Is retroperitoneal fibrosis an autoimmune disease?

September 26, 2025 •

3 min read

Affecting approximately 1 in 200,000 people per year, retroperitoneal fibrosis (RPF) is a rare disorder characterized by the development of excessive fibrous tissue. This aggressive inflammation raises a crucial question for patients and clinicians alike: is retroperitoneal fibrosis an autoimmune disease? The answer is nuanced, with a significant link to immune system dysfunction.

Quick Summary

Retroperitoneal fibrosis (RPF) is not always a classic autoimmune disease, but a large portion of idiopathic cases are considered part of the autoimmune spectrum, especially IgG4-related disease. An abnormal immune response drives the characteristic inflammation and fibrosis in many cases. The cause is often unknown, but a strong autoimmune component is increasingly recognized.

Key Points

Autoimmune Link is Strong: The majority of idiopathic RPF cases are now understood to have a significant autoimmune or immune-mediated basis, driven by an abnormal inflammatory response.
IgG4-Related Disease Connection: A large subset of RPF is part of IgG4-related disease, a systemic autoimmune condition characterized by high IgG4-producing plasma cells.
Idiopathic vs. Secondary: RPF is classified as either idiopathic (cause unknown, often immune-related) or secondary (caused by drugs, infections, or malignancy), with distinct management implications.
Treatment with Steroids: Many RPF patients, particularly those with IgG4-RD, respond well to corticosteroids, highlighting the inflammatory nature of the disease.
Diagnosis is Multifaceted: Diagnosis requires imaging (CT, MRI) and may involve a biopsy to rule out malignancy and confirm the presence of fibrosis and specific cell types, like IgG4 plasma cells.
Risk Factors and Complications: Smoking, asbestos exposure, and other autoimmune conditions are risk factors, with the main complication being obstructive uropathy that can lead to kidney failure.

Understanding Retroperitoneal Fibrosis (RPF)

Retroperitoneal fibrosis, also known as Ormond's disease, is a rare disorder involving the formation of fibrous, inflammatory tissue behind the abdominal lining. This tissue can compress vital structures like the aorta and ureters, potentially leading to kidney damage and obstructive uropathy. While more common in men aged 40 to 60, the precise cause is often unclear.

The Autoimmune Connection: Idiopathic vs. Secondary RPF

RPF is classified as either idiopathic (IRPF) or secondary. IRPF makes up about 70% of cases with no known trigger, while secondary RPF (30%) is linked to factors like medications, infections, or malignancies. Growing evidence suggests a significant autoimmune or immune-mediated element in IRPF. This is supported by patients' positive response to immunosuppressive treatments, the association of IRPF with other autoimmune conditions, elevated inflammatory markers, and the presence of autoantibodies in some cases.

The Prominent Role of IgG4-Related Disease

A key development in understanding RPF's autoimmune aspect is the recognition of IgG4-related disease (IgG4-RD), a systemic disorder involving IgG4-producing plasma cells and fibrosis. A substantial number of IRPF cases are now diagnosed as IgG4-RD. This is important because IgG4-related RPF often features higher serum IgG4 levels, involvement of multiple organs, and a better response to steroid therapy compared to non-IgG4-related IRPF. The connection to IgG4-RD is further solidified by specific tissue characteristics and the response to therapies targeting antibody-producing B-cells.

Potential Triggers and Associated Conditions

Beyond the autoimmune link, several factors may trigger the inflammation in RPF. These include environmental exposures like cigarette smoke and asbestos, inflammation of the aorta (aortitis), and associations with other systemic conditions such as Erdheim-Chester disease or sarcoidosis.

Signs, Symptoms, and Diagnosis

Early RPF symptoms are often non-specific, such as dull pain in the abdomen or back. As the fibrosis grows, more severe issues can arise, including kidney problems from blocked ureters, leg and foot swelling due to compressed veins, and systemic symptoms like weight loss and fatigue. Diagnosis typically involves imaging like CT or MRI to see the fibrous mass. A biopsy may be needed to rule out malignancy and confirm the diagnosis. Blood tests for inflammatory markers, kidney function, and sometimes IgG4 levels help in diagnosis and differentiating RPF types.

