scholarly journals Clinical Study of MAP2K1-Mutated Langerhans Cell Histiocytosis in Children

2021 ◽  
Author(s):  
Ying Yang ◽  
Chanjuan Wang ◽  
Dong Wang ◽  
Lei Cui ◽  
Na Li ◽  
...  
Keyword(s):  
Clinical Features ◽  
Langerhans Cell Histiocytosis ◽  
Disease Onset ◽  
Langerhans Cell ◽  
Bone Involvement ◽  
Common Mutation ◽  
Lung Involvement ◽  
Mutation Site ◽  
Significant Difference ◽  
Mutation Group

Abstract Purpose To analyze the genetic and clinical features of children with MAP2K1-mutated Langerhans cell histiocytosis (LCH). Methods We compared the clinical features of 37 children with MAP2K1-mutated LCH with those of the BRAFV600E mutation group (n = 133) and no known mutation group (n = 59) in the same period. Results We found 13 mutations of the MAP2K1 gene, which were mainly concentrated at p.53–62 and p.98–103. The most common mutation site was c.172_186del (12/37). Compared with the BRAFV600E mutation group, the patients with MAP2K1 mutations were mainly characterized by single system multiple bone involvement (P = 0.022), with later disease onset (P = 0.029) as well as less involvement of risk organs, especially liver (P = 0.024). There was no significant difference in clinical features compared with the no known mutation group. The 2-year progression-free survival rate of first-line treatment (ChiCTR1900025783, 07/09/2019) in MAP2K1-mutated patients was 65.6% ± 9.5%. The prognosis of patients with lung involvement was poor [HR (95% CI) = 6.312 (1.769–22.526), P = 0.005]. More progression or relapses could be found in patients with bony thorax involvement (8/17 vs. 2/20, P = 0.023), yet involvements in other sites of bones, such as craniofacial bone involvement (8/26 vs. 2/11, P = 0.688) and limb bone involvement (5/12 vs. 5/25, P = 0.240), were not correlated to disease progression or relapse. Conclusion The children with MAP2K1-mutated LCH have specific clinical features requiring clinical stratification and precise treatment. MAP2K1-mutated patients with lung involvement (especially with bony thorax involvement) had poor prognosis.

scholarly journals Unusual sites of bone involvement in Langerhans cell histiocytosis: a systematic review of the literature

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Nahid Reisi ◽  
Pouran Raeissi ◽  
Touraj Harati Khalilabad ◽  
Alireza Moafi
Keyword(s):  
Systematic Review ◽  
Dendritic Cells ◽  
Rare Disease ◽  
Langerhans Cell Histiocytosis ◽  
Case Reports ◽  
Langerhans Cell ◽  
The Other ◽  
Bone Involvement ◽  
Intracranial Extension ◽  
Pathologic Fractures

Abstract Background Langerhans cell histiocytosis (LCH) is a rare disease that originates from the uncontrolled proliferation and accumulation of bone marrow-derived immature myeloid dendritic cells. Dendritic cells are a type of histiocyte that play an important role in the human immune system and are found in the bone, skin, stomach, eyes, intestines, and lungs. Objective This systematic review aimed to collect and report published case reports of rare bone disease caused by LCH to avoid misdiagnoses or delays in diagnosis. Methods We systematically searched Scopus, PubMed, Embase, and Web of Sciences from August 1, 2000 to December 31, 2019. Studies reporting cases of LCH with rare bone involvement were included. Results We identified 60 articles including 64 cases. Of the identified cases, 31 (48.4%) involved children, and 33 (51.6%) involved adults. Additionally, 46.9% (30 individuals) were from Asian countries. The mean age of the children was 7.6 ± 4.3 years and that of the adults was 36 ± 12 years. The findings indicated that unifocal bone involvements were the most prevalent form of the disease (68.7%), and, overall, the skull and chest wall were the most commonly affected bones in both adults and children. The spine and long bones were the second most commonly affected bones in children, and the spine and jaw were the second most commonly affected bones in adults. Pain and swelling were the most frequent presenting signs among the investigated cases, and loss of consciousness, myelopathy, nerve palsy, visual loss, torticollis and clicking sounds were rare signs. Osteolytic lesions were the most frequent radiologic feature (62.5%), and intracranial hemorrhage, fluid–fluid level, dura and intracranial extension and pathologic fractures were rare radiological features. Total excision, curettage and observation in the unifocal group of patients and systemic chemotherapy in the other groups (i.e., multifocal and multisystem) were the most frequent management approaches. The recovery rates of the unifocal and multifocal groups were 77.3% and 81.8%, respectively, while that of the multisystem group was 55.5%. The rates of recurrence and mortality in the multisystem group were 11% and were higher than those in the other groups. Conclusions LCH is a rare disease that can affect any organ in the human body. However, bone is the most commonly involved organ, and rare bone involvements may be the first or only symptom of the disease due to the rarity of such lesions; a lack of familiarity with them may result in misdiagnosis or delayed diagnosis.

