-
Journal of Investigative Medicine High... 2024Hemophagocytic lymphohistiocytosis (HLH) secondary to is rare, impacting <1% globally, with a mortality rate of up to 31%. Herein, we present a rare case of HLH... (Review)
Review
Hemophagocytic lymphohistiocytosis (HLH) secondary to is rare, impacting <1% globally, with a mortality rate of up to 31%. Herein, we present a rare case of HLH secondary to , affecting a 57-year-old female with rheumatoid arthritis. Extensive investigations were unrevealing and despite broad-spectrum antibiotics, her condition worsened, leading to respiratory failure requiring extracorporeal membrane oxygenation (ECMO) support, shock requiring multiple vasopressors, and acute kidney injury (AKI) requiring hemodialysis. Diagnosis confirmed disseminated histoplasmosis (DHP), prompting Amphotericin B and methylprednisolone treatment, resulting in significant improvement and discharge with posaconazole therapy. Secondary HLH, primarily arising from severe infections like DHP, is discussed. Limited research exists on this condition in human immunodeficiency virus (HIV)-seronegative individuals. Diagnosis involves HLH-2004 and HScore criteria. Managing histoplasmosis-associated HLH remains challenging due to multiorgan failure risks and treatment complexities and needs further research.
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Histoplasmosis; Female; Middle Aged; Antifungal Agents; Histoplasma; Amphotericin B
PubMed: 38813977
DOI: 10.1177/23247096241258074 -
Haematologica May 2024Not available.
Not available.
PubMed: 38813710
DOI: 10.3324/haematol.2024.285146 -
Internal Medicine (Tokyo, Japan) May 2024We herein report an unusual case of Erdheim-Chester disease (ECD), a rare non-Langerhans cell histiocytosis, and emphasize its unique presentation and diagnostic...
We herein report an unusual case of Erdheim-Chester disease (ECD), a rare non-Langerhans cell histiocytosis, and emphasize its unique presentation and diagnostic challenges. Our patient exhibited uncommon symptoms and significant organ involvement, particularly pancreatic enlargement that is not typically associated with ECD. Contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) and EUS-fine needle aspiration (EUS-FNA) play crucial roles in the comprehensive assessment of the disease, demonstrating their superiority in identifying and characterizing elusive ECD lesions. This is the first report to document pancreatic lesions in patients with ECD evaluated using CEH-EUS. EUS-FNA is valuable for diagnosing rare diseases, including ECD, with diffuse pancreatic enlargement.
PubMed: 38811216
DOI: 10.2169/internalmedicine.3864-24 -
Asian Pacific Journal of Cancer... May 2024Disease reactivation/refractory remains a major challenge in managing Langerhans cell histiocytosis (LCH). Outcomes and late sequelae should be explored.
BACKGROUND
Disease reactivation/refractory remains a major challenge in managing Langerhans cell histiocytosis (LCH). Outcomes and late sequelae should be explored.
METHODS
A multi-institutional retrospective study was conducted to describe clinical characteristics, predictive factors, outcomes and late sequelae of pediatric reactivation/refractory LCH in Thailand.
RESULTS
In all, 47 patients were studied, 25 (53.2%) patients had disease reactivation and 22 (46.8%) patients had refractory LCH. The median reactivation and refractory time were 1.59 and 0.33 years from diagnosis, respectively (p <0.001). The most common site of reactivation/refractory was the bone (n = 26, 55%), and 20 (42.6%) patients developed late sequelae. The 5-year overall survival (OS) was 76.1%. Patients with reactivation and refractory LCH performed similarly in 5-year OS (88% vs. 63%, p = 0.055). Prognostic factors associated with mortality were liver, spleen, hematopoietic system and lung reactivation (p <0.05). Lung reactivation was the only independent risk factor associated with the survival outcome (p = 0.002).
CONCLUSIONS
The outcomes of pediatric patients between reactivation and refractory LCH in Thailand were similarly desirable and mortality was minimal although late sequelae may evolve. Pulmonary reactivation/refractory was an independent risk factor associated with survival.
Topics: Humans; Histiocytosis, Langerhans-Cell; Male; Female; Retrospective Studies; Child; Prognosis; Child, Preschool; Thailand; Survival Rate; Infant; Follow-Up Studies; Adolescent; Risk Factors
PubMed: 38809656
DOI: 10.31557/APJCP.2024.25.5.1831 -
Endocrinology, Diabetes & Metabolism... Apr 2024RET mutations are implicated in 60% of medullary thyroid cancer (MTC) cases. The RET-selective tyrosine kinase inhibitor selpercatinib is associated with unprecedented...
