Scientific Letter
Organizing Pneumonia Associated With Subclinical HSV Extrapulmonary Infection in an Immunocompetent Host: A Case Report
Neumonía organizada secundaria a una infección extrapulmonar subclínica por HSV en un huésped inmunocompetente: a propósito de un caso
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It does not present infiltrates.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Diego Ferrer-Pargada, David Iturbe, Sandra Tello, Sheila Izquierdo, Elena Peña, Cristina Castrillo Bustamante, Javier Gómez-Roman" "autores" => array:7 [ 0 => array:2 [ "nombre" => "Diego" "apellidos" => "Ferrer-Pargada" ] 1 => array:2 [ "nombre" => "David" "apellidos" => "Iturbe" ] 2 => array:2 [ "nombre" => "Sandra" "apellidos" => "Tello" ] 3 => array:2 [ "nombre" => "Sheila" "apellidos" => "Izquierdo" ] 4 => array:2 [ "nombre" => "Elena" "apellidos" => "Peña" ] 5 => array:2 [ "nombre" => "Cristina" "apellidos" => "Castrillo Bustamante" ] 6 => array:2 [ "nombre" => "Javier" "apellidos" => "Gómez-Roman" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2659663624000948?idApp=UINPBA00004N" "url" => "/26596636/0000000600000004/v10_202410240804/S2659663624000948/v10_202410240804/en/main.assets" ] "itemAnterior" => array:17 [ 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"nombre" => "Santa Cruz" "apellidos" => "Roberto" ] 1 => array:2 [ "nombre" => "Domeniconi" "apellidos" => "Gustavo" ] 2 => array:2 [ "nombre" => "Favot" "apellidos" => "Carolina" ] 3 => array:2 [ "nombre" => "Pagano" "apellidos" => "Fernando" ] 4 => array:2 [ "nombre" => "Choi" "apellidos" => "Marcelo" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2659663624000882?idApp=UINPBA00004N" "url" => "/26596636/0000000600000004/v10_202410240804/S2659663624000882/v10_202410240804/en/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "Organizing Pneumonia Associated With Subclinical HSV Extrapulmonary Infection in an Immunocompetent Host: A Case Report" "tieneTextoCompleto" => true "saludo" => "Dear Editor," "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Anna Michela Gaeta, Anna Annunziata, Giuseppe Fiorentino" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Anna Michela" "apellidos" => "Gaeta" "email" => array:1 [ 0 => "amgaeta84@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Anna" "apellidos" => "Annunziata" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Giuseppe" "apellidos" => "Fiorentino" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Respiratory Division, Hospital Universitario Severo Ochoa, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Intensive Care, Azienda Ospedaliera di Rilievo Nazionale dei Colli, Naples, Italy" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Neumonía organizada secundaria a una infección extrapulmonar subclínica por HSV en un huésped inmunocompetente: a propósito de un caso" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1231 "Ancho" => 1867 "Tamanyo" => 192396 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Chest CT at the time of admission showing bilateral, non-segmental airspace consolidation with bronchogram, consistent with OP. (B) Chest CT at 15 days follow-up showing bilateral reduction of consolidations after oral acyclovir and intravenous corticosteroids treatment. (C, D) Anteroposterior and lateral chest X-rays at 12 months follow-up demonstrating normal findings.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Our case concerns a 45-year-old smoker (10 pack/year) hospitalized with moderate respiratory distress (PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> 170<span class="elsevierStyleHsp" style=""></span>mmHg), pleuritic pain, no fever and a three-week history of progressive shortness of breath and non-productive cough. He denied recent sick contacts, travels, inhalation exposures, reporting a history of Herpes Simplex Virus Type 2 (HSV-2) genital infection a year prior without other medical conditions. The patient had no history of high-risk sexual behavior or other sexually transmitted infections. He also reported no drug use and a weekly alcohol intake of approximately 12<span class="elsevierStyleHsp" style=""></span>g.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Chest computed tomography (CT) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A) revealed bilateral lung consolidations with a likely organizing pneumonia (OP) pattern. Serum C-reactive protein (CRP) was 14.4<span class="elsevierStyleHsp" style=""></span>mg/dL. White blood cell (WBC) count was 19,700/μL with neutrophilia. Hemoglobin, coagulation parameters, serum biochemical tests, cryoglobulins, tumor markers, autoimmune antibodies, rheumatoid factor were within normal ranges. Serological tests for Hepatitis A Virus (HAV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV); Legionella and pneumococcal urinary antigens; blood and sputum cultures were all negative.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Amoxicillin–clavulanic and azithromycin were started without significant improvement. Bronchoalveolar lavage (BAL) cultures for fungi, bacteria, mycobacteria; multiplex respiratory Polymerase Chain Reaction (PCR) panel for Influenza Virus Types A and B, Respiratory Syncytial Virus (RSV), Human Metapneumovirus (hMPV), Adenovirus, Parainfluenza Virus (PIV), Rhinovirus/Enterovirus, Coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Human Bocavirus (HBoV), Human Parainfluenza Virus (HPIV), Human Coronavirus (HCoV), Herpes Simplex Virus Types 1 and 2 (HSV-1/2), Cytomegalovirus (CMV) and Mycoplasma pneumoniae; Aspergillus galactomannan, β-3-glucan returned negative results.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Transbronchial lung biopsy (TBLB) samples were insufficient for histological evaluation. BAL cytology excluded malignancy. BAL cell count indicated OP with a mixed pattern, showing lymphocytosis (35%), neutrophilia (10%), and CD4/CD8 of 0.8. Clinical conditions rapidly deteriorated (PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> 80<span class="elsevierStyleHsp" style=""></span>mmHg), precluding TBLB repetition for histological confirmation.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Considering the history of HSV-2 infection, HSV-1/2 serology was performed despite the absence of genital lesions, revealing IgM titer of 1.3 and negative IgG (both negative if <0.9). We initiated oral acyclovir at 800<span class="elsevierStyleHsp" style=""></span>mg twice daily for 10 days, resulting in clinical improvement (PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> 190<span class="elsevierStyleHsp" style=""></span>mmHg), seroconversion to negative HSV-1/2 IgM and positive IgG titers (9.26). Subsequently, we commenced intravenous methylprednisolone at 40<span class="elsevierStyleHsp" style=""></span>mg daily, yielding significant enhancement in clinical (PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> 332<span class="elsevierStyleHsp" style=""></span>mmHg) and radiological findings (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). The patient was discharged on two-month-tapering course of oral prednisone, starting at 50<span class="elsevierStyleHsp" style=""></span>mg daily, remaining recurrence-free for 12 months (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C, D).