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 Table of Contents  
Year : 2023  |  Volume : 3  |  Issue : 2  |  Page : 72-75

Hydropneumothorax – Rare presentation of pulmonary embolism with methylenetetrahydrofolate reductase mutation with hyperhomocysteinemia

Department of Pulmonary Medicine, TNMC and BYL Nair Hospital, Mumbai, Maharashtra, India

Date of Submission07-Nov-2022
Date of Acceptance06-Dec-2022
Date of Web Publication02-May-2023

Correspondence Address:
Dr. Unnati Desai
Department of Pulmonary Medicine, TN Medical College and BYL Nair Hospital, Mumbai - 400 008, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jalh.jalh_35_22

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Pulmonary embolism (PE) is a relatively common cardiovascular event with high early mortality rates. Many risk factors play a role in the causation of PE including acquired as well as inherited. Methylenetetrahydrofolate reductase (MTHFR) gene mutation is one of the inherited etiologies for PE which cause hyperhomocysteinemia which can lead to PE. This in turn can result in secondary complications such as pneumothorax or hydropneumothorax, which are rare presentations of PE. Hereby, we present this unique case of a 17-year-old boy who presented with a hydropneumothorax which on further evaluation was found to be a complication of bilateral PE which was due to hyperhomocysteinemia with MTHFR A1298C mutation. Hence, we present this unique case with rare presentation as well as rare etiology for PE. This shows the significance for considering PE as one of the differentials in situations such as cavitations, pneumo or hydropneumothoraces, and hyperhomocysteinemias.

Keywords: Hyperhomocysteinemia, methylenetetrahydrofolate reductase mutation, pulmonary embolism

How to cite this article:
Kunjumon SA, Neenu N, Utpat KV, Desai U, Raj K A, Sable SB. Hydropneumothorax – Rare presentation of pulmonary embolism with methylenetetrahydrofolate reductase mutation with hyperhomocysteinemia. J Adv Lung Health 2023;3:72-5

How to cite this URL:
Kunjumon SA, Neenu N, Utpat KV, Desai U, Raj K A, Sable SB. Hydropneumothorax – Rare presentation of pulmonary embolism with methylenetetrahydrofolate reductase mutation with hyperhomocysteinemia. J Adv Lung Health [serial online] 2023 [cited 2023 Jun 11];3:72-5. Available from: https://www.jalh.org//text.asp?2023/3/2/72/375538

  Introduction Top

Pulmonary embolism (PE) is a common cardiovascular event with high early mortality rates.[1] Knowledge about its risk factors will help the physician to choose appropriate and timely diagnostic and prophylactic strategies.[2] The interplay between acquired and genetic risk factors leads to the development of PE. Methylenetetrahydrofolate reductase (MTHFR) gene mutation is one of the inherited causes of PE which can cause hyperhomocysteinemia. PE can cause pulmonary infarction leading to pneumothorax or hydropneumothorax. We present a case of a 17-year-old boy who presented with hydropneumothorax on evaluation and was found to have PE due to hyperhomocysteinemia with MTHFR A1298C mutation. Hereby, we present this unique case with a rare presentation and rarer etiology for PE.

  Case Report Top

A 17-year-old boy presented with complaints of 1-month history of cough which was predominantly dry with no diurnal or seasonal variation, right-sided chest pain which was pleuritic type, and sudden onset of breathlessness corresponding to Modified Medical Research Council grade 4 for the last 1 day. It was not associated with orthopnea, paroxysmal nocturnal dyspnea, or wheeze. There were no complaints of fever or leg swelling. There was no history of any trauma. He had no significant family or past medical history. On general examination, pulse rate was 132/min, respiratory rate of 32/min, blood pressure of 110/60 mm of mercury, and pulse oximetry saturation of 88% on room air. On respiratory system examination, he had reduced movements on palpation on the right side of the chest along with hyper resonant notes on percussion and decreased breath sounds on auscultation on the right lung fields. On investigation, the chest radiograph (CXR) was suggestive of right-sided hydropneumothorax [Figure 1]. Contrast-enhanced computed tomography (CT) thorax was done which was suggestive of right-sided hydropneumothorax with collapsed lung [Figure 2]. Emergency pigtail catheter insertion was done [Figure 3]. His complete blood count showed microcytic hypochromic anemia with a hemoglobin count of 8.5 g/dL. Other routine blood tests were normal. Pleural fluid on routine microscopic examination was straw-colored, exudative, and lymphocyte predominant. Pulmonary tuberculosis was ruled out by negative sputum and pleural fluid gene Xpert and acid-fast bacilli smear and culture reports which did not detect or grow Mycobacterium tuberculosis. Other infective etiologies were ruled out by normal white blood cell counts and negative sputum and pleural fluid gram stain and culture reports.
Figure 1: Chest radiography suggestive of right-sided hydropneumothorax

