International Journal for Doctor of Medicine and  Medical Students (IJDMMS)

Abstract

Leukemoid reaction (LR) is a reactive hematologic condition characterized by an extreme white blood cell count elevation, typically >50,000/µL, in response to severe stressors outside the bone marrow, most notably infections. Although LR can mimic leukemia, its etiology is fundamentally different and reversible once the underlying cause is addressed. Infections represent the most common and clinically important triggers for LR, including bacterial, viral, parasitic, and fungal pathogens. This systematic review synthesizes the current understanding of infectious causes of leukemoid reactions, examines the underlying mechanisms, clinical presentations, diagnostic challenges, and management strategies. Recognizing infectious triggers has implications for timely diagnosis, appropriate antimicrobial therapy, and avoidance of unnecessary oncologic workup.

Keywords: leukemoid reaction, infection, leukocytosis, bacterial infections, viral infections, diagnostic approach

Introduction

A leukemoid reaction( LR) is defined as a  pronounced leukocytosis with white blood cell( WBC) counts  generally exceeding  50,000 cells per microliter, accompanied by a ascendance  of mature neutrophils or other leukocyte lineages as a systemic response to stressors unconnected to primary hematological  malice( e.g.,  habitual myelogenous leukemia( CML) or  habitual neutrophilic leukemia)( Wikipedia, n.d.; Dobrianskyi et al., 2024). LR can arise from different causes  similar as  malice,  medicines, hemorrhage, and critically, infections( Dobrianskyi et al., 2024; Tarekegn et al., 2021). Among these,  contagious etiologies are the most frequent and clinically significant triggers for LR( Mitchell et al., 2013; Dobrianskyi et al., 2024).

 Infection- induced LR can pose significant  individual challenges due to its imbrication with primary hematologic  conditions and severe systemic  seditious responses. Prompt recognition of  contagious causes can expedite applicable antimicrobial  remedy and improve patient  issues. This methodical  review aims to synthesize the being literature on  contagious causes of LR,  interpret pathophysiological mechanisms, discuss  individual considerations, and highlight clinical  operation strategies.

 Methods

 Search Strategy and Selection Criteria

 We performed a methodical  literature search using databases including PubMed, Oxford Academic, and ScienceDirect with keywords  similar as “ leukemoid reaction infection ”, “  contagious causes leukemoid  response ”, “ leukemoid  response bacterial viral fungal ”. Search terms were combined with Boolean operators to capture a comprehensive spectrum of  papers. Primary emphasis was on studies reporting  contagious triggers of LR in humans.

 Inclusion criteria

 Studies involving  mortal subjects.

 papers agitating  contagious etiologies of LR.

 Case reports, case series,  experimental studies, and review  papers published in English.

 Exclusion criteria

 papers  fastening solely onnon-infectious causes of LR.

 Studies without clear clinical data.

 Data birth and Quality Assessment

 From  named  papers, data were  uprooted on

1. Type of infection.

2. Clinical presentation.

3. Leukocyte parameters.

4. Diagnostic methods.

5. Treatment outcomes.

Quality assessment favored peer-reviewed clinical research, cohort studies, and well-documented case reports.

Results

Overview of Leukemoid Reaction and Infection

The leukemoid response( LR) is a reactive,non-neoplastic hematological phenomenon characterized by  pronounced leukocytosis,  generally exceeding  50,000 cells/ µL, and is most generally driven by pronounced neutrophilia( Wikipedia, n.d.; Dobrianskyi et al., 2024). Unlike hematological malignancies  similar as  habitual myeloid leukemia, LR represents an  inflated but  flash response of the bone marrow to external physiological or pathological stressors. supplemental blood smears in LR  frequently demonstrate mature neutrophils with a left shift,  poisonous granulation, and Döhle bodies, reflecting  violent  seditious or  contagious stimulation rather than clonal proliferation.

