Egyptian experience in Langerhans cells histiocytosis: frequent multisystem affection and reactivation rates.

Background: Histiocytoses are unique disorders; their clinical presentations vary from self-healing lesions to life-threatening disseminated disease. Objectives: We aimed to evaluate the different clinical presentations, frequency of reactivations, and treatment outcome of Langerhans cell histiocytosis among Egyptian children. Methods: we restrospectively analyzed the data of 37 Langerhans cell histiocytosis patients (LCH) registered at Ain Shams University Children's Hospital for clinicopathological features, treatment modalities and their outcomes. Results: Twenty seven (73%) of the studied patients with LCH had multisystem disease (MS), 24 (88.9%) of them had risk organ involvement (MS RO+) and only 3 without risk organ (MS RO-). Most of the patients received LCH III protocols. Eleven patients (29.7%) had reactivations with median time till reactivation of 17 months (IQR 5-23).Reactivation rates were 40% and 50% in patients with no evidence of active disease (NAD) and those with active disease better (AD better) at week 6 evaluation respectively (p = 0.71).We report 9 deaths (all had MS RO+, two died after reactivation and 7 had progressive disease. The 5 years EFS and OS were 49.4% and 81.2% respectively. Risk stratification did not significantly affect the EFS or OS (p = 0.64 and p = 0.5 respectively). Conclusion: A high reactivation rate was encountered in children with LCH and MS-RO + irrespective of 6 weeks response to induction therapy. A high mortality in patients with progressive disease necessitates a possible earlier aggressive salvage in such group.

Langerhans cell histiocytosis presenting as a rapidly evolving frontotemporal syndrome.

Langerhans cell histiocytosis (LCH) is a rare disorder in adults which usually manifests with involvement of multiple organ systems, including the central nervous system. We describe an unusual case of biopsy-proven LCH presenting with frontotemporal-dominant cognitive impairment with hypothalamic involvement, along with multisystem disease. We propose that the dementia was probably an immune-mediated process triggered by LCH which responded dramatically to high-dose steroids.

Pneumothorax in Patients with Pulmonary Langerhans Cell Histiocytosis.

INTRODUCTION: Pneumothorax often develops in pulmonary Langerhans cell histiocytosis (PLCH), but some patients take a long time to be correctly diagnosed. OBJECTIVES: This study assessed the frequency of pneumothorax in PLCH and analysed the role of chest computed tomography (CT) in the prompt diagnosis. PATIENTS AND MATERIAL: Of the 90 patients with PLCH seen from 2000 to 2015, 29 (32%) had pneumothorax as the initial finding. In this group, 18 (62%) patients were diagnosed within 1 month, whereas the diagnosis was delayed for 4-120 months in 11 (38%) patients. RESULTS: Patients who had pneumothorax as the initial sign of PLCH tended to be younger (mean age 27.7 ± 7.92 vs. 39.9 ± 13.21 years; P = 0.0001), male (69% vs. 43%; P = 0.028), smoked less (mean pack/years 8.4 ± 6.85 vs. 19 ± 17.16; P = 0.003), and had a significantly lower mean FVC (77.96 ± 19.62 vs. 89.47 ± 21.86% pred.; P = 0.015) and FEV1 (68.6 ± 19.93 vs. 79.4 ± 21.48% pred.; P = 0.03 than patients who had no pneumothorax. Recurrent pneumothorax was diagnosed more frequently in the group with a delayed diagnosis (82% vs. 39%; P = 0.02). CT was performed in all of the patients who were diagnosed promptly, but in none of the patients with a delayed diagnosis. CONCLUSIONS: Patients who had pneumothorax as the initial sign of PLCH were younger, more frequently men, and had greater respiratory impairment than those who had no pneumothorax. CT in patients with pneumothorax led to a correct diagnosis of this disease.

Lung Function in Pregnancy in Langerhans Cell Histiocytosis.

Pulmonary Langerhans cell histiocytosis (LCH) is a rare disease, affecting usually young people. The course of the disease is variable. In some pulmonary LCH patients a severe lung destruction and progression in spite of chemotherapy is observed, but in others just a cessation of smoking induces a regression of the disease. In the present study we seek to determine the influence of pregnancy on pulmonary function in LCH patients, an unchartered area of research. We addressed the issue by investigating eight pregnant women out of the 45 women hospitalized with the diagnosis of pulmonary LCH in the period from 2000 to 2015. For five of the eight pregnant women it was the second gestation. The median follow-up period was 120 months (range 72-175 months). Ten healthy children were born by a C-section. Two spontaneous miscarriages in the seventh week of gestation, and one tubal ectopic pregnancy were recorded. We found that pregnancy did not significantly influence pulmonary function assessed by the following indices: forced expiratory volume in 1 s (FEV1), lung vital capacity (VC), total lung capacity (TLC), residual volume (RV), diffusing capacity of the lungs for carbon monoxide (DLCO), and the distance and arterial oxygen saturation in 6-min walk test. Only one patient in the third trimester of pregnancy experienced bilateral pneumothorax, with persistent air leak. In all patients, delivery and postpartum period were uneventful. We conclude that pregnancy in pulmonary LCH patients is safe and not associated with deterioration of pulmonary function or blood oxygenation.

