Scientific Letter
Alveolar Microlithiasis and its Distinctive Clinical and Radiological Disassociation
Microlitiasis alveolar y su peculiar disociación clínico-radiológica
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A) Radiografía posteroanterior de tórax que muestra un patrón micronodular fino, bilateral y simétrico, de predominio en lóbulos inferiores, dando la imagen típica en «tormenta de arena». Radiolucencia vertical lineal subpleural bilateral, más evidente en el lado izquierdo que en la imagen B se corresponde con quistes subpleurales. B, C y D) La tomografía axial computarizada de tórax muestra extensas áreas de vidrio esmerilado, con un engrosamiento septal interlobulillar y reticular intralobulillar, de predominio en lóbulos inferiores, que representa un patrón <span class="elsevierStyleItalic">«crazy paving»</span>. En la imagen D son evidentes las microcalcificaciones confluentes de distribución predominantemente peribroncovascular en segmentos posteriores de lóbulos inferiores y subpleural. E) Restos de calcosferito intraalveolar con imagen típica en «capas de cebolla». Fibrosis secundaria de la pared alveolar. (Magnificación original x40; tinción hematoxilina-eosina).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Laura Cuesta Lujano, Álvaro Gutiérrez Domingo, Luis Fernández Ollero" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Laura" "apellidos" => "Cuesta Lujano" ] 1 => array:2 [ "nombre" => "Álvaro" "apellidos" => "Gutiérrez Domingo" ] 2 => array:2 [ "nombre" => "Luis" "apellidos" => "Fernández Ollero" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S1579212918302210" "doi" => "10.1016/j.arbr.2018.07.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212918302210?idApp=UINPBA00003Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289617303174?idApp=UINPBA00003Z" "url" => "/03002896/0000005400000009/v1_201809020416/S0300289617303174/v1_201809020416/es/main.assets" ] ] "itemAnterior" => array:19 [ "pii" => "S1579212918302684" "issn" => "15792129" "doi" => "10.1016/j.arbr.2018.02.023" "estado" => "S300" "fechaPublicacion" => "2018-09-01" "aid" => "1844" "copyright" => "SEPAR" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Arch Bronconeumol. 2018;54:491-2" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 617 "formatos" => array:3 [ "EPUB" => 94 "HTML" => 308 "PDF" => 215 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific letter</span>" "titulo" => "Telemedicine in Sleep Apnea: A Simple Approach for Nasal Pressure (CPAP) Treatment" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "491" "paginaFinal" => "492" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Telemedicina en la apnea del sueño: un abordaje simple para la presión positiva continua nasal (CPAP)" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Onintza Garmendia, Monique C. 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"apellidos" => "Montserrat" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S0300289618300553" "doi" => "10.1016/j.arbres.2018.02.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289618300553?idApp=UINPBA00003Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212918302684?idApp=UINPBA00003Z" "url" => "/15792129/0000005400000009/v1_201809020413/S1579212918302684/v1_201809020413/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "Alveolar Microlithiasis and its Distinctive Clinical and Radiological Disassociation" "tieneTextoCompleto" => true "saludo" => "To the Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "493" "paginaFinal" => "494" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Laura Cuesta Lujano, Álvaro Gutiérrez Domingo, Luis Fernández Ollero" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Laura" "apellidos" => "Cuesta Lujano" "email" => array:1 [ 0 => "lauracuestalujano@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" => "Álvaro" "apellidos" => "Gutiérrez Domingo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Luis" "apellidos" => "Fernández Ollero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Radiodiagnóstico, Hospital Universitario Virgen Macarena, Sevilla, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Universitario Virgen Macarena, Sevilla, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Microlitiasis alveolar y su peculiar disociación clínico-radiológica" ] ] "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" => 2500 "Ancho" => 2500 "Tamanyo" => 677030 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Alveolar microlithiasis. (A) Posteroanterior chest X-ray showing a fine bilateral, symmetric micronodular pattern, predominantly in the lower lobes, producing the typical sand-storm image. Bilateral subpleural linear vertical radiolucencies, more obvious in the left side, corresponding in image B with subpleural cysts. (B–D) Chest computed tomography showing extensive ground-glass opacities, with interlobular septal and intralobular reticular thickening, mainly in the lower lobes, showing a crazy-paving pattern. Image D clearly shows confluent microcalcifications distributed primarily in the peribronchovascular space in posterior segments of the lower and subpleural lobes. (E) Remains of intra-alveolar calcospherites with a typical onion-skin image. Secondary fibrosis of the alveolar wall. (Original magnification ×40; hematoxylin-eosin staining).