TNF-α-238GA, IL-1α-889CC and IL-10–819CC Polymorphisms Confere an Increased Risk to Develop Multisystem Langerhans Cell Histiocytosis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1331-1331
Author(s):  
Paola De Filippi ◽  
Cesare Danesino ◽  
Diego Ferrarese ◽  
Annalisa De Silvestri ◽  
Carla Badulli ◽  
...  
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Bone Lesion ◽  
Multiple Organ ◽  
Langerhans Cell ◽  
Cytokine Network ◽  
Regional Lymph Nodes ◽  
Cytokines And Chemokines ◽  
Increased Risk ◽  
Tnf Α ◽  
Disseminated Disease

Abstract Langerhans cell Histiocytosis (LCH) (OMIM 604856) is a rare disorder affecting any age, with a highly variable clinical course, usually related to the number and type of organs affected at the time of presentation. The symptoms range from a solitary bone lesion that does not require treatment to a disseminated disease with multiple-organ involvement and a high mortality rate, despite aggressive treatment. The pathogenesis of LCH remains unclear, although deregulated growth, activity and trafficking of Langerhans cells (LC) are implicated. The ability of LC to migrate from the epidermis to regional lymph nodes is of pivotal importance for the induction of immune response and there is increasing evidence that both cytokines and chemokines are implicated in this function. We report the analysis of polymorphisms in genes coding for different cytokines in a population of patients with LCH in comparison to an Italian control population (n=140). We studied 40 patients, with a mean age at the disease of onset of 6.1 (±5.0) years; the 15 with single-system (SS) disease had a mean age of 7.1 (±3.9) years, while the 25 with multi-system (MS) disease had a mean age of 5.3 (±5.3) years. The Cytokine Genotyping Tray (Pel-Freez, Milwaukee, USA) was used for the detection of the following polymorphisms: Il-1α-889 C/T, Il-1β (−511 C/T; +3962 T/C), IL-1R pst1 1970 C/T, IL-RA mspa1 11100 T/C, IL-4Rα +1902 G/A, IL-12 -1188 C/A, γ IFN UTR 5644 A/T, TNF α (−308 G/A; −238 G/A), IL-2 (−330 T/G; +160 G/T), IL-4 (−1098T/G; −590 T/C; −33 T/C), IL-6 (−174 G/C; nt565 G/A), IL-10 (−1082 G/A; −819 C/T; −592 C/A). The following polymorphisms showed a different distribution in patients versus controls: IL-4–33 (p=0.048); IL-4–590 (p=0.005); IL-1α-889 (p=0.009). The correspondence analysis of these variables showed that genotypes IL-4 -33TT, IL-4 -590 TC and-1β+3962TT confer an increased risk of developing SS disease, while genotypes TNF-α-238GA, IL-1α-889CC and IL-10–819CC give an increased risk of developing MS disease. The present study supports the concept that constitutional variants affecting the cytokine network may induce susceptibility to develop LCH and also affect its manifestations. Figure Figure

Isolated Langerhans Cell Histiocytosis Bone Lesion in Pediatric Patients

2015 ◽  
Vol 153 (5) ◽  
pp. 751-757 ◽  
Author(s):  
Aren Bezdjian ◽  
Abdullah A. Alarfaj ◽  
Namrata Varma ◽  
Sam J. Daniel
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Pediatric Patients ◽  
Bone Lesion ◽  
Langerhans Cell

scholarly journals Langerhans Cell Histiocytosis as Cause of Central Diabetes Insipidus: Case Report

2018 ◽  
Vol 37 (01) ◽  
pp. 76-79 ◽  
Author(s):  
Diana Nascimento ◽  
Manoel Teixeira ◽  
Eberval Figueiredo
Keyword(s):  
Diabetes Insipidus ◽  
Langerhans Cell Histiocytosis ◽  
Clinical Presentation ◽  
Bone Lesion ◽  
Langerhans Cell ◽  
Vital Functions ◽  
Hypothalamic Pituitary Axis ◽  
The Individual ◽  
Single Bone ◽  
Made In

AbstractLangerhans cell histiocytosis (LCH) is a rare disease of the monocyte-macrophage system, characterized by the aberrant proliferation of specific dendritic cells. The clinical presentation ranges from a single bone lesion to widespread multiorgan involvement. This disease is usually considered to be a disease of childhood; however, the diagnosis is frequently made in adulthood. The course of the disease is fairly unpredictable and varies from spontaneous resolution to progress into a debilitating form, which compromises the vital functions with occasional fatal consequences. Langerhans cell histiocytosis exhibits a predilection for the hypothalamic-pituitary-axis, with diabetes insipidus being the most common endocrine consequence related to the disease, which may be prior to diagnosis or develop at any time during the course of the disease. The diagnosis of LCH should be based on histologic and immunophenotypic examination of a lesional biopsy, although other testing may be done, depending on the symptoms. There is no established, widely agreed-upon treatment of LCH, in general. The treatment depends upon the individual patient and the extent and areas of involvement. The present article aims to describe the case of a 26-year-old male patient whose symptoms started with a headache and occipital bone lesion that progressed later with diabetes insipidus.

