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      Asymptomatic pulmonary cryptococcosis presenting with mixed lesions of infiltrative and nodular shadow in an immunocompromised patient

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          Abstract

          Pulmonary cryptococcosis (PC) is a rare fungal lung infection that usually occurs in immunocompromised hosts. We report a rare case of PC with asymptomatic and mixed lesions of infiltrative and nodular shadows. A woman in her 50s with a 7-year history of methotrexate treatment for rheumatoid arthritis (RA) presented with abnormal chest shadows on annual examination. Chest CT revealed two tiny nodules and two infiltrative shadows in the right lower lobe of the lung. We suspected lung cancer, cryptogenic organising pneumonia or RA-interstitial lung disease. However, transbronchial lung biopsy and positivity for serum cryptococcal antigen confirmed the diagnosis of PC. We initiated treatment with fluconazole, which drastically reduced the chest shadows without any adverse events. Since PC can present with several pulmonary shadows, it should be considered as a differential diagnosis of any pulmonary lesion.

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          Most cited references8

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          Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america.

          Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)-infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary cryptococcosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients.
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            Methotrexate and its mechanisms of action in inflammatory arthritis

            Despite the introduction of numerous biologic agents for the treatment of rheumatoid arthritis (RA) and other forms of inflammatory arthritis, low-dose methotrexate therapy remains the gold standard in RA therapy. Methotrexate is generally the first-line drug for the treatment of RA, psoriatic arthritis and other forms of inflammatory arthritis, and it enhances the effect of most biologic agents in RA. Understanding the mechanism of action of methotrexate could be instructive in the appropriate use of the drug and in the design of new regimens for the treatment of RA. Although methotrexate is one of the first examples of intelligent drug design, multiple mechanisms potentially contribute to the anti-inflammatory actions of methotrexate, including the inhibition of purine and pyrimidine synthesis, transmethylation reactions, translocation of nuclear factor-κB (NF-κB) to the nucleus, signalling via the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway and nitric oxide production, as well as the promotion of adenosine release and expression of certain long non-coding RNAs.
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              Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study.

              A high frequency of infections complicating rheumatoid arthritis (RA) has been described in reports of case series. This retrospective longitudinal cohort study was undertaken to compare the frequency of infections in a population-based incidence cohort of RA patients with that in a group of individuals without RA from the same population. RA patients included all members of an incidence cohort of Rochester, Minnesota residents ages >or=18 years who were first diagnosed as having RA between 1955 and 1994. One age- and sex-matched subject without RA was selected for each patient with RA. Study subjects were followed up by review of their entire medical record until death, migration from the area, or study end (January 1, 2000), and details of all documented infections, along with information on potential risk factors for infection, were recorded. Hazard ratios for infections were estimated using stratified Andersen-Gill proportional hazards models, with adjustment for potential confounders. The 609 RA patients and 609 non-RA study subjects (mean age 58.0 years; 73.1% female) were followed up for a mean of 12.7 years and 15.0 years, respectively, reflecting higher mortality among the group with RA. Hazards ratios for objectively confirmed infections, infections requiring hospitalization, and any documented infection in patients with RA were 1.70 (95% confidence interval [95% CI] 1.42-2.03), 1.83 (95% CI 1.52-2.21), and 1.45 (95% CI 1.29-1.64), respectively, after adjustment for age, sex, smoking status, leukopenia, corticosteroid use, and diabetes mellitus. Sites of infection with the highest risk ratios were bone, joints, skin, soft tissues, and the respiratory tract. In this study, patients with RA were at increased risk of developing infections compared with non-RA subjects. This may be due to immunomodulatory effects of RA, or to agents with immunosuppressive effects used in its treatment.
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                Author and article information

                Journal
                BMJ Case Rep
                BMJ Case Rep
                bmjcr
                bmjcasereports
                BMJ Case Reports
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                1757-790X
                2022
                1 December 2022
                1 December 2022
                : 15
                : 12
                : e253113
                Affiliations
                [1 ]departmentRespiratory Medicine , National Hospital Organisation Kyoto Medical Center , Kyoto, Japan
                [2 ]departmentPathology , National Hospital Organisation Kyoto Medical Center , Kyoto, Japan
                Author notes
                [Correspondence to ] Dr Osamu Kanai; okanai.kmc@ 123456gmail.com
                Author information
                http://orcid.org/0000-0003-0736-3317
                http://orcid.org/0000-0002-6148-6820
                http://orcid.org/0000-0002-6902-9085
                Article
                bcr-2022-253113
                10.1136/bcr-2022-253113
                9716928
                36455984
                4eeb9656-679a-4fe8-bd2a-22e62b9aa08d
                © BMJ Publishing Group Limited 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:  http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 17 November 2022
                Funding
                Funded by: the National Hospital Organization’s fiduciary funds;
                Award ID: None
                Categories
                Case Reports: Reminder of important clinical lesson
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                1524
                1560
                1309
                1330
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                508
                523
                Custom metadata
                unlocked

                cryptococcosis,cryptococcus,infections,pneumonia (infectious disease),pneumonia (respiratory medicine)

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