scholarly journals Bisphosphonate Therapy in Langerhans Cell Histiocytosis: An International Retrospective Descriptive Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2209-2209 ◽  
Author(s):  
Deepak Chellapandian ◽  
Polyzois Makras ◽  
Gregory Kaltsas ◽  
Cor van den Bos ◽  
Anne-Sophie Carret ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Langerhans Cell Histiocytosis ◽  
Bone Pain ◽  
Conflicts Of Interest ◽  
Treatment Strategies ◽  
Bisphosphonate Therapy ◽  
Langerhans Cell ◽  
Bone Lesions ◽  
Multisystem Disease ◽  
Pathologic Fractures

Abstract Introduction: Langerhans cell histiocytosis (LCH) is a monoclonal disorder characterized by proliferation and accumulation of atypical Langerhans cells and in up to 55% of all cases somatic mutations in BRAF proves to be the driver. Although uncommon, it is potentially fatal and carries significant morbidity. Bone involvement in LCH can be destructive, painful and often associated with pathologic fractures. There is no consensus in the treatment strategies for bone LCH which could vary from simple curettage with biopsy and/or intralesional steroids to more toxic systemic chemotherapy. However, the number of treatments for this disease is limited and other options need to be explored. Bisphosphonates are osteoclast inhibitors that can target certain osteoclast markers expressed by the multinucleated giant cells in the skin, bone and lymph nodes LCH lesions and can potentially be used to alleviate bone pain and possibly control the progression of disease activity. Purpose: To evaluate the efficacy and safety of bisphosphonates in treating bone LCH and extra-osseous disease. Methods: An international multicenter retrospective chart review was conducted in children and adults with LCH who received bisphosphonates between 1995 and 2014. Results: Eighteen patients were identified from 4 centers. All received bisphosphonates therapy either at diagnosis or at ≥ 1st reactivation. Median age at start of bisphosphonates was 23.7 years (range 5.7-38.3 years), and median follow-up time post-bisphosphonate therapy was 2.8 years (range 0.9-5.0 years). Patients had either single system bone disease or bone lesions as part of their multisystem disease. Patients were treated with different bisphosphonates with majority received zoledronic acid (n=10), followed by pamidronate (n=4) and alendronate (n= 3); one patient received both pamidronate and zoledronic acid. All patients reported significant reduction in pain to either no or mild pain after administration of bisphosphonates. Thirteen of 18 patients (72%) achieved complete remission (CR) in their bone lesions, including lesions in skin (n=1), lung (n=1) and pituitary (n=1); 2 had partial response and 3 had no response. Among the 13 CR patients, 12 had no active disease for a median of 4.1 years (range 2.8 - 5.1 years) and 1 developed radiographic neurodegeneration after 2 years. Bisphosphonate therapy was well tolerated by all patients with no major toxicity. Progression-free survival (PFS) was 75 ± 11% at 3 years, with a trend favoring better PFS (P=0.24) in patients with no or first reactivation compared with those having ≥ 2 reactivations. Conclusion: Bisphosphonates is a well-tolerated medication that can significantly improve bone pain in patients with bone LCH, and may even be effective in treating extra-osseous disease. A prospective randomized trial evaluating the role of bisphosphonates in multifocal bone LCH is warranted. Disclosures No relevant conflicts of interest to declare.

scholarly journals Paediatric Langerhans Cell Histiocytosis Disease: Long-Term Sequelae in the Hypothalamic Endocrine System

2021 ◽  
pp. 1-9
Author(s):  
Elisa Vaiani ◽  
Guido Felizzia ◽  
Fabiana Lubieniecki ◽  
Jorge Braier ◽  
Alicia Belgorosky
Keyword(s):  
Anterior Pituitary ◽  
Langerhans Cell Histiocytosis ◽  
Endocrine System ◽  
Langerhans Cell ◽  
Hormone Deficiency ◽  
Bone Lesions ◽  
Pituitary Hormone ◽  
Multisystem Disease ◽  
Anterior Pituitary Hormone

