1. Retroperitoneal Fibrosis Uptodate 2015 ®
순천향대학교 서울병원
신장내과 R3 김윤석

2. 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"

3. 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

4. Etiology and Risk factors (1)

5. Etiology and Risk factors (2)

6. 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 (95% CI )
Without smoking: OR of 4.22 (95% CI )

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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)

13. 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 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 Sep;65(9):
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 Jul;71(7)

14. 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

15. 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