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Alveolar microlithiasis is a rare autosomal recessive congenital disease, characterized by the accumulation of countless calcospherites (microliths formed of phosphorus and calcium) in the alveolar space. It was first described in 1918 by Harbitz,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> and very few cases have been published in the literature to date. In a recent review, Castellana et al.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a> studied a total of 1022 cases from 65 countries worldwide, mainly in Asia (56.3%) and Europe (27.8%), the most affected countries being Turkey, China, Japan, India, and Italy. In Spain, only 38 cases have been described in total, equivalent to 3.7%.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of a 19-year-old man, referred to our center with suspected interstitial disease and a clinical picture of a 1-month history of dry cough, and chest X-ray showing a fine, bilateral micronodular pattern, predominantly in the lower fields (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). On examination, the patient was eupneic at rest, with basal oxygen saturation of 98%. The only findings of note were some fine crackles in both lung bases on lung auscultation. High-resolution computed tomography (HRCT) was requested, which reported findings suggestive of alveolar microlithiasis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B–D). Diagnostic confirmation was obtained with a transbronchial biopsy, the pathology report of which found numerous intra- and extra-alveolar calcifications, with formation of calcospherites and secondary fibrosis of the alveolar wall, all consistent with alveolar microlithiasis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>E).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">After 2 years of follow-up, the patient has been mainly asymptomatic, living a normal life with no treatment. He only reports occasional bloody sputum when performing intense physical exercise. Functional lung tests have been relatively stable, with a vital capacity of 79%, forced expiratory volume in 1 second 85%, Tiffeneau index 91%, and diffusing capacity of the lung 66%. His first-degree relatives (parents and sister) were recommended to have chest X-rays, which were normal.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The patient remains in follow-up in the respiratory medicine clinic of our center. The disassociation between his clinical and radiological features is very striking, as is his progress.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Alveolar microlithiasis is a rare disease caused by a mutation in the SLC34A2 gene that encodes the sodium-phosphate cotransporter type IIb, expressed in type II alveolar cells.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> These cells are responsible for the production of lung surfactant, which is fundamentally made up of phospholipids. The degradation product of lung surfactant is phosphate that must be removed from the alveolar spaces. SLC34A2 dysfunction reduces phosphate clearance and leads to the formation of calcospherites.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">2–5</span></a> This gene is also expressed in the mammary glands, small intestine, kidneys, pancreas, ovaries, liver, testes,<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a> placenta and prostate, so in some cases the lungs are not the only organs affected.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a> Our patient underwent 2 testicular ultrasound examinations that were normal.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The disease affects both sexes, although it occurs predominantly in men, except in Spain, Italy and France, where there is a greater prevalence in women. It develops in all age groups, although it is usually diagnosed between the 2nd and 3rd decade of life. The youngest patients diagnosed were premature twins,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a> while an 84-year-old woman was the oldest diagnosed case.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a> Clinical–radiological disassociation is a clinical characteristic of this entity, and patients can have very few symptoms in combination with very marked radiological findings. Most patients are asymptomatic at diagnosis, with normal lung function or a very mild restrictive pattern, and changes in the lung parenchyma are found by chance. In the most severe cases, cyanosis and nail clubbing are the first visible signs. The most common symptom is dyspnea, followed by dry cough, chest pain, sporadic hemoptysis, and asthenia. The disease course in some patients is slow, but most progress to lung fibrosis with respiratory failure and cor pulmonale.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">8,9</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The diagnostic procedure consists mainly of imaging tests (chest X-ray and HRCT) and a pathology study (bronchoalveolar lavage and transbronchial biopsy). Chest X-ray is characterized by the presence of multiple fine bilateral and symmetrical calcified micronodules, diffusely arranged, producing a typical sand-storm pattern. Vertical linear radiolucencies between the pulmonary parenchyma and the ribs are also characteristic of alveolar microlithiasis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A) due to subpleural cystic changes.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a> A recent retrospective study by Francisco et al.