Organ affected: Retroperitoneal

Common questions about RPF monitoring and treatment

After learning that you have retroperitoneal fibrosis (RPF), it is normal to have many questions that do not fit neatly into a single appointment:

• The initial emotion may be relief, if you have previously been told that you might have cancer.

• You may also feel confusion: what caused this and why did it happen to me?

• And you may be uncertain. Is this new diagnosis really right? What is going to come next?

If you’ve just been diagnosed with RPF, it is natural to wonder whether every new ache or pain represents a worsening of the disease. You may be surprised that much of your bloodwork – even your blood IgG4 level, for example – is normal. And finally, you will be curious about how this condition is treated and what you can expect in the future.

In this lesson, we will walk through common questions patients and caregivers ask about IgG4-related RPF. The goal is not to replace your care team’s advice. The goal is to help you understand the thinking behind follow-up decisions, so your next conversation with your clinician feels clearer and more productive.

1. If I have back, hip, or flank pain, does that mean RPF is active?

Not always. Back and hip pain are very common, and most back pain is caused by muscles, joints, discs, or nerves rather than RPF. Still, RPF can cause back, flank, abdominal, groin, or side pain because the inflamed tissue sits deep in the back of the abdomen.

A helpful clue is the pattern of pain. RPF pain may be steady, deep, and not clearly tied to one movement. Pain that gets worse only with a certain position, stretch, or activity may point more toward a musculoskeletal cause, such as a joint, tendon, or muscle problem.

The safest approach is to tell your care team when pain is new, persistent, severe, or different from your usual pattern. Your clinician may ask questions about leg swelling, urine output, and blood pressure, or perform investigations such as blood tests to measure kidney function or imaging studies to see how current evidence of RPF compares to previous studies.

2. Can RPF be active if my IgG4, ESR, and CRP tests are normal?

Yes, it can, and this is one of the reasons that assessing RPF is challenging. Blood tests are can be useful, but they often do not tell the whole story. Serum IgG4 level means the amount of IgG4 antibody measured in the blood. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are inflammation markers that are sometimes useful, as well. Elevations in these markers are not specific to disease activity in RPF, however, and must be interpreted in the context of a patient’s overall clinical picture. ¹

Doctors do not make RPF decisions from blood tests alone. They combine your symptoms, exam, kidney tests, urine tests, and imaging, and what they understand about this history of your problem to make the next decisions about management.

A normal lab result can be reassuring, but it should not be the only piece of information used to decide whether RPF is quiet.

3. Which scan is best: CT, MRI, MRCP, ultrasound, or PET/CT?

It’s not a matter of which is best, but rather, which may provide the best information at the current time or answer a question about changes in your condition. Each imaging test answers a different question.

A CT scan can show the size, shape, and location of RPF tissue. It is often useful for seeing whether there is soft tissue around the aorta, iliac vessels, or ureters. CT can be a practical screening tool when the question is whether RPF is present and it is probably the test through which RPF is found most often.

An MRI can also show RPF tissue and may be used when clinicians want more detail without radiation. It may be especially useful in some people who need repeated imaging because MRI studies, in contrast to CT studies, do not involve ionizing radiation in order to obtain images.

An MRCP is a special type of MRI that focused on the bile ducts and pancreas. It can be very helpful for pancreatitis or bile duct questions, but it may not fully evaluate the retroperitoneal space unless the scan is ordered and protocolized for that purpose. An MRCP is often paired with an MRI of the abdomen if it is known that particular attention must be paid to the pancreas and bile ducts.

An ultrasound can be helpful for checking hydronephrosis, which means swelling of a kidney because urine is backing up. Ultrasound may not show the full RPF tissue as clearly as CT or MRI, but it can help answer the question of whether or not hydronephrosis is present.

A PET/CT scan can show areas of active inflammation by looking for regions of increased glucose uptake. Processes that are metabolically active (as inflammation is, for example) are associated with high glucose uptake by the cells in the involved area. PET/CT offers the ability to measure the degree of disease activity. PET/CT may help show the distribution of disease, guide biopsy, and assess treatment response in selected cases.²

4. What does PET activity mean?

PET activity usually means that tissue is using more glucose than expected. In inflammatory disease, this can suggest active inflammation. But PET activity is not a diagnosis by itself. Infection, cancer, healing tissue, and other inflammatory conditions can also “light up.”

