Chronic Chilblain Like Lesions Associated with the Covid-19 Pandemic

Background/Aims We report the features of chronic chilblain-like digital lesions newly presenting since the start of the covid-19 pandemic. Comparison with primary perniosis and acrocyanosis, reveals a unique phenotype which appears to be a long-covid phenomenon. Methods The case records of 26 patients with new onset persistent chilblain-like lesions presenting to the Rheumatology service of St George's University Hospital, London between Autumn 2020 and Spring 2022 were reviewed. Demographic and clinical features, serology, imaging, treatment response and outcome up to Summer 2022 were collated retrospectively. Results Chilblain-like lesions first occurred between September and March;2019/ 2020 6 cases, 2020/2021 18 cases and 2021/2022 2 cases. Mean age 35.4 (17-60) years, 88% female, 85% white, all non-smokers. Median body mass index (BMI) 20.2, range 17.0 - 33.2. BMI underweight (<18.5) in 27%. All cases reported new red-purple-blue colour changes of the fingers, some with pain, swelling and pruritis, affecting both hands in 12, one hand in 6, and both hands and feet in 8 cases. There was a past history of cold sensitivity or primary Raynaud's in 54%. Covid was confirmed in 3 cases, 2 - 8 months prior to onset of chilblain-like symptoms. Possible covid, unconfirmed, was suspected in 5 cases, 1 - 11 months earlier. Affected digits appeared diffusely erythro-cyanotic in 81%, with blotchy discrete maculo-papular erythematous lesions in 42%, some with both features. Involvement was asymmetric in 54%, thumbs spared in 69%. Complement was low in 50% (8/16), ANA positive in 26% (6/23). MRI of hands showed phalangeal bone marrow oedema in keeping with osteitis in 4 of 7 cases. More severe signs and symptoms were associated with low BMI, low C3/4 and a past history of cold sensitivity or Raynauds. Cold avoidance strategies were sufficient for 58%. Pain prompted a trial of NSAIDs, aspirin, nitrates, calcium channel blockers, hydroxychloroquine, oral or topical corticosteroid or topical tacrolimus in 42%. In general, these were minimally effective or not tolerated. 4 severe cases received sildenafil or tadalafil, effective in 2. In 27% complete remission occurred during the first summer season after symptoms commenced, median duration 6 (range 2 - 10) months. In the remaining 19 cases, chilblain-like symptoms returned or worsened in the subsequent second winter period, with 6 of 19 entering remission the following summer. For the remaining 13 persistent cases the total duration of symptoms spans more than a year, and in four cases more than 2 years. Conclusion This series illustrates a distinct chronic chilblain-like condition. Features similar to primary perniosis include female predominance, middle age, pruritic painful blotchy lesions, asymmetry and low BMI. Features in keeping with acrocyanosis include chronicity, extensive diffuse erythro-cyanotic discoloration, relative improvement in warm weather and lack of association with smoking.

Cutaneous manifestations of COVID-19.

COVID - 19 can be accompanied by a variety of cutaneous abnormalities, which mainly include vascular lesions chilblain - like lesions, livedo reticularis, purpura, ecchymosis, acral cyanosis, gangrene, etcand inflammatory lesionsdiffuse erythema, morbilliform exanthem, acute urticaria, varicella- like exanthem, etc. Some types of skin lesions may be the first symptom or the only clinical manifestation of COVID-19.Copyright © 2022 Chinese Journal of Dermatology. All rights reserved.

