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Blood Sep 2022Sutimlimab, a first-in-class humanized immunoglobulin G4 (IgG4) monoclonal antibody that selectively inhibits the classical complement pathway at C1s, rapidly halted... (Randomized Controlled Trial)
Randomized Controlled Trial
Sutimlimab, a first-in-class humanized immunoglobulin G4 (IgG4) monoclonal antibody that selectively inhibits the classical complement pathway at C1s, rapidly halted hemolysis in the single-arm CARDINAL study in recently transfused patients with cold agglutinin disease (CAD). CADENZA was a 26-week randomized, placebo-controlled phase 3 study to assess safety and efficacy of sutimlimab in patients with CAD without recent (within 6 months prior to enrollment) transfusion history. Forty-two patients with screening hemoglobin ≤10 g/dL, elevated bilirubin, and ≥1 CAD symptom received sutimlimab (n = 22) or placebo (n = 20) on days 0 and 7 and then biweekly. Composite primary endpoint criteria (hemoglobin increase ≥1.5 g/dL at treatment assessment timepoint [mean of weeks 23, 25, 26], avoidance of transfusion, and study-prohibited CAD therapy [weeks 5-26]) were met by 16 patients (73%) on sutimlimab, and 3 patients (15%) on placebo (odds ratio, 15.9 [95% confidence interval, 2.9, 88.0; P < .001]). Sutimlimab, but not placebo, significantly increased mean hemoglobin and FACIT-Fatigue scores at treatment assessment timepoint. Sutimlimab normalized mean bilirubin by week 1. Improvements correlated with near-complete inhibition of the classical complement pathway (2.3% mean activity at week 1) and C4 normalization. Twenty-one (96%) sutimlimab patients and 20 (100%) placebo patients experienced ≥1 treatment-emergent adverse event. Headache, hypertension, rhinitis, Raynaud phenomenon, and acrocyanosis were more frequent with sutimlimab vs placebo, with a difference of ≥3 patients between groups. Three sutimlimab patients discontinued owing to adverse events; no placebo patients discontinued. These data demonstrate that sutimlimab has potential to be an important advancement in the treatment of CAD. This trial was registered at www.clinicaltrials.gov as #NCT03347422.
Topics: Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal, Humanized; Bilirubin; Double-Blind Method; Hemoglobins; Humans; Treatment Outcome
PubMed: 35687757
DOI: 10.1182/blood.2021014955 -
Journal of General and Family Medicine May 2021Primary acrocyanosis is a benign condition characterized by persistent blue discoloration of the peripheral extremities caused by vasospasm.
Primary acrocyanosis is a benign condition characterized by persistent blue discoloration of the peripheral extremities caused by vasospasm.
PubMed: 33977015
DOI: 10.1002/jgf2.416 -
Open Access Macedonian Journal of... Sep 2019Understanding the mechanisms of cancer immune-tolerance is one of the most important challenges. Several studies have demonstrated the potential anticarcinogenic effects... (Review)
Review
Understanding the mechanisms of cancer immune-tolerance is one of the most important challenges. Several studies have demonstrated the potential anticarcinogenic effects of beta-blockers, in patients with prostate cancer, breast cancer, and melanoma. At the other side variety of dermatoses may be caused or aggravated by β-blockers-psoriasis, lichen planus-like drug eruptions (LDE), acrocyanosis, alopecia etc. Beta-blockers have been shown to improve the prognosis of melanoma patients significantly. Propranolol inhibits melanoma by downregulating the tumour angiogenesis but also tumour cell proliferation, invasiveness and local immune suppression. Studies showed that only β3-but, not β2-adrenoceptors, were up-regulated under hypoxia in peripheral blood mononuclear cells and selectively expressed in immune cell sub-populations including Treg, MDSC, and NK. They increased NK and CD8 number and cytotoxicity. Catecholamines may retard melanoma progression and that β-blockers may have unrecognised potential as a therapeutic intervention for melanoma, in the prevention of the growth of melanoma in all stages and as adjuvant therapy with other targeted and immune therapies for melanoma.
