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LetterResearch Letter

Isolated Neutropenia in Systemic Lupus Erythematosus

Nouf A. Alhammadi, Dafna D. Gladman, Jiandong Su and Murray B. Urowitz
The Journal of Rheumatology March 2023, 50 (3) 459-460; DOI: https://doi.org/10.3899/jrheum.220373
Nouf A. Alhammadi
1University of Toronto Lupus Clinic, Schroeder Arthritis Institute, Krembil Research Institute, Toronto Western Hospital, Toronto, Ontario Canada;
2King Khalid University, Abha, Saudi Arabia.
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Dafna D. Gladman
1University of Toronto Lupus Clinic, Schroeder Arthritis Institute, Krembil Research Institute, Toronto Western Hospital, Toronto, Ontario Canada;
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Jiandong Su
1University of Toronto Lupus Clinic, Schroeder Arthritis Institute, Krembil Research Institute, Toronto Western Hospital, Toronto, Ontario Canada;
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Murray B. Urowitz
1University of Toronto Lupus Clinic, Schroeder Arthritis Institute, Krembil Research Institute, Toronto Western Hospital, Toronto, Ontario Canada;
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  • For correspondence: m.urowitz@utoronto.ca
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To the Editor:

Lymphopenia is the most commonly found leukocyte abnormality in patients with systemic lupus erythematosus (SLE). Neutropenia prevalence varied from 20% to 40% in a systematic literature review.1 Most of the neutropenia episodes occurring in patients with SLE are mild, but approximately 5% of patients may experience moderate (≥ 500/mm3 ≤ absolute neutrophil count [ANC] < 1000/mm3) to severe neutropenia (ANC < 500/mm3).2 The proposed pathogenesis of neutropenia in SLE includes increased peripheral destruction of granulocytes by circulating antineutrophil antibodies,3 increased margination or changes in marginal and splenic pool,4 and decreased granulocytopoiesis in the bone marrow.5,6

Isolated neutropenia might be benign in certain ethnicities7; however, its role in patients with SLE is not very clear. Therefore, the aim of our study was to determine the prevalence of isolated neutropenia in outpatients with SLE and whether it is associated with increased risk of infection.

The Toronto Lupus Cohort (TLC) was founded in 1970 and currently has 2045 patients. Patients with isolated neutropenia on at least 2 consecutive visits with a gap between visits of ≤ 24 months were identified. Index date was the second visit with neutropenia or second normal neutrophil count in the controls.

All patients fulfilled American College of Rheumatology (ACR) classification criteria for SLE or 3 ACR criteria and a positive biopsy for SLE.8 Patients are followed regularly at 2- to 6-month intervals according to a standardized research protocol that captures demographic, clinical, laboratory, and therapeutic variables, along with major comorbidities.

Neutropenia was defined as ANC < 1500/mm3. Mild neutropenia was defined as neutropenia ≥ 1000/mm3 to < 1500/mm3, moderate/severe neutropenia was a neutrophil count < 1000/mm3. Disease duration was 8 (IQR 3-14) years. Infection rate was calculated in the groups, 1 year after index date.

This study has been approved by the University Health Network Research Ethics Board (ID#11-0397-AE) and patients have provided written consent.

The baseline characteristics of the patients were compared between patients who experienced isolated neutropenia and those with combined neutropenia and lymphopenia. Means with SDs and medians with IQRs were used to describe continuous variables; counts with percentages were used to describe categorical variables; t test or chi-square test was used to compare groups. The percentage and rate of infection in the 2 groups were determined.

Of the 2045 patients in the TLC, 170 (8.3%) patients were found to have neutropenia. Thirty patients (1.5%) had severe neutropenia and the rest were mild to moderate. Isolated neutropenia was found in 35 (1.7%) patients, of whom 29 (82.9%) had mild-to-moderate neutropenia and 6 (17.1%) had severe neutropenia. The characteristics of patients with isolated neutropenia and neutropenia/lymphopenia were similar except for Black race, which was more common in isolated neutropenia; azathioprine was more frequently taken in patients with neutropenia/lymphopenia (Table 1). Infection occurred in 17.6% (243/1385) with no neutropenia, 6.5% (2/31) with isolated neutropenia, and 21.9% (28/128) with neutropenia/lymphopenia (Table 2). Systemic Lupus Erythematosus Disease Activity Index 2000 scores were 4.0 vs 5.2, respectively; the results were not statistically significant, as illustrated in Table 1.

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Table 1.

Characteristics of patients with neutropenia.

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Table 2.

Infection rate within 1 year in patients with no neutropenia, isolated neutropenia, and combined neutropenia/lymphopenia.

Isolated neutropenia is not prevalent in patients with SLE in general but is more common in Black patients. The risk of infection did not increase in the group with isolated neutropenia compared to combined (neutropenia and lymphopenia) leukopenia and patients with SLE without neutropenia. More prospective studies are needed to better assess etiological factors and the possible pathogenesis of isolated neutropenia in patients with SLE.

  • Copyright © 2023 by the Journal of Rheumatology

REFERENCES

  1. 1.↵
    1. Carli L,
    2. Tani C,
    3. Vagnani S,
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    . Leukopenia, lymphopenia, and neutropenia in systemic lupus erythematosus: Prevalence and clinical impact--A systematic literature review. Semin Arthritis Rheum 2015;45:190-4.
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  2. 2.↵
    1. Martinez-Banos D,
    2. Crispin JC,
    3. Lazo-Langner A,
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    . Moderate and severe neutropenia in patients with systemic lupus erythematosus. Rheumatology 2006;45:994-8.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Rustagi PK,
    2. Currie MS,
    3. Logue GL
    . Complement-activating antineutrophil antibody in systemic lupus erythematosus. Am J Med 1985;78:971-7.
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    1. Boxer LA,
    2. Greenberg MS,
    3. Boxer GJ,
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    . Autoimmune neutropenia. N Engl J Med 1975;293:748-53.
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  5. 5.↵
    1. Yamasaki K,
    2. Niho Y,
    3. Yanase T
    . Granulopoiesis in systemic lupus erythematosus. Arthritis Rheum 1983;26:516-21.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Starkebaum G,
    2. Price TH,
    3. Lee MY,
    4. Arend WP
    . Autoimmune neutropenia in systemic lupus erythematosus. Arthritis Rheum 1978;21:504-12.
    OpenUrlCrossRefPubMed
  7. 7.↵
    1. Atallah-Yunes SA,
    2. Ready A,
    3. Newburger PE
    . Benign ethnic neutropenia. Blood Rev 2019;37:100586.
  8. 8.↵
    1. Hochberg MC
    . Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997;40:1725.
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Isolated Neutropenia in Systemic Lupus Erythematosus
Nouf A. Alhammadi, Dafna D. Gladman, Jiandong Su, Murray B. Urowitz
The Journal of Rheumatology Mar 2023, 50 (3) 459-460; DOI: 10.3899/jrheum.220373

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Isolated Neutropenia in Systemic Lupus Erythematosus
Nouf A. Alhammadi, Dafna D. Gladman, Jiandong Su, Murray B. Urowitz
The Journal of Rheumatology Mar 2023, 50 (3) 459-460; DOI: 10.3899/jrheum.220373
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