Acquired skin hyperpigmentation following intravenous polymyxin B treatment: a cohort study

Mattos, Karen Prado Herzer; Lloret, Gustavo Rafaini; Cintra, Maria Letícia; Gouvêa, Isabela Romão; Betoni, Taís Rodrigues; Mazzola, Priscila Gava; Moriel, Patrícia

doi:10.1111/pcmr.12468

Cited by 24 publications

(30 citation statements)

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“…2 Polymyxin B intravenous treatment has been associated with SH, predominantly of the head and neck. [3][4][5] According to Mattos et al,5 the incidence of SH is 15%; it is not related to sun exposure as the exposed skin of the shoulders and trunk is spared. The first changes typically appear on the third day of treatment as gradual and diffuse darkening of the head and neck skin in shades of brown.…”

Section: What Is Known and Objectivementioning

confidence: 99%

Skin hyperpigmentation following intravenous polymyxin B treatment associated with melanocyte activation and inflammatory process

et al. 2017

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What is known and objective Polymyxins were widely used until the 1960s; however, they fell into disfavour owing to their toxicity. The subsequent growth of infections caused by multidrug-resistant Gram-negative bacteria has led to renewed use of this class of antimicrobials in clinical practice. Acquired skin hyperpigmentation (SH) following intravenous polymyxin B treatment has been previously reported, but little is known about its pathogenesis, clinical course and treatment. To improve understanding of these issues, we conducted a prospective study of adult patients receiving intravenous polymyxin B treatment. Methods Patients receiving intravenous polymyxin B treatment were followed throughout the course of treatment. Clinical, dermatoscopic, histologic and immunohistochemical skin properties of patients who presented with SH were studied. Results and discussion Skin hyperpigmentation was noted in 8% of patients (n=20/249); however, clinical, dermatoscopic, histologic and immunohistochemical examinations were performed only in three patients for whom the consent of relatives was obtained. Histologic and immunohistochemical findings showed an abundant melanocyte-pigmented dendritic network. Langerhans cells' hyperplasia and dermal IL-6 overexpression were also found, presumably for an inflammatory process due to polymyxin B use. As polymyxin B causes the release of histamine, which is known for its melanogenic effect, it is possible that skin darkening is associated with this inflammatory mediator. What is new These clinical and dermatoscopic findings contribute to a better understanding of how the pigmentary reaction manifests following intravenous polymyxin B treatment. Conclusion We concluded that hyperpigmentation due to intravenous polymyxin B treatment is associated with an inflammatory process and subsequent melanocyte activation. Although the pigmentary disorder neither influences the outcome of the therapy nor warrants discontinuation of treatment, it nevertheless considerably affects the patient's quality of life.

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Section: What Is Known and Objectivementioning

confidence: 99%

Skin hyperpigmentation following intravenous polymyxin B treatment associated with melanocyte activation and inflammatory process

et al. 2017

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“…3 Maintenance of standardized doses is not always possible because of the nephrotoxicity that affects approximately 60% of patients receiving intravenous administration. 6 Currently, there is a lack of data with few studies available on the association of the clinical outcomes of treatment with polymyxin B and the occurrence of adverse drug events. 4,5 Nephrotoxicity and neurotoxicity are wellknown adverse reactions related to the use of polymyxin B, although SH was also recently reported as a side effect.…”

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confidence: 99%

“…4,5 Nephrotoxicity and neurotoxicity are wellknown adverse reactions related to the use of polymyxin B, although SH was also recently reported as a side effect. 6 Currently, there is a lack of data with few studies available on the association of the clinical outcomes of treatment with polymyxin B and the occurrence of adverse drug events. This study aims to evaluate real medical practice, assess the clinical outcomes of a very toxic antimicrobial treatment and highlight the consequences of its inadequate use on bacterial resistance and public health in general.…”

