Retroperitoneal Fibrosis: Symptoms, Types, Causes and Treatment

Retroperitoneal fibrosis (RPF) is a rare and enigmatic condition where abnormal fibrous tissue develops in the retroperitoneum—the space behind the abdominal organs. This tissue can entrap vital structures such as the aorta, ureters, and other organs, leading to a host of complications. Although RPF remains poorly understood, advances in imaging and immunology have shed light on its presentations, causes, and evolving treatment strategies. In this article, we explore the key symptoms, various types, underlying causes, and evidence-based treatments for retroperitoneal fibrosis.

Symptoms of Retroperitoneal Fibrosis

RPF often develops insidiously, meaning its symptoms can be subtle at first. Many people initially attribute their discomfort to more common conditions, which often delays diagnosis. However, understanding the hallmark symptoms can prompt timely evaluation and intervention.

Symptom	Description	Consequence	Source(s)
Pain	Dull, constant pain in lower back, abdomen, or hips	Common presenting symptom, may radiate	1 2 3 4 5 6
Weight Loss	Unintentional weight reduction	May indicate systemic involvement	1 5
Constitutional	Fatigue, fever, malaise	Systemic inflammation	5 9 13
Ureteral Obstruction	Difficulty urinating, flank pain	Can cause hydronephrosis, renal failure	1 5 7 9 13
Vascular Symptoms	Swelling/pain in legs, scrotal swelling	From vessel compression or obstruction	2 5

Table 1: Key Symptoms

Common Presenting Complaints

The most frequent symptoms are persistent, dull pain in the lower back, hips, or abdomen. This pain is typically non-specific and can last for weeks or months before more serious symptoms develop. Weight loss and general malaise are also common, reflecting underlying inflammation or immune activation 1 3 4 5.

Renal and Urinary Symptoms

A major clinical concern in RPF is the entrapment of the ureters, which are the tubes that drain urine from the kidneys to the bladder. When these become compressed, patients may experience flank pain, reduced urine output, or even signs of renal failure. In severe cases, this can progress to chronic kidney disease or acute renal failure if left untreated 1 5 9 13.

Vascular and Systemic Manifestations

The fibrous tissue can encase blood vessels such as the aorta and the inferior vena cava. This can lead to swelling of the legs, scrotal swelling in men, or even bowel symptoms if blood flow to the intestines is affected. Constitutional symptoms like fever and fatigue may also be present, particularly in more aggressive or systemic cases 2 5 9 13.

Less Common Features

Occasionally, RPF may cause symptoms outside the retroperitoneum, such as involvement of the pancreas, bile ducts, or even the mediastinum. These atypical presentations are more likely in cases associated with IgG4-related disease 6 8 10 11.

Types of Retroperitoneal Fibrosis

RPF is not a single disease but a spectrum of disorders with different triggers and associations. Recognizing these types is crucial for guiding treatment and predicting outcomes.

Type	Key Features	Distinguishing Factor	Source(s)
Idiopathic	No identifiable cause, immune-mediated, often middle-aged men	Most common (~75%); may overlap with IgG4-RD	5 7 9 10 11 12 13
IgG4-related	Elevated IgG4, multi-organ involvement	Now recognized subset of idiopathic cases	8 10 11 12 13
Secondary	Linked to drugs, malignancy, infection, radiation	Clear precipitating factor	5 7 10 12
Malignant	Due to cancer infiltration	Mimics RPF, needs biopsy for diagnosis	6 7

Table 2: Types of Retroperitoneal Fibrosis

Idiopathic Retroperitoneal Fibrosis (IRF)

This is the most common form of RPF, accounting for about three-quarters of cases. It tends to affect adults in their 50s and 60s, with a slight male predominance. The pathogenesis is believed to be immune-mediated, and IRF is often associated with other autoimmune conditions 5 7 9 10 13.

IgG4-Related Retroperitoneal Fibrosis

Recent research has identified a subset of RPF cases as part of the spectrum of IgG4-related disease (IgG4-RD). These patients may have elevated serum IgG4 levels and often present with involvement of multiple organs, such as the pancreas (autoimmune pancreatitis), bile ducts, lungs, or thyroid. IgG4-RPF can be difficult to distinguish from idiopathic cases without specific testing 8 10 11 12 13.

Secondary Retroperitoneal Fibrosis

Secondary RPF is less common and is linked to a clear external cause. Key triggers include:

• Chronic use of certain drugs (e.g., ergot derivatives, beta-blockers)
• Malignancies, especially lymphomas and metastatic cancers
• Infections (tuberculosis, chronic urinary tract infections)
• Radiation therapy to the abdomen or pelvis
• Rare histiocytic disorders (e.g., Erdheim-Chester disease) 5 7 10 12

Malignant-Associated RPF

Some malignant tumors can mimic RPF radiologically and clinically. Biopsy is often necessary to distinguish malignant RPF from benign forms, especially when atypical features or rapid progression are noted 6 7.

Causes of Retroperitoneal Fibrosis

Understanding what causes RPF is pivotal for preventing recurrence and tailoring treatment. While many cases are idiopathic, ongoing research has unveiled both immune and environmental contributions.