 Among the different etiologies of leukemoid response,  contagious causes constitute the most  current and clinically significant category, accounting for a substantial proportion of reported cases across multiple clinical cohorts( Mitchell et al., 2013; Dobrianskyi et al., 2024). Severe bacterial infections, particularly those associated with systemic  seditious response syndrome and sepsis, are frequently implicated. These  contagious triggers induce excessive cytokine release   similar as granulocyte colony- stimulating factor( G- CSF), interleukin- 6, and tumor necrosis factor- α  which in turn accelerates granulopoiesis and  supplemental neutrophil release.

 A cohort analysis investigating the etiological spectrum of leukemoid response demonstrated that  contagious causes were responsible for  roughly 48 of LR cases among adult patients( Mitchell et al., 2013). In this study, patients with infection- related leukemoid responses generally displayed positive blood cultures, hemodynamic instability, and features  harmonious with severe sepsis or septic shock. Importantly, infection- associated LR was also correlated with increased in- hospital mortality, highlighting its value as a prognostic marker rather than  simply a laboratory abnormality( Mitchell et al., 2013). The degree of leukocytosis in these cases  frequently  matched  complaint  inflexibility and systemic inflammatory burden.

likewise,  posterior analyses have  corroborated that  contagious etiologies of leukemoid response encompass a broad and evolving spectrum of pathogens. While classical bacterial infections  similar as pneumonia,intra-abdominal sepsis, and urinary tract infections remain dominant, arising  substantiation indicates that viral, fungal, and atypical organisms can also provoke leukemoid  responses under certain circumstances ( Tarekegn et al., 2021). Viral infections, particularly those associated with severe  seditious responses or secondary bacterial superinfection, have decreasingly been recognized as potential triggers. This expanding etiological  geography underscores the  significance of thorough clinical evaluation and microbiological investigation when encountering extreme leukocytosis, as accurate identification of the underlying cause is critical for timely management and prognostication.  

 Discussion

 Pathophysiology of Infection- Induced Leukemoid Reaction

 LR results from a profound activation of the vulnerable system in response to a severe systemic or localized infection. Mechanistically, microbial antigens and pathogen- associated molecular patterns( PAMPs) trigger  ingrain vulnerable pathways, leading to elevated neutrophil production and release from the bone marrow. Cytokines  similar as G- CSF, IL- 6, and TNF- α play critical  places in driving granulopoiesis and neutrophilia( Unger, 2018). The result is a  pronounced increase in circulating leukocytes,  frequently mimicking leukemic processes.

Bacterial Infections

 Clostridioides difficile

 Significant leukemoid reactions have been reported in severe Clostridioides difficile infections, particularly in fulminant disease. LR in C. difficile is associated with high toxin production and systemic inflammation, with some cases requiring targeted antimicrobial therapy and surgical intervention( Jafri, 2025). Severe leukocytosis in C. difficile may exceed  50,000/ µL and is linked with poor prognosis.

 Tuberculosis and Other Gram-Negative Infections

 Disseminated tuberculosis and other severe bacterial infections  similar as shigellosis and severe pyogenic infections have been associated with LR. Shigella dysenteriae infections, in particular, show high rates of leukemoid responses in children and have been well documented in pediatric cohorts( Long & Vodzak, 2018). also, bloodstream infections leading to sepsis  frequently drive pronounced leukocytosis with neutrophil predominance.

 Viral Infections

 Viral infections are less generally recognized as triggers for LR, and when they  do, they  frequently present with atypical features. Severe COVID- 19, for  illustration, has been documented to cause LR in hospitalized cases,  probably due to a hyperinflammatory cytokine response with vulnerable system dysregulation( Tarekegn et al., 2021). contagious mononucleosis caused by Epstein- Barr virus( EBV) represents another viral cause, where LR can mimic hematologic malignancies.

