Evaluation of the influence of genetic variants in Cereblon gene on the response to the treatment of erythema nodosum leprosum with thalidomide.

BACKGROUND: Erythema nodosum leprosum (ENL) is an acute and systemic inflammatory reaction of leprosy characterised by painful nodules and involvement of various organs. Thalidomide is an immunomodulatory and anti-inflammatory drug currently used to treat this condition. Cereblon (CRBN) protein is the primary target of thalidomide, and it has been pointed out as necessary for the efficacy of this drug in others therapeutics settings. OBJECTIVES: In this study, we aimed to evaluate the influence of CRBN gene variants on the dose of thalidomide as well as its adverse effects during treatment of ENL. METHODS: A total of 103 ENL patients in treatment with thalidomide were included in this study. DNA samples were obtained from saliva and molecular analysis of CRBN gene were performed to investigate the variants rs1620675, rs1672770 and rs4183. Different genotypes of CRBN variants were evaluated in relation to their influence on the dose of thalidomide and on the occurrence of adverse effects. FINDINGS: No association was found between CRBN variants and thalidomide dose variation. However, the genotypes of rs1672770 showed association with gastrointestinal effects (p = 0.040). Moreover, the haplotype DEL/C/T (rs4183/rs1672770/rs1620675) was also associated with gastrointestinal adverse effects (p = 0.015). MAIN CONCLUSIONS: Our results show that CRBN variants affect the treatment of ENH with thalidomide, especially on the adverse effects related to the drug.

Erythema nodosum leprosum associated with minocycline.

Erythema nodosum leprosum is defined by the appearance of tender skin nodules, which can be accompanied by fever, joint pain, neuritis, edema, malaise and/or lymphadenopathy. The authors describe the case of a 19-year-old Angolan black woman, resident in Portugal for the last 10 years, diagnosed with Hansen's disease at the age of 12, irregular with follow-up and non-compliant with treatment. She was referred to our clinic with painful nodules and pustules on the upper limbs, diffuse facial infiltration with pustules and fever, after initiating minocycline with the intention of treating acne. Diagnosis of erythema nodosum leprosum was confirmed by the presence of acid-fast bacilli in the skin smear and also in skin biopsy. Minocycline was suspended and the patient was treated with systemic steroids, with prompt clinical improvement. Our case is reported to alert clinicians to this unusual presentation of erythema nodosum leprosum in a patient treated with highly bactericidal drugs that were not intended to treat Hansen's disease.

Type 2 lepra reaction with HIV1 co-infection: a case report with interesting management implications.

A patient co-infected with leprosy and Human Immunodeficiency Virus (HIV)-type 1 who developed type 2 lepra reaction in the absence of antiretroviral therapy is presented. The reaction responded only after initiating anti retroviral therapy (ART) despite normal CD4+ counts. The present report suggests that type 2 reactions in leprosy and HIV co-infected patients may not always be the typical manifestation of immune reconstitution inflammatory syndrome (IRIS) and stresses the importance of considering concomitant HIV infection in refractory lepra reactions. Extensive research is required into the manifestations of HIV in leprosy patients.

Lepromatous leprosy associated with the use of anti-TNF α therapy: case report.

TNF blockers have been used in the treatment of several types of chronic inflammatory arthritis, especially rheumatoid arthritis. However, many doubts regarding the safety and high risk of infectious diseases in these patients remain. The main objective of this report was to present a case of lepromatous leprosy in a rheumatoid arthritis patient using TNF blockers. The development of adverse events should be rigorously observed, especially those related to infectious agents. Thus, appropriate investigation of skin lesions in patients receiving anti-TNFα therapy is recommended, as the initial clinical manifestation may be unusual, particularly in endemic regions in Brazil.

Hanseníase virchowiana associada ao uso de inibidor do fator de necrose tumoral α: relato de caso / Lepromatous leprosy associated with the use of anti-TNF α therapy: case report

A terapia anti-TNFα tem sido amplamente utilizada em diversas artropatias inflamatórias crônicas, em especial artrite reumatoide (AR). No entanto, há preocupações quanto à segurança e ao risco de doenças infecciosas nos pacientes. O objetivo deste artigo é descrever um caso de hanseníase, forma virchowiana, em paciente com AR em uso de terapia anti-TNFα. Dessa forma, a vigilância dos eventos adversos deve ser rigorosa, especialmente no que diz respeito às doenças infecciosas. É recomendada investigação apropriada de lesões cutâneas em paciente recebendo terapia anti-TNFα, visto que o quadro clínico inicial pode ser inespecífico, especialmente em regiões endêmicas como o Brasil.

TNF blockers have been used in the treatment of several types of chronic inflammatory arthritis, especially rheumatoid arthritis. However, many doubts regarding the safety and high risk of infectious diseases in these patients remain. The main objective of this report was to present a case of lepromatous leprosy in a rheumatoid arthritis patient using TNF blockers. The development of adverse events should be rigorously observed, especially those related to infectious agents. Thus, appropriate investigation of skin lesions in patients receiving anti-TNFa therapy is recommended, as the initial clinical manifestation may be unusual, particularly in endemic regions in Brazil.

Prolonged treatment with recombinant interferon gamma induces erythema nodosum leprosum in lepromatous leprosy patients.

10 patients with borderline and lepromatous leprosy were selected for a prolonged trial with recombinant interferon gamma (rIFN-gamma). Patients received 30 micrograms intradermally for six injections over a 9-d period, and then either 100 micrograms intradermally every 1 mo for 10 mo or every 2 wk for 5 mo (total, 1.2 mg). Erythema nodosum leprosum (ENL) was induced in 60% of the patients within 6-7 mo, as compared with an incidence of 15% per year with multiple drug therapy alone. The mean whole-body reduction in bacterial index over the first 6 mo was 0.9 log units. Cutaneous induration at the intradermal injection sites of greater than or equal to 15 mm predicted the development of a subsequent reactional state. Monocytes obtained from patients receiving the lymphokine demonstrated an increased respiratory burst and a 2.5-5.1-fold increase in tumor necrosis factor alpha (TNF-alpha) secretion in response to agonists. Patients in ENL had an even higher release of TNF-alpha from monocytes as well as high levels of TNF-alpha in the plasma (mean, 2,000 pg/ml). Thalidomide therapy was required to treat the systemic manifestations of ENL. Control of toxic symptoms with thalidomide was associated with a 50-80% reduction in agonist-stimulated monocyte TNF-alpha secretion. IFN-gamma enhanced the monocyte release of TNF-alpha by 3-7.5-fold (agonist dependent) when added to patient's cells in vitro, and this could be suppressed by the in vitro addition of 10 micrograms/ml of thalidomide.