Ileocecal ulcers accompanied by relapsing polychondritis: a case report
© Kawakami et al.; licensee Springer. 2014
Received: 17 November 2014
Accepted: 18 November 2014
Published: 7 December 2014
Mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome is a rare overlap syndrome that includes features characteristic of both Behçet’s disease (BD) and relapsing polychondritis (RP).
A 30-year-old female complained of lower abdominal pain and bloody stools during medical treatment for RP. Total colonoscopy revealed oval-shaped deep ulcers on the terminal ileum similar to those of intestinal BD. After performing the ileocecal resection, both RP and gastrointestinal lesions relapsed, but improved with infliximab treatment.
Discussion and evaluation
During medical treatment for RP, we experienced a rare case with ileocecal ulcers similar to intestinal BD. Although our case did not meet the diagnosis criteria of intestinal BD because of the lack of BD’s major clinical symptoms, intestinal lesions shared quite similar features with intestinal BD. Our case could possibly be a rare subtype of MAGIC syndrome that had the features characteristic of both intestinal BD and RP.
We described a rare case of ileocecal ulcers without any BD symptoms but accompanied by RP, possibly be a subtype of MAGIC syndrome.
Behçet’s disease (BD) is a chronic relapsing inflammatory disease with multiorgan system involvement which is clinically characterized by oral aphthae, genital ulcers, cutaneous lesions, and ophthalmologic manifestations. BD patients are common in Asia, the Middle East and the Mediterranean regions; however, it is uncommon in Western countries (Sakane et al. 1999). It is reported that 3–16% of the patients with BD have gastrointestinal (GI) tract involvement (Hisamatsu et al. 2014). BD patients with GI lesions are subcategorized as intestinal BD because these patients often have severe GI complications and a poor prognosis. In typical cases of intestinal BD, patients often develop an oval-shaped deep ulcer in the ileoceacal lesion which sometimes causes massive bleeding and perforation. Recently, the consensus statements for the diagnosis and management for intestinal BD has been proposed from the Japanese Committee of Experts (Hisamatsu et al. 2014; Kobayashi et al. 2007). In this statement, diagnostic criteria and therapeutic strategy are mentioned. According to the statement, besides GI lesions, BD symptoms such as mouth, eye, skin, and genital lesions are necessary for the diagnosis of intestinal BD (Kobayashi et al. 2007).
Relapsing polychondritis (RP) is a rare and chronic disease characterized by recurrent inflammation episodes of the cartilaginous tissue and other proteoglycanrich tissues (McAdam et al. 1976; Damiani and Levine 1979). Patients with RP have diverse symptoms in the auricle, nose, eyes, tracheal cartilage, joints, heart, and blood vessels. The etiology of RP is unknown, but an autoimmune origin has been hypothesized. Approximately 30% of the cases are associated with other auto-immune diseases (McAdam et al. 1976). Criteria for diagnosis, suggested by McAdam et al. (1976), include three or more of the following clinical features: 1) bilateral auricular chondritis, 2) nonerosive seronegative inflammatory polyarthritis, 3) nasal chondritis, 4) ocular inflammation, 5) respiratory tract chondritis, and 6) audiovestibular damage, with compatible histological features in a cartilage biopsy specimen.
Mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome is a rare overlap syndrome that includes features characteristic of both BD and RP (Firestein et al. 1985). Although there have been no established diagnosis criteria, both mucosal symptoms (oral aphthae or genital ulcers) and cartilage inflammation are thought to be necessary for the diagnosis of MAGIC syndrome as Firestein et al. initially described in 1985 (Firestein et al. 1985). Most of the cases reported as MAGIC syndrome had no GI lesions. However, a few cases of MAGIC syndrome with GI lesions besides mucosal lesions and cartilage inflammation (Firestein et al. 1985; Imai et al. 1997; Kotter et al. 2006; Minami et al. 2009) have been reported. Until now, there has been no other case report of RP with typical Behçet’s GI lesions without any mucosal lesions.