 Parasitic and Fungal Infections

 Although  lower frequent, parasitic infections  similar as severe visceral larva migrans and fungal infections can be associated with LR or  analogous hyperleukocytic states. Candidemia and  circulated fungal infections may cause variable leukocytic responses, including neutrophilia or eosinophilia( Long & Vodzak, 2018).

 Clinical Presentation and Diagnostic Considerations

 Cases with infection-  convinced LR  generally present with signs and symptoms of severe infection  similar as fever, hypotension, organ dysfunction, and systemic inflammatory response syndrome( SIRS). Laboratory findings show  pronounced leukocytosis with a left shift and increased immature granulocyte forms. Differentiating LR from hematologic malignancies  similar as CML is essential and requires  probative  individual tests including leukocyte alkaline phosphatase( LAP) score,  supplemental blood smear evaluation, cytogenetic studies( e.g., BCR- ABL1), and bone marrow analysis if necessary.

 Management and Prognosis

 The cornerstone of managing LR due to infections is prompt identification and treatment of the underlying infection. Antibiotic or antiviral therapy tailored to the pathogen often results in resolution of the leukemoid  response. Supportive care, including hemodynamic support in sepsis, is critical. Prognosis varies with infection severity; for example, LR associated with severe sepsis or C. difficile colitis carries high morbidity and mortality( Mitchell et al., 2013; Jafri, 2025).

 Conclusion

Infections represent the most frequent and clinically consequential causes of leukemoid responses, accounting for a significant proportion of cases observed in adult and pediatric populations alike. Among  contagious triggers, bacterial pathogens play a predominant role. Organisms  similar as Clostridioides difficile, Shigella species, and bacteremias associated with sepsis are  constantly implicated in precipitating  pronounced leukocytosis,  frequently exceeding  50,000 cells/ µL. These infections  generally provoke an  violent systemic  seditious response, with the release of cytokines  similar as granulocyte colony- stimulating factor( G- CSF) and interleukin- 6, which drive accelerated myelopoiesis and  supplemental neutrophil mobilization. The  inflexibility of leukocytosis  frequently correlates with the  acridity of the bacterial pathogen and the extent of systemic involvement, making it not only a laboratory finding but also a implicit prognostic  index of clinical  issues.

 Severe viral infections have also been decreasingly recognized as able of eliciting leukemoid responses. Viral agents  similar as SARS- CoV- 2, responsible for COVID- 19, and Epstein- Barr virus( EBV) can provoke extreme leukocytosis under specific circumstances, particularly when associated with  violent vulnerable activation or secondary bacterial infections. In these cases, the vulnerable system responds robustly,  occasionally mimicking the hematologic profile seen in bacterial-  convinced leukemoid  responses. The underpinning mechanisms involve both direct stimulation of bone marrow hematopoiesis by viral- mediated cytokine release and  circular effects through systemic inflammation.

 Accurate diagnosis of infection- induced leukemoid response requires a comprehensive approach that integrates clinical context, detailed laboratory evaluation, and the methodical  exclusion of hematologic malignancies  similar as  habitual myeloid leukemia or myeloproliferative neoplasms. supplemental blood smear examination, inflammatory labels, cultures, and imaging studies  each contribute to differentiating reactive leukocytosis from clonal  diseases. Beforehand recognition of the  contagious etiology is  pivotal, as timely  inauguration of applicable antimicrobial or antiviral  remedy can significantly influence patient outcomes. Delay in identification and treatment may result in  complaint progression, sepsis- related complications, or increased mortality.

thus, the  operation of leukemoid responses necessitates a binary focus identifying and treating the underlying infection while continuously monitoring hematologic parameters. Clinical alert, prompt microbiological workup, and tailored  remedial interventions are  vital in  mollifying complications and ensuring favorable  vaticinations in cases exhibiting extreme leukocytosis due to  contagious causes. This integrated approach not only addresses the immediate hematologic abnormality but also improves overall case care and survival in severe  contagious  scripts.

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