A fatal case of DRESS induced by strontium ranelate associated with HHV-7 reactivation

Drago, Francesco; Cogorno, Ludovica; Broccolo, Francesco; Ciccarese, Giulia; Parodi, Aurora

doi:10.1007/s00198-015-3384-7

Cited by 15 publications

(16 citation statements)

References 18 publications

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“…A search of peer‐reviewed literature yielded total 113 reports of SCAR, including SJS/TEN ( n = 63) and DRESS ( n = 50; Table 3). 7,9,13,25–28 These reported SCAR cases were associated with 5 AOA, including alendronate, ibandronate, risedronate, zoledronic acid and SR. Among 63 cases of SJS/TEN, alendronate ( n = 34) and SR ( n = 13) were identified as the most common offending medications to cause SJS/TEN.…”

Section: Resultsmentioning

confidence: 98%

The risk of anti‐osteoporotic agent‐induced severe cutaneous adverse drug reactions and their association with HLA

Chen

Chu

et al. 2020

Acad Dermatol Venereol

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Background There is increasing use of anti‐osteoporotic agents (AOA) worldwide for prevention or management of patients with osteoporosis. However, there have been reports of severe cutaneous adverse reactions (SCAR) induced by AOA. A recent study showed weak association between HLA and strontium ranelate (SR)‐SCAR. Objective To characterize patients with AOA‐SCAR and investigate the HLA association and utility of in vitro diagnostic methods. Methods We enrolled 16 cases with AOA‐cutaneous adverse drug reactions (cADR), including SCAR (n = 10: 8 with Stevens–Johnson syndrome [SJS] and 2 with drug rash with eosinophilia and systemic symptoms [DRESS]) and maculopapular exanthema (MPE) (n = 6) from Taiwan and Hong Kong. We analysed the clinical characteristics, outcomes, HLA alleles and in vitro testing of AOA‐SCAR, and tolerability to alternative drugs. We further performed literature review and meta‐analysis on the HLA association of AOA‐SCAR. Results Our data showed strontium ranelate is the most common causality of AOA‐SCAR in Asian populations. There was no cross‐hypersensitivity of SR‐SCAR with other AOA. HLA genotyping showed that SR‐SJS was most significantly associated with HLA‐A*33:03 (Pc = 5.17 × 10−3, OR: 25.97, 95% CI: 3.08–219.33). Meta‐analysis showed that HLA‐A*33:03 was associated with SR‐SJS (P = 5.01 × 10−5; sensitivity: 85.7%) in Asians. The sensitivity of lymphocyte activation test (LAT) for identifying the culprit drug of SR‐SJS was 83.3%. Conclusions Strontium ranelate is identified as the most notorious AOA associated with SCAR. The HLA‐A*33:03 genetic allele and LAT testing may add benefits to the diagnosis of SR‐SCAR in patients whose reaction developed while taking multiple drugs.

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Section: Resultsmentioning

confidence: 98%

The risk of anti‐osteoporotic agent‐induced severe cutaneous adverse drug reactions and their association with HLA

Chen

Chu

et al. 2020

Acad Dermatol Venereol

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“…O ranelato de estrôncio é um medicamento não bisfosfonado, alternativa para prevenção e tratamento de fraturas osteoporóticas (DRAGO et al, 2016), utilizado principalmente por mulheres pós-menopausa na redução do risco de fraturas de vértebras e do quadril (NONPROPRIETARY, 2011). O fármaco age de duas formas: na formação óssea, através da replicação do precursor dos osteoblastos e síntese de colágeno em cultura de células ósseas; e na redução da reabsorção óssea, através da diminuição da diferenciação dos osteoclastos e da atividade de reabsorção, promovendo assim um reequilíbrio da renovação óssea a favor da formação do osso (PROTOS, 2015).…”

Section: Discussionunclassified

“…A síndrome DRESS é uma forte reação adversa a medicamentos, se manifestando por meio de rash cutâneo maculopapular difuso, febre, anormalidades hematológicas (leucocitose, eosinofilia ou linfócitos atípicos), e envolvimento sistêmico de múltiplos órgãos, sendo mais frequentemente acometido o fígado (DRAGO et al, 2016). Os fármacos que apresentam um risco muito alto para o desenvolvimento de DRESS são alopurinol, sulfassalazina e minociclina, seguidos pelo RE e dapsona, estes últimos apresentando um risco intermediário (ADWAN, 2017).…”

Section: Discussionunclassified

“…No trabalho de Cacoub et al (2013), foram relacionados 47 casos confirmados de DRESS induzidos pelo RE, sendo que desses, 10 pacientes permaneceram com algum dos sintomas relacionados à síndrome e um veio a óbito, demonstrando a importância do reconhecimento e intervenção precoce frente a esta condição. Não existe padrão-ouro para o diagnóstico de DRESS (DI MEO et al, 2016), sendo utilizados como referência, os critérios diagnósticos propostos pelo Japanese Research Committee on Severe Cutaneous Adverse Drug Reaction (DRAGO et al, 2016). Estes critérios são: rash cutâneo maculopapular após 3 semanas do início do uso da medicação; sintomas clínicos prolongados após descontinuação do uso da droga; linfadenopatia; febre; anormalidades leucocitárias; anormalidade no fígado, parâmetro mais comumente associado às reações cutâneas (CACOUB et al, 2013).…”

