Systemic lupus erythematosus combined with Wilson's disease: a case report and literature review.

BACKGROUND: Systemic lupus erythematosus (SLE) and Wilson's disease (WD) are both systemic diseases that can affect multiple organs in the body. The coexistence of SLE and WD is rarely encountered in clinical practice, making it challenging to diagnose. CASE REPORT: We present the case of a 9-year-old girl who initially presented with proteinuria, haematuria, pancytopenia, hypocomplementemia, and positivity for multiple autoantibodies. She was diagnosed with SLE, and her blood biochemistry showed elevated liver enzymes at the time of diagnosis. Despite effective control of her symptoms, her liver enzymes remained elevated during regular follow-up. Laboratory tests revealed decreased serum copper and ceruloplasmin levels, along with elevated urinary copper. Liver biopsy revealed chronic active hepatitis, moderate inflammation, moderate-severe fibrosis, and a trend towards local cirrhosis. Genetic sequencing revealed compound heterozygous mutations in the ATP7B gene, confirming the diagnosis of SLE with WD. The girl received treatment with a high-zinc/low-copper diet, but her liver function did not improve. Upon recommendation following multidisciplinary consultation, she underwent liver transplantation. Unfortunately, she passed away on the fourth day after the surgery. CONCLUSIONS: SLE and WD are diseases that involve multiple systems and organs in the body, and SLE complicated with WD is rarely encountered in the clinic; therefore, it is easy to misdiagnose. Because penicillamine can induce lupus, it is not recommended. Liver transplantation is indicated for patients with liver disease who do not respond to medical treatment with WD. However, further research is needed to determine the optimal timing of liver transplantation for patients with SLE complicated with WD.

[Huangpu Tongqiao Capsule improves cognitive impairment in rats with Wilson disease by inhibiting endoplasmic reticulum stress-mediated apoptosis pathway].

OBJECTIVE: To investigate the neuroprotective effect of Huangpu Tongqiao Capsule (HPTQ) in a rat model of Wilson disease (WD) and explore the underlying mechanisms. METHODS: SD rat models of WD were established by feeding of coppersupplemented chow diet and drinking water for 12 weeks, and starting from the 9th week, the rats were treated with low-, moderate- and high-dose HPTQ, penicillamine, or normal saline by gavage on a daily basis for 3 weeks. Copper levels in the liver and 24-h urine of the rats were detected, and their learning and memory abilities were evaluated using Morris water maze test. HE staining was used to observe morphological changes of CA1 region neurons in the hippocampus, and neuronal apoptosis was detected with TUNEL staining. Hippocampal expressions of endoplasmic reticulum stress (ERS)-mediated apoptosis pathway-related proteins GRP78, CHOP, caspase-12, cleaved caspase-9, and cleaved caspase-3 at both the mRNA and protein levels were detected using RT-qPCR, immunofluorescence assay or Western blotting. RESULTS: Compared with normal control rats, the rat models with copper overload-induced WD exhibited significantly increased copper levels in both the liver and 24-h urine, impaired learning and memory abilities, obvious hippocampal neuronal damage in the CA1 region and increased TUNEL-positive neurons (P<0.01), with also lowered mRNA and protein expressions of GRP78, CHOP, caspase-12, cleaved caspase-9, and cleaved caspase-3 in the hippocampus (all P<0.01). Treatments with HPTQ and penicillamine significantly lowered copper level in the liver but increased urinary copper level, improved learning and memory ability, alleviated neuronal damage and apoptosis in the hippocampus, and decreased hippocampal expressions of GRP78, CHOP, caspase-12, cleaved caspase-9, and cleaved caspase-3 in the rat models (P<0.01 or 0.05). CONCLUSION: HPTQ Capsule has neuroprotective effects in rat models of WD possibly by inhibiting ERS-mediated apoptosis pathway.

Resolution of Wing-Beating Tremor and Magnetic Resonance Imaging Lesions in Wilson's Disease Following Penicillamine.

