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Blood Advances Jun 2024Autoimmune hemolytic anemia (AIHA) is a rare autoantibody-mediated disease. For steroid and/or rituximab-refractory AIHA, there is no consensus on optimal treatment....
Autoimmune hemolytic anemia (AIHA) is a rare autoantibody-mediated disease. For steroid and/or rituximab-refractory AIHA, there is no consensus on optimal treatment. Daratumumab, a monoclonal antibody targeting CD38, could be beneficial by suppression of CD38+ plasma cells and thus autoantibody secretion. In addition, because CD38 is also expressed by activated T cells, daratumumab may also act via immunomodulatory effects. We evaluated the efficacy and safety of daratumumab monotherapy in an international retrospective study including 19 adult patients with heavily pretreated refractory AIHA. In warm AIHA (wAIHA, n = 12), overall response was 50% with a median response duration of 5.5 months (range, 2-12), including ongoing response in 2 patients after 6 and 12 months. Of 6 nonresponders, 4 had Evans syndrome. In cold AIHA (cAIHA, n = 7) overall hemoglobin (Hb) response was 57%, with ongoing response in 3 of 7 patients. One additional patient with nonanemic cAIHA was treated for severe acrocyanosis and reached a clinical acrocyanosis response as well as a Hb increase. Of 6 patients with cAIHA with acrocyanosis, 4 had improved symptoms after daratumumab treatment. In 2 patients with wAIHA treated with daratumumab, in whom we prospectively collected blood samples, we found complete CD38+ T-cell depletion after daratumumab, as well as altered T-cell subset differentiation and a severely diminished capacity for cell activation and proliferation. Reappearance of CD38+ T cells coincided with disease relapse in 1 patient. In conclusion, our data show that daratumumab therapy may be a treatment option for refractory AIHA. The observed immunomodulatory effects that may contribute to the clinical response deserve further exploration.
Topics: Humans; Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal; Female; Male; Middle Aged; Adult; Aged; Retrospective Studies; Treatment Outcome; ADP-ribosyl Cyclase 1
PubMed: 38507742
DOI: 10.1182/bloodadvances.2024012585 -
Clinical, Cosmetic and Investigational... 2024Systemic sclerosis (SSc) is a relatively rare collagenosis manifested as microvasculopathy, excessive cutaneous and visceral fibrosis in a background of autoimmune...
PURPOSE
Systemic sclerosis (SSc) is a relatively rare collagenosis manifested as microvasculopathy, excessive cutaneous and visceral fibrosis in a background of autoimmune alteration. Autoimmune vasculopathy in SSc occurs early and begins with endothelial cell activation followed by blood vessel intimal proliferation in a context of defective angiogenesis. The alteration of peripheral micro and macrocirculation in SSc is evident through vascular lesions, such as Raynaud's phenomenon, telangiectasias, acrocyanosis, digital ulcers, gangrene, peripheral pulse deficiency. Our paper details the results of the study on the association between telangiectasias and other types of immune-mediated peripheral vascular lesions that can be identified in SSc. The presence of these peripheral vascular lesions can provide information about the magnitude of the peripheral vasculopathy.
PATIENTS AND METHODS
A total of 37 patients diagnosed with SSc, recruited from a university clinic in Bucharest between February 2019 and March 2020, were enrolled in an observational study. We evaluated the presence of telangiectasias, as a stigma of autoimmune microvasculopathy, and their association with other immune-mediated peripheral vascular lesions that may be present in SSc.
RESULTS
The presence of telangiectasias was identified in the absence, but especially in the presence of acrocyanosis and digital ulcerations, and patients with peripheral pulse deficiency almost always had telangiectasias. Less than a quarter of the patients with digital ulcers progressed unfavorably to gangrene, and only one required amputation, telangiectasias being present not only in the patient with amputation but in all patients with gangrene.
CONCLUSION
We appreciate that telangiectasias may be the clinical expression of peripheral vasculopathy characteristic of SSc, they can often be present in association with other peripheral vascular lesions and may represent a valuable indicator for the gangrene risk of digital ulcerations in SSc.
PubMed: 38292323
DOI: 10.2147/CCID.S432422 -
La Revue de Medecine Interne Oct 2020Puffy hand syndrome is a rare complication of intravenous drug addiction. Diagnosis is based on the patient's history and clinical examination.
INTRODUCTION
Puffy hand syndrome is a rare complication of intravenous drug addiction. Diagnosis is based on the patient's history and clinical examination.
OBSERVATIONS
A woman and two men, aged 42, 39 and 36 years old, are described. All had a history of intravenous drug use of heroin and oral buprenorphine misuse. Puffy hand syndrome appeared during drug addiction (n = 2) or after its withdrawal (n = 1). It was associated with acrocyanosis (n = 1) or injection scars (n = 1). Upper limb ultrasonography showed sequelae of venous (n = 3) or arterial (n = 1) thrombosis. An upper limb lymphoscintigraphy in one patient showed decreased radionuclide uptake of axillary lymph node and subdermal reflux tracer in the forearm. Treatment was based on low-stretch bandages to reduce the volume and then elastic compression sleeve for long-term stabilization.
