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Case Reports in Dermatology 2024Multicentric Castleman's disease (MCD) with cutaneous involvement has rarely been discussed in dermatologic literature, with few reports. Cutaneous lesions in MCD may...
Efficacy of Siltuximab and 1,927 nm Fractional Laser for the Treatment of Cutaneous Manifestations in Castleman's Disease: The Role of Dermoscopy and Reflectance Confocal Microscopy for Lesion Evaluation.
INTRODUCTION
Multicentric Castleman's disease (MCD) with cutaneous involvement has rarely been discussed in dermatologic literature, with few reports. Cutaneous lesions in MCD may induce deep scars, causing a significant impact in the daily life of the patients. The treatment of Castleman's disease (CD) is usually a challenge, especially in case of cutaneous involvement.
CASE PRESENTATION
We report the case of a 35-year-old Caucasian man with a 3-year-old history of MCD with cutaneous involvement that we treated with a combined therapy characterized by siltuximab and 1,927 nm fractional laser. The patient showed a therapeutic response, characterized by a reduction of systemic symptoms and cutaneous manifestations.
CONCLUSION
We believe that the combination of siltuximab and 1,927 nm fractional laser might have a synergistic beneficial role in patients with cutaneous iMCD and maximize esthetic outcomes. Anyway, additional evidence is needed to validate our findings.
PubMed: 38590388
DOI: 10.1159/000536483 -
Drugs in Context 2024Castleman disease (CD) is a group of lymphoproliferative disorders that share common histopathological features yet have widely different aetiologies, clinical features...
Castleman disease (CD) is a group of lymphoproliferative disorders that share common histopathological features yet have widely different aetiologies, clinical features and grades of severity as well as treatments and outcomes. Siltuximab is currently the only therapy approved by the FDA and EMA for idiopathic multicentric CD and is recommended as first-line therapy in treatment guidelines. Despite the extensive characterization of siltuximab treatment in clinical trials, available evidence from real-world practice is still scant. This collection of clinical experiences focuses on patients treated with siltuximab therapy, particularly regarding the idiopathic multicentric CD diagnostic work-up, and on treatment administration in patients with complex disease entering differential diagnosis with CD or concomitant diseases. Thus, these data help further characterize and improve the use of siltuximab in real practice in terms of effectiveness and safety of long-term administration as well as consequences of treatment interruption.
PubMed: 38510313
DOI: 10.7573/dic.2023-9-4 -
Medicine Feb 2024Castleman disease (CD) was first included in the CSCO lymphoma diagnosis and treatment guidelines in 2021. Its diagnosis relies on lymph node pathological examination....
RATIONALE
Castleman disease (CD) was first included in the CSCO lymphoma diagnosis and treatment guidelines in 2021. Its diagnosis relies on lymph node pathological examination. Observation, surgical resection of the lesion, radiotherapy, chemotherapy, and medical therapy (e.g., rituximab, siltuximab, steroids) can be used. Due to the traumatic, incurable, and recurrent nature of surgical treatment, drug therapy has many side effects and is expensive. Exploring effective traditional Chinese medicine (TCM) comprehensive treatment methods for this disease is important and necessary.
PATIENT CONCERNS
The main symptom was recurrent lymphadenopathy, which had been surgically removed 5 times in the past. This time, lymph node enlargement occurred again, and the local hospital recommended surgical resection again. The patient could not tolerate another surgical treatment. Other targeted treatments are not available due to financial constraints.
DIAGNOSES
The case was diagnosed as CD by pathological examination, which is an important basis for the diagnosis of this disease.
INTERVENTIONS
The patient was treated with surgery in the early stage several times, later came to our hospital for the trinity of TCM integrated treatment program, which combines oral TCM with external application of TCM and intravenous drip of TCM as a syndrome of positive deficiency and phlegm-toxin internalization, and the therapeutic principle.
OUTCOMES
After nearly 3 years of comprehensive treatment with TCM, the enlarged lymph nodes could not be touched, and there was no fatigue, fever, or weight loss. During this period, the patient did not undergo surgery, chemotherapy and other western medicine treatment, and lived a normal life. It not only met the patient's expectation but also confirmed that the TCM treatment was indeed effective.
LESSONS
This case report confirms that TCM is safe and effective in the treatment of CD, which is worthy of promotion. In clinical practice, the individualized treatment for the patient, the duration of treatment, and the different disease states also affect the treatment outcome.
Topics: Humans; Castleman Disease; Medicine, Chinese Traditional; Treatment Outcome; Lymphadenopathy
PubMed: 38306555
DOI: 10.1097/MD.0000000000037110 -
International Journal of Medical... 2024Osteoporosis (OP) and diabetes are prevalent diseases in orthopedic and endocrinology departments, with OP potentially arising as a complication of diabetes. However,...
