Fibrosis of the retroperitoneum

Such a rare disease as retroperitoneal fibrosis is characterized by excessive growth of fibrous tissue behind the posterior outer surface of the stomach and intestines - that is, in the retroperitoneal space. Fibrous tissue is rough, dense, grows in the area between the spinal column and organs such as the pancreas, kidneys, ureters, etc. With a strong growth, pressure is exerted on these organs, which leads to the appearance of secondary pathologies and symptoms.

Fibrosis of the retroperitoneal space has another name - Ormond's disease. This name is due to the fact that it was the urologist Ormond who first described the disease in the middle of the last century and associated it with a nonspecific inflammatory process in the retroperitoneal tissue. There are other less common terms: fibrous peritonitis, retroperitoneal fibrosis, etc. 

Epidemiology

Retroperitoneal fibrosis is more often diagnosed in men 40-60 years old, but can occur at any other age. The incidence of the disease depending on sex is 2:1 (men and women).

The cause of retroperitoneal fibrosis can be detected in only 15% of cases. In general, the disease is considered relatively rare. One Finnish study showed a prevalence of 1.4 per 100,000 inhabitants and an incidence of 0.1 per 100,000 person-years. [1]However, another study reported a higher incidence of 1.3 per 100,000.[2]

In childhood, pathology occurs only in isolated cases.

Retroperitoneal fibrosis is predominantly bilateral, although unilateral involvement also occurs. The most common localization of the disease process is the zone IV-V of the lumbar vertebrae, however, the pathology can spread to the entire area from the lower bend of the spine to the pelvis-ureteral region.

Upon reaching a large size of the pathological focus, the aorta and the inferior vena cava can be affected.

Causes of the retroperitoneal fibrosis

Experts still cannot point to the exact causes of the appearance of retroperitoneal fibrosis. It is assumed that the disease occurs on the basis of inflammatory or immune reactions. Some doctors associate the appearance of pathology with systemic connective tissue disorders. The found basic pathogenetic criterion is the increased expression of the IgG4 complex by plasma cells.

Retroperitoneal fibrosis often becomes a secondary pathology due to a number of possible causes:

• Diseases affecting the kidneys, ureters or other structures located in close proximity to the retroperitoneal tissue.
• Tumor malignant processes, including rectal cancer, prostate carcinoma, bladder cancer.
• Infectious processes (brucellosis, tuberculosis, toxoplasmosis).
• Pelvic-renal reflux, kidney injury with extravasation of urine.
• Abdominal injuries, internal hemorrhages, lymphoproliferative disorders, lymphadenectomy operations, colectomy, aortic interventions.
• Radiation therapy with effects on the organs of the abdominal cavity and small pelvis.
• Long-term use of ergot preparations, as well as Bromkriptin, Hydralazine, Methyldopa, large doses of antibiotics and β-blockers.
• Allergic intolerance to medicines, cases of hypersensitive reactions to medicines and chemicals.

The role of hereditary predisposition is not completely excluded: in particular, some cases of development of retroperitoneal fibrosis were associated with carriage of the human leukocyte marker HLA-B27. Other possible genetic associations are currently being explored.

Risk factors

There are several factors that can lead to the formation of retroperitoneal fibrosis. These include:

• tumor malignant processes;
• chronic inflammation of the pancreas;
• chronic hepatitis;
• tuberculosis of the spinal column;
• radiation damage;
• injuries of the lower back and abdominal cavity, internal hemorrhages;
• intoxication (chemical, drug).

Many patients fail to find any relationship with any factors. In such cases, they talk about the idiopathic origin of retroperitoneal fibrosis.