CONCLUSION
Puffy hand syndrome seen in intravenous drug addicts is poorly understood. It is a chronic complication despite the cessation of drug use. This syndrome has to become more widely known because its management is mandatory, although symptomatic.
Topics: Adult; Buprenorphine; Diagnosis, Differential; Female; Hand; Heroin Dependence; Humans; Lymphedema; Male; Opiate Substitution Treatment; Substance Abuse, Intravenous; Syndrome
PubMed: 32674894
DOI: 10.1016/j.revmed.2020.05.020 -
Blood Nov 2021
Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Aged; Aged, 80 and over; Anemia, Hemolytic, Autoimmune; Cyanosis; Female; Humans; Male; Middle Aged; Piperidines; Protein Kinase Inhibitors; Retrospective Studies
PubMed: 34293088
DOI: 10.1182/blood.2021012039 -
Journal of Child Neurology Sep 2021Ethylmalonic encephalopathy is a rare autosomal recessive mitochondrial disorder caused by pathogenic biallelic variants in the gene. The phenotype of this disease has...
Ethylmalonic encephalopathy is a rare autosomal recessive mitochondrial disorder caused by pathogenic biallelic variants in the gene. The phenotype of this disease has been attributed to deficiency in the mitochondrial sulfur dioxygenase leading to many downstream effects. Ethylmalonic encephalopathy classically presents with developmental regression, petechiae, acrocyanosis, and chronic diarrhea. The neurologic phenotype includes hypotonia, spastic diplegia, ataxia, and developmental delay. As more patients with this condition are described, the neurologic phenotype continues to expand. Although strokelike episodes or metabolic strokes have been studied in other mitochondrial disorders, they have not been thoroughly reported in this disorder. Herein, we describe 3 patients with ethylmalonic encephalopathy who presented clinically with strokelike episodes and strokelike abnormalities on brain magnetic resonance imaging in the setting of acute illness, and the long-term sequelae with evolution into cystic changes in one of these subjects.
Topics: Adolescent; Brain; Brain Diseases, Metabolic, Inborn; Child; Child, Preschool; Diagnosis, Differential; Female; Humans; Infant; Magnetic Resonance Imaging; Male; Purpura; Stroke; Time
PubMed: 33900143
DOI: 10.1177/08830738211006507 -
Advances in Skin & Wound Care Mar 2021Forthcoming.
GENERAL PURPOSE
Forthcoming.
TARGET AUDIENCE
This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care.
LEARNING OBJECTIVES/OUTCOMES
Forthcoming.
ABSTRACT
This review article focuses on the pathogenesis, clinical features, and diagnostic testing of the common pathologies that can manifest as chilblains-like lesions. These differentials include COVID toes, Raynaud phenomenon, acrocyanosis, critical limb ischemia, thromboangiitis obliterans, chilblains associated with lupus erythematosus, and idiopathic chilblains. The authors present a helpful mnemonic, ARCTIC, to assist clinicians in recognition and diagnosis.
PubMed: 33797425
DOI: 10.1097/01.ASW.0000737860.47789.3c -
JAMA Dermatology Feb 2021Chilblain-like lesions have been reported during the coronavirus 2019 (COVID-19) pandemic. The pathophysiology of such manifestations remains largely unknown.
IMPORTANCE
Chilblain-like lesions have been reported during the coronavirus 2019 (COVID-19) pandemic. The pathophysiology of such manifestations remains largely unknown.
OBJECTIVE
To perform a systematic clinical, histologic, and biologic assessment in a cohort of patients with chilblain-like lesions occurring during the COVID-19 pandemic.
DESIGN, SETTING, AND PARTICIPANTS
In this prospective case series carried out with a COVID-19 multidisciplinary consultation group at the University Hospital of Nice, France, 40 consecutive patients presenting with chilblain-like lesions were included.
MAIN OUTCOMES AND MEASURES
Patients underwent a thorough general and dermatologic examination, including skin biopsies, vascular investigations, biologic analyses, interferon-alpha (IFN-α) stimulation and detection, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) and serologic analysis.
RESULTS
Overall, 40 consecutive patients with chilblain-like lesions were included. Most patients were young, with a median (range) age of 22 (12-67) years; 19 were male and 21 were female. The clinical presentation was highly reproducible with chilblain-like lesions mostly on the toes. Bullous and necrotic evolution was observed in 11 patients. Acrocyanosis or cold toes were reported in 19 (47.5%) cases. Criteria compatible with COVID-19 cases were noted in 11 (27.5%) within 6 weeks prior to the eruption. The real-time PCR (rt-PCR) testing results were negative in all cases. Overall, SARS-CoV-2 serology results were positive in 12 patients (30%). D-dimer concentration levels were elevated in 24 (60.0%) cases. Cryoglobulinemia and parvovirus B19 serologic results were negative for all tested patients. The major histologic findings were features of lymphocytic inflammation and vascular damage with thickening of venule walls and pericyte hyperplasia. A significant increase of IFN-α production after in vitro stimulation was observed in the chilblain population compared with patients with mild-severe acute COVID-19.
