Spontaneous remission in a case of idiopathic retroperitoneal fibrosis

Case report

A 54-year-old lady was referred to the general medical clinic due to progressive back, abdominal and groin pain with a history of weight loss. She had previous negative investigations by the urologist due to haematuria, A mid infra-renal aortic aneurysm of 24 mm was discovered incidentally whilst undertaking an MRI pelvis, during investigation of her groin pain by the gynaecologists. The MRI was ordered to further delineate a suspected fibroid. She was also awaiting review by the vascular surgeons.

On examination she appeared well. Blood pressure was 155/95 in both arms. Examination of the cardiovascular, respiratory and neurological system was unremarkable. Examination of her abdomen demonstrated mild discomfort in the left upper quadrant, but no clear masses and no lymphadenopathy. Hip and lumbar spine movements were normal. There were no rashes. Routine blood testing was within normal limits; however, inflammatory markers were raised with a C-reactive protein (CRP) of 54 mg/L, and an erythrocyte sedimentation rate (ESR) of 84 mm/h.

Following discussion with the vascular surgeons she underwent an MRA to further delineate her vasculature, as well as a CT chest, abdomen and pelvis. Imaging demonstrated mediastinitis and retroperitoneal fibrosis with bilateral hydronephrosis. The aneurysm previously seen on MRI, was on MRA a large area of inflammatory tissue surrounding the aorta, which had displaced the inferior vena cava to the right. There was no evidence of large vessel vasculitis. An autoimmune screen was negative, as was serological testing for evidence of histoplasmosis, Aspergillus and blastomyces. A CT-guided biopsy confirmed a fibrotic process on histopathology rather than malignant disease. A mantoux and serial early morning urine did not suggest concurrent tuberculosis infection. On questioning the patient, and examining case notes, there was no suggestion of previous exposure to drugs associated with retroperitoneal fibrosis. An echocardiogram demonstrated normal cardiac function and structure, and pulmonary function tests were within normal parameters.

Despite the hydronephrosis her renal function was initially normal. Later in the year, however, she underwent bilateral ureteric stenting after an isotope renogram demonstrated a deterioration in renal function. After discussion she declined immunosuppressive therapy with corticosteroids due to possible side effects. She was treated symptomatically and over the course of 12 months her pain subsided and her weight improved. During this time her inflammatory markers showed a steady decline, the final measurement of ESR and CRP was 37 mm/h and 5.3 mg/L respectively. Repeat scanning demonstrated improvement. The para-aortic fibrotic mass reduced in size over a 12-month period, the maximal thickness of the cuff tissue anterior to the aorta had reduced in size from 13.32 mm to 5.88 mm (Figure 1(a) and (b)). OPEN IN VIEWER

She was reluctant to have repeat scanning due the radiation dose; however, continues to attend the clinic for ongoing assessment and remains well.

Discussion

Idiopathic retroperitoneal fibrosis, sometimes known as Ormond’s disease, is a rare condition. ¹ It presents commonly after the fourth decade of life and has a male preponderance. ² It affects the soft tissues of the retroperitoneum and the disease process has been proposed to be secondary to an exaggerated inflammatory response to atheroma, specifically a component of ceroid. ³ Leakage of this matter into the periaortic region leads to a widespread autoimmune inflammatory response (periaortitis). On microscopic examination of the tissue, there is sclerosis with inflammatory infiltrate rich in plasma cells, which are usually IgG4 positive. There is also B and T lymphocytes present as well as macrophages. ⁴ One hypothesis is that previous drug exposure may act as a hapten, which triggers an autoimmune response.

Although most cases are idiopathic, there are some known causes of retroperitoneal fibrosis. These are listed in Table 1.

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Table 1.

Secondary causes of retroperitoneal fibrosis.

Causes
Infective	Blastomyces, TB, histoplasmosis, actinomycosis
Malignant	Carcinoid, sarcoma, Hodgkins and non-Hodgkins lymphoma
Drugs	Betablockers, methyldopa, hydralazine, bromocriptine, ergot derivatives, methysergide
Other	Radiation therapy and surgery

Clinical presentation has been classically associated with ureteric obstruction, the first published case described as such, and is usually an insidious process with loin or back pain the predominant complaint. ⁵ The pain is usually progressive, and non-colicky, though other symptoms may relate to the mass and inflammatory effect in the localised area. Testicular swelling is well described as is haematuria. The marked inflammatory response may also lead to weight loss.

Goals of treatment in retroperitoneal fibrosis are removal of a precipitating agent, remission with immunosuppressive therapy, relief of mass effect, e.g. ureteric stents and monitoring response. With the case we have described there were no offending agents to remove, and she underwent bilateral ureteric stents.

Immunosuppressive therapy has been well reported, though evidence relies on case series rather than large randomised trials. Glucocorticoids form the basis of therapy. In a number of small series of trials 60 mg of prednisolone achieved remission in a statistically significant number of patients.^6,7 The length of treatment depends on response, though tapering is usually undertaken over a year. Prednisolone alone achieves remission in over 90% of cases. There is increasing amount of investigation in the use of tamoxifen as monotherapy due to its anti-inflammatory and anti-fibroplastic properties, though a recent head to head study of monotherapy with tamoxifen versus prednisolone suggested the latter to be superior in achieving remission. ⁸

Agents such as methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide and cyclosporine have all been studied as adjunctive therapy to glucocorticoids and in resistant cases. A study of 26 patients compared prednisolone therapy with azathioprine versus oral or intravenous cyclophosphamide with all patients achieving remission. ⁹ There is therefore, no gold standard agent to use in glucocorticoid resistant cases to date, though work is ongoing.

Immunosuppressive treatment is confounded by side effects and complications, particularly when using high dose long term corticosteroid, although remission is likely to be achieved. The case we describe is the only case, to our knowledge, documenting spontaneous remission without immunosuppressive therapy. There may be some justification in monitoring the ongoing disease progress in patients by change in inflammatory markers and appearances on CT scanning rather than proceeding to corticosteroid treatment particularly when there are concerns regarding the potential for side effects.