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Frontiers in Immunology 2021Pathogenic gain-of-function variants in complement Factor B were identified as causative of atypical Hemolytic Uremic syndrome (aHUS) in 2007. These mutations generate a...
Pathogenic gain-of-function variants in complement Factor B were identified as causative of atypical Hemolytic Uremic syndrome (aHUS) in 2007. These mutations generate a reduction on the plasma levels of complement C3. A four-month-old boy was diagnosed with hypocomplementemic aHUS in May 2000, and he suffered seven recurrences during the following three years. He developed a severe hypertension which required 6 anti-hypertensive drugs and presented acrocyanosis and several confusional episodes. Plasma infusion or exchange, and immunosuppressive treatments did not improve the clinical evolution, and the patient developed end-stage renal disease at the age of 3 years. Hypertension and vascular symptoms persisted while he was on peritoneal dialysis or hemodialysis, as well as after bilateral nephrectomy. C3 levels remained low, while C4 levels were normal. In 2005, a heterozygous gain-of-function mutation in Factor B (K323E) was found. A combined liver and kidney transplantation (CLKT) was performed in March 2009, since there was not any therapy for complement inhibition in these patients. Kidney and liver functions normalized in the first two weeks, and the C3/C4 ratio immediately after transplantation, indicating that the C3 activation has been corrected. After remaining stable for 4 years, the patient suffered a B-cell non-Hodgkin lymphoma that was cured by chemotherapy and reduction of immunosuppressive drugs. Signs of liver rejection with cholangitis were observed a few months later, and a second liver graft was done 11 years after the CLKT. One year later, the patient maintains normal kidney and liver functions, also C3 and C4 levels are within the normal range. The 12-year follow-up of the patient reveals that, in spite of severe complications, CLKT was an acceptable therapeutic option for this aHUS patient.
Topics: Atypical Hemolytic Uremic Syndrome; Complement Factor B; Gain of Function Mutation; Humans; Infant; Kidney Transplantation; Liver Transplantation; Male
PubMed: 34721423
DOI: 10.3389/fimmu.2021.751093 -
Clinical Autonomic Research : Official... Dec 2021In neuropathic postural tachycardia syndrome, peripheral sympathetic dysfunction leads to excessive venous blood pooling during orthostasis. Up to 84% of patients report...
PURPOSE
In neuropathic postural tachycardia syndrome, peripheral sympathetic dysfunction leads to excessive venous blood pooling during orthostasis. Up to 84% of patients report leg pain and weakness in the upright position. To explore possible pathophysiological processes underlying these symptoms, the present study examined muscle excitability depending on body position in patients with neuropathic postural tachycardia syndrome and healthy subjects.
METHODS
In ten patients with neuropathic postural tachycardia syndrome and ten healthy subjects, muscle excitability measurements were performed repeatedly: in the supine position, during 10 min of head-up tilt and during 6 min thereafter. Additionally, lower leg circumference was measured and subjective leg pain levels were assessed.
RESULTS
In patients with neuropathic postural tachycardia syndrome, muscle excitability was increased in the supine position, decreased progressively during tilt, continued to decrease after being returned to the supine position, and did not completely recover to baseline values after 6 min of supine rest. The reduction in muscle excitability during tilt was paralleled by an increase in lower leg circumference as well as leg pain levels. No such changes were observed in healthy subjects.
CONCLUSIONS
This study provides evidence for the occurrence of orthostatic changes in muscle excitability in patients with neuropathic postural tachycardia syndrome and that these may be associated with inadequate perfusion of the lower extremities. Insufficient perfusion as a consequence of blood stasis may cause misery perfusion of the muscles, which could explain the occurrence of orthostatic leg pain in neuropathic postural tachycardia syndrome.
Topics: Heart Rate; Humans; Leg; Muscles; Pain; Postural Orthostatic Tachycardia Syndrome; Tachycardia; Tilt-Table Test
PubMed: 34674068
DOI: 10.1007/s10286-021-00830-5 -
International Journal of... 2021Hypercoagulability is a risk factor of thromboembolic events in COVID-19. Anti-phospholipid (aPL) antibodies have been hypothesized to be involved. Typical COVID-19...
BACKGROUND
Hypercoagulability is a risk factor of thromboembolic events in COVID-19. Anti-phospholipid (aPL) antibodies have been hypothesized to be involved. Typical COVID-19 dermatological manifestations of livedo reticularis and digital ischemia may resemble cutaneous manifestations of anti-phospholipid syndrome (APS).
OBJECTIVES
To investigate the association between aPL antibodies and thromboembolic events, COVID-19 severity, mortality, and cutaneous manifestations in patients with COVID-19.