Osteoporosis (OP) and diabetes are prevalent diseases in orthopedic and endocrinology departments, with OP potentially arising as a complication of diabetes. However, the mechanism underlying diabetes-induced osteoporosis (DOP) remains enigmatic, and drug discovery in this domain is restricted, hindering research into the DOP's etiology and treatment. With the ultimate goal of preventing OP in diabetic patients, the objective of this study is to mine the genes and pathways linked to DOP using bioinformatics and databases. The present study employed text mining as the initial approach to retrieve genes commonly associated with diabetes and OP. Subsequently, functional annotation was conducted to investigate the roles and functionalities. In order to explore the interactions between proteins relevant to DOP, we constructed protein-protein interaction (PPI) networks. Furthermore, to obtain key genes and candidate drugs for DOP treatment, we conducted drug-gene interaction (DGI) analysis, complemented by a thorough examination of transcriptional factors (TFs)-miRNA co-regulation. The results through text mining revealed 110 genes that are commonly associated with both diabetes and OP. Subsequent enrichment analysis narrowed down the list to 95 symbols that were involved in PPI analysis. After DGI analysis, we identified 7 genes targeted by 11 drugs, which represent candidates for treating DOP. This study unveils ANDECALIXIMAB, SILTUXIMAB, OLOKIZUMAB, SECUKINUMAB, and IXEKIZUMAB as promising potential drugs for DOP treatment, demonstrating the significance of utilizing text mining and pathway analysis to investigate disease mechanisms and explore existing therapeutic options.
Topics: Humans; MicroRNAs; Diabetes Mellitus; Computational Biology; Data Mining; Drug Discovery
PubMed: 38250601
DOI: 10.7150/ijms.90829 -
Blood Reviews Mar 2024Idiopathic multicentric Castleman disease (iMCD) is a rare disease, and it is likely underdiagnosed because of the heterogeneity of clinical manifestations and... (Review)
Review
Idiopathic multicentric Castleman disease (iMCD) is a rare disease, and it is likely underdiagnosed because of the heterogeneity of clinical manifestations and laboratory findings. While the disease leads to significant morbidity and mortality, its causes are not yet fully elucidated. There have been significant advances in diagnosis and treatment of iMCD in the past decade, including the approval of the anti-IL-6 antibody siltuximab. In this review, we provide an update of the many new developments and publications surrounding iMCD.
Topics: Humans; Castleman Disease
PubMed: 38087716
DOI: 10.1016/j.blre.2023.101161 -
Iranian Journal of Allergy, Asthma, and... Oct 2023Inflammatory bowel disease (IBD) manifests as chronic inflammation within the gastrointestinal tract. The study focuses on a long noncoding RNA (lncRNA) known as...
Inflammatory bowel disease (IBD) manifests as chronic inflammation within the gastrointestinal tract. The study focuses on a long noncoding RNA (lncRNA) known as Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). MALAT1's misregulation has been linked with various autoimmune diseases and regulates proinflammatory cytokines. The role of IL6 in immune-triggered conditions, including IBD, is another focal point. In this research, the expression of MALAT1 and IL6 in IBD patients was meticulously analyzed to uncover potential interactions. The study involved 33 IBD patients (13 with Crohn's disease and 20 with ulcerative colitis) and 20 healthy counterparts. Quantitative real-time polymerase chain reaction determined the MALAT1 and IL6 gene expression levels. The competitive endogenous RNA (ceRNA) regulatory network was constructed using several tools, including LncRRIsearch and Cytoscape. A deep dive into the Inflammatory Bowel Disease database was undertaken to understand IL6's role in IBD. Drugs potentially targeting these genes were also pinpointed using DGIdb. Results indicated a notable elevation in the expression levels of MALAT1 and IL6 in IBD patients versus healthy controls. MALAT1 and IL6 did not show a direct linear correlation, but IL6 could serve as MALAT1's target. Analyses unveiled interactions between MALAT1 and IL6, regulated by hsa-miR-202-3p, hsa-miR-1-3p, and has-miR-9-5p. IL6's pivotal role in IBD-associated inflammation, likely interacting with other cytokines, was accentuated. Moreover, potential drugs like CILOBRADINE for MALAT1 and SILTUXIMAB for IL6 were identified. This research underscored MALAT1 and IL6's potential value as targets in diagnosis and treatment for IBD patients.
Topics: Humans; Cytokines; Inflammation; Inflammatory Bowel Diseases; Interleukin-6; MicroRNAs; RNA, Long Noncoding
PubMed: 38085149
DOI: 10.18502/ijaai.v22i5.13997 -
European Journal of Case Reports in... 2023Castleman disease (CD) is a rare lymphoproliferative disorder with various subtypes, including the HHV-8-negative/idiopathic multicentric CD (iMCD). The diagnosis of...
