Rheumatology Advance Access originally published online on January 11, 2007
Rheumatology 2007 46(4):717-718; doi:10.1093/rheumatology/kel417
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mycophenolate mofetil for maintenance of remission in idiopathic retroperitoneal fibrosis
Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK
Correspondence to: Dr Ramesh Jois, Department of Rheumatology, East block, Level-2, Norfolk and Norwich University Hospital, Colney lane, Norwich NR4 7UY, UK. E-mail: rammi09{at}yahoo.com
 |
Introduction |
|---|
 Top Introduction DiscussionReferences |
|---|
SIR, Retroperitoneal fibrosis (RPF) is a rare disease characterized by periaortic inflammation and fibrosis that extends to adjacent abdominal structures. Early recognition and treatment is important to prevent secondary complications such as renal failure (secondary to ureteric obstruction). We have recently reviewed the epidemiology, clinical features and management of RPF in this journal [1]. Medical management consists mainly of use of steroids [2] and immunosuppressive drugs. Azathioprine [3], cyclophosphamide [3], methotrexate [4] and ciclosporin [5] have been used successfully for disease control associated with regression of the periaortic mass. We report a patient with RPF (idiopathic type) who was treated with steroids, methotrexate and cyclophosphamide but disease control was eventually achieved with mycophenolate mofetil (MMF).
A 52-yr-old lady presented with a 5-month history of lethargy, profuse nocturnal sweating, weight loss, diffuse chest and abdominal pain. She was treated with atenolol for migraine. She smoked cigarettes for 15 pack years. Clinical examination was normal. Initial investigations revealed raised inflammatory markers: erythrocyte sedimentation rate (ESR) 130 mm/h and C-reactive protein (CRP) 190 mg/l. Full blood count, renal/bone/hepatic profile were normal. Infection screen was negative. Chest X-ray was normal. A contrast-enhanced computed tomography (CT) scan of her chest and abdomen (Fig. 1A) showed enhancing soft tissue around the abdominal aorta, proximal coeliac axis and superior mesenteric artery (SMA). There was no evidence of hydronephrosis or spread to other structures. This appearance was suggestive of RPF (periaortitis). Temporal artery biopsy, ANA, ANCA, anti-phospholipid antibody, serum electrophoresis and VDRL were performed to exclude secondary causes and were normal.
|
She was treated with prednisolone 60 mg daily with a plan to gradually taper the dose and with this her symptoms and inflammatory markers improved (ESR 4 mm/h CRP 7 mg/l). However, her abdominal pain recurred when the dose of prednisolone was reduced to 20 mg daily. Methotrexate 7.5 mg weekly was added as a steroid-sparing agent. A repeat CT scan 6 months later (Fig. 1B) showed dramatic improvement and resolution of the periaortic tissue around the major abdominal arteries. Prednisolone was reduced to 15 mg, but methotrexate had to be discontinued due to abnormal liver function test.
After 7 months, her symptoms of abdominal discomfort, sweating and fatigue recurred. ESR was 80 mm/h and CRP 52 mg/l. A repeat CT scan this time showed left-sided hydronephrosis in addition to recurrence of periaortic inflammatory tissue (Fig. 1C). She was treated with intravenous pulse—Cyclophosphomide (1000 mg fortnightly, six pulses), and then commenced on MMF (2.5 g daily).
Four months after the start of MMF, she was asymtomatic. Her CRP normalized, prednisolone was reduced to 5 mg daily, and a repeat CT scan revealed complete resolution of the left hydronephrosis along with considerable reduction in the amount of soft tissue encasing the aorta and SMA (Fig. 1D). Fifteen months since the commencement of MMF she remains well, and her CRP is 15 mg/l.
|
Discussion |
|---|
|
TopIntroductionDiscussionReferences |
|---|
RPF is a rare disease with an estimated annual incidence of 0.1 per 100 000 person-years and a prevalence of 1.38 per 100 000 [6]. In view of the rarity of this disease, evidence for treatment is mainly in the form of either case reports or small series of patients. Hence it is important to report both positive and negative outcomes of treatment.