Background: The wing-beating tremor, characteristic of Wilson's disease (WD), is a disabling symptom that can be resistant to anti-copper and anti-tremor medications. Phenomenology Shown: This video illustrates severe bilateral wing-beating tremor, moderate head and lower limb tremors, mild cervical dystonia, and subtle cerebellar ataxia, with nearly resolution after penicillamine treatment. Educational Value: This case highlights a typical aspect of WD, emphasizing the importance of early detection and treatment, and its correlation with MRI findings. Highlights: This case highlights the typical wing-beating tremor in Wilson's disease and its correlation with the involvement of the dentato-rubro-thalamic pathway. The early diagnosis and initiation of treatment with penicillamine resulted in an excellent clinical and radiological response.

Adherence to medical treatment for Wilson's disease in children and adolescents: a cohort study from Turkey.

BACKGROUND: This study aimed to assess medication adherence and demographic, clinical, and psychopathological parameters such as quality of life, depression, and anxiety levels that can affect pediatrics with Wilson's Disease (WD). METHODS: A prospective cohort study was conducted at an outpatient clinic in Turkey among pediatric patients (2 to 18 years) with WD between November 2022 and April 2023. The Medication Adherence Report Scale (MARS-5) as a subjective and Medication Possession Ratio (MPR) as an objective assessment were scored. Physical, genetic and biochemical parameters, the Pediatric Quality of Life Inventory (PedsQL) for both parents and patients, Childhood Depression Inventory, State Trait Anxiety Inventory were also administered. RESULTS: A total of 30 pediatric outpatients who were prescribed D-penicillamine (n = 27) or trientine (n = 3) as chelators and zinc (n = 29) and pyridoxine (n = 19) as supplements were included. Proteinuria (n = 3), skin rash (n = 2), and gastrointestinal upset (n = 2) were observed. When the correlation between MARS-5 and duration of follow-up was examined, a significant negative correlation was found (p = 0.014). According to MPRs, non-adherence rates (missed doses ≥ 20%) were 29.6%, 17.2% and 5.3% for D-penicillamine, zinc and pyridoxine, respectively. PedsQL scores were higher than those of parents, with a positive correlation between them (p < 0.001). Also, there was a significant positive correlation between PedsQL and State Anxiety Inventory (p < 0.001). Comparing the change in urinary copper levels between different levels of treatment knowledge, significant differences were observed between high- and low levels (p = 0.043). CONCLUSIONS: Overall, nonadherence rates were 23.3% based on MARS-5 and 5.3-29.6% based on MPR. It is essential to consider factors such as the duration of follow-up, biochemical parameters, treatment knowledge, quality of life and anxiety as potential influencers of medication adherence.

Glutathione Protects other Cellular Thiols against Oxidation by CuII-Dp44mT.

Cu-thiosemicarbazones have been intensively investigated for their application in cancer therapy or as antimicrobials. Copper(II)-di-2-pyridylketone-4,4-dimethyl-thiosemicarbazone (CuII-Dp44mT) showed anticancer activity in the submicromolar concentration range in cell culture. The interaction of CuII-Dp44mT with thiols leading to their depletion or inhibition was proposed to be involved in this activity. Indeed, CuII-Dp44mT can catalyze the oxidation of thiols although with slow kinetics. The present work aims to obtain insights into the catalytic activity and selectivity of CuII-Dp44mT toward the oxidation of different biologically relevant thiols. Reduced glutathione (GSH), L-cysteine (Cys), N-acetylcysteine (NAC), D-penicillamine (D-Pen), and the two model proteins glutaredoxin (Grx) and thioredoxin (Trx) were investigated. CuII-Dp44mT catalyzed the oxidation of these thiols with different kinetics, with rates in the following order D-Pen>Cys≫NAC>GSH and Trx>Grx. CuII-Dp44mT was more efficient than CuII chloride for the oxidation of NAC and GSH, but not D-Pen and Cys. In mixtures of biologically relevant concentrations of GSH and either Cys, Trx, or Grx, the oxidation kinetics and spectral properties were similar to that of GSH alone, indicating that the interaction of these thiols with CuII-Dp44mT is dominated by GSH. Hence GSH could protect other thiols against potential deleterious oxidation by CuII-Dp44mT.