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Figure 2: CECT thorax suggestive of right-sided hydropneumothorax with collapsed lung. CECT: Contrast-enhanced computed tomography

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Figure 3: Chest radiography suggestive of right-sided hydropneumothorax with pigtail in situ

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Figure 4: CTPA showing filling defects (red arrows) in bilateral distal basal segmental branches of bilateral lower lobe suggestive of pulmonary thromboembolism. CTPA: Computed tomography pulmonary angiography

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Further, as our patient was tall and thin, Marfan syndrome is one of the differential diagnoses for spontaneous pneumothorax. It was ruled out by clinical evaluation, normal ophthalmic and normal two-dimensional echocardiography evaluation, and no pleural blebs on CT. A CT pulmonary angiogram was done in view of persistent tachycardia and chest pain as well as a significantly high simplified Wells score and elevated D-dimer (3800 ng/ml) value. It was suggestive of bilateral lower lobe chronic pulmonary thromboembolism with right hydropneumothorax with an underlying collapsed lung [Figure 4]. His bilateral lower limb Doppler study was normal. In view of PTE in a young patient, we evaluated him with a thrombophilia profile which was suggestive of MTHFR A1298C homozygous mutation. His serum homocysteine levels were elevated and other levels were negative. Hence, we diagnosed the patient as a case of right-sided secondary hydropneumothorax due to PTE with hyperhomocysteinemia with MTHFR gene mutation. The patient was managed with pigtail insertion and oral anticoagulants and homocysteine supplementation. He improved clinically and the pigtail was removed after full lung expansion. He was discharged on oral anticoagulants, oral folic acid, pyridoxine, and cyanocobalamin supplementation

  Discussion Top

PE is a relatively common acute cardiovascular disease with high early mortality rates which, despite advances in diagnosis and treatment over the past 30 years, have not changed significantly.[1] High clinical suspicion together with timely application of risk stratification scores such as modified Wells score is needed for diagnosis in cases of PE with atypical presentation. Risk factors for PE include age, history of venous thromboembolism, active malignancy, or another disabling condition such as heart or respiratory failure, congenital or acquired coagulation disorders, hormone replacement therapy, and oral contraception.[1] In recent decades, multiple inherited causes have been recognized as the causative factors for PTE which include protein C deficiency, protein S deficiency, factor V Leiden mutation, antithrombin III deficiency, and hyperhomocysteinemia. Hyperhomocysteinemias have an increased risk of systemic thromboembolic events.[3] Elevated levels of homocysteine are associated with an increased risk for blood clots in the veins. Homocysteine is formed in the body when the amino acid methionine, which is a building block of the proteins in our food and body is metabolized and excreted in the urine. During this breakdown process, the homocysteine can be recycled to be reused to build other proteins. For the recycling process, Vitamins B12, B6, and folate are needed.[4] For efficient recycling, the enzyme MTHFR is also required. Inherited mutations in the gene can lead to the production of an MTHFR enzyme that is not optimally active and as a result may lead to elevated homocysteine levels. Humans have 2 MTHFR genes, one inherited from each parent. Some people have a genetic mutation in one or both of their MTHFR genes. Those with a mutation in one MTHFR gene are called heterozygous for the MTHFR mutation and if mutations are present in both genes, those are called homozygous mutations. Heterozygous mutation from a medical perspective is irrelevant. MTHFR C677T mutation is the most common MTHFR mutation. Another common MTHFR mutation is MTHFR A1298C.[5] Our patient had an MTHFR A1298C mutation. The occurrence of thromboembolism due to hyperhomocysteinemia can be shown by various hypotheses such as the toxic effect of homocysteine on vascular endothelium and defective methionine metabolism due to aberration in methylation of the cell membrane and cell DNA.[6] This cause of PE is highly significant as this can be rectified with the supplementation of high doses of multivitamins, including folate, Vitamin B6, and Vitamin B12.[7]

