Systemic lupus erythematosus patients sometimes present with pathologicallu confirmed lupus interstitial cystitis. Treatment with prednisone has not been observed to be successful. Two patients are presented who were successfully treated with intravesical dimethyl sulfoxide (DMSO).

Systemic Lupas erythematosus (SLE) is an autoimmune disease entity with multiorgan involvement. Although the involvement of the genirourinary tract has been traditionally represented by lomerulonephritis, the appearance of interstitial cystitis-like signs and symptoms has recently been postulated as a manifestation of the SLE constellation. ^1,2 Attempts to treat this aspect of the disease with steroids have been largely unsuccessful,^1,2 although at least 1 recent case treated successfully with prednisone has appeared in the literature. ³ We present 2 cases of interstitial cystitis, hereafter referred to as lupus cystitis, sucessfully treated with intravesical dimethyl sulfoxide (DMSO).

Case 1

A forty six year old white woman with well-documented systemic lupus erythematosus presented with dysuria, frequency of urination and suprapubic pain. Urine analysis showed 0-1 red blood cells and no pyuria. Culture of the urine was sterile. Her SLE had been diagnosed thriteen years previously with a biopsy of a malar rash, which had subsequently involved her arms and legs on exposure to the sun. She had also had episodes of fatigue, malaise, high fevers (to 104°F orally), and arthralgias. She also gave a history of mental state changes, including episodes of lethargy and disorientation. These manifestations had responded well to prednisone (80 mg/day p.o.).

An intravenous pyelogram performed as part of the workup for her irritative symptoms was normal. Cystoscopy revealed typical findings usually associated with interstitial cystitis, including patches of hemorrhage submucosally after bladder distention cystoscopically. A biopsy taken at this time confirmed the diagnosis of interstitial cystitis. DMSO was instilled intravesically on three occasions at monthly intervals. Fifty cc of a 50 per cent solution were intstilled, and retained for one hour. There was marked improvement of the symptoms with each instillation, with complete resolution soon after the third dose. The patient has not had recurrent bladder symptoms in fifteen months.

Case 2

A thirty one-year-old while woman with a fifteen-year history of documented SLE was admitted to hospital with fever (to 104°F) arthralgias, and a skin abscess of the thigh. She had had several episodes of high fevers, and arthralgias, and had been on oral steroids for many years. She also had a history of COPD secondary to pulmonary interstitial fibrosis, arteriosclerotic heart disease manifested as angina pectoris, and seizure disorders, for which she was taking diphenylhydantoin. Her complaints at the time of a prior admission had also included severe dysuria, frequency and occasional suprapubic discomfort. Urine analysis and cultures had been negative. An IVP performed after overall condition stabilized had been normal. Cystoscopy had revealed marked cystitis with areas of hemorhage and erythema. A biopsy had confirmed the diagnosis of interstitial cystitis, and silver nitrate had been instilled without any amelioration of symptoms. Subsequent instillation of hydrocortisone (Solu-Cortef) had also been fruitless.

During this admission cystoscopy and biopsy were repeated and confirmed prior findings. Fifty cc of a 50 per cent solution of DMSO were instilled in the bladder and retained for one hour. The patient experienced a lessening of the symptoms although there was residual dysuria and frequency. Repeated instillations were performed at monthly intervals for two months, then every six months thereafter for five more doses with marked improvement with each administration of DMSO. Three years after the last instillation of DMSO the patient remains totally asymptomatic.

Interstitial cystitis has been considered an autoimmune disease for many years. Indeed, the first article linking this entity to the collagen diseases, specifically lupus erythematosus, appeared in 1938. ⁴ For many years the treatment of interstitial cystitis was based on corticosteroids,^5,7 or immunosuppressive agents, especially azathioprine. ⁸ Although success rates ranged from fair to good, side effects made the use of these agents limited. It was not until 1968 that the first published report of intravesical dimethyl sulfoxide (DMSO) in the treatment of interstitial cystitis appeared. ⁹ Since then, other investigators have confirmed its therapeutic value. ¹⁰ Contemporaneously, large series of pathologic and clinical analyses of patients with SLE failed to mention bladder involvement. ^11,12 More recently, published reports of bladder involvement in patients with SLE have appeared. ^1,3 The bladder findings in lupus cystitis, both clinically and pathologically, have been similar to those of patients with isolated interstitial cystitis (that is, not associated with SLE). Clinically, the patients have presented with typical irritative symptoms, including frequency, suprapubic discomfort, and dysuria. Pathologically, immunofluorescent deposits on the blood vessels of the bladder wall have been found in patients with interstitial cystitis, and SLE,^1,2 whereas bladder tissue of patients with isolated interstitial cystitis has not always been demonstrated to have muscle or epithelium antibodies. ^13-14