Zoledronic acid for relapsed Langerhans cell histiocytosis with isolated skull bone lesion

2019 ◽  
Vol 61 (3) ◽  
pp. 315-317 ◽  
Author(s):  
Ko Kudo ◽  
Tatsuhiko Tanaka ◽  
Akie Kobayashi ◽  
Kiminori Terui ◽  
Etsuro Ito
Keyword(s):  
Zoledronic Acid ◽  
Langerhans Cell Histiocytosis ◽  
Bone Lesion ◽  
Langerhans Cell ◽  
Skull Bone

Inflammatory serum cytokines and chemokines increase associated with the disease extent in pediatric Langerhans cell histiocytosis

Cytokine ◽  
2017 ◽  
Vol 97 ◽  
pp. 73-79 ◽  
Author(s):  
Akira Morimoto ◽  
Yukiko Oh ◽  
Sachie Nakamura ◽  
Yoko Shioda ◽  
Tomomi Hayase ◽  
...  
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Disease Extent ◽  
Serum Cytokines ◽  
Cytokines And Chemokines

scholarly journals A Painful Shoulder Revealing Langerhans Cell Histiocytosis

2020 ◽  
pp. 24-27
Author(s):  
N. A. R. Ranaivo ◽  
M. L. Rakotomahefa Narison ◽  
M. Bemena ◽  
S. H. Raobijaona
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Clinical Presentation ◽  
Bone Lesion ◽  
Langerhans Cell ◽  
Irregular Boundary ◽  
X Ray ◽  
Multidisciplinary Consultation ◽  
Life Threatening ◽  
Spontaneous Improvement ◽  
The Right

Introduction: Langerhans cell histiocytosis is a systemic proliferative disease. It is a rare disease that can affects all tissues. Evolution can be spontaneously favorable. Multi-organ involvement may be life-threatening. We report the case of an toddler with bone lesion and issues. Case Report: It was a 33-month-old infant with right shoulder pain. Clinically, she had a swelling in the front side of the right shoulder with a limited abduction. X-ray of the right shoulder showed osteolysis with an irregular boundary of the right humeral head. The blood work was normal. In view of the painful swelling of the right shoulder, a biopsy was performed. Histological examination confirmed the diagnosis of Langerhans histiocytosis. A conservative treatment was decided after a multidisciplinary consultation meeting. After six months, spontaneous improvement was noted. Conclusion: Langerhans cell histiocytosis is a proliferative pathology that can affect one or more organs. The clinical presentation is polymorphic according to the affected organ. An extension assessment is fundamental in the management in order to determine the treatment.

scholarly journals SURG-34. MULTIDISCIPLINARY MANAGEMENT OF A PATIENT WITH OPTIC PATHWAY-HYPOTHALAMIC LANGERHANS CELL HISTIOCYTOSIS: A CASE REPORT

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii210-ii210
Author(s):  
John Emmanuel Custodio ◽  
Kevin Paul Ferraris ◽  
Joseph Erroll Navarro ◽  
Kenny Seng ◽  
Jose Carlos Alcazaren ◽  
...  
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
S100 Protein ◽  
Visual Fields ◽  
Langerhans Cell ◽  
Normal Body Mass Index ◽  
Team Approach ◽  
Hypothalamic Region ◽  
Suprasellar Region ◽  
Increased Risk ◽  
History Of

