1-year survival in haemophagocytic lymphohistiocytosis: a nationwide cohort study from England 2003-2018.

Haemophagocytic lymphohistiocytosis (HLH) is a lethal syndrome of excessive immune activation. We undertook a nationwide study in England of all cases of HLH diagnosed between 2003 and 2018, using linked electronic health data from hospital admissions and death certification. We modelled interactions between demographics and comorbidities and estimated one-year survival by calendar year, age group, gender and comorbidity (haematological malignancy, auto-immune, other malignancy) using Cox regression.

Temporal Trends in the Incidence of Hemophagocytic Lymphohistiocytosis: A Nationwide Cohort Study From England 2003-2018.

Hemophagocytic lymphohistiocytosis (HLH) is rare, results in high mortality, and is increasingly being diagnosed. We aimed to quantify the incidence of diagnosed HLH and examine temporal trends in relation to age and associated diseases. Using national linked electronic health data from hospital admissions and death certification cases of HLH that were diagnosed in England between January 1, 2003, and December 31, 2018.

The international dataset on the association between Langerhans Cell Histiocytosis and other malignancies.

This article presents the international dataset of cases in which the association of Langerhans cell Histiocytosis (LCH) with other malignancies (AM) was documented occurring at any age before, concurrently or after LCH. These data are mostly derived from previously published manuscripts or from completed case report forms (CRFs) by Histiocyte Society (HS) members or colleagues. In particular, for each case of LCH-AM, the database reports all the available data about clinical and biologic characteristics of the two tumors, as well about treatment and status at follow-up.

Incidence, prevalence and survival in patients with Langerhans cell histiocytosis: A national registry study from England, 2013-2019.

This analysis is the largest population-based study to date to provide contemporary and comprehensive epidemiological estimates of all third edition of the International Classification of Diseases for Oncology (ICD-O-3) coded Langerhans cell histiocytosis (LCH) from England. People of all ages were identified from the National Cancer Registration Dataset using ICD-O-3 morphologies 9751-9754 for neoplasms diagnosed in 2013-2019. A total of 658 patients were identified, of whom 324 (49%) were children aged <15 years.

Langerhans cell histiocytosis and associated malignancies: A retrospective analysis of 270 patients.

Purpose: The frequency of Langerhans cell histiocytosis (LCH) and associated malignancies (AM) is greater than statistically expected. Here, we analyze LCH-AM co-occurrence in both children and adults.

Methods: Between 1991 and 2015, data were collected by regular questionnaires to members of the Histiocyte Society and searches in PubMed and Abstract Books.

Incidence and survival of haemophagocytic lymphohistiocytosis: A population-based cohort study from England.

Background: Haemophagocytic lymphohistiocytosis (HLH) is a rare hyper-inflammatory condition with poor outcomes.

Objectives: Few population-based estimates of the incidence and survival in adults exist. We aimed to provide these data for England.

A validation study of the identification of haemophagocytic lymphohistiocytosis in England using population-based health data.

We assessed the validity of coded healthcare data to identify cases of haemophagocytic lymphohistiocytosis (HLH). Hospital Episode Statistics (HES) identified 127 cases within five hospital Trusts 2013-2018 using ICD-10 codes D76.1, D76.

Management of children and young people with idiopathic pituitary stalk thickening, central diabetes insipidus, or both: a national clinical practice consensus guideline.

Unexplained or idiopathic pituitary stalk thickening or central diabetes insipidus not only harbours rare occult malignancies in 40% of cases but can also reflect benign congenital defects. Between 2014 and 2019, a multidisciplinary, expert national guideline development group in the UK systematically developed a management flowchart and clinical practice guideline to inform specialist care and improve outcomes in children and young people (aged <19 years) with idiopathic pituitary stalk thickening, central diabetes insipidus, or both. All such cases of idiopathic pituitary stalk thickening and central diabetes insipidus require dynamic pituitary function testing, specialist pituitary imaging, measurement of serum β-human chorionic gonadotropin and alpha-fetoprotein concentrations, chest x-ray, abdominal ultrasonography, optometry, and skeletal survey for occult disease.

Additive Prognostic Impact of Gastrointestinal Involvement in Severe Multisystem Langerhans Cell Histiocytosis.

Objective: To evaluate the prognostic impact of gastrointestinal involvement on the survival of children with Langerhans cell histiocytosis (GI-LCH) registered with the international clinical trials of the Histiocyte Society.

Study Design: This was a retrospective analysis of 2414 pediatric patients registered onto the consecutive trials DAL-HX 83, DAL-HX 90, LCH-I, LCH-II, and LCH-III.

Results: Among the 1289 patients with single-system LCH, there was no single case confined to the GI tract; 114 of 1125 (10%) patients with multisystem LCH (MS-LCH) had GI-LCH at initial presentation.

Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study.

We report the largest prospective study thus far on hematopoietic stem cell transplantation (HSCT) in hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. Although all patients with HLH typically need intensive anti-inflammatory therapy, patients with FHL also need HSCT to be cured. In the international HLH-2004 study, 187 children aged <18 years fulfilling the study inclusion criteria (5 of 8 diagnostic criteria, affected sibling, or molecular diagnosis in FHL-causative genes) underwent 209 transplants (2004-2012), defined as indicated in patients with familial/genetic, relapsing, or severe/persistent disease.

Management of severe pulmonary Langerhans cell histiocytosis in children.

