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 Table of Contents  
CASE REPORT
Year : 2014  |  Volume : 5  |  Issue : 4  |  Page : 164-167

Tuberculosis and autoimmune hemolytic anemia: Case report and literature review


1 Department of Internal Medicine, Farwaniya Hospital, Kuwait City, Kuwait
2 Department of Hematology, Farwaniya Hospital, Kuwait City, Kuwait

Date of Web Publication13-Dec-2014

Correspondence Address:
Dr. Hussain Bahbahani
Department of Internal Medicine, Farwaniya Hospital, Kuwait City
Kuwait
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1658-5127.146953

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  Abstract 

Tuberculosis (TB) is a mycobacterial infectious disease that can affect any organ system. The wide varieties of manifestations that TB can present with make the disease a challenge for treating physicians. Anemia is commonly seen in patients with TB, and it is usually anemia of chronic disease. However, the occurrence of autoimmune hemolytic anemia in the setting of TB infection is rare.

Keywords: Autoimmune hemolysis, hemolytic anemia, tuberculosis


How to cite this article:
Bahbahani H, Al-Rashed M, Almahmeed M. Tuberculosis and autoimmune hemolytic anemia: Case report and literature review. J Appl Hematol 2014;5:164-7

How to cite this URL:
Bahbahani H, Al-Rashed M, Almahmeed M. Tuberculosis and autoimmune hemolytic anemia: Case report and literature review. J Appl Hematol [serial online] 2014 [cited 2023 Sep 30];5:164-7. Available from: https://www.jahjournal.org/text.asp?2014/5/4/164/146953


  Introduction Top


We report a 24-year-old female who presented with disseminated tuberculosis (TB) and autoimmune hemolytic anemia (AIHA). The anemia did not respond to anti-TB medications alone, and steroid was added. This case illustrates the importance of recognizing TB as a cause of AIHA, especially in areas where the disease is common in order to initiate appropriate management as some patients might respond to anti-TB treatment alone. However, steroid therapy is an option when hemolysis fails to respond to anti-TB treatment.


  Case Report Top


A 24-year-old Ethiopian female, previously healthy, presented to our Accident and Emergency Department with fatigue, intermittent fever and abdominal pain lasting 1-month. Also, she had a productive cough of yellowish sputum, but no hemoptysis. There was a history of anorexia and weight loss of 8 kg. She denied any history of drug use, contact with TB patients or recent travel.

On physical examination, patient looked pale and cachectic. Vital signs on admission include Temperature 38.7°C, pulse 95/min, and blood pressure 110/70. Examination of the chest revealed bilateral coarse crackles heard mainly on right-middle and lower lung zones. Abdomen was soft, lax with generalized tenderness and no hepatosplenomegaly.

Apart from small right axillary lymph node, no lymphadenopathy could be detected clinically. Initial investigations were as follow: White blood cell 8.4 × 10 9 /L (N 3.9-11.1), hemoglobin 46 g/L (N 118-148), mean corpuscular volume 104 fL (N 82-98), reticulocytes %7.13 (N 0.58-3.26), platelets 353 × 10 9 /L (N 150-450), lactate dehydrogenase 485 U/L (N 100-190), total bilirubin 24.2 umol/L (N 3-20), and direct bilirubin 5 umol/L (N 0-5). Peripheral blood smear showed polychromasia and spherocytosis. Haptoglobin level was 0.06 g/L (N 0.16-2). Both hemoglobin electrophoresis and G6PD level were normal. Direct coombs test was positive for IgG and C3d indicating warm AIHA. Chest X-ray is shown in [Figure 1]. She underwent computed tomography (CT) scan of the chest and abdomen, which demonstrates bilateral pleural effusion with multiple ill-defined patches of consolidation and many enlarged lymph nodes encasing the splenic vein displaying marginal enhancement with low attenuation centrally.
Figure 1: Chest X-ray shows right hilar adenopathy, middle lobe consolidation, bilateral nodular lesions affecting the upper lobes mainly and minimal pleural effusion

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The imaging studies together with being from an area with high TB prevalence made us think of disseminated TB infection complicated by AIHA as a first differential diagnosis, and further tests were carried out to confirm our suspicion.

Tuberculin skin test was 18 mm (strongly positive), sputum for acid-fast bacilli X three negative, antinuclear antibody, HIV, HbsAg, anti-hepatitis C virus antibody, Epstein-Barr virus and cytomegalovirus serology were all negative. The patient refused lymph node biopsy.

