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American Journal of Ophthalmology Case... Sep 2024We report a patient who initially visited the ophthalmology clinic for a vision loss diagnosed with Erdheim-Chester Disease (ECD).
PURPOSE
We report a patient who initially visited the ophthalmology clinic for a vision loss diagnosed with Erdheim-Chester Disease (ECD).
OBSERVATIONS
ECD is a rare non-Langerhans cell histiocytosis characterized by multisystemic organ involvement and poor prognosis. Our patient had complete vision loss due to prominent orbital involvement before any systemic symptoms appeared. This case demonstrates variable clinical manifestations of ECD.
CONCLUSIONS AND IMPORTANCE
Painless bilateral proptosis with poor response to steroid treatment should prompt consideration for ECD and systemic evaluation. In addition, in the absence of typical clinical manifestations, a thorough evaluation of the biopsy can be crucial for an accurate diagnosis.
PubMed: 38872875
DOI: 10.1016/j.ajoc.2024.102087 -
Clinical Practice and Cases in... May 2024A 52-year-old female presented to the emergency department with four days of right periorbital pain, ipsilateral temporal headache, diplopia, and photophobia. Physical...
CASE PRESENTATION
A 52-year-old female presented to the emergency department with four days of right periorbital pain, ipsilateral temporal headache, diplopia, and photophobia. Physical examination of the right eye revealed painful ophthalmoplegia, cranial nerves III and VI paresis, increased intraocular pressure, and mild proptosis. Magnetic resonance venogram and magnetic resonance imaging orbits with contrast demonstrated an abnormal signal surrounding the right cavernous sinus/petrous apex. Tolosa-Hunt syndrome (THS) was diagnosed. Per neurology recommendations, the patient was placed on a steroid regimen over the course of three weeks. She was discharged on hospital day nine following resolution of symptoms. She had no recurrence of symptoms or residual deficits noted at her two-week follow-up appointment.
DISCUSSION
With an estimated annual incidence of one case per million, THS is a sinister etiology of unilateral headache, painful ophthalmoplegia, and oculomotor palsy. Tolosa-Hunt syndrome is caused by granulomatous inflammation in the cavernous sinus and is highly responsive to corticosteroids. Magnetic resonance imaging studies of the cavernous sinus and orbital apex are highly sensitive for THS and characteristically show enlargement and focal-enhancing masses within the affected cavernous sinus.
PubMed: 38869347
DOI: 10.5811/cpcem.2582 -
Frontiers in Endocrinology 2024The current clinical practice lacks sufficient objective indicators for evaluating thyroid-associated ophthalmopathy (TAO). This study aims to quantitatively assess TAO...
BACKGROUND
The current clinical practice lacks sufficient objective indicators for evaluating thyroid-associated ophthalmopathy (TAO). This study aims to quantitatively assess TAO by evaluating levator palpebrae superioris (LPS) using Dixon-T2WI.
METHODS
The retrospective study included 231 eyes (119 patients) in the TAO group and 78 eyes (39 volunteers) in the normal group. Dixon-T2WI provided data on maximum thickness of LPS (LPS_T) and signal intensity ratio (LPS_SIR) between the muscle and ipsilateral brain white matter. TAO diagnosis and assessment of its activity and severity were quantitatively determined using LPS_T and LPS_SIR.
RESULTS
In the TAO group, LPS_T and LPS_SIR were higher than those in the normal group ( < 2.2e-16). The upper lid retraction (ULR) ≥ 2 mm group exhibited higher LPS_T and LPS_SIR compared to the ULR < 2 mm and normal groups. Optimal diagnostic performance was achieved with an AUC of 0.91 for LPS_T (cutoff: 1.505 mm) and 0.81 for LPS_SIR (cutoff: 1.170). LPS_T ( = 2.8e-07) and LPS_SIR ( = 3.9e-12) in the active phase were higher than in the inactive phase. LPS_T and LPS_SIR showed differences among the mild, moderate-to-severe, and sight-threatening groups ( < 0.05). ROC showed an AUC of 0.70 for LPS_T (cutoff: 2.095 mm) in judging the active phase, and 0.78 for LPS_SIR (cutoff: 1.129). For judging the moderate-to-severe and above, AUC was 0.76 for LPS_T (cutoff: 2.095 mm) and 0.78 for LPS_SIR (cutoff: 1.197).
CONCLUSION
The maximum thickness and SIR of LPS provide imaging indicators for assisting in the diagnosis and quantitative evaluation of TAO.