During medical treatment for RP, we experienced a rare case with ileocecal ulcers similar to intestinal BD. Although our case did not meet the diagnosis criteria of intestinal BD because of the lack of BD’s major clinical symptoms, intestinal lesions shared quite similar features with intestinal BD. Our case could possibly be a rare subtype of MAGIC syndrome that had the features characteristic of both intestinal BD and RP. In this report, we have reported the case precisely and made a discussion focused on the diagnosis and treatment with literature review.
Laboratory data on the first visit
3.2 × 106/μl
47.7 × 104/μl
Intestinal BD is a subcategory of BD that develops characteristic inflammation in the GI tracts. Although some cases involve the esophagus or small intestine (Hisamatsu et al. 2014), patients often have an oval-shaped deep ulcer in the ileocecal lesion. Patients with intestinal BD have symptoms such as abodominal pain, bloody stools and diarrhea. Sometimes massive bleeding or perforation can occur which leads to a poor prognosis. Our patient also had lower abdominal pain and bloody stool during RP treatment that were consistent with intestinal BD symptoms. As for the diagnosis of intestinal BD, Japanese expert’s committee proposed the diagnosis criteria initially in 2007 (Kobayashi et al. 2007). Recently, they published the 2nd edition of this statement (Hisamatsu et al. 2014). According to their statement, the diagnosis of intestinal BD could be made if the patient meets the following criteria: A) There is a typical oval-shaped large ulcer in the terminal ileum, and clinical findings meet the diagnostic criteria of BD or, B) There are ulcerations or inflammation in the small or large intestine, and clinical findings meet the diagnostic criteria of BD. Furthermore, acute appendicitis, infectious enteritis, tuberculosis, Crohn’s disease, nonspecific colitis, drug-associated colitis and other diseases that mimic intestinal BD should be excluded by clinical findings, radiology, and endoscopy. Our case developed deep oval-shaped ulcers in the terminal ileum resembling those of intestinal BD. Gross findings of the resected specimen showed that ileocecal valve was highly deformed and destroyed by deep ulcers. Histological examination revealed that nonspecific inflammation and ulcers had reached the muscularis propria. There were no specific findings such as granulomas, CMV-infected cells, vasculitis or thrombus formation. These GI findings itself were quite similar to those of intestinal BD. However, we could not confirm a diagnosis of intestinal BD because of the lack of oral aphthoid ulcers, eye symptoms, skin lesions or genital ulcers which were necessary for the diagnosis. We believed there was a high possibility that the present case could be related to intestinal BD. The disease concept of “Simple ulcer”, which is defined as deep ileocecal ulcers difficult to distinguish from intestinal BD but lacks the other clinical symptoms of BD, has been advocated in Japan (Murano et al. 2011). Although it is an inconclusive discussion, the simple ulcer has been considered to be related to intestinal BD.
RP is a rare and chronic disease characterized by recurrent inflammation episodes of cartilaginous tissue and other proteoglycan-rich tissues. RP is a multisystem autoimmune disease and can coexist with a systemic vasculitis. Although some cases of RP accompanied by ulcerative colitis was reported (Firestein et al. 1985; Benito Calavia et al. 1997; Kawano et al. 2001), GI symptoms are uncommon in RP (Firestein et al. 1985) and there have been few reports of intestinal BD with RP. The criteria for the diagnosis of RP were proposed by McAdam et al. (1976), which include three or more of the following clinical features: 1) bilateral auricular chondritis, 2) nonerosive seronegative inflammatory polyarthritis, 3) nasal chondritis, 4) ocular inflammation, 5) respiratory tract chondritis, and 6) audiovestibular damage, with compatible histological features in a cartilage biopsy specimen. These criteria were slightly expanded by Damiani and Levine (1979) to include reaction to treatment with corticosteroids or dapsone (Damiani and Levine 1979). Our patient had scleritis, auricular pain, and vertigo. Because these clinical findings, auricle biopsy results and the response to corticosteroid fulfilled the above diagnostic criteria, we were able to confirm our diagnosis of RP.