PubMed: 31850134
DOI: 10.3889/oamjms.2019.781 -
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 -
Cold Spring Harbor Molecular Case... Feb 2022Ethylmalonic encephalopathy (MIM #602473) is a rare autosomal recessive metabolic condition caused by biallelic variants in (MIM #608451), characterized by global...
Ethylmalonic encephalopathy (MIM #602473) is a rare autosomal recessive metabolic condition caused by biallelic variants in (MIM #608451), characterized by global developmental delay, infantile hypotonia, seizures, and microvascular damage. The microvascular changes result in a pattern of relapsing spontaneous diffuse petechiae and purpura, positional acrocyanosis, and pedal edema, hemorrhagic suffusions of mucous membranes, and chronic diarrhea. Here, we describe an instructive case in which ethylmalonic encephalopathy masqueraded as meningococcal septicemia and shock. Ultrarapid whole-genome testing (time to result 60 h) and prompt biochemical analysis facilitated accurate diagnosis and counseling with rapid implementation of precision treatment for the metabolic crisis related to this condition. This case provides a timely reminder to consider rare genetic diagnoses when atypical features of more common conditions are present, with an early referral to ensure prompt biochemical and genomic diagnosis.
Topics: Brain Diseases, Metabolic, Inborn; Humans; Mitochondrial Proteins; Nucleocytoplasmic Transport Proteins; Purpura; Sepsis
PubMed: 35165146
DOI: 10.1101/mcs.a006193 -
Open Access Macedonian Journal of... Jan 2018Acrocyanosis is an uncommon complaint belonging to the acro-syndromes. It typically presents with coolness and bluish discolourations of hands, feet, ears, nose, lips... (Review)
Review
Acrocyanosis is an uncommon complaint belonging to the acro-syndromes. It typically presents with coolness and bluish discolourations of hands, feet, ears, nose, lips and nipple. The most frequently affected parts of the body are the hands. This review discusses physical factors, vascular disorders, infectious diseases, haematological disorders, solid tumours genetic disorders, drugs, eating disorders, and spinal disease presenting as or leading to acrocyanosis.
PubMed: 29484025
DOI: 10.3889/oamjms.2018.035 -
Blood Aug 2013Cold agglutinin disease is a rare and poorly understood disorder affecting 15% of patients with autoimmune hemolytic anemia. We reviewed the clinical and pathologic... (Review)
Review
Cold agglutinin disease is a rare and poorly understood disorder affecting 15% of patients with autoimmune hemolytic anemia. We reviewed the clinical and pathologic features, prognosis, and management in the literature and describe our institutional experience to improve strategies for accurate diagnosis and treatment. Retrospective analysis identified 89 patients from our institution with cold agglutinin disease from 1970 through 2012. Median age at symptom onset was 65 years (range, 41 to 83 years), whereas the median age at diagnosis was 72 years (range, 43 to 91 years). Median survival of all patients was 10.6 years, and 68 patients (76%) were alive 5 years after the diagnosis. The most common symptom was acrocyanosis (n = 39 [44%]), and many had symptoms triggered by cold (n = 35 [39%]) or other factors (n = 20 [22%]). An underlying hematologic disorder was detected in 69 patients (78%). Thirty-six patients (40%) received transfusions during their disease course, and 82% received drug therapy. Rituximab was associated with the longest response duration (median, 24 months) and the lowest proportion of patients needing further treatment (55%). Our institution's experience and review of the literature confirms that early diagnostic evaluation and treatment improves outcomes in cold agglutinin disease.
Topics: Anemia, Hemolytic, Autoimmune; Disease Management; Humans; Prognosis; Retrospective Studies
PubMed: 23757733
DOI: 10.1182/blood-2013-02-474437 -
Indian Journal of Dermatology 2017Approximately, 140 million people worldwide live permanently at high altitudes (HAs) and approximately another 40 million people travel to HA area (HAA) every year for...