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confidence: 99%

Polymyxin B clinical outcomes: A prospective study of patients undergoing intravenous treatment

et al. 2019

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Summary What is known and objective Polymyxins, especially polymyxin B, has become the last line of therapy against Gram‐negative pathogens’ carbapenemase producers. However, given increasing use of polymyxin B in clinical settings its therapeutic value has been evaluated worldwide due to its toxic effects. The aim of this study was to assess the efficacy and safety of antimicrobial therapy with polymyxin B in patients with multidrug‐resistant bacteria in Brazil. Methods This was a prospective cohort study in a 403‐bed academic tertiary care centre, located in the countryside of Brazil. Patients receiving polymyxin B intravenous treatment for at least 72 hours were eligible for the study. Antimicrobial susceptibility, adverse reactions and clinical outcomes were submitted for descriptive analysis. Main outcomes measure the following: Patients' conditions following treatment (Treatment Success, Mortality, Treatment Failure, Inadequate Empiric Treatment or Indeterminate Response) and toxicities induced by polymyxin B (nephrotoxicity and skin hyperpigmentation). Results and discussion Among 247 patients, treatment success was achieved in 25.1%, while mortality was observed in 32.8%. Empirical therapy was prescribed for 26.3% of the patients. Nephrotoxicity was reported in 40.5%. The carbapenemase producer, Klebsiella pneumonia, was the bacterium most associated with mortality (22.2%). Conclusions Even though polymyxin B is currently the main therapy against carbapenemase producers, its use demands robust criteria to lead to positive clinical outcomes.

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“…Hyperpigmentation caused by medications are reported in the literature and more recently the reaction has been described for polymyxin B 4 , affecting adults 4,7,8 and pediatric/neonatal patients 6,7,8,9 , whose percentage varying between 8-15% of the patients who presented the reaction with the use of the drug in two studies 2,5 .…”

Section: Discussionmentioning

confidence: 99%

“…Men were most affected by this reaction 2,[4][5][6][7][8][9] , however, skin color seems to have more relevance in this process. In one study only 11.1% of patients with hyperpigmentation were Caucasian, who would be classified among the I-III 10 phototypes on the Fitzpatrick scale, however, this same group represented 78.4% of the patients who did not present skin hyperpigmentation 5 , while most reports describe patients who would be classified from phototype IV (Table 2).…”

Section: Discussionmentioning

confidence: 99%

Dois casos de hiperpigmentação cutânea induzido pela polimixina B

et al. 2019

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Introdução: O processo de hiperpigmentação cutânea envolve mecanismos bioquímicos e imunológicos que estimulam a melanogênese e apesar da nefrotoxicidade consistir na reação adversa mais relevante da polimixina B, o antimicrobiano também está associado a esta alteração. Relato do caso: Caso1: paciente masculino diagnosticado com Linfoma de Hodgkin, que desenvolveu hiperpigmentação cutânea após iniciar tratamento com meropenem, anidulafungina e polimixina B devido a um quadro de choque séptico. Caso 2: paciente masculino admitido na UTI por rebaixamento do nível de consciência e suspeita de IAMCSST, diagnosticado com endocardite e pericardite, que também apresentou hiperpigmentação cutânea durante terapia com anfotericina B e polimixina B. Conclusão: Após criteriosa avaliação da ordem cronológica e medicamentos utilizados pelos pacientes, concluímos que a polimixina B desencadeou a hiperpigmentação em ambos. Por fim, baseado ao mecanismo desta reação e aos achados científicos, estudos clínicos que possam evidenciar um provável efeito farmacológico com o uso de antagonistas H2 são necessários.

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Acquired skin hyperpigmentation following intravenous polymyxin B treatment: a cohort study

Cited by 24 publications

References 8 publications

Skin hyperpigmentation following intravenous polymyxin B treatment associated with melanocyte activation and inflammatory process

Skin hyperpigmentation following intravenous polymyxin B treatment associated with melanocyte activation and inflammatory process

Polymyxin B clinical outcomes: A prospective study of patients undergoing intravenous treatment

Dois casos de hiperpigmentação cutânea induzido pela polimixina B

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