Intestinal pseudo-obstruction as a presenting manifestation of systemic lupus erythematosus: case report and review of the literature.

Abstract: A case of intestinal pseudo-obstruction as a presenting manifestation of systemic lupus erythematosus is presented. Systemic lupus erythematosus is an autoimmune disease with a wide spectrum of unpredictable multisystemic presentations. A case of systemic lupus erythematosus that was diagnosed in a patient whose initial presentation for the disease was acute renal failure, hydronephrosis, intestinal pseudo-obstruction, and false-positive syphilis serologies is presented. There have been 18 other cases of intestinal pseudo-obstruction associated with systemic lupus erythematosus to date in the English literature. A variety of gastrointestinal syndromes have been increasingly recognized as possible manifestations of systemic lupus erythematosus, and this case illustrates in particular that intestinal pseudo-obstruction may be a presenting manifestation of this disorder.

Key Words: hydronephrosis, intestinal pseudo-obstruction, renal failure, systemic lupus erythematosus

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Discussion

Systemic lupus erythematosus is the most prevalent autoimmune disease, with an annual incidence of 60 per 1 million population and a prevalence of 500 per 1 million population. (1) Overall, systemic lupus erythematosus is most prevalent in the 20- to 40-year age group, with a female-to-male ratio of 9:1. Because of its myriad of multisystemic clinical presentations, systemic lupus erythematosus is known as one of the great medical mimics alongside tuberculosis, syphilis, and human immunodeficiency virus. I present a case of systemic lupus erythematosus in a patient whose initial presentation for the disease was renal failure and intestinal pseudo-obstruction. The patient met criteria for the diagnosis of systemic lupus erythematosus according to criteria of the American College of Rheumatology, including malar rash, arthritis, renal disorder with >0.5 g/dl/24 h protein, immunologic disorder with positive anti-Smith antibodies, false-positive Venereal Disease Research Laboratory test, positive antinuclear antibody, and hematologic disorder with Coombs-positive hemolytic anemia. (1) She did not meet criteria for other connective tissue diseases such as scleroderma, dermatopolymyositis, or overlap syndromes that have been reported in association with intestinal pseudo-obstruction. (1), (2)

Gastrointestinal complications have been increasingly observed as manifestations of systemic lupus erythematosus. Up to 50% of patients with established systemic lupus erythematosus have gastrointestinal complaints at any time during the course of their illness. (1) These include mesenteric vasculitis, inflammatory bowel disease, pancreatitis, and less commonly motility disorders such as intestinal pseudo-obstruction. (1)

Intestinal pseudo-obstruction has been described in only 18 prior cases in association with systemic lupus erythematosus. (3), (4) Intestinal pseudo-obstruction is defined as small bowel obstruction that occurs in the absence of mechanical or obstructive factors. Identification of systemic lupus erythematosus as the underlying pathologic process in this patient with small bowel obstruction was important because this facilitated steroidal therapy for reversal of the intestinal pseudo-obstruction and nephropathy and averted unnecessary surgical intervention.

This patient presented with classic symptoms of intestinal pseudo--obstruction, including abdominal pain and distension, vomiting, alternating diarrhea and constipation, weight loss, and radiographic signs of gaseous small bowel distension and air fluid levels. (3) Paradoxically, constipation and diarrhea may both be observed in patients with intestinal pseudo-obstruction because predominant small intestinal involvement may lead to bacterial overgrowth and steatorrhea, whereas predominant colonic involvement leads to constipation. (5), (6) However, this all occurs in the absence of mechanical obstruction. Therefore, patients present with normal findings on gastroscopy, colonoscopy, and small bowel studies. Manometry studies in these patients demonstrate widespread gastrointestinal abnormalities, including small intestinal hypomotility; delayed gastric emptying; decreased lower esophageal sphincter pressure; and weakened contraction and migratory complexes in the stomach, antrum, duodenum, and jejunum. (3), (5), (6)