</p><p id="par0030" class="elsevierStylePara elsevierViewall">The organizing pneumonia (OP), characterized by intra-alveolar fibroblasts and collagen, is an inflammatory condition reversible with corticosteroids.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> OP has been anecdotally described as secondary immune response to diverse viral infections in immunocompromised hosts or those with severe comorbidities.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">2–4</span></a> Etiological hypotheses include prolonged viral shedding or T-cell immunity dysfunction.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">2,4</span></a> While histology is the diagnostic gold standard, BAL cell count, and radiology are crucial when TBLB results are inconclusive.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> HSV pneumonia is a rare, severe illness primarily affecting immunocompromised individuals, with a 1–5% incidence in patients with hematologic malignancies.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a> The prevalence in the immunocompetent hospitalized population with severe respiratory illness round about 2%, often as a secondary colonizer rather than the primary pathogen, with approximatively 6 cases reported in literature.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">4,5</span></a> Diagnosis requires viral detection via PCR in BAL, the gold standard test.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Based on anamnesis and serologic findings, we initiated acyclovir with rapid improvement, further enhanced by corticosteroids. Diagnosing subclinical HSV-2 reactivation via urethral swabs is difficult. PCR is highly sensitive (98%) and specific (97%), but due to intermittent viral shedding, a negative result doesn’t rule out the virus. Proper timing or serological assays are needed for confirmation.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a> In our case serology assays were chosen as the initial, less invasive diagnostic approach.</p><p id="par0040" class="elsevierStylePara elsevierViewall">On the other hands, a false negative in PCR for HSV from BAL is highly improbable, with the test showing a sensitivity typically ranging between 96% and 100% in various studies and 100% specificity.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">4,5</span></a> Initial recovery with antiviral therapy supported the diagnosis of OP secondary to extrapulmonary HSV subclinical activation,<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">4,5</span></a> likely inducing a lung immune reaction.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">2,4,5</span></a> Acyclovir plausibly eliminated the immunological trigger.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">4,5</span></a> HSV pneumonia and OP can coexist, with few cases reported.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a> However, to the best of our knowledge, no previous reports of OP secondary to asymptomatic HSV viral shedding have been documented. The case underscores the importance of considering OP as potentially related to extrapulmonary viral infections, even in atypical scenarios of comorbidity-free hosts, as shown by our findings. Supported by clinical-anamnestic data, it suggests incorporating viral serology as supplementary diagnostic tool for OP etiology.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Informed consent</span><p id="par0045" class="elsevierStylePara elsevierViewall">Informed consent was obtained for the publication of this paper.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0050" class="elsevierStylePara elsevierViewall">There was not funding source for this study.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Authors’ contributions</span><p id="par0055" class="elsevierStylePara elsevierViewall">Anna Michela Gaeta drafted the manuscript.</p><p id="par0060" class="elsevierStylePara elsevierViewall">All authors critically reviewed and revised the manuscript draft for important intellectual content and approved the final version for submission.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Conflicts of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare that they have not conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Informed consent" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Authors’ contributions" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Conflicts of interest" ] 4 => array:1 [ "titulo" => "References" ] ] ] "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" => 1231 "Ancho" => 1867 "Tamanyo" => 192396 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Chest CT at the time of admission showing bilateral, non-segmental airspace consolidation with bronchogram, consistent with OP. (B) Chest CT at 15 days follow-up showing bilateral reduction of consolidations after oral acyclovir and intravenous corticosteroids treatment. (C, D) Anteroposterior and lateral chest X-rays at 12 months follow-up demonstrating normal findings.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0035" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Utility of high-resolution computed tomography and BAL in cryptogenic organizing pneumonia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Jara-Palomares" 1 => "L. Gomez-Izquierdo" 2 => "D. Gonzalez-Vergara" 3 => "E. Rodriguez-Becerra" 4 => "E. Marquez-Martin" 5 => "E. 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Johnston" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/cid/ciab1056" "Revista" => array:7 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "2022" "volumen" => "74" "numero" => "Suppl. 2" "paginaInicial" => "S134" "paginaFinal" => "S143" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35416970" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/26596636/0000000600000004/v10_202410240804/S2659663624000894/v10_202410240804/en/main.assets" "Apartado" => array:4 [ "identificador" => "85987" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Cartas científicas" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/26596636/0000000600000004/v10_202410240804/S2659663624000894/v10_202410240804/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2659663624000894?idApp=UINPBA00004N" ]
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