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MRI of the left knee showing multiple focal bone marrow lesions which hyperintensive on PD FS (a) hypointensive on T1WI (b) and no bones cortical thickness before treatment (a, b); diffuse bone marrow lesions, femur cortical thickness and osteonecrosis areas (c, d) 1 month after the treatment with IFN-α beginning; diffuse bone marrow lesions become less intensive, femur cortical thickness and osteonecrosis areas (e, f) 6 months after the treatment with IFN-α
Source publication
Erdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocytosis associated with BRAFV600E mutations in more than 50% of cases and presenting with 95% with skeletal lesions. However, cutaneous, pulmonary, large vessels and central nervous system involvement can also occur. We report a case of a 25-year-old woman who was admitted in 2018 fo...
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Purpose:
We examined abnormal pituitary imaging (API) and associated endocrine dysfunction in subjects with ECD.
Methods:
A cross-sectional descriptive examination of a natural history cohort study diagnosed with ECD was conducted at a clinical research center. Subjects underwent baseline endocrine tests of anterior and posterior pituitary funct...
Citations
... The first step in the suggested treatment algorithm is to use BRAF inhibitors in positive BRAF-mutation patients, a common drug used in all positive BRAfmutation malignancies [128,129]. Biological agents such as interferon alpha and anti-cytokine with no clear mechanism showed high efficacy in ECD patients [130,131]. Chemotherapy is prescribed for partial remission and to keep the patient stable [132,133]. Radiotherapy and surgery have a limited role in ECD treatment [134]. ...
... • Interferon alpha and anti-cytokine agents [130,131] • Recurrent proto-oncogene mutations [113,114] • Bone X-rays ...
Purpose
Histiocytosis is one of the most challenging diseases in medical practice. Because of the broad spectrum of clinical manifestations, systemic involvements, unknown etiology, and complex management, different types of histiocytosis are still a big question mark for us. Orbital histiocytosis is characterized by the abnormal proliferation of histiocytes in orbital tissues. It could affect the orbit, eyelid, conjunctiva, and uveal tract. Orbital histiocytosis can cause limited eye movement, proptosis, decreased visual acuity, and epiphora. In this study, we review the novel findings regarding the pathophysiology, diagnosis, and treatment of different types of histiocytosis, focusing on their orbital manifestations.
Method
This review was performed based on a search of the PubMed, Scopus, and Embase databases or relevant published papers regarding orbital histiocytosis on October 9th, 2023. No time restriction was proposed, and articles were excluded if they were not referenced in English.
Results
391 articles were screened, most of them being case reports. The pathophysiology of histiocytosis is still unclear. However, different mutations are found to be prevalent in most of the patients. The diagnostic path can be different based on various factors such as age, lesion site, type of histiocytosis, and the stage of the disease. Some modalities, such as corticosteroids and surgery, are used widely for treatment. On the other hand, based on some specific etiological factors for each type, alternative treatments have been proposed.
Conclusion
Significant progress has been made in the detection of somatic molecular changes. Many case studies describe various disease patterns influencing the biological perspectives on different types of histiocytosis. It is necessary to continue investigating and clustering data from a broad range of patients with histiocytosis in children and adults to define the best ways to diagnose and treat these patients.
... The origin of ECD is currently unknown and its clinical manifestations are diverse and highly heterogeneous, ranging from single-lesion forms to multiple-system involvement, and including slowly progressing unifocal forms to rapidly evolving life-threatening disease. Almost any organ can be involved, but the most common sites include the long bones, retroperitoneal fibrosis, interstitial lung disease, pericardial and myocardial infiltration, the central nervous system (CNS), the retro-orbital region, and large-vessel involvement [4][5][6]. The lack of specific manifestations and markers and its difficult differential diagnosis thus present challenges. ...
Background:
ECD is a rare non-Langerhans cell histiocytosis with diverse and heterogeneous clinical manifestations, ranging from single-lesion forms to multi-system involvement, including slowly progressing unifocal forms to rapidly evolving life-threatening disease.
Case presentation:
A female patient presented with a 2-month history of fever. Imaging revealed multiple thromboses, bone destruction, an abnormal pituitary stalk, and clinical manifestations of diabetes insipidus. Excisional biopsy of a tibial lesion was sent for microscopic examination, and subsequent immunohistochemical testing was positive for expression of CD68 and CD163, and negative for expression of the immune markers CD1a, S100, and langerin. This confirmed the diagnosis of ECD. Treatment with methylprednisolone to inhibit the immune inflammatory response along with anti-cytokine therapy with an interleukin-6 antagonist resulted in satisfactory disease control.
Conclusion:
We report a rare case of multiple thromboses, embolism, and multiple organ involvement as the main presentation of ECD, suggesting that ECD should be considered in patients presenting with multiple thromboses associated with multisystem damage. We successfully treated our patient with glucocorticoids and interleukin-6 antagonist. This patient's response to treatment suggests that hormone therapy and cytokine/chemokine therapy may be a potential novel treatment for patients with ECD without gene mutations.
... In addition, the CNS symptoms in ECD exhibit a variety, with cerebellar and pyramidal syndrome being the most common neurological signs, and other features described include seizures, headache, neuropsychiatric signs, cognitive impairment, sensory impairment, and cranial nerve palsy (10,12). Multisystemic organs, including diabetes insipidus (13), skin disease with xanthelasma-like lesions (XLL) (14), perirenal fat infiltration (15), and lung and heart involvement (16), are all affected, which provides a challenge for pediatricians to identify differences from ECD. In this study, the case was complex and rare because the patient first developed clinical manifestations of polydipsia and polyuria, followed by limitation of movement in the left eye. ...
