One of the problems physicians can encounter in medicine is when 2 more diseases with a similar presentation coexist simultaneously, making it more likely for the less prominent diagnosis to be missed. Carillo-Rocha and colleagues described such a patient in a recent case study.
The patient was diagnosed with myelodysplastic syndrome and pulmonary arterial hypertension (PAH). “The coexistence of myelodysplastic syndrome and PAH is not a common finding and often goes unnoticed because symptoms such as dyspnea can be confused with the underlying pathology,” the researchers wrote.
Reaching the PAH Diagnosis
The 62-year-old man was referred due to progressive dyspnea from minor exertion, presyncope, and fatigue. Initial examination demonstrated the following:
- Integument paleness.
- Collapsible jugular plethora neck grade II.
- Normal physical respiratory examination.
- Rhythmic heart with reinforcement of the second heart sound and tricuspid insufficiency murmur.
- Nontender hepatomegaly.
- Lower limb edema.
The patient had epilepsy from childhood and type 2 diabetes mellitus and had experienced an ischemic-type cerebrovascular event 4 months earlier. Nine months earlier, he had been diagnosed with myelodysplastic syndrome with multilineage dysplasia by bone marrow aspiration and karyotype; this was treated with danazol 200 mg and hematology follow-up.
His kidney function, thyroid hormone levels, liver function tests, and serum electrolytes were normal, and he was negative for COVID-19. Other laboratory findings were as follow:
- Normochromic normocytic anemia (hemoglobin 9.7 g/dl).
- Decreased reticulocytes (0.1%)
- Arterial blood gas in ambient air: PaO2: 71 mmHg, PaCO2: 44.9 mmHg, sO2: 92.1%, pH: 7.44.
Further investigations followed:
- Electrocardiogram demonstrated sinus rhythm with incomplete right bundle branch block.
- Chest X-ray revealed enlargement of the right pulmonary artery (23 mm).
- Chest angiogram showed pulmonary artery trunk of 34 mm, pulmonary artery / ascending aorta ratio of 1.3, cardiomegaly, and hepatomegaly. “Egg and banana sign”, typical of PAH, was seen due to the head displacement of the pulmonary artery.
- Transthoracic echocardiogram showed a dilated right atrium and a hypertrophic right ventricle.
- Respiratory function tests with bronchodilator challenge were normal.
- Six-minute walking test was 330 meters (63% of predicted). The patient experienced a significant drop in oxygen saturation (80%) and the Borg scale registered moderate dyspnea.
- Right heart catheterization reported mean pulmonary arterial pressure of 28 mm Hg and peripheral vascular resistance of 3.3 Wood units. Pulmonary artery wedge pressure was 8 mm Hg.
A diagnosis of precapillary PAH was made. The patient was started on phosphodiesterase inhibitor-type monotherapy 3 times a day and demonstrated clinical improvement.
Myelodysplastic Syndrome and PAH
Robert P, Hasserjian of the Massachusetts General Hospital Department of Pathology explained: “Myelodysplastic syndromes consist of clonal bone marrow diseases associated with ineffective hematopoiesis, manifesting as morphologic dysplasia in hematopoietic elements and peripheral cytopenias.”
Of the different variants of myelodysplastic syndrome, the most common is myelodysplastic syndrome with multilineage dysplasia. This is when dysplasia is observed in at least 10% of the primitive cells of a few cell types in the bone marrow. According to the World Health Organization, myelodysplastic syndrome can be classified as primary if no underlying cause is found and secondary if one exists.
Read more about PAH etiology
And how are myelodysplastic syndrome and PAH connected? Carillo-Rocha and colleagues wrote, “Often patients with myelodysplastic syndrome have evidence of chronic disseminated intravascular coagulation, resulting in micro thrombosis in the pulmonary circulation with secondary PAH.”
With regards to PAH diagnosis, Kim and George explained, “At present, a diagnosis of PAH is only accepted as confirmed (or excluded) by right heart catheterization. PAH is defined as a mean pulmonary arterial pressure greater than or equal to 20 mmHg at rest. PAH is defined as precapillary PAH with mean pulmonary arterial pressure greater than or equal to 20 mm Hg, pulmonary artery wedge pressure less than or equal to 15 mmHg, and pulmonary vascular resistance greater than 3 Wood units.”
Read more about PAH diagnosis
According to this definition, the patient in this case study can be clearly diagnosed with precapillary PAH. Hence, we could deduce that the patient’s myelodysplastic syndrome predisposed him to developing PAH. Myelodysplastic syndrome can raise the pulmonary arterial pressure via various mechanisms, causing a hypermetabolic state that results in a high cardiac output. Both diseases are rare: the annual incidence of myelodysplastic syndrome is around 1 to 8 cases per 100,000 population, while the annual incidence of (idiopathic) PAH is around 0.2 cases per 100,000 population.
Given the coexistence of both diseases, the prognosis is poor. Carillo-Rocha wrote, “PH in patients with myelodysplastic syndrome confers a poor prognosis and can result in death. Treatment with specific drugs is usually uncertain; the report of clinical cases using bosentan has shown favorable results.”
The main takeaway from this case study is that physicians should be aware of the link between hematological diseases and PAH. In hematological diseases such as myelodysplastic syndrome, PAH is a complication that can result in increased morbidity and mortality. An abnormal echocardiogram should alert physicians to the possibility of a PAH diagnosis and compel them to conduct further investigations, such as right heart catheterization.
Carrillo-Rocha DL, Roldan-Valadez E, Cueto-Robledo G, Garcia-Cesar M, Cueto-Robledo HD. Review of the myelodysplastic syndrome as a cause of group V pulmonary arterial hypertension: an orphan disease in an orphan pulmonary hypertension group. Curr Probl Cardiol. 2022;101110. doi:10.1016/j.cpcardiol.2022.101110
Kim D, George MP. Pulmonary hypertension. Med Clin North Am. 2019;103(3):413-423. doi:10.1016/j.mcna.2018.12.002
Hasserjian RP. Myelodysplastic syndrome updated. Pathobiology. 2019;86(1):7-13. doi:10.1159/000489702