The haemodialysis patient with night sweats, ascites, and increased CA 125

(Section Editor: K. Kühn)

Roland Sessler, Hasan Konyar, Georg Hasche and Christof J. Olbricht

Zentrum für Innere Medizin, Klinik für Nieren- und Hochdruckkrankheiten, Katharinenhospital Stuttgart, Stuttgart, Germany

Case

The patient is a 47-year-old Philippine woman with end-stage renal disease since 1996 due to diabetic nephropathy. She has been living in Germany since 1982, but travelled to the Philippines each year for some weeks for vacation. In the past medical history, enlargement of mediastinal lymph nodes was noticed since 1995, but without any pulmonary infiltrations. Mediastinoscopic biopsy at that time revealed a non-caseating granulomatous lymphadenitis. No further work-up was done and several chest X-rays had been unchanged in the following years.

In February 1999 the patient reported persistent mild vaginal bleeding, night sweats, and low-grade fever. A weight loss of 5 kg and an erythropoietin-resistant anaemia were noted.

The physical examination revealed a tense abdomen but was otherwise normal. A tuberculin skin test was negative. Ultrasound showed large quantities of ascites in the whole abdomen, without signs of portal hypertension. A gynaecological pelvic examination was unremarkable.

Laboratory examination revealed a microcytic anaemia with haemoglobin 9.2 g/dl, platelet count 444 000/µl, white cell count 8000/µl, with 70% neutrophils, 8% lymphocytes, 20% monocytes, 1% eosinophils, and 1% basophils in the differential count. Calcium, LDH, bilirubin, and liver enzymes were within normal limits. Serum albumin was slightly reduced to 39 g/l.

As ovarian cancer was suspected, the serum level of CA 125 was measured and found to be increased to 297 U/ml (normal <30 U/l). Serological markers for hepatitis B and C and HIV were negative.

A chest X-ray was unremarkable, with no signs of congestive heart failure or pulmonary infiltration, but CT-scan of the chest a few days later revealed infiltrates of the right lung and enlargement of a calcified lymph node in the right mediastinum (Figure 1Go). Bronchoscopy was not performed. A CT scan of the abdomen and pelvis showed perihepatic ascites and calcification of an enlarged lymph node para-aortal (Figure 2Go).



View larger version (136K):
[in this window]
[in a new window]
 
Fig. 1. Computed tomography of the chest showing pulmonary infiltrates of the right lung and calcification of a lymph node in the right mediastinum.

 


View larger version (178K):
[in this window]
[in a new window]
 
Fig. 2. Computed tomography of the abdomen. Note the enlargement of a calcified lymph node para-aortal close to the left renal hilus and the predominantly perihepatic ascites.

 
Diagnostic paracentesis revealed yellow clear ascitic fluid with glucose 89 mg/dl, leukocytes 1300/µl, total protein content 61 g/l, no erythrocytes, LDH 616 U/l, and cholesterol 78 mg/dl. Ascitic fluid cytology showed predominantly lymphocytes and monocytes, some neutrophils, but no malignant cells. No acid-fast bacilli were identified on smear examination of ascites and gastric aspirates. Laparoscopy showed a fibrinous peritonitis with multiple adhesions of the peritoneum. No tumour was found. No biopsy was taken because of easy bruising of the peritoneum with the risk of bleeding.

Because of the granulomatous lymphadenitis in the past medical history, tuberculous peritonitis was considered in the differential diagnosis. Ascites was examined for Mycobacterium tuberculosis by polymerase chain reaction, and was found positive.

A diagnosis of pulmonary and peritoneal tuberculosis was made and tuberculostatic treatment was started with rifampicin (450 mg/day), isoniazid (300 mg/day), and ethambutol (250 mg/day (patient's body weight 50 kg)) with regular ophthalmological check-up. The patient's condition improved rapidly. The ascites subsided and the serum level of CA 125 returned to normal. Some weeks later, the culture of the ascitic fluid finally yielded Mycobacterium tuberculosis, sensitive to all common antitubercular drugs.

Discussion

Tuberculous peritonitis is one cause among many others that have to be considered in patients with end-stage renal failure and ascites [1]. Haemodialysis patients are up to 16 times more likely to acquire tuberculosis, compared to the general population [2]. This may be due to impaired cellular immunity in patients with chronic renal failure [3]. Signs and symptoms may be non-specific with an insidious onset, loss of weight, and low-grade fever [4]. In our patient, we initially suspected ovarian cancer because of the new-onset ascites, vaginal bleeding, and increased serum level of CA 125. But further diagnostic work-up revealed tuberculous peritonitis.

