Interstitial cystitis and ileus in pediatric-onset systemic ... - Springer Link

3 downloads 0 Views 62KB Size Report
interstitial cystitis · Paralytic ileus · Systemic lupus erythematosus · Thrombocytopenia. Introduction. Systemic lupus erythematosus (SLE) is an autoimmune.
Pediatr Nephrol (2000) 14:859–861

© IPNA 2000

B R I E F R E P O RT

Hiroshi Tanaka · Shinobu Waga · Takashi Tateyama Tohru Nakahata · Tatsuo Ito · Kazuhiko Sugimoto Yoshiki Kakizaki · Kazuhiko Tomimoto Masaru Yokoyama

Interstitial cystitis and ileus in pediatric-onset systemic lupus erythematosus Received: 1 September 1999 / Revised: 2 December 1999 / Accepted: 3 December 1999

Abstract A girl aged 11 years presented with autoimmune hemolytic anemia with thrombocytopenia, and subsequently developed severe abdominal pain, vomiting, and pollakiuria. X-ray findings of her abdomen demonstrated paralytic ileus with intestinal wall thickening. Intravenous pyelography revealed bilateral hydroureter with mild hydronephrosis and contracted bladder. Pathological examination of her bladder revealed interstitial cystitis, with evidence of focal deposition of IgG and C3 in a granular pattern on small blood vessel walls. She was diagnosed as having systemic lupus erythematosus (SLE) associated with paralytic ileus and chronic interstitial cystitis. Although initiation of high-dose prednisolone therapy resulted in a gradual improvement in clinical symptoms, reducing the dosage of prednisolone caused a relapse. To our knowledge, the combination of paralytic ileus and chronic interstitial cystitis is quite uncommon in pediatric-onset SLE. Key words Autoimmune hemolytic anemia · Chronic interstitial cystitis · Paralytic ileus · Systemic lupus erythematosus · Thrombocytopenia

Introduction Systemic lupus erythematosus (SLE) is an autoimmune disorder with multiorgan involvement. Although the typH. Tanaka · S. Waga · T. Tateyama · T. Nakahata · T. Ito K. Sugimoto · Y. Kakizaki · M. Yokoyama Department of Pediatrics, Hirosaki University, School of Medicine, Hirosaki 036-8562, Japan K. Tomimoto Division of Pediatrics, Aomori Rosai Hospital, Hachinohe 031-8551, Japan H. Tanaka (✉) Department of Pediatrics, Hirosaki University, School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan e-mail: [email protected] Tel.: +81-172-395070, Fax: +81-172-395071

ical clinical manifestation of the urinary tract is glomerulonephritis, chronic interstitial cystitis has been reported as an uncommon manifestation in patients with SLE [1–11]. Moriuchi et al. [5] reported a strong association of chronic interstitial cystitis and disease of the intestinal tract, and suggested that such patients comprise a distinct subgroup of SLE. However, these clinical manifestations have rarely been reported in childhood SLE [7, 11]. We encountered an 11-year-old girl with autoimmune hemolytic anemia (AIHA) associated with thrombocytopenia. She was diagnosed as having SLE, and subsequently developed paralytic ileus and chronic interstitial cystitis. We report here another case of childhood lupus cystitis.

Case report An 11-year-old girl presented in June 1994 with fatigue and lowgrade fever. Laboratory investigation at that time revealed severe anemia (hemoglobin 4.7 g/dl), a positive direct Coombs test, depressed haptoglobin of 5 mg/dl (normal range 50–300 mg/dl), low levels of C3 (60 mg/dl, normal range 70–130 mg/dl) and C4 (4 mg/dl, normal range 20–50 mg/dl), a false-positive serological test for syphilis, and a negative titer of anti-nuclear antibody (ANA). Bone marrow aspiration findings were unremarkable. Thus the tentative diagnosis of “idiopathic” AIHA was made, This was treated by prednisolone (60 mg daily), with a rapid improvement in her AIHA. However, prednisolone tapering resulted in the emergence of thrombocytopenia without AIHA. Plateletassociated IgG increased to 211.2 ng/107 cells (normal range 9.0–25.0). Platelet counts fluctuated between 7,000 and 40,000/µl, and conventional prednisolone therapy had little effect on the thrombocytopenia. Because of prednisolone-resistant thrombocytopenia, a partial splenic artery embolization was performed in September 1995. There was some improvement in the platelet count (up to 100×103/µl). Serological tests for ANA at this time were positive at a titer of 1:80 with a speckled pattern. She was diagnosed as having probable SLE. Urinalysis showed no abnormalities during the clinical course of AIHA and thrombocytopenia. In April 1996, when she was on prednisolone, 15 mg daily, she developed colic abdominal pain and frequent vomiting. Abdominal X-ray films demonstrated dilatations and fluid accumulations in the small and large bowels, suggesting paralytic ileus. Ultrasonography and intravenous pyelography disclosed bilateral hydroureter with mild hydronephrosis and a mild contracted bladder. She was given prednisolone, 60 mg daily, and treated with total parental nutrition. Although the therapy resulted in a gradual sub-

