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\title{Hypereosinophilic Syndrome Mimicking COVID-19 Disease}



\author[1]{Pembe Derin Oygar}%
\author[1]{Berna Oguz}%
\author[1]{mustafa cemaloğlu}%
\author[1]{tekin aksu}%
\author[1]{yasemin ozsurekci}%
\affil[1]{Hacettepe University Faculty of Medicine}%


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  \date{May 14, 2024}


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To the editor:

Hypereosinophilic syndrome is a diverse group of disorders with
eosinophilia and end-organ damage. Any organ system may be involved,
cardiopulmonary and neurologic diseases being the most common causes of
morbidity and mortality\textsuperscript{1}. HES is more commonly seen in
adults but has been reported in pediatric population as well. Formerly
pediatric patients who present with marked eosinophilia (1500/mm3) for
at least 6 months' duration without other known causes of eosinophilia
and with evidence of organ involvement used to be diagnosed as HES.
Recently the International Cooperative Working Group on Eosinophil
Disorders (ICOG-EO) defined HES as blood hypereosinophilia (HE) or
tissue HE associated with HE-related organ damage irrespective of time
(precluding the absence of an alternative diagnosis for the organ
dysfunction)\textsuperscript{2} . 2019 ended with the emergence of a
novel coronavirus, SARS-Co-V2, leading to a pandemic with a high attack
rate causing COVID-19 disease. Since the beginning of pandemic pulmonary
findings defined for COVID-19 are considered to be pathognomonic hence,
chest tomography is suggested to be superior to polymerase chain
reaction tests in the diagnosis of adult COVID-19
patients\textsuperscript{3}.

16 -year- old female referred with the diagnosis of COVID-19 pneumonia
and myocarditis. She had worsening cough for the last 10 days, initially
diagnosed with pneumonia and started on antibiotics. Upon becoming
dyspneic and feverish she was hospitalized. Computed tomography (CT) of
the chest was reported to be suggestive of COVID-19 with bilateral
peripheral consolidation areas and nodules with surrounding ground glass
appearance (Figure 1a,b). Her COVID-19 PCR was negative for 3 times
during this 10-day course of illness. Echocardiography revealed findings
consistent with myocarditis. She was started on favipravir and
intravenous immunoglobulin (IVIG) and referred to our hospital for
potential extracorporeal membrane oxygenation (ECMO) requirement. On
admission, her physical examination revealed tachycardia, tachypnea and
hypoxia, subcostal and suprasternal retractions and bilaterally
diminished breath sounds, no hepatosplenomegaly was present.

Laboratory findings were white blood cell count (WBC) 29200
/mm\textsuperscript{3}(4100-11200), absolute eosinophil count (AEC)
16370 /mm\textsuperscript{3} (100-500), hemoglobin (Hb) 12.5 g/dl
(11.7-15.5 ) , thrombocyte count 406 000/
mm\textsuperscript{3}(159000-388000), peripheral blood smear revealed
68\% eosinophils. Cardiac enzymes were elevated; brain natriuretic
peptide (BNP) 725.4 pg /ml (0-100), troponin -I 3769.5 ng/l (8.4-18.3),
creatinine kinase myocardial band (CK-MB) 26.1\selectlanguage{greek}µ\selectlanguage{english}g/l (0.6-6.3) , alanine
transferase (ALT) 31U/l, (\textless{}39)aspartic acid transferase (AST)
44 U/l (\textless{}56). Electrocardiogram (ECG) was at sinus rhythm,
with normal PR and QT intervals. The voltages were suppressed, and there
was no negative T-waves. Echocardiogram was repeated confirming
myocarditis with a hypokinetic area on the apex of left ventricle. COVID
PCR test repeated and found to be negative on two occasions obtained at
24 hours interval. She had been diagnosed with asthma for the last 2
years with frequent attacks and was on combined formoterol and
budesonide inhaler treatment. There was no history of sinusitis or rash.
Abdominal ultrasonography was normal. Stool examination revealed no
parasites, there was no history of drugs. CMV, Herpes, EBV, Hepatitis B
and C, Parvovirus serology and PCR were negative. Anti-neutrophil
cytoplasmic antibody (ANCA) was also negative and total Ig E was 1796
mg/dl (1.31-165), Vitamin B12 level was 227ng/L (200-590). Bone marrow
aspiration revealed increased numbers of eosinophilic precursor cells
(14\% eosinophilic metamyelocytes) as well as mature eosinophils (34\%)
with no malignant cell and no cytogenetic abnormalities (Figure 1). Bone
marrow biopsy showed a normocellular marrow with increased eosinophilic
precursors, except reticulin fibrosis and mast cells. Flow cytometric
evaluation showed no atypical population, JAK2V617F mutation was
negative, and leukemia defining translocations including BCR/ABL1,
CBFB/MYH11 were negative. Clonal hyper-eosinophilia associated
rearrangements including PDGFRA, PDGFRB, FGFR1 were also negative. Upon
re-evaluation of chest CT with these clinical and laboratory findings,
radiology department stated that HES or Churg-Strauss should be
considered as potential diagnoses as well as COVID-19 (Figure 2).
CT-angiography showed no findings of vasculitis or vascular occlusion.