Abstract Langerhans cell histiocytosis (LCH) of the Central Nervous System (CNS) is rare. Isolated involvement of the hypothalamic region is much more extremely rare with only 0.04 to 0.6% of the cases. We report a case of a 33 year-old female who presented with a one-year history of amenorrhea and a five-month history of intermittent headache, memory lapse, and somnolence. The patient was of normal body mass index with normal visual acuity and intact visual fields. Laboratory examinations revealed panhypopituitarism with central diabetes insipidus. Cranial magnetic resonance imaging showed a large lobulated mass measuring 1.9 x 2.2 x 2 cm in the suprasellar region which extended to the pituitary infundibulum, hypothalamus and retrochiasmatic region, with surrounding edema. The patient underwent right orbitozygomatic craniotomy and subtotal excision of the mass through subfrontal and transsylvian approaches. Histopathological examination of langerhans cells were observed with positive immunohistochemical stain for CD1a and S100 protein antigen markers establishing a diagnosis of CNS LCH. Thoracoabdominal computed tomography scan and bone scan were done postoperatively and showed no evidence of extracranial lesions. The patient had been receiving prednisone and vinblastine based chemotherapy regimen. She remains to be asymptomatic and on close surveillance. To date, there is no standardized treatment strategy for CNS LCH in the adult population. An accurate histopathologic diagnosis and a specialized multidisciplinary team approach especially involving Oncology, Neurosurgery, Ophthalmology and Endocrinology are critical to optimally tailor possible effective treatment options for patients with this similar disease. Long-term follow-up is crucial due to the increased risk of local recurrence and multisystemic involvement.

scholarly journals Hemophagocytic Lymphohistiocytosis (HLH) in Langerhans Cell Histiocytosis (LCH): A Multicenter Retrospective Descriptional Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 707-707 ◽  
Author(s):  
Deepak Chellapandian ◽  
Rui Zhang ◽  
Michael Jeng ◽  
Cor Van Den Bos ◽  
Vicente Santa-María López ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Langerhans Cell Histiocytosis ◽  
Conflicts Of Interest ◽  
Interleukin 2 ◽  
Langerhans Cell ◽  
Braf V600e ◽  
Bone Lesions ◽  
Normal Reference ◽  
Increased Risk

Abstract Introduction: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia characterized by the accumulation of CD1a+ CD207+ histiocytes. Hemophagocytic lymphohistiocytosis (HLH), a non-malignant histiocytic disorder, is typified by the accumulation and activation of CD8+ T cells and macrophages, which secrete high levels of pro-inflammatory cytokines. The co-existence of LCH and HLH has been reported, albeit rarely, and is believed to be associated with a poorer outcome. To better understand the relationship between these two conditions, in this study we sought to describe the incidence, risk factors for development, and outcome of HLH when it develops in children and young adults with multisystem-LCH (MS-LCH). Methods: We conducted a retrospective study involving 14 centers and collected data on 384 MS-LCH patients aged less than 30 years and who were diagnosed between year 2000 and 2015. Data collected on the eligible patients included clinical information at the time of LCH diagnosis, clinical and laboratory parameters at HLH diagnosis (for those who developed HLH), treatment and disease outcome. Patients who developed HLH were classified as having "true-HLH", which was defined as disease fulfilling 5 of 8 HLH-2004 diagnostic criteria or as "HLH-like" disorder, which was defined as fulfilling <5 of 8 HLH diagnostic criteria but whose disease status was suggestive of HLH and treated with HLH- and/or LCH-directed therapy. Results: Of 384 MS-LCH patients, 44 (11%) were identified with HLH (29 with true HLH and 15 with an HLH-like disorder), ranging in age from 15 days to 20.6 years (median, 1.12 years). The majority of MS-LCH patients who also had HLH were females (n=27) and had accompanying risk organ (liver, spleen and/or hematopoietic system) involvement (RO+) (n=40), as opposed to non-HLH MS-LCH patients. Among nine HLH patients tested for BRAF V600E mutation status, eight were found to be positive. Twenty (45%) patients developed HLH (true or HLH-like) concurrent (±7 days) with LCH diagnosis, while 24 (55%) developed HLH >7 days before or after LCH diagnosis. The 3-year cumulative incidence of HLH (true or HLH-like) in MS-LCH was 16.8%. The 5-year overall survival of LCH patients without HLH was 98 ± 9%, while survival for those with an HLH-like disorder or true-HLH was 75 ± 12% and 70 ± 14%, respectively (P<0.0001). Age <2 years, female gender, RO+ and lack of bone involvement at LCH diagnosis were each independently associated with increased risk for HLH. Among 20 HLH patients with available data, the median soluble interleukin-2 receptor level (sIL-2R) was 16,220 U/mL (range, 1,149 to 60,420 U/mL) (normal reference <2,400 U/mL), ferritin was 505 ng/mL (range, 28 to 26,660 ng/mL) (normal reference <500 ng/mL), and sIL-2R/ferritin ratio was 42. Conclusion: The development of HLH in patients with MS-LCH was not uncommon and associated with a poorer prognosis. Young females with RO+ MS-LCH who lack bone lesions at LCH diagnosis were at increased risk of developing HLH. Ferritin levels appear to be lower in comparison to patients who develop HLH in other contexts. There are overlapping features between MS-LCH and HLH that make the clinical distinction between these disorders difficult. Accordingly, improved biomarkers are needed to facilitate the identification of HLH in patients with MS-LCH. It is anticipated that early identification of HLH and prompt intervention may improve the outcome for affected individuals. Future prospective studies are needed to better understand the underlying mechanisms and identify more effective therapies. Disclosures No relevant conflicts of interest to declare.

