RARE DISEASE
Erdheim-Chester disease
Erdheim-Chester disease
Erdheim-Chester disease
Drug discovery
2
drugs
With orphan designations
Overview
Erdheim-Chester disease (ECD) is a rare, multisystemic histiocytic neoplasm characterized by BRAF V600E (50-60% of cases) and other MAPK pathway mutations. It manifests with xanthogranulomatous infiltration of bones, retroperitoneal tissues, cardiovascular system, CNS, and other organs, causing osteosclerosis, diabetes insipidus, and organ dysfunction. Treatment revolves around targeted inhibitors, with improved survival rates linked to early molecular testing and interdisciplinary management [1][6][9][12].
Categories: rare skin diseases, rare systemic and rheumatological diseases
Research Papers
459 drug discovery papers about Erdheim-Chester disease, with 7 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
459 drug discovery papers about Erdheim-Chester disease, with 7 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-24 | Adult-Onset Central Nervous System Erdheim-Chester Disease Successfully Treated With Cladribine and Cytarabine: Case Report and Literature Review.
Erdheim-Chester disease (ECD) is a rare histiocytic disorder with heterogeneous clinical manifestations. Central nervous system (CNS) involvement is associated with poor prognosis. Although targeted therapies have improved outcomes in patients with mitogen-activated protein kinase (MAPK) pathway alterations, optimal treatment strategies for adult patients with CNS ECD are still lacking. We describe a 24-year-old female with isolated CNS ECD without pathogenic genetic alterations. The disease was refractory to corticosteroids, radiotherapy, and cladribine monotherapy. Combination therapy with cladribine and cytarabine (Ara-C) led to clinical improvement and remission on radiologic imaging, and toxicities were acceptable. This case suggests that combination chemotherapy may represent an optimal therapeutic strategy for adult patients with CNS ECD. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.
2026-09-18 | Case Report: Erdheim-Chester disease presenting as abdominal cocoon syndrome
Erdheim-Chester disease (ECD) is a rare histiocytic neoplasm driven by MAPK pathway mutations. Although it frequently involves the bones, heart, and kidneys, initial manifestations predominantly affecting the gastrointestinal tract and mesentery are exceedingly rare, often leading to significant delays in clinical diagnosis. This report describes a 61-year-old female patient who presented with recurrent abdominal pain over several months and was initially diagnosed with a conventional “adhesive bowel obstruction” at an external hospital. However, surgical exploration revealed a classic “abdominal cocoon” presentation and symptoms showed no significant improvement postoperatively. Abdominal CT upon admission revealed diffuse thickening of the peritoneum, omentum, and mesentery with substantial peritoneal and pelvic effusion. Laboratory findings revealed autoimmune serological abnormalities, including positive ANA, anti-SSA, and anti-Ro-52 antibodies, without characteristic clinical manifestations of a defined connective tissue disease. Pathological review of resected specimens revealed extensive foamy histiocytic proliferation in the small intestine and greater omentum, with immunohistochemical findings supporting ECD and molecular confirmation of the BRAF V600E mutation. Systemic PET-CT further delineated multisystem infiltration, and bone marrow evaluation ruled out the possibility of overlapping myeloid tumors. Following multidisciplinary team (MDT) confirmation, the patient received vemurafenib-based targeted therapy, together with hydroxychloroquine following rheumatologic evaluation for the associated immunological abnormalities, resulting in substantial clinical improvement. This case highlights a rare gastrointestinal manifestation of ECD mimicking a surgical disorder and underscores the importance of integrating imaging, pathology, and molecular testing in patients with atypical intestinal manifestations.
2026-09-09 | Case Report: Pediatric Erdheim-Chester disease with cerebral ventricular system infiltration and epiphyseal involvement.
Erdheim-Chester disease (ECD) is an extremely rare non-Langerhans cell histiocytosis, a category of hematologic disorders characterized by the proliferation of foamy histiocytes. ECD predominantly affects adults, and pediatric cases with cerebral ventricular system involvement are exceptionally rare, with only a few previous reports. Moreover, epiphyseal involvement has not been characterized by magnetic resonance imaging (MRI) in children with ECD. Here we present a pediatric case of ECD involving both the cerebral ventricular system and epiphyses, highlighting diagnostic challenges and novel imaging findings relevant to pediatric hematologists. An 11-year-old boy presented with progressive gait disturbance, growth retardation, left knee pain, dysuria, and nocturia over two years. Imaging revealed a mass in the right lateral ventricle, patchy osteosclerosis of the tibial epiphyses, and bilateral cerebellar white matter lesions showing the "crab sign" (central cavitation within the dentate nuclei on Fluid Attenuated Inversion Recovery (FLAIR) sequences). The ventricular mass was surgically resected. Histopathology and immunohistochemistry (CD68+, CD163+, CD1a-) confirmed the diagnosis of ECD, and molecular analysis detected a BRAF V600E mutation (6.40%). The patient received dabrafenib (a BRAF inhibitor), interferon alpha-2b, and desmopressin. At the 32-month follow-up, the patient had become non-ambulatory and exhibited speech delay, partly due to poor medication adherence, highlighting that even brief interruption of dabrafenib therapy can lead to rapid disease progression. For pediatric hematologists, this case strongly demonstrates that continuous administration of dabrafenib is essential for controlling disease in children with BRAF V600E-mutated ECD. This report presents a rare pediatric case of ECD characterized by involvement of both the cerebral ventricular system and epiphyses. We suggest that persistent bladder wall thickening (≥1.5 cm) may serve as a novel imaging indicator of urinary tract involvement in ECD, although histological confirmation is required. The "crab sign" could aid in the early diagnosis of central nervous system involvement. Importantly, this case illustrates that continuous administration of dabrafenib is crucial for disease management in children with BRAF V600E-mutated ECD, as even a brief interruption in therapy can result in rapid and severe deterioration. Our findings highlight the necessity of multimodal imaging and molecular analysis for accurate diagnosis and targeted therapeutic strategies in pediatric ECD.
