Elsevier

The Lancet

Volume 367, Issue 9506, 21–27 January 2006, Pages 241-251
The Lancet

Seminar
Retroperitoneal fibrosis

https://doi.org/10.1016/S0140-6736(06)68035-5Get rights and content

Summary

Retroperitoneal fibrosis encompasses a range of diseases characterised by the presence of a fibro-inflammatory tissue, which usually surrounds the abdominal aorta and the iliac arteries and extends into the retroperitoneum to envelop neighbouring structures—eg, ureters. Retroperitoneal fibrosis is generally idiopathic, but can also be secondary to the use of certain drugs, malignant diseases, infections, and surgery. Idiopathic disease was thought to result from a local inflammatory reaction to antigens in the atherosclerotic plaques of the abdominal aorta, but clinicolaboratory findings—namely, the presence of constitutional symptoms and the high concentrations of acute-phase reactants—and the frequent association of the disease with autoimmune diseases that involve other organs suggest that it might be a manifestation of a systemic autoimmune or inflammatory disease. Steroids are normally used to treat idiopathic retroperitoneal fibrosis, although other options—eg, immunosuppressants, tamoxifen—are available. The outlook is usually good, but, if not appropriately diagnosed or treated, the disease can cause severe complications, such as end-stage renal failure. Here, we review the different aspects of retroperitoneal fibrosis, focusing on idiopathic retroperitoneal fibrosis and on the differential diagnosis associated with the secondary forms.

Section snippets

Epidemiology and diagnosis

The epidemiological characteristics of retroperitoneal fibrosis are not well established, and only data on the idiopathic form are available: a report of a study done in Finland13 noted that idiopathic retroperitoneal fibrosis has an incidence of 0·1 per 100 000 person-years and a prevalence of 1·38 per 100 000 inhabitants in the study area. No clear ethnic predisposition has emerged.

Men are affected twice to three times as often as women; the mean age at presentation is 50–60 years, but

Idiopathic retroperitoneal fibrosis

The pathogenesis of idiopathic retroperitoneal fibrosis is unclear. The leading theory was proposed by Mitchinson and Parums,8, 9, 10 who first defined chronic periaortitis as a range of diseases—including idiopathic retroperitoneal fibrosis—characterised by advanced aortic atherosclerosis, medial thinning, and pronounced adventitial and periaortic inflammation and fibrosis. These investigators suggested that chronic periaortitis could be a consequence of a local inflammatory reaction to

Pathology

The typical macroscopic appearance of idiopathic retroperitoneal fibrosis is that of a white, hard retroperitoneal plaque of varying thickness, which surrounds the abdominal aorta, the iliac vessels, and, in most instances, the inferior vena cava and the ureters. The plaque usually develops between the origin of the renal arteries and the pelvic brim, although presacral extension is not uncommon; only in rare cases does it extend anteriorly to the mesenteric root or posteriorly to the spinal

Clinical manifestations

The clinical manifestations of idiopathic and secondary retroperitoneal fibrosis often overlap, thus they are not useful in the differential diagnosis between the two disease groups. The clinical signs and symptoms that herald the onset of retroperitoneal fibrosis are non-specific; however, patients usually report two types of manifestations: localised (likely due to the presence of the retroperitoneal mass and its mechanic or compressive effects) and systemic (possible expression of the

Laboratory findings

The results of routine laboratory tests are consistent with inflammatory disease: concentrations of acute-phase reactants, such as ESR and CRP, are high in 80–100% of patients.11, 56, 58 These laboratory tests are often used to monitor the clinical course of the disease,56 though they do not always reliably mirror disease activity.59 Azotemia usually depends on the extent of ureteral obstruction. Mild-to-moderate anaemia is usually noted, to which both chronic inflammation and—when

Imaging

Imaging studies are essential in the diagnosis and management of retroperitoneal fibrosis, and can sometimes help to differentiate between idiopathic and secondary disease.

Sonography should be done as a first-line study, especially when an azotemic patient is being assessed; on ultrasound, idiopathic retroperitoneal fibrosis appears as a hypoechoic or isoechoic mass, which can involve the ureters and, thus, cause unilateral or bilateral hydronephrosis.

