Case Report Journal of Clinical Case Reports

Volume 13:05, 2023

ISSN: 2165-7920 Open Access

A Case Report of Invasive Aspergillosis in a Patient Treated

with Ruxolitinib
Arvinder Cheema, Sajjad Ali* and Pranatharthi Chandrasekar
Division of Infectious Diseases, University of Wayne State, Detroit, Michigan, USA

Abstract
Invasive Aspergillosis (IA) is a severe opportunistic infection that typically affects immunocompromised patients. Ruxolitinib is a selective Janus
kinase inhibitor which is used for steroid-refractory acute Graft-vs.-Host Disease (GVHD). Several case reports have described serious opportunistic
infections in Ruxolitinib-treated Primary Myelofibrosis (PMF) patients but no routine antifungal prophylaxis is recommended in these patients. We
present an interesting case of 77-year-old man with previous history of treated MDS several years ago currently on Ruxolitinib for GVHD who was
found to have new cavitary lung lesion on routine imaging.
Keywords: Invasive aspergillosis • Ruxolitinib • GVHD

donor about 5 years ago. His post-transplant course was complicated with
Introduction Graft vs. Host Disease (GVHD) manifesting as bronchiolitis obliterans 1 year
after the transplant and he was treated with high dose steroids, tacrolimus
Ruxolitinib, an inhibitor of Janus-Associated Kinases (JAK) 1 and 2, was and ruxolitinib. His steroids were successfully weaned off and he was only on
initially approved by the FDA in 2011 for the treatment of myelofibrosis and Tacrolimus and ruxolitinib and was doing well.
was later approved for polycythemia vera in 2014 [1]. In the initial randomized
clinical trials, ruxolitinib treatment exerted hematological side effects, mainly On admission patient was afebrile, BP was stable, O2 saturation was
dose-related anemia, thrombocytopenia and neutropenia, while data on around 95% on 2 liters oxygen. Physical examination revealed awake and alert
infections were not initially systematically captured, with the exception of a patient not in severe respiratory distress, chest auscultation revealed bilateral
signal for herpes zoster virus infections [2]. Given the prominent role of coarse crackles at bases. Cardiovascular exam showed no JVD, murmur or
peripheral edema. Neuro exam was non-focal.
JAK/STAT signaling downstream of diverse cytokine receptors, increasing
evidence suggests that ruxolitinib-dependent JAK1/2 inhibition exerts Initial laboratory studies revealed total white blood cell count 3.8, Absolute
immunosuppressive effects, leading to enhanced susceptibility to infection Neutrophil Count (ANC) was 2.4 and hemoglobin was 11, with platelet count
[3]. In the case of fungal infections, the importance of JAK-STAT signaling of 164, serum creatinine was normal. LFTs were also unremarkable. Chest
downstream of type I-III interferons and other cytokines in host immune radiograph showed 4 cm Right Upper Lob (RUL) cavitary lesion (Figure
defense is beginning to unravel. For example, in neutrophils, cell-intrinsic 1). Computed tomography of chest was done which confirmed the RUL
STAT1 activation via IFN-λ/IFNLR1 signaling leads to reactive-oxygen species cavitary lesion. Blood cultures and sputum cultures were sent and patient
production for efficient Aspergillus clearance [4]. was empirically started on broad spectrum antibiotics which were later
discontinued after consultation with infectious disease. Further infectious work
Herein, we present a patient who developed invasive aspergillosis while
receiving ruxolitinib therapy for Graft vs. Host Disease (GVHD). This case
report highlights the high degree of immunosuppression with ruxolitinib that
may lead to invasive fungal infections in immunocompromised host and the
need for heightened vigilance for opportunistic infections while on JAK 1 and 2
inhibitor medications like ruxolitinib.

Case Presentation
A 77-year-old male who presented to emergency department for dry
cough and progressive exertional dyspnea since last few months. His medical
history was notable for Myelodysplastic Syndrome (MDS) and he underwent
Allogenic peripheral blood stem cell transplant from matched unrelated

*Address for Correspondence: Sajjad Ali, Division of Infectious Diseases,

University of Wayne State, Detroit, Michigan, USA; Tel: 16178527101, E-mail:
[email protected] , [email protected]
Copyright: © 2023 Cheema A, et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the
original author and source are credited.
Received: 17 July, 2023; Manuscript No. jccr-23-106736; Editor Assigned: 19
July, 2023; PreQC No. P-106736; Reviewed: 31 July, 2023; QC No. Q-106736;
Revised: 07 August, 2023, Manuscript No. R-106736; Published: 16 August,
2023, DOI: 10.37421/2165-7920.2023.13.1575 Figure 1. Chest radiograph AP view showing 4 cm right upper lobe cavitary lesion.
Cheema A, et al. J Clin Case Rep, Volume 13:05, 2023

