of RPF depends on the underlying cause. In patients with idiopathic RPF, glucocorticoids are traditionally considered the mainstay of treatment. The medical literature describes an 80% response rate when treating RPF with steroids alone¹.

• Rituximab has also been used with good effect¹⁰.

• Drainage of the upper urinary tract can be performed as a temporary measure. Percutaneous nephrostomy helps restore renal function, fluid, electrolyte and acid-base balance prior to surgery.

• Surgery may be required to resolve urinary tract obstruction or obstruction of other structures⁶.

• Laparoscopic ureterolysis is very effective for patients with RPF of all causes, with morbidity and efficacy comparable to open surgery.

Complications

• Hypertension.

• Fibrosis may cause compression of the major arteries, veins and lymphatics, resulting in thrombophlebitis, arterial insufficiency and lower limb oedema.

• Obstruction of the duodenum and colon may cause bowel obstruction.

• Obstruction of the common bile duct may cause jaundice.

• Spinal involvement may cause neurological abnormalities in the lower limbs.

Prognosis

Symptoms often begin to improve within a few days of starting treatment and CT imaging may demonstrate resolution of the mass a few weeks later. Full resolution will depend on the degree of severity of the disease and the degree of entrapment of retroperitoneal structures at presentation - particularly renal or bowels¹.

• Idiopathic (non-malignant) RPF has a generally good prognosis unless not appropriately diagnosed or treated, when the disease can cause severe complications - eg, end-stage kidney disease.

• Malignant RPF has a poor prognosis. Most patients only live for 3-6 months after receiving a diagnosis of malignant RPF.

• Lifelong follow-up is required for possible progressive or recurrent disease.