Based on high clinical probability of TB, the patient was started empirically on anti-TB medications (isoniazid, rifampicin, ethambutol, pyrazinamide) with pyridoxine. Three units of packed red blood cells (PRBCS) were given on admission because of symptomatic anemia. Patient hemoglobin increased to 98 g/L after blood transfusion but after few days dropped again to 54 g/L despite the use of anti-TB medications. At this point, 2 units of PRBCS were transfused to the patient, and prednisolone (1 mg/kg/day) was added to the anti-TB medications. Importantly, after commencing steroid therapy, patient didn't require any further blood transfusion. Her hemoglobin increased to 11 g/L, and she was discharged in good clinical condition on anti-TB medications and prednisolone (1 mg/kg/day).

On regular follow-up, the patient was doing well, tolerating the medications with no noticeable side effects. The sputum culture for acid-fast bacilli, which was sent on last admission, came positive for mycobacterial TB sensitive to all anti-TB medications, confirming our clinical suspicion. One month after starting steroid, the hemoglobin level reached 136 g/L, but the patient had persistent reticulocytes (8.38%) and the haptoglobin level low (0.06) indicating ongoing hemolysis. After approximately 2 months, there was no evidence of ongoing hemolysis, and the prednisolone dose was tapered slowly over 6 weeks. She tolerated the withdrawal of steroid with no evidence of rebound hemolysis. Blood investigations throughout the course of treatment are summarized in [Table 1].
Table 1: Blood investigations throughout the course of treatment

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  Discussion Top


Hematological abnormalities are common in patients with TB. Anemia is present in 50-60% of miliary TB patients. [1],[2] Possible mechanisms include nutritional deficiency, malabsorption syndrome, marrow suppression, and failure of iron utilization. However, the association of immune hemolytic anemia with TB is relatively rare. Experimental animal study showed that the injection of tubercle bacilli or their products produce hemolytic anemia, pancytopenia and myelofibrosis. [3]

Disseminated TB may provoke a marked proliferation of reticuloendothelial tissues, resulting in varied and severe hematological disorders through immune mechanisms. [4] In addition, there have been reports on drug-induced AIHA, especially concerning rifampicin and isoniazid. [5]

As far as we know, 16 cases of AIHA in association with TB have been reported in the literature [Table 2], 3 of which were pediatric cases.
Table 2: Summary of case reports in English literature from 1974 to 2013

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The majority of the reported cases were disseminated or extra pulmonary TB. All four patients diagnosed as warm hemolysis [6],[7],[8],[9] responded to anti-TB treatment alone without requiring transfusions or steroid therapy, whereas the lowest hemoglobin reported in these cases was 35 g/L. Although one of these cases [9] had a blood transfusion before starting anti-TB treatment, no further blood transfusion were required after commencing anti-TB medications. On the other hand, out of the five [4],[10],[11],[12],[13] cold hemolysis cases, two [4],[13] required steroid treatment. Both two patients with mixed hemolysis [14],[15] required steroid therapy. One of which also had splenectomy for subcapsular splenic hematoma [14] with improvement in hemolysis afterwards. The other mixed [15] hemolysis case had a relapse 2 months after tapering steroid therapy, and was restarted on steroids with a prolonged slow-tapering course.

The use of steroid in some types of TB infection is well-documented. Nevertheless, some clinicians have generally avoided prescribing corticosteroids for active infection because of their known immunosuppressive effects and concern about long-term complications. In addition, there is no enough evidence about the short and long-term impact of steroid treatment in AIHA on TB disease. However, treatment with corticosteroids improved survival for the patient with bacterial meningitis, tuberculous meningitis, tuberculous pericarditis and are considered beneficial and safe for a wide variety of infections, while on the appropriate antibiotic treatment. [16] In the case presented here, the diagnosis of TB was initially based on clinical and radiological findings, as we didn't isolate the organism until later on. Steroid treatment was not added from the beginning because it can complicate her current disseminated TB infection, and the hemolysis may respond to anti-TB medications alone. Unlike previously reported cases of warm hemolysis, [6],[7],[8],[9] our patient was given steroids 2 weeks after starting anti-TB treatment because of the continued requirement for transfusions, with stabilization of hemoglobin afterwards. She was started on such high dose of steroid (prednisolone 1 mg/kg/day) instead of a smaller dose for two reasons. First, her hemoglobin continued to drop despite the use of full anti-TB medication and blood products were not readily available for transfusion and hence we could not start a smaller dose and escalate it later as the condition was critical. Second, the previously reported cases about TB and AIHA that used steroid as adjunctive therapy had the same protocol although some of them did not comment on the steroid dose and none mentioned lower dose.