2026-08-27 | Erdheim-Chester disease diagnosed and treated at the Hematology and Oncology Clinic of the Brno University Hospital in the last 26 years. Description of 6 cases and an overview of the symptoms and treatment of this disease
Erdheimova-Chesterova choroba (ECD) je malign histiocytrn nemoc, kter je obvykle provzen systmovou zntlivou reakc, kter me bt zhodnocena jako horeka nejasnho pvodu (fever of unknown origin). Charakteristick jsou osteosklerotick kostn zmny. Typickm znakem je zven akumulace osteotropnch radiofarmak v okol kolennch kloub (hot knees) a tvorba retroperitonelnch infiltrt. ECD me postihnout prakticky kterkoli orgn. Jej incidence v dospl populaci byla stanovena v Evrop i v USA na 3 ppady/10 milion dosplch. Poet diagnostikovanch ppad v poslednch letech narst z dvodu lep informovanosti lka. Na hematonkologick klinice v Brn jsme za poslednch 26 let diagnostikovali a lili est ppad ECD. Ke stanoven diagnzy vedly: bolesti v dolnch konetinch s atypickou strukturou skeletu (dva ppady), diabetes insipidus (dva ppady), B-symptomy, febrilie a nava (dva ppady), retroperitoneln fibrza (dva ppady), typick obraz pro ECD na scintigrafii skeletu proveden z jin indikace (jeden ppad), oboustrann exoftalmus (jeden ppad). Vechny pacienty jsme lili kladribinem asto doplnnm o infuze cyklofosfamidu. Lbu meme hodnotit jen u 4 pacient, dva z nich jsou v kompletn a dva v parciln remisi, dlka sledovn tchto pacient je 208, 196, 83 a 30 msc. Pt pacient ije, ale pestal dochzet do na ambulance a u estho pacienta v dob hodnocen probh lba. Clem textu je upozornit na pznaky, kter mohou ECD ohlaovat, a na jej lbu. Diagnzu mohou stanovit ortopedov clenou biopsi kosti, urologov odbrem histologie z retroperitonea, endokrinologov pi hledn piny diabetu insipidu. Z dostupnch zobrazovacch metod nejlpe informuje FDG-PET/CT vyeten o rozsahu choroby. Pro odhalen vech osteosklerotickch loisek je vhodn zobrazen pomoc radiofarmak, kter detekuj novotvorbu kosti (scintigrafie skeletu anebo NaF-PET/CT).
2026-08-05 | Erdheim-Chester Disease: A Rare Non-Langerhans Cell Histiocytosis with Pathognomonic Multisystem Imaging Findings: Case Report Illustrating the Classic Radiological Triad
Background: Erdheim?Chester disease (ECD) is a rare non-Langerhans cell histiocytic neoplasm characterised by xanthogranulomatous infiltration of multiple organ systems by foamy CD68-positive, CD1a-negative histiocytes. The condition produces a highly characteristic constellation of skeletal, retroperitoneal and cardiovascular imaging findings, and in the majority of cases the radiologist is the first physician to raise the diagnosis. Case Presentation: We report a case of ECD in a middle-aged male who presented with insidious bilateral knee pain, polyuria and incidentally detected renal impairment. Plain radiographs of both lower limbs demonstrated bilateral, symmetric metadiaphyseal osteosclerosis of the distal femora and proximal tibiae with characteristic sparing of the epiphyses. Contrast-enhanced computed tomography (CECT) of the abdomen revealed symmetric perinephric soft-tissue infiltration producing the ?hairy kidney? appearance with thickened bridging perirenal septa, bilateral hydroureteronephrosis, and circumferential periaortic soft tissue extending from the descending thoracic aorta to the iliac bifurcation, constituting the ?coated aorta? sign. CT of the thorax showed smooth interlobular septal thickening, pericardial thickening and a right atrial pseudotumour. Magnetic resonance imaging of the sella demonstrated loss of the posterior pituitary bright spot with infundibular thickening. Technetium-99m methylene diphosphonate (99mTc-MDP) bone scintigraphy showed intense symmetric tracer uptake in the distal femora and proximal tibiae. Management and Outcome: Image-guided biopsy of the perinephric soft tissue demonstrated foamy histiocytes within a fibrotic stroma that were immunoreactive for CD68 and negative for CD1a and S100, confirming the diagnosis. Molecular analysis identified a BRAF V600E mutation, and targeted therapy with a BRAF inhibitor was initiated. Interval imaging at six months showed regression of the periaortic and perinephric soft tissue with improvement in hydronephrosis. Conclusion: This case underscores the pivotal role of imaging in the recognition of ECD. The triad of bilateral symmetric metadiaphyseal osteosclerosis of the long bones, hairy kidneys and coated aorta is sufficiently distinctive to permit a confident radiological suggestion of the diagnosis, allowing targeted biopsy, molecular characterisation and early institution of MAPK-directed therapy.
proteins
2026-08-28 | Treatment of Erdheim-Chester disease from the perspective in 2026.
With the discovery of new drugs, treatment of Erdheim-Chester disease (ECD) is gradually evolving and changing. The text provides an overview of effective drugs available in 2026 for patients with ECD. Treatment options: We consider it appropriate to divide treatment into treatment targeting the inflammatory reaction induced by ECD, and treatment targeting malignant histiocytes. To suppress the inflammatory reaction, high doses of glucocorticoids can be used, but only short-term. For long-term suppression of the inflammatory reaction, anakinra is most commonly used. In rare cases, a similar effect has been reported with canakinumab, as well as with sirolimus and anti-TNF drugs. Anakinra is used both alone and in combination with other drugs. ECD cells, like histiocytosis cells from Langerhans cells, are derived from a monocytic lineage, which similarly to the lymphocytic lineage, is very sensitive to cladribine (2-chloro-2'-deoxyadenosine). This drug is the most effective cytostatic agent for patients with ECD. In several smaller clinical studies, the benefit of treatment with interferon alfa has been described. Thus, interferon alfa, despite its side effects, represents one of the treatment options. In cases of severe ECD and the presence of the BRAFV600E mutation, two drugs are recommended - vemurafenib and dabrafenib. For patients with a severe course without the BRAFV600E mutation, MEK kinase inhibitors trametinib and cobimetinib are recommended. The literature contains conflicting conclusions in studies evaluating the dependence of the effectiveness of these drugs on the detection of mutations in the MAPK signaling pathway. Targeted therapy is associated with numerous side effects, as well as the risk of relapse after its discontinuation. If the administered drugs trigger an inflammatory response, anakinra is again used to suppress it. Treatment of ECD always requires an assessment of the extent of the disease and degree of organ damage in order to choose the appropriate therapy.
2026-07-25 | Cerebrovascular involvement in Erdheim-Chester disease: a case report and systematic literature review.
Intracranial perivascular/vascular infiltrations and stenoses related to Erdheim-Chester disease (ECD), often associated with ischemic events, are rarely documented. This study aims to characterize intracranial perivascular/vascular infiltrations and stenoses. We first report a new case of strokes revealing ECD with intracranial arterial involvement. We then searched all English- and French-language publications from database inception to November 2025 across 12 different search interfaces, including grey literature sources. Vascular involvement was defined by the presence of intracranial perivascular/vascular infiltrations and stenosis on imaging and/or histopathological evidence of small-vessel involvement. Cases with intracranial nodules or masses abutting vessels but without clear longitudinal perivascular infiltration were excluded. We present a case of recurrent strokes with intracranial vertebral and basilar artery wall stenosis, and aortitis. Initially diagnosed as giant cell arteritis, the patient was treated with corticosteroids, cyclophosphamide followed by methotrexate, but relapsed. The identification of tibial osteosclerosis led to the diagnosis of ECD, with a favorable response to anakinra. Twelve relevant articles were retrieved, in addition to our own case. Most patients exhibited focal cerebrovascular signs (11/13) and associated parenchymal involvement (11/13). Intracranial perivascular/vascular infiltrations and stenoses involved the carotid arteries (7/13), the vertebrobasilar arteries (1/13), or both territories (4/13). Aorta was involved in 8/12 cases. Among the nine patients with available follow-up data, five had poor overall or neurovascular outcomes. Intracranial perivascular/vascular infiltrations and stenoses, which leads to recurrent focal ischemic events, represents a likely underdiagnosed CNS pattern in ECD, referred to as "cerebrovascular ECD", which worsens overall prognosis. Vascular imaging should be included in brain MRI protocols for patients with ECD, given the overlap with parenchymal involvement.