Pathogenesis

In the vast majority of cases, the development of retroperitoneal fibrosis is associated with the presence of lymphocytic plasma cells that produce IgG4. The disease is often systemic in nature, since fibrotic changes are also noted in the lymph nodes, pancreas, and pituitary structures. Tumor edema of the affected organs, fibrous sclerotic reaction and lymphoplasmic infiltration of varying intensity are noted. The fibrous process leads to compression of the ureter and vasculature (circulatory and lymphatic), as well as the kidneys.[3]

In some cases, the formation of retroperitoneal fibrosis is due to the appearance of malignant tumors. There is an increase in fibrous tissue against the background of the presence of malignant cells in the retroperitoneal space, or in the event of lymphoma, sarcoma, in the presence of metastases from other organs.[4]

Fibrous infiltrate is represented by multiple lymphocytes, lymphocytic plasmocytes, macrophages, less often neutrophils. Pro-inflammatory structures are interspersed with collagen clusters that coalesce near small vessels. The disease is classified as associated with IgG4 if there is a moire fibrous pattern, eosinophilic infiltration, phlebitis obliterans. Tissue cells of the myeloid series are degranulated, an active inflammatory-fibrotic reaction is traced.[5]

Symptoms of the retroperitoneal fibrosis

The clinical picture of retroperitoneal fibrosis is most often characterized by the following symptoms:

• vague pain in the abdomen, side, lower back, groin;
• periodically elevated temperature, which then normalizes and rises again, often accompanied by chills;
• swelling of the lower body;
• venous disorders, thrombophlebitis;
• sometimes - increased blood pressure;
• emaciation;
• diarrhea, nausea, indigestion, increased gas formation and other dyspeptic phenomena;
• an attack of renal colic;
• urinary disorders (more often - dysuria, hematuria);
• feeling of heaviness in the legs, severe fatigue.

The primary symptomatology in the development of retroperitoneal fibrosis is due to a deterioration in blood circulation in the abdominal cavity. The initial clinical picture may include the following signs:

• dull pain in the abdomen or back, with the inability to determine a clear localization;
• pain in the side, lower limb;
• swelling and pallor of one or two lower extremities.

With the progression of the disease, abdominal pain becomes severe, and other symptoms join:

• loss of appetite;
• emaciation;
• temperature rise;
• nausea, dyspepsia;
• lack of urination;
• clouding of consciousness.

In the future, there may be signs of renal failure.[6]

First signs

The most common first complaint of patients with retroperitoneal fibrosis is persistent, dull pain in the abdomen, or lower back, or right and left hypochondrium. The pain radiates to the groin, external genitalia, legs. The early stage of the pathology can be manifested by a moderate increase in temperature and leukocytosis, an increase in ESR. 

Gradually, signs appear that indicate compression of the tubular retroperitoneal structures: arterial hypertension, pyelonephritis, and hydronephrosis develop. Chronic renal failure appears somewhat later: over a period of 4 weeks to two years. Partial or complete ureteral obstruction occurs in approximately 80% of patients, and oligo or anuria develops in 40% of cases.[7]

Stages

Clinical symptoms in retroperitoneal fibrosis depend on the stage of the pathological process. As a rule, the disease is characterized by slow development, with gradual progression. During its course, the disease goes through the following stages:

1. The initial period of the development of the disease.
2. The active period, characterized by the spread of the cellular and fibrous process to the retroperitoneal structures.
3. The period of compression by fibrous masses of structures involved in the pathological process.[8]

Forms

It is customary to distinguish between primary (idiopathic) retroperitoneal fibrosis and secondary lesion. Specialists point to an autoimmune origin of idiopathic retroperitoneal fibrosis. Secondary pathology usually develops as a result of other various painful conditions and diseases:

• malignant tumors;
• infectious lesions;
• chronic liver pathologies;
• diseases of the intestines, pancreas;
• urogenital pathologies;
• tuberculous lesions of the spinal column;
• various intoxications (including medications).[9]

Primary idiopathic retroperitoneal fibrosis most often starts from the retroperitoneal tissue that surrounds the iliac vessels, with further spread to the sacral promontory and hilum of the kidney.[10]

Complications and consequences

Every second patient with retroperitoneal fibrosis develops high blood pressure, compression of the ureters with further development of renal failure.[11]

Long-term complications can be:

• excessive accumulation of fluid in the abdominal cavity (ascites);
• vascular disorders (phlebitis, thrombosis);
• hydrocele in men;
• obstruction of the bile ducts, jaundice;
• intestinal obstruction;
• compression of the spine, compression of the spinal nerves, impaired blood supply to the spinal cord.