CONCLUSIONS AND RELEVANCE
Taken together, our results suggest that chilblain-like lesions observed during the COVID-19 pandemic represent manifestations of a viral-induced type I interferonopathy.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04344119.
Topics: Adolescent; Adult; Aged; COVID-19; Chilblains; Child; Female; Humans; Interferon-alpha; Male; Middle Aged; Prospective Studies; Young Adult
PubMed: 33237291
DOI: 10.1001/jamadermatol.2020.4324 -
Future Cardiology Jun 2023Hypertrophic cardiomyopathy (HCM) is a rare and heterogeneous disorder in newborns, which can predispose them to other cardiac conditions such as myocardial infarction...
Hypertrophic cardiomyopathy (HCM) is a rare and heterogeneous disorder in newborns, which can predispose them to other cardiac conditions such as myocardial infarction (MI). This case report describes the clinical presentation of a premature infant born at 30 weeks of gestation, who developed cardiac failure due to myocardial ischemia. The newborn exhibited distal acrocyanosis and respiratory distress shortly after birth. Echocardiography revealed significant left ventricular hypercontractility and hypertrophy, along with moderate pericardial effusion, tricuspid regurgitation and mitral regurgitation. Despite treatment with furosemide and inotropes, the patient's condition deteriorated, leading to demise after 14 days. Early detection of MI in newborns with vascular complications and HCM plays a crucial role in their management. In conclusion, the coexistence of acute MI and hypertrophic cardiomyopathy may be indicative of a fatal outcome. Hypertrophic cardiomyopathy (HCM) is a rare and heterogeneous disorder in newborns, which can predispose them to other cardiac conditions such as MI. This case report describes the clinical presentation of a premature infant born at 30 weeks of gestation, who developed cardiac failure due to myocardial ischemia. The newborn exhibited distal acrocyanosis and respiratory distress after birth. Echocardiography revealed significant left ventricular hypercontractility, moderate pericardial effusion, tricuspid regurgitation and mitral regurgitation. Despite treatment, the patient's condition deteriorated, leading to demise after 14 days. Early detection of MI in newborns with vascular complications and HCM plays a crucial role in their management. In conclusion, the coexistence of acute MI and hypertrophic cardiomyopathy may be indicative of a fatal outcome.
Topics: Humans; Infant, Newborn; Mitral Valve Insufficiency; Tricuspid Valve Insufficiency; Pericardial Effusion; Cardiomyopathy, Hypertrophic; Myocardial Infarction; Myocardial Ischemia; Heart Failure; Respiratory Distress Syndrome
PubMed: 37539705
DOI: 10.2217/fca-2022-0130 -
La Revue Du Praticien May 2020
Topics: Cyanosis; Erythromelalgia; Frostbite; Humans; Raynaud Disease
PubMed: 33058653
DOI: No ID Found -
Taiwanese Journal of Obstetrics &... Nov 2020Symmetrical peripheral gangrene (SPG) is an uncommon but important clinical syndrome. We present a case of acute chorioamnionitis complicated with SPG.
OBJECTIVE
Symmetrical peripheral gangrene (SPG) is an uncommon but important clinical syndrome. We present a case of acute chorioamnionitis complicated with SPG.
CASE REPORT
A 33-year-old female (gravida 5, para 2) was admitted with preterm premature rupture of membranes (PPROM) at 20 weeks and four days of gestation. She received cervical cerclage four days ago. Seven days after the diagnosis of PPROM, she developed fever, tachypnea and tachycardia. Termination of pregnancy was decided for clinical diagnosis of sepsis. After the abortus was born, gangrene change on the nose was noticed. Afterwards, this patient developed acrocyanosis of extremities. SPG developed following sepsis with intravascular disseminated coagulation (DIC). After intensive care, the patient underwent hyperbaric oxygen therapy and fasciectomy of the left forearm.
CONCLUSION
We suggest awareness of SPG associated with acute chorioamnionitis. Early recognition of SPG, multidisciplinary care, and treatment of its underlying conditions are the mainstays of management.
Topics: Acute Disease; Adult; Cerclage, Cervical; Chorioamnionitis; Diagnosis, Differential; Disseminated Intravascular Coagulation; Female; Fetal Membranes, Premature Rupture; Foot; Gangrene; Humans; Medical Illustration; Pregnancy; Pregnancy Complications, Cardiovascular; Upper Extremity
PubMed: 33218425
DOI: 10.1016/j.tjog.2020.09.032