Upskilling haematological services for WGS and germline assessments through a regional skin biopsy training programme

NHS England Genomics introduced whole genome sequencing (WGS) with standard-of- care (SoC) genetic testing for haemato-oncology patients who meet eligibility criteria, including patients with acute leukaemia across all ages, and exhausted SoC testing. Alongside, the role of germline mutations in haematological cancers is becoming increasingly recognised. DNA samples are required from the malignant cells (somatic sample) via a bone marrow aspirate, and from non-malignant cells (germline sample) for comparator analysis. Skin biopsy is considered the gold-standard tissue to provide a source of fibroblast DNA for germline analysis. Performing skin punch biopsies is not within the traditional skillset for haematology teams and upskilling is necessary to deliver WGS/germline testing safely, independently and sustainably. A teaching programme was designed and piloted by the dermatology and haematology teams in Sheffield and delivered throughout the NHS trusts in North East & Yorkshire Genomic Laboratory Hub. The training programme consisted of a 90-min session, slides, video and practical biopsy on pork belly or synthetic skin, designed to teach up to six students at one time. To disseminate best practice, the standard operating procedure and patient information used routinely in Sheffield were shared, to be adapted for local service delivery. From January 2021 to December 2022, 136 haematology staff from 11 hospitals, including 34 consultants, 41 registrars, 34 nurses and 8 physician associates, across the NEY GLH region completed the skin biopsy training programme. Feedback from the course was outstanding, with consistently high scores in all categories. Practical components of the course were especially valued;98.6% (71/72) trainees scored the practical element of the programme a top score of 5 out of 5, highlighting that despite the challenges of delivering face-to- face teaching due to COVID-19, teaching of practical skills was highly valued;training in this way could not have been replicated virtually. Costs of the programme have been approximately 16 000, including consultant input and teaching/educational materials. Recent support has been provided by a separately funded Genomic Nurse Practitioner (GNP), with succession planning for the GNP to take over leadership from the consultant dermatologist. Plans are in place to use the remaining budget to disseminate the programme nationally. Our training programme has shown that skin biopsy can be formally embedded into training for haematology consultants, trainees, nursing team, and physician associates. Delivery of training can be effective and affordable across regional GLHs with appropriate leadership and inter-speciality coordination, and ultimately sustainable with specialist nursing staff, including GNPs.

Dermatomyositis with Specific Autoantibodies Appearing after Sars-Cov-2 Infection or Mrna Vaccination: Hints at a Shared Pathogenetic Mechanism

Background. Environmental factors such as infections and vaccines are known to trigger dermatomyositis (DM), and during the recent SARS-CoV-2 pandemic this has become even clearer. SARS-CoV-2 infection may share features with anti-MDA5 DM, such as rapidly progressive lung involvement, cutaneous lesions and cytokine release syndrome. A few case reports of DM following SARSCoV-2 vaccination have been published, suggesting the onset of an aberrant immune response leading to DM with specific autoantibody signatures and severe organ impairment. Methods. Clinical and laboratory data of the 2 case reports were obtained from electronic clinical charts in Humanitas Research Hospital (Rozzano, Milan, Italy). Autoantibody analysis was performed by protein-immunoprecipitation for anti-MDA5 and immunoblot for anti-Ro52 and TIF1gamma antibodies as per protocol. Results. Case report 1 is a 71-year-old woman who developed fever, cough, and anosmia, which resolved spontaneously in two weeks, but did not undergo a nasopharyngeal swab, while her relatives were diagnosed with SARS-CoV-2 infection. When symptoms improved, she developed arthralgia and skin lesions on her face, chest, and hands for which she started topical treatment, with negative SARSCoV-2 nasopharyngeal swab and positive serum test for IgG against SARS-CoV-2 spike protein. For the persistence of the skin rash and arthralgia, she was admitted to our Department in March 2021. Blood tests showed mild elevation of C reactive protein (2.1 mg/L -normal value NV<5), aspartate (84 UI/L) and alanine aminotransferase (133 UI/L -NV<35), ferritin (595 ng/ml -NV<306), troponin I (19 ng/L -NV<14), and BNP (251 pg/ml -NV<100) with normal complete blood cell count, creatine kinase, C3 and C4. IgG antibodies for SARS-CoV-2 spike protein were confirmed to be elevated (96 AU/ml -NV<15). Autoantibodies associated with connective tissue diseases were tested and only anti-MDA5 antibodies were positive at immunoprecipitation. A punch biopsy of a Gottron-like lesion on the left hand showed leukocytoclastic vasculitis. We observed reduced capillary density with neoangiogenesis and ectasic capillaries at the nailfold capillaroscopy. EKG and ecocardiography were normal, while cardiac magnetic resonance detected abnormalities in the parametric sequences, consistent with signs of previous myocarditis. A lung CT scan revealed pulmonary emphysema while respiratory function tests demonstrated reduced volumes (FVC 82%, FEV1 64%, inadequate compliance CO diffusion test). Based on the biochemical and clinical findings, a diagnosis of anti-MDA5-associated DM with skin and heart involvement was made and treatment with low-dose methylprednisolone (0.25 mg/kg daily) and azathioprine 100 mg was started, then switched to mycophenolate because not effective on skin lesions. Case report 2 is an 84-year-old woman with history of colon cancer (surgical treatment) and oral lichen treated with low doses steroids in the last 2 years. After the 2nd dose of SARS-CoV-2 mRNA vaccination, in March 2021 she developed skin rash with V-sign, Gottron's papules, periungueal ulcers, muscle weakness and fatigue, thus she performed a rheumatologic evaluation. Blood tests showed mild elevation of creatine kinase (484 UI/L, NV <167), CK-MB (9.6ng/ml, NV <3.4), BNP (215 pg/ml -NV<100) with normal values of complete blood cell count, C3 and C4. Anti-Ro52kDa and TIF1gamma were positive at immunoblot, thus we confirmed a diagnosis of DM. The clinical evaluation also showed active scleroderma pattern at nailfold capillaroscopy, normal echocardiography, bronchiectasia but not interstitial lung disease at lung CT, and normal respiratory function tests (FVC 99%, FEV1 99%, DLCO 63%, DLCO/VA 81%). A PET-CT scan was performed to exclude paraneoplastic DM, and treatment with steroids and mycophenolate was started. Conclusions. SARS-CoV-2 may induce mechanisms for escaping the innate immunity surveillance and causing autoimmune diseases, but more clinical and functional studies are needed to demonstrate this possible association.

