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Neurological Sciences : Official... Nov 2023Ethylmalonic encephalopathy (EE) is a rare intoxication-type metabolic disorder with multisystem involvement. It is caused by mutations in ETHE1, which encodes the ETHE1... (Review)
Review
BACKGROUND
Ethylmalonic encephalopathy (EE) is a rare intoxication-type metabolic disorder with multisystem involvement. It is caused by mutations in ETHE1, which encodes the ETHE1 enzyme in the mitochondrial matrix that plays a key role in hydrogen sulfide (HS) detoxification acting as a sulphur dioxygenase.
RESULTS
This review focuses on the clinical, metabolic, genetic and neuroradiological features of 70 reported cases, including two new cases. The common manifestations of EE are psychomotor regression, hypotonia, developmental delay, petechia, pyramidal signs, chronic diarrhoea, orthostatic acrocyanosis and failure to thrive, respectively. A significant difference was found in EMA and C4 levels (p=0.003, p=0.0236) between classical and mild phenotypes. Urinary EMA, C4 and C5 levels were found to exhibit normal values in milder cases during attack-free periods. The most common ETHE1 gene homozygous state mutations were (p.R163Q) (c.488G>A), exon 4 deletion, (p.R163W)(c.487C>T), (p.Glu44ValfsTer62)(c.131_132delAG) and (p.M1I)(c.3G>T) mutations, respectively. Fifty-two patients underwent cranial MRI. Basal ganglia signal alterations were detected in 42 cases. Of the 70 cases, eight had a mild phenotype and slow neurological progression with low levels of ethylmalonic acid (EMA) and C4 acylcarnitine. The current age of alive patients in the published articles with mild phenotype was significantly higher than the classical phenotype. (p=0.002). Reducing the accumulation and inducing detoxification of sulfide is the main long-term treatment strategy for EE, including metronidazole, N-acetylcysteine (NAC), dietary modification, liver transplantation and continuous renal replacement therapy (CRRT).
CONCLUSION
Measuring EMA and C4 acylcarnitine during metabolic attacks is critical to diagnosing EE, allowing for early treatment initiation to prevent further encephalopathic crises. Experience with liver transplantation, diet and CRRT, is currently limited. An early multidisciplinary approach with combination therapies is vital to prevent irreversible neurological damage.
PubMed: 37458841
DOI: 10.1007/s10072-023-06904-8 -
Cutis May 2023Patients with eating disorders (EDs) frequently experience malnutrition that may lead to nutritional dermatoses. Effects of malnutrition and starvation on the skin may... (Review)
Review
Patients with eating disorders (EDs) frequently experience malnutrition that may lead to nutritional dermatoses. Effects of malnutrition and starvation on the skin may include xerosis, lanugo, pruritus, acrocyanosis, carotenoderma, telogen effluvium, and other hair and mucosal findings. Although these dermatologic sequelae often are reported among patients with EDs, the pathomechanisms of these cutaneous symptoms are poorly understood. This article reviews the existing literature on nutritional dermatoses to clarify visible signs that should heighten clinical suspicion for an underlying ED. The skin may present the first visible signs of an otherwise occult ED diagnosis, offering the dermatologist a special opportunity for early diagnosis and coordination with a multidisciplinary team for ED treatment.
Topics: Humans; Skin; Feeding and Eating Disorders; Skin Diseases; Hair; Malnutrition
PubMed: 37406318
DOI: 10.12788/cutis.0765 -
Journal of Primary Care & Community... 2023Acrocyanosis and erythema pernio are 2 dermatologic manifestations of vasospastic changes. Primary care providers should consider that these conditions can occur as...
INTRODUCTION
Acrocyanosis and erythema pernio are 2 dermatologic manifestations of vasospastic changes. Primary care providers should consider that these conditions can occur as primary or idiopathic conditions and as secondary conditions related to another disease or medication. Herein we describe a case of acrocyanosis and erythema pernio attributed to vincristine therapy.
CASE DESCRIPTION
A 22-year-old man was evaluated for discomfort and red lesions involving the toes of both feet for several weeks. He had completed chemotherapy 1 month earlier for Ewing sarcoma in the right femur. Local control for the primary tumor included wide local excision and reconstruction with a vascularized fibular allograft from the right fibula. On examination, his right foot was dark blue and cool. Toes on both feet had nonpainful erythematous papules. After the case was discussed with the patient's oncology team, the diagnosis was medication-induced acrocyanosis of the right foot and bilateral erythema pernio. Treatment consisted of supportive care to keep the feet warm and promote circulation to the feet. At 2-week follow-up, the patient's symptoms and the appearance of his feet had markedly improved.
DISCUSSION
Primary care clinicians should be able to recognize dermatologic manifestations of vasospastic changes, including acrocyanosis and erythema pernio, and rule out possible secondary causes, such as pharmacologic agents. This patient's history of therapy for Ewing sarcoma prompted consideration of medication-induced vasospastic changes most likely related to the adverse vasospastic effects of vincristine. Symptoms should improve with cessation of the offending medication.
