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:
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Low-grade fever
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Sore mouth
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Odynophagia
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Gingival pain and swelling
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Skin abscesses
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Recurrent sinusitis and otitis
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Signs and symptoms of pneumonia (eg, cough, dyspnea)
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Perirectal pain and irritation
Patients with agranulocytosis usually present with the following:
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Sudden onset of malaise
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Sudden onset of fever, possibly with chills and prostration
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Stomatitis and periodontitis accompanied by pain
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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, 42, 12]
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. [43, 44]
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.
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:
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Fever
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Stomatitis
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Periodontal infection
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Cervical lymphadenopathy
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Skin infection
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Splenomegaly (see the image below)
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Associated petechial bleeding
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Perirectal infection
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Growth retardation in children
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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.
Febrile neutropenia is defined as a single oral temperature measurement of ≥38.3° C (101° F) or a temperature of ≥38.0° C (100.4° F) sustained over 1 hour. [11] In agranulocytosis, fever may be 40°C or higher. 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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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.
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Doppler sonogram at the splenic hilum reveals hepatofugal venous flow in a patient with portal hypertension.
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Two neutrophils among red blood cells. Courtesy of Britannica (https://www.britannica.com/science/neutrophil).
Tables
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 |
Thrombocytopenia with absent radii (TAR) |
Autosomal recessive |
RBM8A |
Thrombocytopenia, MDS, absent radii, abnormal ulna |
Diamond-Blackfan anemia |
Autosomal dominant, X-linked recessive |
RPS19, RPL5, RPS26 |
Macrocytic anemia, other cytopenias, solid tumors, short stature, abnormal thumbs, cardiac septal defect |
Fanconi syndrome |
Autosomal recessive (rarely, X-linked recessive or autosomal dominant) |
FANCA, FANCC, FANCG |
Pancytopenia, solid tumors, skin hyperpigmentation and café au lait spots, abnormal thumbs |
Dyskeratosis congenita |
X-linked recessive, autosomal dominant, autosomal recessive |
DKC1, TINF2 |
Pancytopenia, MDS, nail dystrophy, leukoplakia, solid tumors |
Source: Modified from Berliner et al, 2004. [23] AML = acute myeloid leukemia; G-CSF = granulocyte colony-stimulating factor; MDS = myelodysplastic syndrome. |
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