Vertebral Langerhans-cell histiocytosis in childhood--a differential diagnosis of spinal osteomyelitis

BACKGROUND: The Langerhans cell histiocytosis has lots of different manifestations. Symptoms are not specific enough to identify the disease. In cases of vertebral Langerhans cell histiocytosis it is sometimes difficult to differentiate the lesions from spinal osteomyelitis. PATIENTS: Six children with Langerhans cell histiocytosis who had an operative treatment at our clinic in 1981 to 1995 have been reviewed. All patients had a localised vertebral presentation at the onset of the disease. METHODS: In this study we have been showed the clinical, radiological, histological and laboratory findings of our patients with Langerhans cell histiocytosis for an average of six years. Especially the use of diagnostic tools has been examined. RESULTS: Diagnostic tools such as radiogram, computerised tomography, bone scan and MRI and their value in finding the correct diagnosis have been described. Especially the use of MRI in early diagnosing has been discussed. Early changes in MRI have been presented as well as the useful radiological signs and MRI signs to differentiate Langerhans cell histiocytosis and spinal osteomyelitis. CONCLUSIONS: Vertebral Langerhans cell histiocytosis in childhood is a possible differential diagnosis to spinal osteomyelitis.     

High frequency ventilation in the neonatal period

There are three forms of high frequency ventilation, high frequency jet ventilation (HFJV, up to 400/min), high frequency oscillation (HFO, up to 40 Hz), and high frequency positive pressure ventilation (HFPPV, rates between 60 and 150/min). The first two forms of ventilation are still experimental and have been used only in critically ill children where respiratory failure has been unresponsive to more conventional therapy. Unfortunately, however, HFJV has already been associated with a high incidence of tracheal lesions. High-frequency positive pressure ventilation, on the other hand, using conventional ventilators, has been used and studied widely. Certain neonatal ventilators function suboptimally at increased rates, resulting in a reduction in tidal exchange with a consequent clinical deterioration. Using appropriate ventilators, arterial oxygen tensions improve and carbon dioxide tensions are reduced at fast rates in non-paralysed infants. Air-trapping, however, may be a problem in infants paralysed and ventilated at fast rates. HFPPV have been associated with a reduced incidence of pneumothoraces, but there is no knowledge of the effect of this form of ventilation on subsequent lung growth.Abbreviations IPPV intermittent positive pressure ventilation - I:E inspiratory:expiratory - HFPPV high frequency positive pressure ventilation - HFJV high frequency jet ventilation - HFO high frequency oscillation - VLBW very low birthweight - PEEP positive end expiratory pressure - RDS respiratory distress syndrome - BDP bronchopulmonary dysplasia - FiO₂ inspired oxygen concentration - PIE pulmonary interstitial emphysema     

Concomitant nodal involvement by Langerhans cell histiocytosis and Hodgkin's lymphoma

A 10‐year‐old girl with a family history of Hodgkin's lymphoma presented with a 2 month history of cervical lymphadenopathy and weight loss. Biopsy indicated concomitant nodal involvement by Langerhans cell histiocytosis and Hodgkin's lymphoma. Such an association is rare, especially so in children, but is not an isolated phenomenon, thereby prompting the question of whether Langerhans cell histiocytosis is a reactive or a neoplastic process.     

Distending pressure in infants with respiratory distress syndrome

The application of distending pressure to 40 babies with the respiratory distress syndrome (RDS) is described. Pressures greater than 10 cm H₂O were rarely used. On starting distending pressure, considerable improvements in blood gases occurred in all but 4 babies, 2 of whom had pneumothoraces and the other rapidly deteriorated and died from an intraventricular haemorrhage shortly afterwards.In 27 babies the distending pressure was applied for hypoxaemia during the course of the disease. 16 survived without further intervention, though one case eventually required long-term continuous distending pressure (CDP) for pulmonary oedema. 11 out of the 27 required intermittent positive pressure ventilation (IPPV), with 6 survivors.In 13 other babies who had not received CDP previously, the technique was used to assist weaning from IPPV. It sustained oxygenation in each case, and 12 of these babies survived.Seven babies developed pneumothoraces and 2 babies intrapulmonary cysts. 6 babies died, 3 with pneumothoraces. The overall incidence of intraventricular haemorrhage was 3 proven and 2 suspected cases. There was no evidence that distending pressure in any form increased the incidence of intracranial haemorrhage.     

Langerhans cell histiocytosis with involvement of nails and lungs in an adolescent

Skin and/or pulmonary involvement occur frequently in Langerhans cell histiocytosis (LCH) whereas nail involvement is rare. Herein, we present a case of LCH with initial nail disease and subsequent lung involvement causing recurrent pneumothoraces. Systemic chemotherapy was applied and intrapleural bleomycine and thoracoscopic pleurodesis with talc were performed. Although prognosis is not satisfactory in LCH with recurrent pneumothorax and nail involvement, the patient is under follow-up with no evidence of skin lesions, nail involvement, and pneumothorax for the last 10 months.     

