Patients suffering from retroperitoneal fibrosis show a pathological proliferation of connective tissue in the retroperitoneal space that may compromise different organs, e.g., kidneys, ureters and aorta.
Symptoms associated with RPF are generally very unspecific. The most common symptom is lower back or abdominal pain and patients often report difficulties to localize its origin . Due to inflammation, patients may present with fever. Loss of appetite, nausea and consecutive weight loss may be observed as well as anemia and jaundice. If blood flow to and from one of the lower limbs is restricted, the respective leg may swell and turn cyanotic. Movements may be impaired. Less frequently, intestinal hemorrhages occur.
Somewhat surprisingly, only 10% of RPF patients experience problems while urinating. Upon bilateral ureteral obstruction, however, such symptoms will develop rapidly. Oliguria but also polyuria may be observed and further examination will reveal hydronephrosis and hypertension . If left untreated, these events result in kidney failure. Limited kidney function may aggravate nausea and provoke vomiting.
Abdominal or rectal examination may reveal the presence of a retroperitoneal mass in a smaller share of patients.
While physical examination, laboratory analyses of blood and urine samples allow for an evaluation of the overall condition of the patient, definitive diagnosis of RFP can only be attained by histopathological analysis of a biopsy. Diagnostic imaging techniques have to be applied to assess the extend of tissue compromise.
With regards to hemogram and blood biochemistry, parameters indicating anemia, inflammation and renal problems will be altered. In detail, a normocytic normochromic anemia can often be observed. Increased levels of C-reactive protein and prolonged erythrocyte sedimentation rates point at tissue inflammation. Urea and creatinine levels are often enhanced. Hypergammaglobulinemia and the presence of antinuclear autoantibodies support the suspicion of an autoimmune process . Alkaline phosphatase levels are frequently elevated and may even be considered a marker of RFP .
Urine analysis does usually not reveal any pathological findings. In some cases, hematuria or pyuria may result from damage to the urinary tract.
Further diagnostics are based on imaging techniques. Standard radiographic imaging may be helpful to detect renal enlargement due to hydronephrosis or neoplasms, but is little sensitive towards RPF and ureteral obstruction. Computed tomography scans are superior to standard radiographic imaging, but should also be carried out utilizing contrast agents. Intravenous urography or retrograde pyeolography may be applied to visualize the urinary tract and significantly improve sensitivity of imaging diagnostics. A classic triad of delayed excretion of contrast agents due to hydronephrosis, medial deviation of the middle third of one or both ureters and their tapering at the level of the fourth and fifth lumbar vertebrae has been described for RPF . These symptoms are, however, not specific and may be found in a significant share of healthy controls. Of note, catheterization for retrograde pyeolography is usually not hindered by RPF. Lymphatic vessels are more easily compressed by excess connective tissue than blood vessels and ureters. Thus, lymphangiography may be of help to identify RFP before any of the before mentioned structures are compromised. Such an examination may reveal delayed passage of contrast agents, obstruction of flow and possibly non-visualizability of lymphatic vessels in the lumbar area. If magnetic resonance imaging is conducted, findings vary with fluid contents of fibrotic tissue. In this context, early stages of RFP are associated with high fluid contents and thus appear with high T2 signal intensity while this is no longer the case in advanced RFP and diminished fluid content. Corticosteroid-induced reduction of edema also decreases T2 signal intensity. Inhomogeneities visible in any of the aforementioned imaging techniques may indicate the presence of malignant neoplasms.
Ultrasonographic exams are used to assess response to therapy in follow-ups rather than for diagnosis.
If analysis of blood samples and findings of diagnostic imaging support the diagnosis of RFP, a biopsy needs to be obtained. This is frequently done as part of a surgical intervention to relieve ureteral obstruction, but laparoscopic procedures should be preferred if the latter is not required. Here, morbidity and costs are significantly lower. Core needle biopsies do often not provide sufficient tissue for diagnosis.
Spontaneous remission has been observed in rare cases.
Immunosuppressive therapy with corticosteroids has been proven very effective in treating RFP, particularly in early stages of the disease . Furthermore, azathioprine has been administered to reduce the autoimmune response behind RFP . Current research focuses on the employment of progesterone and estrogen-receptor modulator tamoxifen in RFP treatment.
Drug therapy may even replace surgery if such interventions are not feasible due to the overall condition of the patient. However, ureteral obstruction may require ureterolysis in order to fully regain functionality of this side's urinary tract. Ureteral stents may pose an alternative treatment option although they should not be considered long-term solutions.
Relapses are common and may occur until years after initial diagnosis. It has been reported that wrapping up the ureter in retroperitoneal fat after ureterolysis may delay recurrence of ureteral obstruction.
If RPF is not associated with malignancies and a possibly underlying disease can be treated, prognosis is good . Full functionality of the urinary tract is usually regained. However, if RPF develops as a sequelae of malignant neoplasms, prognosis is poor.
The majority of RPF cases is deemed idiopathic because no underlying pathological condition can be identified. However, the hypothesis of RPF being an IgG4-related disease, i.e., a disease characterized by fibrosis and infiltration of lymphocytes that produce antibodies of type IgG4, is gaining consent  . It is supported by the fact that many RPF patients respond to immunosuppressive therapy.
An association between malignant neoplasms and RPF has been proven. Excess proliferation of retroperitoneal connective tissue may, however, also result from chemotherapy or irradiation applied to treat cancer. RPF seems to develop more frequently after abdominal aortic aneurysm and subsides after repair of the former. Moreover, iatrogenic RPF has been described. Here, the condition may be induced by use of beta-sympatholytics, methyldopa or methysergide and others. Abuse of illegal drugs like cocaine may trigger RPF as well as traumas and/or inflammation, e.g., glomerulonephritis, systemic vasculitis, mediastinitis, spondylitis. Additionally, a relation between RPF and hormonal disorders like hypopituitarism, hypothyroidism and Hashimoto's thyroiditis may exist. An association to autoimmune diseases like systemic lupus erythematosus has been proposed.