Majority of patients with PE tend to complain primarily of acute-onset or worsened resting dyspnea. Other presentations include tachypnea, dyspnea, chest pain, hemoptysis, and syncope. Minor embolisms involving the peripheral arteries can even present as pulmonary infarction syndrome. Chest radiography or CT of the chest can show peripheral triangular- or wedge-shaped opacities.[1] Cavitatory pulmonary infarction accounts for approximately 1% of all nontuberculous cavities. Cavitation after pulmonary infarction may result from either aseptic necrosis of the infarcted lung or from septic necrosis of the infarcted lung or from secondary bacterial infection with subsequent abscess formation.[8] Pleural-based cavities can rupture and can result in pneumothorax or hydropneumothorax. However, the incidence of pneumothorax or hydropneumothorax secondary to pulmonary infarction has not been precisely estimated in the literature.

Ours is a rare case with rare etiology and having this rarer presentation of hydropneumothorax which has resulted from pulmonary thromboembolism that had happened due to hyperhomocysteinemia which in turn was due to MTHFR mutation. In our case, a homozygous mutation of MTHFR A1298C leads to hyperhomocysteinemia and endothelial injury resulting in thrombus formation leading to PE. The cavitation and hydropneumothorax were secondary to pulmonary infarction. Our case shows the significance of giving high clinical suspicion for PE as well as the use of scores such as modified Wells score for the timely diagnosis and early management or prevention of PE cases, especially those with atypical or rare presentations, particularly in emergency departments. Our case stresses the fact that PE should be kept as one of the differentials for cavitations, pneumothorax, or hydropneumothorax. Moreover, inherited causes for PE should always be suspected and worked up meticulously when the patient belongs to a younger age group and has no other predisposing factors for PE.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Bĕlohlávek J, Dytrych V, Linhart A. Pulmonary embolism, part I: Epidemiology, risk factors and risk stratification, pathophysiology, clinical presentation, diagnosis and nonthrombotic pulmonary embolism. Exp Clin Cardiol 2013;18:129-38.  Back to cited text no. 1
Cho KH, Jeong MH, Sim DS, Hong YJ, Kim JH, Ahn Y, et al. Pulmonary thromboembolism due to severe hyperhomocysteinemia associated with a methyltetrahydrofolate reductase mutation. Korean J Intern Med 2013;28:112-5.  Back to cited text no. 2
Wells PS, Anderson DR, Bormanis J, Guy F, Mitchell M, Gray L, et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet 1997;350:1795-8.  Back to cited text no. 3
Moll S, Varga EA. Homocysteine and MTHFR mutations. Circulation 2015;132:e6-9.  Back to cited text no. 4
Varga EA, Sturm AC, Misita CP, Moll S. Cardiology patient pages. Homocysteine and MTHFR mutations: Relation to thrombosis and coronary artery disease. Circulation 2005;111:e289-93.  Back to cited text no. 5
Engbersen AM, Franken DG, Boers GH, Stevens EM, Trijbels FJ, Blom HJ. Thermolabile 5,10-methylenetetrahydrofolate reductase as a cause of mild hyperhomocysteinemia. Am J Hum Genet 1995;56:142-50.  Back to cited text no. 6
Naurath HJ, Joosten E, Riezler R, Stabler SP, Allen RH, Lindenbaum J. Effects of vitamin B12, folate, and vitamin B6 supplements in elderly people with normal serum vitamin concentrations. Lancet 1995;346:85-9.  Back to cited text no. 7
Libby LS, King TE, LaForce FM, Schwarz MI. Pulmonary cavitation following pulmonary infarction. Medicine (Baltimore) 1985;64:342-8.  Back to cited text no. 8


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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