Just another urinary tract infection?

(Section Editor: M. G. Zeier)

Jan Hinrich Bräsen, Ulrich Thiel, Wolfgang Schneider and Ursula Göbel

Franz Volhard Clinic and Departments of Urology, Pathology and Medicine, Klinikum Buch, Berlin, Germany

Case

A 64-year-old woman presented with dysuria. She was treated with various antibiotics for 8 months without relief. Three months prior to admission, she was prescribed a cream for vaginal mycosis which did not help. She claimed that she had lower abdominal pain above the pubic region, which was relieved by voiding. She also explained that she spent much of each night on the toilet and that urinating 20 times per night was nothing at all unusual. She had type 2 diabetes mellitus which required insulin for the past year. On examination, with the exception of suprapubic tenderness, nothing remarkable was found. Several urine cultures had been obtained, which were either confusing or non-revealing, perhaps due to the fact that the patient was invariably ingesting an antibiotic prescribed by one of numerous physicians.

The patient had a normal haemoglobin and haematocrit. Her blood leucocyte count was normal, although her C reactive protein level was elevated at 45 mg/l. The creatinine concentration was 238 µmol/l. Other serum chemistries were unremarkable, including autoantibodies. Her urinalysis revealed many leucocytes and erythrocytes per high power field. No casts or dysmorphic erythrocytes were seen, although a few bacteria were evident. She had a urine protein concentration of 0.75 g/l. A urine culture revealed Torulopsis glabrata. Cultures for tuberculosis were negative. Ultrasound examination revealed that the kidneys were reduced in size. The bladder was small with a thickened wall. A computerized tomographic (CT) scan of the bladder is shown in Figure 1Go. A diagnostic procedure was performed.



View larger version (164K):
[in this window]
[in a new window]
 
Fig. 1. A CT scan of the lower abdomen shows a bladder reduced in size with a thickened wall (arrow). The somewhat distended ureters (1 and 2, double-headed arrows) can be seen.

 

Question

What is your diagnosis?

Answer to quiz on preceding page

The patient underwent cystoscopy with biopsy. Figure 2Go shows a haematoxylin- and eosin-stained section of the bladder wall. The detrusor musculature shows evidence of some fibrosis. In the second panel, stained for chloracetate-ASD-esterase, a marked mast cell infiltrate can be appreciated (mast cell number 41/mm2). These findings are typical of interstitial cystitis. The patient refused any additional treatment and demanded discharge. Her request was granted and she was prescribed tramadol and itraconazole.



View larger version (94K):
[in this window]
[in a new window]
 
Fig. 2. (A) A haematoxylin and eosin stain of a deep bladder biopsy. The detrusor smooth muscle reveals signs of fibrosis. (B) A chloracetate-ASD-esterase stain revealing copious amounts of mast cells (arrowheads) in the bladder wall, consistent with interstitial cystitis.

 
Interstitial cystitis is a chronic inflammatory bladder disorder of unknown cause. Because there is no clear definition, diagnosis is based mainly on exclusion. Typical symptoms consist of chronic irritative voiding, urinary frequency, urgency, nocturia, and lower abdominal pain, which is often associated with bladder filling and relieved by urination. Like bacterial cystitis, interstitial cystitis is far more common in women (~90%) than men, with a prevalence up to 67 per 100 000 women [1]. The diagnosis requires a thorough history, cystoscopy under anaesthesia with hydrostatic bladder distension and deep biopsies. Cystoscopically, interstitial cystitis is characterized by petechial mucosal haemorrhages termed glomerulations. In severe cases the bladder capacity is reduced and occasionally features ulcerations called Hunner's ulcer. Bladder biopsies can exclude other diseases such as carcinoma and tuberculosis. Histological abnormalities, such as fibrosis of the detrusor muscle, are not specific.

The aetiology is unknown. Autoimmune, allergic, neurological, infectious, vascular and mechanical mechanisms, as well as a defective gycoprotein/ glycosaminoglycan barrier, have been proposed. The presence of mast cells, eosinophils and T lymphocytes within the bladder wall suggests involvement of the immune system.

Moreover, the association with other diseases including thyroid disorders, lupus erythaematosus, Sjögren's syndrome and inflammatory bowel disease also suggests an autoimmune pathogenesis [1]. Patients with interstitial cystitis have a 100-fold increased risk of developing inflammatory bowel disease and a 30-fold incresased risk of association with lupus erythematosus and Sjögren's syndrome [3,4]. Accordingly, laboratory findings often reveal reduced complement C4 and increased IgG levels, as well as ANA antibody titres >1:40, often including SS-A/Ro and SS-B/La [5]. Tryptase, a mast cell enzyme, is frequently elevated in 24 h urine samples. In patients with Sjögren's syndrome and distal renal tubular acidosis, the increased potassium content of the urine may lead to an increased influx into the bladder wall, causing sensory symptoms and tissue damage [6]. Interstitial cystitis may also be a local expression of a primary systemic disease.

As the aetiology and pathogenesis are unclear, there is no specific efficient treatment available for interstitial cystitis [7]. Bladder training with application of spasmolytic agents into the bladder may improve symptoms and inhibit further bladder shrinkage [8].

Notes

Supported by an educational grant from

References

  1. Curhan GC, Speizer FPE, Hunter DJ, Curhan SG, Stampfer MJ. Epidemiology of interstitial cystitis: a population based study. J Urol1999; 161: 549–552[ISI][Medline]
  2. Van De Merwe JP, Arendsen HJ. Insterstitial cystitis: a review of immunological aspects of the aethiology and pathogenesis, with a hypothesis. BJU Int2000; 85: 995–999[ISI][Medline]
  3. Van de Merwe J, Kamerling R, Arendsen E, Mulder D, Hooijkaas H. Sjögren's syndrome in patients with interstitial cystitis. J Rheumatol1993; 20: 962–966[ISI][Medline]
  4. Alagiri M, Chottiner S, Ratner V, Slade D, Hanno PM. Interstitial cystitis: unexplained association with other chronic disease and pain syndromes. Urology1997; 49: 52–57[ISI][Medline]
  5. Ochs RL, Stein TW, Peebles CL, Gittes RF, Tan EM. Autoantibodies in interstitial cystitis. J Urol1994; 151: 587–592[ISI][Medline]
  6. Parsons CL, Greenberger M, Gabal L, Bidair M, Barme G. The role of urinary potassium in the pathogenesis and diagnosis of interstitial cystitis. J Urol1998; 159: 1862–1866[ISI][Medline]
  7. Propert KJ, kSchaeffer AJ, Brensinger CM et al. A prospective study of interstitial cystitis: results of longitudinal followup of the interstitial cystitis data base cohort. J Urol2000; 163: 1434–1439[ISI][Medline]
  8. Barbalias BA, Liatsikos EN, Athanasopoulos A, Nikiforidis G. Interstitial cystitis: bladder training with intravesical oxybutynin. J Urol2000; 163: 1818–1822[ISI][Medline]




This Article
Extract
FREE Full Text (PDF)
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Disclaimer
Request Permissions
Google Scholar
Articles by Bräsen, J. H.
Articles by Göbel, U.
PubMed
PubMed Citation
Articles by Bräsen, J. H.
Articles by Göbel, U.