Many complications can be fatal. In particular, pathological processes in the ureters provoke the development of pyelonephritis, hydronephrosis, and chronic renal failure. Approximately 30% of patients have atrophic changes in the kidneys, aortic changes are observed, which can ultimately lead to the development of an aneurysm.

Diagnostics of the retroperitoneal fibrosis

Retroperitoneal fibrosis is difficult to diagnose. First, the disease is relatively rare. Secondly, it has no specific symptoms and disguises itself as a variety of other pathologies. There is no specificity in the results of laboratory tests. Very often, patients are prescribed incorrect, inaccurate treatment: instead of retroperitoneal fibrosis, patients are treated for urological and gastroenterological pathologies that are not related to fibrotic processes. Meanwhile, the disease worsens and spreads, worsening the prognosis.

In order to suspect the presence of retroperitoneal fibrosis in a patient, the doctor must adhere to the following diagnostic algorithm:

• Analyzes in the laboratory demonstrate the following pathological changes:
  • increased levels of pro-inflammatory markers (ESR, C-reactive protein);
  • an increase in IgG4 of more than 135 mg / dl against the background of histological signs.
• Mandatory studies are the levels of urea, creatinine, glomerular filtration rate - to assess renal function.
• Urinalysis may show hematuria, proteinuria, low specific gravity.
• Instrumental diagnostics should include imaging techniques such as magnetic resonance imaging and computed tomography. Computer diagnostics makes it possible to distinguish between idiopathic and secondary fibrous pathology. Ultrasound examination is necessary to confirm the initial stage of the development of the disease process, to obtain characteristics of hydronephrosis, to identify changes in the aorta. To obtain clearer results, contrasting is used. To reveal hidden infectious-inflammatory and malignant diseases, positron emission tomography is prescribed.
• To clarify the diagnosis, a biopsy is indicated. The early stage of development of the fibrous process is characterized by the detection of hypervascular tissue with perivascular lymphocytic infiltrate, as well as macrophages with lipid inclusions. At a late stage in the development of retroperitoneal fibrosis, a characteristic avascular mass is detected that does not have cellular structuring.

Differential diagnosis

The symptoms of a retroperitoneal abscess often have much in common with other pathological conditions - in particular, with urological pathologies:

• bilateral hydronephrosis (renal dropsy);
• ureteral strictures (abnormal narrowing of the canal);
• achalasia of the ureters (neuromuscular dysplasia).

The main difference between retroperitoneal fibrosis and the above pathologies is the obstruction of the ureters in the area of their intersection with the iliac vessels: an expansion of the ureters is noted above this intersection, and no changes are detected below it.

Treatment of the retroperitoneal fibrosis

Therapeutic measures for retroperitoneal fibrosis depend on the exact location of the pathology, on its scale, on the degree of compression of the internal organs and the presence of an infectious component. Since the disease is rare, with a poorly understood etiology, today there is no single standard for its treatment. There is no clear definition of the role of conservative therapy and the optimal method of surgical treatment.

The scale of medical measures in general depends on the underlying cause of the development of retroperitoneal fibrosis. For example, intoxication fibrosis disappears after the cessation of the action of the toxic agent. If we are talking about a malignant tumor process, then the treatment is appropriate.

The idiopathic form of retroperitoneal fibrosis in many patients is cured by the use of immunosuppressants and proteolytic drugs. According to indications, they resort to anti-inflammatory, antibacterial, detoxification and symptomatic therapy. Surgery may be prescribed in the development of acute conditions or in the ineffectiveness of medical measures.

If chronic pyelonephritis is diagnosed, appropriate therapy for the disease is prescribed.

Surgery

Patients with the initial stage of retroperitoneal fibrosis without clear indications for surgical treatment are prescribed drug therapy with the use of corticosteroid and proteolytic drugs.