up including fungal sputum cultures, sputum for AFB, serum beta D-glucan and Diagnosis of IA can be made by several different methods 3 such as
galactomannan levels were also sent. histopathologic/cytologic and culture examination of tissue and fluid specimens,
by serum and Bronchoalveolar Lavage (BAL) galactomannan assay by chest
Pulmonology was consulted and patient was planned for bronchoscopy
Computed Tomographic (CT) scan and by bronchoscopy with BAL.
with bronchoalveolar lavage, but meanwhile sputum culture report came
back with growth of mold. Patient was started on Voriconazole 6 mg/kg q12 Antifungal prophylaxis against Aspergillosis is recom-
hourly for 2 doses followed by 4 mg/kg q12h and ruxolitinib was held. Serum mended in patients with
aspergillus Ag came back positive 1.52, serum beta-D glucan level was also
significantly elevated to more than 500, cryptococcal antigen was negative. • Hematologic disorders with poorly functioning neutrophils (e.g.,
Patient ultimately underwent bronchoscopy with BAL which confirmed aplastic anemia and variants thereof, MDS), acute leukemia with
diagnosis of Aspergillus Fumigatus. Patient was continued on Voriconazole repeated and/or prolonged neutropenia, or a history of IA prior to
but unfortunately his respiratory status got worse and he was transferred to transplantation.
ICU and started on high flow oxygen followed by non-invasive ventilation with • Chronic immunosuppression associated with GVHD (corticosteroid
BiPAP. He also developed persistent visual hallucinations which were attributed equivalent of >1 mg/kg/day of prednisone for >2 weeks and/or the use
to Voriconazole so it was switched to Isavuconazole. His respiratory status did of other anti-GVHD therapies, such as lymphocyte-depleting agents,
deteriorate further, at this time CT chest was repeated and repeat cultures or Tumor Necrosis Factor α (TNF-α) inhibition, for refractory GVHD.
were sent to look for secondary causes of superimposed bacterial infections.
CT chest showed worsening of cavitary lesions (Figure 2). His repeat blood • Mold colonization pre- or post–lung transplant, mold infections
cultures, sputum cultures and final BAL cultures were negative for bacterial found in explanted lungs, fungal infections of the sinus and single-
infection and sputum for AFB smear was also negative for mycobacteria or lung transplant recipients, recipients receiving immunosuppression
non-tuberculous mycobacteria. augmentation with either thymoglobulin, alemtuzumab, or high-dose
corticosteroids.
He was continued on Isavuconazole. Although his serum fungal markers
level was trending down including beta D glucan and serum galactomannan • Other Solid Organ Transplant (SOT) recipients based on the
levels but clinically patient got worse with encephalopathy and breathing did institutional epidemiology of infection and assessment of individual
not improve so decision was made by the family to deescalate the care and not risk factors [5].
to proceed to endotracheal intubation. Patient was made DNR/DNI followed by Ruxolitinib is a selective Janus kinase inhibitor which was approved
Comfort Measures Only (CMO) and ultimately, he passed away. by Food and Drug Administration in May 2019, for steroid-refractory acute
GVHD in adult and pediatric patients 12 years and older. It is also used for
Results and Discussion intermediate or high-risk myelofibrosis, including PMF, post-polycythemia vera
myelofibrosis and post-essential thrombocythemia myelofibrosis in adults.
Invasive Aspergillosis (IA) is a severe opportunistic infection that typically Several case reports have described serious opportunistic infections
affects immunocompromised patients. Classic risk factors include chronic in Ruxolitinib-treated PMF patients. A thorough literature review was done
neutropenia, hematopoietic stem cell transplant and solid organ transplant, by Palma Manduzio to analyze the relationship among Ruxolitinib, immune
prolonged treatment with high corticoid doses, hematological tumors, cytotoxic system and infections [6]. Infections were recognized early and late after
chemotherapy, the acquired immunodeficiency syndrome and chronic treatment. For bacterial infections; the majority of case reports described
granulomatous disease. Use of certain biologic agents such as Bruton’s disseminated tuberculosis, including Pott’s disease. For viral infections; it was
tyrosine kinase inhibitors and venetoclax, a B-cell leukemia/lymphoma-2 Herpes Simplex Virus (HSV) possible reactivation and Hepatitis B Virus (HBV)
inhibitors also raise the risk of invasive aspergillosis. IA is characterized by reactivation and for fungal and protozoan infections; it was Pneumocystis
progression of the infection across tissue planes. One hallmark of this infection Jiroveci (PJP), Cryptococcus and toxoplasma.
is vascular invasion with subsequent infarction and tissue necrosis.
In another case report, a 30-year-old male with acute myeloblastic
leukemia with complete remission and secondary myelodysplastic syndrome
developed a graft-vs.-host disease treated with Ruxolitinib. The patient
developed IA manifesting as retinal necrosis.

Conclusion
Although our patient was also on Tacrolimus and Ruxolitinib for chronic
GVHD along with physiologic dosage of steroids for adrenal insufficiency,
routine antifungal prophylaxis is not recommended in these patients. More
data is needed to fully understand the effects of these immunosuppressive
agents and whether or not antifungal prophylaxis should be provided in these
patients. Precautions should be implemented to improve adequate screening,
prophylaxis and prompt treatment of infections. Furthermore, the patients
should be warned about the possibility of reactivation of infections.

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Cheema A, et al. J Clin Case Rep, Volume 13:05, 2023

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"Treatment of aspergillosis: Clinical practice guidelines of the Infectious Diseases Chandrasekar. “A Case Report of Invasive Aspergillosis in a Patient Treated with
Society of America." Clin Infect Dis 46 (2008): 327-360. Ruxolitinib.” J Clin Case Rep 13 (2023): 1575.

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