Retroperitoneal Fibrosis

What is Retroperitoneal Fibrosis?

Retroperitoneal fibrosis is an uncommon condition where the immune system causes ongoing inflammation and scarring in the area behind the abdominal cavity, particularly around the main blood vessels of the aorta and vena cava. This constant scarring can start to press on other structures in the same region, such as the tubes that carry urine from the kidneys to the bladder (ureters), the main artery (aorta), and main vein (vena cava).

This condition could happen on its own or it could be related to certain medications or other immune system issues. It might not cause any symptoms, but typically it causes a dull ache or discomfort in the lower back, sides, lower abdomen and groin. Other non-specific symptoms can include high blood pressure and poor kidney function (azotemia). Sometimes, the condition is discovered by chance during tests for other unrelated conditions, and in some cases, doctors may need to take a small piece of tissue (biopsy) to confirm the diagnosis.

The main treatment is medication, like steroids, to reduce the inflammation and scarring. Some severe cases may need surgery.

Retroperitoneal fibrosis used to be known as Ormond disease, named after the American doctor who first described it in 1948. However, the condition was actually first reported in 1905 by a French doctor. It’s also been referred to under a number of different terms like chronic periureteritis and fibrous retroperitonitis, but these terms are no longer used today.

What Causes Retroperitoneal Fibrosis?

Over 70% of cases of a condition called retroperitoneal fibrosis were previously not linked to a specific cause. However, many of these cases are now believed to be caused by a type of immune disorder named immunoglobulin G4 (IgG4)-related disease. This was first identified as a specific disease in 2003 and can affect different parts of the body. In fact, between 35% to 60% of all cases of retroperitoneal fibrosis, previously considered to have no known cause, are now attributed to IgG4-related disease. This has led to a new way of classifying retroperitoneal fibrosis – whether it’s related to IgG4 or not.

Around 30% of retroperitoneal fibrosis cases do have a known cause. It has been found that several medications have been linked to the development of this condition, particularly drugs like methysergide, methyldopa, bromocriptine, and other similar chemicals. Other medications that are inferred include beta blockers, hydralazine, and pain medication. Moreover, biological drugs, such as those that inhibit tumor necrosis factor (a protein involved in inflammation), have also been identified as secondary causes of this condition.

The condition also accounts for about 4% to 10% of a specific kind of abdominal swelling known as abdominal aortic aneurysms. Certain types of cancer, including carcinoid tumors, lymphomas, sarcomas, and colorectal, breast, prostate, and bladder cancers account for 8% of cases of retroperitoneal fibrosis, with lymphoma being the most common. In these cases, treating the underlying cancer is highly recommended.

Other causes of retroperitoneal fibrosis include infections such as actinomycosis, histoplasmosis, and tuberculosis, along with radiation therapy to the abdomen, abdominal bleeding, and major abdominal surgeries. Interestingly, exposure to substances like asbestos and tobacco smoke significantly increases the risk of getting this condition – each of these factors could increase the risk by 3 to 4 times. If one’s been exposed to both asbestos and a lot of tobacco smoke, the risk can go up 8 to 12 times!

Researchers also think that a molecule called ceroid, often found in fatty build-ups in blood vessels, could potentially trigger inflammation in the area around the aortic artery, hence contributing to the development of retroperitoneal fibrosis.

Risk Factors and Frequency for Retroperitoneal Fibrosis

Retroperitoneal fibrosis affects the back of the stomach and its true incidence isn’t known. However, each year, it’s estimated that 1.4 out of every 100,000 people will be affected by this condition. Most commonly seen in individuals aged 40 to 60, retroperitoneal fibrosis can still occur in children and older adults.

It seems to affect men more than women, with a ratio of about 2 to 3 males for every female afflicted. The frequency of a related disease, known as IgG4-related disease, is also unknown. For more information on IgG4-related disease, StatPearls’ companion resource can be consulted.

• Retroperitoneal fibrosis affects about 1.4 out of every 100,000 people each year.
• It typically affects individuals aged 40 to 60, but can occur in children and older adults.
• Men are more commonly affected than women, with a ratio of approximately 2 to 3 males diagnosed for every female.

