bubble_chart Overview

Idiopathic Retroperitoneal Fibrosis (RPF) is a rare disease first described by Albaran in 1905. It wasn't until Ormond reported two cases in 1948 that it gained widespread attention. The typical clinical manifestation involves ureteral compression due to retroperitoneal fibrosis, sometimes accompanied by venous obstruction. Based on certain features or possible etiological factors, this condition has been referred to by various names such as "fibrous retroperitonitis," "Gerota's fasciitis," "retroperitoneal vasculitis," "sclerosing retroperitoneal granuloma," "periureteral inflammatory fibrosis," and "chronic periureteritis." In recent years, literature on its etiology, pathology, clinical presentation, and CT findings has increased.

bubble_chart Etiology

The etiology of this disease is unknown and may be related to the following factors:

1. **Allergy Theory**: RPF is often accompanied by abdominal aortic aneurysm-like dilation, severe aortic wall calcification, ureteral obstruction, and peri-aortitis. Recently, Bullock suggested that RPF is an allergic reaction caused by the leakage of insoluble inflammatory lipids from the thinned aortic wall due to inherent atherosclerotic ecchymosis. Therefore, it should be renamed "chronic peri-aortitis." Sometimes, an insoluble polymer of oxidized lipids and proteins can be found in macrophages and lymph nodes around atherosclerotic vessels and within atherosclerotic ecchymotic plaques. Immunohistochemical studies show that this substance contains IgG and small amounts of IgM. These changes may result from an autoimmune reaction, particularly since the condition responds well to steroid therapy, supporting this hypothesis.

2. **Ergot Compound Theory**: Graham reported two cases of RPF in patients treated with methysergide. Later, a group of 27 cases of RPF was reported in patients taking methysergide for headaches, with many cases resolving after discontinuation of the drug. These observations suggest a causal relationship between methysergide and RPF. However, Blandy et al. noted that none of the RPF cases reported in the UK had taken this drug or any other ergot compounds. Methysergide is a 5-hydroxytryptamine (5-HT) blocker that increases endogenous 5-HT levels through competitive inhibition at receptor sites. Graham proposed that in susceptible patients, 5-HT may trigger an abnormal fibrotic reaction resembling carcinoid syndrome. 2-Bromoergocryptine (bromocriptine), a derivative of ergot alkaloids but not a 5-HT blocker, has also been associated with retroperitoneal and mediastinal fibrosis. It is possible that ergot alkaloids act as haptens, inducing allergic or autoimmune reactions, though conclusive evidence is lacking.

3. **Other Causes**: Some suggest RPF is linked to analgesic use, while others suspect β-adrenergic receptor blockers. However, Pryor argues that these drugs were more likely used to treat hypertension caused by RPF rather than being the disease's cause.

bubble_chart Pathological Changes

The pathological features are characterized by a dense fibrous tissue band centered around the lower abdominal aorta, extending to the surrounding common iliac vessels and occasionally reaching the inferior vena cava. Its upper edge is usually below the renal arteries, but fibrosis may occasionally occur around the thoracic aorta. It presents as a flat, firm, gray-white fibrous patch with typically clear boundaries and no encapsulation. As the lesion progresses, it envelops the structures in the retroperitoneal space without invading their walls. Typically, both ureters eventually become encased.

Histological changes: The fibrous tissue exhibits varying degrees of inflammatory changes. It appears to progress from an acute phase with abundant lymphocytes, plasma cells, some eosinophils, and rich small blood vessels to a chronic phase with relatively fewer cells and vessels. Cooksey examined surgical biopsy specimens from 10 cases and concluded that histological changes are unrelated to the disease stage. The affected ureteral tissue shows edema, lymphocyte infiltration in the suburothelial layer, and fibrosis of the muscular layer. Calcifications may be present within the fibrous tissue, and lymphatic vessels within the patch are completely obliterated. Adjacent tissues remain normal. Ureteral "obstruction" may be related to the loss of peristaltic function.

