
NVM James, MM Bheri and M Taube
Department
of Urology,
Mr.MM
Bheri
Associate
Urologist,
E
mail: sum71114@aol.com
SMJ 2006 51(3): 50
Interstitial
Cystitis (IC) is of unknown aetiology, but recently has been
associated with Sjogren’s syndrome. This association is much stronger than was
originally recognised. In these patients the question has always been
whether the bladder symptoms were a manifestation of IC or an autoimmune
process. The beneficial response seen in some patients to steroids tends to
support the latter. We report a case of severe IC associated with Sjogren’s
syndrome in whom bladder symptoms responded to a course of steroids where other
conventional management did not help. We believe that a high index of suspicion
for the association of these two diseases would help treat some of the
refractory cases of IC with a trial of corticosteroids.
Key
Words: Interstitial Cystitis, Sjogren’s syndrome
Interstitial
Cystitis (IC) is a syndrome of unknown aetiology characterised by bladder and/or
pelvic pain and irritable voiding symptoms without evidence of overt infection.
It is recognised that IC is sometimes associated with a number of diseases such
as allergies, Irritable bowel Syndrome, Fibromyalgia, Inflammatory Bowel
Disease, Systemic Lupus Erythematosus and Sjogren’s syndrome. Studies have
shown a strong association between IC and Sjogren’s syndrome. This association
is much stronger than was generally recognised. We report a case supporting this
observation and stress on the need to have a high index of suspicion for this
combination in all patients with IC.
A 50-year-old male
presented with rapid onset of urinary frequency, urgency, dysuria, nocturia
(often as much as 6 to 8 times) and reduced flow rate. He was diagnosed in the
past to have Sicca Syndrome having suffered from dry gritty eyes and dry mouth.
Schirmer’s test had confirmed dry eyes. It was interesting to note that the
patient had been suffering from frequency of micturition and nocturia for some
time but had put it down to excessive water consumption, associated with his dry
mouth. He had no signs of a concurrent connective tissue disorder and had a
negative Rheumatoid factor, ANA and ESR. He was placed on antibiotics by his GP
for clinically suspected UTI. However
multiple urine cultures were negative for infection. Cystoscopy done initially
revealed an inflamed bladder and biopsies confirmed severe inflammation along
with the presence of numerous plasma cells (Figure 2
& 3).
Intravesical Sodium Hyaluronate infusions over a 3 month period were tried.
These did not help and the patient had worsening symptoms that greatly affected
his family and professional life.
He
was brought in once again for a cystourethroscopy, which revealed bladder
appearance typical of Interstitial Cystitis with Glomerulations and Hunner type
Ulcers (Figure 1).
Repeat bloods for immunological markers revealed a positive titre for
Anti Nuclear Antibody and elevated Rheumatoid Factor.
Having
already had an unsuccessful course of Sodium Hyaluronate Infusion he was
commenced on oral steroids. Patient improved and was symptomatically better on
discharge. Patient has since been reviewed by an Immunologist and has been
commenced on Azathioprine and has had Intravesical Dimethylsulfoxide
installation. Patient has been symptomatically better on follow up.
IC
is a Chronic Inflammatory Bladder disease .It was first described in1915, when
Hunner described it as a ‘rare type of bladder ulcer in women’.4
Despite intensive research its prevalence, aetiology, diagnosis and appropriate
treatment remain elusive.5 Although aetiology is poorly understood,
autoimmune mechanism is implicated as one of the causes of IC.8 90%
of IC occurs in women and prevalence is reported to be 52-67 cases per 100,000
women.11 Its impact on quality of life, loss of work time, associated
depression and anxiety are only now becoming apparent.10 Fister1
first reported a case of IC in a patient with SLE in 1938, linking IC with an
autoimmune disease. In 1993, Van De Merwe et al12 studied 10 patients
with IC, 2 of who were diagnosed with Sjogrens syndrome. Further studies at
Rotterdam showed a strong association between IC and Sjogren’s syndrome.13
In this study 28% of IC patients had definite or probable Sjogren’s syndrome.
