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Neutropenia Clinical Presentation

  • Author: Christopher D Braden, DO; Chief Editor: Emmanuel C Besa, MD  more...
 
Updated: Feb 26, 2016
 

History

Patients with neutropenia often present with infection. Other sequelae may reflect concurrent pancytopenia, such as anemic symptoms (eg, fatigue, weakness, dyspnea on exertion) and manifestations of thrombocytopenia (eg, petechiae, purpura, epistaxis). For further information on pancytopenia, refer to Bone Marrow Failure.

Common presenting symptoms of neutropenia include the following:

  • Low-grade fever
  • Sore mouth
  • Odynophagia
  • Gingival pain and swelling
  • Skin abscesses
  • Recurrent sinusitis and otitis
  • Symptoms of pneumonia (eg, cough, dyspnea)
  • Perirectal pain and irritation

Patients with agranulocytosis usually present with the following:

  • Sudden onset of malaise
  • Sudden onset of fever, possibly with chills and prostration
  • Stomatitis and periodontitis accompanied by pain
  • Pharyngitis, with difficulty in swallowing

Determine if a fever is present, because the physician must be aware of a possible life-threatening infection. Obtaining a history of infections may aid in the current diagnostic workup. A history of periodically recurring infections is suggestive of cyclic neutropenia. A strong family history of recurrent infections, usually beginning in childhood, is strongly indicative of a genetic defect. Congenital neutropenia is suggested by a personal history of lifelong infections, family history of recurrent infections, documentation of longstanding neutropenia since childhood or adolescence, and absence of any other blood abnormality.

A family history of infections or sudden death may be an indication of inherited disorders. The maternal medical history (in neonatal neutropenia) may indicate inherited disorders or adverse effects of maternal medications. Records of past complete blood counts (CBCs) establish the chronicity of the neutropenia. Determining the age at onset aids in the differential diagnosis.

A patient with agranulocytosis may have experienced a recent viral infection, although such infections are rarely associated with severe neutropenia. Certain bacterial infections may also precede agranulocytosis.

Chronic, benign familial neutropenia is suggested by a history of long-standing neutropenia without an increased risk of infection. These patients do not generate increased leukocyte counts with infection, but they have fevers and other symptoms, such as tachycardia, when infected.

A history of autoimmune diseases may be associated with antineutrophil antibodies. Such antibodies may also be the only manifestation of autoimmune disease. A number of test methods are available, but none is widely used.

Primary immune neutropenia is uncommon. Secondary immune neutropenia may be associated with systemic lupus erythematosus, rheumatoid arthritis, and Felty syndrome.[2, 45, 14]

Obtaining a careful drug history may reveal the offending agent and spare the patient from an extensive diagnostic workup. Patients often report a history of a new drug being used or a recent change in medication. However, the offending medication may no longer be in use; therefore, the inquiry should extend back for some time. A history of occupational or accidental exposure to chemicals or physical agents (eg, ionizing radiation) may be noted.[46, 47]

If treatment is not promptly instituted, the infection progresses to generalized sepsis, which may become life threatening.

Go to Pediatric Autoimmune and Chronic Benign Neutropenia for complete information on this topic.

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Physical Examination

Physical examination of a patient with neutropenia should focus on finding signs of an infection. The skin examination focuses on rashes, ulcers, or abscesses. The oral mucosa examination assesses for aphthous ulcers, thrush, or periodontal disease. Lymphadenopathy is a possible indication of a disseminated infection or, possibly, malignancy. For perirectal infections, look for abscesses or mucous membrane abnormalities. For perineal infections, look for rashes, abscesses, or lymphadenopathy. Lung infections are usually bacterial or fungal pneumonias.

Physical findings on examination of a patient with neutropenia may include the following:

  • Fever
  • Stomatitis
  • Periodontal infection
  • Cervical lymphadenopathy
  • Skin infection
  • Splenomegaly (see the image below)
  • Associated petechial bleeding
  • Perirectal infection
  • Growth retardation in children
    The margins of this massive spleen were palpated e The margins of this massive spleen were palpated easily preoperatively. Medially, the 3.18-kg (7-lb) spleen crosses the midline. Inferiorly, it extends into the pelvis.

