High prevalence of cryofibrinogenemia in patients with chilblains during the COVID-19 outbreak.

BACKGROUND: Many cutaneous manifestations have been described in possible association with the COVID-19 pandemic, including acral lesions resembling chilblains. The underlying pathomechanisms of COVID-19 chilblains are not fully understood. The aim of this study was to describe the clinical, pathological, and laboratory findings of a series of patients who developed chilblains during the COVID-19 outbreak and to investigate the possible factors that could be involved in the pathogenesis of these lesions. METHODS: We conducted a prospective cohort study that included 54 patients who presented with chilblains during the highest peak in the incidence of COVID-19 in Cantabria (northern Spain). Skin biopsies were performed on 10 of these patients who presented with recent lesions. Laboratory investigations, including immunological analysis, serological studies, and the assessment of cryoproteins, were also performed. RESULTS: Most patients presented erythematous plaques located on the toes and/or purpuric macules located on the feet. Histopathological findings were compatible with those of idiopathic chilblains. Immunohistochemical evaluation showed C3d and C4d deposits in the vessel walls in seven cases. The autoimmunity panel was negative in most of our series. Cryoprotein testing showed positive cryofibrinogen in two-thirds (66.7%) of the patients assessed. On follow-up, most patients presented almost complete resolution, although six patients required prednisone and antiaggregant drug treatment. CONCLUSIONS: This study shows, for the first time to our knowledge, a high prevalence of cryofibrinogenemia in patients with chilblains during the COVID-19 pandemic. Cryofibrinogenemia could be implicated in the pathogenesis of chilblains related to COVID-19.

Most chilblains observed during the COVID-19 outbreak occur in patients who are negative for COVID-19 on polymerase chain reaction and serology testing.

BACKGROUND: Acral lesions, mainly chilblains, are the most frequently reported cutaneous lesions associated with COVID-19. In more than 80% of patients tested, nasopharyngeal swabs were negative on reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 when performed, and serology was generally not performed. METHODS: A national survey was launched on 30 March 2020 by the French Society of Dermatology asking physicians to report cases of skin manifestations in patients with suspected or confirmed COVID-19 by using a standardized questionnaire. We report the results for acral manifestations. RESULTS: We collected 311 cases of acral manifestations [58.5% women, median age 25.7 years (range 18-39)]. The most frequent clinical presentation (65%) was typical chilblains. In total, 93 cases (30%) showed clinical suspicion of COVID-19, 67 (22%) had only less specific infectious symptoms and 151 (49%) had no clinical signs preceding or during the course of acral lesions. Histology of skin biopsies was consistent with chilblains. Overall, 12 patients showed significant immunological abnormalities. Of the 150 (48%) patients who were tested, 10 patients were positive. Seven of 121 (6%) RT-PCR-tested patients were positive for SARS-CoV-2, and five of 75 (7%) serology-tested patients had IgG anti-SARS-CoV-2. Tested/untested patients or those with/without confirmed COVID-19 did not differ in age, sex, history or acral lesion clinical characteristics. CONCLUSIONS: The results of this survey do not rule out that SARS-CoV-2 could be directly responsible for some cases of chilblains, but we found no evidence of SARS-CoV-2 infection in the large majority of patients with acral lesions during the COVID-19 lockdown period in France. What is already known about this topic? About 1000 cases of acral lesions, mainly chilblains, were reported during the COVID-19 outbreak. Chilblains were reported to occur in young people within 2 weeks of infectious signs, which were mild when present. Most cases did not have COVID-19 confirmed by reverse transcription polymerase chain reaction (RT-PCR), and few serology results were available. What does this study add? Among 311 patients with acral lesions, mainly chilblains, during the COVID-19 lockdown period in France, the majority of patients tested had no evidence of SARS-CoV-2 infection. Overall, 70 of 75 patients were seronegative for SARS-Cov-2 serology and 114 of 121 patients were negative for SARS-CoV-2 RT-PCR.

Demographical, laboratory and associated findings in patients with perniosis.

BACKGROUND: Perniosis is a cold-induced inflammatory disorder of the acral areas. The objective of this study was to investigate the demographic characteristics, associated factors, clinical and laboratory findings in patients with perniosis and to compare those findings between patients who had recurrent and acute disease. METHODS: Thirty-four patients with perniosis were investigated retrospectively for age, gender, occupation, smoking and diet histories, associated diseases, family history of perniosis, precipitating factors, the month of onset and the duration of perniosis, the distribution of the lesions and the results of laboratory investigations. RESULTS: Fifteen patients were male and 19 were female. The ages of the patients ranged from 15 to 57 years. Thirteen patients were working as sales people, which was the most common occupation. Sixteen patients were smokers. While 25 of the patients had encountered perniosis for the first time, in 9 of the patients, there were recurrent lesions. Diseases other than perniosis were recorded in 6 of the patients. The laboratory tests revealed mild leukopenia in 2, antinuclear antibody (ANA) positivity in 3, mild rise in albumin level in serum protein electrophoresis in 1 patient. ANA positivity was significantly higher in patients with recurrent disease. CONCLUSION: Perniosis was more common in women and below 40 years. We found no significant laboratory findings except ANA positivity in patients with recurrent perniosis.

[Perniosis and lupus anticoagulant]. / Perniosis y anticoagulante lúpico.

Five patients with acral chilblains and lupus anticoagulant activity revealed by coagulation analysis are reported. Three patients suffered a systemic lupus erythematosus, and two of them a completely developed antiphospholipid syndrome as well. Another case had chronic cutaneous lupus with only facial discoid lesions, and in the last one the lupus anticoagulant was likely related to a chronic liver infection of hepatitis B virus because she had not erythematous lupus. There are few dermatologic references about chilblain associated to lupus anticoagulant. Certain evidences suggest a pathogenic relation of this findings.

[Hemorheologic study of different forms of vasomotor acrosyndromes]. / Etude hémorhéologique au cours des différentes formes d'acrosyndromes vasomoteurs.

Hemorheologic disorders are a frequent finding in circulating blood during vascular diseases (arterial disease of lower limb, cerebrovascular accidents). They participate in thrombogenesis and tissue ischemia production, and also in microcirculatory disturbances as shown by behavior in microvessels of red cells with decreased hereditary deformability (sickle cell anemia). Active alterations in erythrocyte rheology have also been demonstrated during vascular diseases in relation to inflammation: cell-protein inflammatory reaction, action of leukocytes. Therapy should be adapted for these microcirculatory disorders by suitable specific clinical trials.