This patient's age and gender are consistent with the epidemiology of the 18 previous cases of systemic lupus erythematosus and intestinal pseudo-obstruction. In this group of 18 patients, there was a mean age of onset of 29 years (range, 15-47 yr) and a female-to-male ratio of 8:1. In one-half of these patients (9 of 18), intestinal pseudo-obstruction heralded the diagnosis of systemic lupus erythematosus. (3)

The pathophysiology of intestinal pseudo-obstruction is ineffective intestinal propulsion and intestinal hypomotility. (3), (4) It is postulated that a generalized vasculitis involving inflammatory fibrinoid deposits affects the smooth muscle of the small intestine, leading to small bowel obstruction. (3-5) Smooth muscle dysfunction as a result of vasculitis may be more diffuse, as ureterovesical distension has been reported in patients with intestinal pseudo-obstruction. Mok and Wong (3) reported the coexistence of small bowel hypomotility and ureterohydronephrosis in 12 of 18 patients with intestinal pseudo-obstruction. Our patient's renal ultrasound demonstrated hydronephrosis, which is consistent with the possibility for coexistent urologic dysfunction. Thus, our patient's renal failure appears to be multifactorial from prerenal and intrinsic renal causes, including volume depletion from vomiting and diarrhea, mesangioproliferative changes in the glomerulus, and hydronephrosis arising from a possible vasculitis in the smooth muscles of the ureters and bladder.

The differential diagnosis of intestinal pseudo-obstruction in our patient who was eventually diagnosed with systemic lupus erythematosus included mechanical causes such as tumor, volvulus, and adhesions from her history of femoral hernia surgery; and nonmechanical causes such as gastroenteritis, paralytic ileus, celiac sprue, and narcotic bowel syndrome. Narcotic bowel was initially considered as a diagnosis for this patient who had a history of IV drug use, but drug screen was negative for illicit drugs. Narcotic bowel syndrome is a form of intestinal pseudo-obstruction characterized by chronic opiate use leading to ileus, vomiting, and abdominal pain. (7) The clinical manifestations of narcotic bowel can be remedied by clonidine during the period of narcotic withdrawal. (7) It is important to differentiate intestinal pseudo-obstruction arising from narcotic bowel versus that from systemic lupus erythematosus, because the treatment for the former is clonidine and treatment for the latter is steroids and promotility agents. Our patient was a diagnostic challenge because her history of femoral surgery and drug use led us to strongly consider alternate diagnoses such as surgical adhesions and narcotic bowel initially before the appropriate diagnosis of systemic lupus erythematosus.

Causes of intestinal pseudo-obstruction can be categorized into primary and secondary causes. Smooth muscle disorders, including familial visceral myopathy and sporadic visceral myopathy, are rare primary causes of intestinal pseudo-obstruction. Connective tissue disorders such as progressive systemic sclerosis, systemic lupus erythematosus, and dermatopolymyositis are secondary causes of intestinal pseudo-obstruction. (5) Other rare secondary causes of intestinal pseudo-obstruction include progressive muscular dystrophy, amyloidosis, diffuse lymphoid infiltration, Parkinson's disease, myxedema, pheochromocytoma, and opiate drugs. (5)

Therapy for intestinal pseudo-obstruction consists of bowel rest with parenteral nutrition, and high-dose IV steroids. Solu-Medrol (Pharmacia & Upjohn, Kalamazoo, MI) is initiated at 1 mg/kg/d for 3 days, followed by oral prednisone 1 mg/kg/d. (3), (4) In addition, pharmacologic stimulation of gut motility can be achieved with octreotide or erythromycin. (3) Octreotide is a somatostatin analogue that is administered subcutaneously to induce migratory motor complexes in the small intestine. (8) One previous patient with systemic lupus erythematosus and intestinal pseudo-obstruction was treated successfully with adrenocorticotropic hormone. (3) In our case, this patient was successfully treated with a combination of IV steroids and erythromycin, with clinical remission observed within 1 week of therapy. Long-term outcome with intestinal pseudo-obstruction in patients with systemic lupus erythematosus is not well defined. In one small series of six patients, small bowel motility was restored to normal between 1 and 8 weeks after onset of symptoms. In these patients, prednisone was continued up to 2 months' duration, and all were in remission at 48 months of follow-up. (3) Azathioprine was used for maintenance therapy in 6 of the 18 previously reported cases of patients with systemic lupus erythematosus and intestinal pseudo-obstruction. (3) This suggests that intestinal pseudo-obstruction secondary to systemic lupus erythematosus may require chronic immunosuppression for sustained remission. Our patient has been in remission after 1 year without the necessity for chronic steroids or other immunosuppressants.

