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Systemic lupus erythematosus complicated by Crohn’s disease: a case report and literature review
© Yamashita et al.; licensee BioMed Central Ltd. 2012
Received: 20 May 2012
Accepted: 29 November 2012
Published: 5 December 2012
Although patients with systemic lupus erythematosus (SLE) may experience various gastrointestinal disorders, SLE and Crohn’s disease (CD) rarely coexist. The diseases may have gastrointestinal (GI) manifestations, laboratory results, and radiographic findings that appear similar and consequently differentiating between GI involvement in CD and in SLE may be difficult. We present the case of a patient with SLE and CD who developed continuous GI bleeding and diarrhea that was initially treated as SLE-related colitis to little effect.
A 55-year-old Japanese woman with systemic lupus erythematosus (SLE) developed continuous gastrointestinal bleeding and diarrhea since the patient was aged 30 years that was initially treated as SLE-related colitis. Although a longitudinal ulcer and aphthous ulcers in the colon were observed every examination, biopsy showed only mild inflammation and revealed neither granuloma nor crypt abscess. The patient underwent surgery for anal fistulas twice at 50 and 54 years of age and her symptoms were atypical of lupus enteritis. Colonoscopy was performed again when the patient was 55 years of age because we suspected she had some type of inflammatory bowel disease (IBD). Cobblestone-like inflammatory polyps and many longitudinal ulcers were detected between the descending colon and the cecum. Macroscopic examination strongly suggested CD. Histopathological examination revealed non-caseating granuloma and no evidence of vasculitis, consistent with CD. Introduction of infliximab dramatically relieved the patient’s melena and abdominal symptoms.
Diagnostic criteria for CD and SLE overlap, making them difficult to diagnose correctly. It is important to consider CD for patients who have SLE with gastrointestinal manifestations. The pathology of lupus enteritis should be clarified through the accumulation of cases of SLE combined with CD.
Systemic lupus erythematosus (SLE) and Crohn’s disease (CD) are multisystem diseases characterized by widespread tissue damage . The diseases may have gastrointestinal (GI) manifestations, laboratory results, and radiographic findings that appear similar and consequently differentiating between GI involvement in CD and in SLE may be difficult. There are, in fact, few reports suggesting an association between these diseases [2–8].
We present the case of a patient with SLE and CD who developed continuous GI bleeding and diarrhea that was initially treated as SLE-related colitis to little effect.
Introduction of infliximab dramatically relieved the patient’s melena and abdominal symptoms. Infliximab was administered at a dose of 5 mg/kg body weight (340 mg) at weeks 0, 2, and 6, and then every 8 weeks thereafter. Regarding inflammatory responses after 1 month of infliximab administration, the CRP level normalized from 1.19 mg/dl to 0.06 mg/dl, and the erythrocyte sedimentation rate (ESR) from 48 mm/hr to 14 mm/hr. The Harvey-Bradshaw index (HBI) score was also reduced from 5 to 0. The patient had sustained lack of inflammatory response and negative test results for fecal occult blood. Ultimately, the PSL dose was reduced to 5 mg/day, and both MTX and TAC were tapered to discontinuation. As of May 2012, remission is maintained with infliximab, 5 mg/day PSL, and 3 g/day SASP. However, the aCL-β2GPI antibody titers remain high.
Comparison of reported patients with SLE complicating Crohn disease
SLE disease duration
Result of biopsy
ANA 1280× Anti-DNA 160×
Deep linear and ulceration, pseudopolyps, skip lesion
Acute and clonic inflammation
mPSL40mg/d. d iv
ANA 1280× Anti-DNA 50×
Multiple ulcers with linear ulcer, skip lesion, Pseudpolyps
Infiltration of chronic inflammatory cells in the lamina proprial mucosa with marked depletion of goblet cells without vasculitis
Blood stained stool
ANA 80× Anti-dsDNA 80×positive LE cell
Intermittent hematochezia, tenesmus and loose bowel movements
Multiple ulcers with linear ulcer, diffuse aphthous ulcers
active colitis with noncaceating granulomas
She developed SLE four years after developing Crohn’s disease.
ANA 160× Anti-dsDNA 800IU/ml pANCA positive
Longitudinal ulcers and mucosal erosion
Focal cryptitis with noncaceating granuloma
Lower abdominal pain, Perianal abscess
ANA 320× Anti-dsDNA320× Anti-DNA 26IU/ml positive LE cell
Longitudinal ulcers, linear ulcer, cobble stone appearance, Pseudpolyps
Non-specific colitis without vasculitis
Emergent operation with
Transmural fibrosis and
a right hemicolectomy was performed.
inflammation with lymphocyte aggregation, but no evidence of vasculitis.
Prednisone 10mg b.i.d.
