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

Abstract

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.

Combined Pulmonary Tuberculosis with Pulmonary and Pleural Cryptococcosis in a Patient Receiving Ruxolitinib Therapy

“…Although a solid conclusion regarding a relationship between cryptococcosis and ruxolitinib therapy has not been established, a plausible association should be considered based on several case reports and series published in the literature. 4 Although male sex seems to be predominated, a gender preference and this infection have not been confirmed. We believe an immune defect, especially cell-mediated immunity, would rather play a significant role in pathogenesis.…”

“…and Cryptococcus spp. 3,4 At present, there are only two case reports having pulmonary cryptococcosis secondary to ruxolitinib treatment. Both the patients had isolated pulmonary involvement without cryptococcal antigenemia and showed clinical improvement after suspending ruxolitinib and receiving antifungal therapy.…”

“…5,6 Moreover, combined cryptococcosis and other infections in ruxolitinib-treated patients are rare. Only two patients, one with disseminated histoplasmosis and cryptococcal meningitis 7 and cryptococcal fungemia and another with cellulitis caused by Mycobacterium haemophilum, 4 have been reported. Combined pulmonary TB and cryptococcosis with widespread pulmonary involvement, pleural empyema, lymphadenopathy and cryptococcal antigenemia, similar to the present case, has never been reported.…”

“…3 At present, there are only seven case reports regarding ruxolitinib-associated cryptococcal infection. 4 Nevertheless, the co-occurrence of cryptococcosis and other infections is extremely rare. Combined TB and potentially life-threatening cryptococcal infection in a ruxolitinib-treated patient has never been reported.…”

Ruxolitinib inhibits cytokine production by human lung macrophages without impairing phagocytic ability

“…Given the JAK-STAT pathway's role for many cytokines and growth factors involved in the immune response and lung homeostasis, JAK-STAT inhibition can also lead to pulmonary adverse events. Safety data from clinical trials and metaanalyses have highlighted the elevated risk of infectious complications in patients on ruxolitinib (Khalid et al, 2021;Tsukamoto et al, 2018;Wysham and Sullivan, 2013;Sayabovorn and Chongtrakool, 2021). Furthermore, we have reported on suspected cases of ruxolitinib-induced pulmonary alveolar proteinosis in recipients of hematopoietic stem cell allografts (Salvator et al, 2018;Salvator Hélène et al, 2021).…”