Rituximab therapy for patients with Langerhans cell histiocytosis-associated neurologic dysfunction.

OBJECTIVE: Since patients with langerhans cell histiocytosis and neurologic dysfunction (LCH-ND) often have incomplete treatment responses we sought a new treatment regimen. Because of clinical benefit from rituximab in multiple sclerosis patients with neurodegeneration, we evaluated its use in patients with LCH-ND. PARTICIPANTS: Eight LCH-ND patients who had failed prior therapies. METHODS: Charts of the 8 patients treated with rituximab were reviewed. Signs/symptoms and MRI responses were assessed. RESULTS: Seven of eight patients experienced some clinical improvement: gait abnormalities and tremors in four children, proprioceptive deficits in 2, and dysarthria/dysphagia in 2. Five of eight patients demonstrated improvement in intellectual/behavioral/psychological symptoms. CONCLUSION: These findings suggest that prospective studies are warranted to define safety and efficacy of rituximab for patients with LCH-ND.

Treatment of Multifocal Multisystem BRAF Positive Langerhans Cell Histiocytosis with Cladribine, Surgery and Allogenic Stem Cell Transplantation.

Langerhans cell histiocytosis (LCH) is a very rare disease in adults and as well a very rare cause of sellar expansion. The clinical presentation can be heterogeneous, from a single bone lesion to potentially fatal, widespread disease. We describe the difficulties with the diagnosis and treatment of LCH as well as successful treatment with cladribine chemotherapy and allogeneic stem cell transplantation.

Clinical Analysis of 122 Cases of Langerhans Cell Histiocytosis.

Objective To investigate the features of Langerhans cell histiocytosis (LCH). Method Skin lesions,systemic involvement,imaging characteristics,laboratory tests,immunophenotying,treatment response,and survival of 122 LCH patients treated at our center from February 1983 to August 2013 were retrospectively analyzed. Results LCH was associated with diverse skin lesions. Lung was the most involved organ,followed by bone,skin,lymph nodes,liver,spleen,oral cavity,and thyroid. Multisystem LCH was more common than single-system LCH. Single-system LCH was mostly treated by surgery,whereas multisystem LCH by combined chemotherapy. Conclusion LCH has diverse clinical manifestations,with lungs being the most often involved organ. Surgery or chemotherapy is the mainstream treatment.

Clinical Manifestations of Respiratory Bronchiolitis as an Incidental Finding in Surgical Lung Biopsies: A Retrospective Analysis of a Large Austrian Registry.

BACKGROUND: While respiratory bronchiolitis (RB) is a frequent histopathological finding in smoker's lungs, RB-associated interstitial lung disease (RB-ILD) remains a rare disease. OBJECTIVES: We analyzed how the histological finding of RB was associated with clinical information in a series of 684 consecutive surgical lung biopsies. METHODS: Retrospective analysis with delineation of clinical manifestations, smoking habits, pulmonary function test, and blood gas analysis in patients with RB in surgical lung biopsy. In 240 of these biopsies, RB was diagnosed, and in 146 of these cases a full clinical dataset was available. RESULTS: The final diagnosis of these 146 patients was consistent with RB-ILD (n = 18), pulmonary Langerhans cell histiocytosis (n = 7), various ILD (n = 9), spontaneous pneumothorax (n = 43), traumatic pneumothorax (n = 5), lung cancer (n = 41), various benign lung tumors (n = 8), and chronic pulmonary effusion (n = 15). Smoking history was positive in 93% of patients, 72% revealed centrilobular emphysema in their biopsy, and 58% described dyspnea as the main symptom. Amongst these diagnoses there were significant differences in age and smoking habits, but only small distinctions in pulmonary function test and blood gas analysis. Out of the patients with RB-ILD, 17% developed lung cancer in the later course. CONCLUSION: RB is strongly related to smoking, emphysema, and dyspnea and frequently associated with lung cancer. RB-ILD is a rare disease that may represent a considerable risk for lung cancer. Pulmonary function testing and blood gas analysis do not differ between RB-associated diseases. The finding of RB should prompt further diagnostic workup, and in case of RB-ILD, entail regular screening for lung cancer.

The natural history of skin-limited Langerhans cell histiocytosis: a single-institution experience.