HYPEREOSINOPHILIC SYNDROME FOLLOWING the BNT162B2 (BIONTECH/PFIZER) VACCINATION

Background: Some reports of small vessel vasculitis following nSARS-CoV2 vaccination are reported in the literature (1, 2). Objectives: We purpose to report the case of small-medium vessel vasculitis after BNT162b2 (BioNTech/Pfzer) vaccination. Methods: We present the case of a 48 years old man with an unremarkable history who underwent BNT162b2 vaccination. Results: Five days after the frst shot of BNT162b2 vaccine, the patient refer the onset of left inguinal adenopathy, and erythematous dermatitis of the trunk. Ultrasound of the groin found increase bilateral inguinal lymph nodes with reactive characters. Contextually, erythematous, itchy and painful nodular lesions appear in the lower and upper limbs as well as acrocyanosis and paresthesia in the right hand and foot. The tests performed showed thrombocytopenia and eosinophilia. While, CRP, search for fecal parasites, pANCA, cANCA, ANA, RAST test, serum tryptase were all absent. Haematological evaluation, bone marrow biopsy, karyotype and molecular biology (FIP1L1/PDGFRa), were performed, all results negative. The patient was admitted in Internal Medicine ward for worsening of skin lesions and of acrocyanosis with gangrenous lesions at the tips of the fourth fnger of the right hand. An angio-CT showed an occlusion of the right ulnar artery. At electromyography an axonal sensory neuropathy was found. The skin biopsy showed fbrinoid necrosis of venules of the superfcial vascular plexus associated with numerous eosinophils, lymphocytes and karyorrhetic debris (Figure 1). High-resolution CT scan described diffuse minimal accentuation of the interstitial texture with micronodular aspects and some ground glass appearance. The diagnosis of hypereosinophilic syndrome was made. Therapy with Methylprednisolone 500 mg/daily for 3 days then Prednisone 1 mg/kg daily in association with IL-5 inhibitor (mepolizumab) with good clinical response, in addition to anticoagulation with warfarin was started. Conclusion: To our knowledge this might be the frst case of (HES) following COVID vaccine. As our experience, due to the short commercialization of anti-nSARs-CoV2 vaccines, is limited further studies are needed to explore the possible effect on small-medium vessels.

Immune-mediated Acute Limb Ischemia: A Rare Complication of SARS-CoV-19 Infection

Occurrence of acute limb ischaemia (ALI) in patients with SARS-CoV-2 is an uncommon complication. COVID-19 has been associated with thrombotic disease secondary to a hypercoagulable state. COVID-19 appears to cause a hypercoagulable state through mechanisms unique to SARS-CoV-2 and centres on the cross-talk between thrombosis and inflammation. The proposed hypothesis includes a severely heightened inflammatory response that leads to thrombotic inflammation, through a mechanism such as cytokine storm, complement activation, and endothelitis. The innate and adaptive immune responses result in immunemediated thrombosis, leading to thrombotic complications, such as myocardial infarction, pulmonary embolism, deep vein thrombosis, and stroke. The activation of coagulation (D-dimer) and thrombocytopenia are important prognostic markers in SARSCoV- 19 infections. At our institution, we found six patients to have ALI and reviewed their characteristics and outcomes. Our findings showed that in severe COVID-19 disease, the association of ALI had high mortality. Materials and methods: It is a retrospective observational study performed at Bangalore Baptist hospital during the COVID-19 pandemic (August 2020 to August 2021). We report a case series of 6 ALI patients aged between 30 and 55 years. All the patients were tested positive for SARS-CoV-2 disease. All our patients received standard treatment care as per institution protocol for SARS-CoV-2 disease. They were all commenced on therapeutic anticoagulation at admission to ICU. Baseline coagulation profile and inflammatory markers and their trends were followed in all patients. The diagnosis of ALI in all ventilated patients was done clinically by the presence of pallor, pulselessness, acrocyanosis, blisters, and dry care unit with SARS-CoV-2 disease, 6 patients had developed limb ischemia (1.4%). Male and female preponderance was equal. Among 6 patients, 1 was newly detected diabetes mellitus, 2 were diabetic and hypertensive of which one had right upper limb post-polio paralytic sequelae, and the rest had no co-morbidities. The mean duration of ICU stay and mechanical ventilation days was 22 days and 17.8 days, respectively. All the patients had lower limb ischemia of which 3 were unilateral. Discoloration extended up to the ankle joint in almost all cases. As these patients were on the ventilator secondary to severe hypoxemia or vasopressor support, they were managed conservatively. Two patients presented with stroke, pyelonephritis with acute kidney injury, and septic shock requiring high vasopressor support. 5 of 6 patients died during the course of treatment (mortality 83%). All patients showed high inflammatory markers especially D-dimer during the initial development phase of limb ischemia. 1 survived patient required bilateral foot amputation due to dry gangrene. Conclusion: Limb ischemia with tissue necrosis is a dreadful complication and is associated with high mortality. High incidence of thrombosis despite therapeutic anticoagulation raises a question about pathophysiology unique to COVID-19. Evidence of inflammatory-mediated thrombosis and endothelial injury are possible explanations which would support the use of immunotherapy in addition to anticoagulation for the treatment of thrombotic events. Further insight into the cause and management of thrombosis is needed.

