Erythema Nodosum Leprosum: Update and challenges on the treatment of a neglected condition

Costa, Perpétua do Socorro Silva; Fraga, Lucas Rosa; Kowalski, Thayne Woycinck; Daxbacher, Egon Luiz Rodrigues; Schüler‐Faccini, Lavínia; Vianna, Fernanda Sales Luiz

doi:10.1016/j.actatropica.2018.02.026

Cited by 45 publications

(46 citation statements)

References 78 publications

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“…In total, 51 documents met the inclusion criteria (Fig 1). This included 23 articles published in scientific journals [1,8,9,11,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41], 3 postgraduate studies sensu stricto [3,4,10], 6 protocols, manuals, or books published by the MoH and WHO [18][19][20][42][43][44], 1 epidemiological bulletin [45], 13 laws [17,[46][47][48][49][50][51][52][53][54][55][56][57], data from 2 databases of the MoH [58,59], and content from 3 internet sites with the domain ".org"…”

Section: Methodsmentioning

confidence: 99%

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The organization, weaknesses, and challenges of the control of thalidomide in Brazil: A review

2020

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The drug thalidomide has resurged in the world market under restrictive conditions for marketing and use. In Brazil, there are still cases of pregnant women using thalidomide even after the implementation of laws that regulate the control of use (Law No. 10.651/2003 and Collegiate Board Resolution No. 11/2011). The objective of this study was to discuss the control of thalidomide use in Brazil, based on a scoping review of the scientific literature, documents, and data from the Ministry of Health. A total of 51 studies and documents related to the following subthemes were selected: (1) organization of access and use of thalidomide in the health system; (2) epidemiological and population characteristics of people affected by leprosy; and (3) occurrence of pregnancy and cases of embryopathy with the use of thalidomide. The results showed that Brazil has no unified information database about thalidomide patients. Furthermore, there is inconsistency in the accreditation of public health centers that dispense this medicine, in a country that has a high consumption of thalidomide in the Unified Health System. A large part of this amount of dispensed medicine is intended for the treatment of erythema nodosum leprosum, mainly in the North, Northeast, and Central-West regions of the country, which are endemic for leprosy. This disease is the only one among the clinical indications of the medicine approved in Brazil that does not have a Clinical Protocol and Therapeutic Guidelines. The control of thalidomide use in Brazil presents historical regulatory failures. These are currently linked to the organization and structure of primary healthcare in the country, as well as to the lack of leadership of the Ministry of Health and National Health Surveillance Agency when it comes to managing the process of control of this use.

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Section: Methodsmentioning

confidence: 99%

“…Leprosy is a chronic infectious disease in which diagnosed cases are classified according to the clinical presentation (indeterminate, tuberculoid, dimorphic, or lepromatous) and the number of cutaneous lesions (multibacillary or paucibacillary) [18,25].…”

Section: Epidemiological Profile Of Leprosy and Population Characterimentioning

confidence: 99%

The organization, weaknesses, and challenges of the control of thalidomide in Brazil: A review

2020

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“…Japan adopted the USA guideline with little modification with respect to the Dose. Regarding Brazil, even though strict special recommendation has been in management protocol of ENL, still cases of embryopathy and baby born with phacomelia is seen 13 . The countries in Europe also follow similar recommendation of dosage of 300 mg and indications as given by the recommendation by USA and its manufacturer 14 .…”

Section: Continue Dosing At Least 2 Weeksmentioning

confidence: 99%

Rationale use of Thalidomide in erythema nodosum leprosum - A non-systematic critical analysis of published case reports

Thangaraju

Venkatesan

Gurunthalingam

et al. 2020

Rev. Soc. Bras. Med. Trop.

