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Year : 2021  |  Volume : 15  |  Issue : 1  |  Page : 36-38

Chronic pulmonary thromboembolism in a patient of erythema nodosum leprosum treated with thalidomide and corticosteroid

Department of Medicine, BRD Medical College, Gorakhpur, Uttar Pradesh, India

Date of Submission17-Nov-2021
Date of Decision13-Jan-2022
Date of Acceptance26-Jan-2022
Date of Web Publication13-Apr-2022

Correspondence Address:
Dr. Sangam Singh
SR BRD Medical College, Gorakhpur, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/upjimi.upjimi_5_21

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Thalidomide is the drug of choice for erythema nodosum leprosum (ENL) in men. Its use in patients with multiple myeloma has been reported to cause venous thrombosis. Postulated mechanism is an increase in procoagulant state with the use of thalidomide along with corticosteroids in the underlying hyperviscosity in multiple myeloma. We report a case of superficial and deep vein thrombosis and chronic pulmonary vein embolism in a patient of ENL treated with thalidomide and corticosteroid. An increase in procoagulant state with the use of these two medicines along with a persistent inflammatory state in ENL and an increased risk of venous thrombosis in type 3 hypersensitivity together may have resulted in thrombus formation.

Keywords: Anticoagulant, COVID-19, CPTE, erythema nodosum leprosum, procoagulant, thalidomide, VTE

How to cite this article:
Singh S, Mittal M, Awasthi M, Chaudhary N. Chronic pulmonary thromboembolism in a patient of erythema nodosum leprosum treated with thalidomide and corticosteroid. J Intern Med India 2021;15:36-8

How to cite this URL:
Singh S, Mittal M, Awasthi M, Chaudhary N. Chronic pulmonary thromboembolism in a patient of erythema nodosum leprosum treated with thalidomide and corticosteroid. J Intern Med India [serial online] 2021 [cited 2023 Mar 24];15:36-8. Available from: http://www.upjimi.com/text.asp?2021/15/1/36/343031

[TAG:2]Introduction [/TAG:2]

Thalidomide and corticosteroid use in a patient of erythema nodosum leprosum (ENL) may cause both superficial vein thrombosis and deep vein thrombosis (DVT).[1]

  Case Description Top

A 45-year-old male presented with chief complaints of pain and swelling in the left calf region for the past 45 days, gradually progressive dyspnea on exertion for the past 1 month with increased severity and dyspnea at rest for the past 6–7 days. He had been previously diagnosed with lepromatous leprosy (LL), and treatment with multibaccilarry (MB) regimen (rifampicin 600 mg once monthly, clofazine both daily [50 mg] and monthly [300 g] dose, and dapsone 100 mg daily) for the same was started 1 year back; however, after few months of therapy, he developed ENL. He was prescribed thalidomide 100 mg twice daily and prednisolone with plan to taper medications according to the response of treatment. The patient did not return for follow-up and had been self-medicating with thalidomide and prednisolone in varying doses for the past 9 months. No treatment records were available. The patient did not have any other significant history and denied consumption of tobacco, alcohol, or any other substance. On admission to the emergency, his blood pressure was 100/60 mmHg, pulse rate was 118/min regular, respiratory rate was 26/min at rest. Jugular pressure (JVP) was elevated. CVS examination revealed a systolic murmur in tricuspid area suggestive of tricuspid regurgitation (TR). There was tender hepatomegaly and bilateral pitting type ankle edema. There was marked swelling of the left leg up to mid-thigh with tenderness of calf. His hematological and biochemical profile was unremarkable. Autoimmune markers including antinuclear antibody (ANA) and antiphospholipid antibody (APS) were negative. Since the findings were suggestive of DVT with a suspicion of right heart failure, further investigations were planned. A 2D echo showed grossly dilated Right Atria and Right Ventricle with severe TR and a calculated pulmonary artery pressure of 57 mmHg [Figure 1]. Color Doppler of the left lower limb was also done. There were dilation and intraluminal thickening without color uptake in great saphenous, left distal superficial femoral, popliteal, short sephanous, posterior tibial, and anterior tibial veins, which was suggestive of multiple venous thrombosis (chronic superficial vein thrombosis and DVT). Computed tomography pulmonary angiography was done which showed filling defects in both right and left main pulmonary arterial branch and segmental branches of both lungs, upper and lower lobe and right middle lobe with dilated pulmonary trunk (32 mm) [Figure 2].
Figure 1: Doppler tracing of tricuspid valve showing RVSP 57 mmHg

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Figure 2: (a and b) Computed tomography pulmonary angiography of the patient showing filling defect in right and left main pulmonary artery branches, segmental branches in both lungs upper and lower lobe and right middle lobe causing partial narrowing of the main branches, with dilated pulmonary trunk (32 mm)

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He was diagnosed as chronic pulmonary thromboembolism (CPTE) with multiple venous thrombosis (superficial vein thrombosis and DVT). He was started on rivoroxaban (15 mg BD) and diuretics and his symptoms started to resolve gradually in the next few days and switched to rivoroxaban 20 mg daily single dose with diuretics. On close follow-up of 1–2 months duration, his symptoms subsided and have only mild breathlessness on performing exertion work.

