The Journal of Emergency Medicine, Vol. 44, No. 2, pp.

469–471, 2013
Copyright Ó 2013 Elsevier Inc.
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Case Presentations of the Harvard

EOSINOPHILIA AND RASH

Liza Gonen, MD,* William D. Binder, MD,*† Eric S. Nadel, MD,*†‡ and David F. M. Brown, MD*†
*Division of Emergency Medicine, Harvard Medical School, Boston, Massachusetts, †Department of Emergency Medicine, Massachusetts
General Hospital, Boston, Massachusetts, and ‡Department of Emergency Medicine, Brigham and Women’s Hospital, Boston,
Massachusetts
Reprint Address: David F. M. Brown, MD, Department of Emergency Medicine, Massachusetts General Hospital, 55 Fruit Street, Founders 114,
Boston, MA 02114

Dr. Liza Gonen: Today’s case is that of a 59-year-old Dr. David F. M. Brown: Can you describe the physi-
woman who presented to the Emergency Department cal examination?
(ED) with cough, weakness, and rash. The patient re- Dr. Gonen: The patient was alert, in no distress, and
ported that she had been feeling progressively ill for answered questions appropriately. Vital signs were nota-
about 1 year, with chronic cough and fatigue, and had ble for a temperature of 38.5 C (101.4 F), heart rate 107
been diagnosed with asthma 9 months before this ED pre- beats/min, blood pressure 124/80 mm Hg, respiratory rate
sentation. One week before presentation, the patient be- 14 breaths/min, and oxygen saturation 97% on room air.
gan to develop numbness and weakness in both hands The pupils were equal and reactive, the conjunctiva were
and the left foot. On the day before presentation, she de- pink, and the neck was supple. Aside from being slightly
veloped a rash. The rash first appeared on the abdomen tachycardic, the cardiac examination was unremarkable,
and then spread down both legs. The patient denied head- with normal heart sounds and no murmurs. The lung ex-
ache or sore throat, although she did report subjective fe- amination was notable for bibasilar crackles. The abdo-
vers and chills. She reported progressive dyspnea on men was soft and non-tender to palpation. Neurologic
exertion and chronic rhinitis in addition to the cough, examination revealed clear mental status with normal ori-
which was frequently productive of clear sputum and oc- entation. Motor strength was normal and symmetric. The
casional flecks of blood. The patient denied abdominal sensory examination was normal to light touch. The skin
pain, vomiting, and diarrhea, and had no recent travel. was notable for multiple purpuric and petechial lesions
The patient’s additional past medical history was nota- over the abdomen and extending down bilaterally into
ble only for chronic low back pain. About 6 weeks before the lower extremities.
presentation, she had completed a course of prednisone, Dr. Cheryl Lynn Horton: How did you proceed with
which did seem to help with the chronic coughing symp- the initial evaluation in the ED?
toms. She was then started on montelukast and albuterol. Dr. Gonen: We obtained labs and a chest radiograph.
She had never smoked, reported rare social alcohol use, Basic serum chemistries and renal function were normal.
and denied any illicit drug or over-the-counter supple- A complete blood count (CBC) revealed a white blood
ment use. The patient was born in Portugal, but has lived cell count of 12,000 cells/mm3, hematocrit 34%, and
in the United States for 40 years. She is married and lives a platelet count of 201,000/mm3. The most notable fea-
with her husband and two children. ture was the white blood cell differential, which

469
470 L. Gonen et al.