In RPF, PET/CT can sometimes help clinicians decide whether a mass-like area is metabolically active and whether treatment is working. Newer research supports PET/CT as a useful tool for treatment monitoring and prediction in RPF, but it is still one piece of the whole picture. ³

A practical way to think about PET is this: PET can show where the immune system may be active, while CT or MRI shows the structure and size of the tissue. Doctors often need both kinds of information, plus kidney tests and symptoms, to make a treatment decision.

5. What counts as remission or a flare?

Remission means the disease is quiet and that it is not causing active problems. In RPF, remission may mean that symptoms have improved, that urine is draining normally from the kidneys, that kidney function is stable, and that imaging confirms improvement or stability in the amount of fibrosis present in the retroperitoneum. In contrast, a flare of RPF means that disease activity has returned or worsened after a period of control.

6. When does RPF need treatment?

RPF usually needs treatment when it is active. At such times, there may be evidence that the region of RPF is growing, and the patient may have recurrent symptoms (e.g., flank pain, leg swelling). RPF that is active again may threaten kidney function by causing hydronephrosis or it may affect other organs in the retroperitoneum, with a variety of potential consequences.

The need for treatment is urgent when urine flow is blocked and the condition of hydronephrosis is established, posing a risk of permanent kidney injury. In those situations, doctors may need to restore adequate drainage of the kidney through the placement of either a ureteral stent or a nephrostomy tube. While those mechanical interventions are being performed, plans for establishing or re-establishing control of the underlying inflammation need to begin, as well. Close collaboration between different types of clinicians, for example, between rheumatologists and urologists, are critical at such times.

If RPF is stable, kidney drainage is safe, kidney function is steady, and symptoms are mild or absent, the care team may choose careful monitoring instead of immediate treatment. Monitoring is not “doing nothing.” It is a planned way of watching closely so treatment can begin if the disease changes.

7. Why do some people need maintenance therapy?

Maintenance therapy means treatment used to keep disease quiet after it has improved. This is different from induction therapy, which is the first stronger treatment used to calm active inflammation.

Steroids (prednisone, for example) usually work quickly, but they are not a good long-term solution for many people because of the inevitable side effects that develop over time. Clinicians often look for steroid-sparing medicines that help maintain remission, such as methotrexate, azathioprine, or mycophenolate in selected cases. A 2025 randomized trial in idiopathic RPF found that low-dose prednisone plus methotrexate was approximately as good as standard-dose prednisone for remission and led to a reduction in total glucocorticoid steroid exposure.⁵

For IgG4-RD, B-cell therapy may also be used. Inebilizumab, a CD19-directed B-cell-depleting treatment, reduced flare risk in the MITIGATE trial and became the first FDA-approved treatment for adults with IgG4-RD in 2024.⁶

8. How do doctors decide when to repeat rituximab or another B-cell treatment?

There is no single schedule that fits every person. Doctors consider your organs involved, past flare pattern, infection history, immunoglobulin levels, kidney function, imaging, and how long you usually stay well after treatment.

B-cell depletion can be like cutting the grass. The grass always grows back at some point, so some people need to be treated with maintenance therapy on a regular basis if a disease recurrence would pose an immediate threat to the patient’s overall health or to the function of a specific organ.

On the other hand, overtreatment can also be problematic, because immunosuppression caused by B-cell depletion when it is not needed may predispose patients to other sets of complications, particularly increased risks of some types of infections. For these reasons, the timing of treatment always involves balances of potential benefits and risks.

The most important point is that maintenance decisions are individualized. A person who relapses frequently needs a different plan than someone whose disease remains quiet for long periods after treatment.

9. Should I wait for my IgG4 level to rise before treatment?

Not necessarily. If your IgG4 level was high at diagnosis and tracks well with your disease, it may help your doctor follow activity. But IgG4 levels do not work perfectly for everyone as an indication of relapse.

Doctors usually do not wait for one blood test to become abnormal if there are stronger signs of active disease, such as hydronephrosis, worsening kidney function, growth on imaging, new organ involvement, or clear return of symptoms. On the other hand, a mildly abnormal IgG4 level by itself may not mean treatment is needed.

Rather than focusing only on the IgG4 level or any single test, the better question is: What pattern do my labs, imaging, symptoms, and kidney tests show together?