Challenging diagnosis of Wilson's disease: A case report.

Wilson's disease is arare inherited disorder of copper met abolism. If le f t untre ated, i t can turn into a multi systemic disease with copper deposition in the liver, brain, a nd other tissues. Diagnosi s of Wilson's is delayed in Pak ist an by many ye a rs on average due to va riabl e presen tations. In ad olescents, the initial s igns a re more likely to b e neuropsychiatric. Here we present a case of Wilso n's disease that pre sented initially with he patic symptoms and did not have signs specific to the di sea s e such as Kayser-Fleischer rings. Our case was diagnosed to be Wilson's Disease on ly on further investigat ions and s ubsequently the patient was treated with chela tion therapy using D-Penicillamine.Wilson's Disease should be kept in mind as a differential diagno sis in adolesce nt patients that present with unexplained acute liver failure and cytopenias without any neurological symptoms, as a missed diagnosis can prove to be fatal.

A case of Wilson's disease combined with intracranial lipoma and dysplasia of the corpus callosum with review of the literature.

BACKGROUND: Wilson's disease (WD) is an inherited disorder of copper metabolism. Agenesis of the corpus callosum is the complete or partial absence of the major united fiber bundles connecting the cerebral hemispheres. Intracranial lipoma is an adipose tissue tumor resulting from an abnormal embryonic development of the central nervous system. The simultaneous occurrence of these three disorders is rare and has not been reported. This report focuses on the pathogenesis and association between the three disorders and highlights the importance of recognizing and effectively managing their coexistence. CASE PRESENTATION: The purpose of this study was to present a patient with coexisting WD, intracranial lipoma, and corpus callosum dysplasia. We reviewed a female patient hospitalized in 2023 with clinical manifestations of elevated aminotransferases and decreased ceruloplasmin, as well as genetic testing for an initial diagnosis of Wilson's disease. Subsequently, a cranial MRI showed corpus callosum dysplasia with short T1 signal changes in the cerebral falx, leading to a final diagnosis of Wilson's disease combined with intracranial lipoma and corpus callosum dysplasia. The patient's WD is currently stable after treatment with sodium dimercaptosulfonamide (DMPS) and penicillamine, and the patient's abnormal copper metabolism may promote the growth of intracranial lipoma. CONCLUSION: The pathogenesis of WD combined with intracranial lipoma and corpus callosum dysplasia is complex and clinically rare. The growth of intracranial lipomas may be associated with abnormal copper metabolism in WD. Abnormal copper metabolism affects lipid metabolism and triggers inflammatory responses. Therefore, early diagnosis and treatment are beneficial for improvement. Each new case of this rare co-morbidity is important as it allows for a better assessment and understanding of these cases' more characteristic clinical manifestations, which can help estimate the course of the disease and possible therapeutic options.

Macrophages morphology and cytokine reeducation by ex situ copper thiol complexes.

OBJECTIVE: To study the reeducation effect of copper thiol complexes on macrophage morphology and cytokine expression. METHODS: The effect of copper thiol complexes was assessed on murine macrophages by the cell morphology observed through optical microscopy, while the expression of cytokines by protein abundance after stimulation. A viability experiment was performed on PMBC to confirm that copper complexes do not affect other cells. RESULTS: The M1 shape was reported after treatment with copper thiol complexes at 1-200 µM, while M2 behavior was documented between 50 and 800 µM. Surprisingly, a thin elongate morphology was observed between 400-800 µM like the M2 shape. The expression of M1 cytokines was noted ranging from 1 to 100 µM, with the highest yield at 1 µM (2243 pg/µL) for the copper-penicillamine complex. M2 production behavior was observed at 1-800 µM, with the highest abundance close to 1150 pg/µL (200-400 µM) was quantified from the copper-cysteine complex. Finally, LCCu complexes did not induce a cytotoxic response on PBMC while exhibiting a high IL-4 and IL-10 production, similar to their gold analogs. CONCLUSIONS: The capacity of copper thiol complexes to reeducate M1 to M2 morphoexpression can be promising for cell protection by using copper thiol penicillamine or immuno-regeneration of tissues when using copper thiol cysteine.