demonstrated 48% neutrophils, 9% lymphocytes, 41% activating factor and prostaglandins, which allow them
eosinophils, and 1% monocytes. The chest radiograph re- to mediate effects on bronchial and vascular smooth mus-
vealed diffuse interstitial pulmonary opacities (Figure 1). cle and affect vascular permeability.
Dr. Chioma Agbo: What is the differential diagnosis When thinking about the differential for eosinophilia
for the eosinophilia noted on the CBC? in the clinical setting, I use the mnemonic ‘‘NAACP,’’
Dr. Gonen: Eosinophils typically account for <5% of which stands for Neoplasm, Asthma/allergy, Adrenal
the peripheral leukocyte count. They are primarily tissue- suppression, Collagen-vascular diseases, and Parasite/
dwelling cells and can be present in extravascular sites in helminthic infections. Hematologic neoplasms such as
100 greater concentrations than in peripheral blood. A the FAB M4 phenotype of acute myelomonocytic leuke-
variety of clinical conditions can lead to an increased mia can result in severe hypereosinophilia, whereas
number of circulating peripheral eosinophils, which can Hodgkin and non-Hodgkin lymphoma can result in
be categorized as mild (351 to 1500 cells/mm3), moderate a modest eosinophilia (5). Asthma can produce a mild eo-
(>1500 to 5000 cells/mm3), and severe (>5000 cells/ sinophilia, whereas helminthic infections can result in
mm3) eosinophilia (1). mild, moderate and, infrequently, severe levels of eosino-
Eosinophils are multi-functional leukocytes that func- philia. Of note, single-celled parasitic infections such as
tion primarily as mediators of humoral immunity. In re- Giardia and Entamoeba do not necessarily produce any
sponse to various stimuli, the eosinophil modulates peripheral eosinophilia (5). Drug allergies and other aller-
immune responses through a diverse series of mecha- gic reactions can also produce a spectrum of peripheral
nisms. The cells contain granules composed of multiple eosinophilia, usually in the mild-to-moderate range. In
compounds, including major basic protein, eosinophil the majority of these cases, the eosinophilia occurs in re-
peroxidase, and eosinophil-derived neurotoxin, which sponse to overproduction of interleukin-5, typically by
have cytotoxic effects on a variety of tissues, both patho- activated CD4+ helper T cells, which differentiate in re-
genic and host. Additionally, they secrete and can trigger sponse to parasitic infections, allergic or hypersensitivity
the release of an array of pro-inflammatory cytokines, reactions, or malignant cells, most frequently adenocarci-
chemokines, and lipid mediators (2). nomas or lymphomas (6).
Accumulating evidence suggests that eosinophils have A careful travel history and investigation for parasitic,
an increasingly prominent role in the immune response to particularly helminthic, and fungal infections, is crucial.
bacterial and viral pathogens (3). Additionally, they are A history of exposures to medications must be elicited,
recognized to have tumoricidal activity, and high infiltrat- as eosinophilia can be one component of a wider drug re-
ing eosinophil counts have been associated with favor- sponse, as in DRESS (drug-induced rash, eosinophilia,
able prognoses in squamous cell esophageal carcinoma, and systemic symptoms) syndrome, or occasionally, the
gastric cancer, and other solid organ malignancies (4). lone presenting sign. A history of weight loss, arthralgias,
In addition, eosinophils contain leukotrienes, platelet- rashes, and lymphadenopathy should be elicited from the
patient. It is important to remember that asthma rarely
elicits more than a mild eosinophilia. A more pronounced
eosinophilic response in conjunction with respiratory
symptoms should prompt consideration of Churg-Strauss
syndrome or allergic bronchopulmonary aspergillosis.
Dr. Emily Brown: What is the relationship between
eosinophilia and adrenal suppression?
Dr. William Binder: Although the mechanism is un-
clear, an association between peripheral eosinophilia and
relative adrenal insufficiency has been reported (7). It has
been suggested that the presence of eosinophilia in criti-
cally ill patients in the intensive care unit is associated
with relative adrenal insufficiency and may indicate the
need for exogenous glucocorticoid supplementation
(7,8). It would seem that, particularly in the critical care
setting, new-onset eosinophilia should be regarded as
a warning sign for insufficient adrenocortical function.
Dr. Eric Nadel: The patient did not travel, although she
was from Portugal originally. It does not seem likely that
Figure 1. Chest radiograph demonstrating bilateral diffuse she would suddenly develop a severe peripheral eosino-
interstitial pulmonary opacities. philia from a parasitic disease. Furthermore, she did not
Eosinophilia and Rash 471

appear to be adrenally suppressed. She does have multi- or computed tomography scanning (Loeffler syndrome),
system disease with skin, respiratory, and neurologic sys- asthma, paranasal sinus abnormalities, and biopsy of
tem involvement. What diagnoses were considered? blood vessels containing extravasated eosinophils (11).
Dr. Gonen: We had no evidence of a neoplasm, and as Diagnosis is typically confirmed with an assay for perinu-
noted, the severity of the eosinophilia with the respiratory clear anti-neutrophil cytoplasmic antibodies (p-ANCA),
symptoms precluded asthma from the final diagnosis. Al- and treatment consists of targeting the respiratory as
though strongyloides can suddenly produce an elevation well as vasculitic symptoms, which often do not follow
in eosinophils, the skin findings and pulmonary infiltrates the same clinical trajectory. Systemic corticosteroids are
suggested that an alternative diagnosis was more likely. highly effective for both sets of symptoms. However, tar-
The multi-system disease suggests a vascular process, geted inhaled or nasal corticosteroids for the respiratory
and the patient has many of the symptoms indicative of symptoms, combined with steroid-sparing cytotoxic drugs
a small-to-medium vessel vasculitis: evidence of pulmo- for the vasculitic component, may be sufficient. Still,
nary infiltrates on chest radiograph (CXR), long-standing many patients have persistent steroid-dependent asthma
sinusitis/rhinitis, paresthesias attributable to mononeuri- despite control of the vasculitic features (5).
tis multiplex, adult-onset asthma, and palpable purpura. A preliminary diagnosis of CSV was made in our pa-
Of the small-/medium-vessel vasculitides, the association tient and she underwent a skin biopsy, which showed ev-
with a moderate-to-severe peripheral eosinophilia is sug- idence of leukocytoclastic vasculitis with numerous
gestive of Churg-Strauss syndrome. Although Wegener extravasated eosinophils. The p-ANCA returned positive
granulomatosis and microscopic polyangiitis should be and the patient was evaluated by the rheumatology and
considered, the lack of renal involvement and predomi- pulmonary services and started on high-dose steroids
nance of lower lung findings in our patient make these di- and cyclophosphamide. Symptoms improved rapidly
agnoses much less likely. and there was resolution of eosinophilia within 72 h.
Dr. Binder: Churg-Strauss vasculitis (CSV) is rather The patient was discharged on high-dose steroids. Unfor-
uncommon. It has an annual incidence of 0.5–6.8 per tunately, 2 months later the patient presented to the ED
million persons. The mean age at the time of diagnosis with weakness and lethargy and was found to have a jeju-
is 48 years. Interestingly, leukotriene receptor antago- nal perforation requiring small bowel resection. Since
nists—which this patient was receiving—may contribute this last admission, the patient has been managed with
to the development or perhaps trigger the onset of Churg- a regimen of tapering steroids and cyclophosphamide,
Strauss syndrome (9). and has done well.
Dr. Gonen: CSV involves the classic triad of asthma,
eosinophilia, and vasculitis. This disease often presents in
three phases, the first of which is a prodromal period that REFERENCES
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for Churg-Strauss vasculitis? What treatments are gener- care unit. J Am Coll Surg 1996;183:589–96.
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