bubble_chart Clinical Manifestations

The early symptoms of RPF are insidious. The main manifestations include nonspecific back pain, abdominal pain, and flank pain, presenting as persistent dull or aching pain. It can occur at any age, even in newborns, but is most common in middle-aged individuals. Male patients are twice as likely as females to be affected, and both Caucasians and Black individuals can develop the disease. The onset is usually subtle, with a prolonged course, and diagnosis is often delayed for months or even years after the appearance of vague symptoms. Pain is the most common and often the earliest symptom, typically felt as a dull discomfort in the lower abdomen, flank, or lumbosacral region. Other symptoms may include anorexia, weight loss, and fatigue. Unilateral or bilateral leg swelling, scrotal swelling, or low-grade fever may also occur. Occasionally, a mass may be palpable in the abdomen or pelvis. In advanced stages, clinical manifestations often result from compression or involvement of adjacent organs. For example, ureteral stenosis can lead to proximal infection or dilation, causing flank or costovertebral angle pain, frequent urination, and nocturia. Bilateral ureteral obstruction may suddenly result in anuria. Since hydronephrosis or kidney infection is common, flank tenderness is frequently observed. Hypertension is common (one of the causes of headache) and is often due to renal obstruction, as blood pressure may normalize after ureteral decompression, surgical release, or removal of a non-functioning kidney. Gastrointestinal symptoms may be related to uremia or direct damage to the gastrointestinal tract (e.g., displacement or stenosis). Cases of biliary and pancreatic duct stenosis have been reported. Involvement of the portal or splenic vein can lead to portal hypertension, resulting in esophageal varices and ascites. Fibrosis may also obstruct lymphatic or venous drainage in the retroperitoneum or mesentery, causing protein-losing enteropathy or malabsorption. Compression or obstruction of retroperitoneal lymphatics, veins, or small vessels can lead to unilateral or bilateral leg swelling, penile swelling, or scrotal edema. Other possible findings include engorged or varicose abdominal wall veins, lower limb thrombosis, weak distal pulses, and intermittent claudication. RPF may coexist with fibrosis in other areas (e.g., mediastinum, bile ducts) and can even lead to sclerosing cholangitis or Peyronie's disease (fibrous, painful penile erection due to fibrous cavernositis).

bubble_chart Auxiliary Examination

1. Laboratory tests often show increased erythrocyte sedimentation rate, varying degrees of anemia and leukocytosis, occasionally eosinophilia, and elevated α and λ globulins on protein electrophoresis. Urinalysis may be normal or show a small number of white blood cells and red blood cells. In the late stage [third stage], uremia may occur. Therefore, when the urine of a uremic patient appears normal, attention should be paid to whether it is caused by retroperitoneal fibrosis.

2. X-ray examination: Intravenous urography may reveal displacement of one or both ureters. A diagnostically significant finding is the gradual tapering of the mid-ureter with segmental stenosis, which differs from the stenosis caused by tumors or stones—the latter lacks gradual tapering and only shows irregular narrowing. When the gastrointestinal tract is involved, double-contrast X-ray imaging may reveal segmental narrowing of affected intestines, such as the duodenum. Pelvic fibrosis can lead to rectal stenosis and straightening, accompanied by an elevated bladder in a teardrop shape. Venography can demonstrate stenosis of the inferior vena cava or iliac veins.

3. CT and MRI: Most cases can detect fibrous plaques or abnormal soft tissue masses, with enhanced scans showing dense fibrous tissue characteristics. Due to the lateral spread of fibrosis, the angles between the aorta and the left psoas muscle, as well as between the inferior vena cava and the right psoas muscle, may change. These imaging modalities can also reveal proximal ureteral dilation. While MRI is not superior to CT in displaying fibrous patches, it can show changes in vascular flow velocity. Therefore, CT is the preferred initial examination, and MRI is chosen when further hemodynamic assessment is needed.