Pulmonary and mediastinal lesions in children with Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is an uncommon group of disorders affecting mainly children and young adults. In children, pulmonary involvement occurs mostly in the disseminated forms; isolated pulmonary lesions are unusual. A retrospective study was undertaken on a group of 42 children diagnosed with LCH over a 19-year period. Eight children (19 %) had radiological evidence of pulmonary involvement. The lung lesions were either present at the time of diagnosis or, when appearing during the course of the disease, always coinciding with exacerbation or recurrence of the disease in other sites. Lung involvement did not appear to be an unfavourable prognostic factor. However, the toxic effects of treatment on the lungs might lead to important pulmonary sequelae. Received: 3 February 1997 Accepted: 23 June 1997     

Exploring the differential diagnosis of hemorrhagic vesicopustules in a newborn

Hemorrhagic vesicles in a newborn present a challenging differential diagnosis including both infectious and neoplastic disorders. Patients should be evaluated in an efficient manner to arrive at the correct diagnosis as quickly as possible. We present here an interesting case that outlines the methodical workup that ultimately revealed the diagnosis of congenital Langerhans cell histiocytosis. After a diagnosis of Langerhans cell histiocytosis is made, it is important to evaluate the patient thoroughly for systemic involvement. Historically, the diagnosis of congenital self-healing Langerhans cell histiocytosis was used to delineate a benign self-limited disorder limited to the skin with spontaneous resolution during the first several months of life; this disorder may also be referred to as "self-regressive Langerhans cell histiocytosis." However, some newborns with initial skin-only Langerhans cell histiocytosis progress to have multisystem disease after spontaneous resolution has occurred. For this reason, the nomenclature is changing. We suggest using the term "skin-only Langerhans cell histiocytosis." Periodic long-term follow-up is recommended to monitor for relapse or progression to systemic disease.     

A case of Langerhans cell histiocytosis presented with pneumothorax

Pneumothorax (PTX) is an unusual complication of Langerhans cell histiocytosis (LCH) in childhood. Spontaneous PTX is rare in childhood, and it is very rare in infancy. There are no specific recommendations for the treatment of PTX from LCH described in the literature. We are presenting a 19-month-old boy, who suddenly developed left-sided PTX with infiltrations in both lungs. He presented with PTX and skin lesions. He had a prolonged cardiac arrest, and although resuscitation was successful he required continuing ventilatory support (intermittent positive-pressure ventilation). Because he suddenly developed right-sided PTX and died on the second day of the admission, his LCH diagnosis was made only postmortem. So, he did not receive chemotherapy. It is likely that intermittent positive-pressure ventilation during the operation induced the development of much more multiple lung bullae, which subsequently ruptured, and/or it facilitated the development of the right-sided PTX. The patients with PTX and skin lesions, including babies, most likely have LCH and specific chemotherapy should be started in emergency, even before the final diagnosis is achieved.     

Gastrointestinal tract involvement in Langerhans cell histiocytosis: case report and literature review

Digestive tract involvement in Langerhans cell histiocytosis is exceedingly rare. We report a case of Langerhans cell histiocytosis in an otherwise thriving neonate presenting with hematochezia, anemia, and rash. We also review the few cases of Langerhans cell histiocytosis with gastrointestinal involvement reported in the English-language medical literature. Although gastrointestinal involvement can range in severity from mild to life-threatening, its presence may be indicative of multisystemic disease, and aggressive treatment should be considered.     

Severe isolated pulmonary Langerhans cell histiocytosis in a 6-year-old girl

Langerhans cell histiocytosis (LCH) usually affects different organs or bones. Isolated pulmonary disease is rare in childhood. We report about a 6-year-old girl with progressive pulmonary insufficiency, onset of clubbing at 4 years of age and honeycombing lung infiltrations on X-ray films. The radiological suspicion of primary pulmonary LCH was confirmed by the presence of CD1a positive cells in the bronchoalveolar lavage fluid. Other organs were not involved. The girl was treated according to the LCH-III International Study Protocol with a good response. Follow-up showed no reactivation of LCH but a reduced vital capacity and signs of interstitial pulmonary involvement on a CT scan. CONCLUSION: Langerhans cell histiocytosis should be considered in the aetiology of cystic lung diseases. Early responders to treatment have a high likelihood of becoming free of disease. However, pulmonary fibrosis is an important mechanism of lung remodelling in pulmonary Langerhans cell histiocytosis and the long-term prognosis is unclear.     

