Coccidioidomycosis in Patients Treated With Ruxolitinib

Kusne, Yael; Kimes, Kathryn E; Feller, Fionna; Patron, Roberto L.; Banacloche, Juan Gea; Blair, Janis E.; Vikram, Holenarasipur R.; Ampel, Neil M.

doi:10.1093/ofid/ofaa167

Cited by 9 publications

(4 citation statements)

References 10 publications

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“…From those results, the most common opportunistic pathogens that benefit from these immune defects include bacteria, mycobacteria, viruses, and fungi, similar to those seen in human immunodeficiency virus (HIV)-related infections. The causative pathogens in previously reported cases of ruxolitinib-associated infections are summarized in Table 1 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Consistent with the foregoing, it appears that Cryptococcus and nontuberculous mycobacteria were able to simultaneously infect our patient due to the downregulation of multiple cytokines.…”

Section: Discussionsupporting

confidence: 84%

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Cryptococcal fungemia and Mycobacterium haemophilum cellulitis in a patient receiving ruxolitinib: a case report and literature review

2021

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Background Ruxolitinib is a novel oral Janus kinase inhibitor that is used for treatment of myeloproliferative diseases. It exhibits potent anti-inflammatory and immunosuppressive effects, and may increase the risk of opportunistic infections. Here, we report a rare case of Cryptococcus neoformans and Mycobacterium haemophilum coinfection in a myelofibrosis patient who was receiving ruxolitinib. Case presentation A 70-year-old Thai man who was diagnosed with JAK2V617F-mutation-positive primary myelofibrosis had been treated with ruxolitinib for 4 years. He presented with cellulitis at his left leg for 1 week. Physical examination revealed fever, dyspnea, desaturation, and sign of inflammation on the left leg and ulcers on the right foot. Blood cultures showed positive for C. neoformans. He was prescribed intravenous amphotericin B deoxycholate with a subsequent switch to liposomal amphotericin B due to the development of acute kidney injury. He developed new onset of fever after 1 month of antifungal treatment, and the lesion on his left leg had worsened. Biopsy of that skin lesion was sent for mycobacterial culture, and the result showed M. haemophilum. He was treated with levofloxacin, ethambutol, and rifampicin; however, the patient eventually developed septic shock and expired. Conclusions This is the first case of C. neoformans and M. haemophilum coinfection in a patient receiving ruxolitinib treatment. Although uncommon, clinicians should be aware of the potential for multiple opportunistic infections that may be caused by atypical pathogens in patients receiving ruxolitinib.

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Section: Discussionsupporting

confidence: 84%

“…Types of organisms and infections in previously reported cases of ruxolitinib-associated infection[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] …”

mentioning

confidence: 99%

Cryptococcal fungemia and Mycobacterium haemophilum cellulitis in a patient receiving ruxolitinib: a case report and literature review

2021

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“…There has been one case report of DCM in a patient receiving vedolizumab (α4β7 integrin) for Crohn's disease [43] and one diagnosed with a pulmonary nodule while receiving abatacept (CTLA4) [39]. In a recent case series of 135 patients receiving ruxolitinib (JAK1/JAK2 inhibitor) [44], 8 developed symptomatic coccidioidomycosis; 4 had coccidioidomycosis preceding ruxolitinib, and each had primary pulmonary disease while on therapy. The remaining 4 developed disseminated disease between 1 month and 1 year from therapy initiation.…”

Section: Exogenous Risks Of Infection and Disseminated Diseasementioning

confidence: 99%

The Known and Unknown “Knowns” of Human Susceptibility to Coccidioidomycosis

Hsu

2024

JoF

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Coccidioidomycosis occurs after inhalation of airborne spores of the endemic, dimorphic fungus, Coccidioides. While the majority of individuals resolve the infection without coming to medical attention, the fungus is a major cause of community-acquired pneumonia in the endemic region, and chronic pulmonary and extrapulmonary disease poses significant personal and economic burdens. This review explores the literature surrounding human susceptibility to coccidioidomycosis, including chronic pulmonary and extrapulmonary dissemination. Over the past century of study, themes have emerged surrounding factors impacting human susceptibility to severe disease or dissemination, including immune suppression, genetic susceptibility, sex, pregnancy, and genetic ancestry. Early studies were observational, frequently with small numbers of cases; several of these early studies are highly cited in review papers, becoming part of the coccidioidomycosis “canon”. Specific genetic variants, sex, and immune suppression by TNF inhibitors have been validated in later cohort studies, confirming the original hypotheses. By contrast, some risk factors, such as ABO blood group, Filipino ancestry, or lack of erythema nodosum among black individuals, are repeated in the literature despite the lack of supporting studies or biologic plausibility. Using examination of historical reports coupled with recent cohort and epidemiology studies, evidence for commonly reported risk factors is discussed.

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“…In recent years, ruxolitinib prescription has been expanded to various diseases due to its immunosuppressive and anti-inflammatory effects. Ruxolitinib has been effective against steroid-refractory graft-versus-host disease 4 and coccidioidomycosis 5 . During the coronavirus disease 2019 (COVID-19) pandemic, ruxolitinib was used to treat severe COVID-19 cases in a single-blind, randomised controlled trial involving multi centres 6 .…”

Section: Introductionmentioning

confidence: 99%

Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice

Lee

Hamzah

Leong

et al. 2021

Sci Rep

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Ruxolitinib is the first janus kinase 1 (JAK1) and JAK2 inhibitor that was approved by the United States Food and Drug Administration (FDA) agency for the treatment of myeloproliferative neoplasms. The drug targets the JAK/STAT signalling pathway, which is critical in regulating the gliogenesis process during nervous system development. In the study, we assessed the effect of non-maternal toxic dosages of ruxolitinib (0–30 mg/kg/day between E7.5-E20.5) on the brain of the developing mouse embryos. While the pregnant mice did not show any apparent adverse effects, the Gfap protein marker for glial cells and S100β mRNA marker for astrocytes were reduced in the postnatal day (P) 1.5 pups' brains. Gfap expression and Gfap+ cells were also suppressed in the differentiating neurospheres culture treated with ruxolitinib. Compared to the control group, adult mice treated with ruxolitinib prenatally showed no changes in motor coordination, locomotor function, and recognition memory. However, increased explorative behaviour within an open field and improved spatial learning and long-term memory retention were observed in the treated group. We demonstrated transplacental effects of ruxolitinib on astrogenesis, suggesting the potential use of ruxolitinib to revert pathological conditions caused by gliogenic-shift in early brain development such as Down and Noonan syndromes.

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Coccidioidomycosis in Patients Treated With Ruxolitinib

Cited by 9 publications

References 10 publications

Cryptococcal fungemia and Mycobacterium haemophilum cellulitis in a patient receiving ruxolitinib: a case report and literature review

Cryptococcal fungemia and Mycobacterium haemophilum cellulitis in a patient receiving ruxolitinib: a case report and literature review

The Known and Unknown “Knowns” of Human Susceptibility to Coccidioidomycosis

Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice

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