In agranulocytosis, fever (often 40°C or higher) may be present. Rapid pulse and respiration may be evident. Hypotension and signs of septic shock may be apparent if infection has been present. Painful aphthous ulcers may be found in the oral cavity. Swollen and tender gums may be present. Usually, purulent discharge is not present, because not enough neutrophils exist to form pus. Skin infections are associated with painful swelling, but erythema and suppuration are usually absent.

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Contributor Information and Disclosures
Author

Christopher D Braden, DO Hematologist/Oncologist, Chancellor Center for Oncology at Deaconess Hospital

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching; Received consulting fee from Novartis for speaking and teaching; Received honoraria from Celgene for speaking and teaching.

Acknowledgements

Ariel Distenfeld, MD Clinical Professor, Department of Medicine, New York University School of Medicine

Disclosure: Nothing to disclose.

John E Godwin, MD, MS Professor of Medicine, Chief Division of Hematology/Oncology, Associate Director, Simmons Cooper Cancer Institute, Southern Illinois University School of Medicine

John E Godwin, MD, MS is a member of the following medical societies: American Association for the Advancement of Science, American Heart Association, and American Society of Hematology

Disclosure: Nothing to disclose.

Kush Sachdeva, MD Southern Oncology and Hematology Associates, South Jersey Healthcare, Fox Chase Cancer Center Partner

Disclosure: Nothing to disclose.

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Bilateral interstitial infiltrates in a 31-year-old patient with influenza pneumonia.
Anteroposterior chest radiograph in a young ED patient presenting with cough and malaise. The radiograph shows a classic posterior segment right upper lobe density consistent with active tuberculosis. This woman was admitted to isolation and started empirically on a 4-drug regimen in the ED. Tuberculosis was confirmed on sputum testing. Image courtesy of Remote Medicine, remotemedicine.org.
Lateral chest radiograph in a 31-year-old patient with influenza pneumonia. Image courtesy of Remote Medicine, remotemedicine.org.
The margins of this massive spleen were palpated easily preoperatively. Medially, the 3.18-kg (7-lb) spleen crosses the midline. Inferiorly, it extends into the pelvis.
Doppler sonogram at the splenic hilum reveals hepatofugal venous flow in a patient with portal hypertension.
Table 1. Genetic (Hereditary) Conditions in Agranulocytosis [24]
Syndrome Inheritance Gene Clinical Features
Cyclic neutropenia Autosomal dominant ELA2 Alternate 21-day cycling of neutrophils and monocytes
Kostmann syndrome Autosomal recessive Unknown Stable neutropenia, no MDS or AML
Severe congenital neutropenia Autosomal dominant ELA2 (35-84%) Stable neutropenia, MDS or AML
Autosomal dominant GFI1 Stable neutropenia, circulating myeloid progenitors, lymphopenia
Sex linked Wasp Neutropenic variant of Wiskott-Aldrich syndrome
Autosomal dominant G-CSFR G-CSF–refractory neutropenia, no AML or MDS
Hermansky-Pudlak syndrome type 2 Autosomal recessive AP3B1 Severe congenital neutropenia, platelet dense-body defect, oculocutaneous albinism
Chediak-Higashi syndrome Autosomal recessive LYST Neutropenia, oculocutaneous albinism, giant lysosomes, impaired platelet function
Barth syndrome Sex linked TAZ Neutropenia, often cyclic; cardiomyopathy, methylglutaconic aciduria
Cohen syndrome Autosomal recessive COH1 Neutropenia, mental retardation, dysmorphism
Source: Modified from Berliner et al, 2004.[24]



AML = acute myeloid leukemia; G-CSF = granulocyte colony-stimulating factor; MDS = myelodysplastic syndrome.



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