Langerhans cell histiocytosis (LCH) is a disorder of the mononuclear phagocyte system that can affect almost any organ and system. The most common central nervous system (CNS) manifestation in LCH is the infiltration of the hypothalamic-pituitary region leading to destruction and neurodegeneration of CNS tissue. The latter causes the most frequent endocrinological manifestation, that is, central diabetes insipidus (CDI), and less often anterior pituitary hormone deficiency (APD). The reported incidence of CDI is estimated between 11.5 and 24% and is considered a risk factor for neurodegenerative disease and APD. Three risk factors for development of CDI are recognized in the majority of the studies: (1) multisystem disease, (2) the occurrence of reactivations or active disease for a prolonged period, and (3) the presence of craniofacial bone lesions. Since CDI may occur as the first manifestation of LCH, differential diagnosis of malignant diseases like germ cell tumours must be made. APD is almost always associated with CDI and can appear several years after the diagnosis of CDI. Growth hormone is the most commonly affected anterior pituitary hormone. Despite significant advances in the knowledge of LCH in recent years, little progress has been made in preventing long-term sequelae such as those affecting the hypothalamic-pituitary system.

scholarly journals Langerhans-Cell Histiocytoses - Epidemiology, Classification, Clinical Features, Diagnosis, Complications, Treatment and Prognosis

2016 ◽  
Vol 9 (1) ◽  
pp. 3-16 ◽  
Author(s):  
Vera E. Papochieva ◽  
Dimitrinka S. Miteva ◽  
Penka I. Perenovska ◽  
Guergana Petrova
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Eosinophilic Granuloma ◽  
Langerhans Cell ◽  
Unknown Etiology ◽  
Bone Lesions ◽  
Multisystem Disease ◽  
The Past ◽  
System Disease ◽  
Young Smokers ◽  
Underlying Pathology

Summary Histiocytoses comprise a group of diverse diseases of unknown etiology with various clinical presentation and evolution. The underlying pathology is characterised by accumulation and infiltration of variable numbers of cells of the monocyte-macrophage line in the affected tissues and organs. Histiocytoses are divided into three major classes: Langerhans cell histiocytosis (LCH), non- Langerhans cell histiocytosis, and malignant histiocytic disorders. The term LCH (also known in the past as histiocytosis X) encompasses the following rare diseases: Eosinophilic Granuloma, Hand-Schuller-Christian disease, Letterer-Siwe disease, Hashimoto-Pritzker disease, in which accumulation of pathologic Langerhans cells (LCs) leads to tissue damage. LCs usually reside in the skin and ensure protection against infections by destroying foreign substances. LC accumulation is caused by antigen stimulation and inadequate immune response. Thus, clinical LCH manifestations range from isolated disease with mono- or multifocal bone lesions to disseminated multisystem disease. LCH is a rare disease, affecting mainly children and young smokers, aged 20-50 years. Lung involvement in LCH usually presents as a mono-system disease and is characterized by Langerhans cell granulomas (LCG) infiltrating and impairing the distal bronchioles. The definite diagnosis is based on lung biopsy of CAT selected LCG areas. So far, there is no an effective treatment, but the better understanding of the mechanisms involved in the pathogenesis of the disease would help in the development of effective therapeutic strategies in the future.

Treatment of Langerhans cell histiocytosis bone lesions with zoledronic acid: a case series

2011 ◽  
Vol 93 (6) ◽  
pp. 782-786 ◽  
Author(s):  
Shanthi Sivendran ◽  
Harold Harvey ◽  
Allan Lipton ◽  
Joseph Drabick
Keyword(s):  
Zoledronic Acid ◽  
Langerhans Cell Histiocytosis ◽  
Case Series ◽  
Langerhans Cell ◽  
Bone Lesions

scholarly journals Pediatric Langerhans Cell Histiocytosis (LCH) Clinical Outcome in Hospital Civil De Guadalajara, México

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4951-4951 ◽  
Author(s):  
Katterine Rojas Rodríguez ◽  
Veronica Soto ◽  
Carlos Rodriguez-Galindo ◽  
Paola M. Friedrich ◽  
Edwin Guzmán ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Langerhans Cell Histiocytosis ◽  
Disease Risk ◽  
Conflicts Of Interest ◽  
Systemic Disease ◽  
Giant Cells ◽  
Langerhans Cell ◽  
Induction Treatment ◽  
Multisystem Disease ◽  
Clonal Proliferation

