|Year : 2021 | Volume
| Issue : 2 | Page : 78-80
A case report of coinfection of cytomegalovirus colitis and tuberculosis of the intestine in an older patient with heterozygous beta-thalassemia-induced immunodeficiency
Sunny Singhal, Gaurav Desai, Aparajit Ballav Dey
Department of Geriatric Medicine, All India Institute of Medical Sciences, Delhi, India
|Date of Submission||10-May-2021|
|Date of Decision||09-Jul-2021|
|Date of Acceptance||10-Jul-2021|
|Date of Web Publication||22-Oct-2021|
Dr. Sunny Singhal
57, Chandra Kala Colony, Durgapura, Jaipur, Rajasthan
Source of Support: None, Conflict of Interest: None
While thalassemia major is a known immunodeficient state, reports of thalassemia minor presenting with immunodeficiency are rare. We present a 66-year-old male with acute abdomen, hemorrhagic colitis, and septic shock. He was diagnosed with coinfection of intestinal tuberculosis and cytomegalovirus colitis secondary to an immunodeficient state due to heterozygous beta-thalassemia.
Keywords: Beta-thalassemia in the elderly, cytomegalovirus and tuberculosis in the elderly, immunosenescence, secondary immunodeficiency
|How to cite this article:|
Singhal S, Desai G, Dey AB. A case report of coinfection of cytomegalovirus colitis and tuberculosis of the intestine in an older patient with heterozygous beta-thalassemia-induced immunodeficiency. J Indian Acad Geriatr 2021;17:78-80
|How to cite this URL:|
Singhal S, Desai G, Dey AB. A case report of coinfection of cytomegalovirus colitis and tuberculosis of the intestine in an older patient with heterozygous beta-thalassemia-induced immunodeficiency. J Indian Acad Geriatr [serial online] 2021 [cited 2021 Nov 27];17:78-80. Available from: http://www.jiag.com/text.asp?2021/17/2/78/329015
| Introduction|| |
Beta-thalassemia is a hereditary hemoglobinopathy caused by defective synthesis of beta-chains of hemoglobin. People with thalassemia have an increased risk for systemic infections which is one of the most common causes of death among them. The increased risk of infections may be caused by blood transfusion, splenectomy, iron overload, or immunity defect. Homozygous thalassemia is a known immunodeficiency condition in children and young adults. However, heterozygous thalassemia is not known to result in an immunodeficient state, and it generally runs a more benign course., Coinfection of tuberculosis (TB) and cytomegalovirus (CMV) is usually seen in an immunodeficient state and hence a search for an underlying cause must be made. Moreover, its presentation for the first time in the elderly is unusual.
| Case Report|| |
A 66-year-old male presented with a 10-day history of fever, right lower abdominal pain, and vomiting. Investigations revealed leukocytosis and increased bilirubin. His past history was not significant. On examination, he was anemic and icteric. Abdominal examination revealed a tender right iliac fossa mass (3 cm × 2 cm) without hepatosplenomegaly or ascites. Rest of the systemic examination was normal. The remainder of his investigations revealed raised inflammatory markers (erythrocyte sedimentation rate and C-reactive protein) and transaminitis (aspartate aminotransferase – 131 IU/L and alanine aminotransferase – 163 IU/L). Imaging revealed wall thickening involving the terminal ileum, cecum, ascending colon, and part of the transverse colon with fat stranding suggestive of inflammation. Subsequently, he was managed conservatively with intravenous fluids and antibiotics (piperacillin-tazobactam and metronidazole).
After a week of hospitalization, he suffered an episode of hematochezia. An urgent sigmoidoscopy was done, and it showed the presence of altered blood in the rectum. Subsequent colonoscopy revealed transverse ulcers in the cecum and transverse colon with deformed ileocecal (IC) valve which prompted a possible diagnosis of TB of the intestine or Crohn's disease. The biopsy fragments were positive for TB-polymerase chain reaction (PCR), and the histopathology demonstrated inflammatory granulation tissue with viral inclusions in the endothelial cells which stained positive for CMV. The patient was started on antitubercular therapy (6 months) and valganciclovir (900 mg twice a day for 6 weeks) and gradually improved after 1 month of treatment.
In view of the atypical coinfection, an immunodeficiency state was considered, and he was extensively evaluated for the same. The patient had no past history of steroids or other immunosuppressants or other relevant history. Despite detailed evaluation, no immunodeficient state was found. A more detailed analysis of the immunology profile revealed a normal number of total T (CD3+) cells, altered CD4/CD8 ratio (<1), and reduced T-cell function. CD19+ B-cells were decreased in number with raised immunoglobulin G. Natural killer cells (NK cells) were normal in number but had increased perforin activity. In view of persistent anemia (3 months after hospital discharge) with the peripheral smear showing microcytic hypochromic anemia and a recent diagnosis of beta-thalassemia in the grandson, hemoglobin analysis by high-performance liquid chromatography was done which revealed heterozygous beta-thalassemia in the patient. The patient revisited us 5 months later with a recurrence of acute abdomen. Evaluation revealed perforation peritonitis for which an emergency hemicolectomy was performed. Nevertheless, he developed septic shock and succumbed to the illness.
