An Unusual Cause of Abdominal Pain

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An Unusual Cause of Abdominal Pain

• Jeffrey H. Phillips, M.D., F.A.C.P.
• Internal Medicine Clinical Update
• March 24, 2004

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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 Alzheimers. 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.

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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

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Diagnostic work-up (June03)

• 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

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CT June, 2003
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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

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Who ya' gonna call...?
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Who ya gonna call?

• Surgery?
• Gastroenterology?
• Rheumatology?
• Oncology?
• Urology?
• Chief of Medicine?

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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

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Idiopathic retroperitoneal fibrosis

• Annual incidence 0.2 to 0.5 per 100,000
• Average age 50 MF ratio 21
• 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

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Pathogenesis

• Cause unknown probably autoimmune response to
  an insoluble lipid called ceroid leaking through
  thinned arterial walls (circulating ceroid Abs
  in gt90 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

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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

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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, Hashimotos thyroiditis,
  Wegeners

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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

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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

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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)

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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

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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

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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

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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

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Office visit Prednisone, mg Imuran, mg ESR, Hb
Aug. 9 60 - 141, 8.3(Cr 1.9)
Aug. 15 60 - 89, 9.4
Aug. 29 60 - 11, 11.1 (Cr 1.1)
Sep. 24 40 - 18, 12.2
Oct. 29 35 - 12, 13.6
Dec. 16 30 50 13, 13.2
Jan. 7 25 50 13, 13.0
Jan. 27 20 50 9, 13.3
Feb. 19 15 50 8, 12.9
Mar. 16 10 50 11, 13.0
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CT images June, 2003 September,
2003
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CT imagesMarch 19, 2004
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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

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• Early diagnosis and prompt treatment preserve
  organ function