2026-03-15 | Single-center real-world data on the efficacy, safety, and current availability of pegylated interferon-α in hematologic neoplasms
Aims: Pegylated interferon-α (PEG-IFN-α) offers improved pharmacokinetics compared with conventional interferon-α (IFN-α), yet real-world data on its clinical activity and safety across heterogeneous hematologic neoplasms are limited. This study aimed to evaluate the real-world efficacy, durability of response, and toxicity of PEG-IFN-α in patients with diverse hematologic neoplasms. Methods: This retrospective study evaluated the efficacy, duration of response, and toxicity of PEG-IFN-α using patient medical records and hospital electronic registries. Thirty patients were included: polycythemia vera (PV, n=12), essential thrombocytosis (ET, n=6), chronic myeloid leukemia (n=2), primary myelofibrosis (n=1), systemic mastocytosis (SM,n=3), hypereosinophilic syndrome (HES, n=1), Erdheim–Chester disease (ECD, n=4), and lymphomatoid granulomatosis (LYG, n=1). Results: PEG-IFN-α was initiated due to resistance to prior therapies in 12 patients (40%), intolerance or toxicity in 10 patients (33.3%), and as first-line treatment in 8 patients (26.7%). Among PV patients, a complete response was achieved in 41.6% and a partial response in 50%. In ET patients, 83.3% achieved a complete response, while 16.7% showed no response. All patients with SM demonstrated clinical improvement when PEG-IFN-α was used as first-line therapy. In ECD patients, follow-up PET imaging showed stable disease in two patients, partial response in one, and no response in one. Partial responses were also observed in patients with HES and LYG. Treatment-related toxicity occurred in 8 patients (26.6%) and led to treatment discontinuation in 6 patients (20%) (including cytopenias, influenza-like symptoms, and elevated liver enzymes). Conclusion: In this real-world cohort, PEG-IFN-α showed encouraging activity across several hematologic neoplasms, with toxicity and discontinuation rates in line with previously published series of conventional interferon-α; however, its clinical use remains limited by regulatory and access constraints.
2026-02-20 | Multiple opportunistic infections revealing Erdheim-Chester disease: an atypical presentation.
This case describes a man in his mid 60s from Mexico who presented with respiratory failure and elevated inflammatory biomarkers. Initial investigations revealed multiple opportunistic infections. A PET-CT scan showed variable uptake in bilateral intraconal masses, dural venous sinuses, paranasal sinuses, lungs, pericardium and both distal femurs. Bone biopsy confirmed clonal histiocytosis (CD68+, CD163+, Fascin+, BRAF-V600E+), leading to a diagnosis of Erdheim-Chester disease (ECD), a rare non-Langerhans histiocytosis affecting multiple systems.As vemurafenib was unavailable in Mexico, pegylated interferon alpha (PEG-IFN-α) was initiated, producing significant clinical and biomarker improvement. The patient was discharged in stable condition and continues close multidisciplinary follow-up with infectious disease, cardiology, nephrology, pulmonology and haematology teams.This case highlights the importance of considering ECD in the differential diagnosis of multisystem diseases of unknown origin, especially with unusual manifestations such as multiple opportunistic infections, and reinforces the value of a coordinated, multidisciplinary approach in managing complex presentations.
2025-11-03 | Clinical and molecular predictors of interferon-α response in erdheim-chester disease and myeloproliferative neoplasm.
Abstract Background: Erdheim–Chester disease (ECD) is a rare clonal histiocytosis driven by MAPK pathway somatic mutations, causing multi-organ histiocytic infiltration. While kinase inhibitors are effective, their universal availability and long-term tolerability remain challenges. Interferon-alpha (IFN-α) still serves as frontline therapy for selected ECD patients and is employed in other myeloid neoplasms. However, reliable predictors of IFN-α response remain elusive. This study aimed to identify clinical and molecular factors associated with the efficacy of IFN-α in a large international cohort of ECD and myeloproliferative neoplasm (MPN). Methods We retrospectively analyzed 377 patients (ECD n=300; MPN n=77) treated with IFN-α across centers in France, Italy, and the United States. Clinical and molecular data were retrieved from medical records. Clonal hematopoiesis (CH) was defined by the presence of myeloid gene mutations in blood/bone marrow without overt hematological malignancy. Response was assessed by PET–CT (ECD) or standard guidelines (MPN); non-response was defined by progressive disease. Results We analyzed 300 ECD patients (median age 59 years; 87% men; 67% BRAFV600Emutation) treated with interferon as first (n=255), second (n=40), and third line (n=5) therapy. The overall response rate (ORR) was 83% (n=249). Responders were older at diagnosis (median age 59 years vs 54; p=0.0189), at the first symptom onset (56 vs 51; p=0.0231), and at IFN-α initiation (59 vs 54; p=0.0175), with longer disease duration (58 months [44–67] vs 10.8 [4–25]; p<0.0001), and less frequently women (11% vs 19%; p=0.0262). Regarding the prediction of response, the multivariable logistic regression model identified women (OR=0.36, 95% CI 0.14–0.95; p=0.0406), digestive tract involvement (OR=0.20, 95% CI 0.06–0.68; p=0.0109) as negative predictors, whereas ENT involvement (OR=3.99, 95% CI 1.42–11.19; p=0.0089), and CH (OR=2.81, 95% CI 1.13–6.98; p=0.0270) were positive predictors. Among 255 first-line IFN-α patients, the ORR was 76% (n=195). Sixty patients (23%) had disease progression. Responders were older at diagnosis (59 years vs 54; p=0.05), had higher baseline CRP (83% vs 36%; p=0.0448) and more myeloid gene driver mutation on NGS ( median 1 [1–2] vs 0 [0–1]; p=0.0013). In this group, CH was the sole independent predictor of response (OR=20.02, 95% CI 3.2–199; p=0.0009).Within the CH subgroup (n=86; 93% response), women sex (OR=0.15, 95% CI 0.02–0.82; p=0.0288) and digestive tract involvement (OR=0.13, 95% CI 0.02–0.94; p=0.0437) were negative predictors, while ENT lesions (OR=9.09, 95% CI 1.15–227.2; p=0.0345) predicted improved response. Among 77 MPN patients, 79% (n=61) achieved response. The use of IFN-α as first line treatment was frequent in responders (72% vs 43%; p=0.0416) and predicts response (OR=3.328, 95% CI 1.077-10.73, p=0.0368) in univariate analysis. In the pooled cohort (n=377), responders (n=310) more often received IFN-α as first-line therapy (83% vs 70%; p=0.015). Among patients having NGS (predominantly ECD, n=175), responders had higher CH prevalence (53% vs 29%; p=0.0171). Multivariable logistic regression confirmed women's sex (OR=0.35, 95% CI 0.15-0.82, p=0.015) as negative predictors, whereas CH (OR=2.64, 95% CI 1.14-6.56, p=0.02) predicted improved response. Conclusion This multicenter study, the largest to evaluate IFN-α outcomes in ECD, identifies key clinical and molecular predictors of response. Crucially, CH defines a unique subgroup with enhanced IFN-α sensitivity, highlighting the potential for molecular treatment stratification.
