Primary cutaneous histoplasmosis in an immunocompromised patient with long-standing rheumatoid arthritis

Lise, Michelle Larissa Zini; Staub, Henrique Luiz

doi:10.1590/1806-9282.62.09.816

Cited by 2 publications

(4 citation statements)

References 9 publications

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“…Histoplasma capsulatum is the causative agent of endemic mycoses in the United States and South America (1–3). While immunocompetent patients cope with the infection, immunocompromised patients often develop a progressive disease leading to death if untreated (4–6). H.…”

Section: Introductionmentioning

confidence: 99%

The HIF-1α/LC3-II Axis Impacts Fungal Immunity in Human Macrophages

et al. 2019

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The fungal pathogen Histoplasma capsulatum causes a spectrum of disease, ranging from local pulmonary infection to disseminated disease. The organism seeks residence in macrophages, which are permissive for its survival. Hypoxia-inducible factor 1α (HIF-1α), a principal regulator of innate immunity to pathogens, is necessary for macrophage-mediated immunity to H. capsulatum in mice. In the present study, we analyzed the effect of HIF-1α in human macrophages infected with this fungus. HIF-1α stabilization was detected in peripheral blood monocyte-derived macrophages at 2 to 24 h after infection with viable yeast cells. Further, host mitochondrial respiration and glycolysis were enhanced. In contrast, heat-killed yeasts induced early, but not later, stabilization of HIF-1α. Since the absence of HIF-1α is detrimental to host control of infection, we asked if large amounts of HIF-1α protein, exceeding those induced by H. capsulatum, altered macrophage responses to this pathogen. Exposure of infected macrophages to an HIF-1α stabilizer significantly reduced recovery of H. capsulatum from macrophages and produced a decrement in mitochondrial respiration and glycolysis compared to those of controls. We observed recruitment of the autophagy-related protein LC3-II to the phagosome, whereas enhancing HIF-1α reduced phagosomal decoration. This finding suggested that H. capsulatum exploited an autophagic process to survive. In support of this assertion, inhibition of autophagy activated macrophages to limit intracellular growth of H. capsulatum. Thus, enhancement of HIF-1α creates a hostile environment for yeast cells in human macrophages by interrupting the ability of the pathogen to provoke host cell autophagy.

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Section: Introductionmentioning

confidence: 99%

The HIF-1α/LC3-II Axis Impacts Fungal Immunity in Human Macrophages

et al. 2019

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“…A small number of case reports exist in the current literature that present cases of PCH. In all the cases, evidence for pulmonary disease or dissemination is absent and most cases describe a history of direct inoculation as was present in this case 2–8…”

Section: Discussionmentioning

confidence: 72%

“…Interestingly, two case reports exist detailing cases of PCH in patients with rheumatoid arthritis (as in the case presented here), one on long-term steroids and the other on the disease-modifying agent, methotrexate. Both cases presented with nodular ulcerative lesions 4 5…”

Section: Discussionmentioning

confidence: 99%

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Unusual case of cellulitis due to primary cutaneous histoplasmosis

Paul¹,

Kuhlenschmidt

2018

BMJ Case Rep

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A 63-year-old white man with a history of rheumatoid arthritis on adalimumab was admitted to the hospital for left arm swelling and erythema. On physical examination, the patient was afebrile and non-toxic appearing and there was tense oedema of the left forearm. Initial laboratory work was unremarkable except for elevated inflammatory markers. MRI of the arm showed non-specific findings of inflammation. The patient was started on empiric antibiotics but did not improve. Given the patient’s immunosuppression, early consideration was given to fungal or mycobacterial causes. Initial serum fungal studies were negative and the patient was taken for diagnostic local incision and biopsy of the left volar forearm. Grocott’s methenamine silver and periodic acid–Schiff staining revealed fungal organisms resembling Histoplasma and intraoperative fungal cultures grew Histoplasma capsulatum confirming the diagnosis. The patient was treated with a 6-month course of itraconazole with improvement in his condition and eventual complete resolution.

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Primary cutaneous histoplasmosis in an immunocompromised patient with long-standing rheumatoid arthritis

Cited by 2 publications

References 9 publications

The HIF-1α/LC3-II Axis Impacts Fungal Immunity in Human Macrophages

The HIF-1α/LC3-II Axis Impacts Fungal Immunity in Human Macrophages

Unusual case of cellulitis due to primary cutaneous histoplasmosis

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