Signs and Symptoms of Retroperitoneal Fibrosis

Retroperitoneal fibrosis is a condition that can cause a range of symptoms, the most common of which is an undefined discomfort that is often described as a dull pain in the abdomen, back, groin, or sides. This affects over 90% of patients. In men, pain in the testicles is also common, affecting more than half of the patients. The pain often projects to the groin area, isn’t typically sharp or colicky, isn’t influenced by body movement or physical activities, and usually worsens at night. Nonsteroidal anti-inflammatory drugs (NSAIDs) can usually control this pain. The condition can often present with obstructive uropathy, which is found in about 80% of cases, while involvement of the gastrointestinal system is less common. Fatigue and significant weight loss are other frequent symptoms, seen respectively in roughly 60% and 54% of patients.

The condition can obstruct the inferior vena cava, the large vein that carries deoxygenated blood from the lower half of the body back to the heart, due to external compression from the fibrous mass in the retroperitoneal area. This can lead to deep venous thrombosis and swelling of the lower extremities. Patients might also experience pain during leg exertion due to compromised arteries in the lower extremities, or symptoms of mesenteric ischemia (inadequate blood supply to the small intestine) due to compression of the mesenteric arteries. The fibrous mass often locates around the distal aorta between the fourth and fifth lumbar vertebrae, causing potential hydronephrosis (a condition where kidneys swell due to the inability to dispose of urine).

• Loss of appetite
• Lack of urine production
• Elevated blood urea nitrogen levels due to obstruction of both ureters (in over 50% of cases)
• Feeling unwell in general
• A buildup of fluid in the scrotum or an enlarged vein in the scrotum (for up to 60% of men with retroperitoneal fibrosis)
• Low, unexplained fever
• Lower urinary issues like pain during urination, urinating often, or feeling an urgent need to urinate
• Nausea
• Reduced urine production
• Inflammation of veins
• Thinning of kidney cortex (in 8% to 30% of cases)
• High blood pressure due to kidney problems (in 30% to 60% of cases)
• Inflammation of veins with clot formation
• Vomiting

In advanced stages of the disease, symptoms such as fluid buildup in the abdominal cavity, bowel obstruction, yellowing of the skin and eyes, swelling in the peripheries, spinal cord compression, and thrombosis can appear. Retroperitoneal fibrosis should be considered as a possibility in patients with chronic, unclear, dull abdominal or side pain (either on one or both sides) connected with newly found kidney failure or high blood pressure. However, it’s often first identified incidentally during imaging for other problems or unrelated conditions.

Physical exams may reveal tenderness at the angle between the last rib and the spine (CVA), and high blood pressure due to the fibrous mass impinging on the kidney artery can be frequent. Swelling in the lower extremities, signs of inflammation of veins with clot formation or deep vein thrombosis may be present. Men may commonly experience tenderness in the testicles, and a buildup of fluid in the scrotum might be present. In children, issues with extending the hip, and pain or discomfort extending to the hip or buttock region might be observed.

Testing for Retroperitoneal Fibrosis

Retroperitoneal fibrosis is a disease that often found unexpected when checking for issues like urinary tract blockage, unidentified kidney failure, or blood vessel problems. To assess you, the doctor will normally do a laboratory test and some form of kidney ultrasound or CT scan (a type of powerful X-ray).

In the blood results, there aren’t any clear or unique results that indicate retroperitoneal fibrosis, but some things could hint to the doctor about your condition:

– The enzyme alkaline phosphatase might be higher than usual, which could reflect your disease activity.
– Creatinine and blood urea nitrogen levels, two things that show how well your kidneys are working, might be high, particularly if there is a blockage in your urinary system.
– You could have normocytic anemia, a type of blood disorder that could be associated with kidney issues and chronic inflammation – inflammation that lasts for a long time or constantly recurs.
– A urine test could also be recommended.

Around 60% of people with unexplained retroperitoneal fibrosis have what’s known as positive antinuclear antibody (ANA) titers; these can help predict if the disease will come back after treatment. Levels of two markers that show inflammation in your body – ESR and CRP – are often increased in half or two-thirds of retroperitoneal fibrosis patients. These can be helpful signs of how well the treatment is working.

Your thyroid will be checked, as around a quarter of those with retroperitoneal fibrosis will also have an autoimmune disease of the thyroid, often showing specific antibodies.

Additional tests could include checking the levels of different antibodies in your blood, the concentration of a specific type of antibody known as IgG4, and a test called serum protein electrophoresis and free light chain assay, which checks the amount of different proteins in your blood.

To confirm the diagnosis, the doctor will need to use imaging tests, such as a CT scan or an MRI. However, these can’t definitively tell whether retroperitoneal fibrosis is benign (relatively harmless) or malignant (more serious). If initial medication doesn’t improve the condition, or in cases with specific symptoms, the doctor might perform a biopsy – removing a small piece of the affected area to examine more closely.

