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Orphanet Journal of Rare Diseases Jun 2024In pediatric multi-system high risk organs (RO +) Langerhans cell histiocytosis (LCH), failing 1st line treatment has the highest mortality. We aim to present the...
BACKGROUND
In pediatric multi-system high risk organs (RO +) Langerhans cell histiocytosis (LCH), failing 1st line treatment has the highest mortality. We aim to present the outcome of failure of 1st line whether due to disease progression (DP) at end of induction or reactivation (REA) after initial better status response.
PATIENTS AND METHODS
Sixty-seven RO + LCH patients with hemopoietic, hepatic or splenic involvement, treated between 2007 and 2019 were retrospectively analyzed. The median follow-up (IQR) is 6 years (4-8.8 y).They were subjected to 2 eras of treatment; one with salvage by 2-Cda based regimen (2-CdABR) and another without.
RESULTS
Of 67 patients, M/F 40/27, median age 1.74 y (0.2-10 y), 42 failed 1st line (62.7%). Of them DP n = 22 (52%) and REA n = 20 (48%). Of those with DP, 9/22 patients received 2-CdABR, where 5 survived in better status. While the remaining 13 did not receive 2-CdABR and all of them died. Otherwise, of those with REA, 12/20 reactivated on RO + mode. Of them, 8/12 received 2-CdABR, where only one survived in better status and the remaining 4 received vinblastine-based regimen,where 2 died and 2 were rescued. RO + 5-year overall survival (OS) was 65% (CI 95% 54 -78) while the event free survival (EFS) 36% (26.3-50.1). The OS of DP 27% (14-54) versus REA 67% (49-93) p 0.004. OS of DP with 2-CdABR 56% (31-97.7) versus 8% without (2-51), p < 0.001. While OS of REA with 2-CdABR 38% (13-100) versus 74% without (53-100) p 0.7.
CONCLUSION
Survival of RO + remains limited. Failure of 1st line in RO + due to DP carries worse prognosis in relation to REA. In DP those who were not salvaged by 2-CdABR, showed dismal outcome. This could not be shown when applied in REA.
Topics: Humans; Histiocytosis, Langerhans-Cell; Male; Female; Child; Child, Preschool; Infant; Retrospective Studies; Salvage Therapy; Treatment Outcome
PubMed: 38910253
DOI: 10.1186/s13023-024-03232-8 -
BMJ Open Jun 2024Although the prognosis of Langerhans cell histiocytosis (LCH) is excellent, the high recurrence rate and permanent consequences, such as central diabetes insipidus and...
INTRODUCTION
Although the prognosis of Langerhans cell histiocytosis (LCH) is excellent, the high recurrence rate and permanent consequences, such as central diabetes insipidus and LCH-associated neurodegenerative diseases, remain to be resolved. Based on previous reports that patients with high-risk multisystem LCH show elevated levels of inflammatory molecules, we hypothesised that dexamethasone would more effectively suppress LCH-associated inflammation, especially in the central nervous system (CNS). We further hypothesised that intrathecal chemotherapy would effectively reduce CNS complications. We administer zoledronate to patients with multifocal bone LCH based on an efficacy report from a small case series.
METHODS AND ANALYSIS
This phase II study (labelled the LCH-19-MSMFB study) is designed to evaluate the significance of introducing dexamethasone and intrathecal chemotherapy for multisystem disease and zoledronate for multifocal bone disease in previously untreated, newly diagnosed children, adolescents (under 20 years) and adults under 40 years. The primary endpoint is the 3-year event-free survival rate by risk group of under 20 years and the 3-year event-free survival rate of 20 years and over.
ETHICS AND DISSEMINATION
This study was approved by the Central Review Board of the National Hospital Organisation Nagoya Medical Centre (Nagoya, Japan) on 21 January 2022 and was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp/en-latest-detail/jRCTs041210027). Written informed consent will be obtained from all patients and/or their guardians.
TRIAL REGISTRATION NUMBER
jRCTs041210027.
Topics: Humans; Histiocytosis, Langerhans-Cell; Child; Adolescent; Japan; Adult; Dexamethasone; Young Adult; Zoledronic Acid; Male; Female; Clinical Trials, Phase II as Topic; Child, Preschool; Bone Density Conservation Agents
PubMed: 38910000
DOI: 10.1136/bmjopen-2024-084159 -
Ocular Oncology and Pathology Jun 2024Mitogen-activated protein kinase kinase (MEK) inhibitors are targeted anticancer agents that are prescribed to treat a broad range of cancers. Despite their strong...