Management and Treatment Approaches

RPF treatment focuses on relieving obstruction and controlling inflammation. High-dose corticosteroids are often the first treatment, especially for IgG4-related RPF. Other immunosuppressants like tamoxifen, mycophenolate mofetil, or rituximab may be used to reduce steroid dependence or for maintenance. Surgical procedures, such as placing ureteral stents, may be necessary for severe blockages to protect kidney function.

Comparison of Idiopathic and IgG4-Related RPF


Feature	Idiopathic (Non-IgG4) RPF	IgG4-Related RPF
Incidence	Accounts for a significant portion of IRPF cases.	Represents a large subset (35-60%) of idiopathic RPF.
Gender	Often shows a male predominance.	Greater male predominance observed.
Onset Age	Can have an earlier age of diagnosis compared to IgG4-related RPF.	Typically older age at disease onset.
Multi-Organ Involvement	Generally confined to the retroperitoneum.	Frequently involves multiple organs (pancreas, salivary glands, etc.).
Allergic Conditions	Less frequently associated with allergic diseases.	More commonly associated with allergic diseases and asthma.
IgG4 Levels	Serum IgG4 levels are typically normal or only mildly elevated.	Serum IgG4 levels are often significantly elevated, though not always.
Eosinophil Count	Typically a lower eosinophil count.	Often associated with elevated eosinophils.
Treatment Response	Responds well to steroids but may require longer courses.	Often shows a rapid and excellent response to steroid therapy.
Relapse Rate	Can experience relapse, but possibly lower than IgG4-RD.	Relapse is common, often correlating with inflammatory markers.

Conclusion: Navigating the Complexities

While not all retroperitoneal fibrosis cases are strictly autoimmune, a clear autoimmune component, particularly in the idiopathic form, is increasingly recognized. The strong link to IgG4-related disease, a systemic autoimmune disorder, has transformed the diagnostic and treatment approaches for many patients. Distinguishing between idiopathic RPF and its IgG4-related subtype is crucial for guiding treatment and understanding potential for relapse. Ongoing research into the autoimmune mechanisms of RPF is vital for developing better treatments. For up-to-date medical information, consult a healthcare provider or reliable sources like the National Institutes of Health.

Frequently Asked Questions

Idiopathic retroperitoneal fibrosis (IRPF) is a form of RPF where the cause is unknown. While it's not a secondary reaction to an external factor like a drug or infection, it is strongly suspected to have an autoimmune or immune-mediated origin.

IgG4-related disease is a systemic autoimmune disorder that can affect multiple organs, including the retroperitoneum. A significant percentage of what was previously considered idiopathic RPF is now classified as IgG4-related RPF, as it shares key histopathological features and elevated serum IgG4 levels.

Early symptoms are often non-specific but may include a dull, persistent pain in the lower abdomen, back, or flank. Systemic symptoms like fatigue, unexplained weight loss, and low-grade fever can also occur.

Diagnosis typically begins with imaging, like a CT or MRI, to identify the fibrous mass. To determine the cause, doctors use blood tests to look for inflammatory markers and autoantibodies, and may perform a biopsy of the tissue to rule out malignancy and identify specific cell types, like IgG4-positive plasma cells.

While medication can effectively manage the disease and induce remission, it often requires long-term treatment. Corticosteroids and immunosuppressants are the primary medical treatments. However, the condition can sometimes relapse, especially after discontinuing medication.

The prognosis depends heavily on the extent of the fibrosis, whether it's related to malignancy, and the degree of kidney damage. If caught early and managed effectively, especially if it's an IgG4-related case, the outlook is generally good. However, the condition can lead to permanent kidney damage if left untreated.

IgG4-related RPF is a specific subtype of idiopathic RPF associated with elevated serum IgG4 levels and multi-organ involvement. It is more likely to be associated with allergic conditions and has a higher relapse rate than non-IgG4 idiopathic RPF, despite often having a rapid initial response to steroids.