... As the molecular pathogenesis of ECD disease has been explored, many therapeutic options, including interferon-a (IFN-a), BRAF, MEK targeted therapy, and anti-cytokine biotherapy, have been widely used to treat ECD. IFN-a has been shown to regulate dendritic cell maturation and activation (15) and is often recommended as a first-line treatment for nonlife-threatening presentations, which has been shown to improve survival. In recent years, almost 54%-57.5% of patients with ECD have been reported to carry BRAF V600E -activating mutations in the RAS-RAF-MEK-extracellular signal-regulated kinase signaling pathway (1,17). ...
Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis caused by the expression of CD68-positive and CD1a-negative foam tissue cells, which is polar in pediatric patients. The study reports a case of an 8-year-old Chinese boy who presented with polydipsia and polyuria for 4 years, followed by central nervous system symptoms. Magnetic resonance imaging (MRI) showed a large lesion in the lateral ventricle. The histiocytes stained positively for CD68, CD163 and negatively for CD1a, glial fibrillary acidic protein (GFAP) and langerin, and were partially positive for S100 by immunohistochemical assay. More importantly, BRAFV600E staining was positive in tissue, and the BRAFV600E mutations was also detected by real-time quantitative PCR (RT-qPCR) in the intracranial lesion tissue. According to our review of the literature, this is a rare case of ECD in the ventricle, with a younger age.
... Dále se často vyskytuje deprese či cytopenie, která je způsobena supresivním účinkem na kostní dřeň. Výskyt nežádoucích účinků často vyžaduje přerušení léčby [30,54,55]. ...
Erdheim-Chester disease is a rare inflammatory myeloid clonal disease which is classified into histiocytoses. It is characterized by excessive production and accumulation of foamy histiocytes and Touton giant cells in various tissues and organs. Foamy histiocytes and Touton giant cells produce proinflammatory cytokines and chemokines and contain somatic mutations in genes activating the MAPK/ERK signaling pathway, but also in genes activating the PI3K/AKT signaling pathway. BRAFV600E is the most common somatic mutation. Furthermore, somatic mutations in the MAP2K1, KRAS, NRAS, ARAF or PIK3CA genes are abundant. Erdheim-Chester dis-ease is a multisystemic disease in which any organ can be affected, especially the long bones of the lower extremities, but also the cardiovascular system, retroperitoneum, endocrine system, central nervous system, lungs, skin or orbit. The dia-gnosis is difficult because of the various manifestations of this disease. The disease occurs mainly in adults and is more common in men than in women. Targeted treatment by kinase inhibitors, interferon a, cytokine blockers or cladribine is used for the treatment.
Erdheim–Chester disease (ECD) is a rare, non‐Langerhans histiocytic disease, with the manifestation of cutaneous lesions becoming further recognised and understood. Most commonly presenting with xanthelasma‐like lesions, cutaneous manifestations are the first noticeable sign of ECD in a significant number of patients. Other commonly reported cutaneous lesions of ECD include panniculitis‐like lesions and granuloma annulare‐like lesions. While previously reported papular lesions of ECD include crusty yellow and erythematous papules, small, pink to fleshy coloured papules, and verruca plana‐like papules, papulonodular eruptions consistent with fibrous histiocytomas are a rare and underreported sequala of ECD. Here, we report an 86‐year‐old male with a history of prostate and bladder cancer who presented with eruptive fibrous histiocytomas, prompting workup that lead to a diagnosis of ECD. The patient received expedited imaging given the rare association of eruptive fibrohistiocytic lesions with malignancy, revealing diffuse perinephric and urothelial soft tissue thickening and enhancement, which was biopsied and found to harbour the BRAF V600E mutation. One could reasonably hypothesise that the pathologic mechanism occurring in the perinephric and urothelial soft tissue areas of this patient bodes similarities to the cutaneous sites consistent with the fibrohistiocytic lesions. This may present a potential clue to the poorly understood origin and pathogenesis of ECD.
Erdheim–Chester disease (ECD) is a rare clonal histiocytic neoplasm with less than 1200 documented cases to date. The disease is life-threatening and difficult to recognize, although increasing awareness as well as the integration of clinical, imaging, pathology information and genetic studies have led to a recent exponential increase in new reported cases.. ECD affects multiple organs and systems, including skeletal, neurologic, and cardiovascular. Pulmonary, retroperitoneal, and cutaneous lesions have also been reported in various combinations. Until the discovery that more than half of ECD patients harbor the BRAF-V600E mutation or other mutations in the mitogen-activated protein kinase (MAPK) and RAS pathways, Interferon-a was the first-line treatment. Nowadays BRAF- and MEK-inhibitors targeted therapies are the mainstay of treatment. Ophthalmologic involvement occurs in 25-30% of ECD cases, usually in the form of orbital involvement presenting with exophthalmos and ophthalmoplegia. Other ophthalmologic manifestations include palpebral xanthelasmas, anterior uveitis and vitritis, optic disk edema, choroidal infiltration, recurrent serous retinal detachment, retinal drusen–like deposits and etinal pigment epithelial changes. ECD patients can also present with ocular symptoms as a result of adverse effects of the treatment regimens. In some cases with smoldering or protean symptoms, the emergence of eye manifestations triggered the diagnosis. Ophthalmologists have to be aware of the disease, recognize the constellation of ECD symptoms, and contribute to the diagnosis, treatment, and follow-up of ECD patients.