Immigrant status appeared to be a risk factor for tuberculosis [5], although it remains speculation whether our Philippine patient acquired tuberculosis in Germany or during her vacations in the Philippines.

Tuberculous peritonitis results from haematogenous seeding of the peritoneum and is usually preceded by pulmonary tuberculosis. Retrospectively, we think that our patient had long-standing latent tuberculosis of the mediastinal lymph nodes, as indicated by the granulomatous mediastinal lymphadenitis found in 1995. The tuberculous peritonitis was part of a reactivation of tuberculosis in our patient.

CA 125 is a glycoprotein secreted by mesothelial cells [6]. The increased serum level of CA 125 in our patient is due to the activation of peritoneal mesothelial cells by the inflamed peritoneum. Increased serum levels of CA 125 are a useful marker of epithelial ovarian cancer but can also be seen in other abdominal and extra-abdominal malignant or benign diseases, indicating that specificity of CA 125 is low and increased levels just reflect activation of mesothelial cells lining the peritoneum, pleura, or pericardium, whatever the stimulus is [79].

The increase of CA 125 in our patient is not due to renal insufficiency. Menzin et al. [10] found no impaired metabolism or clearance of CA 125 in female haemodialysis patients. Increase of CA 125 in tuberculous peritonitis has been described in patients with normal renal function [11]. CA 125 normalizes under anti-tubercular therapy, indicating that CA 125 might serve as a control of therapy.

Teaching points

(i) In the haemodialysis patient with new-onset of ascites, do not forget tuberculous peritonitis.
(ii) Increase of CA 125 is not specific for ovarian cancer, but rather indicates activation of mesothelial cells in response to various stimuli.

Acknowledgments

The authors wish to thank Professor I. P. Arlart (Katharinenhospital Stuttgart) for the CT scans.

Notes

Supported by an educational grant from

Fresenius Medical Care

Correspondence and offprint requests to: Dr R. Sessler, Katharinenhospital, Klinik für Nieren- und Hochdruckkrankheiten, Kriegsbergstr 60, D-70174 Stuttgart, Germany. Back

References

  1. Franz M, Hörl WH. The patient with end-stage renal failure and ascites. Nephrol Dial Transplant1997; 12: 1070–1078[Free Full Text]
  2. Woeltje KF, Mathew A, Rothstein M, Seiler S, Fraser VJ. Tuberculosis infection and anergy in hemodialysis patients. Am J Kidney Dis1998; 31: 848–852[ISI][Medline]
  3. Newberry WM, Sanford JP. Defective cellular immunity in renal failure: depression of reactivity of lymphocytes to phytohemagglutinin by renal failure serum. J Clin Invest1971; 50: 1262–1271[ISI][Medline]
  4. Mitwalli A. Tuberculosis in patients on maintenance dialysis. Am J Kidney Dis1991; 5: 579–582
  5. Belcon MC, Smith EK, Kahana LM, Shimizu AG. Tuberculosis in dialysis patients. Clin Nephrol1982; 17: 14–18[ISI][Medline]
  6. Zeillemaker AM, Verbrugh HA, Hoynck van Papendrecht AAGM 125 secretion by peritoneal mesothelial cells. J Clin Pathol1994; 47: 263–265[Abstract]
  7. Jacobs I, Bast RC. The CA 125 tumour-associated antigen: a review of the literature. Hum Reprod1989; 4: 1–12[Abstract]
  8. Kabawat SE, Bast RC Jr, Bhan AK, Welch WR, Knapp RC, Colvin RB. Tissue distribution of a coelomic-epithelium-related antigen recognized by the monoclonal antibody OC125. Int J Gynecol Pathol1983; 2: 275–285[ISI][Medline]
  9. Lazzarino M, Orlandi E, Klersy C et al. Serum CA 125 is of clinical value in the staging and follow-up of patients with non-Hodgkin's lymphoma. Cancer1998; 82: 576–582[ISI][Medline]
  10. Menzin AW, Kobrin S, Pollak E, Goodman DBP, Rubin SC. The effect of renal function on serum levels of CA 125. Gynecol Oncol1995; 58: 375–377[ISI][Medline]
  11. O'Riordan DK, Deery A, Dorman A, Epstein OE. Increased CA 125 in a patient with tuberculous peritonitis: a case report and a review of published works. Gut1995; 36: 303–305[Abstract]