An Unusual Cause of Abdominal Pain Jeffrey H. Phillips, M.D., F.A.C.P. Internal Medicine Clinical Update March 24, 2004
History of illness • 63 year old African American man presents June, 2003 with 3 weeks of nausea and periumbilical abdominal discomfort • PMH: mild intermittent asthma; BPH; tonsillectomy • MEDS: prn albuterol ALLERGIES: None • FH: Father with Alzheimer’s. Brother with DM. • SH: retired insurance exec.; nonsmoker x 40 years; no alcohol x 2 years; one coffee per day; exercises regularly • ROS: weight down 10 pounds; otherwise neg.
Physical exam • VS: BP 130/70, HR 70, RR 14, T 98.3 • No jaundice or rash • Sclera anicteric; no oral ulcers; no adenopathy • Normal cardiopulmonary exam • Abdomen soft; mildly tender in the epigastric and periumbilical areas; bowel sounds normal • No hernias; 1+ prostate; stool guaiac negative
Diagnostic work-up (June’03) • WBC 6100, Hb 11.8, platelets 411,000; BUN/Cr 20/1.1, LFTs, lipase, PSA normal; globulin slightly elevated at 4.5 • UGI: moderate GE reflux; otherwise negative • Sonogram: normal liver and pancreas; hypoechoic tissue encasing abdominal aorta; no adenopathy • CT abdomen: 4 x 5 cm periaortic mass from SMA origin down to iliac arteries; compatible with matted nodes, probable lymphoma; no aorta aneurysm seen • CT directed needle biopsies: abnormal but nondiagnostic
CT – June, 2003
Diagnostic work-up (July ’03) • Hospitalized in July for open biopsy • Path consistent with idiopathic retroperitoneal fibrosis (special stains negative for lymphoma) • Pertinent labs: • ESR 141 • CRP 5.77 • ANA, cANCA normal • H/H 8.3/26.3; platelets 631,000 • BUN/Cr 24/1.9
Who ya' gonna call...?
Who ya’ gonna call…? • Surgery? • Gastroenterology? • Rheumatology? • Oncology? • Urology? • Chief of Medicine?
Idiopathic retroperitoneal fibrosis • First described by French urologist Albarran in 1905 • Established as clinical entity by Ormond in 1948 with description of two cases • Characterized by the extensive development of inflammatory fibrotic tissue in the retroperitoneum • Often leading to compression and obstruction of ureters and adjacent organs
Idiopathic retroperitoneal fibrosis • Annual incidence: 0.2 to 0.5 per 100,000 • Average age 50; M:F ratio 2:1 • No ethnic differences • Pathology: dense plaque in the RP, starting at aortic bifurcation, enveloping aorta, IVC, ureters • Bilateral in two thirds of cases • May involve gonadal, celiac, SM, renal arteries
Pathogenesis • Cause unknown; probably autoimmune response to an insoluble lipid called ceroid leaking through thinned arterial walls (circulating ceroid Abs in >90% patients) • Increased production of cytokines (interleukins and Th2) mediates inflammation/fibrosis • Early stage: plaque highly vascular with deposition of collagen and infiltrates of polyclonal B and CD4 T cells • Inflammatory tissue is gradually replaced by fibrosis • Most clinical features secondary to mass effect of fibrosis on adjacent structures
Clinical features • 80% present with dull, poorly localized, noncolicky pain in back, flank, or abdomen • Weight loss, nausea, malaise less frequent • Increasing urinary obstruction with decreased volume or flank pain • Impingement of the IVC or aorta may produce lower extremity edema, thrombophlebitis, claudication, or intestinal ischemia
Diagnosis • Elevated ESR in 80 to 90% • Mild normochromic, normocytic anemia • Elevated BUN/Cr • Imaging depends on presentation: IVP vs. sonogram vs. CT abdomen; MRI may image best • Biopsy necessary to exclude secondary causes • May coexist with other immune-mediated diseases: • PBC, RA, SLE, PAN, GN, ankylosing spondylitis, fibrosing mediastinitis, Hashimoto’s thyroiditis, Wegener’s
Treatment - Surgical • Indicated in cases with severe ureteral or other organ involvement (ureterolysis) • Cystoscopically placed ureteral stents may obviate need for open surgery • Open biopsy also necessary to exclude lymphoma or metastaic cancer as cause of fibrotic process
Treatment - Medical • Corticosteroids • First used in 1958 • Suppress inflammatory response • Best if started in early stages • Typical regimen is prednisone 40 to 60 mg daily tapered to 10 mg daily over 3 to 6 months and then continued several years at low dose • Pulse dosing or alternate day dosing are options
Steroid Therapy for Idiopathic Retroperitoneal Fibrosis: Dose and DurationKardar, et al. Journal of Urology (2002) 168: 550-555 • Prospective study of 12 patients with IPF over 10 year period treated with alternate day steroids • 60 mg q.o.d. x 2 months, 40 mg q.o.d. x 2 weeks, 20 mg q.o.d. x 2 weeks, 10 mg q.o.d. x 2 weeks, and then 5 mg daily for 2 years • Follow-up of 26 to 132 months (median 63) • Only 2 patients failed (1 non-responder and 1 with recurrent symptoms and elevated ESR)
Treatment - Medical • Immunosuppressive agents • Azathioprine • Cyclophosphamide • Methotrexate • Mycophenolate mofetil • Typically given initially with steroids • May serve as a steroid sparing agent • May be first-line when surgery not an option
Immunosuppressive Therapy for Idiopathic Retroperitoneal Fibrosis: A Retrospective Analysis of 26 CasesMarcolongo, et al. AJM (2004) 116: 194-197 • 26 patients with IRF and ureteral obstruction over a 12 year period treated with ureteral stents or nephrostomy • All patients received prednisone (1 to 1.5 mg/kg for 3 weeks, then tapered over 6 months) and • Azathioprine 2.5 mg/kg/d x 6 months then reduced to 1.5 mg/kg x 6 months or • Cyclophosphamide 2 mg/kg/d x 3months and tapered and discontinued within 6 months • Treatment failure rate: 1 per 100 patient-years • This study showed increased safety with azathioprine
Tamoxifen • Effective in pelvic desmoid tumors • Thought to increase production of transforming growth factor-B, an immunosuppressive cytokine that modulates fibroblast activity • Also inhibits protein kinase C, an obligatory mediator of cell proliferation • Relatively safe though may increase risk of thromboembolism and ovarian cancer • Several small series show effectiveness
Prognosis • Resolution is rare without treatment • Over time, mass less likely to respond to medical therapy (less inflammation and more fibrosis) • Renal insufficiency resolves or significantly improves with treatment • Ureteral obstruction may recur in up to 50% treated with surgery alone, compared to 10% treated with steroids, and 1% with steroids plus immunosuppressive therapy
CT imagesJune, 2003 September, 2003
CT imagesMarch 19, 2004
Conclusions • 80% present with dull, poorly localized pain in back, flank, or abdomen; ESR elevated in 80% to 90% • CT or MRI, and biopsy help exclude secondary causes • Surgery often necessary for ureteral involvement • Steroids with or without immunosuppresive therapy is mainstay of treatment and offers best prognosis • Long-term follow-up is necessary
Early diagnosis and prompt treatment preserve organ function
