Scientific Letter
Acute Respiratory Distress Syndrome Secondary to Histoplasmosis-induced Hemophagocytic Lymphohistiocytosis
Síndrome de distrés respiratorio agudo secundario a linfohistiocitosis hemofagocítica inducida por histoplasmosis
Julio Arturo Huapayaa,
, Elizabeth Yogiaveetilb, Syed Qamera, Mary Sidawyc, Eric Andersonb
Corresponding author
a Division of Internal Medicine, Medstar Georgetown University Hospital, Washington, DC, United States
b Division of Pulmonary and Critical Care Medicine, Medstar Georgetown University Hospital, Washington, DC, United States
c Department of Pathology, Medstar Georgetown University Hospital, Washington, DC, United States
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(A) Bibasilar linear infiltrates seen on admission. (B) Diffuse bilateral alveolar infiltrates with air bronchogram seen 12<span class="elsevierStyleHsp" style=""></span>h after admission.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Acute respiratory distress syndrome (ARDS) is a condition that carries high mortality and can be caused by sepsis or pneumonia.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">1</span></a> Histoplasmosis can cause a lung infection varying from mild pneumonitis to ARDS.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">2</span></a> This endemic mycosis can also cause disseminated infection and is catastrophic in immunocompromised patients.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">3</span></a> In transplant populations, it has an incidence of 1–3 cases per 1000 patients and is more prevalent in hepatic and renal transplants.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">4–6</span></a> Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune derangement of defective natural killer cells and macrophage overactivation. HLH is a rare complication of histoplasmosis but carries a mortality of up to 50%. Optimal treatment of infection-associated HLH is controversial and data is limited.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">7,8</span></a> Some physicians advocate for the use immunosuppression in addition to antifungal therapy, whereas others will only treat the underlying infection. Notably, current evidence suggests that this latter approach has less mortality.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">3,9–11</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We present a case of a 46-year-old Korean male who underwent a deceased donor kidney transplant in 2014 secondary to diabetic nephropathy. He presented with vomiting, diarrhea and fever and was initially treated for viral gastroenteritis. Chest X-ray (CXR) on admission showed bibasilar linear infiltrates (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). His clinical status rapidly deteriorated and he was admitted to the intensive care unit and was started on low-dose vasopressors. Patient's hemodynamics continued to worsen with respiratory failure requiring high-flow nasal cannula due to hypoxemia. He rapidly developed ARDS and required intubation with low-tidal volume ventilation and paralytics. Chest X-ray revealed diffuse bilateral alveolar infiltrates with air bronchogram (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B) and chest computed tomography revealed tree-in-bud infiltrates and splenomegaly. Laboratory data was notable for pancytopenia, transaminitis, ferritin of 16,624<span class="elsevierStyleHsp" style=""></span>ng/mL, elevated LDH, normal triglycerides and a positive urine and serum <span class="elsevierStyleItalic">Histoplasma</span> antigen. He had several environmental and animal exposures including bats, rats, animal droppings and mold along subway tunnels. Work-up including acid-fast Bacilli smear and culture, hepatitis panel, <span class="elsevierStyleItalic">Bartonella</span>, <span class="elsevierStyleItalic">Human Immunodeficiency Virus (HIV)</span>, <span class="elsevierStyleItalic">Legionella</span>, <span class="elsevierStyleItalic">Cryptococcus</span>, <span class="elsevierStyleItalic">Parvovirus</span>, <span class="elsevierStyleItalic">Human Herpes Virus 6</span>, <span class="elsevierStyleItalic">Adenovirus</span>, <span class="elsevierStyleItalic">Epstein-barr Virus</span> and <span class="elsevierStyleItalic">Cytomegalovirus</span> polymerase chain reaction tests were negative. Bronchoalveolar lavage revealed numerous fungal organisms in the form of budding yeasts without evidence of pseudohyphae, consistent with <span class="elsevierStyleItalic">Histoplasma Capsulatum</span>. Culture data confirmed the diagnosis. The patient rapidly improved and was successfully extubated after starting amphotericin B, followed by itraconazole. Soluble IL-2 receptor came back elevated (14,150<span class="elsevierStyleHsp" style=""></span>pg/mL) a few days later. Tacrolimus and mofetil mycophenolate had been initially stopped due to worsening renal function but were restarted before discharge. The patient was fully recovered at 6-month follow up.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">This case highlights that patients with significant immunosuppression can develop severe ARDS secondary to histoplasmosis.