Severe ARDS due to Ruxolitinib discontinuation syndrome: case presentation and literature review.

Discontinuation of Ruxolitinib (RUX), a JAK1/JAK2 inhibitor, can induce symptom-relapse and even life-threatening adverse events. Due to increasing use of RUX, this so-called RUX discontinuation syndrome (RDS) is becoming more prevalent. To create better awareness for this potentially fatal syndrome, we present a case of an adult male who developed a fatal RDS. Our case presented with acute respiratory failure and a shock-like syndrome, with the need for mechanical ventilation, venovenous-extracorporeal membrane oxygenation (ECMO) and vasopressors. Respiratory symptoms quickly improved after initiation of corticosteroids, but disease course was complicated with a spontaneous spleen rupture leading to hemorrhagic shock and eventually death. This case report is the first case of severe RDS necessitating vv-ECMO and complicated with spleen rupture. Clinicians should be aware of this potentially lethal syndrome as it can present acutely but be effectively treated with corticosteroids and/or restarting JAK-inhibitors.

Houthuys JF ，Wilmer AP ，Peetermans M ，Meersseman P ，Devos T ... -  《Heliyon》

Light and shade of ruxolitinib: positive role of early treatment with ruxolitinib and ruxolitinib withdrawal syndrome in patients with myelofibrosis.

Baek DW ，Cho HJ ，Lee JM ，Kim J ，Moon JH ，Sohn SK ... -  《-》

Rapid Hepatomegaly From Ruxolitinib Discontinuation Syndrome.

Ruxolitinib (RUX) is a Food and Drug Administration-approved Janus Kinase (JAK) inhibitor shown to be effective in improving hypercatabolic symptoms and splenomegaly in patients with myelofibrosis (MF). RUX therapy provides symptomatic benefits for MF patients but is often discontinued for various reasons including worsening cytopenias. Ruxolitinib Discontinuation Syndrome (RDS) involves an acute cytokine-storm rebound phenomenon that can manifest as an acute relapse of symptoms, worsening splenomegaly, respiratory distress, systemic inflammatory response syndrome, or disseminated intravascular coagulopathy. We present the case of a patient with JAK2-positive post-polycythemia vera MF, whose RUX therapy was discontinued due to an active gastrointestinal (GI) bleed and worsening cytopenias. The patient had recently started azacitidine and was on the drug combination prior to hospitalization. The patient developed what appears to be the first case of acute onset accelerated massive hepatomegaly, a previously undescribed clinical manifestation of RDS. Although rare, medical professionals should maintain a high suspicion of RDS in hospitalized patients following the discontinuation of RUX.

van Rensburg RJ ，Hale S ，Calara A ，Dabb K ，Dandamudi U ，Desai P ... -  《-》

Favorable COVID-19 course despite significant comorbidities in a ruxolitinib-treated patient with primary myelofibrosis.

COVID-19 carries a high risk of severe disease course, particularly in patients with comorbidities. Therapy of severe COVID-19 infection has relied on supportive intensive care measures. More specific approaches including drugs that limit the detrimental "cytokine storm", such as Janus-activated kinase (JAK) inhibitors, are being discussed. Here, we report a compelling case of a 55-yo patient with proven COVID-19 pneumonia, who was taking the JAK1/2 inhibitor ruxolitinib in-label for co-existing primary myelofibrosis for 15 months prior to coronavirus infection. The patient had significant comorbidities, including chronic kidney disease, arterial hypertension, and obesity, and our previous cohort suggested that he was thus at high risk for acute respiratory distress syndrome (ARDS) and death from COVID-19. Since abrupt discontinuation of ruxolitinib may cause fatal cytokine storm and ARDS, ruxolitinib treatment was continued and was well tolerated, and the patient´s condition remained stable, without the need for mechanical ventilation or vasopressors. The patient became negative for SARS-CoV-2 and was discharged home after 15 days. In conclusion, our report provides clinical evidence that ruxolitinib treatment is feasible and can be beneficial in patients with COVID-19 pneumonia, preventing cytokine storm and ARDS.

Koschmieder S ，Jost E ，Cornelissen C ，Müller T ，Schulze-Hagen M ，Bickenbach J ，Marx G ，Kleines M ，Marx N ，Brümmendorf TH ，Dreher M ... -  《-》

The impact of venovenous extracorporeal membrane oxygenation on cytokine levels in patients with severe acute respiratory distress syndrome: a prospective, observational study.

Burrell AJC ，Lubnow M ，Enger TB ，Nanjayya VB ，Philipp A ，Malfertheiner MV ，Lunz D ，Bein T ，Pellegrino VA ，Müller T ... -  《Critical Care and Resuscitation》