Frequency of cervical hpv in women with COVID-19 infection

Aim: At the beginning of 2020, the Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus emerged in China. While there are several studies currently being performed to investigate the multi-organ symptoms of COVID-19 infection, significant attention has yet to be paid to its presence in the cervix. This article aims to establish a medical hypothesis of its association with HPV infection as well as the potential impact of COVID-19 infection on the female genital tract. Material(s) and Method(s): This prospective cohort study was performed in ... Research and Training Hospital between January 1 and July 30, 2020. Cervicovaginal samples (co-test) were taken at the gynecological oncology unit, and both HPV screening and Pap smear were studied with the liquid-based method. Two groups of patients who were confirmed by PCR test to have had COVID-19 infection in the last 6 months and patients who did not have a history of infection were included in the study. Result(s): A total of 310 participants were evaluated in the study. Of these participants, 30 (9.7%) were confirmed to have undergone COVID-19 by PCR test. There was no significant difference between the total positive smear results in both groups. However, the rate of HPV-16 positive patients was significantly higher in the COVID-19 group (2.5% vs 10.0%, p=0.027). Discussion(s): As a result, COVID-19 infection may increase the frequency of HPV-16. Apart from this, it can be said that this increase is not reflected in the frequency of cervical cytopathology.Copyright © 2022, Derman Medical Publishing. All rights reserved.

Systemic lupus erythematosus cutaneous flare following COVID-19 vaccination: A case report

Objective: To present a case of a SLE cutaneous flare following COVID-19 vaccination in a patient with low disease activity Background: Disease flare in a patient with underlying autoimmune rheumatic disease (AIRD) after vaccination had already been experienced with other vaccines, such as influenza, hepatitis B, and HPV vaccines. Given the relatively unknown safety profile of the COVID-19 vaccine among patients with AIRD, the probability of a disease flare is not a remote possibility. Several case reports available had already reported few cases of AIRD disease flare following vaccination, some of which requiring escalation of the treatment regimen. Molecular mimicry, as had been described with other vaccines, is still implicated as the possible explanation for such a phenomenon. Case: A 57 year old female with systemic lupus erythematosus with nephritis since 1994 with low disease activity, maintained on hydroxychloroquine and low dose methylprednisolone daily who developed multiple well-defined elevated erythematous and pruritic plaques on both thighs, spreading to the face, scalp, trunk, and extremities 3 weeks after receiving her first dose of viral vector vaccine. Work-ups included eosinophilia on CBC, elevated ESR, anti-dsDNA, ferritin, and LDH, with low C3, with proteinuria and hematuria on urinalysis. She was admitted and her glucocorticoid was increased and tapered accordingly. Skin punch biopsy with alcian blue staining was also done which revealed interface dermatitis consistent with lupus erythematosus. Few days after increasing her glucocorticoid, cutaneous lesions gradually resolved and she was discharged improved. She received her second dose of vaccine 2 months after her first dose with no reported incidents of adverse events. Conclusion(s): This is one of the few cases of a reported SLE flare confirmed by disease activity index and biopsy-confirmed skin rashes. The development of such an adverse reaction to a vaccine may be relatively low but still possible due to intricate interaction of the immune system and vaccine.