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">2</span></a> This has mainly been described in patients with HIV who can also develop HLH as a rare complication.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">3</span></a> The current treatment of primary HLH is based on immunosuppression<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">12</span></a> but there is not consensus on the treatment of infection-associated HLH.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">8</span></a> Moreover, the literature in organ transplants patients is limited. One study reported less mortality in patients who do not receive additional immunosuppression, although only a small number of patients were included in that study.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">3</span></a> Our patient met five criteria for HLH, including fever, splenomegaly, pancytopenia, high ferritin level and elevated IL2 soluble receptor. He had an excellent response to treatment targeting histoplasmosis without the use of steroids or further immunosuppression. In the largest case series of 11 cases of patients with histoplasmosis-induced HLH, the mortality was 46% at 30 days and 63% at 90 days, with increased mortality up to 80% in the group who received immunosuppression.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">3</span></a> The study included nine patients with HIV and two with renal transplants.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">3</span></a> Further evidence of HLH and histoplasmosis in kidney transplant is scarce. Nieto et al. report two cases, one successfully treated with antifungals alone and one with a fatal outcome after receiving increased immunosuppression.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">9</span></a> Similarly, Contreras et al. report a renal transplant patient who successfully responded to antifungal therapy alone.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">10</span></a> Lo et al. describe a successful experience of two kidney transplant patients who received only dual antifungal therapy with amphotericin and itraconazole.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">11</span></a> Notably, there were no acute rejections in spite of decreased immunosuppression. Therefore, it should be highlighted that limiting immunosuppression may be necessary if patients are refractory to antifungal therapy to ensure complete resolution of Histoplasmosis infection. In our patient, we held immunosuppression on admission and he did not experience any complications. Limitations related to the small number of patients and the possibility of treatment bias in patients who were sicker should be considered. Prospective treatment studies would be ideal, but they are unlikely given the rarity of this disease. In conclusion, our case adds to the limited literature that suggests that treatment of an underlying infection in HLH alone could lead to rapid resolution of this otherwise lethal disorder. Further data is needed to define the role of immunosuppression in treating this condition.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 874 "Ancho" => 2091 "Tamanyo" => 114729 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Chest X-ray on admission and at 12-h follow-up. (A) Bibasilar linear infiltrates seen on admission. (B) Diffuse bilateral alveolar infiltrates with air bronchogram seen 12<span class="elsevierStyleHsp" style=""></span>h after admission.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:12 [ 0 => array:3 [ "identificador" => "bib0065" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acute respiratory distress syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "B.T. Thompson" 1 => "R.C. Chambers" 2 => "K.D. Liu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMra1608077" "Revista" => array:6 [ "tituloSerie" => "N. Engl. J. Med." 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 41 | 9 | 50 |
| 2024 September | 52 | 14 | 66 |
| 2024 August | 73 | 36 | 109 |
| 2024 July | 69 | 22 | 91 |
| 2024 June | 53 | 25 | 78 |
| 2024 May | 91 | 25 | 116 |
| 2024 April | 38 | 21 | 59 |
| 2024 March | 40 | 20 | 60 |
| 2024 February | 30 | 20 | 50 |
| 2023 March | 13 | 3 | 16 |
| 2023 February | 65 | 20 | 85 |
| 2023 January | 38 | 20 | 58 |
| 2022 December | 76 | 23 | 99 |
| 2022 November | 75 | 20 | 95 |
| 2022 October | 77 | 30 | 107 |
| 2022 September | 55 | 24 | 79 |
| 2022 August | 47 | 41 | 88 |
| 2022 July | 47 | 47 | 94 |
| 2022 June | 51 | 33 | 84 |
| 2022 May | 54 | 23 | 77 |
| 2022 April | 99 | 40 | 139 |
| 2022 March | 92 | 38 | 130 |
| 2022 February | 95 | 17 | 112 |
| 2022 January | 86 | 29 | 115 |
| 2021 December | 41 | 33 | 74 |
| 2021 November | 53 | 33 | 86 |
| 2021 October | 116 | 45 | 161 |
| 2021 September | 26 | 26 | 52 |
| 2021 August | 25 | 27 | 52 |
| 2020 October | 0 | 2 | 2 |
| 2020 March | 30 | 11 | 41 |
| 2020 February | 44 | 13 | 57 |
| 2020 January | 1 | 1 | 2 |
| 2019 November | 0 | 2 | 2 |
| 2019 September | 4 | 0 | 4 |
| 2019 August | 24 | 4 | 28 |
| 2019 February | 2 | 0 | 2 |
Show all
