ARTICLE
Interstitial cystitis (IC) associated with systemic lupus erythematosus
(SLE) was termed lupus cystitis by Orth et al. [1] in 1983. Although
eleven cases of IC were found out of 35 autopsies of SLE patients [2],
manifestations are estimated to be present in 0.1-1% of all SLE cases.
In addition, IC is accompanied not only with SLE but also with Sjögren's
disease and rheumatoid arthritis. Although one case of SLE overlapping
with systemic scleroderma, Sjögren's disease and mixed connective
tissue disease (MCTD) has been reported [3], IC associated with MCTD reported
here is very rare.
Case report
A 64-year-old Japanese woman consulted the Department of Dermatology
in Ogaki Municipal Hospital with swelling and exudative erythema on the
bilateral fingers and dorsal surfaces of the hands on February 19, 1999.
These symptoms had gradually worsened from 6 years previously. She had
suffered from hepatitis C from 1978 and received right hemicolectomy because
of ascending colon cancer in 1991. However, she had not been given radiotherapy
and anti-cancer drugs for colon cancer. She had complained of severe infrapubic
pain and pollakisuria with nausea, vomiting and diarrhea since 1987, and
the pain had become intolerable. Urinalysis revealed no abnormality and
urine culture was negative. Intravenous urography showed a markedly reduced
bladder capacity and a thick and irregular bladder wall, but neither hydronephrosis
nor hydroureters. The clinical diagnosis of IC was made, and prednisolone
was given 5-20 mg/day discontinuously. Since this treatment was not effective
at all and the bladder symptoms were severe, cystectomy was performed
in 1996. The bladder taken by cystectomy was markedly shrunken, and showed
bleeding on the mucosal surface (Fig.
1A), and the bladder capacity was approximately 50 ml. Histological
findings of the bladder showed ulcer formation in the mucous membrane,
and marked infiltration of mononuclear cells, edema and fibrosis in the
submucosal tissue (Fig. 1B).
Ziehl-Neelsen stain was negative.
She has noticed Raynaud's phenomenon and morning
stiffness of the fingers from November, 1998. Exudative erythema, swelling
and sclerosis were seen on the bilateral fingers and dorsal aspects of
the hands at the first clinical examination (Fig.
2A). Sclerodactyly on the fingers was also observed. Histological
findings of the skin biopsy specimen from the dorsal aspect of left ring
finger showed swelling of the capillary walls, mononuclear cell infiltration
around capillaries and edema in the dermis (Fig.
2B). Laboratory data were leukocyte count: 3,010/mul (normal 3,500-9,900),
AST: 130 IU/l (normal 5-40), ALT: 68 IU/l (normal 3-35), IgG: 3,460 mg/dl
(normal 960-2,200), IgA: 955 mg/dl (normal 130-460), IgM: 203 mg/dl (normal
50-360), CH50: 10 U/ml (normal 30-40), anti-nuclear antibody titer: 1:
2,560 (speckled type) (normal < 20), anti-U1 RNP antibody titer: 69.5
by enzyme-linked immunosorbent assay (normal < 15.0). Anti-single strand
DNA, anti-double strand DNA, anti-Sm, anti-SS-A, anti-SS-B, anti-Scl-70,
anti-centromere and anti-mitochondria antibodies were all negative. Cryoglobulin
was also negative in her serum. The values of serum aldolase, myoglobin
and CK were within normal ranges. Computed tomography showed lung fibrosis.
A diagnosis of MCTD [4] following IC was made. The patient has no family
history of these diseases.
Discussion
IC encompasses a major part of the painful bladder disease complex with
negative urine cultures. Painful bladder diseases include not only autoimmune
diseases but also non-autoimmune diseases such as radiation cystitis,
cyclophosphamide cystitis, tuberculosis cystitis and benign or malignant
tumors of bladder [5]. Although a long history of bladder symptoms and
negative urine cultures strongly suggest this disease, cystoscopy with
deep bladder biopsies is necessary to rule out other diseases and to confirm
IC. Lupus cystitis, that is IC complicated with SLE, is found in 0.1-1%
of all SLE cases [6]. On the other hand, the incidence of autoimmune disease
in the IC population is low; only 2 out of 225 IC patients [7]. The question
has been raised as to whether the bladder symptoms represent a simple
association of these two diseases or rather are a manifestation of lupus
involvement of the bladder [8]. The beneficial response of the cystitis
of SLE to steroids tends to support the latter view [8]. However, the
precise mechanisms involved in lupus cystitis remain obscure [6]. Immune
complex-mediated vasculitis may have an important role because the deposition
of the immune complex containing IgG and C3 was demonstrated along the
small articuoles in the bladder of some patients [9], while the involvement
of various cytokines in lupus cystitis is also suspected [10].
Anti-nuclear antibody and anti-U1 RNP antibody
were unfortunately not determined in the present case before 1999, and
the relationship between the onset of MCTD and IC is unclear. However,
as mild leukocytopenia was found in 1991 and the patient noticed swelling
of the fingers and hands in 1993, there is a possibility that she had
suffered from both IC and MCTD simultaneously at least since 1993. However,
since these skin symptoms gradually exacerbated and Raynaud's phenomenon
and morning stiffness of fingers were noticed from 1998, it is likely
that IC preceded the MCTD symptoms. There are several cases in which cystitis
preceded other symptoms of SLE by several years [10]. Lupus cystitis should
be thus taken into account in patients with IC [10].
As for the treatment of lupus cystitis, oral steroid (prednisolone 40-120
mg/day or 1 mg/kg/day), steroid pulse therapy (methylprednisolone 1g/day
for three days) and immunosuppressive drugs have been reported to be effective
[9-11]. However, we could not give steroid pulse therapy or higher doses
of oral steroid to our patient, because she refused to consult our hospital
continuously for steroid therapy. These treatments might have been effective
in this patient.
REFERENCES
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