MMF is a potent inhibitor of inosine monophosphate dehydrogenase (IMPDH) which is a key enzyme in de novo synthesis of purines. Since T- and B-lymphocytes critically depend on purine synthesis for proliferation, inhibition of this key enzyme results in a potent cytostatic effect on the lymphocytes. MMF also inhibhits various other lymphocyte functions like antibody formation, endothelial cell adhesion and recruitment of leucocytes to sites of inflammation. Although the pathogenesis of RPF is unclear, recent evidence suggests that it could be a B-cell dominant disease process. The evidence for this is the finding of lymphocytes (both B and T) and plasma cells in the aortic media and adventitia [7], increased expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in the aortic adventitial infiltrates [8] and finally several infiltrating B-cells showing clonal or oligoclonal immunoglobulin heavy chain rearrangement [9]. MMF may thus have a role in the treatment of RPF. The successful use of MMF to control disease activity in RPF has not been studied well. It is evident from literature review that there has been only one isolated report of successful use of MMF in disease control for as long as 14 months since initiation [10]. MMF was used as the initial immunosuppressive agent in this patient along with prednisolone (which was discontinued after one year). Our patient has done well since starting MMF, and her disease has been under control for almost 15 months since initiation. Although the initial response may have been due to cyclophosphamide, maintenance of immunosuppression with MMF has led to resolution of her symptoms, normalizing the inflammatory markers, reduction in steroid dosage along with a reduction in periaortic inflammatory tissue and hydronephrosis. Warnatz et al.'s [3] recent report of 20 patients with RPF included two patients who were treated with MMF as the initial immunosuppressive agent, and both did not respond. It is not clear from their report as to how long these patients received MMF. However, more evidence is necessary to confirm the exact role of MMF as an additional immunosuppressive agent in the armamentarium of drugs to treat RPF. We recommend that MMF should be tried as an alternative immunosuppressant in patients who fail to respond to the more routinely used drugs mainly for maintenance of remission.
The authors have declared no conflicts of interest.
|
References |
|---|
|
TopIntroductionDiscussionReferences |
|---|
- Jois RN, Gaffney K, Marshall T, Scott DGI. (2004) Chronic Periaortitis. Rheumatology 43:1441–6.
[Abstract/Free Full Text] - Kardar AH, Kattan S, Lindstedt E, Hanash K. (2002) Steroid therapy for idiopathic retroperitoneal fibrosis: dose and duration. J Urol 168:550–5.[CrossRef][Web of Science][Medline]
- Warnatz K, Keskin AG, Uhl M, et al. (2005) Immunosuppressive treatment of chronic periaortitis: a retrospective study of 20 patients with chronic periaortitis and a review of the literature. Ann Rheum Dis 64:828–33.
[Abstract/Free Full Text] - Scavalli AS, Spadaro A, Riccieri V, et al. (1995) Long-term follow up of low-dose methotrexate therapy in one case of idiopathic retroperitoneal fibrosis. Clin Rheumatol 14:481–4.[CrossRef][Web of Science][Medline]
- Marzano A, Trapani A, Leaone N, et al. (2001) Treatment of idiopathic retroperitoneal fibrosis using cyclosporine. Ann Rheum Dis 60:427–8.
[Abstract/Free Full Text] - Uibu T, Oksa P, Auvinen A, et al. (2004) Asbestos exposure as a risk factor for retroperitoneal fibrosis. Lancet 363:1422–6.[CrossRef][Web of Science][Medline]
- Parums DV, Choudhury RP, Shields SA, Davies AH. (1991) Characterisation of inflammatory cells associated with idiopathic retroperitoneal fibrosis. Br J Urol 67:564–8.[Web of Science][Medline]
- Ramshaw AL and Parums DV. (1994) The distribution of adhesion molecules in chronic periaortitis. Histopathology 24:23–32.[Web of Science][Medline]
- Oshiro H, Ebihara Y, Serizawa H, et al. (2005) Idiopathic retroperitoneal fibrosis associated with immuno-hematological abnormalities. Am J Med 118:782–6.[CrossRef][Web of Science][Medline]
- Grotz W, von Zedtwitz I, Andre M, Schollmeyer P. (1998) Treatment of retroperitoneal fibrosis by mycophenolate mofetil and corticosteroids. Lancet 352:1195.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||