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  Table of Contents    
CASE REPORT  
Year : 2023  |  Volume : 66  |  Issue : 1  |  Page : 188-190
Cold antibody autoimmune hemolytic anemia following varicella infection


1 Department of Medicine, PIMS, Puducherry, India
2 Consultant Physician, DM Wayanad Institute of Medical Sciences, Wayanad, Kerala, India
3 Department of Pathology, PIMS, Puducherry, India
4 Department of Medicine, DM Wayanad Institute of Medical Sciences, Wayanad, Kerala, India

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Date of Submission17-Jul-2021
Date of Decision18-Jul-2021
Date of Acceptance19-Jul-2021
Date of Web Publication18-Jan-2023
 

   Abstract 


Introduction: Autoimmune hemolytic anemia (AIHA) is a rare complication of chicken pox. In adults, such AIHA is due to warm antibodies. We report a case of cold antibody AIHA following chicken pox in a young female. Case Report: A 24-year-old female presented with clinical and laboratory features consistent with hemolytic anemia 5 days after the onset of chicken pox. Her hemoglobin levels dropped rapidly during the course of admission from 7.9 to 3.8 g/dL with evidence of ongoing haemolysis in the form of rising total and indirect bilirubin. Peripheral smear revealed red cell agglutinates and erythrophagocytosis. Direct Coomb's test (DCT) was positive for C3d suggesting a cold antibody AIHA. Since test for Donath Landsteiner antibody was negative, and all other tests for common causes of hemolytic anemia were noncontributory, it was presumed to be due to chicken pox. The fulminant course necessitated a short course of oral steroids to which she responded with rise in hemoglobin and no further hemolysis. Two weeks later, her peripheral smear was normal and DCT negative. Conclusion: In patients presenting with acute onset anemia following chicken pox, possibility of cold antibody AIHA must be considered and appropriate testing pursued. Despite lack of empiric evidence, short course of steroids may be beneficial if drop in hemoglobin is rapid with evidence of fulminant hemolysis, showing no abatement after first week.

Keywords: Cold antibodies, corticosteroids, Direct Coomb's test, hemolytic anemia; varicella zoster

How to cite this article:
Carvalho G, D'silva A, Chandran P, Manuel K, Kinglsey, Basheer A. Cold antibody autoimmune hemolytic anemia following varicella infection. Indian J Pathol Microbiol 2023;66:188-90

How to cite this URL:
Carvalho G, D'silva A, Chandran P, Manuel K, Kinglsey, Basheer A. Cold antibody autoimmune hemolytic anemia following varicella infection. Indian J Pathol Microbiol [serial online] 2023 [cited 2023 Feb 7];66:188-90. Available from: https://www.ijpmonline.org/text.asp?2023/66/1/188/367978





   Introduction Top


Autoimmune hemolytic anemias (AIHA) are characterized by presence of autoantibodies against red cell surface antigens leading to hemolysis. The autoantibodies may be warm (mainly IgG) – reactive at 37°C or cold (mainly IgM, occasionally IgG or IgA) – reactive at temperatures below 37°C. Cold agglutinin syndrome accounts for 25% of all AIHA[1] and comprises of primary chronic cold agglutinin disease, acute and chronic secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria. Cold agglutinin syndrome secondary to infection is associated with infections by mycoplasma pneumoniae and Epstein-Barr virus and only rarely reported following infections by Cytomegalovirus, Influenza A, varicella zoster, Rubella, Legionella pneumophilia, and Chlamydia species.

Chicken pox usually occurs in children; cerebellar ataxia, encephalitis, and transverse myelitis are recognized complications. AIHA is following varicella-zoster infection. We present the case of a young female who presented with hemolytic anemia following varicella infection.


   Case Report Top


A 24-year-old female was admitted with history of maculo-papular rash on the face, trunk, and extremities which evolved into vesicles followed by crusting, typical of Chicken pox 5 days ago. On the fourth day, she developed fever and yellowish discoloration of eyes. On examination, she had pallor, icterus, and crusted lesions on the trunk and extremities.

Initial investigations revealed total bilirubin of 5.1 mg/dL, direct fraction of 0.6 mg/dL, and hemoglobin of 7.9 gm/dL. Total leukocyte counts were 16,500/cu.mm with neutrophilia. Renal and other liver function tests and coagulation profile were as follows: urea – 131 mg/dL, creatinine –2.1 mg/dL, AST –192 U/L, ALT –33 U/L, alkaline phosphatase –76 U/L, GGT –48 U/L, total protein – 6 gm/dL, albumin –3.5 gm/dL, globulin –2.5 gm/dL, PT/INR –12.7 s/1.06, and aPTT –26.8 s.

She was started empirically on antibiotics, in view of sepsis, and supportive treatment including antipyretics and intravenous fluids.

