Letter - Clinical
Langerhans cell histiocytosis: a rare case of the multisystemic form in an infant
Thaís Oliveira Utiyama
, Maria Laura Malzoni, Thalita Gabrieli Sanches Vasques, Cassiano Tamura Vieira Gomes
Corresponding author
Faculty of Medical and Health Sciences of Sorocaba, Pontifícia Universidade Católica de São Paulo, Sorocaba, SP, Brazil
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After a short period of apparent improvement, the lesions recurred. There were no systemic manifestations.</p><p id="par0015" class="elsevierStylePara elsevierViewall">On physical examination, angiomatous papules with hematic crusts on top and some flat, hypochromic, shiny papules were observed, also affecting the palmoplantar region and the oral cavity (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Therefore, the diagnostic hypotheses of LCH, congenital cytomegalovirus (CMV), leukemia cutis, and severe combined immunodeficiency were suggested. A biopsy was performed, and serologies were requested (HIV, CMV, rubella, toxoplasmosis, VDRL) which were negative, whereas screening for congenital immunodeficiency showed no alterations.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Histopathology revealed chronic dermatitis associated with the presence of cells suggestive of Langerhans cells (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Immunohistochemistry showed positivity for CD1a, CD68, S100 protein; Ki67 was positive in 70% of the cells (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). Once the diagnosis of LCH was confirmed, the investigation of other organs through a myelogram and computed tomography of the chest, abdomen, and pelvis led to the classification of the case as multisystemic LCH due to pulmonary and hepatic involvement. Treatment was started with weekly vinblastine 3 mg/m<span class="elsevierStyleSup">2</span> + prednisone 20 mg/m<span class="elsevierStyleSup">2</span>, according to the <span class="elsevierStyleItalic">Brazilian Society of Histiocytosis</span> guideline. The condition improved significantly, but after about two months the skin lesions returned, and the pulmonary condition worsened, requiring oxygen therapy. A new chemotherapy regimen with Cladribine (2-CdA) was introduced, according to the Japanese protocol. The patient remains stable and is being followed by the oncology team.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">The incidence of LCH ranges from two to nine cases per million children under 15 years of age, with a peak between one and three years of age.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> It can affect one or multiple organs, with the following being considered at risk: liver, spleen, and bone marrow. Most patients have single-system involvement (70%).<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The most frequently affected organs are the bones, followed by the skin, but in infants, cutaneous manifestations are the main findings. Dermatologically, they present as a seborrheic-like dermatitis, and less often as hemorrhagic lesions, although these are favorable conducive to diagnosis.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The pathogenesis remains unclear, with theories that support both a reactional and a neoplastic nature. Characterization as a neoplastic disorder is supported by the finding of a mutation in the BRAF V600E gene, and activation of the MAP kinase (MAPK) pathway.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The diagnosis depends on the clinical, anatomopathological and immunohistochemical correlation. Histopathologically, varying amounts of Langerhans cells with a “coffee bean” appearance are observed. Positive immunohistochemistry for CD1a and CD207 (langerin) establishes the diagnosis.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Treatment will depend on disease extent and severity. When the involvement is solely cutaneous, spontaneous resolution is common. For multisystem disease, treatment with systemic steroids and vinblastine for 12 months is the first-line regimen.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">LCH is a serious disease that, due to its very diverse clinical manifestation, is often diagnosed late, delaying treatment. The presence of a dermatologist in the clinical staff allows its early identification, with a significant impact on patient prognosis.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0060" class="elsevierStylePara elsevierViewall">None declared.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors' contributions</span><p id="par0065" class="elsevierStylePara elsevierViewall">Thaís Oliveira Utiyama: Drafting and editing of the manuscript; critical review of the literature; critical review of the manuscript.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Maria Laura Malzoni: Effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the manuscript; approval of the final version of the manuscript.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Thalita Gabrieli Sanches Vasques: Critical review of the manuscript.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Cassiano Tamura Vieira Gomes: Approval of the final version of the manuscript.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0085" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Financial support" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Authors' contributions" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflicts of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-05-12" "fechaAceptado" => "2021-06-05" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "⋆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Study conducted at the Faculty of Medical and Health Sciences of Sorocaba, Pontifícia Universidade Católica de São Paulo, Sorocaba, SP, Brazil.</p>" ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2240 "Ancho" => 1675 "Tamanyo" => 307126 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Angiomatous papules with hematic crusts on top and some flat, hypochromic papules, with a shiny appearance on the trunk.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1796 "Ancho" => 1675 "Tamanyo" => 443768 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Chronic dermatitis associated with the presence of cells suggestive of Langerhans cells (Hematoxylin & eosin 100X).</p>" ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 978 "Ancho" => 1675 "Tamanyo" => 270767 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Positive immunohistochemistry for CD1a.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Langerhans cell histiocytosis in children: History, classification, pathobiology, clinical manifestations, and prognosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J. 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Techasatian" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00431-019-03356-1" "Revista" => array:6 [ "tituloSerie" => "Eur J Pediatr" "fecha" => "2019" "volumen" => "178" "paginaInicial" => "771" "paginaFinal" => "776" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30826864" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Langerhans cell histiocytosis: progress and controversies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "O. Abla" 1 => "B. Rollins" 2 => "S. Ladisch" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/bjh.16099" "Revista" => array:6 [ "tituloSerie" => "Br J Haematol" "fecha" => "2019" "volumen" => "187" "paginaInicial" => "559" "paginaFinal" => "562" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31309539" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Langerhans cell histiocytosis in children: Diagnosis, differential diagnosis, treatment, sequelae, and standardized follow-up" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J. Krooks" 1 => "M. Minkov" 2 => "A.G. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 22 | 7 | 29 |
| 2024 October | 134 | 79 | 213 |
| 2024 September | 189 | 101 | 290 |
| 2024 August | 189 | 122 | 311 |
| 2024 July | 141 | 95 | 236 |
| 2024 June | 104 | 67 | 171 |
| 2024 May | 108 | 74 | 182 |
| 2024 April | 105 | 78 | 183 |
| 2024 March | 108 | 64 | 172 |
| 2024 February | 125 | 77 | 202 |
| 2024 January | 66 | 52 | 118 |
| 2023 December | 85 | 64 | 149 |
| 2023 November | 85 | 98 | 183 |
| 2023 October | 83 | 87 | 170 |
| 2023 September | 85 | 77 | 162 |
| 2023 August | 97 | 33 | 130 |
| 2023 July | 100 | 41 | 141 |
| 2023 June | 153 | 64 | 217 |
| 2023 May | 133 | 71 | 204 |
| 2023 April | 84 | 13 | 97 |
| 2023 March | 37 | 48 | 85 |
| 2023 February | 41 | 33 | 74 |
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