Penicillamine-induced Stevens Johnson Syndrome-toxic Epidermal Necrolysis (SJS-TEN) Overlap in an HIV-infected Patient with Wilson's Disease and Hepatitis B.

INTRODUCTION: Stevens-Johnson syndrome (SJS) and Toxic epidermal necrolysis (TEN) are severe adverse drug reactions characterized by widespread blistering and mucositis. Wilson's disease is a rare, autosomal recessive disorder that results in excessive copper accumulation in the body, where penicillamine is an effective treatment option for copper chelation. Penicillamineinduced SJS-TEN is a rare but potentially fatal adverse effect. There is increased susceptibility to SJS/TEN in HIV infection due to immunosuppression and chronic liver disease due to impaired hepatic function. OBJECTIVE: To diagnose and manage the occurrence of the rare severe adverse cutaneous drug reactions in the backdrop of immunosuppression and chronic liver disease. CASE REPORT: We are reporting penicillamine-induced SJS-TEN overlap in a 30-year-old male with Wilson's disease, HIV and Hepatitis B who was treated with intravenous immunoglobulins. The patient later developed neurotrophic ulcer in the right cornea as a delayed sequela. CONCLUSION: Our case report emphasizes that there is an increased predisposition to SJS/TEN in immunocompromised and chronic liver disease patients. Physicians should be well aware of the potential danger of SJS/TEN in this subset of patients, even while prescribing a relatively safer drug.

Enantioselective Target Transport-Mediated Nanozyme Decomposition for the Identification of Reducing Enantiomers in Asymmetric Nanochannel Arrays.

Enantioselective identification of chiral molecules is regarded as one of the key issues in biological and medical sciences because of their configuration-dependent effects on biological systems. In this study, we developed an electrochemical platform based on a tandem recognition-reaction zone design in TiO2 nanochannels for the specific recognition of reducing enantiomers. In this system, MIL-125(Ti) Ti-metal-organic frameworks, in situ grown in TiO2 nanochannels, provided a homochiral recognition environment via postmodification with l-tartaric acid (l-TA); MnO2 nanosheets possessing both glucose oxidase (GOD)- and peroxidase (POD)-mimicking activities served as the target-reactive zone at the end of the nanochannels. The use of penicillamine (Pen) enantiomers as model-reducing targets facilitated the passage of d-Pen through the homochiral recognition zone, owing to its lower affinity with l-TA. The passed Pen molecules reached the responsive zone and induced a target concentration-dependent MnO2 disassembly. Such target recognition event impaired the cascade GOD- and POD-like activities of MnO2. Combining the enantioselectivity of the recognition nanochannels with the cascade enzyme-like activity of MnO2 toward glucose and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate), the quantitative identification of l- and d-Pen was achieved through the changes in transmembrane ionic current induced by the generated charged products. This recognition-reaction zone design paves an effective way for developing a promising electrochemical platform for the identification of reducing enantiomers with improved selectivity and sensitivity.

Evaluation of vitamin B6 supplementation in Wilson's disease patients treated with D-penicillamine.