Topics: Male; Humans; Young Adult; Adult; Chilblains; Vincristine; Sarcoma, Ewing; Erythema
PubMed: 37335086
DOI: 10.1177/21501319231181879 -
Expert Opinion on Biological Therapy May 2023Cold agglutinin disease (CAD) is a difficult-to-treat autoimmune hemolytic anemia and B cell lymphoproliferative disorder associated with fatigue, acrocyanosis, and a... (Review)
Review
INTRODUCTION
Cold agglutinin disease (CAD) is a difficult-to-treat autoimmune hemolytic anemia and B cell lymphoproliferative disorder associated with fatigue, acrocyanosis, and a risk of thromboembolic events. Cold-induced binding of autoantibody agglutinates red blood cells and triggers the classical complement pathway, leading to predominantly extravascular hemolysis.
AREAS COVERED
This review summarizes clinical and experimental antibody-based treatments for CAD and analyzes the risks and benefits of B cell and complement directed therapies, and discusses potential future treatments for CAD.
EXPERT OPINION
Conventional treatment of CAD includes a B cell targeted treatment approach with rituximab, yielding only limited treatment success. The addition of a cytotoxic agent (e.g. bendamustine) increases efficacy, but this is accompanied by an increased risk of neutropenia and infection. Novel complement directed therapies have emerged and were shown to have good efficacy against hemolysis and safety profiles but are expensive and unable to address circulatory symptoms. Complement inhibition with sutimlimab may be used as a bridging strategy until B cell directed therapy with rituximab takes effect or continued indefinitely if needed. Future antibody-based treatment approaches for CAD involve the further development of complement directed antibodies, a combination of rituximab and bortezomib, and daratumumab. Non-antibody based prospective treatments may include the use of Bruton tyrosine kinase inhibitors.
Topics: Humans; Anemia, Hemolytic, Autoimmune; Rituximab; Antibodies, Monoclonal; Hemolysis; B-Lymphocytes
PubMed: 37128907
DOI: 10.1080/14712598.2023.2209265 -
Infection and Drug Resistance 2023Chlamydia is a zoonotic pathogen that mainly infects poultry and pet birds. This Gram-negative obligate intracellular parasite also causes human psittacosis, the...
Chlamydia is a zoonotic pathogen that mainly infects poultry and pet birds. This Gram-negative obligate intracellular parasite also causes human psittacosis, the severity of which varies from mild flu-like symptoms to life-threatening severe pneumonia, including sepsis, acute respiratory distress syndrome, and multiple organ failure. Inhalation of aerosols from contaminated bird excreta through the respiratory tract is the main route of transmission to humans. Here, we present a case of pneumonia accompanied by lower extremity atherosclerotic occlusive disease. A 48-year-old man was admitted to the emergency department with a four-day history of cough and dyspnea. A detailed history revealed his contact with domestic pigeons. The results of metagenomic next-generation sequencing of bronchoalveolar lavage fluid suggested infection. Antibacterial agents were switched to targeted doxycycline, but in the next week, skin examination revealed acrocyanosis of both lower extremities, and the remarkable palpable purpura progressively worsened. Re-examination of the lower extremity vascular ultrasound suggested left dorsalis pedis artery occlusion and right peroneal vein thrombosis, which resulted in the amputation of both legs. This case is the first report of pneumonia combined with arterioocclusive sclerosis of both lower extremities.
PubMed: 37077253
DOI: 10.2147/IDR.S393256 -
Journal of Clinical Medicine Mar 2023Although an increasing number of real-life data confirm large-scale clinical trial findings on the efficacy and safety of SARS-CoV-2 vaccines, rare but severe adverse...
Although an increasing number of real-life data confirm large-scale clinical trial findings on the efficacy and safety of SARS-CoV-2 vaccines, rare but severe adverse reactions have begun to emerge. Here, we report a full-blown hypereosinophilic syndrome (HES) following a BNT162b2 (BioNTech/Pfizer) vaccine. A 48-year-old man developed, 5 days after the first shot of the SARS-CoV-2 vaccine, erythematous and painful nodular lesions in the lower and upper limbs accompanied by widespread itching, acrocyanosis with gangrenous lesions at the tips of the first and fourth fingers of the right hand, as well as paresthesia in the right hand and foot. Investigations revealed isolated eosinophilia, occlusion of the right ulnar artery, and electromyography alteration compatible with multifocal sensory neuropathy, as well as minimal accentuation of the interstitial texture with some ground glass appearance. Despite treatment with prednisone in combination with warfarin, he developed thrombosis of the left ulnar artery. Therefore, therapy with an IL-5 inhibitor and acetylsalicylic was successfully added. Given the time interval between the onset of clinical manifestations and the vaccine shot, we believe that the mRNA vaccine triggered the eosinophilic response. This case evidences a possible link between HES and the SARS-CoV-2 vaccination. Mepolizumab, an IL-5 inhibitor, might be considered in steroid refractory cases.