METHODS
aPL antibodies [anti-beta2-glycoprotein-1 (B2GP1) and anti-cardiolipin (aCL) antibodies] were titered in frozen serum samples from hospitalized COVID-19 patients and the patients' clinical records were retrospectively analyzed.
RESULTS
173 patients were enrolled. aPL antibodies were detected in 34.7% of patients, anti-B2GP1 antibodies in 30.1%, and aCL antibodies in 10.4%. Double positivity was observed in 5.2% of patients. Thromboembolic events occurred in 9.8% of patients, including 11 pulmonary embolisms, 1 case of celiac tripod thrombosis, and six arterial ischemic events affecting the cerebral, celiac, splenic, or femoral-popliteal arteries or the aorta. aPL antibodies were found in 52.9% of patients with vascular events, but thromboembolic events were not correlated to aPL antibodies (adjusted OR = 1.69, = 0.502). Ten patients (5.8%) had cutaneous signs of vasculopathy: nine livedo reticularis and one acrocyanosis. No significant association was observed between the presence of cutaneous vasculopathy and aPL antibodies ( = 0.692).
CONCLUSIONS
Anti-phospholipid antibodies cannot be considered responsible for hypercoagulability and thrombotic events in COVID-19 patients. In COVID-19 patients, livedo reticularis and acrocyanosis do not appear to be cutaneous manifestations of APS.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Anticardiolipin; Antibodies, Antiphospholipid; COVID-19; Female; Hospitalization; Humans; Italy; Male; Middle Aged; Retrospective Studies; SARS-CoV-2; Seroepidemiologic Studies; Skin Diseases; Vascular Diseases; beta 2-Glycoprotein I
PubMed: 34541915
DOI: 10.1177/20587384211042115 -
Acta Dermato-venereologica Dec 2021Numerous cases of chilblains have been observed in the course if the COVID-19 pandemic. The aims of this study were to provide comprehensive follow-up data for patients...
Numerous cases of chilblains have been observed in the course if the COVID-19 pandemic. The aims of this study were to provide comprehensive follow-up data for patients reporting chilblains, and to determine the risk factors for incomplete recovery. Patients referred to 5 hospitals in France between March and May 2020 for chilblains were surveyed on December 2020. A teleconsultation was offered. Among 82 patients reporting chilblains, 27 (33%) reported complete recovery, 33 (40%) had recurrences of chilblains after their hands and feet had returned to normal, and 22 (27%) developed persistent acral manifestations, mostly acrocyanosis, with or without further recurrences of chilblains. Most recurrences of chilblains occurred during the following autumn and winter. A past history of chilblains was not associated with recurrences or persistent acral manifestations. Women had a significantly higher risk of developing recurrences or persistent acral manifestations (odds ratio 1.30; 95% confidence interval 1.06-1.59). In conclusion, two-thirds of patients reporting chilblains at the start of the COVID-19 pandemic experienced persistent or recurrent acral manifestations after a 10-month follow-up.
Topics: Biopsy; COVID-19; Chilblains; Female; Humans; Pandemics; SARS-CoV-2
PubMed: 34515805
DOI: 10.2340/00015555-3930 -
Clinical and Experimental Dermatology Feb 2022Acute pseudoperniosis (PP) has a recognized association with COVID-19 and tends to occur without cold precipitation in young, healthy patients, often without a clear...
BACKGROUND
Acute pseudoperniosis (PP) has a recognized association with COVID-19 and tends to occur without cold precipitation in young, healthy patients, often without a clear history of COVID-19. These lesions usually resolve within 2 weeks and without long-term sequelae. In the early months of 2021, patients with delayed and protracted PP began to emerge. We have called this presentation 'tardive COVID-19 PP (TCPP)'.
AIM
To consolidate and expand knowledge on TCPP, we describe the clinical characteristics, treatments and outcomes of 16 patients with TCPP who were reviewed by our outpatient dermatology service.
RESULTS
The initial clinical manifestations were erythema, swelling and PP of the fingers in 56.2%, and of the toes in 31.2%, desquamation in 56.2% and acrocyanosis in 12.5%. Ten patients had eventual involvement of all acral sites. The median duration of symptoms was 191 days. Six patients reported close contact with a confirmed or suspected case of COVID-19, but only two had positive COVID-19 tests. Four patients experienced complete or almost complete resolution of symptoms, while the rest remain under active treatment.
CONCLUSION
Unlike acute PP, TCPP has a protracted and delayed presentation that is typically associated with profound acrocyanosis. Patients with TCPP represent a new phenomenon that is part of the post-COVID-19 syndrome, with risk factors and pathophysiology that are not yet fully understood. Our data indicate that likely predisposing factors for developing TCPP include young age, a preceding history of cold intolerance and an arachnodactyloid phenotype. Anorexia, connective tissue disorders or sickle cell trait may also predispose to TCPP. In addition, low titre antinuclear antibody positivity, the presence of cryoglobulins, or low complement levels may represent further risk factors. Finally, prolonged low temperatures are also likely to be contributing to the symptoms.