MAGIC syndrome was initially described by Firestein et al. (1985). MAGIC syndrome is defined as an overlap syndrome that includes features characteristic of both BD and RP. Although a few authors suggest that MAGIC syndrome is not a disease entity but merely the association of BD with polychondritis (Kotter et al. 2006; Kotter 2006), many authors support the concept of this syndrome (Imai et al. 1997; Orme et al. 1990; Kim et al. 2005; Caceres et al. 2006; Nanke et al. 2006; Hidalgo-Tenorio et al. 2008; Mekinian et al. 2009; Geissal and Wernick 2010; Gertner 2004). They suggest that the similarities in the clinical manifestations and pathological findings in BD and RP lead a common pathogenetic pathway, so that there is a close relationship between both diseases (Orme et al. 1990; Kim et al. 2005; Hidalgo-Tenorio et al. 2008; Mekinian et al. 2009; Gertner 2004).
Summary of the cases of MAGIC syndrome with GI lesions
Firestein et al. (1985)
Duodenal ulcer, intestinal fistula
Imai et al. (1997)
Kotter et al. (2006)
Minami et al. (2009)
Auricular chondritis, nasal chondritis
In conventional therapy for intestinal BD, 5-aminosalicylic acid (5-ASA) systemic corticosteroid, and immunosuppressive agents have been used (Hisamatsu et al. 2014). However, many patients become refractory to these drugs. Recently, the efficacy of anti-tumor necrosis factor (TNF)α antibodies, such as infliximab and adalimumab was reported (Sfikakis et al. 2001; Travis et al. 2001; Hassard et al. 2001; Kram et al. 2003; Ju et al. 2007; Byeon et al. 2007; Naganuma et al. 2008; Iwata et al. 2011; Kinoshita et al. 2013). The 2nd edition of the consensus statement of the Japanese Experts Committee described that infliximab and adalimumab should be considered as a standard therapy for intestinal BD (Hisamatsu et al. 2014). As for the treatment for RP, various drugs including corticosteroid, NSAIDs, colchicine, hydroxychloroquine, dapsone, methotrexate, azathioprine, cyclophoshamide, and cyclosporine have been used (Kemta Lekpa et al. 2012). In many cases, corticosteroid can be effective; however, not all patients respond adequately. In recent years, several patients were reported to be treated with infliximab successfully (Kemta Lekpa et al. 2012). Pharmacological treatment options for MAGIC syndrome are comprised of NSAIDs, colchicines, corticosteroids, immunosuppressants, and biologics, but there is no specific treatment. To date, only three cases of MAGIC syndrome treated with anti-TNFα have been reported (Hidalgo-Tenorio et al. 2008; Mekinian et al. 2009; Geissal and Wernick 2010). They were all treated with IFX (3 ~ 5 mg/kg) and two of the cases have continued to be in remission.
Our case was corticosteroid dependent and refractory. Although both RP symptoms and GI symptoms improved during steroid pulse therapy before the operation, the symptoms relapsed after stopping the therapy. Furthermore, after the ileocecal resection, both RP and GI lesions relapsed at the same time when reducing the prednisolone dosage. As mentioned above, infliximab has been reported to be effective to RP, intestinal BD and MAGIC syndrome. As a result, we administrated infliximab in order to avoid the continuous high dose usage of steroids. The patient dramatically demonstrated good response to infliximab. Examples of administering biologic therapies such as infliximab to treat patients with intestinal BD, RP, and MAGIC syndrome have gradually increased (Hisamatsu et al. 2014; Kobayashi et al. 2007; Hidalgo-Tenorio et al. 2008; Mekinian et al. 2009; Geissal and Wernick 2010; Kemta Lekpa et al. 2012; Hatemi et al. 2012). Considering the good response to infliximab in other cases and ours, TNFα may play a fundamental role in MAGIC syndorome. Further investigations are necessary to establish the appropriate therapeutic strategy for MAGIC syndrome.
We described a rare case of ileocecal ulcers without any BD symptoms but accompanied by RP, possibly be a subtype of MAGIC syndrome. Additional cases and further investigation are required to clarify the pathogenesis of this rare syndrome.
Written informed consent was obtained from the patient for the publication of this report and any accompanying images.
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