INTRODUCTION
Mitogen-activated protein kinase kinase (MEK) inhibitors are targeted anticancer agents that are prescribed to treat a broad range of cancers. Despite their strong efficacy profile, MEK inhibitors have been associated with ocular toxicities, most notably, self-limited serous detachments of the neurosensory retina. In this report, we outline 3 cases of a rarely documented toxicity, MEK inhibitor-associated ocular hypertension.
CASE PRESENTATIONS
In the first case, a 69-year-old female with metastatic cholangiocarcinoma presented with an intraocular pressure (IOP) of 25 mm Hg right eye (OD) and 27 mm Hg left eye (OS) 2 months after starting trametinib therapy. Similarly, in the second case, a 26-year-old female with Langerhans cell histiocytosis presented with an elevated IOP of 24 mm Hg bilaterally (OU) 13 months after beginning treatment with an investigational MEK inhibitor. In the third case, a 46-year-old male with Langerhans cell histiocytosis presented with a new onset of elevated IOP of 24 mm Hg 21 days after initiating treatment with cobimetinib. All 3 patients' IOP returned to normal following dorzolamide/timolol administration and continued their cancer therapy.
DISCUSSION/CONCLUSION
This report presents 3 cases of elevated IOP in patients taking three distinct MEK inhibitors which would suggest that IOP-elevating effects exist across the class of MEK inhibitors. All 3 patients had a satisfactory response to topical pressure-lowering drops while continuing their life-preserving MEK inhibitor drug dose, indicating that discontinuation of therapy may not be necessary. Due to the increasing use of MEK inhibitors, it is important that ophthalmologists familiarize themselves with the broad range of potential adverse ocular effects of MEK inhibitors.
PubMed: 38882021
DOI: 10.1159/000535427 -
JAAD Case Reports Jun 2024
PubMed: 38873574
DOI: 10.1016/j.jdcr.2024.04.018 -
Journal of the Korean Society of... May 2024Developmental dysplasia of the hip is a condition characterized by hip joint instability due to acetabular dysplasia in infancy, necessitating precise ultrasound... (Review)
Review
Developmental dysplasia of the hip is a condition characterized by hip joint instability due to acetabular dysplasia in infancy, necessitating precise ultrasound examination. Legg-Calvé-Perthes disease is caused by a temporary disruption in blood flow to the femoral head during childhood, progressing through avascular, fragmentation, re-ossification, and residual stages. Slipped capital femoral epiphysis is a condition where the femoral head shifts medially along the epiphyseal line during adolescence due to stress, such as weight-bearing. Differentiating between transient hip synovitis and septic arthritis may require joint fluid aspiration. Osteomyelitis can be associated with soft tissue edema and osteolysis. When multiple lesions are present, it is essential to distinguish between Langerhans cell histiocytosis and metastatic neuroblastoma. This review will introduce imaging techniques and typical findings for these conditions.
PubMed: 38873372
DOI: 10.3348/jksr.2024.0021 -
American Journal of Ophthalmology Case... Sep 2024We report a patient who initially visited the ophthalmology clinic for a vision loss diagnosed with Erdheim-Chester Disease (ECD).
PURPOSE
We report a patient who initially visited the ophthalmology clinic for a vision loss diagnosed with Erdheim-Chester Disease (ECD).
OBSERVATIONS
ECD is a rare non-Langerhans cell histiocytosis characterized by multisystemic organ involvement and poor prognosis. Our patient had complete vision loss due to prominent orbital involvement before any systemic symptoms appeared. This case demonstrates variable clinical manifestations of ECD.
CONCLUSIONS AND IMPORTANCE
Painless bilateral proptosis with poor response to steroid treatment should prompt consideration for ECD and systemic evaluation. In addition, in the absence of typical clinical manifestations, a thorough evaluation of the biopsy can be crucial for an accurate diagnosis.
PubMed: 38872875
DOI: 10.1016/j.ajoc.2024.102087 -
Case Reports in Gastroenterology 2024Langerhans cell histiocytosis (LCH) is a rare hematologic condition which can affect multiple organ systems and has variable presentation. LCH is more commonly seen as a...