scholarly journals Management and outcomes of pneumothorax in adult patients with Langerhans cell Histiocytosis

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Pierre Le Guen ◽  
Sylvie Chevret ◽  
Emmanuelle Bugnet ◽  
Constance de Margerie-Mellon ◽  
Gwenaël Lorillon ◽  
...  
Keyword(s):  
Lung Function ◽  
Thoracic Surgery ◽  
Langerhans Cell Histiocytosis ◽  
Recurrent Events ◽  
Langerhans Cell ◽  
First Episode ◽  
Factors Associated ◽  
Increased Risk ◽  
Ipsilateral Recurrence

Abstract Background Pneumothorax may recur during pulmonary Langerhans cell histiocytosis (PLCH) patients’ follow-up and its management is not standardised. The factors associated with pneumothorax recurrence are unknown. Methods In this retrospective study, PLCH patients who experienced a pneumothorax and were followed for at least 6 months after the first episode were eligible. The objectives were to describe the treatment of the initial episode and pneumothorax recurrences during follow-up. We also searched for factors associated with pneumothorax recurrence and evaluated the effect on lung function outcome. Time to recurrence was estimated by the Kaplan Meier method and the cumulative hazard of recurrence handling all recurrent events was estimated. Univariate Cox models and Andersen-Gill counting process were used for statistical analyses. Results Fourty-three patients (median age 26.5 years [interquartile range (IQR), 22.9–35.4]; 26 men, 39 current smokers) were included and followed for median time of 49 months. Chest tube drainage was the main management of the initial pneumothorax, which resolved in 70% of cases. Pneumothorax recurred in 23 (53%) patients, and overall 96 pneumothoraces were observed during the study period. In the subgroup of patients who experienced pneumothorax recurrence, the median number of episodes per patient was 3 [IQR, 2–4]. All but one recurrence occurred within 2 years after the first episode. Thoracic surgery neither delayed the time of occurrence of the first ipsilateral recurrence nor reduced the overall number of recurrences during the study period, although the rate of recurrence was lower after thoracotomy than following video-assisted thoracic surgery (p = 0.03). At the time of the first pneumothorax, the presence of air trapping on lung function testing was associated with increased risk of recurrence (hazard ratio = 5.08; 95% confidence interval [1.18, 21.8]; p = 0.03). Pneumothorax recurrence did not predict subsequent lung function decline (p = 0.058). Conclusions Our results show that pneumothorax recurrences occur during an “active” phase of PLCH. In this observational study, the time of occurrence of the first ipsilateral recurrence and the overall number of pneumothorax recurrences were similar after conservative and thoracic surgical treatments. Further studies are needed to determine the best management to reduce the risk of pneumothorax recurrence in PLCH patients.

scholarly journals Adult Langerhans Cell Histiocytosis with Hepatic and Pulmonary Involvement

2015 ◽  
Vol 2015 ◽  
pp. 1-4
Author(s):  
Bruno Araujo ◽  
Francisco Costa ◽  
Joanne Lopes ◽  
Ricardo Castro
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Early Stage ◽  
Biliary Tree ◽  
Pulmonary Involvement ◽  
Multiple Organ ◽  
Langerhans Cell ◽  
Liver Involvement ◽  
Unknown Etiology ◽  
Multisystem Disease ◽  
Organ Systems

Langerhans cell histiocytosis (LCH) is a rare proliferative disorder of Langerhans cells of unknown etiology. It can involve multiple organ systems with different clinical presentation, which complicates the diagnosis. It can range from isolated to multisystem disease with different prognosis. Although common among children, liver involvement is relatively rare in adults and frequently overlooked. Natural history of liver LCH fits into two stages: an early stage with infiltration by histiocytes and a late stage with sclerosis of the biliary tree. Pulmonary findings are more common and include multiple nodules in different stages of cavitation, predominantly in the upper lobes. We present a case of adult LCH with pulmonary and biopsy proven liver involvement with resolution of the hepatic findings after treatment.

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