Hepatic involvement of Langerhans cell histiocytosis in children—imaging findings of computed tomography,magnetic resonance imaging and magnetic resonance cholangiopancreatography

Background

Langerhans cell histiocytosis is a rare disease that occurs mainly in children, and hepatic involvement is generally a poor prognostic factor.

Objective

To describe CT and MRI findings of hepatic involvement of Langerhans cell histiocytosis in children, especially the abnormal bile duct manifestation on magnetic resonance cholangiopancreatography (MRCP).

Materials and methods

Thirteen children (seven boys, six girls; mean age 28.9 months) were diagnosed with disseminated Langerhans cell histiocytosis. They underwent CT (n?=?5) or MRI (n?=?4), or CT and MRI examinations (n?=?4) to evaluate the liver involvement.

Results

Periportal abnormalities presented as band-like or nodular lesions on CT and MRI in all 13 children. The hepatic parenchymal lesions were found in the peripheral regions of the liver in seven children, including multiple nodules on MRI (n?=?6), and cystic-like lesions on CT and MRI (n?=?3). In 11 of the 13 children the dilatations of the bile ducts were observed on CT and MRI. Eight of the 13 children underwent MR cholangiopancreatography, which demonstrated stenoses or segmental stenoses with slight dilatation of the central bile ducts, including the common hepatic duct and its first-order branches. The peripheral bile ducts in these children showed segmental dilatations and stenoses.

Conclusion

Stenosis of the central bile ducts revealed by MR cholangiopancreatography was the most significant finding of liver involvement in Langerhans cell histiocytosis in children.     

Eyelid nodule: a rare presentation of Langerhans cell histiocytosis

Langerhans cell histiocytosis occurring as an isolated tumor of eyelid has rarely been reported. We report an unusual case of a 5-year-old boy who presented with a smooth nodular lesion over the right lower eyelid accompanied with hyperemia for a month. The biopsy and CD1a positivity confirmed it to be Langerhans cell histiocytosis. It was localized to the eyelid as no other organ was involved. Although Langerhans cell histiocytosis of the eyelid is exceptional, it must be included in the differential diagnosis of eyelid nodular lesions and the diagnostic and the subsequent management must be multidisciplinary.     

Isolated pulmonary Langerhans cell histiocytosis presenting with recurrent pneumothorax

We describe the outcome of a 20-month-old female and a 6-year-old male, both of whom had acutely developed severe respiratory distress with tachypnea, cyanosis and, in Patient 2, thoracic pain. Chest X-ray and CT scan showed interstitial pulmonary involvement and a bullous process with bilateral pneumothoraces for both children. Pulmonary biopsy confirmed the diagnosis of Langerhans cell histiocytosis (LCH). Laboratory testing and skeletal radiography did not reveal any other involvement of LCH. The patients received chemotherapy (prednisone, vinblastine, 6-mercaptopurine). They had recurrent episodes of pneumothorax during follow-up and placement of chest tubes was the treatment chosen. They were asymptomatic, with regression of bullae and disappearance of pneumothorax at 58 and 63 months of follow-up, respectively. Pulmonary function tests done during follow-up were normal in both patients. Despite severe pulmonary involvement, conservative surgical treatment and moderate chemotherapy produced good results in these two rare cases.     

Langerhans cell histiocytosis manifesting as recurrent simultaneous bilateral spontaneous pneumothorax in early infancy

Langerhans cell histiocytosis (LCH) is a rare disorder characterized by infiltration of either single or multiple organs by a distinct cell type that is S-100 and CD1a positive and contains ultrastructural Birbeck granules on electron microscopy. Historically, LCH included four main clinical forms: Letter-Siwe disease, Hand-Schuller-Christian disease, eosinophilic granuloma (together grouped as histiocytosis) and Hashimoto-Pritzker disease. The writing group of the Histiocytotic Society in 1987 proposed the uniform term of 'Langerhans cell histiocytosis' to encompass all the aforementioned eponymous forms. Lung involvement occurs in up to half of all children with multisystem disease and usually parallels overall disease activity. Spontaneous pneumothorax (SP) occurs in approximately 10% of children with pulmonary disease and may be a fatal complication. Patients with pulmonary LCH are likely predisposed to the development of pneumothorax based on destructive changes in the lung parenchyma. Here, we report a case of multisystem LCH in which the patient presented at 2 months of age because of simultaneous bilateral pneumothorax.     

Etoposide (VP16) in the treatment of multisystem Langerhans cell histiocytosis (histiocytosis X)

Ten children with Langerhans cell histiocytosis (histiocytosis X) either resistant to or intolerant of corticosteroids received etoposide (VP16). Nine responded. In one instance, partial diabetes insipidus was temporarily reversed. There was no major toxicity. Etoposide should be seriously considered as therapy for patients with LCH in whom the toxicity/benefit ratio of steroid therapy is unacceptably high.     