4. B-mode ultrasound: PRF masses appear as hypoechoic or anechoic, lacking specific features. It can also assess the degree of urinary tract obstruction and hydronephrosis.

bubble_chart Diagnosis

The diagnosis of this disease emphasizes the importance of enhancing awareness and maintaining high vigilance. Patients who frequently take painkillers, methylergonovine, or other medications, and present with unexplained back pain, abdominal pain, dull pain in the lumbosacral region or lower abdomen, as well as portal hypertension, ascites, or protein-losing enteropathy, should be considered for possible diagnosis of this condition. B-ultrasound, CT, and X-ray examinations can provide valuable assistance in diagnosis.

bubble_chart Treatment Measures

1. Glucocorticoids

Early administration of glucocorticoids, especially when inflammatory tissue predominates, can show effects within weeks. Most reports indicate significant efficacy, even leading to noticeable reduction or disappearance of the mass. It is generally believed that better results may be achieved when the medication is used during the early stage of cellular infiltration, before fibrosis becomes dominant. For patients with mild-grade II urinary tract lesions, elderly or frail individuals, or those with systemic diseases, prednisone-type drugs are more suitable. Sometimes, they are also used for preoperative preparation or postoperative recurrence prevention. The initial dose is 30–60 mg of prednisone or prednisolone per day, gradually reduced to the lowest effective maintenance dose after the condition stabilizes, for a minimum of 3 months. Some have achieved better results by combining hormones with azathioprine, though the efficacy of radiotherapy remains uncertain. The mechanism of action of these drugs is the suppression of inflammatory responses.

2. Surgical Intervention

Although fibrosis itself rarely requires surgical resection, once extensive fibrosis develops, hormonal therapy is often ineffective. Surgery is necessary when organ compression affects function.

Performing a one-time bilateral ureterolysis, wrapping the ureter with the greater omentum, and relocating the ureter laterally can achieve better and sustained relief. Simple ureterolysis has a high recurrence rate. Sometimes, freeing the ureter may cause irreparable injury. These challenges often lead to the selection of various bridging surgical methods, such as ileal ureteral interposition, psoas hitch repair, Boari flap reimplantation, or renal autotransplantation.

In advanced stages, for severe urinary tract obstruction, percutaneous nephrostomy drainage can be performed. This method is superior to retrograde ureteral catheterization or stenting, as it not only promptly alleviates symptoms but also allows monitoring of renal function through urine electrolyte measurements, enabling most patients to avoid hemodialysis.

bubble_chart Prognosis

Retroperitoneal fibrosis is a disease with a certain degree of self-limitation and slow progression, and occasionally the inflammatory process may resolve spontaneously. If it is drug-induced (such as methysergide), discontinuation of the drug may lead to gradual recovery, which can take anywhere from several months to several years. The mortality rate of retroperitoneal fibrosis is about 9%, with the usual cause of death being renal insufficiency, often due to delayed diagnosis. The prognosis is relatively good when appropriate treatment is effective.

bubble_chart Differentiation

RPF should be differentiated from retroperitoneal lymphoma, proliferative lymphadenitis, metastatic tumors, primary tumors, periaortic hematoma, and amyloidosis. In addition to clinical manifestations, imaging examinations are primarily used.

The characteristic features of RPF include a large, homogeneous mass closely connected to the aorta; no significant compression or displacement of the aorta itself or surrounding organs; unchanged distance between the aorta and vertebral body; and medial displacement of the ureter in cases of stenosis.

1. Lymphoma

Retroperitoneal lymphoma has a wide distribution and appears as large nodular masses with uneven density on plain scans, possibly accompanied by mesenteric lymphadenopathy. There is no significant change after enhancement, and the distance between the aorta and vertebral body increases.

2. Metastatic tumors

Metastatic tumors lack fibrous tissue and present as discontinuous para-aortic lymphadenopathy. Enlarged mesenteric lymph nodes strongly suggest malignancy. After enhancement, the masses show uneven nodular enhancement. The final diagnosis still relies on histocytological examination.