Intravenous urography usually reveals the

Associated autoimmune diseases

Patients with idiopathic retroperitoneal fibrosis often have mild manifestations of an autoimmune disease—eg, presence of autoantibodies and raised concentrations of acute-phase reactants. In others, their disease actually develops in the setting of well defined systemic autoimmune disorders—eg, systemic lupus erythematosus, vasculitic syndromes60, 65—or associates with the so-called organ-specific autoimmune diseases—eg, Hashimoto's thyroiditis, sclerosing cholangitis.11 The most important

Differential diagnoses

In addition to the above discussed idiopathic and secondary forms of retroperitoneal fibrosis, the retroperitoneum can also be affected by another group of fibrosing disorders, which, unlike retroperitoneal fibrosis, are primarily characterised by a prominent fibroblast proliferation that may or may not be associated with an inflammatory component.80

Retroperitoneal fibromatosis is histologically characterised by a uniform proliferation of fibroblasts, arranged in interlacing bundles. It

Treatment and course

The aims of treatment of idiopathic retroperitoneal fibrosis are multiple: to stop the progression of the fibro-inflammatory reaction, to inhibit or relieve the obstruction of the ureters or other retroperitoneal structures, to switch off the acute-phase reaction and its systemic manifestations, and to prevent disease recurrence or relapse.

Corticosteroids are the most used drugs. They suppress the synthesis of most of the cytokines involved in the acute-phase reaction, reduce the inflammatory

Future perspectives

Retroperitoneal fibrosis is a largely obscure and multifaceted disease. Diagnostic criteria are needed, as are new methods for the differential diagnosis between the idiopathic and secondary forms of the disease. Studies on the complex pathogenesis of the idiopathic disease could elucidate the role of immune-mediated mechanisms and provide new clues for treatment. Finally, the optimum dose and duration of steroid therapy and the role of other potentially useful agents, such as

Search strategy and selection criteria

We searched PubMed without any date limits and EMBASE between 1980 and 2005, mainly using the search terms “retroperitoneal fibrosis” and “periaortitis”; we largely selected articles published in English during the past 10 years without excluding older papers that we considered to be highly relevant to the topics discussed in this Seminar. We also included some review papers and a book chapter, providing insightful overviews on retroperitoneal fibrosis and related diseases.

References (103)

  • H Oshiro et al.

    Idiopathic retroperitoneal fibrosis associated with immuno-hematological abnormalities

    Am J Med

    (2005)
  • VV Waters

    Hydralazine, hydrochlorothiazide and ampicillin associated with retroperitoneal fibrosis: case report

    J Urol

    (1989)
  • BF Finan et al.

    Renal papillary necrosis and retroperitoneal fibrosis secondary to analgesic abuse

    J Urol

    (1981)
  • S Chander et al.

    High 2-deoxy-2-[18F]-fluoro-D-glucose accumulation in a case of retroperitoneal fibrosis following resection of carcinoid tumor

    Mol Imaging Biol

    (2002)
  • A Seth et al.

    Retroperitoneal fibrosis: a rare complication of Pott's disease

    J Urol

    (2001)
  • JW Moul

    Retroperitoneal fibrosis following radiotherapy for stage I testicular seminoma

    J Urol

    (1992)
  • F Rabbani et al.

    Clinical outcome after retroperitoneal lymphadenectomy of patients with pure testicular teratoma

    Urology

    (2003)
  • S Ahmad

    Methyldopa and retroperitoneal fibrosis

    Am Heart J

    (1983)
  • AH Kardar et al.

    Steroid therapy for idiopathic retroperitoneal fibrosis: dose and duration

    J Urol

    (2002)
  • R Marcolongo et al.

    Immunosuppressive therapy for idiopathic retroperitoneal fibrosis: a retrospective analysis of 26 cases

    Am J Med

    (2004)
  • RM Saldino et al.

    Medial placement of the ureter: a normal variant, which may simulate retroperitoneal fibrosis

    J Urol

    (1972)
  • M Schirmer et al.

    18F-fluorodeoxyglucose positron emission tomography: a new explorative perspective

    Exp Gerontol

    (2003)
  • H Izzedine et al.

    Retroperitoneal fibrosis due to Wegener's granulomatosis: a misdiagnosis of tuberculosis

    Am J Med

    (2002)
  • HR Hellstrom et al.