Patients with pulmonary Langerhans cell histiocytosis (LCH) typically have a benign course but may have extensive cystic lung disease with rare life-threatening complications including multiple and recurrent pneumothoraces and respiratory failure. We report seven severely affected pediatric patients treated with chemotherapy, aggressive chest tube management, and pleurodesis of whom five survived. Patients with extraordinary amounts of pulmonary cystic disease and multiple pneumothoraces due to LCH can have remarkable, curative outcomes with early recognition, optimal LCH-directed therapy, and supportive care.

Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. In the HLH-94 study, with an estimated 5-year probability of survival (pSu) of 54% (95% confidence interval, 48%-60%), systemic therapy included etoposide, dexamethasone, and, from week 9, cyclosporine A (CSA). Hematopoietic stem cell transplantation (HSCT) was indicated in patients with familial/genetic, relapsing, or severe/persistent disease.

Presentation of childhood cancers to a paediatric shared care unit.

Objective: To describe the pathways by which children with cancer present to a shared care oncology unit.

Design: A population-based retrospective cohort study of children diagnosed with cancer between the years 2004 and 2014.

Setting: District General Hospital with a level 2 Paediatric Oncology Shared Care Unit.

Haematopoietic stem cell transplantation for refractory Langerhans cell histiocytosis: outcome by intensity of conditioning.

Patients with Langerhans cell histiocytosis (LCH) refractory to conventional chemotherapy have a poor outcome. There are currently two promising treatment strategies for high-risk patients: the first involves the combination of 2-chlorodeoxyadenosine and cytarabine; the other approach is allogeneic haematopoietic stem cell transplantation (HSCT). Here we evaluated 87 patients with high-risk LCH who were transplanted between 1990 and 2013.

Langerhans cell histiocytosis (LCH): guidelines for diagnosis, clinical work-up, and treatment for patients till the age of 18 years.

These guidelines for the management of patients up to 18 years with Langerhans cell histiocytosis (LCH) have been set up by a group of experts involved in the Euro Histio Net project who participated in national or international studies and in peer reviewed publications. Existing guidelines were reviewed and changed where new evidence was available in the literature up to 2012. Data and publications have been ranked according to evidence based medicine and when there was a lack of published data, consensus between experts was sought.

Role of the 2-week urgent referral pathway in childhood cancer.

Objective: To evaluate the role of the urgent 2-week referral pathway in facilitating the early diagnosis of childhood cancer.

Design: Retrospective case notes review of all children referred via the pathway and all children diagnosed as having cancer via other means over a period of 3½ years (January 2007-July 2010).

Setting: District general hospital with a shared care oncology service.

Superior vena cava obstruction: dangers of a missed diagnosis.

We report the case of a 7 year old girl who presented to the Children's Emergency Department with a 6 week history of bilateral facial and neck swelling. She had felt generally unwell, tired, with a recent onset of dry cough, and had presented multiple times to her general practitioner (GP) who after initially unsuccessfully trying an antihistamine, had given her five courses of soluble Betamethasone (corticosteroid) over six weeks, for presumed allergy; this temporarily relieved her symptoms for a couple of days each time. On subsequent referral to Accident and Emergency she was found to have a superior mediastinal mass, with a left pleural effusion and mediastinal deviation to the right.

Paediatric presentation of familial cerebral cavernoma.

We report the case of a 13-year-old male who presented with headaches and was presumed to have a brain tumour. He was subsequently found to have multiple cerebral cavernomas with haemorrhage and positive family history. We review the literature on familial cavernomas.

High incidence of hearing loss in long-term survivors of multisystem Langerhans cell histiocytosis.

Background: Ear involvement in the acute phase of Langerhans cell histiocytosis (LCH) is commonly seen and well documented, but the long-term sequelae are less well described, particularly in relation to hearing loss.

Methods: We investigated 40 patients with biopsy-proven multisystem LCH >5 years from the end of treatment, using detailed audiological assessment and CT/MRI imaging of the petrous temporal bones.

Results: The incidence of ear involvement in the acute phase of disease was 70%.

Diagnostic omission errors in acute paediatric practice: impact of a reminder system on decision-making.

Background: Diagnostic error is a significant problem in specialities characterised by diagnostic uncertainty such as primary care, emergency medicine and paediatrics. Despite wide-spread availability, computerised aids have not been shown to significantly improve diagnostic decision-making in a real world environment, mainly due to the need for prolonged system consultation. In this study performed in the clinical environment, we used a Web-based diagnostic reminder system that provided rapid advice with free text data entry to examine its impact on clinicians' decisions in an acute paediatric setting during assessments characterised by diagnostic uncertainty.

Long term morbidity and health related quality of life after multi-system Langerhans cell histiocytosis.

Background: Langerhans' cell histiocytosis, a clonal multisystem disorder, can affect children or adults resulting in long term sequelae. However, the overall morbidity for survivors has not been formally determined.

Patients And Methods: We performed a cross-sectional study of 40 unselected long term survivors of childhood multisystem Langerhans cell histiocytosis, involving clinical examination, health-related quality of life assessment, brain imaging, neuropsychometry, endocrine assessment, respiratory function tests and audiometry.

Intraocular Langerhans cell histiocytosis in a neonate resulting in bilateral loss of vision.

Intraocular involvement in Langerhans cell histiocytosis (LCH) is rare. We describe the case of a neonate with congenital disseminated LCH involving skin, liver, spleen, and intraocular structures including uvea and retina. Early and aggressive treatment according to the LCH-II treatment protocol was administered and resulted in remission of the disease.