A genetic component seems likely .
RPF is considered a rare disease. In a study realized in Northern Europe, an overall incidence of 1 per 1,000,000 person years and a prevalence of less than 2 per 100,000 individuals has been estimated . Another study has been conducted several years later and reported an incidence of more than 1 per 100,000 person years .
RPF usually strikes adults aged 40 to 60 years. Men seem to be affected up to three times as often as women.
The retroperitoneal space is delimited by diaphragm, parietal peritoneum, transverse fascia and pelvis. An anterior pararenal, perirenal and posterior pararenal section result from subdivision of the overall retroperitoneal space by the kidneys. While there is retroperitoneal fat in the latter, the kidneys themselves, adrenal glands and ureters and their respective vessels are located in the perirenal space. The anterior pararenal sector contains secondarily retroperitoneal organs, i.e., organs that did not develop retroperitoneally but that were relocated here at a later point in time. Thus, they once possessed mesenteries, but these have grown together with the parietal peritoneum. There position is a lot more fixed than those of the primarily retroperitoneal organs ubicated in the other sections. Secondarily retroperitoneal organs are pancreas, duodenum, ascending and descending colon. Also, aorta, inferior vena cava as well as additional blood and lymphatic vessels are located in the anterior pararenal space.
While still most cases of RPF are deemed idiopathic, this disease is increasingly recognized as an autoimmune disease. Epitopes located in atherosclerotic plaques have been proposed as triggering antigens. Indeed, diagnostic imaging as well as autopsies have shown that atherosclerotic plaques in the abdominal aorta often serve as point of origin of fibrosis. It has been hypothesized that lesions to the arterial wall may allow insoluble lipids such as ceroid to diffuse into the periaortic connective tissue. Here, it could provoke an immune response. The presence of anti-ceroid antibodies and ceroid-containing macrophages in local lymph nodes seem to confirm this theory. This pathogenetic mechanism accounts for the fact that this disease has also been termed chronic periaortitis .
While this hypothesis may be convincing, RPF may also occur in children whose abdominal aorta does not contain atherosclerotic plaques. Thus, additional factors have to be involved in RPF pathogenesis. As has been indicated above, certain drugs may trigger RPF, possibly by stimulating an autoimmune reaction in form of haptens.
Avoidance of certain drugs that have been shown to trigger RFP may contribute to prevention of this disease. However, RFP is a rare disease and the benefit of ceasing such therapies may not outweigh its downsides.
The retroperitoneal space harbors kidneys, adrenal glands, ureters, aorta, inferior vena cava and other vessels. These organs are not covered by the peritoneum and do not possess mesenteries. With regards to the spine, the retroperitoneal space is located ventral of the inferior lumbar vertebrae.
The pathological condition of excess proliferation of connective tissue in the retroperitoneal space is called retroperitoneal fibrosis (RPF). This disease is also termed Ormond's disease in honor of the urologist who discovered the condition in the past century. The etiology of RPF is unclear, but many patients benefit from an immunosuppressive therapy with corticosteroids and this fact suggests an immune pathogenesis  . About one out of ten RPF patients is also diagnosed with metastasizing malignant neoplasms and a pathogenetic association between both conditions is likely .
RPF may cause obstruction of the above mentioned organs, particularly of the thin ureters. Symptoms correspond to ureteral obstruction and are rather unspecific. The disease may also provoke hypertension and lower back pain. While urographic examination may reveal the former and further diagnostic imaging may support a tentative diagnosis of RPF, only a histopathologic analysis of a biopsy allows for confirming this diagnosis. Besides corticosteroids, cytostatic drugs may be administered to inhibit connective tissue proliferation. Many patients will require surgical intervention to relieve ureteral obstructions.
Due to the possible relation between RPF and malignant neoplasms, all patients diagnosed with RPF should undergo a thorough examination to rule out the presence of malignancies. If detected, they should be treated accordingly.
The retroperitoneal space is located in front of the lumbar spine. It is anatomically separated from the intra-abdominal area and harbors kidneys, ureters, abdominal aorta, important veins and lymphatic vessels. Connective tissue is also present in the retroperitoneal space. If this tissue starts to proliferate excessively, it may compress the aforementioned structures and provoke a pathological condition termed retroperitoneal fibrosis (RPF).
No specific cause can be identified for the majority of RPF cases. However, recent research results have supported the hypothesis of an autoimmune pathogenesis, i.e., an immune response against endogenous structures may cause inflammation and fibrosis. It has been speculated that atherosclerotic plaques present in the abdominal aorta may be the starting point of RPF.
In about 10% of RPF cases, the disease is related to the presence of malignant tumors.
Only unspecific symptoms are developed by RPF patients. The most common ones are lower back or abdominal pain, fever, loss of appetite, nausea and loss of weight. Patients may feel tired and weak and show yellowish discoloration of eyes and mucous membranes.
Legs may swell and turn bluish if blood flow to and from the lower limbs is restricted due to compression of blood vessels in the retroperitoneal space.
Some patients experience difficulties urinating.
Physical examination, analysis of blood and urine samples may prompt a slight suspicion for RPF. This will be confirmed with diagnostic imaging approaches that allow visualization of the patient's urinary tract. Therefor, contrast agents will be passed through kidneys and ureters.
Definitive diagnosis requires histopathological analysis of biopsy samples. Such tissue samples are often obtained during surgical interventions.