Hansen’s disease in an HIV patient complicated by deep vein thrombosis: a rare complication of thalidomide therapy

ARTICLE

Auteur(s) : Sandra Medeiros¹, Candida Fernandes¹, Nídia Martins², João Machado², Heinz Kutzner³, Ana Afonso⁴, Raquel Vieira¹, Fernando Maltez⁵, Jorge Cardoso¹

¹Dermatology Department, Curry Cabral Hospital, Rua da Beneficiencia n°8, 1069-166 Lisbon, Portugal
²Internal Medicine Department, Curry Cabral Hospital
³Dermatopathologie, Friedrichshafen, Germany
⁴Pathology Department, Curry Cabral Hospital
⁵Infectious Disease Department, Curry Cabral Hospital

A 33-year-old man HIV₁-positive (born in Angola and a resident of Portugal since 1997), treated with high antiretroviral treatment (HAART) since 1999, was diagnosed with borderline leprosy, in a type 2 reaction, and was treated with multibacillary-multidrug therapy, as defined by the WHO, in combination with prednisolone (60 mg/day). Three months later, thalidomide therapy (200 mg/day) was successfully introduced to control severe and recurrent Erythema Nodosum Leprosum (ENL). Six weeks later, the patient developed dyspnea and severe edema in both legs (figure 1).

Homan’s sign was positive and a doppler ultrasonography revealed massive adherent thrombosis in both popliteal and femoral veins, extending to the common iliac vein. Angio-CT was consistent with pulmonary thromboembolism with pulmonary infarction. A potential prothrombotic state was excluded following analysis of erythrocyte and platelet counts, lipidemia, proteins C and S blood levels, search for resistance to activated protein C and antithrombin III levels, lupus anticoagulant, anticardiolipin or anti-β₂-glycoprotein antibodies. Moreover, the patient did not have any other associated thrombotic risk factors, including cigarette smoking, infrequent or heavy hard drug use, immobility, malignancy, heart disease, inflammatory bowel disease, nor a history of previous thrombotic episodes.

Thalidomide therapy was discontinued and the patient was treated with subcutaneous low-molecular weight heparin (enoxaparin 80 mg b.i.d.) and oral warfarin. His condition progressively improved and, after successful anticoagulation therapy, thalidomide was safely restarted and a vena cava filter implanted. One year later the patient remains well, medicated with MB-MDT, thalidomide 200 mg/day, warfarin and prednisolone (10 mg/day).

The first reports of thrombotic complications related to thalidomide therapy were observed in a series of 5 patients, 4 with lupus erythematous and 1 with severe atopic dermatitis (all with thrombotic risk factors) [1]. In addition, thalidomide-triggered thrombosis had been reported in patients with cicatritial pemphigoid, sarcoidosis or aphthosis and during the treatment of malignancy (multiple myeloma and renal-cell carcinoma), particularly when associated with chemotherapy [2-5]. Almost 6500 ENL patients who did not respond to other treatment drugs have been treated with thalidomide. Among them, DVT was reported in only two patients but neither had associated pulmonary thrombosis. The first patient received concomitant dexamethasone-cyclophosphamide pulses [4] and the second was similarly treated with prednisolone [5]. In those cases DVT developed after eight and six weeks post thalidomide therapy, respectively, but in neither case was thalidomide restarted. Interestingly, in our patient this drug was safely restarted two weeks later following successful anticoagulation therapy and one year later the patient is still being treated (with concomitant corticosteroids) without further complications. In retrospect, we recognize that it was possible in our patient that corticotherapy and HIV infection contributed to thrombosis development. In fact, Vetrichevel et al. recently suggested that there was a possibility of thrombosis in patients receiving thalidomide therapy together with corticosteroids i.e., both drugs have a synergistic, suppressive effect on thrombomodulin because they inhibit/decrease the production of TNF-α [5]. Currently available epidemiological evidence also suggests that chronic HIV infection is associated with a two- to ten-fold increased risk of venous thrombosis in comparison to an age-matched control population [6]. The hypercoagulable state present in many HIV patients is associated with an increased risk of haemostatic changes and of superimposed infections. HAART has also been associated with an amplified risk of DVT by some investigators, however, the data are insufficient to support these claims [6].

This case highlights the increased thrombosis risk following thalidomide therapy in an HIV/leprosy co-infected patient without major thrombotic risk factors, even when used as an indicated treatment for ENL, and highlights the possible danger of not diagnosing DVT in an ENL patient since edema of both legs is a common occurrence during this reaction.

Acknowledgements

References

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