Retroperitoneal Fibrosis Uptodate 2015 ® 순천향대학교 서울병원 신장내과 R3 김윤석

Introduction Definition Presence of inflammatory and fibrous retroperitoneal tissue Encases the ureters or abdominal organs Idiopathic or secondary to other causes part of the disease spectrum of "chronic periaortitis"

Epidermiology Incidence Most commonly occurs in 40 to 60 years of age In Finland: 0.1 per 100,000 person-years In Netherlands: 1.3 per 100,000 person-years Most commonly occurs in 40 to 60 years of age Male-to-female ratios of 2 to 3 : 1, male predominant

Etiology and Risk factors (1)

Etiology and Risk factors (2)

Etiology and Risk factors (3) Retroperitoneal hemorrhage Surgery Lymphadenectomy, colectomy, aortic aneurysmectomy Multiplicative increase in risk of retroperitoneal fibrosis Exposure to asbestos with or without smoking With smoking: OR of 12.04 (95% CI 4.32-38.28) Without smoking: OR of 4.22 (95% CI 2.14-8.33)

Pathogenesis Unclear, but two leading theories Local inflammatory reaction to aortic atherosclerosis Incited by oxidized LDL Finding in patients with chronic periaortitis Activated T and B lymphocytes in the media and adventitia High levels of interleukins, antibodies to oxidized LDL Systemic autoimmune disease Frequent presence of constitutional symptoms Increased acute phase reactants, autoantibodies IgG4-related disease: infiltration of IgG4-producing plasma cells

Clinical manifestations (ROS) Lower back abdomen or flank pain (m/c, over 90%) Dull & poorly localized Not affected by activity or posture Radiating to inguinal area Systemic complaints malaise, anorexia, weight loss, fever, nausea, vomiting Obstructive uropathy Gross hematuris is uncommon Urgency, frequency, dysuria is common

Clinical manifestations (P/Ex) Hypertensive(due to renal artery impingement) In Nethelands study, 57% patient present hypertension In North america, 33% new-onset hypertension was related to RPF Lower extremity edema Thrombophlebitis, deep vein thrombosis Obstruction of IVC and/or iliac veins Hydrocele, varicocele Compression of retroperitoneal vessels

Laboratory findings Elevation in the serum BUN/Cr Among 40 patients with newly diagnosed RPF(Italy study) 72 to 78% had ureteral obstruction 44 to 50% had renal failure ESR and CRP are elavated Reflecting the inflammatory nature Ultrasonography One randomized trial, 72 to 78% had uni or bilateral obstruction Limitation d/t body habitus, bowel gas, bony structure

Diagnosis Imaging study of choice is CT Definitive diagnosis may require a biopsy Location of the mass is atypical Clinical, laboratory, radiologic findings suggest malignancy or infection Patient does not respond to initial therapy Inflammatory infiltrate consists of B and T lymphocytes, macrophages, and plasma cells Prominent fibrous tissue consists of type-I collagen, fibroblast MRI

Managements (1) Glucocorticoids (mainstay of therapy) Prednisone 1 mg/kg per day (maximum dose 80 mg/day) for 4 wks If improvement is observed, taper the dose over 2 to 3 months Maintain 10mg/day for an additional 6 to 18 months Relapse rate is lower, but a/w adverse effects Glucocorticoids-resistant disease No improvement within 4 to 6 wks, should repeat CT or biopsy High dose prednisone (1mg/kg per day) for another 2 to 4 months With high dose prednisone, other immunosupressive agents (azathioprine, MTX, MMF, cyclophosphamide, cyclosporine) can be used. Prefer to add MTX d/t steroid sparing effect MTX start with 7.5mg/wk, increase 2.5mg monthly, max dose 20mg Cr > 2.0 , MMF should be taken (d/t renal toxicity of MTX)

Managements (2) Investigative therapies Refractory to combined glucocorticoid and MTX, TNF-α monoclonal antibody (infliximab) 5mg/kg at week 0,2,6,8 and weekly thereafter for 3 years Clin Exp Rheumatol. 2012 Sep;30(5):776-8 In addition to predinosone and MTX, IL-6 Rc antibody (toclizumab, 8mg/kg every 4wk for 6 months) Arthritis Rheum. 2013 Sep;65(9):2469-75 Refractory disease was treated with rituximab (375 mg/m2 a week for four consecutive weeks) without additional therapy, still in remission at 18 months after therapy Ann Rheum Dis. 2012 Jul;71(7)

Managements (3) Interventional procedure Double-J stents insertion Percutaneous nephrostomy Open surgey Technical difficulty Suggesting underlying malignancy (to obtain a definite diagnosis) Lack of regression after medical therapy Persistant encasement of organs

Case 55세 남자환자 특이 내과적 과거력 없으며 4일전부터 두통, 오심, 간헐적인 좌상복부통증 있어 식사 잘 못하였고 두통으로 지역의원 신경과에서 특이 이상 소견 없다 들으며 두통은 호전 양상이나 내원 당일 오후부터 복통과 오심 악화되어 응급실 경유 AKI 로 입원함. 2/4 Abdominal USG Lt hydronephrosis and dilatation of proximal ureter 2/5 APCT(E) soft tissue density around abdominal aorta and IMA bifurcation 2/6 D-J stent insertion 2/6 serum IgG4 level: pending