Physical tools such as CT scan, MRI, renal ultrasound etc help visualize and diagnose the condition as well as keep track of treatment efficiency. They offer insights into the stage and extent of retroperitoneal fibrosis and any associated lymph node enlargement or tumors. These tests can also be used to guide a biopsy to confirm the diagnosis.

In some cases, a specific type of imaging called positron emission tomography (PET) can identify areas of increased metabolic activity, which indicates more active parts of the disease. Although PET is not as reliable as CT or MRI for initial diagnosis, it is useful in monitoring the progress of the disease after diagnosis.

In specific scenarios, lymphangiography – an imaging study of the lymphatic system – can be beneficial. This technique can help reveal any obstruction in lymphatic vessels before urinary blockage from retroperitoneal fibrosis occurs.

In complex cases, it becomes necessary to retrieve a small sample of tissue from your body, for analysis under a microscope, this is known as a biopsy. This step is often ignored in straightforward cases but becomes necessary in situations that suggest the presence of an underlying health problem. Clinically, the biopsy is recommended in cases like failure to respond to initial treatment, suspicion of a prior disease that could involve the retroperitoneum, and clinical, imaging, or laboratory findings that suggest a possible underlying malignancy. The biopsy is also needed when the imaging results and ongoing symptoms do not match, when an open surgery to treat vascular or urinary obstruction by retroperitoneal fibrosis is decided, and when the mass appears to infiltrate the surrounding structures linked with retroperitoneal fibrosis, or for atypical locations of the mass.

Treatment Options for Retroperitoneal Fibrosis

If you are suffering from retroperitoneal fibrosis, your initial treatment will depend on how severe your symptoms are. For instance, if you are showing signs of a blockage in the tubes (ureters) that move urine from your kidneys to your bladder, you’ll need immediate medical attention. Usually, this involves finding ways to relieve the pressure in the blocked tubes, like inserting a small tube or a stent. While both procedures are effective, inserting a stent is generally preferred because it’s easier to do and most people feel better afterwards. In 95% of cases, these stents can be successfully removed once you’ve had appropriate treatment with steroids, usually within 30 days.

If you’re really sick and struggling with an imbalance of salts in your body (electrolytes), a nephrostomy tube (a tube that directly drains your kidneys) may be the first step. After the pressure on your kidneys has been relieved, doctors must keep a close eye on you for ‘postobstructive diuresis’. This is a condition where your body produces a large amount of urine after a blockage has been relieved. It usually ends within 48 hours, but it can put you at risk of severe dehydration and low blood pressure also called ‘hypovolemic shock’.

Once obstacles to kidney drainage have been overcome, the treatment plan typically includes glucocorticoid therapy for at least 4 weeks. This type of medication reduces inflammation and has a success rate of around 80%. You will likely see a reduction in pain and other inflammatory symptoms quickly after starting this medication, often within a few days. Your kidney function should also start to improve within two weeks.

The choice of medication and the duration of treatment can vary significantly depending on the patient’s needs. Some common options include prednisone, a type of glucocorticoid, which can be taken orally and gradually decreased over time. Azathioprine, a drug that suppresses your immune system, is traditionally used when steroid therapy is ineffective. Tamoxifen, an estrogen modulator, has shown modest effectiveness in treating retroperitoneal fibrosis, according to some small studies. You might also be treated with methotrexate, an immunosuppressant often used in autoimmune disorders, or another newer immunosuppressant called mycophenolate mofetil.

However, long-term use of treatments like these can have side effects such as weight gain, diabetes, high blood pressure, fluid retention, and decreased resistance to infections. Therefore, it is essential to monitor your response to therapy closely. Your doctor should assess your progress clinically within the first month to see how well the treatment is managing your pain and improving any blockage. Follow-up lab tests and CT scans will also be done at regular intervals to monitor the size of the fibrotic mass (thickened fibrous tissue).

If the medication route is ineffective or there are complications from double J stenting and nephrostomy management, surgical treatment called ‘ureterolysis’ might be necessary. This procedure involves separating the ureters from the fibrotic mass around them and moving them to a new location. This doesn’t stop the progression or recurrence of the disease but prevents future blockages. The decision to do surgery is based on a variety of factors including your overall health condition and the response to the initial treatment.

It’s important to keep monitoring the disease even after you completed your treatment. Your doctors will check for disease recurrence with regular tests, such as ultrasounds, lab tests, and CT scans for several years. That’s because the disease could come back years after treatment, with rates estimated at around 20-50% over 5-15 years.