INTRODUCTION: Wilson's disease (WD) is a copper metabolism disorder characterised by a progressive accumulation of this metal mainly in the liver and the brain. Treatment is based on the removal of copper operated by the chelators, among which, D-penicillamine (DP) is prescribed as a first-line treatment in most situations. There is some evidence in linking the use of DP with a risk of vitamin B6; therefore, vitamin supplementation is sometimes recommended, although non-consensually. The objective of our study was to evaluate the level of vitamin B6 in WD patients treated with DP with and without associated supplementation. METHODOLOGY: All WD patients followed at the National Reference Centre for WD in Lyon between January 2019 and December 2020 treated with DP for more than 1 year were included and separated in two groups according to vitamin B6 supplementation. The level of vitamin B6 was measured by the determination of pyridoxal phosphate (PLP). RESULTS: A total of 37 patients were included. Average age of 23.3±14.8 years, 15 patients with <18 years. Median duration of treatment was 51 (55.8) months. 15 patients were under vitamin B6 supplementation and 22 had interrupted it for more than 1 year. The median PLP level was significantly higher in the group with supplementation, 137.2 (86.7) nmol/L vs 64.9 (30.8) nmol/(p<0.01). No patient had a PLP level<35 nmol/L. CONCLUSION: Long-term stable WD patients under DP treatment probably do not need vitamin B6 supplementation.

D-penicillamine-associated neutropenia in a Doberman pinscher.

Copper-associated hepatitis in dogs results from elevated copper levels secondary to increased intake or decreased clearance. Treatment is through establishing a negative copper balance and can include chelation therapy. Traditionally, chelation therapy in dogs is uses D-penicillamine, which has been shown to have severe side effects in humans. Side effects have not been well-documented in dogs but can include nephrotoxicity and dermatologic reactions. This article is the first to report neutropenia in a dog secondary to chelation therapy using D-penicillamine. In this case, a complete blood (cell) count (CBC) collected before initiation of chelation therapy was normal and neutropenia was documented 4 mo after starting therapy. A cytologic examination of bone marrow confirmed a myeloid hypoplasia. Following discontinuation of D-penicillamine, the neutropenia resolved. Based on this case report, periodic CBC rechecks following the initiation of D-penicillamine chelation therapy are recommended to guide treatment decisions. Key clinical message: Dogs with confirmed copper-associated hepatitis should be treated cautiously with D-penicillamine for chelation therapy. D-penicillamine may adversely affect bone marrow, causing a leukopenia characterized by neutropenia. It is recommended that clinicians periodically monitor neutrophil counts while treating dogs with D-penicillamine.

Neutropénie associée à la D-pénicillamine chez un Doberman pinscher. L'hépatite associée au cuivre chez le chien résulte de niveaux élevés de cuivre secondaires à une augmentation de l'apport ou à une diminution de la clairance. Le traitement consiste à établir un bilan négatif du cuivre et peut inclure une thérapie par chélation. Traditionnellement, la thérapie par chélation chez le chien utilise la D-pénicillamine, dont il a été démontré qu'elle a de graves effets secondaires chez l'homme. Les effets secondaires n'ont pas été bien documentés chez les chiens, mais peuvent inclure une néphrotoxicité et des réactions dermatologiques. Cet article est le premier à rapporter une neutropénie chez un chien secondaire à un traitement par chélation utilisant la D-pénicillamine. Dans ce cas, une numération globulaire complète (CBC) recueillie avant le début du traitement par chélation était normale et une neutropénie a été documentée 4 mois après le début du traitement. Un examen cytologique de la moelle osseuse a confirmé une hypoplasie myéloïde. Après l'arrêt de la D-pénicillamine, la neutropénie a disparu. Sur la base de ce rapport de cas, des vérifications périodiques de la CBC après le début du traitement par chélation de la D-pénicillamine sont recommandées pour guider les décisions de traitement.Message clinique clé :Les chiens atteints d'hépatite associée au cuivre confirmée doivent être traités avec prudence avec de la D-pénicillamine pour le traitement par chélation. La D-pénicillamine peut affecter négativement la moelle osseuse, provoquant une leucopénie caractérisée par une neutropénie. Il est recommandé aux cliniciens de surveiller périodiquement le nombre de neutrophiles lors du traitement des chiens avec de la D-pénicillamine.(Traduit par Dr Serge Messier).

d-Penicillamine@Ag/Cu Nanocluster-Based Fluorescent Nanoneuron for Logic Screening Phosphonate-Type Organophosphate Pesticides and Steganographically Encrypting Information.