The patient was given high flow oxygen support, started on teicoplanin,
meropenem and clarithromycin, carvedilol, enalapril and pulse methyl
prednisolone treatments. On the 5th day of treatment WBC and AEC
declined to 8200 /mm\textsuperscript{3} and 0
/mm\textsuperscript{3}respectively. Corticosteroid dose was tapered
gradually; at the end of 4 weeks WBC and AEC were
14300/mm\textsuperscript{3} and 0/mm\textsuperscript{3} respectively.
After treatment, control chest CT showed regression of lung involvement
findings ( Figure 3).

Since December 2019 the whole world is struggling with a novel corona
virus pandemic and COVID-19, the disease it leads to. With a high attack
rate and so many deaths, it is quite understandable that COVID-19 has
become number one priority diagnosis in everyday practice. The
sensitivity and practicality of molecular tests has been an issue since
the beginning of the pandemic and chest CT is claimed to be more
accurate than PCR \textsuperscript{4} in the diagnosis of COVID-19 which
seems to set a bias in the interpretation of chest CTs. On the other
hand, whether CT is superior in diagnosis of COVID-19 in pediatric
patients who experience viral pneumonia more frequently compared to
adults is yet to be determined. Whether there is a pandemic or not one
has to remember that the art and creativity of medicine is to evaluate
every symptom and sign on a patient-based approach in order to make the
correct diagnosis.

\textbf{References:}

\begin{enumerate}
\tightlist
\item
  Weller PF, Bubley GJ. The idiopathic hypereosinophilic
  syndrome.~\emph{Blood} ~1994; 83:2759-79. {[}\emph{PubMed}{]}
\item
  Simon H, Rothenberg ME, Boschner BS, et al. Refining the definition of
  hypereosinophilic syndrome\emph{J Allergy Clin Immunol} . 2010;126(1):
  45--49. doi:10.1016/j.jaci.2010.03.042.
\item
  Xie X, Zhong Z, Zhao W, Zheng C, Wang F, Liu .CT for typical 2019-nCoV
  pneumonia: relationship to negative RT-PCR testing. Radiology J Chest
  2020; \url{https://doi.org/10.1148/radiol.2020200343}
\item
  Ye, Z., Zhang, Y., Wang, Y.~\emph{et al.}~Chest CT manifestations of
  new coronavirus disease~~~~~~ 2019 (COVID-19): a pictorial
  review.~\emph{Eur
  Radiol}~(2020).~\url{https://doi.org/10.1007/s00330-}~ 020-06801-0
\end{enumerate}\selectlanguage{english}
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