Defective alloantigen-presenting capacity of 'Langerhans cell histiocytosis cells'.

The functional activity of skin cells derived from an infant who died of multisystem Langerhans cell histiocytosis (LCH) was examined. Involved and non-involved skin was obtained at postmortem examination within three hours of death; normal epidermal Langerhans cells and 'LCH cells' were separated by means of dispase digestion. The functional activity of different populations of CD1a positive cells was assessed using the conventional six day allogeneic mixed cell reaction. Compared with Langerhans cells from a healthy control, LCH cells showed minimal functional activity. However, Langerhans cells from non-involved skin showed normal and Langerhans cells overlying involved skin showed augmented functional activity. These findings suggest that LCH is a disease in which abnormal Langerhans cells accumulate and/or proliferate in various tissues but it does not affect the entire Langerhans cell population.     

Simultaneous Occurrence of Viral-Associated Hemophagocytic Syndrome and Langerhans Cell Histiocytosis: A Case Report

Langerhans cell histiocytosis (LCH) is a class I histiocytosis characterized by the presence of the pathologic Langerhans cell, an unique histiocyte. In contrast to LCH, class II histiocytosis is characterized by the proliferation of mononuclear phagocytes other than Langerhans cells and includes sinus histiocytosis with massive lymphadenopathy, viral-associated hemophagocytic syndrome, and familial hemophagocytic lymphohistiocylosis. Until now, these two classes have been considered separate, if related, entities. We report a 10-month-old girl who presented with pyrexia, hepatosplenomegaly, an edematous skin rash, anemia, thrombocytopenia, and a markedly elevated serum IgG and IgM antibody level to cytomegalovirus. Histologic proof of both hemophagocytosis in the liver and bone marrow and LCH in the skin was obtained at presentation. The clinical course and response to treatment over 6.5 years is recorded. Although the etiology of both class I and class II histiocytosis remains unknown, we speculate that the monocytic/macrophage disorder, as well as the LCH, were both triggered by virus or viral-related monokines secreted by activated macrophages.     

Topical nitrogen mustard: an effective treatment for cutaneous Langerhans cell histiocytosis

In 16 children with multisystem Langerhans cell histiocytosis (mean age 22 months, range 5 to 36 months) severe symptomatic skin involvement was treated with topical nitrogen mustard (mechlorethamine hydrochloride). In each case, rapid clinical improvement occurred within 10 days; subsequent complete healing was observed in 14 children, and partial healing in 2 others in whom treatment was a component of palliative care. Mean duration of treatment was 3.5 months (range 2 to 6 months). Systemic treatment was averted in 11 patients because response to topical therapy was so favorable, but bone marrow or respiratory failure led to a fatal outcome in 5 other patients. Adverse effects were minimal. One patient developed contact allergy to topical nitrogen mustard after 2 years of intermittent therapy, but was successfully desensitized and was then able to continue treatment. We conclude that the topical application of nitrogen mustard is an effective treatment for cutaneous Langerhans cell histiocytosis. Although adverse effects were minimal in the short term, there remains concern about the possibility of long-term cutaneous carcinogenicity.     

Secondary acute promyelocytic leukemia following chemotherapy for non-Hodgkin's lymphoma in a child

Of the several kinds of therapy-related leukemia, therapy-related acute promyelocytic leukemia (t-APL) is most closely associated with topoisomerase II inhibitor administration for treatment of malignancies in adults. Although rare in children, the majority of therapy-related malignancies have been etoposide-related APL associated with Langerhans cell histiocytosis. The authors describe the development of t-APL after chemotherapy administered for non-Hodgkin's lymphoma (NHL) in an 8-year-old girl. One month after cessation of the 3-year chemotherapy regimen of doxorubicin and other agents but not etoposide or radiotherapy, the patient was diagnosed with t-APL with positive PML-RARA molecular abnormality. The patient attained a complete remission following treatment with all-trans retinoic acid-containing chemotherapy. Thereafter, she successfully received hematopoietic stem cell transplantation from an HLA-matched sibling donor. Development of t-APL associated with NHL in children appears to be rare.     

Biliary wall calcification in Langerhans cell histiocytosis: report of two cases

Langerhans cell histiocytosis (LCH) is a disorder of unknown pathogenesis affecting one or more organs (unifocal or disseminated form) due to clonal proliferation of Langerhans cells. Liver involvement is more frequent in the disseminated form and the radiological findings of end-stage liver disease due to LCH are similar to those of sclerosing cholangitis. We present the multidetector CT findings in two children with LCH liver involvement and the unique finding of calcification of the biliary wall.