What else can Retroperitoneal Fibrosis be?

When a doctor is trying to figure out if you have retroperitoneal fibrosis (a condition where there is too much fibrous tissue in the back of your abdomen), they look for symptoms that might suggest other possible conditions. Here those conditions:

• Retroperitoneal lymphoma: This is a cancer that can appear around the L4 to L5 level in your spine. If your doctor sees a mass located higher than that level in your scans, they may suspect lymphoma.
• Retroperitoneal Erdheim-Chester disease: This is a rare disease that can cause a variety of symptoms. It can affect the area at the back of your abdomen and cause kidney problems. But usually, it affects your bones and results in bone pain.
• Retroperitoneal lymphangioma: These are non-cancerous tumors that grow in the lymphatic tissue. They can usually be confirmed through histology (studying tissues under a microscope). The treatment typically involves surgery.

Other conditions the doctor may consider include:

• Benign neurogenic tumors such as schwannomas and neurofibromas
• Castleman disease
• Diseases that cause inflammation and damage to blood vessels, like eosinophilic angiomatosis with polyangiitis and granulomatosis with polyangiitis
• Fatty tumors known as lipomas
• Neurofibromatosis, a genetic disorder that disturbs cell growth in your nervous system
• Tumors originating from outside the adrenal gland known as paragangliomas
• A liver disease called primary sclerosing cholangitis
• Sarcoidosis, a disease that causes small patches of red and swollen tissue to develop in the organs of the body
• Cancerous tumors like liposarcomas and leiomyosarcomas
• A long-term autoimmune disease that affects the body’s moisture-producing glands known as Sjögren’s syndrome.

What to expect with Retroperitoneal Fibrosis

Patients usually start feeling better within a few days after the start of treatment. After several weeks, a type of scan called a CT scan may show that the mass (or growth) has significantly reduced. Complete recovery from all related symptoms depends on how severe the disease is and how much it has affected surrounding structures in a part of the body known as the retroperitoneum.

If the medication is not helping to reduce the mass, surgery might be required. The surgeon would aim to remove the firm or hard tissue, called fibrotic tissue, while being careful not to harm the ureters (tubes that carry urine from kidneys to the bladder) and other structures in the retroperitoneum. Tubes known as ureteral catheters can be relatively easily inserted to relieve obstruction in the urinary system, providing relief while waiting for the medication to take effect. Another type of procedure known as a percutaneous nephrostomy may be used if ureteral catheters are not suitable or cannot be inserted.

The outcomes for those dealing with a condition called retroperitoneal fibrosis are typically very good when treated appropriately. This is especially the case for the type related to IgG4, a class of antibodies, which often responds well to steroid therapy. Without medical or surgical treatment, the tubes that carry urine from the kidneys (ureters) may become increasingly obstructed, leading to kidney failure. Most cases improve with steroid therapy, and surgery is typically very successful in cases that do not respond to this type of treatment. However, outcomes are significantly worse for those with retroperitoneal fibrosis due to cancer, with an average survival of only about 3 to 6 months.

Possible Complications When Diagnosed with Retroperitoneal Fibrosis

Retroperitoneal fibrosis might lead to several complications such as:

• Anemia, a condition that happens when your body is short of red blood cells
• Anuria, a state when no urine is produced
• Hypertension, also known as high blood pressure
• Intestinal necrosis, a condition where there is damage and death of the intestines
• Jaundice which causes yellowing of the skin and eyes
• Nausea and vomiting
• Swelling in the scrotum
• Neuropathy, damage to the nerves
• Persistent hydronephrosis, a condition characterized by excess fluid in the kidney due to a backup of urine
• Weight loss
• Thrombosis in the inferior vena cava, which is the formation of a blood clot in a large vein in the abdomen
• Issues with the ureter – the tube that moves urine from kidney to bladder – including narrowing, strictures (scar tissue), fistulas (abnormal connections), loss of blood flow, or damage due to lack of blood
• Side effects from steroids and other treatments
• Progressing kidney failure and death if left untreated
• Postoperative complications following ureterolysis (a procedure to free the ureter from surrounding tissue) are seen in between 8%-16% of all cases
• The necessity for a follow-up surgery in around 20% of ureterolysis cases

Preventing Retroperitoneal Fibrosis

It’s important for patients and their families to fully understand the disease and everything that comes with it. This includes knowing what could happen if they don’t follow their treatment plan, and that surgery might be required if their current medical care doesn’t work. It’s also crucial for patients to know about the importance of regular check-ups over a long period of time, as there is a chance that the disease could come back.