antibodies
2026-05-29 | Rare forms of interstitial lung disease
There is an increased awareness and recognition of rare lung diseases in recent years. Although individually rare, they can collectively represent a considerable part of a pulmonologist's clinical practice. Their rarity often leads to challenges in achieving timely and accurate diagnosis. These conditions are often associated with systemic manifestations, requiring substantial expertise and a deep knowledge of internal medicine. Close collaboration with other specialties is often essential. Pulmonologists can play a critical role in suspecting and establishing the correct diagnosis and also in determining the optimal management strategy. Therefore, it is important for pulmonologists to be familiar with these diseases. This chapter will cover several of these poorly recognized ILDs including amyloidosis, IgG4-related disease, follicular bronchiolitis, diffuse aspiration bronchiolitis, Erdheim–Chester disease, pulmonary alveolar microlithiasis, diffuse pulmonary lymphatic diseases, Hermansky–Pudlak syndrome, and other heritable disorders. Finally, neoplastic disorders that can mimic ILDs are also discussed. To paraphrase a known medical heuristic, when you hear hoof beats, think horses, not zebras, but make sure to know your zebras.
2026-05-25 | Clinical spectrum of pediatric-onset Erdheim-Chester disease: insights from a single-center case series.
Pediatric-onset Erdheim-Chester disease (PECD) is considerably rarer than the adult-onset Erdheim-Chester disease (AECD). This study aimed to characterize the clinical, laboratory, imaging, and outcome features of PECD and to compare similarities and differences with adult-onset cases treated at the same center. We performed a comparative analysis of PECD and AECD patients treated at the same center over the same period, examining differences in clinical presentation, laboratory and imaging findings, treatment responses, and outcomes. Five pediatric and sixty-seven adult patients were included. Central nervous system and hypothalamic or pituitary involvement were observed in over 50% of children. PECD patients demonstrated distinct organ involvement patterns, including lower rates of bone involvement (60.0% vs. 97.0%; P = 0.022) and cardiac or large-vessel involvement (0% vs. 65.7%; P = 0.007) compared with AECD patients. Analysis of skeletal manifestations revealed significantly less appendicular skeleton involvement in children [1/3 (33.3%) vs. 64/65 (98.5%); P = 0.004]. Osteosclerosis was the predominant radiographic pattern in both groups (66.7% in children vs. 83.9% in adults; P = 0.505), while osteolytic lesions were present in roughly one-third of patients in each cohort. Inflammatory markers were significantly lower in the pediatric group (P < 0.05). PECD patients exhibited trends toward higher progression-free survival (80.0% vs. 35.0%; P = 0.196) and overall survival (100% vs. 80.5%; P = 0.382) compared with adults; however, these findings should be interpreted cautiously due to the extremely small pediatric sample size. PECD and AECD differ in clinical manifestations and the intensity of systemic inflammation. Pediatric patients appear to have more favorable survival outcomes. These findings suggest potential age-related differences in disease presentation and inflammatory burden. Nevertheless, validation in larger multicenter cohorts is required, underscoring the necessity for large-scale, multicenter collaborative investigations to inform the development of pediatric-specific management strategies.
2026-03-02 | Clonally Related Chronic Myelomonocytic Leukemia and Erdheim-Chester Disease with KRAS Mutation: A Rare and Challenging Case
n/a.
2026-02-28 | Erdheim-Chester Disease Mimicking a Precentral Meningioma: A Case of Rapid Parenchymal Recurrence and Multisystemic Progression
Abstract: Erdheim-Chester disease (ECD) is a rare non-Langerhans histiocytosis that remains a significant diagnostic challenge, particularly when it presents with dural involvement. We describe the clinical course of a 50-year-old male, originally treated for a presumed precentral meningioma based on a dural mass showing intense enhancement and an atypical T2-hypointense signal. Following surgical resection, the patient experienced a multisystemic flare (thoracic, hepatic, and adrenal) alongside a rapid multifocal parenchymal recurrence in the brain. Biopsy of the thoracic lesion confirmed a BRAF V600E-mutated ECD. This report emphasizes that a "black" T2 signal in a dural mass is a major clinical red flag. Radiologists should systematically correlate such findings with the patient's cardiac history to distinguish ECD from more common dural tumors and avoid unnecessary surgery.
2026-02-18 | Systemic Xanthogranuloma or Erdheim–Chester disease: A systematic review re‐examining the classification challenge
All data are included in the manuscript and in the Supporting Information. Data S1. Figure S1. Table S1. Table S2. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
oligonucleotides
2021-11-16 | MicroRNA-15a-5p acts as a tumor suppressor in histiocytosis by mediating CXCL10-ERK-LIN28a-let-7 axis
Abstract Erdheim–Chester disease (ECD) is characterized by excessive production and accumulation of histiocytes within multiple tissues and organs. ECD patients harbor recurrent mutations of genes associated with the RAS/RAF/MEK/ERK signaling pathway, particularly, the BRAF V600E mutation. Following our previous finding that miR-15a-5p is the most prominently downregulated microRNA in ECD patients compared to healthy individuals, we elucidated its role in ECD pathogenesis. Bioinformatics analysis followed by a luciferase assay showed that chemokine ligand 10 (CXCL10) is a target gene regulated by miRNA-15a-5p. This was confirmed in 24/34 ECD patients that had low expression of miR-15a-5p concurrent with upregulated CXCL10. Overexpression of miR-15a-5p in cell lines harboring BRAF or RAS mutations (Ba/F3, KG-1a and OCI-AML3) resulted in CXCL10 downregulation, followed by LIN28a and p-ERK signaling downregulation and let-7 family upregulation. Overexpression of miR-15a-5p inhibited cell growth and induced apoptosis by decreasing Bcl-2 and Bcl-xl levels. Analysis of sequential samples from 7 ECD patients treated with MAPK inhibitors (vemurafenib/cobimetinib) for 4 months showed miR-15a-5p upregulation and CXCL10 downregulation. Our findings suggest that miR-15a-5p is a tumor suppressor in ECD through the CXCL10-ERK-LIN28a-let7 axis, highlighting another layer of post-transcriptional regulation in this disease. Upregulation of miR-15a-5p in ECD patients may have a potential therapeutic role.
small molecules
2026-09-24 | Adult-Onset Central Nervous System Erdheim-Chester Disease Successfully Treated With Cladribine and Cytarabine: Case Report and Literature Review.
