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Leprosy Mailing List – April 15, 2020
Ref.: (LML) Corona and leprosy
From: Sergio Palma, Rio de Janeiro, Brazil
Dear Pieter,
We thank Dr Ben Naafs for stimulating a discussion about thalidomide in the context of COVID-19 (Ref.: Corona and leprosy, April 9th). The Brazilian Society of Dermatology has been acting in Brazil for 108 years, with over 9,400 associates, and has always been actively involved in leprosy control in the country. In addition, thalidomide is a drug used for a number of different dermatological conditions, such as prurigo nodularis, pyoderma gangrenosum, lupus erythematosus, actinic prurigo, lichen planus, among others (1).
Thalidomide has anti-inflammatory and immunomodulatory effects, inhibiting TNF-α and regulating the production or the role of different cytokines. In this context, it is a drug that could potentially have a beneficial effect on the modulation of inflammatory response triggered by the SARS-CoV-2 virus, mainly mediated by proinflammatory macrophages. Indeed, it has been suggested that blocking TNF may benefit those patients (2).
On the other hand, the use of thalidomide has been associated with thromboembolic phenomena, both in leprosy (3) and in other diseases (4), especially multiple myeloma (5), a serious complication that has been also associated with a poor prognosis of COVID-19 (6). Therefore, a hypothetical benefit of thalidomide against this new disease should be seen as controversial from the beginning. Some light may arise from patients already taking the drug who might come to develop COVID-19; in such situation, thromboembolism must be closely watched.
Contrarily, there is no doubt about the beneficial effect of thalidomide for ENL control (7), and this is why we totally disagree with the guidelines published by the Brazilian Society of Hansen's Disease, which considered that patients treated with thalidomide, regardless of the dose, should be seen as a high-risk group to develop severe forms of COVID-19, thus recommending to adjust its dosage or to even to discontinue the antireactional treatment. Apparently, this recommendation was based on isolated case reports of pulmonary toxicity associated with lenalidomide, a different drug.
We are unaware of any publication that has linked the use of thalidomide to greater susceptibility to viral infections or with lung toxicity. In contrast, thalidomide was proven to be effective in a randomized trial to improve cough and respiratory quality of life in patients suffering from idiopathic pulmonary fibrosis (8). The drug has also been useful to prevent actinic pulmonary fibrosis (9) and bleomycin-induced pulmonary fibrosis in experimental models (10).
The interruption of thalidomide for patients suffering from ENL will cause serious consequences, as the development of even more intense leprosy reactions that may lead to hospitalization at a time of possible reduction in the number of available beds, generating further overload on the health system, when the current priority is the treatment of severe COVID-19 cases.
Thus, we are in agreement with WHO/ILEP/GPZL guidelines, which recommended that treatment of reactions should continue and that the benefit from the steroids will usually outweigh the small increase in the risk of acquiring COVID-19. We want to add that treatment with thalidomide must also be maintained and that thalidomide users will possibly present a negligible increased risk to COVID-19 due to its pharmacological effects.
Finally, we would like to take this opportunity to kindly request you to divulge our Society's Guidelines for leprosy control activities in the context of the pandemic COVID-19, which was published in March 23rd (please find it attached an English version).
Best Regards,
Sérgio Palma – President of SBD
Egon Daxbacher – Treasurer of SBD
Sandra Durães – Coordinator of Leprosy Department at SBD
Gerson Penna – Advisor of Leprosy Department at SBD
Lucia Martins Diniz - Advisor of Leprosy Department at SBD
Maurício Lisboa Nobre - Advisor of Leprosy Department at SBD
References
1. Azulay Rubem David. Talidomida: indicações em Dermatologia. An. Bras. Dermatol. 2004; 79( 5 ): 603-608.
2. Shi Y, Wang Y, Shao C et al. COVID-19 infection: the perspectives on immune responses. Cell Death Differ. 2020 Mar 23 [Epub ahead of print].
3. Vernal S, Brochado M, Bueno-Filho R et al. Anti-phospholipid syndrome in seven leprosy patients with thrombotic events on corticosteroid and/or thalidomide regimen: insights on genetic and laboratory profiles. Revista da Sociedade Brasileira de Medicina Tropical, 2018; 51(1), 99-104.
4. Cesbron E, Bessis D, Jachiet M et al. Risk of thromboembolic events in patients treated with thalidomide for cutaneous lupus erythematosus: A multicenter retrospective study. J Am Acad Dermatol. 2018 Jul; 79(1):162-165.
5. Zangari M, Anaissie E, Barlogie B et al. Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy. Blood. 2001; 98:1614–1615.
6. Cui S, Chen S, Li X et al. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr 9. [Epub ahead of print]
7. Walker SL , Balagon M, Darlong J et al. ENLIST 1: An International Multi-centre Cross-sectional Study of the Clinical Features of Erythema Nodosum Leprosum. PLoS Negl Trop Dis. 2015 Sep; 9(9): e0004065.
8. Haraf R, Flora AS and Assaly R. Thalidomide as a Cough Suppressant in Idiopathic Pulmonary Fibrosis. Am J Ther. 2018 Nov/Dec;25(6):e687-e688.
9. Bian C, Qin WJ, Zhang CY et al. Thalidomide (THD) alleviates radiation induced lung fibrosis (RILF) via down-regulation of TGF-β/Smad3 signaling pathway in an Nrf2-dependent manner.
10. Tabata C, Tabata R, Kadokawa Y et al. Thalidomide prevents bleomycin-induced pulmonary fibrosis in mice. J Immunol. 2007 Jul 1;179(1):708-14.
LML - S Deepak, B Naafs, S Noto and P Schreuder
LML blog link: http://leprosymailinglist.blogspot.it/
Contact: Dr Pieter Schreuder << editorlml@gmail.com
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