Peripheral smear showed normocytic, normochromic RBCs with red cell agglutinates [Figure 1] and neutrophilic leucocytosis with neutrophils showing erythrophagocytosis [Figure 2]. Lactate dehydrogenase (LDH) was markedly elevated 2505 IU/L (Normal <250 IU/L), and reticulocyte count was 0.5%. Malaria antigen test, Dengue serology, and serology for hepatotropic viruses were negative. Blood and urine cultures were negative. ANA was negative too. Ultrasonography of abdomen and chest X-ray were normal.
Figure 1: Peripheral blood smear showing red cell agglutination (Leishman, x40)

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Figure 2: Peripheral blood smear showing erythrophagocytosis by neutrophils (Leishman, x1000)

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Direct Coombs test (DCT) done for evaluation of hemolysis was positive for C3d [Figure 3] confirming a diagnosis of cold antibody AIHA secondary to varicella-zoster infection, there being no other relevant history and all other tests yielding negative results including a negative cold agglutination test for Donath-Landsteiner antibody.
Figure 3: Direct Coomb's test showing a positive (4+) test for C3d antibody

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On the second day of admission, there was a fall in hemoglobin to 4.8 and to 3.8 gm/dL 12 h later. She was transfused 3 units of packed red cells using a warmer. After an initial rise in hemoglobin there was a fall with corresponding rise in bilirubin levels (Total/Direct: 5.1/0.6 at admission to 8.6/1.5 on Day 4). On day 4, peripheral smear showed similar findings of red cell agglutination and erythrophagocytosis and DCT was positive for IgG and C3d (posttransfusion). LDH levels were1785 IU/L and retic count was 1.9% suggesting ongoing hemolysis. She was started on prednisolone at 50 mg per day orally. It was only from day 6 that hemoglobin levels began to show a steady rise with a corresponding decrease in bilirubin levels.

Throughout the hospital stay, she was hemodynamically stable. No further transfusions were required. Steroids were continued for 1 week and tapered rapidly over 10 days. She was discharged after 12 days with hemoglobin of 7.2 gm/dL and total bilirubin of 1.5 mg/dL. On follow-up a week later, she was asymptomatic, and her laboratory tests showed the following results: hemoglobin – 9.2 gm/dL, total bilirubin – 0.6 mg/dL, LDH – 310 IU/L, and DCT – negative. Peripheral smear showed no red cell agglutination or erythrophagocytosis.


   Discussion Top


Very few cases of AIHA following varicella infection have been reported till date.[2–8] These cases had no common epidemiological or clinical features and have been described mostly in children and young adults.

While most other cases of AIHA in young adults were due to warm antibodies, our patient tested positive for cold agglutinins. Similar observation was made by Walia et al.[8] in a 16-year-old girl. On the contrary, all cases of chicken pox-associated AIHA in children were due to cold agglutinins.[6],[7]

The reticulocyte count in our patient was disproportionately low for a hemolytic process (at least initially), a feature also observed by Kumar et al.[2] Several mechanisms are proposed for reticulocytopenia in cases of AIHA; the possible reason in our case could be the destruction of maturing erythrocytes in the marrow by active erythrophages before they appear in the blood.

Despite lack of high-quality evidence, due to the ongoing hemolysis and severe anemia, our patient was started on steroids and rapidly tapered over 2 weeks. Although her hemoglobin improved and hemolysis was stalled, it is difficult to associate this response to steroids based on a single case report. Steroids have been tried in the past with success in warm antibody AIHA following chicken pox, while the cases of cold antibody AIHA resolved spontaneously over a period of 1 week.[2–8]

Our case indicates that short course of steroids may have a role in cold antibody AIHA following chicken pox for control of severe ongoing hemolysis and restoration of rapidly falling hemoglobin levels particularly when illness shows no abatement in the first few days.

This case highlights gaps in literature regarding hematological complications of chicken pox and need for good data on predisposing factors, whether antiviral therapy has preventive role and whether this could be a harbinger of future autoimmune disease warranting need for long-term monitoring. The role of steroids in treatment and its optimum duration also needs to be evaluated. These gaps can only be bridged as more clinical information becomes available in future.

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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Berentsen S, Tjønnfjord GE. Diagnosis and treatment of cold agglutinin mediated autoimmune hemolytic anemia. Blood Rev 2012;26:107–15.  Back to cited text no. 1
    
2.
Kumar KJ, Kumar HC, Manjunath VG, Arun V. Autoimmune hemolytic anemia due to varicella infection. Iran J Pediatr 2013;23:491–2.  Back to cited text no. 2
    
3.
Shamim S, Jamalvi WS. Auto immune hemolytic anemia in a child precipitated by chicken pox. J Coll Physicians Surg Pakistan 2008;18:319–20.  Back to cited text no. 3
    
4.
Kumar M, Kothari N, Gupta BD. Autoimmune haemolytic anaemia in a child due to chickenpox. Indian J Hematol Blood Transfus 2016;32:522.  Back to cited text no. 4
    
5.
Ittyachen A, Jose M, Abraham V. Autoimmune hemolytic anemia secondary to chicken pox. Ann Trop Med Public Heal 2013;6:353.  Back to cited text no. 5
    
6.
Friedman HD, Dracker RA. Cold agglutinin disease after chicken pox. An uncommon complication of a common disease. Am J Clin Pathol 1992;97:92–6.  Back to cited text no. 6
    
7.
Terada K, Tanaka H, Mori R, Kataoka N, Uchikawa M. Hemolytic anemia associated with cold agglutinin during chickenpox and a review of the literature. J Pediatr Hematol Oncol 1998;20:149–51.  Back to cited text no. 7
    
8.
Walia H, Jain R, Bansal RK, Gupta GN. Cold agglutinin disease with erythrophagocytosis by neutrophils occurring during recovery phase of chickenpox. J Lab Physicians 2013;5:146–7.  Back to cited text no. 8
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Correspondence Address:
Aneesh Basheer
Professor of Medicine, DM Wayanad Institute of Medical Sciences, Wayanad, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpm.ijpm_728_21

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