Cause	Description	Risk Factor/Association	Source(s)
Idiopathic	Unknown, likely immune-mediated	Genetic, autoimmune links	5 7 9 10 12 13
IgG4-Related	Autoimmune, IgG4 antibody involvement	Other IgG4-RD conditions	8 10 11 12 13
Drugs	Ergot derivatives, beta-blockers, methysergide	Medication history	5 7 12
Malignancy	Cancer infiltration or paraneoplastic	Lymphoma, ovarian, GI tumors	5 6 7 12
Infections	Chronic infections (TB, UTI)	Geographic, immune status	7 12
Environmental	Asbestos, smoking	Occupational, lifestyle	13
Radiation	Previous abdominal/pelvic radiotherapy	Cancer history	7 12

Table 3: Causes and Risk Factors of RPF

Immune and Autoimmune Mechanisms

Most idiopathic cases are thought to result from immune-mediated inflammation. Genetic predisposition (such as HLA-DRB1*03) and associations with other autoimmune conditions (e.g., Hashimoto’s thyroiditis, psoriasis) support this theory 7 9 13. A key driver in many cases is fibroblast activation by immune cells, leading to excessive collagen deposition and fibrosis 13.

IgG4-Related Disease

A substantial proportion of idiopathic RPF cases are now attributed to IgG4-related disease. This systemic autoimmune disorder is characterized by infiltration of IgG4-positive plasma cells and elevated serum IgG4. Other organs may also be affected, and the condition responds well to immunosuppression 8 10 11 12 13.

Secondary Factors

Chronic exposure to certain drugs (like ergot derivatives and beta-blockers), infections, and environmental factors such as asbestos and smoking have been implicated. These causes are often identified through a careful history and may require discontinuation or treatment of the underlying trigger 5 7 12 13.

Malignancy and Infiltrative Diseases

Some cancers and rare histiocytic diseases can directly infiltrate the retroperitoneum, mimicking or causing secondary RPF. Identifying these requires imaging and sometimes biopsy, especially in atypical or rapidly progressive cases 6 7.

Treatment of Retroperitoneal Fibrosis

Managing RPF is a multi-step process: relieving symptoms, addressing complications (especially ureteral obstruction), and suppressing inflammation to prevent recurrence. Treatment is individualized based on disease type, severity, and underlying cause.

Therapy	Approach	Indication/Effect	Source(s)
Glucocorticoids	Prednisone, prednisolone	First-line, induces remission	5 9 13 14 15
Immunosuppressants	Azathioprine, mycophenolate mofetil	Steroid-sparing, refractory cases	9 13 17
Tamoxifen	Estrogen receptor modulator	Alternative for mild/relapsing disease	14 16
Biologics	Rituximab	Severe/refractory or IgG4-RD	9 13
Urological Intervention	Stenting, nephrostomy, ureterolysis	Relieve obstruction, preserve renal function	1 13 15
Surgery	Ureterolysis	Refractory or complicated cases	13 15

Table 4: Treatment Options for RPF

Medical Therapy

Glucocorticoids are the cornerstone of RPF treatment, especially for idiopathic and IgG4-related cases. High-dose prednisone is typically started and tapered over months. Studies show good rates of remission and symptom control, but relapse is not uncommon, necessitating long-term monitoring 5 9 13 14 15.

Immunosuppressants such as azathioprine and mycophenolate mofetil are often added when steroids alone are insufficient, or as steroid-sparing agents. Combined therapy has shown promising results in reducing mass size and normalizing lab markers 13 17.

Tamoxifen, an anti-estrogen agent, has been used as an alternative, especially in cases where steroids are contraindicated. While some patients respond well, relapse rates are higher compared to glucocorticoids, so it is generally reserved for milder forms or maintenance therapy 14 16.

Biologics like rituximab (a B-cell depleting agent) are emerging as options in refractory cases, particularly those associated with IgG4-RD. Early data suggest efficacy, but more research is needed 9 13.

Interventional and Surgical Management

If RPF causes ureteral obstruction, urological interventions such as ureteral stenting or nephrostomy tubes are crucial to relieve pressure on the kidneys and prevent permanent damage. Surgery (ureterolysis) is reserved for cases unresponsive to medical therapy or with complex anatomical involvement 1 13 15.

Monitoring and Long-Term Care

Patients require regular follow-up with imaging (CT or MRI) and lab tests to monitor for recurrence or progression. Relapses can occur in up to half of patients, making lifelong surveillance important 13 14.

Special Considerations

• Secondary RPF: Treat the underlying cause—discontinue offending drugs, treat infections, or address malignancy as appropriate 5 7 12.
• IgG4-RD: Monitor and manage other organ involvement; respond well to immunosuppression 10 11 12 13.
• Malignant RPF: Requires oncological evaluation and treatment.

Conclusion

Retroperitoneal fibrosis is a complex and rare disorder that can cause significant morbidity if unrecognized. Here’s what to remember:

• Symptoms are often insidious: Look for persistent lower back/abdominal pain, weight loss, and urinary or vascular symptoms.
• Multiple types exist: Idiopathic (including IgG4-related), secondary, and malignant forms require different approaches.
• Causes are diverse: Most cases are immune-mediated, but drugs, infections, environmental exposures, and malignancy can play a role.
• Treatment is evolving: Steroids are first-line, with immunosuppressants, tamoxifen, biologics, and surgical options tailored to individual needs.
• Lifelong monitoring is crucial: Relapse is common, and early intervention prevents complications like kidney failure.

Understanding and managing RPF requires a multidisciplinary, patient-centered approach—one that combines clinical vigilance, timely imaging, and evidence-based therapy to achieve the best outcomes.