PubMed: 36983376
DOI: 10.3390/jcm12062376 -
American Journal of Medical Genetics.... Jun 2023Ethylmalonic encephalopathy (EE) is a rare, severe, autosomal recessive condition caused by pathogenic variants in ETHE1 leading to progressive encephalopathy, hypotonia...
Ethylmalonic encephalopathy (EE) is a rare, severe, autosomal recessive condition caused by pathogenic variants in ETHE1 leading to progressive encephalopathy, hypotonia evolving to dystonia, petechiae, orthostatic acrocyanosis, diarrhea, and elevated ethylmalonic acid in urine. In this case report, we describe a patient with only mild speech and gross motor delays, subtle biochemical abnormalities, and normal brain imaging found to be homozygous for a pathogenic ETHE1 variant (c.586G>A) via whole exome sequencing. This case highlights the clinical heterogeneity of ETHE1 mutations and the utility of whole-exome sequencing in diagnosing mild cases of EE.
Topics: Humans; Brain Diseases, Metabolic, Inborn; Purpura; Brain; Brain Diseases; Mitochondrial Proteins; Nucleocytoplasmic Transport Proteins
PubMed: 36891747
DOI: 10.1002/ajmg.a.63176 -
BMJ Case Reports Feb 2023A man in his 70s, with a recent diagnosis of transitional cell carcinoma of the bladder, reported a 2-month history of discolouration, pain and paraesthesia affecting...
A man in his 70s, with a recent diagnosis of transitional cell carcinoma of the bladder, reported a 2-month history of discolouration, pain and paraesthesia affecting his fingers. Clinical assessment noted peripheral acrocyanosis with areas of digital ulceration and gangrene. Following further work-up to evaluate potential causes, he was diagnosed with paraneoplastic acrocyanosis. He proceeded to undergo robotic cystoprostatectomy and received adjuvant chemotherapy for the management of his cancer. In parallel to the chemotherapy, vasodilatory therapy was administered as two courses of intravenous synthetic prostacyclin analogue iloprost along with sildenafil. This resulted in a significant improvement in digital pain and gangrene with healing of ulceration.
Topics: Male; Humans; Vasodilator Agents; Gangrene; Iloprost; Epoprostenol; Sildenafil Citrate
PubMed: 36810331
DOI: 10.1136/bcr-2022-251417 -
Dermatology Online Journal Oct 2022The breasts are a common location for diffuse dermal angiomatosis (DDA) in a context of obesity and macromastia. The typical clinical presentation includes erythematous...
The breasts are a common location for diffuse dermal angiomatosis (DDA) in a context of obesity and macromastia. The typical clinical presentation includes erythematous or purplish plaques, reticulated telangiectasias, and sometimes livedo reticularis, often complicated by painful ulcerations of the breasts. Biopsy usually confirms a dermal proliferation of endothelial cells staining positively for CD31, CD34 and SMAa and negatively for HHV8. We report herein a woman with DDA of the breasts presenting as diffuse livedo reticularis and acrocyanosis, both long-standing and considered idiopathic following extensive investigations. Since a biopsy of the livedo did not document DDA features in our case, we suggest that our patient's livedo reticularis and telangiectasias could constitute a vascular predisposition for DDA, as its pathogenesis frequently involves an underlying disease involving ischemia, hypoxia, or hypercoagulability.
Topics: Female; Humans; Livedo Reticularis; Endothelial Cells; Angiomatosis; Breast; Telangiectasis
PubMed: 36809137
DOI: 10.5070/D328559248 -
Indian Journal of Dermatology 2022Cutaneous manifestations of coronavirus disease 2019 (COVID-19) range from mild skin rashes to severe vasculitis. In the current study, we evaluated the demographic...
BACKGROUND
Cutaneous manifestations of coronavirus disease 2019 (COVID-19) range from mild skin rashes to severe vasculitis. In the current study, we evaluated the demographic characteristics of the patients with cutaneous vasculitis following COVID-19 infection.
MATERIALS AND METHODS
In the current study, we evaluated 799 hospitalised patients with COVID-19 infection for development of cutaneous vasculitis. Demographic and clinical characteristics of the patients were obtained using questionnaires and patients' records. Cutaneous vasculitis of the suspected patients were confirmed using skin biopsy and direct immunofluorescence.
RESULTS
We detected 24 hospitalised cases with cutaneous vasculitis presenting with petechia, purpura, livedoretcularis and acrocyanosis. Our data showed a significant relationship between male sex, advanced age, C-reactive protein (CRP) level and presence of comorbidities with development of cutaneous vasculitis. In addition, we found a positive association between the severity of COVID-19 infection and occurrence of cutaneous vasculitis.
CONCLUSION
Our findings are suggestive that clinicians must be aware of cutaneous vasculitis risk as prognostic value in the patients with severe COVID-19 infection.
PubMed: 36578723
DOI: 10.4103/ijd.ijd_13_22