Topics: Humans; Graves Ophthalmopathy; Female; Male; Retrospective Studies; Middle Aged; Adult; Oculomotor Muscles; Magnetic Resonance Imaging; Aged; Eyelids; Case-Control Studies
PubMed: 38868741
DOI: 10.3389/fendo.2024.1387217 -
Heliyon Jun 2024The efficacy of rituximab (RTX) in treating steroid-resistant Graves' orbitopathy (GO) has been limitedly studied in Asians. Moreover, RTX has been considered even less...
BACKGROUND AND OBJECTIVES
The efficacy of rituximab (RTX) in treating steroid-resistant Graves' orbitopathy (GO) has been limitedly studied in Asians. Moreover, RTX has been considered even less for patients with steroid-resistant dysthyroid optic neuropathy (DON) who failed to undergo orbital decompression surgery for physical or financial reasons, or who responded poorly to the procedure. This study aimed to investigate the efficacy of RTX in treating steroid-resistant active moderate-to-severe and sight-threatening GO in a Chinese population.
METHODS
Data from 28 patients with steroid-resistant GO prescribed a single dose of 500 mg RTX were retrospectively retrieved. Treatment responses and contributing factors were analyzed.
RESULTS
The median follow-up time was 22 (8-34) weeks. 23 (82.1 %) patients had a positive objective outcome recommended by the European Group on Graves' Orbitopathy (EUGOGO), while 25 (92.6 %) had a decrease in 7-item clinical activity score (CAS) by at least 2. Diplopia, visual dysfunction, and MRI-detected T2 relaxation time of the involved extraocular muscles improved significantly at the last follow-up compared to baseline (81.0 % vs. 47.6 %, 38.9 % vs. 16.7 %, and 87.8 (8.64) vs. 75.8 (10.9) ms, respectively; all values < 0.05). No significant improvement was seen in terms of proptosis and eye muscle duction. Notably, a higher baseline IgG4 to IgG ratio was a predictor for RTX-induced positive EUGOGO outcomes. After RTX treatment, all 8 patients with DON demonstrated inactivation, and 4 improved in visual acuity by ≥ 1 line. No patient with DON experienced obvious deterioration.
CONCLUSION
A single dose of 500 mg RTX seemed to be an effective and tolerable treatment for steroid-resistant GO. However, larger-scale studies with a control group are required for a more solid conclusion. The role of RTX in steroid-resistant DON management where surgery is unavailable or ineffective should be further explored.
PubMed: 38867959
DOI: 10.1016/j.heliyon.2024.e31932 -
Scientific Reports Jun 2024The primary objective of this study is to understand the regulatory role of epigenetics in thyroid-associated ophthalmopathy (TAO) using multi-omics sequencing data. We...
The primary objective of this study is to understand the regulatory role of epigenetics in thyroid-associated ophthalmopathy (TAO) using multi-omics sequencing data. We utilized tRFs sequencing data, DNA methylation sequencing data, and lncRNA/circRNA/mRNA sequencing data, as well as several RNA methylation target prediction websites, to analyze the regulatory effect of DNA methylation, non-coding RNA, and RNA methylation on TAO-associated genes. Through differential expression analysis, we identified 1019 differentially expressed genes, 985 differentially methylated genes, and 2601 non-coding RNA. Functional analysis showed that differentially expressed genes were mostly associated with the PI3K signaling pathway and the IL17 signaling pathway. Genes regulated by DNA epigenetic regulatory networks were mainly related to the Cytokine-cytokine receptor interaction pathway, whereas genes regulated by RNA epigenetic regulatory networks were primarily related to the T cell receptor signaling pathway. Finally, our integrated regulatory network analysis revealed that epigenetics mainly impacts the occurrence of TAO through its effects on key pathways such as cell killing, cytokine production, and immune response. In summary, this study is the first to reveal a new mechanism underlying the development of TAO and provides new directions for future TAO research.
Topics: Humans; Graves Ophthalmopathy; Epigenesis, Genetic; DNA Methylation; Gene Regulatory Networks; Signal Transduction; Inflammation; RNA, Long Noncoding; Gene Expression Profiling; Gene Expression Regulation
PubMed: 38867076
DOI: 10.1038/s41598-024-64415-8 -
BMJ Open Jun 2024Severe Graves' disease is a life-changing condition with poor outcomes from currently available treatments. It is caused by directly pathogenic thyroid-stimulating... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Severe Graves' disease is a life-changing condition with poor outcomes from currently available treatments. It is caused by directly pathogenic thyroid-stimulating hormone receptor-stimulating antibodies (TRAb), which are secreted from plasma cells. The human anti-CD38 monoclonal antibody daratumumab was developed to target plasma cells which express high levels of CD38, and is currently licensed for treatment of the plasma cell malignancy, myeloma. However, it can also deplete benign plasma cells with the potential to reduce TRAb and alter the natural history of severe Graves' disease. This study aims to establish proof of concept that daratumumab has efficacy in patients with severe Graves' disease and will provide important data to inform a choice of dosing regimen for subsequent trials.