Section: Discussionunclassified

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Avaliação da morfologia hepática em ratos norvegicus albinus após administração do ranelato de estrôncio

Oliveira

Pereira

Barreto

et al. 2020

cmbio

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Introdução: o fármaco ranelato de estrôncio (RE) é muito utilizado na terapêutica profilática e no controle da osteoporose. Age sistemicamente diminuindo a reabsorção e aumentando a formação óssea.Objetivo: avaliar a morfologia hepática em ratos norvegicus albinus após administração do RE.Metodologia: estudo experimental com 10 ratos, divididos aleatoriamente em dois grupos, Grupo Controle (GC), sem administração do RE, e Grupo Ranelato de Estrôncio (GRE), ambos acompanhados durante 15 dias, e, em seguida, sacrificados e o fígado de cada animal colocado para fixação no formol a 4% durante 48 horas. Após essa etapa, foram realizados os procedimentos necessários à análise pela microscopia óptica, com lâminas coradas pela hematoxilina & eosina, e picrosirius red.Resultados: nos GC e GRE foram encontradas alterações similares, como reação ductular, dilatação sinusoidal e fibrose perissinusoidal, com intensidades distintas entre os grupos, sendo a reação ductular mais proeminente no GC, e a dilatação sinusoidal e fibrose perissinusoidal mais pronunciada no GRE. Além disso, no GC foram evidenciados achados inflamatórios, como presença de infiltrado inflamatório misto e hiperplasia de células de Kupffer, não visualizados no GRE, implicando numa possível ação anti-inflamatória do RE.Conclusão: pode-se concluir que foram encontrados achados morfológicos no parênquima hepático dos ratos tratados com o RE que os distinguem daqueles não tratados, seja por seu tipo ou intensidade, ainda que esses achados não sejam suficientes para se inferir sobre a incidência de um processo patológico característico.

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“…The most culprit drugs are allopurinol, carbamazepine, and sulfasalazine, and the condition is potentially worsened by β-lactam antibiotics 3 . Concomitantly, DRESS is possibly associated with proliferation of activated CD8+ T lymphocytes directed against viral antigens derived mostly from herpes viruses such as EBV 4 . Astonishingly, in a French report, 16 out of 38 (42%) patients experienced EBV reactivation 5 .…”

Section: Discussionmentioning

confidence: 99%

Drug Reaction with Eosinophilia and Systemic Symptoms Associated with Reactivation of Epstein-Barr Virus and/or Cytomegalovirus Leading to Hemophagocytic Syndrome in One of Two Patients

Liang

Wang

et al. 2018

Ann Dermatol

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Drug reaction with eosinophilia and systemic symptoms (DRESS) is a hypersensitivity reaction characterized by maculopapular rash, exfoliative dermatitis, lymphadenopathy, fever, eosinophilia, and involvement of internal organs. Evidence for reactivation of herpes family viruses has been observed in some DRESS patients, and activated CD8+ T lymphocytes are largely directed against Epstein-Barr virus. Here, we report two cases complicated with this infection. Both patients received antibiotics and non-steroidal anti-inflammatory drugs. These patients manifested clinically with high fever, facial edema, diffuse pruritic erythroderma and maculopapules over the entire body, purpuric rashes in both lower limbs and lymphadenopathy of cervical and inguinal nodes. Laboratory tests revealed abnormal liver function, blood eosinophils, and ferritin levels. The patients recovered completely; however, the female patient developed hemophagocytic syndrome on the 15th day of illness. She developed new itchy rash, and laboratory tests rapidly worsened with fibrinogen levels dramatically reduced to 0.61 g/L. Bone marrow aspiration revealed an increased number of macrophages with hemophagocytosis and a reversed CD4/CD8 ratio of 0.45. These cases suggest that human herpes virus and coagulation function evaluations are necessary in DRESS patients.

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A fatal case of DRESS induced by strontium ranelate associated with HHV-7 reactivation

Cited by 15 publications

References 18 publications

The risk of anti‐osteoporotic agent‐induced severe cutaneous adverse drug reactions and their association with HLA

The risk of anti‐osteoporotic agent‐induced severe cutaneous adverse drug reactions and their association with HLA

Avaliação da morfologia hepática em ratos norvegicus albinus após administração do ranelato de estrôncio

Drug Reaction with Eosinophilia and Systemic Symptoms Associated with Reactivation of Epstein-Barr Virus and/or Cytomegalovirus Leading to Hemophagocytic Syndrome in One of Two Patients

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