SUMMARY
RET mutations are implicated in 60% of medullary thyroid cancer (MTC) cases. The RET-selective tyrosine kinase inhibitor selpercatinib is associated with unprecedented efficacy compared to previous multi-kinase treatments. Langerhans cell histiocytosis (LCH) is a clonal histiocytic neoplasm usually driven by somatic BRAF mutations, resulting in dysregulated MAPK signalling. We describe a 22-year-old woman with metastatic MTC to regional lymph nodes, lung and liver. Tumour tissue harboured a somatic pathogenic RET variant p.(M918T) and selpercatinib was commenced. She experienced sustained clinical, biochemical and radiological responses. Two years later, she developed rapidly progressive apical lung nodules, prompting biopsy. Histopathology demonstrated LCH with a rare BRAF variant p.(V600_K601>D). The lung nodules improved with inhaled corticosteroids. We hypothesize that selective pressure from RET blockade may have activated a downstream somatic BRAF mutation, resulting in pulmonary LCH. We recommend continued vigilance for neoplasms driven by dysregulated downstream MAPK signalling in patients undergoing selective RET inhibition.
LEARNING POINTS
Patients with RET-altered MTC can experience rapid disease improvement and sustained disease stability with selective RET blockade (selpercatinib). LCH is a clonal neoplasm driven by MAPK activation, for which the most common mechanism is BRAF mutation. Both MTC and pulmonary LCH are driven by dysregulated MAPK signalling pathway activation. We hypothesise that the RET-specific inhibitor selpercatinib may have caused the activation of dormant LCH secondary to selective pressure and clonal proliferation.
PubMed: 38804700
DOI: 10.1530/EDM-23-0079 -
Journal of Neurosurgery. Case Lessons May 2024Anaplastic lymphoma kinase (ALK)-positive histiocytosis (ALK-H) is an emerging entity in the category of histiocytic neoplasms that was first reported as a multisystemic...
BACKGROUND
Anaplastic lymphoma kinase (ALK)-positive histiocytosis (ALK-H) is an emerging entity in the category of histiocytic neoplasms that was first reported as a multisystemic disease in three infants in 2008. The clinicopathological spectrum of ALK-H has been expanded to include localized disorders in specific organs, but the features of this subtype are not well known. The authors report a case of ALK-H localized in the central nervous system that was difficult to treat and review the relevant literature.
OBSERVATIONS
The authors reviewed archival histiocytic tumors at their institute and found a pediatric case of ALK-H localized in a cerebellar hemisphere that had previously been reported as histiocytic sarcoma. Chemotherapy (approximately 1 year), additional surgery, and conventional chemotherapy (approximately 2.5 years) led to clinical remission, and maintenance chemotherapy was continued (approximately 1.5 years). Three years after completing treatment, a high-grade glioma was found in a cerebral hemisphere, and the patient died of the glioma 2 years later.
LESSONS
Although the prognosis of ALK-H is generally good according to prior cases, the authors' case required long-term conventional chemotherapy, suggesting the tumor displayed aggressive characteristics. Early administration of ALK inhibitors may be necessary.
PubMed: 38801782
DOI: 10.3171/CASE23466 -
International Journal of Surgery Case... May 2024LCH in adults is rarely encountered, with the preference in children and axial skeleton as predilection site. Limited understanding of adult LCH causes frequent...
INTRODUCTION AND IMPORTANCE
LCH in adults is rarely encountered, with the preference in children and axial skeleton as predilection site. Limited understanding of adult LCH causes frequent misdiagnosis, as our experience in an adult case of LCH threw off our differential diagnosis.
CASE PRESENTATION
A 21-year-old male was referred to our hospital due to pain in his right shoulder. Plain radiograph and MRI showed a solitary well-marginated lytic lesion on the distal third of the clavicle. Together with a clear history and physical exam, the benign bone cyst was suspected and we performed an open biopsy simultaneously with curettage followed by internal fixation using a bone graft. Pathology and immunohistochemistry dismissed our suspicion and confirmed LCH as the main diagnosis. At six months post-surgery, no signs of recurrence were seen on the fixated site nor complained by the patient.