INTRODUCTION: Prior reports of Langerhans cell histiocytosis (LCH) suggest that isolated skin involvement is rare and often progresses to systemic disease. More rapid access to pediatric subspecialty care has likely led to more frequent representation of this condition. The purpose of this study is to characterize the natural history of skin-limited LCH in an era of increased access to pediatric subspecialty care. MATERIALS AND METHODS: A retrospective chart review was performed on all patients newly diagnosed with LCH between 2001 and 2012 at the Children's Hospital of Wisconsin. Extensive review of laboratory, physical examination, and imaging reports was performed and data collected for patients with biopsy-proven skin LCH. RESULTS: Sixteen individuals with skin-limited LCH were identified. The median age at onset of skin eruption was birth (range, birth to 6 mo), and median duration of follow-up was 19.5 months (range, 2 wk to 10 y) from diagnosis. One patient (6%) developed pituitary disease and 1 patient (6%) had refractory skin involvement. All others experienced complete resolution. For patients without progressive or refractory disease, resolution of skin findings occurred within 7 months from onset. DISCUSSION: Progression of skin-limited to multisystem LCH likely may be less frequent than previously described.

The Nikolas Symposia and histiocytosis.

Histiocytoses are a group of rare diseases that involve histiocytes (literally tissue cells (Greek), but in reality tissue-resident macrophages and dendritic cells), which are derived from bone-marrow stem cells. Histiocytoses pose problems similar to those of other rare diseases of childhood. Individual physicians see few cases, disease material is hard to collect and families suffer from lack of information and understanding. In this article, we describe how a series of 'think tank' meetings, the Nikolas Symposia, which have concentrated on Langerhans cell histiocytosis, have furthered our understanding of this enigmatic disease.

Lung transplantation for obstructive lung diseases.

Chronic obstructive pulmonary disease (COPD) represents one of the most common indications for lung transplantation, accounting for approximately one third of all procedures performed worldwide to date. Despite this extensive experience, questions remain about the appropriate timing of transplantation in the natural history of COPD, the optimal procedure to perform, and the survival benefit achieved. Less commonly encountered obstructive lung disorders for which transplantation is occasionally performed include emphysema due to α-1-antitrypsin deficiency, lymphangioleiomyomatosis, and Langerhans cell histiocytosis. Like COPD, the application of transplantation to these rare disorders also poses several questions. This article explores issues that arise when lung transplantation is utilized for treatment of both common and uncommon obstructive lung disorders.

"Blueberry muffin" rash and large right thigh mass: a unique presentation of Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a clonal proliferation of bone marrow derived antigen-presenting cells that can involve a spectrum of cutaneous findings, with or without internal organ involvement. Neonatal LCH almost always presents with skin findings, usually petechial papules and/or erosions in a seborrheic distribution, with or without extracutaneous involvement. Previously described as varying entities, LCH is now considered a single disease process demonstrating a spectrum of clinical findings. We report a unique case of neonatal LCH presenting with a "blueberry muffin" rash in conjunction with a large soft tissue tumor.

Serial computed tomography and lung function testing in pulmonary Langerhans' cell histiocytosis.

Little is known about longitudinal lung function variation in patients with pulmonary Langerhans' cell histiocytosis (LCH). The contribution of serial lung computed tomography (CT) to managing these patients has not been evaluated. This long-term retrospective study included 49 patients who were serially evaluated by lung CT and pulmonary function tests. The lung function variation was categorised as improvement or deterioration. The extent of the CT lesions was correlated with lung function. Lung function deteriorated in ∼60% of the patients. Forced expiratory volume in 1 s (FEV(1)) and diffusing capacity of the lung for carbon monoxide (D(L,CO)) were the parameters that most frequently deteriorated. A subgroup of patients experienced a dramatic decline in FEV(1) within 2 yrs of diagnosis. Airway obstruction was the major functional pattern observed. In a multivariate analysis, % predicted FEV(1)at diagnosis was the only factor associated with the incidence of airway obstruction. The increase in cystic lesions on the lung CTs was associated with impaired lung function but did not anticipate the decline in FEV(1) or D(L,CO). Serial lung function tests are essential for following patients with pulmonary LCH, who frequently develop airway obstruction. A lung CT at diagnosis is informative, but routine sequential CTs seem less useful. A prospective study is needed to characterise those patients with early progressive disease.

Splenomegaly unresponsive to standard and salvage chemotherapy in Langerhans cell histiocytosis: a case of extramedullary hematopoiesis.

Langerhans cell histiocytosis (LCH) is a proliferative disorder of dendritic cells which has evaded efforts to clearly define pathogenesis, diagnostic criteria, and therapeutic response markers. Strides have been made at classification with the recent development of a quantified score of disease severity. Splenic involvement is an indicator of poor prognosis, with spleen size its surrogate marker in evaluation and scoring. We describe a case of pediatric LCH with progressive splenomegaly despite treatment, which when examined at splenectomy revealed no LCH involvement but extramedullary hematopoiesis. These findings thus challenge our understanding of splenomegaly as a marker of disease.