Erdheim-Chester disease (ECD) is a rare histiocytic disorder with heterogeneous clinical manifestations. Central nervous system (CNS) involvement is associated with poor prognosis. Although targeted therapies have improved outcomes in patients with mitogen-activated protein kinase (MAPK) pathway alterations, optimal treatment strategies for adult patients with CNS ECD are still lacking. We describe a 24-year-old female with isolated CNS ECD without pathogenic genetic alterations. The disease was refractory to corticosteroids, radiotherapy, and cladribine monotherapy. Combination therapy with cladribine and cytarabine (Ara-C) led to clinical improvement and remission on radiologic imaging, and toxicities were acceptable. This case suggests that combination chemotherapy may represent an optimal therapeutic strategy for adult patients with CNS ECD. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.
2026-09-18 | Case Report: Erdheim-Chester disease presenting as abdominal cocoon syndrome
Erdheim-Chester disease (ECD) is a rare histiocytic neoplasm driven by MAPK pathway mutations. Although it frequently involves the bones, heart, and kidneys, initial manifestations predominantly affecting the gastrointestinal tract and mesentery are exceedingly rare, often leading to significant delays in clinical diagnosis. This report describes a 61-year-old female patient who presented with recurrent abdominal pain over several months and was initially diagnosed with a conventional “adhesive bowel obstruction” at an external hospital. However, surgical exploration revealed a classic “abdominal cocoon” presentation and symptoms showed no significant improvement postoperatively. Abdominal CT upon admission revealed diffuse thickening of the peritoneum, omentum, and mesentery with substantial peritoneal and pelvic effusion. Laboratory findings revealed autoimmune serological abnormalities, including positive ANA, anti-SSA, and anti-Ro-52 antibodies, without characteristic clinical manifestations of a defined connective tissue disease. Pathological review of resected specimens revealed extensive foamy histiocytic proliferation in the small intestine and greater omentum, with immunohistochemical findings supporting ECD and molecular confirmation of the BRAF V600E mutation. Systemic PET-CT further delineated multisystem infiltration, and bone marrow evaluation ruled out the possibility of overlapping myeloid tumors. Following multidisciplinary team (MDT) confirmation, the patient received vemurafenib-based targeted therapy, together with hydroxychloroquine following rheumatologic evaluation for the associated immunological abnormalities, resulting in substantial clinical improvement. This case highlights a rare gastrointestinal manifestation of ECD mimicking a surgical disorder and underscores the importance of integrating imaging, pathology, and molecular testing in patients with atypical intestinal manifestations.
2026-09-09 | Case Report: Pediatric Erdheim-Chester disease with cerebral ventricular system infiltration and epiphyseal involvement.
Erdheim-Chester disease (ECD) is an extremely rare non-Langerhans cell histiocytosis, a category of hematologic disorders characterized by the proliferation of foamy histiocytes. ECD predominantly affects adults, and pediatric cases with cerebral ventricular system involvement are exceptionally rare, with only a few previous reports. Moreover, epiphyseal involvement has not been characterized by magnetic resonance imaging (MRI) in children with ECD. Here we present a pediatric case of ECD involving both the cerebral ventricular system and epiphyses, highlighting diagnostic challenges and novel imaging findings relevant to pediatric hematologists. An 11-year-old boy presented with progressive gait disturbance, growth retardation, left knee pain, dysuria, and nocturia over two years. Imaging revealed a mass in the right lateral ventricle, patchy osteosclerosis of the tibial epiphyses, and bilateral cerebellar white matter lesions showing the "crab sign" (central cavitation within the dentate nuclei on Fluid Attenuated Inversion Recovery (FLAIR) sequences). The ventricular mass was surgically resected. Histopathology and immunohistochemistry (CD68+, CD163+, CD1a-) confirmed the diagnosis of ECD, and molecular analysis detected a BRAF V600E mutation (6.40%). The patient received dabrafenib (a BRAF inhibitor), interferon alpha-2b, and desmopressin. At the 32-month follow-up, the patient had become non-ambulatory and exhibited speech delay, partly due to poor medication adherence, highlighting that even brief interruption of dabrafenib therapy can lead to rapid disease progression. For pediatric hematologists, this case strongly demonstrates that continuous administration of dabrafenib is essential for controlling disease in children with BRAF V600E-mutated ECD. This report presents a rare pediatric case of ECD characterized by involvement of both the cerebral ventricular system and epiphyses. We suggest that persistent bladder wall thickening (≥1.5 cm) may serve as a novel imaging indicator of urinary tract involvement in ECD, although histological confirmation is required. The "crab sign" could aid in the early diagnosis of central nervous system involvement. Importantly, this case illustrates that continuous administration of dabrafenib is crucial for disease management in children with BRAF V600E-mutated ECD, as even a brief interruption in therapy can result in rapid and severe deterioration. Our findings highlight the necessity of multimodal imaging and molecular analysis for accurate diagnosis and targeted therapeutic strategies in pediatric ECD.
2026-08-27 | Erdheim-Chester disease diagnosed and treated at the Hematology and Oncology Clinic of the Brno University Hospital in the last 26 years. Description of 6 cases and an overview of the symptoms and treatment of this disease
Erdheimova-Chesterova choroba (ECD) je malign histiocytrn nemoc, kter je obvykle provzen systmovou zntlivou reakc, kter me bt zhodnocena jako horeka nejasnho pvodu (fever of unknown origin). Charakteristick jsou osteosklerotick kostn zmny. Typickm znakem je zven akumulace osteotropnch radiofarmak v okol kolennch kloub (hot knees) a tvorba retroperitonelnch infiltrt. ECD me postihnout prakticky kterkoli orgn. Jej incidence v dospl populaci byla stanovena v Evrop i v USA na 3 ppady/10 milion dosplch. Poet diagnostikovanch ppad v poslednch letech narst z dvodu lep informovanosti lka. Na hematonkologick klinice v Brn jsme za poslednch 26 let diagnostikovali a lili est ppad ECD. Ke stanoven diagnzy vedly: bolesti v dolnch konetinch s atypickou strukturou skeletu (dva ppady), diabetes insipidus (dva ppady), B-symptomy, febrilie a nava (dva ppady), retroperitoneln fibrza (dva ppady), typick obraz pro ECD na scintigrafii skeletu proveden z jin indikace (jeden ppad), oboustrann exoftalmus (jeden ppad). Vechny pacienty jsme lili kladribinem asto doplnnm o infuze cyklofosfamidu. Lbu meme hodnotit jen u 4 pacient, dva z nich jsou v kompletn a dva v parciln remisi, dlka sledovn tchto pacient je 208, 196, 83 a 30 msc. Pt pacient ije, ale pestal dochzet do na ambulance a u estho pacienta v dob hodnocen probh lba. Clem textu je upozornit na pznaky, kter mohou ECD ohlaovat, a na jej lbu. Diagnzu mohou stanovit ortopedov clenou biopsi kosti, urologov odbrem histologie z retroperitonea, endokrinologov pi hledn piny diabetu insipidu. Z dostupnch zobrazovacch metod nejlpe informuje FDG-PET/CT vyeten o rozsahu choroby. Pro odhalen vech osteosklerotickch loisek je vhodn zobrazen pomoc radiofarmak, kter detekuj novotvorbu kosti (scintigrafie skeletu anebo NaF-PET/CT).