PHALANGEAL MICROGEODIC SYNDROME: IS THIS VERY RARE CONDITION BECOMING MORE COMMON?

Background/Aims Phalangeal microgeodic syndrome (PMS) is a rare condition with only a handful of published case reports. Most of these cases are recognised in childhood, typically in Japan. It presents with pain and dusky discolouration in the digits, distinct from Raynaud's phenomenon in that the colour change is fixed and pain constant. Symptom onset is related to cold exposure with first presentation usually occurring in winter. Features on magnetic resonance imaging (MRI) are striking and characteristic, with a distinct pattern of bone marrow oedema. Methods We report five cases of MRI-proven PMS all identified in the last 12 months, with symptom onset during the winter. The patients were all female, aged between 25 and 79. One patient was already under the care of rheumatology with an established diagnosis of systemic lupus erythematosus (SLE), but the remainder were De novo referrals presenting specifically with pain and discolouration of the digits. One patient developed symptoms 2 days after receiving the first dose of Pfizer/ Biontech RNA vaccine against COVID-19. One patient had to self-isolate following a COVID-19 contact and developed symptoms shortly thereafter, although there was no proven infection in the affected individual. Results Four out of five cases were managed conservatively, with advice on maintaining core and peripheral temperature and skin integrity. Without any specific therapy, these four cases improved spontaneously to coincide with increasing seasonal temperatures. The fifth case with existing SLE was treated with intravenous pamidronate and subsequently with a calcium channel blocker, with some improvement in symptoms. Conclusion In these authors' experience, it would seem PMS is increasing in incidence. It is unclear if this relates to wider availability and image quality of MRI, clinician bias due to personal experience of more cases or a genuine increase. The winter 2020/21 was particularly cold with sub-zero conditions lasting well into May, which may have impacted on this flurry of new cases. We have identified one prior case report which describes PMS in a patient with existing connective tissue disease. Our patient with SLE appeared to have a more severe clinical presentation requiring additional medical therapy to control the symptoms compared with the four cases where PMS was a standalone condition. Dermatological manifestations of acute COVID-19 infection are well documented in children and include chilblain-like lesions and acrocyanosis. Any association between COVID-19 and PMS is purely hypothetical and would require more study to identify any true relationship.

Mucocutaneous adverse effects following COVID-19 vaccination: a case series with a comprehensive review of the literature

Since coronavirus disease 2019 (COVID-19) vaccines were approved without long-term monitoring, tracking their adverse effects appears to be necessary. Mucocutaneous adverse events are of great importance due to their visibility and the potential effect on inducing fear in patients leading to vaccine hesitancy. We searched PubMed, Google Scholar, and Scopus in this regard, and all of the relevant papers published until June 28, 2021, were included if we could access their full texts. Moreover, we included some of our cases from Iran. We found various mucocutaneous manifestations after COVID-19 vaccination, including local injection site reactions (acute or delayed), urticarial lesions, pityriasis rosea-like rashes, angioedema, morbilliform rashes, pernio-like lesions, acrocyanosis, petechial/ purpuric/ecchymotic lesions, herpes flare-up, herpetiform rashes, oral erosive lesions, acral pustular rashes, erythema multiform, dermographism, herpes zoster, generalized pruritus, contact dermatitis, reaction to dermal fillers and non-specific rashes. We categorized them by their time of initiation (acute or delayed) and site of involvement (local injection site, remote area, or generalized). Delayed local reactions, local injection site reactions, urticarial lesions, and pityriasis rosea-like and morbilliform rashes were among the most common cutaneous adverse events. Dermatologists should be aware of these potential reactions to manage them properly, reassure patients, and encourage them to continue their vaccination.