Massive bloody stool
a high titer of anti-dsDNA antibody (at diagonosis of SLE) a positive result for ANA
Longitudinal ulcers, cobble stone appearance, Pseudpolyps
active colitis with noncaceating granulomas without vasculitis
The present case
SLE is a multisystemic disease; therefore, patients frequently present with GI disorders that may be clinically similar to CD. However, there are some differences . Compared to SLE, CD presents more frequently as diarrhea, abdominal pain, and anal lesions. All seven patients described in Table 1 experienced diarrhea, whereas five experienced abdominal pain, and two had anal lesions. CD has greater ileal involvement with a more segmented distribution than SLE, and radiographs show deep ulcers, fissures, and a cobblestone appearance or fistula formation as well as the macroscopic colonoscopy findings. Plain film radiographs of SLE-related mesenteric vasculitis usually show nonspecific indications of disease, such as segmental bowel dilatation in a thumb-print pattern and an air–fluid level. CT scans reveal the characteristic features of IBD (e.g., a double halo sign and comb-like appearance of the supplying vessels). Angiography of the mesenteric arteries may also provide evidence of vasculitis.
The most common pathological lesions in the GI tract of patients with SLE are chronic, nonspecific mucosal inflammation and ischemic changes due to vascular lesions. However, vasculitis was not confirmed in any of the cases presented in Table 1. Therefore, the abdominal symptoms experienced by patients with both SLE and CD can be attributed to CD alone.
Additionally, perforation rarely occurs in IBD, but is often observed in lupus enteritis, and may be helpful in differential diagnosis . GI lesions associated with SLE are roughly classified into two types: (1) those associated with vasculitis and that frequently cause perforation; and (2) nonspecific ulcerative or granulomatous colitis . The latter indicate that CD is complicating SLE. Therefore, when encountering steroid-resistant SLE-associated enteritis with the typical findings of CD, such as macroscopic findings of cobblestone-like inflammatory polyps, histopathological findings of noncaseating granuloma, and the presence of discontinuous longitudinal ulcers and aphthous ulcers in the colon, a diagnosis of CD should be considered in the differential, and anti-TNF-α therapy should be kept in mind.
Patients with IBD that is treated with sulfasalazine can, in rare cases, develop drug-induced lupus syndrome . Drug-induced lupus syndrome is associated with negative ANA laboratory tests and hypocomplementemia. The patient described here was positive for ANA and anti-dsDNA antibody before the administration of SASP when she was 19 and 31 years old; therefore, drug-induced lupus syndrome was unlikely.
In early CD lesions, such as aphthous ulcers associated with noncaseating granuloma, macrophagic epithelioid cells aggregate in response to antigens from food and enteric bacteria that have invaded the intestinal mucosa. These macrophagic cells produce proinflammatory cytokines, such as interleukin-6 and tumor necrosis factor (TNF)-α, which are considered to be important for the development of CD. It is for this reason that CD is classified as an autoimmune disease . In the case described here, administration of steroids in early-stage SLE might have delayed the onset of obvious lower GI CD lesions.
The overall prevalence of aCL antibodies among CD patients is approximately 22% . Although the patient was strongly positive for aCL antibodies, coagulation factor levels were always within the normal range. Moreover, the patient had no history of thrombosis. Thus, concomitant antiphospholipid syndrome is unlikely.
Glucocorticosteroid is an effective treatment for CD, and can be used to treat severe cases or disease that does not respond well to mesalazine therapy. However, longterm treatment with glucocorticosteroids should be avoided. In case of steroid dependency or steroid refractory TNF-alpha blockers are an effective treatment to induce and maintain remission . In the case described herein, CD activity was not controlled by high-dose PSL therapy or by moderate doses of steroids and SASP. However, a complete response was achieved with anti-TNF-α therapy. TNF-α inhibitors have been reported to cause drug-induced lupus, as well as rashes and arthritis . Fortunately, in this case, SLE symptoms did not worsen. There are, however, occasional reports describing the efficacy of anti-TNF-α therapy for SLE. It has also been reported that, despite levels of antibodies to ds-DNA and cardiolipin being increased, anti-TNF-α therapy did not exacerbate SLE itself but rather achieved a reduction in disease activity and relief of refractory arthritis, nephritis, etc. . TNF-α exerts both deleterious tissue damaging effects mainly through its pro-inflammatory activities and beneficial activities by dampening aggressive autoimmune responses. SLE is a disease with autoimmune disturbance and inflammatory damage, so blocking TNF-α in this autoimmune-prone chronic inflammatory disease may lead to different outcomes, depending on timing and duration of treatment. Thus, infliximab may also be effective for gastrointestinal symptoms associated with SLE.
In conclusion, the diagnostic criteria for CD and SLE overlap, making them difficult to diagnose correctly. It is important to consider the possibility of CD in patients who have SLE with GI manifestations. The status of CD as an autoimmune disease is becoming clear and the pathology of lupus enteritis should be clarified through the accumulation of cases of SLE combined with CD.
Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Series Editor of this journal.
All of authors, H.Yamashita,MD,PhD;Y.Ueda,MD;H.Kawaguchi,MD;A.Suzuki,Md,PhD; Y.Takahashi,MD,PhD;T.Kano,MD; A. Mimori,MD,PhD, belong to the Division of Rheumatic Diseases ,National Center for Global Health and Medicine,Shinjuku-ku, Tokyo-to, Japan.
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