Conclusions

Our case illustrates that intestinal pseudo-obstruction can be the onset manifestation of systemic lupus erythematous in a patient presenting with reversible acute renal failure, hydronephrosis, and small bowel obstruction. Identification of systemic lupus erythematosus as the underlying pathogenesis averted unnecessary surgery and facilitated appropriate steroidal therapy to reverse her nephropathy and bowel obstruction rapidly. Gastrointestinal complications are increasingly being recognized as manifestations of systemic lupus erythematosus, and intestinal pseudo-obstruction should be considered in patients with systemic lupus erythematosus presenting with abdominal pain, and vice versa. More research is necessary to elucidate the pathogenic mechanisms involving concurrent smooth muscle dysfunction of the urologic and gastrointestinal systems.

Bodily pain affects man as a whole down to the deepest layers of his moral being. It forces him to face again the fundamental questions of his fate, of his attitude toward God and fellow man, of his individual and collective responsibility and of the sense of his pilgrimage on Earth.

--Pope Pius XII

Key Points

* Intestinal pseudo-obstruction is a rare cause of small bowel obstruction that occurs in the absence of mechanical obstruction.

* This case illustrates that intestinal pseudo-obstruction may be an onset manifestation of systemic lupus erythematosus.

* Steroidal therapy and promotility agents can rapidly reverse intestinal pseudo-obstruction and avert unnecessary surgery.

Accepted January 9, 2003.

Copyright [c] 2004 by The Southern Medical Association 0038-4348/04/9702-0186

References

(1.) Klippel JH. Systemic lupus erythematosus: Demographics, prognosis, and outcome. J Rheumatol Suppl 1997;48:67-71.

(2.) Nojima Y, Mimura T, Hamasaki K, et al. Chronic intestinal pseudo-obstruction associated with autoantibodies against proliferating cell nuclear antigen. Arthritis Rheum 1996;39:877-879.

(3.) Mok MY, Wong RW, Lau CS. Intestinal pseudo-obstruction in systemic lupus erythematosus: An uncommon but important clinical manifestation. Lupus 2000;9:11-18.

(4.) Perlemuter G, Chaussade S, Wechsler B, et al. Chronic intestinal pseudo-obstruction in systemic lupus erythematosus. Gut 1998;43:117-122.

(5.) Feldman M, Friedman LS, Sleisenger MH (eds): Sleisenger & Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. Philadelphia, W.B. Saunders, 1998, vol 2, ed 6, pp 1821-1830.

(6.) Cacoub P, Benhamou Y, Barbet P, et al. Systemic lupus erythematosus and chronic intestinal pseudoobstruction. J Rheumatol 1993;20:377-381.

(7.) Sandgren JE, McPhee MS, Greenberger NJ. Narcotic bowel syndrome treated with clonidine: Resolution of abdominal pain and intestinal pseudo-obstruction. Ann Intern Med 1984;101:331-334.

(8.) Perlemuter G, Cacoub P, Chaussade S, et al. Octreotide treatment of chronic intestinal pseudoobstruction secondary to connective tissue diseases. Arthritis Rheum 1999;42:1545-1549.