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">10</span></a> assessed the frequency of tomography findings in patients with pulmonary alveolar microlithiasis. The main finding was the presence of diffuse ground glass opacities and intraparenchymal micronodules, observed in 100% of cases, followed by small subpleural nodules (92.3%), subpleural cysts (84.6%), subpleural linear calcifications (69.2%), mosaic crazy-paving pattern (69.2%), and nodular fissures (53.8%). These lesions were distributed primarily in the lower third of the lungs, with no predominance of distribution in the transverse and anteroposterior directions.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">10</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Pathology studies show numerous intra-alveolar calcospherites that are periodic acid-Schiff (PAS) positive on histology, consisting of concentric calcareous layers around a central nucleus of amorphous or granular appearance. This appearance differs from metastatic or dystrophic calcifications in interstitial or vascular compartments. The lungs can weigh up to 5<span class="elsevierStyleHsp" style=""></span>kg and the exterior surfaces are granular and irregular on gross examination, due to microliths protruding through the visceral pleura.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Differential diagnosis includes diseases that occur with a miliary interstitial pattern on radiology, such as tuberculosis, sarcoidosis, pneumoconiosis, and amyloidosis, as well as alveolar proteinosis, due to its typical crazy-paving presentation.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In terms of treatment, no therapies are currently available that will limit disease progression. A small number of studies have shown an improvement in lung function with etidronate disodium (diphosphonate).<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a> Corticosteroids and bronchoalveolar lavage have not been effective, and lung transplantation is the only effective option, especially when it is performed before the disease progresses to an advanced stage.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Cuesta Lujano L, Gutiérrez Domingo Á, Fernández Ollero L. Microlitiasis alveolar y su peculiar disociación clínico-radiológica. Arch Bronconeumol. 2018;54:493–494.</p>" ] ] "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" => 2500 "Ancho" => 2500 "Tamanyo" => 677030 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Alveolar microlithiasis. (A) Posteroanterior chest X-ray showing a fine bilateral, symmetric micronodular pattern, predominantly in the lower lobes, producing the typical sand-storm image. Bilateral subpleural linear vertical radiolucencies, more obvious in the left side, corresponding in image B with subpleural cysts. (B–D) Chest computed tomography showing extensive ground-glass opacities, with interlobular septal and intralobular reticular thickening, mainly in the lower lobes, showing a crazy-paving pattern. Image D clearly shows confluent microcalcifications distributed primarily in the peribronchovascular space in posterior segments of the lower and subpleural lobes. (E) Remains of intra-alveolar calcospherites with a typical onion-skin image. Secondary fibrosis of the alveolar wall. (Original magnification ×40; hematoxylin-eosin staining).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0060" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "Available from: <a class="elsevierStyleInterRef" target="_blank" id="intr0010" href="http://jamanetwork.com/journals/jamainternalmedicine/article-abstract/654194">http://jamanetwork.com/journals/jamainternalmedicine/article-abstract/654194</a> [accessed 19.05.17]" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Extensive calcification of the lungs as a distinct disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "F. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 34 | 28 | 62 |
| 2024 September | 39 | 28 | 67 |
| 2024 August | 55 | 49 | 104 |
| 2024 July | 42 | 37 | 79 |
| 2024 June | 60 | 28 | 88 |
| 2024 May | 76 | 24 | 100 |
| 2024 April | 51 | 39 | 90 |
| 2024 March | 63 | 18 | 81 |
| 2024 February | 48 | 20 | 68 |
| 2023 October | 1 | 1 | 2 |
| 2023 March | 14 | 4 | 18 |
| 2023 February | 54 | 20 | 74 |
| 2023 January | 55 | 34 | 89 |
| 2022 December | 89 | 37 | 126 |
| 2022 November | 72 | 24 | 96 |
| 2022 October | 92 | 37 | 129 |
| 2022 September | 59 | 29 | 88 |
| 2022 August | 59 | 48 | 107 |
| 2022 July | 48 | 50 | 98 |
| 2022 June | 41 | 36 | 77 |
| 2022 May | 72 | 32 | 104 |
| 2022 April | 40 | 22 | 62 |
| 2022 March | 44 | 48 | 92 |
| 2022 February | 42 | 38 | 80 |
| 2022 January | 56 | 29 | 85 |
| 2021 December | 32 | 39 | 71 |
| 2021 November | 42 | 40 | 82 |
| 2021 October | 48 | 34 | 82 |
| 2021 September | 40 | 63 | 103 |
| 2021 August | 38 | 32 | 70 |
| 2021 July | 28 | 32 | 60 |
| 2021 June | 58 | 36 | 94 |
| 2021 May | 34 | 35 | 69 |
| 2021 April | 119 | 60 | 179 |
| 2021 March | 84 | 13 | 97 |
| 2021 February | 33 | 23 | 56 |
| 2021 January | 36 | 17 | 53 |
| 2020 December | 32 | 15 | 47 |
| 2020 November | 26 | 24 | 50 |
| 2020 October | 35 | 16 | 51 |
| 2020 September | 20 | 10 | 30 |
| 2020 March | 94 | 7 | 101 |
| 2020 February | 141 | 21 | 162 |
| 2020 January | 91 | 15 | 106 |
| 2019 December | 102 | 12 | 114 |
| 2019 November | 36 | 20 | 56 |
| 2019 October | 39 | 12 | 51 |
| 2019 September | 57 | 21 | 78 |
| 2019 August | 25 | 16 | 41 |
| 2019 July | 19 | 25 | 44 |
| 2019 June | 46 | 15 | 61 |
| 2019 May | 30 | 28 | 58 |
| 2019 April | 50 | 19 | 69 |
| 2019 March | 35 | 25 | 60 |
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