2026-08-05 | Erdheim-Chester Disease: A Rare Non-Langerhans Cell Histiocytosis with Pathognomonic Multisystem Imaging Findings: Case Report Illustrating the Classic Radiological Triad
Background: Erdheim?Chester disease (ECD) is a rare non-Langerhans cell histiocytic neoplasm characterised by xanthogranulomatous infiltration of multiple organ systems by foamy CD68-positive, CD1a-negative histiocytes. The condition produces a highly characteristic constellation of skeletal, retroperitoneal and cardiovascular imaging findings, and in the majority of cases the radiologist is the first physician to raise the diagnosis. Case Presentation: We report a case of ECD in a middle-aged male who presented with insidious bilateral knee pain, polyuria and incidentally detected renal impairment. Plain radiographs of both lower limbs demonstrated bilateral, symmetric metadiaphyseal osteosclerosis of the distal femora and proximal tibiae with characteristic sparing of the epiphyses. Contrast-enhanced computed tomography (CECT) of the abdomen revealed symmetric perinephric soft-tissue infiltration producing the ?hairy kidney? appearance with thickened bridging perirenal septa, bilateral hydroureteronephrosis, and circumferential periaortic soft tissue extending from the descending thoracic aorta to the iliac bifurcation, constituting the ?coated aorta? sign. CT of the thorax showed smooth interlobular septal thickening, pericardial thickening and a right atrial pseudotumour. Magnetic resonance imaging of the sella demonstrated loss of the posterior pituitary bright spot with infundibular thickening. Technetium-99m methylene diphosphonate (99mTc-MDP) bone scintigraphy showed intense symmetric tracer uptake in the distal femora and proximal tibiae. Management and Outcome: Image-guided biopsy of the perinephric soft tissue demonstrated foamy histiocytes within a fibrotic stroma that were immunoreactive for CD68 and negative for CD1a and S100, confirming the diagnosis. Molecular analysis identified a BRAF V600E mutation, and targeted therapy with a BRAF inhibitor was initiated. Interval imaging at six months showed regression of the periaortic and perinephric soft tissue with improvement in hydronephrosis. Conclusion: This case underscores the pivotal role of imaging in the recognition of ECD. The triad of bilateral symmetric metadiaphyseal osteosclerosis of the long bones, hairy kidneys and coated aorta is sufficiently distinctive to permit a confident radiological suggestion of the diagnosis, allowing targeted biopsy, molecular characterisation and early institution of MAPK-directed therapy.
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2026-08-28 | Treatment of Erdheim-Chester disease from the perspective in 2026.
With the discovery of new drugs, treatment of Erdheim-Chester disease (ECD) is gradually evolving and changing. The text provides an overview of effective drugs available in 2026 for patients with ECD. Treatment options: We consider it appropriate to divide treatment into treatment targeting the inflammatory reaction induced by ECD, and treatment targeting malignant histiocytes. To suppress the inflammatory reaction, high doses of glucocorticoids can be used, but only short-term. For long-term suppression of the inflammatory reaction, anakinra is most commonly used. In rare cases, a similar effect has been reported with canakinumab, as well as with sirolimus and anti-TNF drugs. Anakinra is used both alone and in combination with other drugs. ECD cells, like histiocytosis cells from Langerhans cells, are derived from a monocytic lineage, which similarly to the lymphocytic lineage, is very sensitive to cladribine (2-chloro-2'-deoxyadenosine). This drug is the most effective cytostatic agent for patients with ECD. In several smaller clinical studies, the benefit of treatment with interferon alfa has been described. Thus, interferon alfa, despite its side effects, represents one of the treatment options. In cases of severe ECD and the presence of the BRAFV600E mutation, two drugs are recommended - vemurafenib and dabrafenib. For patients with a severe course without the BRAFV600E mutation, MEK kinase inhibitors trametinib and cobimetinib are recommended. The literature contains conflicting conclusions in studies evaluating the dependence of the effectiveness of these drugs on the detection of mutations in the MAPK signaling pathway. Targeted therapy is associated with numerous side effects, as well as the risk of relapse after its discontinuation. If the administered drugs trigger an inflammatory response, anakinra is again used to suppress it. Treatment of ECD always requires an assessment of the extent of the disease and degree of organ damage in order to choose the appropriate therapy.
2026-07-25 | Cerebrovascular involvement in Erdheim-Chester disease: a case report and systematic literature review.
Intracranial perivascular/vascular infiltrations and stenoses related to Erdheim-Chester disease (ECD), often associated with ischemic events, are rarely documented. This study aims to characterize intracranial perivascular/vascular infiltrations and stenoses. We first report a new case of strokes revealing ECD with intracranial arterial involvement. We then searched all English- and French-language publications from database inception to November 2025 across 12 different search interfaces, including grey literature sources. Vascular involvement was defined by the presence of intracranial perivascular/vascular infiltrations and stenosis on imaging and/or histopathological evidence of small-vessel involvement. Cases with intracranial nodules or masses abutting vessels but without clear longitudinal perivascular infiltration were excluded. We present a case of recurrent strokes with intracranial vertebral and basilar artery wall stenosis, and aortitis. Initially diagnosed as giant cell arteritis, the patient was treated with corticosteroids, cyclophosphamide followed by methotrexate, but relapsed. The identification of tibial osteosclerosis led to the diagnosis of ECD, with a favorable response to anakinra. Twelve relevant articles were retrieved, in addition to our own case. Most patients exhibited focal cerebrovascular signs (11/13) and associated parenchymal involvement (11/13). Intracranial perivascular/vascular infiltrations and stenoses involved the carotid arteries (7/13), the vertebrobasilar arteries (1/13), or both territories (4/13). Aorta was involved in 8/12 cases. Among the nine patients with available follow-up data, five had poor overall or neurovascular outcomes. Intracranial perivascular/vascular infiltrations and stenoses, which leads to recurrent focal ischemic events, represents a likely underdiagnosed CNS pattern in ECD, referred to as "cerebrovascular ECD", which worsens overall prognosis. Vascular imaging should be included in brain MRI protocols for patients with ECD, given the overlap with parenchymal involvement.