- TB workup
- GeneXpert Mycobacterium tuberculosis (MTB) of colon biopsy: Not detected
- TB-PCR for MTB: Positive
- MGIT 960 culture for MTB: Negative after 7 weeks of incubation.
- Colonoscopy: Transverse colon and cecal ulcers with deformed IC valve suggestive of TB
- Ultrasonography abdomen: Retrocecal appendix with surrounding fat inflammation and minimal fluid in RIF and mild thickening in cecal wall suggestive of acute appendicitis/typhlitis
- Computed tomography (CT) enterography: Pulled up cecum with wall thickening with mucosal enhancement extending to the terminal ileum features suggestive of TB
- 18-fluorodeoxyglucose whole-body positron emission tomography-CT: No definite scan of metabolically active inflammatory/infective pathology.
- Histopathology of the cecum and transverse colon: Biopsy from ulcer in the cecum and transverse colon consisted of ulcerated fragments with inflammatory granulation tissue. Viral inclusion in the endothelial cells immunopositive with CMV and suggestive of CMV colitis
- Anemia workup
- Complete blood count (at time of admission)
- Hemoglobin: 9.5 g/dl
- Total leukocyte count: 36,700/μL, neutrophil: 82%, lymphocyte: 8%, monocyte: 8%, and eosinophil and basophil: 1% each
- Platelet count: 2,79,000/μL.
- Complete blood count (3 months after discharge)
- Hemoglobin: 8.9 g/dl
- Total leukocyte count: 7,790/μL
- Platelet count: 2,67,000/μL.
- Peripheral smear: Microcytic hypochromic with polychromasia, target cells, and pencil cells
- Reticulocyte count (corrected): 1.6%
- Serum ferritin: 603.40 ng/ml
- Immunodeficiency workup
- HIV-1 and HIV-2 antibodies: Negative
- Autoimmune profile (RF, ANA [Hep-2], and ANCA): Negative
| Discussion|| |
β-thalassemia is an autosomal recessive disorder of β-globin synthesis and is known to have immunological aberrations. Thalassemic patients have reduced T-lymphocyte proliferation, an altered number of helper T-cells (CD4) and T-suppressor cells (CD8) leading to a reduced CD4:CD8 ratio.,,,, There is also defective chemotaxis and phagocytosis in neutrophils and macrophages, with reduced functioning of the monocyte–macrophage system. Other changes include impaired differentiation, of B-lymphocytes and reduced functioning of the complement system. These changes have been seen in homozygous β-thalassemia.,,,,,,
There is a paucity of data in heterozygous thalassemia patients. Munn et al. 1981 in a study on ten thalassemia intermedia patients found impaired mitogenic responses of T-cells in patients with serum iron levels higher than 200 μg/dl and serum ferritin higher than 600 ng/ml., In another study of 14 patients with thalassemia intermedia, significantly higher proportions of circulating CD8 + cells and a lower percentage of CD4+ cells were seen. This could be both due to underlying thymus-dependent anomaly of T-cell maturation and iron overload. The mechanisms suggested including toxic effects of high iron levels on lymphocyte function and redistribution of B-lymphocytes from the spleen and lymph nodes. There has been improvement in some of the symptoms in patients who have undergone intensive chelation therapy., Zinc deficiency, allogenic stimulation due to repeated blood transfusion, and splenectomy are the other mechanisms implicated in pathophysiology of immune deficiency in thalassemics.,
The immunodeficiency is manifested with increased susceptibility to infections. CMV colitis and TB of the intestine are both seen with increased frequency in any immunodeficient state. CMV infection has also been linked to increased mortality in older adults due to increased cardiovascular deaths. There are two reports of simultaneous infection, with both in an immunodeficient condition presenting as hemorrhagic colitis. The first case was reported in an HIV-positive 32-year-old male while the second case was seen in a 26-year-old woman who received kidney transplant. One of the possible reasons for this suppressed state of the immunity was immunosenescence. The profile of an aging immune system includes an increase in the ratio of CD4:CD8 cells, decreased phagocytic activity, and increased number of NK cells and B-cells. CMV infection has also been implicated as a cause of immunosenescence leading to the reversal of CD4:CD8 ratio as seen in our case. However, it is usually associated with a significant increase in the number of NK cells (with no effect on perforin activity) and B-cells. However, the patient in discussion here had a reduced number of B-cells, normal number of NK cells besides a reversal of the CD4:CD8 ratio which prompted us to look for an alternative diagnosis. As the immune profile of our patient bores a close resemblance to that of beta-thalassemia patients, we believe it had a role in the immunodeficiency of our patient. This is an important finding as heterozygous beta-thalassemia often goes undiagnosed in older people and may be a crucial piece in understanding the puzzle of immunodeficiency in the elderly. Larger cross-sectional and longitudinal studies are needed to further confirm and understand it closely.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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