BACKGROUND
Castleman disease (CD) is a rare lymphoproliferative disorder with various subtypes, including the HHV-8-negative/idiopathic multicentric CD (iMCD). The diagnosis of iMCD remains challenging due to its non-specific presentation, in the form of generalised lymphadenopathies and inflammation. Two clinical presentations have been recently defined: a severe form iMCD-TAFRO and a milder form of iMCD not otherwise specified (iMCD-NOS). identification of interleukin-6 (IL-6) as a major culprit of inflammatory symptoms led to the development of anti-IL-6 therapies, with siltuximab being the approved first-line treatment.
CASE DESCRIPTION
A 16-year-old male presented with recurrent fever, night sweats and several other non-specific symptoms. After extensive evaluations, an excisional lymph node biopsy confirmed the iMCD-NOS diagnosis. The patient received high-dose steroid therapy followed by siltuximab for four years. This treatment was well tolerated with only mild neutropenia not leading to dose adjustment. On siltuximab, the patient developed two mild COVID-19 episodes. His response to siltuximab remained effective throughout four years.
DISCUSSION
The absence of biomarker or causal agent identification poses a diagnostic challenge requiring lymph node histopathology for a definitive diagnosis of iMCD. Anti-IL 6 (siltuximab) is the recommended frontline therapy, suppressing inflammation and halting disease progression. Intravenous administration every 3 to 6 weeks can impact patient quality of life, prompting further research for alternative treatments. High-dose steroids, rituximab, cyclosporine, tacrolimus, lenalidomide or combined chemotherapy such as rituximab-bortezomib-dexamethasone are among the considered options according to disease severity.
CONCLUSION
Overall, long-term siltuximab effectively controlled iMCD symptoms and was well tolerated by this young adult, who endured two mild COVID-19 episodes.
LEARNING POINTS
Lymph node biopsy rather than bone marrow biopsy is needed for the diagnosis of iMCD.We were able to control the patient's condition in the absence of cumulative toxicity during four years of siltuximab anti-IL6 therapy.Immunosuppressive anti-IL6 therapy did not worsen two episodes of COVID-19.
PubMed: 38077710
DOI: 10.12890/2023_004098 -
Journal of Medical Cases Nov 2023TAFRO syndrome, a rapidly progressive and fatal disease, is rare, and its etiology remains unknown. It is characterized by thrombocytopenia, anasarca (edema, pleural...
TAFRO syndrome, a rapidly progressive and fatal disease, is rare, and its etiology remains unknown. It is characterized by thrombocytopenia, anasarca (edema, pleural effusion, and ascites), fever, reticulin fibrosis (or renal insufficiency), and organomegaly with Castleman disease (CD)-like histological features in the lymph nodes. CD is a rare, indolent, lymphoproliferative disorder with no established curative strategies. Most idiopathic multicentric CD cases are controlled with anti-interleukin (IL)-6 therapy (tocilizumab and siltuximab) and/or rituximab. However, it is unclear whether these therapies can be directly applied to treat TAFRO syndrome. Here, we describe stepwise immunotherapy (rituximab induction therapy and cyclosporine maintenance therapy) for two cases of steroid-refractory TAFRO syndrome. A 32-year-old man visited a local hospital with sudden onset of fever and epigastralgia. The diagnosis of TAFRO syndrome was established based on the diagnostic criteria. After rituximab administration, C-reactive protein and IL-6 levels were normalized. However, the ascites persisted, with increased resistance to rituximab. Tocilizumab was also ineffective; therefore, cyclosporine was administered. After the initiation of cyclosporine treatment, the ascites decreased and ultimately disappeared. Twelve months after immunotherapy, the patient remained asymptomatic under cyclosporine maintenance therapy. Similar stepwise immunosuppressive therapy was administered to a 72-year-old man with TAFRO syndrome complicated by renal failure. After rituximab infusion, C-reactive protein was decreased. Although methylprednisolone, rituximab, tocilizumab, and cyclosporine were administered, other laboratory data and clinical symptoms remained unchanged. His level of consciousness subsequently deteriorated due to herpes zoster encephalitis, and he died. We consider the combination of rituximab induction therapy and cyclosporine maintenance therapy to be effective for TAFRO syndrome if initiated at an early stage.
PubMed: 38029058
DOI: 10.14740/jmc4160 -
American Journal of Hematology Jan 2024
Topics: Humans; Interleukin-6; Antibodies, Monoclonal; Castleman Disease
PubMed: 37867418
DOI: 10.1002/ajh.27132