• Users Online: 123
  • Print this page
  • Email this page


 
 
Table of Contents
CASE REPORT
Year : 2022  |  Volume : 13  |  Issue : 4  |  Page : 254-257

Hemophagocytic lymphohistiocytosis after ChAdOx1 nCoV-19 coronavirus vaccination in a patient with no known comorbidities


1 Department of Critical Care Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
2 MBBS Students, Faculty of Medical Sciences, King George's Medical University, Lucknow, Uttar Pradesh, India
3 Department of Pathology, King George's Medical University, Lucknow, Uttar Pradesh, India

Date of Submission05-Jul-2022
Date of Decision21-Jul-2022
Date of Acceptance19-Aug-2022
Date of Web Publication18-Oct-2022

Correspondence Address:
Mr. Shubhajeet Roy
Faculty of Medical Sciences, King George's Medical University, Shah Mina Road, Chowk, Lucknow - 226 003, Uttar Pradesh
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/injms.injms_80_22

Rights and Permissions
  Abstract 


Hemophagocytic lymphohistiocytosis (HLH) is an inflammatory condition where there is marked cytopenia and large-scale activation of macrophages and CD8+ cytotoxic T cells. HLH may be of two types – primary HLH caused by genetic abnormalities and secondary HLH due to infections, malignancies, autoimmune disorders, rheumatologic disorders, and metabolic dysfunctions. We describe a case of HLH following the first dose of the ChAdOx1 nCoV-19 Corona Virus vaccine. In this patient, there was no clear precipitant of HLH. The most probable explanation could be intense immune activation by vaccine constituents producing aberrant activation of inflammatory cytokines. There were no signs of infection or malignancy. Since our patient was clinically stable, his symptoms had resolved and HLH parameters had improved, no HLH-specific therapy was given.

Keywords: ChAdOx1 nCoV-19, COVID-19, hemophagocytic lymphohistiocytosis, immune activation, vaccine


How to cite this article:
Rai N, Misra S, Prajapati S, Roy S, Yadav G. Hemophagocytic lymphohistiocytosis after ChAdOx1 nCoV-19 coronavirus vaccination in a patient with no known comorbidities. Indian J Med Spec 2022;13:254-7

How to cite this URL:
Rai N, Misra S, Prajapati S, Roy S, Yadav G. Hemophagocytic lymphohistiocytosis after ChAdOx1 nCoV-19 coronavirus vaccination in a patient with no known comorbidities. Indian J Med Spec [serial online] 2022 [cited 2022 Dec 1];13:254-7. Available from: http://www.ijms.in/text.asp?2022/13/4/254/358781




  Introduction Top


As the world is moving toward vaccination against COVID-19, new challenges are emerging.[1] Herein, we describe a case of hemophagocytic lymphohistiocytosis (HLH) following the first dose of the ChAdOx1 nCoV-19 Corona Virus vaccine. There have been cases of HLH following ChAdOx1 nCoV-19 Corona Virus vaccine administration, but all of them have been reported in patients with comorbidities.[2] As per our search of the literature, this is the first case of ChAdOx1 nCoV-19 Corona Virus vaccine-induced HLH, in a patient without any comorbidity, to be reported from India.


