Evaluating the Clinical Utility of Testing for
Autoimmune Disorders in the Setting of Leukopenia/Neutropenia in an Ambulatory Hematology Clinic
Devin Malik1*, Joyce Philip2, Amal Hejab2, Alexander Horbal2, Vivek Mendiratta2 and Philip Kuriakose1
1Division of Hematology and Oncology, Henry Ford Hospital & Wayne State University, USA
2Department of Internal Medicine, Henry Ford Hospital & Wayne State University, USA
Submission: June 14, 2018; Published: August 27, 2018
*Corresponding author: Devin Malik, Division of Hematology and Oncology, Henry Ford Hospital & Wayne State University, 2799 W Grand Blvd, Detroit MI 48202, USA, Tel: 313-850-9337; Email:[email protected]
How to cite this article: Devin M, Joyce P, Amal H, Alexander H, Vivek M, et.al. Evaluating the Clinical Utility of Testing for Autoimmune Disorders in the
Setting of Leukopenia/Neutropenia in an Ambulatory Hematology Clinic. Ann Rev Resear. 2018; 3(2): 555610. DOI: 10.19080/ARR.2018.03.555610
Purpose: To determine how many patients seen in our hematology clinic for leukopenia and screened for autoimmunity are being diagnosed with autoimmune conditions.
Methods:This was a retrospective, single institution study done in an ambulatory clinic setting. Data was collected from 2005-2015. Inclusion criteria were having a white blood cell count of less than 3.8K/uL or neutrophil count less than 1.8K/ul and positive antinuclear antibody (ANA) or rheumatoid factor antibody (RF) of greater than 1:80 or 14IU/mL, respectively (institutional cutoffs). Exclusion criteria were a known hematologic disorder, rheumatologic disorder or active chemotherapy
Results:One hundred and ninety-one patients were reviewed for data analysis. Eleven patients were diagnosed with rheumatologic conditions (6%). The majority of these patients had associated findings suggestive of an underlying autoimmune disease.
Conclusions:This study shows that testing for ANA and RF in patients with leukopenia/neutropenia is of limited clinical utility in asymptomatic patients with no other lab abnormalities, and as such it should not be part of a routine work up, unless directed by symptoms.
Leukopenia (WBC count of <3.8K/uL) and/or neutropenia (<1.8K/uL, both institutional lab cutoffs), are commonly encountered by physicians on routine blood testing in otherwise healthy patients. This finding, whether incidental or not, often leads to hematology referrals. A broad work up may be pursued in an attempt to find a definitive diagnosis. We conducted this study to assess the utility of testing for anti-nuclear antibody (ANA) as well rheumatoid factor (RF) in patients with leukopenia/neutropenia, and whether or not a positive serology led to a rheumatologic diagnosis.
After obtaining institutional review board approval, we searched for outpatient hematology consults with a diagnosis of leukopenia and/or neutropenia using ICD-9 and ICD-10 diagnostic codes between 2005-2015 at Henry Ford Hospital. Data points included demographics and antibody serology. Physician documentation was reviewed for additional symptoms such as joint/muscle pain. Patients were excluded if they had a known hematologic disorder, known rheumatologic disorder or were on active chemotherapy. A positive ANA or RF were considered if titers were >1:80 or >14IU/mL (institutional cutoffs). Complete
blood counts were reviewed for patients who were not excluded based on above criteria.
A total of 561 patients were seen in our outpatient clinic during the 10-year interval with an associated diagnostic code for leukopenia/neutropenia. One hundred and ninety-nine were excluded due to incomplete data or inadequate follow up period, 35 patients for known malignancy, 14 for known rheumatologic
disorder, and 122 for being on active chemotherapy. The
remaining 191 patients were reviewed for data analysis. Patient
demographics are summarized in Table 1.
A total of 116 patients (61%) were tested for ANA, of which
27 (23%) were positive. Twenty two of those 27 (81%) patients
were referred to rheumatology, 6 of whom were diagnosed with
rheumatologic diseases (22%). RF was tested in 110 patients
(58%), of which 15 were positive (14%); all were referred to
rheumatology, with 5(42%) being diagnosed with rheumatologic
diseases. Test results, referral rate and rheumatologic diagnosis
are listed in Table 2.
*3 patients were no shows. ** 1 patient developed T-LGL
The majority of patients who were diagnosed with
rheumatologic disorders had associated findings suggestive of
underlying disease - 3 patients with systemic lupus erythematosus
(SLE) had mild thrombocytopenia (100-150K/uL), 1 patient with
mixed connective tissue disease had Raynaud’s phenomenon,
3 patients with rheumatoid arthritis (RA) had arthralgias and 1
had myalgias, all with correlating physical exam or radiographic
Other alternative diagnoses for leukopenia/neutropenia
included drug induced, viral and bacterial infections, hematologic
malignancies, ethnic neutropenia, transient leukopenia, and
Leukopenia can be the result of a primary bone marrow
disorder (myelodysplastic syndrome, myelofibrosis, leukemia)
or a secondary phenomenon as a result of drugs, infection, and
autoimmunity, amongst others. Autoimmune neutropenia can be
primary, occurring in infancy, or secondary in the context of an
autoimmune disorder which usually manifests in adulthood .
The strongest autoimmune association can be made for large
granular lymphocytic leukemia (LGL) and Felty’s syndrome with
rheumatoid arthritis. While the former’s mechanism in causing
neutropenia is unclear, the latter is related to humoral immunity
with antineutrophilic antibodies, although testing for these
antibodies may be unhelpful in diagnosis [2,3]. The treatment
of neutropenia in LGL is with low doses of methotrexate or
cyclophosphamide [4,5], while in Felty’s syndrome treatment of
the underlying RA is often sufficient .
The mechanism of neutropenia in SLE is multifactorial,
including increased neutrophil apoptosis, antineutrophilic
antibodies, and bone marrow dysfunction from antibodies towards
hematopoietic stem cells [7-10]. The degree of neutropenia often
mirrors disease activity and most often responds to immune
suppression. Other connective tissue diseases have a similar
pathophysiology to SLE.
Ambulatory hematology consults for leukopenia/neutropenia
are a common occurrence in practice. Our study showed that
11 patients out of 191 (6%) were found to have an associated
rheumatologic disorder, with the majority having other signs/
symptoms or associated lab abnormalities suggestive of
autoimmune disease. This study shows that testing for ANA and
RF in patients with leukopenia/neutropenia is of limited clinical
utility in asymptomatic patients with no other lab abnormalities,
and it should not be part of a routine work up, unless directed
by symptoms. Primary care providers need to screen for other
abnormalities (symptoms/clinical findings) in order to identify
patients that would benefit most from subspecialty referral.