Letter to the Editor
Granulomatous–lymphocytic interstitial lung disease: A pulmonary complication of common variable immunodeficiency
Enfermedad pulmonar intersticial linfocítica granulomatosa: una complicación pulmonar de la inmunodeficiencia común variable
Cristina Matesanz López
, Beatriz Raboso Moreno, María Teresa Río Ramírez
Corresponding author
Servicio de Neumología, Hospital Universitario de Getafe, Madrid, Spain
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The second picture shows a chest CT with nodules (yellow arrow), lymphadenopathies (red arrow) and small bronchiectasis (blue triangle).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder characterized by loss of B-cell function and defective immunoglobulin production.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Pulmonary complication is one of the most frequent. The most common finding is bronchiectasis, although granulomatous–lymphocytic interstitial lung disease (GLILD) is also possible.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Case 1</span><p id="par0015" class="elsevierStylePara elsevierViewall">A 26-year-old male with a history of CVID and recurrent respiratory infections, presented with pulmonary bilateral nodules, interstitial thickening, and lymphadenopathy. A core needle biopsy was carried out, showing a lymphoid infiltrate with a CD3-CD4 predominance, as also a minimally granulomatous reaction.</p><p id="par0020" class="elsevierStylePara elsevierViewall">During the first years of following-up, a decline in lung function and worsen of symptoms were observed, what motivated the initiation of treatment with prednisone 0.5<span class="elsevierStyleHsp" style=""></span>mg/kg. There was a significant radiological and clinical improvement, which allowed a dose reduction. Complete withdrawal of glucocorticoesteroids was not possible.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In addition, he contracted COVID-19 with a favorable evolution.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Case 2</span><p id="par0030" class="elsevierStylePara elsevierViewall">A 22-year-old male, with a CVID diagnosis, had several respiratory and ear, nose and throat (ENT) infections. Due to this, a thorax high-resolution computed tomography (HRCT) was carried out, which showed hilar and mediastinal lymph nodes with basal and peribronchial nodular opacities. Considering these findings, a core needle biopsy was performed with the initial diagnosis of organizing pneumonia.</p><p id="par0035" class="elsevierStylePara elsevierViewall">However, the evolution of the organizing pneumonia was not typical, so a second core needle biopsy was considered. On this occasion, lung parenchima showed an interstitial inflammatory infiltrate with T cell, predominantly CD3+ and CD4+, apart from patchy areas of collagenized fibrosis. Masson bodies weren’t observed. GLILD diagnosis was established (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Case 3</span><p id="par0040" class="elsevierStylePara elsevierViewall">A 31-year-old woman was diagnosed with CVID due to recurrent sinusitis and mums. A chest HRCT was carried out. It showed hilar and mediastinal adenopathies, bronchiectasis and small nodules. A bronchoscopy was subsequently performed. The BAL was normal but the BTT was also described as non-necrotizing granulomatosis.</p><p id="par0045" class="elsevierStylePara elsevierViewall">With these findings, she was diagnosed with GLILD and corticosteroid treatment was started. The lung parenchima improved and she remained asymptomatic.</p><p id="par0050" class="elsevierStylePara elsevierViewall">However, after 12 years of follow-up, she died due to a non-Hodgkin's lymphoma.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Discussion</span><p id="par0055" class="elsevierStylePara elsevierViewall">In 2017, the British Lung Foundation/United Kingdom Primary Immunodeficiency Network made a consensus statement<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> where GLILD was defined as “a distinct clinico-radio-pathological ILD occurring in patients with CVID, associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and, where possible, excluded.”<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">GLILD is described in 10–30% of patients with CVID, without differences between gender, and it's less common in Blacks.</p><p id="par0065" class="elsevierStylePara elsevierViewall">It is complex to reach the diagnosis, since symptoms are non-specific and it is only suspected in the presence of radiological alterations. This happened in the three cases that we present.</p><p id="par0070" class="elsevierStylePara elsevierViewall">HRCT is the gold standard imaging technique. Sometimes, making the differential diagnosis between GLILD and sarcoidosis can be a challenge. Nodules in GLILD are usually bigger (>1<span class="elsevierStyleHsp" style=""></span>cm) with random or predominantly basal distribution. Hilar lymph nodes can be present in both diseases. The role of PET-CT is being studied to monitor response to treatment and to rule out other organ involvement.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The utility of trans-bronchial biopsy or cryobiopsy is not well defined, although one of our patients was diagnosed thanks to it.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Histology of GLILD is very heterogeneous. Findings include lymphoid hyperplasia, granulomata, organizing pneumonia and pulmonary fibrosis, as described in the cases presented.</p><p id="par0085" class="elsevierStylePara elsevierViewall">An increased risk of malignancies is also reported in CVID. Mainly Non-Hodgkin lymphomas, followed by gastric cancers.</p><p id="par0090" class="elsevierStylePara elsevierViewall">The decision about treatment generally relies upon a combination of clinical and functional parameters. If the patient is asymptomatic and lung function is normal, specific treatment is not recommended.</p><p id="par0095" class="elsevierStylePara elsevierViewall">When a worsening is observed, it is complex to establish a therapeutic algorithm due to a lack of studies. IgG replacement seems to be the first approach, followed by corticosteroids. Biologicals have also been used in this pathology. However, there is still a lack of solid evidence in order to choose the best option.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">We present three different cases with unlike evolution so far. It is, therefore, a compilation of three cases of a rare disease. The main objective is to highlight the importance of early diagnosis and the need to carry out more studies.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Informed consent</span><p id="par0105" class="elsevierStylePara elsevierViewall">Informed consent has not been collected for this article, since the personal data of our patients is not included.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Financing</span><p id="par0110" class="elsevierStylePara elsevierViewall">There was no funding for this article.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conflict of interest</span><p id="par0115" class="elsevierStylePara elsevierViewall">There are no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Case 1" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Case 2" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Case 3" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 4 => array:2 [ "identificador" => "sec0025" "titulo" => "Informed consent" ] 5 => array:2 [ "identificador" => "sec0030" "titulo" => "Financing" ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Conflict of interest" ] 7 => 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" => 373 "Ancho" => 1005 "Tamanyo" => 94561 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The first picture shows a dense interstitial-septal lymphoplasmacytic infiltrate surrounding alveoli (some alveoli are marked with yellow stars) (HE, 20×). The second picture shows a chest CT with nodules (yellow arrow), lymphadenopathies (red arrow) and small bronchiectasis (blue triangle).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Progression of common variable immunodeficiency interstitial lung disease accompanies distinct pulmonary and laboratory findings" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P.J. Maglione" 1 => "J.R. Overbey" 2 => "C. 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