    Retroperitoneal fibrosis with disseminated vasculitis and intrahepatic sclerosing cholangitis

    Am J Med

    (1966)
  • M Doi et al.

    A case of uveitis associated with idiopathic retroperitoneal fibrosis

    Am J Ophtalmol

    (1994)
  • AI Oikarinen et al.

    Modulation of collagen metabolism by glucocorticoids: receptor-mediated effects of dexamethasone on collagen biosynthesis in chick embryo fibroblasts and chondrocytes

    Biochem Pharmacol

    (1988)
  • W Grotz et al.

    Treatment of retroperitoneal fibrosis by mycophenolate mofetil and corticosteroids

    Lancet

    (1998)
  • RJLF Loffeld et al.

    Tamoxifen for retroperitoneal fibrosis

    Lancet

    (1993)
  • N Sakalihasan et al.

    Abdominal aortic aneurysm

    Lancet

    (2005)
  • TF Rehring et al.

    Regression of perianeurysmal fibrosis and ureteral dilation following endovascular repair of inflammatory abdominal aortic aneurysm

    Ann Vasc Surg

    (2001)
  • AL Tambyraja et al.

    Ruptured inflammatory abdominal aneurysm: insights in clinical management and outcome

    J Vasc Surg

    (2004)
  • U von Fritschen et al.

    Inflammatory abdominal aortic aneurysm: a post-operative course of retroperitoneal fibrosis

    J Vasc Surg

    (1999)
  • L Koep et al.

    The clinical significance of retroperitoneal fibrosis

    Surgery

    (1977)
  • J Albarran

    Retention renale par peri-ureterite: liberation externe de l'uretere

    Assoc Fr Urol

    (1905)
  • MJ Mitchinson et al.

    The response of idiopathic retroperitoneal fibrosis to corticosteroids

    Br J Urol

    (1971)
  • LRI Baker et al.

    Idiopathic retroperitoneal fibrosis: a retrospective analysis of 60 cases

    Br J Urol

    (1988)
  • MJ Mitchinson

    Chronic periaortitis and periarteritis

    Histopathology

    (1984)
  • DV Parums

    The spectrum of chronic periaortitis

    Histopathology

    (1990)
  • DV Parums et al.

    Serum antibodies to oxidized low-density lipoproteins and ceroid in chronic periaortitis

    Arch Pathol Lab Med

    (1990)
  • A Vaglio et al.

    Chronic periaortitis: a spectrum of diseases

    Curr Opin Rheumatol

    (2005)
  • DV Parums et al.

    Characterisation of inflammatory cells associated with “idiopathic retroperitoneal fibrosis”

    Br J Urol

    (1991)
  • AL Ramshaw et al.

    Cytokine gene expression in aortic adventitial inflammation associated with advanced atherosclerosis (chronic periaortitis)

    J Clin Pathol

    (1994)
  • Martorana D, Vaglio A, Greco P. et al. Chronic periaortitis and HLA-DRB1*03: another clue to an autoimmune origin....
  • J Klein et al.

    The HLA system: second of two parts

    N Engl J Med

    (2000)
  • C Salvarani et al.

    Positron emission tomography (PET): evaluation of chronic periaortitis

    Arthritis Rheum

    (2005)
  • MJ Mitchinson

    Aortic disease in idiopathic retroperitoneal and mediastinal fibrosis

    J Clin Pathol

    (1972)
  • C Salvarani et al.

    Polymyalgia rheumatica and giant cell arteritis

    N Engl J Med

    (2002)
  • C Chizzolini et al.

    Autoantibodies to fibroblasts induce a proadhesive and proinflammatory fibroblast phenotype in patients with systemic sclerosis

    Arthritis Rheum

    (2002)
  • N Ronda et al.

    Antifibroblast antibodies from systemic sclerosis patients are internalized by fibroblasts via a caveolin-linked pathway

    Arthritis Rheum

    (2002)
  • A Vaglio et al.

    Anti-fibroblast antibodies in idiopathic retroperitoneal fibrosis

    Autoimmun Rev

    (2004)
  • Cited by (591)

    • Chronic periaortitis: A clinical approach

      2023, Revue de Medecine Interne
    • Retroperitoneal tumors and retroperitoneal fibrosis

      2023, Penn Clinical Manual of Urology, Third Edition
    View all citing articles on Scopus
    View full text