Abstract Pediatric Langerhans cell histiocytosis (LCH) clinical outcome in Hospital Civil de Guadalajara, México. Introduction : LCH results from clonal proliferation of functionally and immunophenotyped inmature round Langerhans cells along with eosinophiles, machrophages, lymphocytes and ocasionally multinucleated giant cells (1). Its incidence is 2-10 cases by million of children below 15 yr in US (2). Our objective was to describe the clinical characteristics and treatment outcome of patients with LCH at Departement of Hematology-Oncology of Hospital Civil de Guadalajara México. Methods: It was a retrospective design and 41 pediatric patients below 18 yr were included. The diagnosis was corroborated by pathology and immunohistochemistry. Variables as age, gender, localised vs systemic disease, risk organ commitment, global survival (GS) and event free survival (EFS) were analysed. We used descriptive and inferencial statistics with SPSS program. Results: There were included 41 patients from January 1st 2012 to December 31st 2017. Relation male:female was 1.1:1. Mean presentation was localised disease (58%). Bone was the principal affected structure (34%) and it was 71% to be combined with lung, lymph node and CNS compromise. Risk organ commitment was presented in 32%, being more frecquent bone marrow and liver in 22% each one. Time induction treatment was equal or below 12 weeks in 66% of patients. The 25% of patients had reactivation of LCH, with similar lesions to the beggining in 19.5%. We found statistically significant differences between dead patients (DP) (14.6%) and not dead patients (NDP) (85.4%) in clinical presentation: localised (0% in DP vs 69% in NDP) and systemic disease (100% vs 31%) (p=0,003) and risk organ commitment (100% in DP vs 20% in NDP) (p=0,000). Median age of 13 vs 24 months was for DP and NDP respectively. Conclusion: Dead patients were younger than 13 months old, with systemic disease, and risk organ commitment. We found a later asking of medical advice in DP (6 months) vs NDP (2 months). Keys words: langerhans cell histiocytosis, multisystem disease, risk organ Figure. Figure. Disclosures No relevant conflicts of interest to declare.

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 Langerhans Cell Histiocytosis of the Temporal Bone in Children: Two Cases Report

2021 ◽  
Vol 3 (3) ◽  
pp. 24-26
Author(s):  
Y. Labani ◽  
O. Oulghoul ◽  
O. Benhoummad ◽  
Y. Rochdi ◽  
A. Raji
Keyword(s):  
Computed Tomography ◽  
Temporal Bone ◽  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Bone Lesions ◽  
Self Healing ◽  
Multisystem Disease ◽  
Inflammatory Polyp ◽  
First Case ◽  
Bone Biopsies

Langerhans cell histiocytosis is a rare hematologic disease due to multiplication and accumulation of Langerhans cells, which are immature dendritic cells. The clinical presentation is highly variable and can range from isolated, self-healing skin or bone lesions to life-threatening multisystem disease. We report 2 cases confirmed by Histological and immunohistochemical evaluation of temporal bone biopsies. The first case is a 2-year-old child with chronic bilateral otorrhea and polyuria-polydipsia syndrome. Physical examination showed bilateral retroauricular redness and induration with filling all of the right and left external ear canal. Computed tomography showed osseous lysis of the temporal bone bilaterally. Magnetic resonance imaging of the brain showed the presence of pituitary infiltration. The second case is 2-year-old girl with chronic left otorrhea. Clinical examination objectified the presence of redness and induration in the left mastoid with the presence of an inflammatory polyp filling the entire left external auditory canal. Computed tomography revealed a left temporal bone lysis. Both patients were treated with chemotherapy.

scholarly journals BISPHOSPHONATES IN LANGERHANS CELL HISTIOCYTOSIS: AN INTERNATIONAL RETROSPECTIVE CASE SERIES

2016 ◽  
Vol 8 ◽  
pp. 2016033 ◽  
Author(s):  
Deepak Chellapandian ◽  
Polyzois Makras ◽  
Gregory Kaltsas ◽  
Cor Van den Bos ◽  
Lamia Naccache ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Langerhans Cell Histiocytosis ◽  
Case Series ◽  
Initial Response ◽  
Langerhans Cell ◽  
Bone Lesions ◽  
International Studies ◽  
First Line ◽  
Retrospective Case ◽  
Multisystem Disease