Approximately, 140 million people worldwide live permanently at high altitudes (HAs) and approximately another 40 million people travel to HA area (HAA) every year for reasons of occupation, sports or recreation. In India, whole of Ladakh region, part of Northwest Kashmir, Northern part of Sikkim and Tenga valley of Arunachal are considered inhabited areas of HAA. The low quantity of oxygen, high exposure of ultraviolet (UV) light, very low humidity, extreme subzero temperature in winter, high wind velocity, make this region difficult for lowlanders as well as for tourists. Acute mountain sickness, HA pulmonary edema, HA cerebral edema, and thromboembolic conditions are known to occur in HA. However, enough knowledge has not been shared on dermatoses peculiar to this region. Xerosis, UV-related skin disorders (tanning, photomelanosis, acute and chronic sunburn, polymorphic light eruption, chronic actinic dermatitis, actinic cheilitis, etc.), cold injuries (frostbite, chilblains, acrocyanosis, erythrocyanosis, etc.) nail changes (koilonychias), airborne contact dermatitis, insect bite reaction, and skin carcinoma (basal cell carcinomas, squamous cell carcinomas, and also rarely malignant melanoma) are the dermatoses seen in HAAs. Early diagnosis and knowledge of HA dermatoses may prevent serious consequences of disease and improve the quality of life for the visitors as well as for native of the place.
PubMed: 28216727
DOI: 10.4103/0019-5154.198050 -
Vascular Medicine (London, England) Aug 2011Acrocyanosis is symmetric, painless, discoloration of different shades of blue in the distal parts of the body that is marked by symmetry, relative persistence of the... (Review)
Review
Acrocyanosis is symmetric, painless, discoloration of different shades of blue in the distal parts of the body that is marked by symmetry, relative persistence of the skin color changes with aggravation by cold exposure, and frequent association with local hyperhidrosis of hands and feet. Described over a century ago and despite seeming familiarity, it remains a poorly understood condition that shares much in clinical presentation with other conditions characterized by skin color changes in the distal parts of the body. The diagnosis remains mostly clinical, and pathological mechanisms vary suggesting that acrocyanosis may not be a single entity. We performed an extensive literature review to summarize existing knowledge about the demographics, pathology, diagnosis, and treatment of this condition.
Topics: Cyanosis; Humans; Lower Extremity; Predictive Value of Tests; Regional Blood Flow; Risk Factors; Treatment Outcome; Upper Extremity
PubMed: 21427140
DOI: 10.1177/1358863X11398519 -
Indian Journal of Dermatology Nov 2013It is a functional peripheral vascular disorder characterized by bluish discoloration of skin and mucous membrane due to diminished oxyhemoglobin. It may be due to...
INTRODUCTION
It is a functional peripheral vascular disorder characterized by bluish discoloration of skin and mucous membrane due to diminished oxyhemoglobin. It may be due to central or local tissue oxygenation defects. It is a painful episodic disorder, where trophic changes and ulceration are very rare except in necrotizing variant. By definition, it refers to persistent abnormally deep blue or cyanotic discoloration of skin over extremities (hand and feet most commonly) due to decreased oxyhemoglobin.
ETIOLOGY
It can be both primary and secondary to psychiatric, neurologic, autoimmune, infective, metabolic and other causes. The existing hypothesis suggests the prevailing role of vasospastic reaction over possible blood rheology impairment.[1] As per the current line of thinking, it is due to chronic vasospasm of small cutaneous arteries, and arterioles along with compensatory dilatation in the capillary and post capillary venules causes cyanosis and sweating.
CLINICAL FEATURES
Acrocyanosis is an uncommon condition. It usually presents with coolness and violaceous dusky discolorations of hands and less frequently the feet. Other peripheral part like ear, nose, lips and nipple can also be affected.[2] The changes may be transient after cold exposure but frequently persist during winter and even in summer.
MANAGEMENT
There is no standard and curative medical or surgical treatment of acrocyanosis. In mild cases, it is unnecessary to give any drug treatment. Life style modification, dietary and hygiene counseling, avoidance of cold and reassurance that the bluish skin discoloration does not indicate any serious illness is all that is necessary.
PubMed: 24249890
DOI: 10.4103/0019-5154.119946