Colonoscopy is the most used and valuable method for the diagnosis of IBD. The most common endoscopic manifestation of UC is continuous inflammation involving the distal rectum and extending proximally8, 9. However, the absence of rectal involvement in the endoscopic impression has been noted in fewer than 5% of adult patients without any topical treatment, known as rectal sparing10. In fact, rectal sparing is more common in pediatric patients, patients with fulminant colitis or means the effects of topical and oral therapy. Other studies have found that absolute rectal sparing does not occur in UC patients even after a long-term treatment, patchy histologic inflammation may also be seen in these patients.11. In this case, one of our puzzles was that the rectal mucosa was smooth and intact, the vascular texture was clear, which did not conform to the typical endoscopic manifestations of UC. However, it should be noted that some patients after treatment can be manifested as discontinuous lesions due to the inflammation regression in part of the intestinal. This patient had received short-term sulfasalazine plus hormone enema in another hospital. In the later colonoscopy, we also performed multi-point biopsy and found chronic inflammation of rectal mucosa. Meanwhile, twice bone marrow puncture also ruled out the primary diseases of the blood system. Therefore, we believe that the diagnosis of UC is tenable.
An association between UC and CMV infection was first reported in 196112. In UC, CMV infection may present with 2 coexisting conditions: CMV colitis (where CMV itself causes colitis) or CMV infection13. Some studies have indicated widespread mucosal defect, cobblestone-like appearance, punched out, longitudinal, and irregular ulceration has been suggested as a characteristic colonoscopic finding in patients with UC complicated by CMV infection14, 15. The gold standard for CMV colitis included histologic analysis of the colonic biopsy specimen performed by hematoxylin and eosin staining, an immunohistochemical study and amplification of CMV DNA by a qualitative and quantitative PCR in colonic tissue. But all the methods identify a colonic infection of MCV have their advantages as well as disadvantages, the positive rates are low. Furthermore, the treatment of antivirus with CMV infection in UC patients remains very controversial. It is proposed that whether antiviral therapy should be individualized, study suggested antiviral therapy may be indicated for patients of steroid-refractory/-dependent UC with high-grade or low-grade CMV infection with endoscopically large ulcers3. The serum CMV DNA PCR test of this patient was positive 11 months ago, and the patient was markedly improved after antiviral treatment. Although our case did not meet the gold standard for diagnosis of CMV colitis, he had a history of CMV colitis and had risk factors for reactivation. After treatment of steroid, the symptoms only partially improved, and multiple deep ulcers were found by colonoscopy. Therefore, we chose intravenous ganciclovir for antiviral treatment, and the patient's symptoms improved significantly, his stool returned to normal, and he was discharged after improvement.
The confirmation of AIHA usually depends on the detection of erythrocyte membrane-bound autoantibodies using direct Coombs test 16. However, the negative direct Coombs test does not completely rule out the diagnosis of AIHA. The IgG antibody and/or complement (C3) protein detection method may fail in about 5% of AIHA17. In rare cases of IgA autoantibody mediated AIHA, the direct Coombs test may be negative because the commonly used polyspecific direct Coombs test reagent contains only anti IgG and anticomplement antibodies. In cases suspected of AIHA but with a negative Coombs test, some tests have been used to confirm the antibody sensitization of erythrocytes, such as the complement-fixing, antibody consumption test18, 19, enzyme-linked anti-IgG assays, flow cytometric analysis, and a variety of augmented sensitivity tests 20–24. However, most hospitals usually do not carry out these tests, so confirmed diagnosis of AIHA in patients with negative direct Coombs test is difficult. This case presented a severe refractory anemia inconsistent with disease activity of UC. Although the direct Coombs test was negative, the reticulocyte count and percentage were very high, with the presence of warm autoantibodies of IgA type, the final diagnosis of AIHA is established.
The cases of AIHA may be primary or associated with infection, a lymphoproliferative disease, or an autoimmune disease. AIHA accompanied in UC is rare and highly severe. Although the prevalence of AIHA in UC is low, autoimmune etiology should be considered in the pathogenesis of anemia in UC as well6, 25, 26. Studies showed the prevalence of AIHA is between 0.2–1.7% of all UC patients27, 28, which is noticeably higher than the reported lifetime prevalence in the general population29. To date, the association of UC and AIHA has been few reported in case reports. Hemolytic anemia can occur before, with or after the diagnosis of UC, or several years after colectomy. Marrow in such cases often showed erythroid hyperplasia. But the pathogenesis is uncertain, which may be related to cross antigen and nonspecific immunity. Since both conditions are autoimmune and have connections, steroids and immunosuppressants are effective for both diseases. Since the steroids cannot be used for long-term maintenance treatment, we chose mycophenolate mofetil (MMF) for this case, as research shows MMF is effective in AIHA company with autoimmune or lymphoproliferative diseases. AIHA patients showed a complete or good partial response to MMF treatment30. MMF has been previously reported in IBD patients, especially those who are steroid dependent, refractory or intolerant to more traditional therapies. Furthermore, MMF is generally well tolerated with few side-effects31. This patient was then treated with MMF 2g daily. From then on, the patient has no symptoms, with the reticulocytes, hemoglobin and albumin returned to normal. Both UC and AIHA were benefited from treatment. To our knowledge, this is the first case report about treatment of steroid-dependent UC associated with severe AIHA with oral MMF. By inducing remission of steroid-dependent UC, MMF not only saved the young man from colectomy, but also stopped the treatment of conventional drugs, splenectomy resistance or blood transfusion. Our case suggests that MMF may have a beneficial effect in the treatment of another extraintestinal manifestation, AIHA.
In conclusion, the diagnosis of atypical UC is difficult, and some patients may take opportunistic infection as the first manifestation. Rectal exemption in adults is more common in post-treatment or severe patients, and absolute rectal exemption is very rare. Clinically, there are few cases that meet the gold standard of CMV colitis. For patients with poor treatment effect, positive CMV-DNA in serum, or characteristic manifestations such as longitudinal or deep ulcers, early antiviral treatment can improve the prognosis of patients. AIHA can be secondary to UC, infection, or drugs, in which IgA autoantibody AIHA is a special situation. When gastroenterologist and Immunologist, and hematologist encounter patients with "negative" Coombs test acquired hemolytic anemia, AIHA should be considered in the differential diagnosis. MMF may be an option for the treatment of UC patients with AIHA.