Background: Bone is the most common organ of involvement in patients with Langerhans cell histiocytosis (LCH), which is often painful and associated with significant morbidity from pathological fractures. Current first-line treatments include chemotherapy and steroids that are effective but often associated with adverse effects, whereas the disease may reactivate despite an initial response to first-line agents. Bisphosphonates are osteoclast inhibitors that have shown to be helpful in treating bone lesions of LCH. To date, there are no large international studies to describe their role in treating bone lesions of LCH. Method: We conducted a multicenter retrospective review of 13 patients with histologically proven LCH, who had received bisphosphonates either at diagnosis or at disease reactivation. Results: Ten patients (77%) had a single system bone disease, and 3 (23%) had bone lesions as part of multisystem disease. Median follow-up time post-bisphosphonate therapy was 4.6 years (range, 0.8 to 8.2 years). Treatment with bisphosphonates was associated with significant pain relief in almost all patients. Twelve  (92%) achieved resolution of active bone lesions, and 10 out of them had no active disease for a median of 3.5 years (range, 0.8 to 5 years). One patient did not respond. No major adverse effects were reported in this series.  Conclusion: Bisphosphonates are well-tolerated drugs that can significantly improve bone pain and induce remission in active bone LCH. Future prospective studies evaluating the role of bisphosphonates in LCH are warranted.

Zoledronic acid in treatment of bone lesions by Langerhans cell histiocytosis

2008 ◽  
Vol 27 (1) ◽  
pp. 110-113 ◽  
Author(s):  
Liliana Montella ◽  
Carmela Merola ◽  
Geraldina Merola ◽  
Luigi Petillo ◽  
Giovannella Palmieri
Keyword(s):  
Zoledronic Acid ◽  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Bone Lesions

scholarly journals A Fatal Case of Congenital Langerhans Cell Histiocytosis with Disseminated Cutaneous Lesions in a Premature Neonate

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Michio Inoue ◽  
Yoko Tomita ◽  
Tsuyoshi Egawa ◽  
Tomoaki Ioroi ◽  
Masaaki Kugo ◽  
...  
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Fatal Case ◽  
Premature Neonate ◽  
Langerhans Cell ◽  
Bone Lesions ◽  
X Rays ◽  
Cutaneous Lesions ◽  
Multisystem Disease ◽  
Premature Babies ◽  
Hands And Feet

Background. The outcome of neonates with congenital cutaneous Langerhans cell histiocytosis (LCH) is variable. Observations. We report a case of LCH in a female premature neonate born at 33-week gestation. She had disseminated cutaneous lesions, which consisted of hemorrhagic papules and vesicles, with sparse healthy skin areas, and the hands and feet were contracted with scarring and blackened. She was in respiratory failure although no apparent pulmonary or bone lesions on X-rays were noted. Skin biopsy confirmed a diagnosis of LCH due to observation of CD1a+ Langerhans cells, which lacked expression of E-cadherin and CD56. The patient died 57 hours after birth. Conclusions. Based on this case and the literature survey, the outcome of premature babies with congenital cutaneous LCH lesions is noted to be unfavorable, with the majority of such cases suffering from multisystem disease.

Langerhans cell histiocytosis in a 5-month-old presenting with biparietal masses

2010 ◽  
Vol 6 (4) ◽  
pp. 393-397 ◽  
Author(s):  
Katie L. Pricola ◽  
Jason Karamchandani ◽  
Hannes Vogel ◽  
Gary V. Dahl ◽  
Kristen W. Yeom ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Langerhans Cell Histiocytosis ◽  
Pediatric Population ◽  
Treatment Strategies ◽  
Langerhans Cell ◽  
Surrounding Tissue ◽  
Multisystem Disease ◽  
Initial Manifestation ◽  
Early Presentation ◽  
Radiographic Appearance

Langerhans cell histiocytosis (LCH) is a rare proliferative disorder that occurs most commonly in the pediatric population as a result of pathological clonal proliferation of Langerhans cells with subsequent damage and destruction to surrounding tissue. Clinically, LCH presents in a variety of ways, which often results in prolonged time to diagnosis and subsequently poorer outcomes. In this case report, the authors describe an unusually early presentation of multisystem LCH in a patient at birth, which resulted in a 5-month delay to diagnosis and treatment. This patient presented both atypically young and with an uncommon initial manifestation of multisystem disease with multiple soft-tissue swellings rather than early skin involvement. Additionally, this patient had an unusual radiographic appearance with biparietal skull destruction on initial skull radiographs and biparietal soft-tissue lesions on CT resembling cephalohematoma at 3 months of age. The clinical and radiological evaluation, pathology, and treatment strategies are discussed, with particular attention paid to the importance of further workup of atypical nonresolving cephalohematomas to prevent disease progression and poorer outcomes.

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