2026-03-15 | Single-center real-world data on the efficacy, safety, and current availability of pegylated interferon-α in hematologic neoplasms
Aims: Pegylated interferon-α (PEG-IFN-α) offers improved pharmacokinetics compared with conventional interferon-α (IFN-α), yet real-world data on its clinical activity and safety across heterogeneous hematologic neoplasms are limited. This study aimed to evaluate the real-world efficacy, durability of response, and toxicity of PEG-IFN-α in patients with diverse hematologic neoplasms. Methods: This retrospective study evaluated the efficacy, duration of response, and toxicity of PEG-IFN-α using patient medical records and hospital electronic registries. Thirty patients were included: polycythemia vera (PV, n=12), essential thrombocytosis (ET, n=6), chronic myeloid leukemia (n=2), primary myelofibrosis (n=1), systemic mastocytosis (SM,n=3), hypereosinophilic syndrome (HES, n=1), Erdheim–Chester disease (ECD, n=4), and lymphomatoid granulomatosis (LYG, n=1). Results: PEG-IFN-α was initiated due to resistance to prior therapies in 12 patients (40%), intolerance or toxicity in 10 patients (33.3%), and as first-line treatment in 8 patients (26.7%). Among PV patients, a complete response was achieved in 41.6% and a partial response in 50%. In ET patients, 83.3% achieved a complete response, while 16.7% showed no response. All patients with SM demonstrated clinical improvement when PEG-IFN-α was used as first-line therapy. In ECD patients, follow-up PET imaging showed stable disease in two patients, partial response in one, and no response in one. Partial responses were also observed in patients with HES and LYG. Treatment-related toxicity occurred in 8 patients (26.6%) and led to treatment discontinuation in 6 patients (20%) (including cytopenias, influenza-like symptoms, and elevated liver enzymes). Conclusion: In this real-world cohort, PEG-IFN-α showed encouraging activity across several hematologic neoplasms, with toxicity and discontinuation rates in line with previously published series of conventional interferon-α; however, its clinical use remains limited by regulatory and access constraints.
2026-02-20 | Multiple opportunistic infections revealing Erdheim-Chester disease: an atypical presentation.
This case describes a man in his mid 60s from Mexico who presented with respiratory failure and elevated inflammatory biomarkers. Initial investigations revealed multiple opportunistic infections. A PET-CT scan showed variable uptake in bilateral intraconal masses, dural venous sinuses, paranasal sinuses, lungs, pericardium and both distal femurs. Bone biopsy confirmed clonal histiocytosis (CD68+, CD163+, Fascin+, BRAF-V600E+), leading to a diagnosis of Erdheim-Chester disease (ECD), a rare non-Langerhans histiocytosis affecting multiple systems.As vemurafenib was unavailable in Mexico, pegylated interferon alpha (PEG-IFN-α) was initiated, producing significant clinical and biomarker improvement. The patient was discharged in stable condition and continues close multidisciplinary follow-up with infectious disease, cardiology, nephrology, pulmonology and haematology teams.This case highlights the importance of considering ECD in the differential diagnosis of multisystem diseases of unknown origin, especially with unusual manifestations such as multiple opportunistic infections, and reinforces the value of a coordinated, multidisciplinary approach in managing complex presentations.
2025-11-03 | Clinical and molecular predictors of interferon-α response in erdheim-chester disease and myeloproliferative neoplasm.
Abstract Background: Erdheim–Chester disease (ECD) is a rare clonal histiocytosis driven by MAPK pathway somatic mutations, causing multi-organ histiocytic infiltration. While kinase inhibitors are effective, their universal availability and long-term tolerability remain challenges. Interferon-alpha (IFN-α) still serves as frontline therapy for selected ECD patients and is employed in other myeloid neoplasms. However, reliable predictors of IFN-α response remain elusive. This study aimed to identify clinical and molecular factors associated with the efficacy of IFN-α in a large international cohort of ECD and myeloproliferative neoplasm (MPN). Methods We retrospectively analyzed 377 patients (ECD n=300; MPN n=77) treated with IFN-α across centers in France, Italy, and the United States. Clinical and molecular data were retrieved from medical records. Clonal hematopoiesis (CH) was defined by the presence of myeloid gene mutations in blood/bone marrow without overt hematological malignancy. Response was assessed by PET–CT (ECD) or standard guidelines (MPN); non-response was defined by progressive disease. Results We analyzed 300 ECD patients (median age 59 years; 87% men; 67% BRAFV600Emutation) treated with interferon as first (n=255), second (n=40), and third line (n=5) therapy. The overall response rate (ORR) was 83% (n=249). Responders were older at diagnosis (median age 59 years vs 54; p=0.0189), at the first symptom onset (56 vs 51; p=0.0231), and at IFN-α initiation (59 vs 54; p=0.0175), with longer disease duration (58 months [44–67] vs 10.8 [4–25]; p<0.0001), and less frequently women (11% vs 19%; p=0.0262). Regarding the prediction of response, the multivariable logistic regression model identified women (OR=0.36, 95% CI 0.14–0.95; p=0.0406), digestive tract involvement (OR=0.20, 95% CI 0.06–0.68; p=0.0109) as negative predictors, whereas ENT involvement (OR=3.99, 95% CI 1.42–11.19; p=0.0089), and CH (OR=2.81, 95% CI 1.13–6.98; p=0.0270) were positive predictors. Among 255 first-line IFN-α patients, the ORR was 76% (n=195). Sixty patients (23%) had disease progression. Responders were older at diagnosis (59 years vs 54; p=0.05), had higher baseline CRP (83% vs 36%; p=0.0448) and more myeloid gene driver mutation on NGS ( median 1 [1–2] vs 0 [0–1]; p=0.0013). In this group, CH was the sole independent predictor of response (OR=20.02, 95% CI 3.2–199; p=0.0009).Within the CH subgroup (n=86; 93% response), women sex (OR=0.15, 95% CI 0.02–0.82; p=0.0288) and digestive tract involvement (OR=0.13, 95% CI 0.02–0.94; p=0.0437) were negative predictors, while ENT lesions (OR=9.09, 95% CI 1.15–227.2; p=0.0345) predicted improved response. Among 77 MPN patients, 79% (n=61) achieved response. The use of IFN-α as first line treatment was frequent in responders (72% vs 43%; p=0.0416) and predicts response (OR=3.328, 95% CI 1.077-10.73, p=0.0368) in univariate analysis. In the pooled cohort (n=377), responders (n=310) more often received IFN-α as first-line therapy (83% vs 70%; p=0.015). Among patients having NGS (predominantly ECD, n=175), responders had higher CH prevalence (53% vs 29%; p=0.0171). Multivariable logistic regression confirmed women's sex (OR=0.35, 95% CI 0.15-0.82, p=0.015) as negative predictors, whereas CH (OR=2.64, 95% CI 1.14-6.56, p=0.02) predicted improved response. Conclusion This multicenter study, the largest to evaluate IFN-α outcomes in ECD, identifies key clinical and molecular predictors of response. Crucially, CH defines a unique subgroup with enhanced IFN-α sensitivity, highlighting the potential for molecular treatment stratification.