860

Fig. 1 Bladder mucosa biopsy, showing diffuse edema with interstitial fibrosis and focal perivascular infiltration of mononuclear cells. Thickening of the submucosal arteriolar walls was also seen (hematoxylin and eosin, ×140)

derness and striae cutis on extremities. Her blood pressure was 144/106 mmHg. Urinalysis showed a specific gravity of 1.007, protein 10 mg/dl, 29 erythrocyte sediments per high-power field without leukocyte sediments, and a sterile culture. Laboratory studies showed: white blood cells 10,500/µl with a normal blood film, hemoglobin 16.5 g/dl, hematocrit 49.4%, platelets 119×103/µl, total protein 7.3 g/dl, albumin 4.6 g/dl, total cholesterol 343 mg/dl, urea nitrogen 15 mg/dl, creatinine 0.5 mg/dl, C-reactive protein 0.1 mg/dl, sodium 137 mEq/l, potassium 3.5 mEq/l, chloride 103 mEq/l, IgG 629 mg/dl, IgA 122 mg/dl, and IgM 70 mg/dl. C3 and C4 levels were decreased to 64 mg/dl and 15 mg/dl, respectively. The ANA titer was 1:20, with no detectable antibodies to double-stranded DNA, Sm, SS-A, SS-B, or RNP. A direct Coombs test was positive. Following an episode of macroscopic hematuria, a cystoscopic study was performed, revealing a bladder capacity of 250 ml, inflammatory mucosa, and edema of both ureterovesical junctions. Bladder biopsies disclosed a chronic interstitial cystitis (Fig. 1). Immunofluorescence revealed focal deposits of IgG and C3 in a granular pattern on the small blood vessel wall (Fig. 2a, b). Chronic interstitial cystitis was diagnosed. She was given prednisolone, 60 mg daily, combined with cyclophosphamide, 70 mg daily. From the clinical course, long-term prednisolone treatment was thought to be responsible for her hypertension. Thus anti-hypertensive therapy was also started, with a favorable response. Thereafter, her abdominal pain, nausea, and pollakiuria gradually disappeared, with improvement in her general condition. The dosage of prednisolone was decreased to 17.5 mg daily. Cyclophosphamide was discontinued after a 12-week course, and was replaced by azathioprine, 70 mg daily. In October 1997, when she was receiving 10 mg prednisolone daily, she developed butterfly rash, thrombocytopenia (platelet count 47,000/µl), and hypocomplementemia (C3 51 mg/dl and C4 8 mg/dl). Despite increasing the dosage of prednisolone to 40 mg daily, another episode of abdominal pain, frequent vomiting, and pollakiuria occurred. Thus intravenous methyl-prednisolone pulse therapy (1 g daily) was given for 3 consecutive days. After three courses of the pulse therapy, her clinical symptoms gradually disappeared. Thereafter, despite long-term immunosuppressive treatment, her abdominal pain, pollakiuria, and thrombocytopenia recurred when the dosage of prednisolone was decreased to around 20 mg daily. A 14-week trial course of ciclosporine A (up to 4 mg/kg daily) did not help to relieve her clinical symptoms or allow a reduction in the dosage of prednisolone.

Discussion

Fig. 2 Focal positive immunofluorescence staining for IgG (a ×270) and C3 (b ×135) in a granular pattern was observed in small blood vessels sidence of her abdominal symptoms, reducing the dosage of prednisolone caused relapse. In January 1997, she was referred to our hospital for further treatment. On arrival, she complained of nausea, fatigability, and pollakiuria. Positive physical findings were mild abdominal ten-

In our patient the diagnosis of SLE was based on the presence of four criteria of the American Rheumatism Association (autoimmune hemolytic anemia, false-positive test for syphilis, positive ANA, and malar rash). Although our patient showed no signs of glomerulonephritis, she developed prominent intestinal symptoms and pollakiuria with an episode of macroscopic hematuria. Since the hematuria suggested lower urinary tract involvement, cytoscopic examination was performed, disclosing lesions suggesting chronic interstitial cystitis. Chronic interstitial cystitis is an uncommon primary manifestation of SLE [1–11]. In most reported cases, chronic interstitial cystitis is associated with prominent intestinal symptoms [3–10]. Moriuchi et al. [5] described a strong correlation between chronic interstitial cystitis and intestinal disease, suggesting a unique subgroup of patients with SLE. However, the combination of chronic interstitial cystitis and intestinal disease has rarely been described in pediatric-onset SLE [7]. Alarcon-Segovia et al. [12] reported involvement of the urinary bladder due to interstitial cystitis in 11 of 35 nec-