METHODS AND ANALYSIS
The Graves-PCD trial aims to determine if daratumumab modulates the humoral immune response in patients with severe Graves' disease, and if so, over what time period, and to find an optimal dose. It is a single-blinded, randomised, dose-finding, adaptive trial using four different doses of daratumumab or placebo in 30 adult patients. Part 1 of the trial is dose-finding and, following an interim analysis, in part 2, the remaining patients will be randomised between the chosen dose(s) from the interim analysis or placebo. The primary outcome is the percentage change in serum TRAb from baseline to 12 weeks.
ETHICS AND DISSEMINATION
The trial received a favourable ethical opinion from London-Hampstead Research Ethics Committee (reference 21/LO/0449). The results of this trial will be disseminated at international meetings, in the peer-reviewed literature and through partner patient group newsletters and presentations at patient education events.
TRIAL REGISTRATION NUMBER
ISRCTN81162400.
Topics: Humans; Graves Disease; Antibodies, Monoclonal; Randomized Controlled Trials as Topic; Plasma Cells; Single-Blind Method; Adult; Male; Female; Dose-Response Relationship, Drug
PubMed: 38866568
DOI: 10.1136/bmjopen-2023-079158 -
Frontiers in Endocrinology 2024
Commentary: Efficacy and safety of intravenous monoclonal antibodies in patients with moderate-to-severe active Graves' ophthalmopathy: a systematic review and meta-analysis.
Topics: Humans; Administration, Intravenous; Antibodies, Monoclonal; Graves Ophthalmopathy; Severity of Illness Index; Treatment Outcome
PubMed: 38863931
DOI: 10.3389/fendo.2024.1394616 -
Journal of the ASEAN Federation of... 2024Hypoglycemic disorders are rare in persons without diabetes, and clinical evaluation to identify its etiology can be challenging. We present a case of insulin autoimmune...
Hypoglycemic disorders are rare in persons without diabetes, and clinical evaluation to identify its etiology can be challenging. We present a case of insulin autoimmune syndrome induced by carbimazole in a middle-aged Chinese man with underlying Graves' disease, which was managed conservatively with a combination of dietary modification and alpha-glucosidase inhibitor.
Topics: Humans; Male; Autoimmune Diseases; Graves Disease; Carbimazole; Antithyroid Agents; Middle Aged; Insulin; Insulin Antibodies; Syndrome; Glycoside Hydrolase Inhibitors
PubMed: 38863913
DOI: 10.15605/jafes.039.01.07 -
Journal of the ASEAN Federation of... 2024Infants of mothers with Graves' disease (GD) may develop central hypothyroidism (CH) due to exposure of the foetal hypothalamic-pituitary-thyroid axis to...
Infants of mothers with Graves' disease (GD) may develop central hypothyroidism (CH) due to exposure of the foetal hypothalamic-pituitary-thyroid axis to higher-than-normal thyroid hormone concentrations, primary hypothyroidism (PH) due to transplacental passage of maternal thyroid stimulating hormone receptor antibody (TRAb), antithyroid drugs (ATD) or thyroid dysgenesis secondary to maternal uncontrolled hyperthyroidism. We describe two infants with PH and four infants with CH born to mothers with poorly controlled Graves' disease. All infants required levothyroxine and had normal developmental milestones. While national guideline consensus for high thyroid stimulating hormone (TSH) on neonatal screening is well-established, thyroid function tests (TFTs) should be serially monitored in infants with low TSH on screening, as not all mothers with Graves' disease are diagnosed antenatally.
Topics: Humans; Female; Graves Disease; Pregnancy; Infant, Newborn; Pregnancy Complications; Hypothyroidism; Male; Adult; Infant; Thyroxine; Thyroid Function Tests; Thyrotropin
PubMed: 38863905
DOI: 10.15605/jafes.039.01.06 -
Polish Archives of Internal Medicine Jun 2024
Topics: Humans; Graves Ophthalmopathy; Male; Female; Middle Aged; Adult; Severity of Illness Index
PubMed: 38856675
DOI: 10.20452/pamw.16773