10. Do I need scans every year forever?

Not always. Long-term follow-up matters, but the schedule should fit the person. Repeating CT scans too often can add radiation exposure, so many clinicians try to avoid unnecessary CT imaging when symptoms and labs are stable.

Symptoms and basic labs can guide follow-up in people who are doing well, while imaging is used when there is a reason to look again. That reason might be new symptoms, abnormal kidney tests, rising inflammation markers, concern for recurrence, or a need to check whether hydronephrosis has returned.

For some people, ultrasound or MRI may help reduce radiation exposure. For others, CT may still be the clearest and most useful test. Your care team will weigh clarity, safety, kidney function, contrast risks, and the question being asked.

11. What symptoms should prompt a call to the care team?

The most important thing to look out for is a return of symptoms that remind you of those you had during the time leading up to your RPF diagnosis. When RPF returns, it usually does so in a manner similar to the way it began.

In addition, other specific reasons to alert your care team are the development of new or worsening flank pain, abdominal or groin pain, or back pain; finding blood in the urine; swelling of one or both legs; swelling (in men) of the scrotum, new-onset of high blood pressure, or unexplained weight loss.

12. How can I prepare for my next appointment?

Bring a short written list. It helps your clinician see the pattern.

• New symptoms, when they started, and whether they are constant or movement-related.

• Blood pressure readings, especially if they are higher than usual.

• Any changes in urination, pain with urination, or urinary infections.

• Recent creatinine, eGFR, urinalysis, ESR, CRP, and IgG4 results, if available.

• Dates and reports from CT, MRI, ultrasound, PET/CT, or MRCP.

• Current medicines, steroid dose, last B-cell therapy date, and side effects.

• Questions about whether your disease is active, stable, or scarred.

• Questions about whether treatment, monitoring, or a procedure is the next step.

Summary

RPF follow-up can feel confusing because no single symptom, lab test, or scan tells the whole story. Mild pain does not always mean RPF is active. Normal labs do not always rule it out. PET activity can help show inflammation, but it must be interpreted carefully. CT, MRI, ultrasound, MRCP, and PET/CT each answer different questions.

The heart of RPF care is pattern recognition. Your team is looking at symptoms, kidney drainage, kidney function, blood pressure, imaging, medication risks, and your history of flares. When these pieces are put together, the next step becomes clearer: watch closely, treat inflammation, protect the kidneys, adjust maintenance therapy, or involve urology.

References

1. Tang CYL, Chua WM, Cheng LT, Fong W, Zaheer S, Lam WWM. 18F-FDG PET/CT manifestations of IgG4-related disease. British Journal of Radiology. 2021;94:20210105. https://pmc.ncbi.nlm.nih.gov/articles/PMC8764915/

2. Orozco-Gálvez O, et al. Response to treatment in IgG4-related disease assessed by quantitative PET/CT scan. Clinical Nuclear Medicine. 2021. https://pmc.ncbi.nlm.nih.gov/articles/PMC11669109/

3. Bayerl C, et al. [18F]FDG PET/CT for treatment monitoring and prediction of progression in retroperitoneal fibrosis. European Journal of Nuclear Medicine and Molecular Imaging. 2025. https://link.springer.com/article/10.1007/s00296-024-05611-7

4. Wiber S, IgG4ward Foundation, CanJam Presentation “Retroperitoneal Fibrosis.”

5. Peyronel F, Palmisano A, Maritati F, Alberici F, Urban ML, Gianfreda D, et al. Methotrexate and low-dose prednisone in idiopathic retroperitoneal fibrosis: a randomised clinical trial. Journal of Autoimmunity. 2025;157:103487. https://pubmed.ncbi.nlm.nih.gov/40974866/

6. Stone JH, et al. Inebilizumab for treatment of IgG4-related disease. New England Journal of Medicine. 2025;392:1168-1177. https://pubmed.ncbi.nlm.nih.gov/39541094/

7. Scheel P, IgG4ward! Jam Video Series- Video 4 - Retroperitoneal Fibrosis. https://igg4ward.org/resources/igg4ward-jam-video-series-video-4-retroperitoneal-fibrosis/MBOREE_Film%234_Dr_Scheel_RPF_Breakout_Session.mp4?rlkey=ay4gg8cjlm1amwdo0xib11sio&st=yh3c17a6&dl=0