861

ropsies from SLE patients, but none had lower urinary tract symptoms. Hence, it is thought that interstitial cystitis may have been underestimated in SLE, especially in pediatric-onset SLE. Although the pathogenesis of chronic interstitial cystitis in patients with SLE has not been fully explained [4], immune complex-mediated vasculitis has been suggested [2, 13]. In our patient, perivascular deposition of IgG and C3 in the bladder was observed by immunofluorescence. These findings indicated that immune complex-mediated vasculitis might play a role in the pathogenesis of lupus cystitis. Most reported cases belonging to the subgroup of SLE patients with prominent intestinal disease and lupus cystitis have a relatively unfavorable prognosis [3–5, 7, 8]. Eberhard et al. [7] reported a fatal case of childhood lupus cystitis. In our patient, attempts to control the disease with aggressive immunosuppressive therapy, including ciclosporine A, have not resulted in a favorable clinical course. La Manna et al. [11] previously reported a child with lupus cystitis and no intestinal symptoms, and the improvement of the cystitis with ciclosporine A therapy. Because of the lack of intestinal symptoms, however, their patient may not belong to the subgroup of SLE patients. We have described here a girl who presented with intestinal and lower urinary tract involvement due to SLE that have been reported rarely in children. Despite the use of long-term immunosuppressive therapy, it is difficult to control the disease. Further reports of pediatric patients are needed to confirm the subgroup of childhood SLE in which there is an association of prominent intestinal symptoms and chronic interstitial cystitis.

References 1. Shipton EA (1965) Hunner’s ulcer (chronic interstitial cystitis). A manifestation of collagen disease. Br J Urol 37:443– 449 2. Boye E, Morse M, Huttner I, Erlanger BF, MacKinnon KJ, Klassen J (1979) Immune complex-mediated interstitial cystitis as a major manifestation of systemic lupus erythematosus. Clin Immunol Immunopathol 13:67–79 3. Serna AR de la, Alarcon-Segovia D (1981) Chronic interstitial cystitis as an initial major manifestation of systemic lupus erythematosus. J Rheumatol 8:808–810 4. Orth RW, Weisman MH, Cohen AH, Talner LB, Nachtsheim D, Zvaifler NJ (1983) Lupus cystitis: primary bladder manifestations of systemic lupus erythematosus. Ann Intern Med 98:323–326 5. Moriuchi J, Ichikawa Y, Takaya M, Shimizu H, Tokunaga M, Eguchi T, Izumi M, Ohta W, Katsuoka Y, Naakajima I, Tsutsumi Y, Arimori S (1989) Lupus cystitis and perforation of the small bowel in a patient with systemic lupus erythematosus and overlapping syndrome. Clin Exp Rheumatol 7:533– 536 6. Vincensio GP, Chung-Park M, Ricanaati E, Lee KN, DeBaz BZ (1989) SLE with interstitial cystitis, reversible hydronephrosis and intestinal manifestations. J Rheumatol 16:250–251 7. Eberhard A, Shore A, Silverman E, Laxer R (1991) Bowel perforation and interstitial cystitis in childhood systemic lupus erythematosus. J Rheumatol 18:746–747 8. Meulders Q, Michel C, Marteau P, Grange JD, Mougenot B, Ponco P, Mignon F (1992) Association of chronic interstitial cystitis, protein-losing enteropathy and paralytic ileus with seronegative systemic lupus erythematosus: case report and review of the literatures. Clin Nephrol 37:239–244 9. De Arriba G, Velo M, Barrio V, Gaarciaa-Martin F, Hernando L (1993) Association of interstitial cystitis with systemic lupus erythematosus. Clin Nephrol 39:287–288 10. Kim HJ, Park MH (1996) Obstructive uropathy due to interstitial cystitis in a patient with systemic lupus erythematosus. Clin Nephrol 45:205–208 11. La Manna A, Polito C, Papale MR, Rocco CE, Marte A (1998) Chronic interstitial cystitis and systemic lupus erythematosus in an 8-year-old girl. Pediatr Nephrol 12:139–140 12. Alarcon-Segovia D, Abud-Mendoza C, Reyes-Gutierrez E, Iglesias-Gamarra A, Diaz-Jouanen E (1984) Involvement of the urinary bladder in systemic lupus erythematosus. A pathologic study. J Rheumatol 11:208–210 13. Weisman MH, McDanald EC, Wilson CB (1981) Studies of the pathogenesis of interstitial cystitis in a patient with systemic lupus erythematosus. Am J Med 70:875–881