  Discussion Top

DVT is not an uncommon condition with a risk of thrombosis in age below 55 of less than 2% and more than 5% in age more than 65.[2] Factors predisposing to thrombosis are procoagulant mutation, atherosclerosis, diabetes, hypertension, obesity, active cancer, smoking, immobility, major surgery within 3-month period. Chronic systemic inflammation can also predispose to venous thrombosis. Persistent inflammatory state is associated with decreased antithrombin 3, protein c, which are naturally occurring anticoagulants and endothelial dysfunction, which predispose to prothrombotic stage in many conditions such as Becet disease, Rhematoid Arthritis, ANCA (Anti Nuclear Cytoplasmic Antibodies) vasculitis, and APLA (Antiphospholipid antibodies) syndrome.[3]

ENL is an immune-mediated inflammatory complication affecting mainly LL and borderline leprosy (BL). It can present anytime during, before, or after the therapy. It is a clinical diagnosis in a patient of LL/BL.[4] It is considered a type 3 hypersensitivity response and affects multiple organs causing systemic illness. Type 3 hypersensitivity reaction predisposes to venous thrombosis. This has also been identified in the COVID-19 epidemic, where COVID infection leads to a type 3 hypersensitivity. In COVID-19 infection, an increase in the procoagulant activity has been reported.[5],[6] Symptomatic venous theomboembolism (VTE) is seen in up to 25% patients in the intensive care units and anticoagulation with heparin is the recommended modality of treatment.

In a patient of ENL, a type 3 hypersensitivity reaction, the risk of venous thrombosis, is further increased by the use of thalidomide and corticosteroid. Thalidomide is a synthetic glutamic acid derivative; it is also known to inhibit interleukin-6 (IL-6) production and tumor necrosis factor (TNF)-induced nuclear factor-κB activation in Jurkat cells. TNF alpha is known to enhance neoangiogeneis by itself and/or by interaction with IL-6 which is known to be involved in pathogenesis of multiple myeloma; for this property, it is widely used in patients of multiple myeloma.[7],[8],[9],[10] It is highly teratogenic and is absolutely contraindicated in pregnancy/reproductive age group female.[11] Common adverse effects include sedation, constipation, and sensorimotor polyneuropathy. The most serious and life-threatening adverse effect of thalidomide is VTE.[12] The risk of thrombosis increases significantly; if used together with corticosteroid, the risk is nearly 2%–3% alone and 8% if used along with corticosteroid.

The risk of venous thrombosis with thalidomide in multiple myeloma and other cancer is well known, and there are also multiple case reports to this; multiple myeloma in itself is a hypercoagulable state may be another predisposing factor for thrombosis. However, there are only few case reports in the last decades where a patient of ENL taking thalidomide and corticosteroid develops venous thrombosis.

Here, we report a case of a patient with ENL treated with thalidomide and corticosteroid for long time (9 months), with poor follow-up who develops CPTE with DVT and superficial venous thrombosis, who did not had any previous risk factor venous thrombosis.

We can hypothesize that thalidomide and corticosteroid use together may have produced a prothrombotic state in ENL patient where early stages of thrombus have flourished in preexisting persistent systemic inflammatory state of ENL.

Those patients of ENL who are taking thalidomide with corticosteroid together should be monitored regularly for signs and symptoms of DVT and pulmonary embolism .

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.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Palumbo A, Palladino C. Venous and arterial thrombotic risks with thalidomide: Evidence and practical guidance. Ther Adv Drug Saf 2012;3:255-66.  Back to cited text no. 1
Silverstein MD, Heit JA, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ 3rd. Trends in the incidence of deep vein thrombosis and pulmonary embolism: A 25-year population-based study. Arch Intern Med 1998;158:585-93.  Back to cited text no. 2
Emmi G, Silvestri E, Squatrito D, Amedei A, Niccolai E, D'Elios MM, et al. Thrombosis in vasculitis: From pathogenesis to treatment. Thromb J 2015;13:15.  Back to cited text no. 3
Negera E, Walker SL, Girma S, Doni SN, Tsegaye D, Lambert SM, et al. Clinico-pathological features of erythema nodosum leprosum: A case-control study at ALERT hospital, Ethiopia. PLoS Negl Trop Dis 2017;11:e0006011.  Back to cited text no. 4
Abou-Ismail MY, Diamond A, Kapoor S, Arafah Y, Nayak L. The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management. Thromb Res 2020;194:101-15.  Back to cited text no. 5
Roncati L, Ligabue G, Fabbiani L, Malagoli C, Gallo G, Lusenti B, et al. Type 3 hypersensitivity in COVID-19 vasculitis. Clin Immunol 2020;217:108487.  Back to cited text no. 6
D'Amato RJ, Loughnan MS, Flynn E, Folkman J. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci U S A 1994;91:4082-5.  Back to cited text no. 7
Moreira AL, Sampaio EP, Zmuidzinas A, Frindt P, Smith KA, Kaplan G. Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation. J Exp Med 1993;177:1675-80.  Back to cited text no. 8
Keifer JA, Guttridge DC, Ashburner BP, Baldwin AS Jr. Inhibition of NF-kappa B activity by thalidomide through suppression of IkappaB kinase activity. J Biol Chem 2001;276:22382-7.  Back to cited text no. 9
Bataille R, Chappard D, Klein B. The critical role of interleukin-6, interleukin-1B and macrophage colony-stimulating factor in the pathogenesis of bone lesions in multiple myeloma. Int J Clin Lab Res 1992;21:283-7.  Back to cited text no. 10
Zeldis JB, Williams BA, Thomas SD, Elsayed ME. S.T.E.P.S.: A comprehensive program for controlling and monitoring access to thalidomide. Clin Ther 1999;21:319-30.  Back to cited text no. 11
Eleutherakis-Papaiakovou V, Bamias A, Dimopoulos MA. Thalidomide in cancer medicine. Ann Oncol 2004;15:1151-60.  Back to cited text no. 12


  [Figure 1], [Figure 2]


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