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Introduction: Thalidomide is an anti-tumor necrosis factor alpha (TNF-a) drug used mainly in the management of moderate to severe form of Erythema Nodosum Leprosum (ENL). Because of its teratogenic potential it has to be used under proper supervision. Our critical analysis tries to look into the rationale with which it has been used by means of case reports on lepra reaction. Methods: We looked for the case reports between December 2005 to June 2019 in databases like Pubmed, Embase and other relevant resources. We used search words like "erythema nodosum leprosum(ENL)", "thalidomide", "case report" in different combinations to get relevant reports that focus on thalidomide usage atleast once at any time point during management. The information extracted were indication of thalidomide use, dose, response, outcome, complication if any, along with all the demographic details and geographical distribution. Results: We found 41 case reports eligible for analysis.The information was critically evaluated. From the analysis it was found that 7 of the case report mentioned the exact indication, 4 case report showed irrational use of thalidomide in the case of neuritis without use of steroids, 7 showed proper use of Clofazimine prior to thalidomide initiation, 26 case report showed case report of rationale dose range and in 4 case reports clofazimine was used prior to thalidomide along with the rational dose of thalidomide. Conclusions: This analysis helps to guide the rationale use of thalidomide focussing on few important points that anyone should keep in mind while managing a case of ENL.

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“…It was shown that thalidomide and its derivatives can inhibit significantly post-transcriptionally and post-translationally TNFα in vitro through degrading its mRNA. [7,10,15]. On the other hand, clinical data from patients treated with IMiDs showed also a preferential transient but significant increase in other cytokines like interleukin-2 (IL-2), and interferon-gamma (IFNγ) boosting thus the overall immune system.…”

Section: Erythema Nodosum Leprosum (Enl) and Multiple Myeloma (Mm): Cmentioning

confidence: 99%

“…This is mainly because the exact mechanism by which thalidomide triggers its previously documented devastating effects, and its recent protective/healing effects is still elusive despite numerous publications on its effect on cell proliferation, DNA replication, transcription, synthesis and/or function of growth factors, synthesis and/or function of integrins, angiogenesis, chondrogenesis, and cell death [9]. Although there is no confirmed evidence that its therapeutic efficacy in MM and ENL is due to the direct inhibition of angiogenesis through modulating the expression of angiogenic molecules, yet this mechanism is among the most accepted ones [7,10]. This also raises a possibility that the supposed anti-angiogenic effect of thalidomide is secondary to other unknown activity that can be context dependent.…”

Section: Introductionmentioning

confidence: 99%

A Cautious Note on Thalidomide Usage in Cancer Treatment: Genetic Profiling of the TBX2 Sub-Family Gene Expression is Required

Nemer

Khalil

2019

Drug Res (Stuttg)

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Thalidomide is still by excellence the mysterious drug that fascinated, blurred, misled, and changed the scientific community perspectives and policies. It was introduced in the 1950’s as a sedative drug, then shortly withdrawn because of the devastating birth defects that affected tens of thousands throughout more than 40 countries. Back into the market in the mid 1990’s and 2000’s the drug is now being used to treat skin immune-related conditions and some cancers like multiple myeloma. Despite numerous beneficial effects which led to the development of new analogs, its direct mechanisms of action are still elusive. The identification of CRBN and TBX5 as potential direct ligands for this drug have opened the way to better understand its efficiency and its failure.We hereby review these mechanisms and provide evidence that could explain why thalidomide failed to make it as a drug of choice in lung cancer treatment. Linking the genetic signature of TBX2 subfamily in these tumors to their inability to respond properly to thalidomide raises concerns of worsening lung cancer patients’ health if this drug is utilized.

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Erythema Nodosum Leprosum: Update and challenges on the treatment of a neglected condition

Cited by 45 publications

References 78 publications

The organization, weaknesses, and challenges of the control of thalidomide in Brazil: A review

The organization, weaknesses, and challenges of the control of thalidomide in Brazil: A review

Rationale use of Thalidomide in erythema nodosum leprosum - A non-systematic critical analysis of published case reports

A Cautious Note on Thalidomide Usage in Cancer Treatment: Genetic Profiling of the TBX2 Sub-Family Gene Expression is Required

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