Organophosphate pesticides are used in agriculture due to their high effectiveness and low persistence in eradicating insects and pests. However, conventional detection methods encounter the limitation of undesired detection specificity. Thus, screening phosphonate-type organophosphate pesticides (OOPs) from their analogues, phosphorothioate organophosphate pesticides (SOPs), remains a challenge. Here, we reported a d-penicillamine@Ag/Cu nanocluster (DPA@Ag/Cu NCs)-based fluorescence assay to screen OOPs from 21 kinds of organophosphate pesticides, which can be used for logic sensing and information encryption. Acetylthiocholine chloride was enzymatically split by acetylcholinesterase (AChE) to produce thiocholine, which reduced the fluorescence of DPA@Ag/Cu NCs due to the transmission of electrons from DPA@Ag/Cu NCs donor to the thiol group acceptor. Impressively, OOPs acted as an AChE inhibitor and retained the high fluorescence of DPA@Ag/Cu NCs due to the stronger positive electricity of the phosphorus atom. Conversely, SOPs possessed weak toxicity to AChE, which led to low fluorescence intensity. By setting 21 kinds of organophosphate pesticides as the inputs and the fluorescence of the resulting products as the outputs, DPA@Ag/Cu NCs could serve as a fluorescent nanoneuron to construct Boolean logic tree and complex logic circuit for molecular computing. As a proof of concept, by converting the selective response patterns of DPA@Ag/Cu NCs into binary strings, molecular crypto-steganography for encoding, storing, and concealing information was successfully achieved. This study is expected to advance the progress and practical application of nanoclusters in the area of logic detection and information security while also enhancing the relationship between molecular sensors and the world of information.

Early neurological deterioration in Wilson's disease: a systematic literature review and meta-analysis.

INTRODUCTION: Neurological deterioration, soon after anti-copper treatment initiation, is problematic in the management of Wilson's disease (WD) and yet reports in the literature are limited. The aim of our study was to systematically assess the data according to early neurological deteriorations in WD, its outcome and risk factors. METHODS: Using PRISMA guidelines, a systematic review of available data on early neurological deteriorations was performed by searching the PubMed database and reference lists. Random effects meta-analytic models summarized cases of neurological deterioration by disease phenotype. RESULTS: Across the 32 included articles, 217 cases of early neurological deterioration occurred in 1512 WD patients (frequency 14.3%), most commonly in patients with neurological WD (21.8%; 167/763), rarely in hepatic disease (1.3%; 5/377), and with no cases among asymptomatic individuals. Most neurological deterioration occurred in patients treated with d-penicillamine (70.5%; 153/217), trientine (14.2%; 31/217) or zinc salts (6.9%; 15/217); the data did not allow to determine if that reflects how often treatments were chosen as first line therapy or if the risk of deterioration differed with therapy. Symptoms completely resolved in 24.2% of patients (31/128), resolved partially in 27.3% (35/128), did not improve in 39.8% (51/128), with 11 patients lost to follow-up. CONCLUSIONS: Given its occurrence in up to 21.8% of patients with neurological WD in this meta-analysis of small studies, there is a need for further investigations to distinguish the natural time course of WD from treatment-related early deterioration and to develop a standard definition for treatment-induced effects.

Prevalence and diagnostic value of non-criteria antiphospholipid antibodies for antiphospholipid syndrome in Chinese patients.

