Weeklong history of progressive lower-leg swelling and pelvic pain
Pitting edema extended all the way to the groin, and the abdomen was slightly distended
Ms. L, 67 years old and white, presented with a one-week history of progressive left leg pain and swelling. The swelling started in the distal extremity and progressed proximally. Other symptoms included a dry nocturnal cough and pelvic pain. The patient denied any leg trauma, fevers, chills, nausea, or vomiting. Her past medical history was significant for hypertension, depression, osteoarthritis, and hyperlipidemia.
On examination, Ms.L's BP was 174/100 mm Hg, heart rate 66 beats per minute and regular, respiratory rate 18 breaths per minute, oxygen saturation 94% on room air, temperature 98.9ºF. Her neck was supple, lungs were clear to auscultation, heart sounds were normal, and abdomen was slightly distended; tenderness was present in the left pelvic region. No guarding, rigidity, or organomegaly was detected, but left-sided inguinal lymphadenopathy was noted. The left leg showed 3+ pitting edema extending all the way to the groin. Chronic venous varicosities were also observed. There was nonspecific diffuse mild tenderness. Homans' sign was negative. These findings led to several differential diagnoses: deep venous thrombosis (DVT), elephantiasis, phlegmasia alba dolens (painful white leg), idiopathic retroperitoneal fibrosis (RPF), and pelvic malignancy.
Laboratory findings, especially the blood urea nitrogen, creatinine, and fractionated excretion of sodium level, suggested possible renal disease (Table 1). Urinalysis was normal; no eosinophils were seen. Electrophoresis for serum and urinary protein was unremarkable. All other lab studies were within normal limits.
Further workup included a chest x-ray, which was negative. Ms. L's unilateral leg swelling prompted two venous Doppler studies one week apart, both of which were negative. Abdominal and pelvic CT imaging was ordered after adequate hydration and premedication with N-acetylcysteine (Mucomyst) to avoid further worsening of renal function.
Moderate bilateral hydronephrosis, medial deviation of the ureters (Figure 1), and soft-tissue prominence around the mid-abdominal aorta about one centimeter in length pointed to a diagnosis of RPF. Idiopathic RPF is also known as “Ormond's disease,” “periureteritis” or “sclerosing retroperitoneal granuloma.” In >90% of patients, RPF presents gradually as pain in the flank, lower back, or abdomen. The pain is progressive, unchanged with position, and relieved by nonsteroidal anti-inflammatory drugs (NSAIDs) due to the inflammatory nature of the fibrosis. Constitutional symptoms include malaise, anorexia, fever, nausea, vomiting, and weight loss. Inferior vena caval involvement causes lower-extremity edema, DVT, and phlebitis. Claudication and mesenteric ischemia indicate arterial disease. Ureteral involvement causes hydronephrosis and renal insufficiency.
The nonspecific nature of the symptoms frequently causes the diagnosis to be delayed. Diagnosis is primarily made with the help of imaging studies, including ultrasonography, urography, CT, and MRI. CT is the imaging study of choice. Biopsy helps confirm the diagnosis and rule out malignancy.
RPF is relatively uncommon, with an incidence of one case per 200,000 population. Patients are often 40-60 years of age in a male-to-female ratio of 2:1. The underlying mechanism is inflammatory fibroblast proliferation with extracellular matrix deposition, which is usually benign, but malignancy should be ruled out.
In most patients (approximately 68%), no etiologic factor is found. Recent evidence suggests that RPF is an autoimmune response to ceroid, an insoluble lipid, that has leaked through a thinned arterial wall from atheromatous plaques. Other implicated causes include drugs, abdominal aortic aneurysm, ureteric renal injury, infection, retroperitoneal malignancy, chemotherapy, and post-irradiation therapy. No genetic predominance is seen in malignant RPF. Drugs implicated in causing RPF include methysergide, beta blockers, lysergic acid diethylamide, methyldopa, amphetamines, phenacetin, pergolide, and cocaine.
Drainage of the upper urinary tract can be performed as a temporary treatment measure. Percutaneous nephrostomy and insertion of a double-J stent helps restore renal function and allows time to improve fluid, electrolyte, and acid-base balance prior to surgery. The use of steroids in RPF remains controversial, although some authorities believe that steroids can be used as an adjuvant to surgical ureterolysis. More recently, immunosuppressive drugs, such as azathioprine, cyclophosphamide, and tamoxifen, have been used to treat RPF. In drug-related RPF, cessation of the drug therapy can result in restitution of the urinary tract and disappearance of the symptoms. Significant morbidity may result because of renal failure. Although fatalities do occur, a satisfactory outcome can be expected if renal impairment is not too severe. Unlike idiopathic (nonmalignant) RPF, a distinctly poor prognosis is associated with malignant RPF, which occurs in response to metastatic tumor cells in the retroperitoneum.
Following placement of bilateral ureteral stents, our patient's creatinine decreased to 1.5 mg/dL. An open biopsy showed dense fibrous connective tissue and scattered islands of lymphoid tissue consistent with the diagnosis of idiopathic RPF. No evidence of malignancy was seen. Ms. L also received prednisone 30 mg once a day for one month. Since then, her BP has normalized, and her leg edema has resolved. The ureteral stents were removed after six weeks. Recent labs showed a creatinine of 1.2.