In spite of using such high dose of steroid, she continued to have some evidence of hemolysis (reticulocytosis and low haptoglobin) up to 1-month after starting steroid treatment. For that reason, we continued prednisolone at 1 mg/kg/day for 2 months after which the steroid dose was tapered slowly over 6 weeks with no evidence of rebound hemolysis. In addition, steroid sparing agents like Azathioprine were considered as an alternative but fortunately, she had responded well to prednisolone.

In summary, we reported a case of warm AIHA associated with disseminated TB. Although rare, TB should be considered as a cause of AIHA especially in areas where the disease is common, after excluding other more common causes of hemolysis. The use of steroid therapy alone in untreated TB patients could have deleterious consequences. However, steroid therapy is an option in patients with AIHA associated with TB when hemolysis fails to respond to anti-TB treatment alone.

 
  References Top

1.
Maartens G, Willcox PA, Benatar SR. Miliary tuberculosis: Rapid diagnosis, hematologic abnormalities, and outcome in 109 treated adults. Am J Med 1990;89:291-6.  Back to cited text no. 1
    
2.
Glasser RM, Walker RI, Herion JC. The significance of hematologic abnormalities in patients with tuberculosis. Arch Intern Med 1970;125:691-5.  Back to cited text no. 2
[PUBMED]    
3.
Berkowitz FE. Hemolysis and infection: Categories and mechanisms of their interrelationship. Rev Infect Dis 1991;13:1151-62.  Back to cited text no. 3
[PUBMED]    
4.
Cameron SJ. Tuberculosis and the blood - A special relationship? Tubercle 1974;55:55-72.  Back to cited text no. 4
[PUBMED]    
5.
Ahrens N, Genth R, Salama A. Belated diagnosis in three patients with rifampicin-induced immune haemolytic anaemia. Br J Haematol 2002;117:441-3.  Back to cited text no. 5
    
6.
Murray HW. Transient autoimmune hemolytic anemia and pulmonary tuberculosis. N Engl J Med 1978;299:488.  Back to cited text no. 6
[PUBMED]    
7.
Kuo WH, Yang PC, Kuo SS, Luh KT. Severe immune hemolytic anemia in disseminated tuberculosis with response to antituberculosis therapy. Chest 2001;119:1961-3.  Back to cited text no. 7
    
8.
Khemiri M, Zouari S, Barsaoui S. Autoimmune bicytopenia in pulmonary tuberculosis. Report of a pediatric case. Respir Med CME 2008;1:281-3.  Back to cited text no. 8
    
9.
Safe IP, O'brien C, Ferreira FR, Souza ML, Ramasawmy R. Tuberculosis associated with transient hemolytic anemia responsive to tuberculosis chemotherapy: A case report. Braz J Infect Dis 2013;17:110-1.  Back to cited text no. 9
[PUBMED]    
10.
Wu B, Rong R. Cold agglutinin syndrome with severe haemolytic anaemia in a patient diagnosed of disseminated tuberculosis and concomitant Mycoplasma pneumoniae infection. Transfus Med 2012;22:151-2.  Back to cited text no. 10
[PUBMED]    
11.
Abba AA, Laajam MA, Al Majid FM. Autoimmune hemolytic anemia associated with intestinal tuberculosis. Ann Saudi Med 2002;22:68-9.  Back to cited text no. 11
    
12.
Siribaddana SH, Wijesundera A. Autoimmune haemolytic anaemia responding to anti-tuberculous treatment. Trop Doct 1997;27:243-4.  Back to cited text no. 12
    
13.
Semchyshyn S, Cecutti A. Abdominal pregnancy complicated by genital and renal tuberculosts and hemolytic anemia. Fertil Steril 1975;26:1142-5.  Back to cited text no. 13
[PUBMED]    
14.
Blanche P, Rigolet A, Massault PP, Bouscary D, Dreyfus F, Sicard D. Autoimmune haemolytic anaemia revealing miliary tuberculosis. J Infect 2000;40:292.  Back to cited text no. 14
    
15.
Bakhshi S, Rao IS, Jain V, Arya LS. Autoimmune hemolytic anemia complicating disseminated childhood tuberculosis. Indian J Pediatr 2004;71:549-51.  Back to cited text no. 15
    
16.
McGee S, Hirschmann J. Use of corticosteroids in treating infectious diseases. Arch Intern Med 2008;168:1034-46.  Back to cited text no. 16
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2]


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