Background: The presence of antiphospholipid antibodies (aPLs) plays a pivotal role in the pathogenesis of antiphospholipid antibody syndrome (APS). This study aimed to examine the diagnostic value of a set of non-criteria aPLs and their relevance with APS-related criteria and extra-criteria manifestations. Methods: From a prospectively constructed database, consecutive APS patients consisting of 114 primary APS (PAPS group), 54 with APS secondary to SLE (SAPS group), 9 seronegative APS (SNAPS), as well as 209 patients with systemic lupus erythematosus (SLE) and 88 healthy controls were included in this study. Levels of criteria aPLs, baseline information, and APS-related criteria and extra-criteria features were extracted from the database. Serum levels of non-criteria aPLs including aPC IgG/IgM, aPI IgG/IgM, aPE IgG/IgM/IgA, aPG IgG/IgM/IgA, anti-phosphatidic acid (aPA) IgG/IgM, aSM IgG/IgM, and aPS/PT IgG/IgM were analyzed with AESKULISA® ELISA Test Kits. Results: The addition of aPC IgG/M, aPI IgG/M, aPE IgG/M/A, aSM IgG/M, and aPA IgG/M to aCL or aß2GPI IgG/M could significantly increase diagnostic sensitivity and accuracy. A significant difference between PAPS or SAPS and HC was presented in all non-criteria aPLs except for aSM IgM and aPG IgA. Eight out of nine SNAPS patients were positive for at least 1 aPL. Pregnancy morbidity was associated with aSM IgM (r = 0.22) and aSM IgG (r = 0.15). Pre-eclampsia or premature birth was associated with aSM IgG (r = 0.16), aPI IgG (r = 0.22), aPC IgG (r = 0.16), and aPG IgG (r = 0.18). Stroke was associated with aPI IgG (r = 0.2). The clinical association was also observed in DVT with aPS/PT IgG (r = 0.17). Valve lesion was positively associated with aSM IgM (Fisher test p = 0.039), APS nephropathy was associated with aPC IgG (OR 3.797), and livedo reticularis was associated with aPE IgM (OR 15.391). Conclusion: Additional detection of non-criteria aPLs including aPC IgG/M, aPE IgG/M/A, aPI IgG/M, aSM IgG/M, and aPA IgG/M could assist in APS diagnosis. The positivity of certain aPLs was statistically associated with both criteria and extra-criteria APS clinical manifestations.

[Trigger finger-pitfalls and differential diagnosis]. / Der schnellende Finger ­ Pitfalls und Differenzialdiagnostik.

The differential diagnosis of a trigger finger presents a clinical challenge. This case depicts a 32-year-old male patient who presented with persistent snapping of the right index finger at the metacarpophalangeal joint without localized tenderness despite previous surgical A1-annular ligament release. CT diagnostics demonstrated a prominent articular tuberosity. The MRI showed no pathological findings. Surgical revision with concomitant excision of the tuberosity restored smooth mobility of the index finger.

Neurological worsening in Wilson disease - clinical classification and outcome.

BACKGROUND & AIMS: Prevention of neurological worsening (NW) under therapy is an unmet need in the management of Wilson disease (WD). In this study, we aimed to characterize the occurrence, associated outcomes and potential reversibility of NW in WD. METHODS: From a total cohort of 457 patients with WD, 128 patients with WD and neurological features at any time point (all Caucasian, 63 females, median age at diagnosis 22 years) were identified by chart review at University Hospital Heidelberg and grouped according to initial presentation. The timing and occurrence of NW was assessed following a structured clinical examination during clinical visits. RESULTS: Early NW (within the first 3 months of therapy) was observed in 30 out of 115 (26.1%) patients with neurological or mixed presentation and never in patients with a purely hepatic or asymptomatic presentation (0%). Late NW (after >12 months) was seen in a further 23 (20%) with neurological or mixed presentation and in 13 out of 294 (4.4%) patients with a hepatic or asymptomatic presentation. The median time from start of treatment to late NW was 20 months. Only three patients experienced NW between 3 and 12 months. NW was observed with D-penicillamine, trientine and zinc therapy and was reversible in 15/30 (50%) with early NW and in 29/36 (81%) with late NW. CONCLUSIONS: In this study, we identified two peaks in NW: an early (≤3 months) treatment-associated peak and a late (>12 months of treatment) adherence-associated peak. Early paradoxical NW was attributed to treatment initiation and pre-existing neurological damage, and was not observed in those with a hepatic or asymptomatic presentation. Late NW is likely to be associated with non-adherence. IMPACT AND IMPLICATIONS: In patients with Wilson disease, defined as an excess accumulation of copper which can damage the liver, brain and other vital organs, neurological worsening can occur despite chelation therapy. The study identifies different patterns of 'early' (<3 months) vs. 'late' (>12 months) neurological worsening in relation to initiation of chelation therapy and establishes possible causes and the potential for reversibility. These data should be useful for counseling patients and for guiding the optimal management of chelation therapy.