Secondary acrocyanosis: Case report

Introduction: Acrocyanosis is a painless condition characterized by discoloration of different shades of blue in the distal parts of the body, marked by symmetry and persistence of color changes exacerbated by cold exposure. It is less common than other acrosyndromes (erythromelalgia, Raynaud's phenomenon, erythema pernio) According to its ethiology could be classified: a) Primary: mostly in young adults. B) Secundy: anorexia nervosa, mitochondrial diseases, neoplasms, connective tissue/rheumatologic disorders, cryoglobulinemia, exposure to drugs among others. We describe a case of secondary acrocyanosis. Clinical case: A 15-year-old boy with atopic dermatitis since childhood, was referred by Dermatology to rule out a possible contact eczema in hands, four months long. In the outpatient allergy office he showed painless cold symmetrical erythematous-violaceous macules affecting fingers and hands that aggravated by cold exposure. There was also local hyperhidrosis on a scaly-itchy base in distal areas of both hands without paroxysmal pallor or chilblains. These symptoms had been more evident a month ago and did not respond to topical corticosteroids and anti-H1. Neurologist had prescribed four weeks before amitriptyline to treat headache. Material and methods: Patch test with the standard series of the Spanish Contact Dermatitis and analysis for acrocyanosis screening were performed. Results: Patch tests with the standard battery: negative. Hemoglobin concentration: 16 g/dl, white blood cell count: 5.000/ mm3, platelet: 182.000/mm3, erythrocyte sedimentation rate: < 10 mm/h. Coagulation, urinalysis, immunoglobulin concentrations, C3, C4: normal. Cryoagglutinins, rheumatoid factor, anti-double stranded DNA antibody (Anti-ds-DNA), anti-cardiolipin and anti-Scl 70 antibodies: absents. COVID-19 RT-PCR-test: negative. Lues, HIV and Hepatitis B, C serologies:negatives. Arterial blood gas: pH: 7.43, PaO2: 113 mmHg, PaCO2: 31 mmHg. Chest radiographs: normal. Amitriptyline treatment was discontinued after suspicion of being the causal agent and 15 days later hands were pink and warm. Conclusions: We report a case of secondary acrocyanosis due to amitriptyline, a serotonin reuptake inhibitor. We emphasize the importance of a detailed clinical history to achieve the diagnosis and to verify the reversibility of acrocyanosis when its etiology is due to medication. Physicians should be aware of this possible side effect of tricyclic antidepressants.

A retrospective study on the prevalence of anti-phospholipid antibodies, thrombotic events and cutaneous signs of vasculopathy in 173 hospitalized COVID-19 patients.

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, p = 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 (p = 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.

Acrocyanosis and digital necrosis are associated with poor prognosis in COVID-19.

Acrocyanosis and digital necrosis, which caused by microangiopathic and immunothrombosis phenomenon, may accompanied by microvascular involvement of other organs. Therefore, this finding can play a prognostic role in covid-19 outcome.

A visually striking case of primary acrocyanosis: A rare cause of the blue digit.

Cold environments can trigger a variety of conditions, which, in their acute phase often present to the Emergency Department. Primary acrocyanosis is a distinct, rare condition which may be missed resulting in misdiagnosis and mismanagement. Primary acrocyanosis is a peripheral vascular disorder defined by painless, symmetrical discoloration of the distal appendages and uniquely characterized by persistence of the skin color changes after cold exposure. We present a case of a 24-year-old female who presented to the Emergency Department with peripheral cyanosis after cold exposure and was eventually diagnosed with primary acrocyanosis by Rheumatology. The prognosis for primary acrocyanosis is quite good in comparison to other acrosyndromes and once secondary causes of acrocyanosis have been ruled, out can be managed conservatively with lifestyle modifications and potential follow-up with Rheumatology.