Nevertheless, quite often it is necessary to resort to surgical treatment: the operation is called ureterolysis, which involves the release of the ureters from the surrounding fibrous tissue. Some patients require resection of the ureter and further anastomosis, transplantation of the small bowel segment, or the use of prosthetics.[12], [13]

In the advanced stage, with severe hydronephrosis and the development of chronic pyelonephritis, reconstructive plastic surgery is performed simultaneously with the removal of the urinary canal by the method of pyelo or nephropyelostomy, puncture nephrostomy under ultrasound supervision. After surgery, the patient is prescribed long-term corticosteroid support, which is necessary to inhibit fibrous growth. The most common drug of choice is Cortisol 25 mg daily for 8-12 weeks.

An initial dose of prednisone 1 mg/kg per day (maximum dose 80 mg/day) is usually given over about 4 to 6 weeks. In the future, the dose can be gradually reduced over 1-2 years, depending on the progression of the disease. If the disease does not respond well to steroid therapy alone, immunosuppressants may be used concomitantly with steroids. Agents that have been used with apparent success in case reports and case series include azathioprine, methotrexate, mycophenolate mofetil, cyclophosphamide, cyclosporine. [14]Additionally, drugs that accelerate resorption are used (Lidase, Longidase).[15], [16]

Prevention

Specific prevention of the development of retroperitoneal fibrosis has not been developed, due to the ambiguity of the causes of the disease. This is especially true of idiopathic forms of pathology. Secondary retroperitoneal fibrosis in most cases can be prevented if the following recommendations are followed:

• give up bad habits, do not smoke, do not abuse alcohol;
• avoid stressful situations, physical and emotional overstrain;
• do not overeat, do not starve, eat a little several times a day;
• give preference to high-quality food of plant and animal origin, refuse semi-finished products, fast food, fatty and salty foods, smoked meats;
• observe hygiene rules, brush your teeth regularly, wash your hands before eating, as well as after visiting the street and the restroom;
• more often to be in the fresh air, to observe physical activity;
• avoid abdominal trauma;
• if any symptoms appear, consult a doctor, do not self-medicate;
• after operations on the abdominal cavity, strictly follow all the prescriptions and recommendations of the doctor;
• avoid hypothermia and overheating of the body;
• drink enough clean water daily;
• while eating, pay attention to thoroughly chewing food, do not be distracted by conversations, a computer, etc.

Our health largely depends on our lifestyle. Therefore, following these simple rules will help maintain and preserve it for many years.

Forecast

Retroperitoneal fibrosis is a rare and difficult-to-diagnose disease that often leads to a delayed start of treatment and prolonged ineffective medical measures. Often, patients are mistakenly treated for other similar pathologies or therapy is directed to eliminate already developed complications, such as arterial hypertension, tumor processes, chronic enterocolitis, cholecystopancreatitis, gastric and duodenal ulcers, pyelonephritis, hydronephrosis, chronic renal failure, anuria and etc.

Earlier initiation of therapeutic measures can significantly improve the prognosis of pathology. Retroperitoneal fibrosis in the initial stages of development responds well to treatment with corticosteroid drugs, but therapy should be prescribed before the development of irreversible fibrotic processes. Relapse rates after discontinuation of treatment ranged from less than 10-30%, although one series reported a relapse rate of over 70%. [17]Advanced disease is treated only by surgical intervention, and mortality depends on the degree of obstruction and complications associated with it.

Such a rare disease as retroperitoneal fibrosis is characterized by excessive growth of fibrous tissue behind the posterior outer surface of the stomach and intestines - that is, in the retroperitoneal space. Fibrous tissue is rough, dense, grows in the area between the spinal column and organs such as the pancreas, kidneys, ureters, etc. With a strong growth, pressure is exerted on these organs, which leads to the appearance of secondary pathologies and symptoms.

Fibrosis of the retroperitoneal space has another name - Ormond's disease. This name is due to the fact that it was the urologist Ormond who first described the disease in the middle of the last century and associated it with a nonspecific inflammatory process in the retroperitoneal tissue. There are other less common terms: fibrous peritonitis, retroperitoneal fibrosis, etc.[18]