1H NMR-based metabolomic study of striatal injury in rats with copper-loaded Wilson's disease by Chinese and Western medicine intervention.

OBJECTIVE: To investigate the metabolic mechanisms of Chinese and Western medicines on the metabolic network of striatal injury in a copper-loaded rat model of Wilson disease (WD) from a metabolomic perspective. METHODS: We divided 60 rats into 4 groups of 15 rats each according to a random number table, namely the control group, the model group, the Bushen Huoxue Huazhuo Recipe group, and the penicillamine group, and subsequently replicated the WD copper-loaded rat model according to the literature method for a total of 12 weeks. From the 7th week onwards, each intervention group was given an equivalent dose of the corresponding drug, and the control and model groups were given an equal volume of saline gavage until the end of the model replication. We used 1H NMR metabolomics techniques combined with multivariate statistical methods to describe the changes in the striatal metabolic profile of nerve injury in Wilson's disease and to analyze the effect of different treatments on their biomarker interventions. RESULTS: Nerve cell damage was evident in the WD copper-loaded rat model and could be reduced to varying degrees by different methods of intervention in the striatal nerve cells. The content of glycine, serine metabolism, and valine metabolism decreased in WD copper-loaded rat model; aspartate content increased after penicillamine intervention; glycolytic metabolism, valine metabolism, taurine metabolism, and tyrosine metabolism increased in the group of Bushen Huoxue Huazhuo Recipe. CONCLUSION: Different intervention methods of Chinese and Western medicine affect aspartate, glycolysis, taurine, tyrosine, valine, and carbon metabolism in striatal tissues of WD copper-loaded rats, and can regulate the metabolism of small molecules, which in turn have certain repairing effects on nerve damage in WD copper-loaded rats.

Copper chelation by d-penicillamine alleviates melanocyte death induced by rhododendrol without inhibiting tyrosinase.

Oxidative metabolism of rhododendrol (RD), a skin-whitening ingredient, by tyrosinase has caused leukoderma in a certain population of Japanese consumers. Toxic RD metabolites and reactive oxygen species are proposed causes for the melanocyte death. However, the mechanism by which reactive oxygen species are produced during RD metabolism remains elusive. Some phenolic compounds are known to act as suicide substrates for tyrosinase, resulting in release of a copper atom and hydrogen peroxide during its inactivation. We hypothesized that RD may be a suicide substrate for tyrosinase and that the released copper atom may be responsible for the melanocyte death through hydroxyl radical production. In line with this hypothesis, human melanocytes incubated with RD showed an irreversible decrease in tyrosinase activity and underwent cell death. A copper chelator, d-penicillamine, markedly suppressed the RD-dependent cell death without significantly affecting the tyrosinase activity. Peroxide levels in RD-treated cells were not affected by d-penicillamine. Given the unique enzymatic properties of tyrosinase, we conclude that RD acted as a suicide substrate and resulted in release of a copper atom and hydrogen peroxide, which would collectively impair melanocyte viability. These observations further imply that copper chelation may alleviate chemical leukoderma caused by other compounds.