This association was much stronger than generally recognised. This study also
showed the increased expression of certain growth factor (PD –ECGF, FGF &
VEGF) in the bladder of patients with IC.In addition the expression of CD 44 was
higher in ulcer type IC than in non-ulcer IC.Further studies by Ochs RL et al7
of 96 IC patients have shown almost 36% to be positive for ANA at a titre of
1/40 or greater.
The
prevalence of various European criteria’s for Sjogren’s syndrome was studied
in 100 patients with IC.14 The prevalence was Ocular symptoms 68%,
Oral symptoms 60%, Abnormal ocular test 16%, Abnormal salivary histology 16% and
Antibody to SS-A/Ro or SS-B/La 12%.
It also appears that systemic and autoimmune disorders are
more prevalent in the IC population than the general population with allergy
being the most common IC associated condition.9 Further studies in
Finland have showed patients with Sjogren’s syndrome having symptoms of lower
urinary tract with urinary frequency (27%) and suprapubic pain (36%) being the
most common symptoms. This supports the concept that autoimmune disorders also
have bladder affection.2 Thus the question has always been whether
the bladder symptoms in patients with an autoimmune disorder and associated IC
are due to the association between these two-disease processes and, rather a
manifestation of autoimmune involvement of the bladder. The beneficial response
of cystitis of autoimmune aetiology to steroids tends to support the latter.6
Studies have showed when severe IC is associated with Sjogren’s syndrome a
therapeutic trial of steroid and cyclosporin may be beneficial.11
Horiki et al demonstrated this beneficial effect of steroids in a case of SLE
with various central and peripheral neurogenic disorders presenting with motor
paralytic bladder as a major manifestation.3
However
it must be understood that there is no single treatment that is effective in
treating IC. Most patients however can be maintained in a satisfied, although
definitely not asymptomatic state, punctuated by exacerbations and remissions.15
Interstitial
Cystitis can be a debilitating disease. Its association with autoimmune
disorders needs to be recognised, as there is a beneficial effect of steroids in
treatment of patients with Interstitial Cystitis in association with an
autoimmune disorder.
Fister
GM. Similarity of IC (Hunner’s Ulcer) to Lupus erythematosus. J Urol
40:37,1938
Haarala
M et al: Lower Urinary Tract Symptoms in patients with Sjogren’s syndrome
and SLE. International Urogynecology Journal. 11(2): 84-6, 2000
Horiki
et al: A case of SLE with various central and peripheral neurological
disorders presenting with motor paralytic bladder as a major
manifestation.Ryumachi.1995 Oct; 35(5): 821-6
Hunner
GL. A rare type of bladder ulcer in women: Report of 2 cases Boston med Surg
J 172:660,1916
Leppilahti
M et al: Prevalence of symptoms related to IC in women: a population based
study in Finland. Journal of Urology. 168(1): 139-43, 2002 July
Meulder
et al: Association of Chronic IC, Protein losing enteropathy and paralytic
Ileus with Seronegative SLE. Clin Neph 1992: 37: 239-244
Ochs
RL et al: Auto antibodies in IC. J Urol 1994 Mar; 151(3): 587-92
Oravisto
KJ: Interstitial cystitis as an autoimmune disease. Eur Urol 1980; 6:10-13
Peeker
et al: Intercurrent autoimmune condition in classic and non ulcer IC:
Scandinavian Journal of Urology & Nephrology: 31) 60-3,2003
Shea
0’Malley et al: Quality of life in IC.Urol Intergrada Invest
1999,4:303-306
Shibata
et al: Severe IC associated with Sjogren’s syndrome. Internal Medicine.
43(3): 248-52, 2004 March.
Van
de Merwe et al : Sjogren’s
syndrome in patients with IC. J Rheumatol 20:962-966,1993
Van
de Merwe et al: Systemic aspect of IC, immunology and linkage with
autoimmune disorders. International Journal of Urology. 10 suppl: S35-8,
2003 October
Van
de Merwe. IICPN Publ Nr 2; 2004
Wein et al: IC current and future approaches to diagnosis and treatment. Urol Clin North Am 1994:21:153-161