scholarly journals Childhood Langerhans cell histiocytosis with severe lung involvement: a nationwide cohort study

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Solenne Le Louet ◽  
Mohamed-Aziz Barkaoui ◽  
Jean Miron ◽  
Claire Galambrun ◽  
Nathalie Aladjidi ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Langerhans Cell Histiocytosis ◽  
Treatment Guidelines ◽  
Langerhans Cell ◽  
Infection Prophylaxis ◽  
Lung Involvement ◽  
Multisystem Disease ◽  
Abnormal Chest ◽  
Life Threatening ◽  
Severe Lung

Abstract Background Lung involvement in childhood Langerhans cell histiocytosis (LCH) is infrequent and rarely life threatening, but occasionally, severe presentations are observed. Methods Among 1482 children (< 15 years) registered in the French LCH registry (1994–2018), 111 (7.4%) had lung involvement. This retrospective study included data for 17 (1.1%) patients that required one or more intensive care unit (ICU) admissions for respiratory failure. Results The median age was 1.3 years at the first ICU hospitalization. Of the 17 patients, 14 presented with lung involvement at the LCH diagnosis, and 7 patients (41%) had concomitant involvement of risk-organ (hematologic, spleen, or liver). Thirty-five ICU hospitalizations were analysed. Among these, 22 (63%) were secondary to a pneumothorax, 5 (14%) were associated with important cystic lesions without pneumothorax, and 8 (23%) included a diffuse micronodular lung infiltration in the context of multisystem disease. First-line vinblastine–corticosteroid combination therapy was administered to 16 patients; 12 patients required a second-line therapy (cladribine: n = 7; etoposide-aracytine: n = 3; targeted therapy n = 2). A total of 6 children (35%) died (repeated pneumothorax: n = 3; diffuse micronodular lung infiltration in the context of multisystem disease: n = 2; following lung transplantation: n = 1). For survivors, the median follow-up after ICU was 11.2 years. Among these, 9 patients remain asymptomatic despite abnormal chest imaging. Conclusions Severe lung involvement is unusual in childhood LCH, but it is associated with high mortality. Treatment guidelines should be improved for this group of patients: viral infection prophylaxis and early administration of a new LCH therapy, such as targeted therapy.

PP – 10-YEAR FOLLOW- UP OF A SINGLE-SYSTEM LANGERHANS CELL HISTIOCYTOSIS - MULTIFOCAL BONE INVOLVEMENT

2017 ◽  
Vol 123 (2) ◽  
pp. e66
Author(s):  
RENATA MENDONÇA MORAES ◽  
JOYCE GIMENEZ MENON ◽  
JULIANA ROCHA VERRONE ◽  
JOSÉ DIVALDO PRADO ◽  
FERNANDO AUGUSTO SOARES ◽  
...  
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Bone Involvement ◽  
Single System

Langerhans cell histiocytosis with multifocal bone lesions: comparative clinical features between single and multi-systems