Topics: Acute Disease; Adolescent; Adult; Aged; COVID-19; Chilblains; Cohort Studies; Female; Foot Dermatoses; Hand Dermatoses; Humans; Male; Middle Aged; Time Factors; Young Adult; Post-Acute COVID-19 Syndrome
PubMed: 34411313
DOI: 10.1111/ced.14891 -
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 -
Frontiers in Immunology 2021Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare paraneoplastic disease with a high prevalence of skin... (Clinical Trial)
Clinical Trial
Skin Responses in Newly Diagnosed Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, and Skin Changes (POEMS) Syndrome After Therapy With Low-Dose Lenalidomide Plus Dexamethasone.
BACKGROUND
Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare paraneoplastic disease with a high prevalence of skin symptoms. Few studies have focused on skin responses to systemic treatment of this disease.
OBJECTIVE
To evaluate skin responses after treatment with low-dose lenalidomide plus dexamethasone and determine their relationship with vascular endothelial growth factor (VEGF) and hematological responses.
METHODS
A total of 41 consecutive Chinese patients who were at least 18 years of age with newly diagnosed POEMS syndrome were enrolled. 36 of them completed 12 cycles of treatment. Skin, serum VEGF, hematological and neurological responses were documented at 1, 2, 3, 6, 9, and 12 months during treatment.
RESULTS
Skin manifestations were not associated with serum VEGF levels at baseline. Of the patients with hyperpigmentation, hemangiomas, hypertrichosis, white nails, or acrocyanosis separately, 26/34 (76.5%), 11/30 (36.7%), 14/15 (93.3%), 21/21 (100%), and 4/4 (100%) achieved complete responses at 12 months. Reduction in hyperpigmentation after 12 months reflected a good VEGF response ( = 0.017).
CONCLUSION
Low-dose lenalidomide plus dexamethasone therapy is effective in reversing skin changes in patients with POEMS syndrome.
CLINICAL TRIAL REGISTRATION
Clinicaltrials.gov, identifier NCT01816620.
Topics: Adult; Aged; Biomarkers; Biopsy; Dexamethasone; Drug Therapy, Combination; Duration of Therapy; Female; Humans; Lenalidomide; Male; Middle Aged; POEMS Syndrome; Skin; Symptom Assessment; Treatment Outcome; Vascular Endothelial Growth Factor A; Young Adult
PubMed: 34025681
DOI: 10.3389/fimmu.2021.681360 -
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 -
International Journal of Infectious... May 2021Presented is a patient with dyspnea and painful ulcers finally resulting in multi-organ failure. A detailed history resulted in positive PCR testing for Chlamydia...
Presented is a patient with dyspnea and painful ulcers finally resulting in multi-organ failure. A detailed history resulted in positive PCR testing for Chlamydia psittaci. We emphasize the importance of a definitive history in establishing the correct diagnosis. When clinicians observe dyspnea with multi-organ failure, they should be aware of psittacosis.
Topics: Chlamydophila psittaci; Humans; Multiple Organ Failure; Necrosis; Polymerase Chain Reaction; Psittacosis
PubMed: 33823280
DOI: 10.1016/j.ijid.2021.03.091 -
Archivos de Cardiologia de Mexico Mar 2021The objective is demonstrate the diagnostic process and evolution of a patient with a diagnosis of congenital pulmonary vein stenosis and broncho-pulmonary vascular...
The objective is demonstrate the diagnostic process and evolution of a patient with a diagnosis of congenital pulmonary vein stenosis and broncho-pulmonary vascular malformation. One year old female patient with repeated bronchopneumonia, acrocyanosis, split S2, cardiomegaly, pulmonary hypertension, with a clinical diagnosis of atrial septal defect. The echocardiogram demonstrated left sided vein pulmonary stenosis. The cardiac catheterization demonstrated arterial-venous fistulas apical on the right lung. Magnetic Resonance image and angiography showed an aberrant arterial vessel parallel to the abdominal aorta which flow the right pulmonary lobe. The cardiac tomography angiography reported confluence of right-sided pulmonary veins. A lobectomy is performed. Patient died in post-operative due to massive pulmonary hemorrhaging. This is the first patient mentioned in written literature with pulmonary vein stenosis associated with pulmonary sequestration, with normal venous connection. Echocardiography represents the specific standard study ideal for initial diagnostic for patients with pulmonary vein stenosis.
PubMed: 33725717
DOI: 10.24875/ACM.20000362