RELATED ARTICLE: Case Report

A 35-year-old woman with hypertension and a history of IV drug use presented with 3-day history of crampy, nonradiating, midepigastric, abdominal pain; and distension, anorexia, vomiting, and diarrhea. There was no fever, hematemesis, or hematochezia. She also complained of mild swelling and pain in her knees. She denied chest pain, shortness of breath, headache, or rashes. There was no history of unusual travel or food ingestions, sick contacts, or antibiotic use. She had a history of IV cocaine and heroin abuse and reported that her last use was 1 year before admission. She had been diagnosed 3 years previously with syphilis, for which she had received penicillin therapy. There was a remote surgical history of femoral hernia repair and prior obstetric history significant for four first-trimester miscarriages and no livebirths. There was a strong family history of systemic lupus erythematosus in her mother and aunt. Medications at admission included Norvasc.

The cardiopulmonary examination was significant for a 2/6 systolic ejection murmur and fine basilar crackles. Abdominal examination revealed hypoactive bowel sounds, distended abdomen with diffuse tenderness, and tympany without peritoneal signs. Rectal examination demonstrated heme-negative brown stool without masses.

The musculoskeletal examination showed mild bilateral knee effusion with preserved range of motion. The dermatologic examination was significant for seborrheic dermatitis, nonscarring alopecia, and malar rash, without physical signs of scleroderma including sclerodactyly or telangiectasias.

Complete blood count was significant for a microcytic anemia with hematocrit of 25.1/[micro]1 and mean corpuscular volume of 72.5. Anemia workup was consistent with a combined iron deficiency anemia and Coombs-positive hemolytic anemia. Serum chemistries revealed acute renal failure with blood urea nitrogen of 53 mg/dl and creatinine of 2 mg/dl. Liver function tests were normal except for albumin of 2.6 mg/dl, and amylase and lipase levels were normal. Abdominal flat and up-right films demonstrated multiple air fluid levels and distended loops of small bowel. The urinalysis demonstrated active urinary sediment with 4+ protein and few red blood cell casts, but was negative for illicit drugs. Renal ultrasound showed echogenic kidneys consistent with medical renal disease and mild bilateral hydronephrosis, and 24-hour urine studies demonstrated non-nephrotic range proteinuria with a total of 850 mg protein and creatinine clearance of 50 ml/min. Serologies for connective tissue disease revealed positive antinuclear antibody titer of 1:640 with speckled pattern. Smith antibody was positive but rheumatoid factor, ribonucleotide protein, Ro, La, double-stranded DNA, anti-proliferating cell nuclear antigen, SCL-70, and anticentromeric antibody were all negative. Complement levels were decreased at 40 mg/dl (C3) and 10 mg/dl (C4), and viral hepatitis and human immunodeficiency virus serologies were negative. Lupus anticoagulant and anticardiolipin antibodies were both positive and consistent with her history of multiple early miscarriages. A retrospective chart review showed that the patient had positive rapid plasma reagin serologies for which she had received penicillin injections but negative fluorescein treponema antibody, consistent with false-positive syphilis testing. Repeat antitreponemal tests during this admission confirmed false-positive syphilis serology.

The patient was admitted. Bowel rest was instituted with placement of a nasogastric tube, and hydration was initiated with IV fluids. In consultation with the gastroenterology department, a small bowel contrast study and colonoscopy were performed 1 week into admission, as her obstruction improved, ruling out mechanical obstruction in the small and large intestines. A renal biopsy was performed, demonstrating mild mesangial proliferative changes consistent with Class II lupus nephritis. The patient was initiated on high-dose IV prednisone and erythromycin and weaned to oral feeds by Week 2 of admission. The patient's creatinine stabilized to 1.0 mg/dl with steroidal therapy, and the patient was discharged on oral prednisone 2 mg/kg/d for 2 weeks. At 6-week follow-up, on a maintenance dose of prednisone 10 mg/d, there was complete resolution of the intestinal pseudo-obstruction and hydronephrosis, without recurrence of nephritis.

Hien Nguyen, MD, and Niharika Khanna, MD

Reprint requests to Hien Nguyen, MD, 3808 Daniels Run Court, Fairfax, VA 22030. Email: [e-mail]