Reports of patients with interstitial cystitis and SLE have linked the two entities, suggesting cystitis as a manifestation of SLE. The posibility, however, of the diseases being separate and conincidental entities remains viable. Indeed, post-treatment biopsies of bladder wall in patients with cystitis and SLE have failed to show a change in the immunofluorescent pattern when compared with pretreatment biopsies, so that blood vessel immunofluorescence in bladder tissue may be an incidental finding. It is quite possible that SLE patients who are totally asymptomatic with respect to their micturition habits also have immunoglobulin deposits in their bladder wall. Understandably, no report on the findings of bladder biopsies in SLE patients without cystitis symptoms are to be found in the literature. In reviewing the literature on animal models, no mention is made of bladder involvement in murine or canine models for human SLE. ^15-16 Nevertheless, the occasional regression of both irritative bladder symptoms as well as of systemic lupus manifestations after therapy with steroids makes the connection an attractive pathophysiologic theory that may yet be confirmed.

Dimethyl sulfoxide (DMSO), an industrial solvent which was originally a byproduct of the paper pulp manufacturing process, was first used medicinally in 1964. Its properties when applied to the human skin were noted to include diuresis, local analgesia, anti-inflammation, and vasodilatation. ¹⁷ Originally used (with little success) over the surprapubic area in the treatment of interstitial cystitis,¹⁸ it was not until 1968 that it was applied intravesically with good results. ⁹

The patients described in this report, both of whom met the ARA criteria for the diagnosis of SLE,¹⁹ had undergone various courses of steroid therapy, both intravenously as well as orally, for the exacerbation of their SLE manifestations. Although the overall response to the regimen had been adequeate, their irritative cystitis symptoms remained refractory. Instillation of DMSO intravesically produced dramatic and sustained improvement, to the point of total resolution of their cystitis symptoms. Long-term effects of DMSO on the bladder mucosa of these patients remains to be observed, buth the favorable response, at one year for 1 patient and three years for the other, is so far impressive.

Interstital cystitis in association with systemic lupus erythematosus has been observed in selected lupus patients. Although the exact association of cystitis and lupus is as yet undefined, there is evidence suggesting that the cystitis may be a manifestation of the collagen disease. Previously treated with systemic steroids with uneven and generally unsatisfacory results, lupus cystitis responded dramatically to intravesical DMSO in the 2 cases presented.

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2. Rodriguez de la Serna, and Alarcon-Segovia D: Chronic interstitial cystitis as initial major manifestation of systemic lupus erythematosus Rheumatol 8: 808, 1981.
3. Weisman MH, McDonald EC, and Wilson CB: Studies of the pathogenesis of interstitial cystitis, obstructive uropathy: and intestinal maiabsorption in a patient with systemic lupus erythmatosus. Am J Med 70:875, 1981.
4. Fister GM: Similarity of interstitial cystitis (Hunner ulcer) to lupus erythematosus. J Urol 40: 37, 1938.
5. Hoyt H: Cortisone in urological conditions with a report on a trial in interstitial cystitis, ibid 67: 899, 1952.
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11. Harvey AM, et al: Systemic lupus erythematosus; review of the literature and clinical analysis of 138 cases. Medicine 33: 291 1954.
12. DuBois EL, and Tuffanelli DL: Clinical manifestation of systemic lupus erythmatosus. JAMA 190: 104 1964.
13. Silk MR: Bladder antibodies in interstitial cystitis. J. Urol 103: 307 1970.
14. Gordon HL, Rosen RD, Hersh EM, and Yium JJ: Immunologic aspects of interstitial cystitis. J. Urol 109: 228 1973.
15. Huston DP, and Steinberg AD: Animal model of human ststemic lupus erythematosus. Yale Biol Med 52: 289 1979.
16. Walker SE, et al: Palmerston North mice, a new animal model of systemic lupus erythmatosus. J. Lab Clin Med 92: 923 1965.
17. Kligman AM: Topical pharmacology and toxicology of dimethyl sulfoxide. JAMA 193: 923 1965.
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19. Cohen AS, et al: Preliminary criteria of the classification of systemic lupus erythematosus, Bull Rheumat Dis 21: 643 1971.

Urology, Volume 23, Number 2, February 1984, pp. 125-127.

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