2009 ◽  
Vol 90 (4) ◽  
pp. 506-512 ◽  
Author(s):  
Shinsaku Imashuku ◽  
◽  
Naoko Kinugawa ◽  
Akinobu Matsuzaki ◽  
Toshiyuki Kitoh ◽  
...  
Keyword(s):  
Clinical Features ◽  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Bone Lesions

Clinical Features and Treatment Outcomes of Langerhans Cell Histiocytosis

2014 ◽  
Vol 36 (2) ◽  
pp. 125-133 ◽  
Author(s):  
Bo Eun Kim ◽  
Kyung-Nam Koh ◽  
Jin Kyung Suh ◽  
Ho Joon Im ◽  
Joon Sup Song ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Clinical Features ◽  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell

Adult Orbital Langerhans Cell Histiocytosis With Frontal Bone Involvement

2009 ◽  
Vol 25 (2) ◽  
pp. 157-158 ◽  
Author(s):  
Jason A. Sokol ◽  
Michael Kazim ◽  
Kara M. Kelly ◽  
George Lantos ◽  
Loh-Shan Leung ◽  
...  
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Frontal Bone ◽  
Langerhans Cell ◽  
Bone Involvement

Clinical Features of Pulmonary Langerhans Cell Histiocytosis in Korea

2009 ◽  
Vol 66 (2) ◽  
pp. 98 ◽  
Author(s):  
Chul Kim ◽  
Sung Hwan Jeong ◽  
Jae Jeong Shim ◽  
Seung-Ick Cha ◽  
Choonhee Son ◽  
...  
Keyword(s):  
Clinical Features ◽  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Pulmonary Langerhans Cell Histiocytosis

Langerhans cell histiocytosis mimicking lichen nitidus with bone involvement

2016 ◽  
Vol 58 (3) ◽  
pp. 231-233 ◽  
Author(s):  
Belén Lozano Masdemont ◽  
Laura Gómez-Recuero Muñoz ◽  
Ana Villanueva Álvarez-Santullano ◽  
Verónica Parra Blanco ◽  
Minia Campos Domínguez
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Bone Involvement

scholarly journals Bone metabolism in Langerhans cell histiocytosis

2018 ◽  
Vol 7 (7) ◽  
pp. R246-R253 ◽  
Author(s):  
Athanasios D Anastasilakis ◽  
Marina Tsoli ◽  
Gregory Kaltsas ◽  
Polyzois Makras
Keyword(s):  
Bone Metabolism ◽  
Langerhans Cell Histiocytosis ◽  
Cell Activation ◽  
Immune Cell ◽  
Clinical Investigation ◽  
Langerhans Cell ◽  
Bone Involvement ◽  
Bone Lesions ◽  
Bone Homeostasis ◽  
Mineral Density

Langerhans cell histiocytosis (LCH) is a rare disease of not well-defined etiology that involves immune cell activation and frequently affects the skeleton. Bone involvement in LCH usually presents in the form of osteolytic lesions along with low bone mineral density. Various molecules involved in bone metabolism are implicated in the pathogenesis of LCH or may be affected during the course of the disease, including interleukins (ILs), tumor necrosis factor α, receptor activator of NF-κB (RANK) and its soluble ligand RANKL, osteoprotegerin (OPG), periostin and sclerostin. Among them IL-17A, periostin and RANKL have been proposed as potential serum biomarkers for LCH, particularly as the interaction between RANK, RANKL and OPG not only regulates bone homeostasis through its effects on the osteoclasts but also affects the activation and survival of immune cells. Significant changes in circulating and lesional RANKL levels have been observed in LCH patients irrespective of bone involvement. Standard LCH management includes local or systematic administration of corticosteroids and chemotherapy. Given the implication of RANK, RANKL and OPG in the pathogenesis of the disease and the osteolytic nature of bone lesions, agents aiming at inhibiting the RANKL pathway and/or osteoclastic activation, such as bisphosphonates and denosumab, may have a role in the therapeutic approach of LCH although further clinical investigation is warranted.

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