  Case Report Top


A 35-year-old male, with no comorbidities and who is a chronic alcoholic, but 3 years into abstinence from alcohol started developing fever, backache, right testicular pain, diminished sensorium (GCS of E1 VT M1) requiring invasive ventilation, and reported decreased urine output after receiving the first dose of the ChAdOx1 nCoV-19 Corona Virus vaccine. Computed tomography of the head showed normal findings. Chest X-ray showed bilateral prominent bronchovascular markings and right lower zone consolidation [Figure 1], whereas that of the chest showed mild ground-glass opacities in bilateral lung fields mainly in the upper and middle zones [Figure 2] and [Figure 3]. The tropical fever panel showed negative results, blood and endotracheal aspirate (ETA) cultures were sterile, liver function tests and kidney function tests showed mild derangement (the patient was anuric and had an acute liver failure with multiple organ dysfunction syndromes), and cerebrospinal fluid (CSF) studies were normal. There was mild hepatosplenomegaly, mild testicular swelling, and right-sided inguinal lymphadenopathy. Subsequently, he developed bicytopenia with hemoglobin being 9.0 g/dL, hematocrit of 51%, platelet count 50 × 109/L, and INR of 1.6. His total bilirubin was 4 mg/dL, ferritin 2132 μg/L, triglyceride 358 mg/dL, fibrinogen 1.42 g/L, and serum ammonia 118 IU/L (postdialysis). On cardiovascular system examination, sinus bradycardia along with generalized edema was noted. Electrocardiography showed diffuse ST elevation and bilateral bronchovascular markings were prominent. Penile edema was also present. Bone marrow biopsy and lymph node biopsy both showed hemophagocytosis with engulfment of neutrophils, lymphocytes, and normoblasts, thus making HLH a likely diagnosis [Figure 4], [Figure 5], [Figure 6], [Figure 7]. Soluble CD25 and NK cell functions could not be performed. The extensive evaluation was done to look into the etiology of HLH. SARS-CoV-2 reverse transcriptase–polymerase chain reaction (PCR) test was negative. PCR tests for Epstein–Barr virus (EBV), influenza A (H1N1 and H3N2), influenza B, and cytomegalovirus (CMV) performed from ETA were also negative. Similarly, PCR test from serum sample for EBV, parvovirus B19, CMV, and CSF sample for EBV, parvovirus B19, CMV, and herpes simplex virus-1 were negative as well. Hepatitis B, C, and HIV serologies were negative too. Autoimmune antibodies including complements were also found to be negative. He had persistent fever (38.6°C) for the initial 6 days, with a rise in serum ferritin. Hence, intravenous steroids were started. By the eighth day, the fever subsided with improvement in malaise and lethargy. Two weeks later, the ferritin levels had gone down, platelet count had risen to 1.8 × 1011/L and splenomegaly had resolved.
Figure 1: Chest X-ray anteroposterior view showing bilateral prominent bronchovascular markings, right lower zone consolidation

Click here to view
Figure 2: Mild ground-glass opacities in bilateral lung fields mainly in upper zone

Click here to view
Figure 3: Mild ground-glass opacities in bilateral lung fields mainly in mid zone

Click here to view
Figure 4: Bone marrow aspirate smear showing hemophagocytosis with engulfment of normoblast (black arrowheads showing normoblasts and red arrowhead showing histiocyte) (Leishman Stain, ×1000)

Click here to view
Figure 5: Bone marrow aspirate smear showing hemophagocytosis with engulfment of neutrophils (black arrowheads showing two intact neutrophils and red arrowhead showing histiocyte) (Leishman Stain, ×1000)

Click here to view
Figure 6: Bone marrow aspirate smear hemophagocytosis with engulfment of lymphocyte and red blood cells (black arrowheads showing lymphocytes, blue arrowhead showing red blood cells, and red arrowhead showing histiocyte) (Leishman Stain, ×1000)

Click here to view
Figure 7: Fine needle aspiration smears from inguinal lymph node showing paucicellular aspirate smear with the presence of histiocytes with engulfment of platelets (black arrowhead showing platelet and red arrowhead showing histiocyte) (Leishman Stain, ×1000)

Click here to view



  Discussion Top


HLH is an inflammatory condition where there is marked cytopenia, and signs and symptoms resembling systemic inflammation are present. It is marked by large-scale activation of macrophages and CD8+ cytotoxic T cells which causes systemic inflammation.[3],[4] If untreated, this can lead to multiorgan failure, shock, and death.[5] Even with the current treatment plans, 50% lethality has been noted.[4]

HLH can be of two types – primary HLH caused by genetic abnormalities (either autosomal recessive or X-linked) and secondary HLH due to infections, malignancies, autoimmune disorders, rheumatologic disorders, and metabolic dysfunctions.[6],[7] Cases of familial HLH (a form of primary HLH) have been reported from India, which mostly affects infants and children, but there is literature available of it reporting in adults too.[8]

In a similar set of case series where ChAdOx1 nCoV-19 Corona Virus vaccination was administered, patient 1, who was a known case of controlled type 2 diabetes mellitus, developed symptoms 5 days after vaccination, in whom a temperature of 39.3°C was noted, hepatomegaly was present, hemoglobin was 10.1 g/L, platelet count 54 × 109/L, ferritin 159,076 mcg/L, lactate dehydrogenase (LDH) 536 IU/L, triglyceride 6.3 mmol/L, fibrinogen 0.7 g/L, serum glutamic-oxaloacetic transaminase (SGOT) 132 IU/L, troponin 299 ng/L, CD-25 levels of 4833 pg/mL, and HScore of 259 was noted.[2] Patient 2 who had a stable JAK2 mutant positive essential thrombocythemia, and a history of breast cancer, which was in remission, developed symptoms 7 days after vaccination, in whom a temperature of 39.2°C was noted, no organomegaly was seen, hemoglobin was 11.9 g/L, platelet count 69 × 109/L, ferritin 5529 mcg/L, LDH 1178 IU/L, triglyceride 2 mmol/L, fibrinogen 0.94 g/L, troponin 312 ng/L, CD-25 levels of 9,232 pg/ml, and HScore of 220 was noted.[2] Patient 3 who had ankylosing spondylitis, developed symptoms 8 days after the vaccination, a temperature of 41.2°C was noted, splenomegaly was present, hemoglobin was 10.5 g/L, platelet count 319 × 109/L, ferritin 58,255 mcg/L, LDH 541 IU/L, triglyceride 2.7 mmol/L, fibrinogen 4.17 g/L, SGOT 47 IU/L, troponin 42 ng/L, CD-25 levels of 3575 pg/ml, and HScore of 219 was noted.[2] A comparative study of the aforementioned three cases and the case reported in this report are summarized in [Table 1].
Table 1: Comparison of three similar cases reported in literature and our case