DISCUSSION
Diagnosing LCH involves considering imaging appearances and patient demographics as initial clues. However, confirming the diagnosis requires a biopsy with proven CD1 expression. Currently, the majority of studies recommend confirming the diagnosis before initiating therapy. This precaution is necessary due to the unclear pathophysiology of LCH, which complicates the implementation of specific therapies. Based on benign features of skeletal lesions found from imaging, invasive treatment before biopsy confirmation still gave a satisfactory outcome despite not being in line with the current recommendation.
CONCLUSION
Excisional biopsy and curettage in solitary LCH yield satisfactory outcomes. However, further studies are needed with larger sample sizes and interventional designs.
PubMed: 38796936
DOI: 10.1016/j.ijscr.2024.109801 -
Antibiotics (Basel, Switzerland) Apr 2024Central nervous system (CNS) lesions, especially invasive fungal diseases (IFDs), in immunocompromised patients pose a great challenge in diagnosis and treatment. We...
Central nervous system (CNS) lesions, especially invasive fungal diseases (IFDs), in immunocompromised patients pose a great challenge in diagnosis and treatment. We report the case of a 48-year-old man with acute myeloid leukaemia and probable pulmonary aspergillosis, who developed hyposthenia of the left upper limb, after achieving leukaemia remission and while on voriconazole. Magnetic resonance imaging (MRI) showed oedematous CNS lesions with a haemorrhagic component in the right hemisphere with lepto-meningitis. After 2 weeks of antibiotics and amphotericin-B, brain biopsy revealed chronic inflammation with abscess and necrosis, while cultures were negative. Clinical recovery was attained, he was discharged on isavuconazole and allogeneic transplant was postponed, introducing azacitidine as a maintenance therapy. After initial improvement, MRI worsened; brain biopsy was repeated, showing similar histology; and 16S metagenomics sequencing analysis was positive (, ). Despite 1 month of meropenem, MRI did not improve. The computer tomography and PET scan excluded extra-cranial infectious-inflammatory sites, and auto-immune genesis (sarcoidosis, histiocytosis, CNS vasculitis) was deemed unlikely due to the histological findings and unilateral lesions. We hypothesised possible IFD with peri-lesion inflammation and methyl-prednisolone was successfully introduced. Steroid tapering is ongoing and isavuconazole discontinuation is planned with close follow-up. In conclusion, the management of CNS complications in immunocompromised patients needs an interdisciplinary approach.
PubMed: 38786116
DOI: 10.3390/antibiotics13050387 -
Frontiers in Public Health 2024Scrub typhus, caused by the , is a widespread vector-borne disease transmitted by chigger mites. Hemophagocytic lymphohistiocytosis (HLH) is considered to be one of the...
BACKGROUND
Scrub typhus, caused by the , is a widespread vector-borne disease transmitted by chigger mites. Hemophagocytic lymphohistiocytosis (HLH) is considered to be one of the potentially severe complications. The diagnosis of scrub typhus-associated HLH may be overlooked due to the non-specific clinical characteristics and the absence of pathognomonic eschar.
CASE PRESENTATION
We obtained clinical data from two patients in the South of Sichuan, China. The first case involved a 6-year-old girl who exhibited an unexplained fever and was initially diagnosed with sepsis, HLH, and pulmonary infection. The other patient presented a more severe condition characterized by multiple organ dysfunction and was initially diagnosed with septic shock, sepsis, HLH, acute kidney injury (AKI), and pulmonary infection. At first, a specific examination for scrub typhus was not performed due to the absence of a characteristic eschar. Conventional peripheral blood cultures yielded negative results in both patients, and neither of them responded to routine antibiotics. Fortunately, the causative pathogen was detected in the plasma samples of both patients using metagenomics next-generation sequencing (mNGS) and further confirmed by polymerase chain reaction. Subsequently, they both were treated with doxycycline and recovered quickly.
CONCLUSION
The unbiased mNGS provided a clinically actionable diagnosis for an uncommon pathogen-associated infectious disease that had previously evaded conventional diagnostic approaches.
Topics: Scrub Typhus; Humans; Female; Child; Orientia tsutsugamushi; Lymphohistiocytosis, Hemophagocytic; China; Male; Doxycycline
PubMed: 38784570
DOI: 10.3389/fpubh.2024.1321123 -
Haematologica May 2024Not available.
Not available.
PubMed: 38779720
DOI: 10.3324/haematol.2024.285273