Acute chest syndrome in sickle cell disease/HBE patient, A case report
Ibrahim Khameesa, Waail Rozia,
Mohamed A Yassinb
a Department of Internal medicine, Hamad Medical
Corporation, Doha/Qatar.
b Department of Medical Oncology/ Hematology Section.
Hamad Medical Corporation. Doha/Qatar
Corresponding author:
D. Ibrahim Khamees,
Department of Internal Medicine
Hamad Medical Corporation,
Doha/Qatar.
PO BOX 3050
Ibrahim_khamees@hotmail.com
+974 55169599
D. Waail Rozi,
Department of Internal Medicine
Hamad Medical Corporation,
Doha/Qatar.
PO BOX 3050
Waail.rozi@gmail.com
+974 50041728
D. Mohamed A Yassin
Department of Internal Medicine
Hamad Medical Corporation,
Doha/Qatar.
PO BOX 3050
yassinmoha@gmail.com
+974 55037393
Key words: sickle cell disease, hemoglobin S, hemoglobin E, HBSE, acute
chest syndrome
Key clinical message: The presented case will shed some light on one of
the rarest complications of HBSE disease which is acute chest syndrome,
and will highlight the management of that complication.
Abstract
Hemoglobin S (HBS) and hemoglobin E (HBE) are common hemoglobinopathies,
but combined heterozygosity of HBS and HBE (HBSE) is relatively a rare
disease. Most reports suggest that HBSE is generally benign condition
with few reported complications like vaso-occlusive crises, acute chest
syndrome and bone necrosis. In this report we describe a 17-year-old
male patient presenting with acute chest syndrome treated with exchange
transfusion.
Introduction
HBS, which is the hemoglobin type responsible for sickle cell disease,
is localized mostly in Africa, India and some parts of the Middle East
[1]. In sickle cell disease, there is homozygosity of HBS mutation,
and in stressful conditions like infections hemoglobin will be
deoxygenated and HBS will polymerize in the vessels, leading to multiple
complications including vaso-occlusive pain and acute chest syndrome
[2]. HBE is found mostly in Southeast Asia. Patients who are
homozygous for HBE generally have mild anemia and are clinically
asymptomatic, whereas individuals who are heterozygotes for HBE and Beta
thalassemia for example have a variable clinical spectrum ranging from
mild to very severe disease requiring regular blood transfusion [3].
Due to increasing rate of migrations and marriages happening between
different races, Increasing numbers of patients with compound
heterozygosity for HBS and HBE are found worldwide, and scarce data
about the disease and the complications related to it have been
reported.
Acute chest syndrome is considered the most common cause of death in
sickle cell disease patients. It is defined by the presence of new
radiographic pulmonary infiltrates as well as fever and respiratory
symptoms. Management ranges from pain control and fluid replacement in
mild disease to simple transfusion or exchange transfusion in more
severe presentations [4]. Acute chest syndrome mostly occurs in
Patients who are homozygous for HBS, however there are few reported
cases of acute chest syndrome happening in patients with HBSE disease
[5,6].
Case report
A 17-year-old male patient who is known to have HBSE disease, presented
with a history of chest and back pain for few days prior to admission.
He also complained of non-productive cough for 2 days but denied fever.
On examination, his heart rate was 110 and his respiratory rate was
around 25 with normal temperature of 36.9. On chest exam, he had left
basal crackles with decreased air entry.
Initial laboratory investigations are mentioned in table 1.
Table 1: laboratory investigations
His chest xray showed left retrocardiac and left lower lung zone opacity
suggesting left lower lobe consolidation, shown in (Figure 1)
Figure 1: chest x-ray
The patient was diagnosed to have community acquired pneumonia and
started on ceftriaxone 1000 mg daily for seven days and azithromycin 500
mg daily for three days as inpatient. The patient did not improve and
started requiring oxygen two days after admission, he became more
tachypneic and tachycardiac so he was shifted to the medical intensive
care unit and started on non-invasive ventilation, COVID-19 and all
cultures were negative. Hematology recommended to do hemoglobin
electrophoresis for the patient considering the possibility of acute
chest syndrome. Hemoglobin electrophoresis was done and it showed the
findings in table 2.
Table 2: Hemoglobin electrophoresis
The patient underwent a session of exchange transfusion, then during the
following days the patient improved gradually and was discharged from
the hospital 4 days after the exchange transfusion. He was commenced on
folic acid 5 mg daily and hydroxyurea 500 mg twice a day as a
prophylaxis, with close follow up in hematology clinics.
Discussion
HBS molecule is a result of the replacement of the hydrophilic glutamic
acid by the hydrophobic valine residue at position 6 in the beta globin
chain. This mutation results in the sickle shape of the affected
hemoglobin molecule, which changes to that shape when deoxygenated in
certain situations like infections [7]. This process can causes
several acute complications like acute vaso-occlusive pain, acute chest
syndrome, stroke and priapism [8,9]. Sickle cell disease can result
in some chronic complications as well, for example it can cause chronic
anemia, chronic bone pain and avascular necrosis [10].
HBSE disease is considered a benign condition in general. However, David
Masiello et al., in their review described 26 patients with HBSE
heterozygosity, 9 of them had clear complications attributed to sickling
ranging from acute painful episodes to splenic thrombosis and acute
chest syndrome, all of these patients were above 20 year-old. They
suggested also that patients with HBSE disease should be followed and
managed in the same way like patients with Hb S/b1+thalassemia [11].
Sickling associated complications in HBSE disease are thought to occur
more commonly in people aged more than 20, but some reports described
young patients with this disease who had severe complications as well. A
review done in turkey (An area with a high rate of consanguinity)
reported 20 patients with HBSE disease, two of them had mild
vaso-occlusive crises and one who was diagnosed with the disease at age
of 11 and was started on hydroxyurea, suffered from cerebrovascular
stroke later on [12]. Another case report described a young girl who
was diagnosed with HBSE disease at the age of 5 due to leg pain, where
the images suggested bone infarction. At the age of 7 she had a fatal
massive bone marrow embolism [13].
Acute chest syndrome is uncommon to happen in patients with HBSE
disease. Upon reviewing the literature, we found 5 cases of HBSE disease
complicated by acute chest syndrome [5,6,14,15,16]. In one case
report, a 66 year-old patient with HBSE disease suffered from bone
infarction and acute chest syndrome which improved with simple blood
transfusion of 2 units along with supportive care and was discharged on
hydroxyurea [5]. Another case report presented a 22 year-old patient
with HBSE disease diagnosed with parvovirus B19 infection and acute
chest syndrome, also received simple blood transfusion and improved
[6]. A third paper described a 24 year-old patient with HBSE disease
admitted with acute chest syndrome and managed with supportive therapy
only [16]. Our patient was admitted with acute chest syndrome which
did not resolve with antibiotics, and required exchange transfusion,
after which the patient improved significantly and was discharged on
hydroxyurea.
Conclusion
HBSE disease is thought to be a benign condition, but more and more
reports are being published describe complicated HBSE disease. Increased
number of cases of HBSE disease is expected with the increasing rate of
migrations and interracial marriages. This warrants early follow up of
such patients and early recognition and management of the complications
of this disease especially the severe ones like acute chest syndrome.