Click here to view


In our patient, no exact etiology of HLH could be found. Our case is unique in the sense that, there are no predisposing conditions present which can be the cause of HLH. All the possible viral etiologies had been ruled out, no malignancy or autoimmune disease could be found and other comorbidities were ruled out. Hence, the plausible explanation could be intense immune activation by the constituents of the vaccine which had produced aberrant activation of inflammatory cytokines.[9] It could not be ascertained if he had any genetic predisposition to HLH and the ChAdOx1 nCoV-19 Corona Virus vaccine appeared to be the most likely precipitant of HLH.


  Conclusion Top


Clinicians should be vigilant and aware of the fact that HLH should be considered a differential diagnosis when a patient presents with fever after vaccination for SARS-CoV2. However, people should be inspired to get vaccinated actively and the vaccination drives started by various governments should be supported in all ways. No one should get discouraged by this report as even after close to 2 billion vaccination doses in India, it is an extremely rare complication.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Gianfredi V, Pennisi F, Lume A, Ricciardi GE, Minerva M, Riccò M, et al. Challenges and opportunities of mass vaccination centers in COVID-19 times: A rapid review of literature. Vaccines (Basel) 2021;9:574.  Back to cited text no. 1
    
2.
Attwell L, Zaw T, McCormick J, Marks J, McCarthy H. Haemophagocytic lymphohistiocytosis after ChAdOx1 nCoV-19 vaccination. J Clin Pathol 2022;75:282-4.  Back to cited text no. 2
    
3.
de Campos FP, de Lima PP, Lima FR, Simões AB, Kim EI, Smeili LA, et al. Hemophagocytic lymphohistiocytosis of indeterminate cause: A fatal adult case. Autops Case Rep 2012;2:11-20.  Back to cited text no. 3
    
4.
Hieber ML, Sprute R, Eichenauer DA, Hallek M, Jachimowicz RD. Hemophagocytic lymphohistiocytosis after SARS-CoV-2 vaccination. Infection 2022:1–6. doi: 10.1007/s15010-022-01786-y. Epub ahead of print. PMID: 35218512; PMCID: PMC8881936.  Back to cited text no. 4
    
5.
Fleischmann R, Böhmerle W, von Laffert M, Jöhrens K, Mengel A, Hotter B, et al. Adult hemophagocytic lymphohistiocytosis causing multi organ dysfunction in a patient with multiple autoimmune disorders: When the immune system runs amok. Clin Case Rep 2016;4:165-70.  Back to cited text no. 5
    
6.
George MR. Hemophagocytic lymphohistiocytosis: Review of etiologies and management. J Blood Med 2014;5:69-86.  Back to cited text no. 6
    
7.
Brisse E, Wouters CH, Matthys P. Advances in the pathogenesis of primary and secondary haemophagocytic lymphohistiocytosis: Differences and similarities. Br J Haematol 2016;174:203-17.  Back to cited text no. 7
    
8.
Shabrish S, Kelkar M, Yadav RM, Bargir UA, Gupta M, Dalvi A, et al. The spectrum of clinical, immunological, and molecular findings in familial hemophagocytic lymphohistiocytosis: Experience from India. Front Immunol 2021;12:612583.  Back to cited text no. 8
    
9.
Janka G. Hemophagocytic lymphohistiocytosis: When the immune system runs amok. Klin Padiatr 2009;221:278-85.  Back to cited text no. 9
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
    Tables

  [Table 1]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Abstract
Introduction
Case Report
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed348    
    Printed11    
    Emailed0    
    PDF Downloaded6    
    Comments [Add]    

Recommend this journal