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2026-05-29 | Rare forms of interstitial lung disease
There is an increased awareness and recognition of rare lung diseases in recent years. Although individually rare, they can collectively represent a considerable part of a pulmonologist's clinical practice. Their rarity often leads to challenges in achieving timely and accurate diagnosis. These conditions are often associated with systemic manifestations, requiring substantial expertise and a deep knowledge of internal medicine. Close collaboration with other specialties is often essential. Pulmonologists can play a critical role in suspecting and establishing the correct diagnosis and also in determining the optimal management strategy. Therefore, it is important for pulmonologists to be familiar with these diseases. This chapter will cover several of these poorly recognized ILDs including amyloidosis, IgG4-related disease, follicular bronchiolitis, diffuse aspiration bronchiolitis, Erdheim–Chester disease, pulmonary alveolar microlithiasis, diffuse pulmonary lymphatic diseases, Hermansky–Pudlak syndrome, and other heritable disorders. Finally, neoplastic disorders that can mimic ILDs are also discussed. To paraphrase a known medical heuristic, when you hear hoof beats, think horses, not zebras, but make sure to know your zebras.
2026-05-25 | Clinical spectrum of pediatric-onset Erdheim-Chester disease: insights from a single-center case series.
Pediatric-onset Erdheim-Chester disease (PECD) is considerably rarer than the adult-onset Erdheim-Chester disease (AECD). This study aimed to characterize the clinical, laboratory, imaging, and outcome features of PECD and to compare similarities and differences with adult-onset cases treated at the same center. We performed a comparative analysis of PECD and AECD patients treated at the same center over the same period, examining differences in clinical presentation, laboratory and imaging findings, treatment responses, and outcomes. Five pediatric and sixty-seven adult patients were included. Central nervous system and hypothalamic or pituitary involvement were observed in over 50% of children. PECD patients demonstrated distinct organ involvement patterns, including lower rates of bone involvement (60.0% vs. 97.0%; P = 0.022) and cardiac or large-vessel involvement (0% vs. 65.7%; P = 0.007) compared with AECD patients. Analysis of skeletal manifestations revealed significantly less appendicular skeleton involvement in children [1/3 (33.3%) vs. 64/65 (98.5%); P = 0.004]. Osteosclerosis was the predominant radiographic pattern in both groups (66.7% in children vs. 83.9% in adults; P = 0.505), while osteolytic lesions were present in roughly one-third of patients in each cohort. Inflammatory markers were significantly lower in the pediatric group (P < 0.05). PECD patients exhibited trends toward higher progression-free survival (80.0% vs. 35.0%; P = 0.196) and overall survival (100% vs. 80.5%; P = 0.382) compared with adults; however, these findings should be interpreted cautiously due to the extremely small pediatric sample size. PECD and AECD differ in clinical manifestations and the intensity of systemic inflammation. Pediatric patients appear to have more favorable survival outcomes. These findings suggest potential age-related differences in disease presentation and inflammatory burden. Nevertheless, validation in larger multicenter cohorts is required, underscoring the necessity for large-scale, multicenter collaborative investigations to inform the development of pediatric-specific management strategies.
2026-03-02 | Clonally Related Chronic Myelomonocytic Leukemia and Erdheim-Chester Disease with KRAS Mutation: A Rare and Challenging Case
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2026-02-28 | Erdheim-Chester Disease Mimicking a Precentral Meningioma: A Case of Rapid Parenchymal Recurrence and Multisystemic Progression
Abstract: Erdheim-Chester disease (ECD) is a rare non-Langerhans histiocytosis that remains a significant diagnostic challenge, particularly when it presents with dural involvement. We describe the clinical course of a 50-year-old male, originally treated for a presumed precentral meningioma based on a dural mass showing intense enhancement and an atypical T2-hypointense signal. Following surgical resection, the patient experienced a multisystemic flare (thoracic, hepatic, and adrenal) alongside a rapid multifocal parenchymal recurrence in the brain. Biopsy of the thoracic lesion confirmed a BRAF V600E-mutated ECD. This report emphasizes that a "black" T2 signal in a dural mass is a major clinical red flag. Radiologists should systematically correlate such findings with the patient's cardiac history to distinguish ECD from more common dural tumors and avoid unnecessary surgery.
2026-02-18 | Systemic Xanthogranuloma or Erdheim–Chester disease: A systematic review re‐examining the classification challenge
All data are included in the manuscript and in the Supporting Information. Data S1. Figure S1. Table S1. Table S2. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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2021-11-16 | MicroRNA-15a-5p acts as a tumor suppressor in histiocytosis by mediating CXCL10-ERK-LIN28a-let-7 axis
Abstract Erdheim–Chester disease (ECD) is characterized by excessive production and accumulation of histiocytes within multiple tissues and organs. ECD patients harbor recurrent mutations of genes associated with the RAS/RAF/MEK/ERK signaling pathway, particularly, the BRAF V600E mutation. Following our previous finding that miR-15a-5p is the most prominently downregulated microRNA in ECD patients compared to healthy individuals, we elucidated its role in ECD pathogenesis. Bioinformatics analysis followed by a luciferase assay showed that chemokine ligand 10 (CXCL10) is a target gene regulated by miRNA-15a-5p. This was confirmed in 24/34 ECD patients that had low expression of miR-15a-5p concurrent with upregulated CXCL10. Overexpression of miR-15a-5p in cell lines harboring BRAF or RAS mutations (Ba/F3, KG-1a and OCI-AML3) resulted in CXCL10 downregulation, followed by LIN28a and p-ERK signaling downregulation and let-7 family upregulation. Overexpression of miR-15a-5p inhibited cell growth and induced apoptosis by decreasing Bcl-2 and Bcl-xl levels. Analysis of sequential samples from 7 ECD patients treated with MAPK inhibitors (vemurafenib/cobimetinib) for 4 months showed miR-15a-5p upregulation and CXCL10 downregulation. Our findings suggest that miR-15a-5p is a tumor suppressor in ECD through the CXCL10-ERK-LIN28a-let7 axis, highlighting another layer of post-transcriptional regulation in this disease. Upregulation of miR-15a-5p in ECD patients may have a potential therapeutic role.
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Drug Discovery Landscape
2 orphan drug designations for Erdheim-Chester disease, including 1 approved therapy.
2 orphan drug designations for Erdheim-Chester disease, including 1 approved therapy.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Vemurafenib | small molecules | EMA | Groupe d'étude des histiocytoses | |
vemurafenib [Zelboraf] | small molecules | FDA | Approved | Genentech, Inc. |
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