INTRODUCTION
Langerhans cell histiocytosis (LCH) is a rare hematologic condition which can affect multiple organ systems and has variable presentation. LCH is more commonly seen as a malignancy of childhood. LCH in adulthood can have poor outcomes depending on the involvement of critical organs.
CASE PRESENTATION
We report a case of a 71-year-old female who presented with progressive weakness, weight loss, diarrhea, and jaundice, and had been undergoing outpatient workup for elevated liver enzymes for the last 2 years. She required admission to the intensive care unit for vasodilatory shock, requiring vasopressor and chronotropic support. Imaging showed an underlying multiorgan process involving the gastrointestinal tract, liver, spleen, and central nervous system. A repeat liver biopsy after a prior inconclusive one revealed the diagnosis of multisystem LCH presenting as secondary sclerosing cholangitis.
CONCLUSION
The uniqueness of this multisystem LCH case lies not only in its rarity but also in the diagnostic journey that necessitated a repeat biopsy for a conclusive diagnosis. Early identification and targeted intervention can help in ensuring better patient outcomes, especially when the presentation can overlap with various other possible conditions.
PubMed: 38868155
DOI: 10.1159/000538794 -
Cureus May 2024Spinal cord compression is a neurosurgical emergency. Symptoms of this disorder are highlighted as back pain, ambulatory difficulties, and bladder/bowel incontinence....
Spinal cord compression is a neurosurgical emergency. Symptoms of this disorder are highlighted as back pain, ambulatory difficulties, and bladder/bowel incontinence. Diagnostic imaging is not indicated in many circumstances of nonspecific back pain; however, the addition of neurologic deficits in the setting of back pain justifies radiologic imaging. Various pathologies can cause constriction of the spinal cord due to the delicate nature of spinal cord anatomy. Etiologies may include trauma, neoplasms, and infections. In this report, we present an unusual case of a 31-year-old male who presented to the emergency department with a history of chronic back pain accompanied by neurological deficits, ataxia, and bladder dysfunction. Contrast-enhanced MRI imaging heightened the suspicion of a neoplastic etiology; however, neuropathology revealed a non-neoplastic nature with abnormal lymphohistiocytic infiltrate suspicious for Langerhans cell histiocytosis or infectious etiology. A second opinion was provided by Mayo Clinic Laboratories, resulting in the definitive conclusion that the mass was non-neoplastic and tested negative for SD1a and Langerhin, biomarkers used to diagnose Langerhans cell histiocytosis. This unusual non-neoplastic lesion exemplifies one of many diverse and multifaceted pathologies that can precipitate spinal cord compression. Additionally, these findings underscore the importance of considering both neoplastic and non-neoplastic causes in the differential diagnosis of spinal cord compression, thereby enhancing clinical vigilance and improving patient outcomes for underlying spinal conditions.
PubMed: 38864071
DOI: 10.7759/cureus.60141 -
F1000Research 2023Langerhans Cell Histiocytosis (LCH) is a typically benign disorder that affects infants predominately, with adult occurrence being uncommon. We discuss the case of a...
Langerhans Cell Histiocytosis (LCH) is a typically benign disorder that affects infants predominately, with adult occurrence being uncommon. We discuss the case of a 22-year-old guy who visited our clinic complaining of three months of acute nape pain and upper limb radiculopathy. Notably, the patient had no history of trauma, fall injuries, or tuberculosis. Radiological tests identified a single osteolytic lesion within the C3 vertebral body. The lesion was removed, an anterior C3 corpectomy and discectomy were performed, and the patient's spine was reconstructed with a titanium cage and plating. The patient's nape discomfort and radiculopathy vanished almost instantly after surgery. A definitive diagnosis of LCH was confirmed through histological examination. This case report illustrates the unusual and uncommon occurrence of LCH at the C3 vertebral body, for which fusion surgery was the only viable therapeutic option. The patient's recovery from radiating pain following the surgical procedure demonstrates the effectiveness of the intervention. LCH in the cervical spine is rather rare, but it is nevertheless important to be aware of the possibility of developing it.
Topics: Humans; Histiocytosis, Langerhans-Cell; Cervical Vertebrae; Male; Young Adult; Adult
PubMed: 38854701
DOI: 10.12688/f1000research.139360.1