Multiple opportunistic infection in a male with systemic lupus erythematosus and concomitant human immunodeficiency virus infection

Background/Purpose: Concomitant systemic lupus erythematosus (SLE) and human immunodeficiency virus (HIV) infection cases are rare worldwide. It is established that SLE patients have an increased risk of opportunistic infection due to immune dysregulation, as well as in HIV. Method(s): A case of a 25-year- old Filipino man with systemic lupus erythematosus admitted due to a 1-week intermittent fever associated with headache, loss of appetite, and generalized body weakness was reviewed in a tertiary hospital in the Philippines. Result(s): An initial diagnosis was made from the clinical presentation of Raynaud's phenomenon, an elevated antinuclear antibody (1:320;nuclear, speckled), 2+ proteinuria, thrombocytopenia, and nail fold capillaroscopy findings consistent with mixed connective tissue disease. Patient was started on hydroxychloroquine and prednisone. He was admitted as a case of Streptococcus bacteremia with COVID-19 pneumonia after initial diagnosis, presenting as fever, and thrombocytopenia as low as 23.000/mul. Patient presented with a scaly erythematous annular lesion at his left wrist since December 2021 where a skin punch biopsy showed findings consistent with dermatophytosis. Direct immunofluorescence staining showed deposition of granular IgM (+3), C3 (+1), Fibrinogen (+3), and C1q (+1) in the basement membrane zone consistent with Lupus Erythematosus. Additional findings were oral thrush, dermatophytosis, and Pneumocystis pneumonia. Patient was started on antibiotics, remdesivir, and antifungal medications. Being severely immunocompromised, work up for HIV was initiated. Rapid HIV screening was positive, CD4 count revealed 7 (3.14%), and subsequent confirmatory western blot was positive. Additional treatment included hydroxychloroquine, methylprednisolone pulse therapy, and platelet concentrate transfusion. He was referred for CD4 monitoring, and ARV treatment enrollment, however, the patient expired a month after his discharge. Conclusion(s): This case is thereby reported to document a rare case of systemic lupus erythematosus (SLE) male patient with concomitant HIV, SARS-CoV- 2, and opportunistic infections secondary to AIDS. Diagnosis becomes challenging in patients with autoimmune diseases and multiple infectious diseases as clinical presentations tend to overlap and may show similar manifestations. In this setting, skin biopsy utilizing direct immunofluorescence can help establish an accurate diagnosis especially when clinical features and histopathology are overlapping.

PUTTING THE "SARS” IN "SARS-COVID-19": A CASE OF SARCOID-LIKE INFLAMMATORY REACTION AFTER COVID-19 VACCINATION

SESSION TITLE: Issues After COVID-19 Vaccination Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Sarcoidosis and sarcoid-like reactions tend to be diagnoses of exclusion when evaluating patients with malignancy, and have a number of inciting causes. This is a unique case of a patient diagnosed with non-necrotizing granulomatous inflammation on biopsy of mediastinal lymph nodes and skin lesions after receiving SARS-CoV-2 vaccine, while also being on Temozolamide (TMZ). Biopsy-proven sarcoid has rarely been reported in the literature following SARS-CoV-2 vaccine or TMZ. CASE PRESENTATION: 66-year-old female with a history of prolactinoma complicated by recurrence and progression of disease despite surgery, radiation, and medical therapy, who started her first cycle of TMZ and received her first SARS-CoV-2 vaccine 9 days later. About 2 weeks later, she noted numerous painless "bumps” on her bilateral upper and lower extremities with erythema, without fevers, joint pains, or other symptoms. She underwent a positron emission tomography (PET) scan which demonstrated multiple hypermetabolic subcutaneous lesions, along with intensely hypermetabolic bilateral hilar lymphadenopathy. She underwent punch biopsy notable for sparse inflammation. She underwent her second SARS-CoV-2 vaccine and second cycle of TMZ. After 1 week, she noticed increased induration and erythema over her lesions, and held her TMZ. She underwent incisional biopsy of her thigh which demonstrated granulomatous panniculitis. She also underwent bronchoscopy with endobronchial ultrasound (EBUS) and transbronchial needle aspiration (TBNA) of her paratracheal and subcarinal lymph nodes, which demonstrated non-necrotizing granulomatous inflammation. Labs were only significant for ACE level of 60u/L (normal<40u/L). With a relative paucity of symptoms and no other obvious vital organ involvement, she was not treated, continued her TMZ without flares, and her symptoms self-resolved after opting out of the third SARS-CoV-2 vaccine. DISCUSSION: Sarcoid-like inflammatory reactions have rarely been reported in the literature following SARS-CoV-2 vaccine or TMZ. One case of panniculitis secondary to TMZ administration was reported that improved after discontinuation of TMZ [1]. Our patient continued TMZ therapy without further symptoms, which makes TMZ less likely as her inciting cause. Three cases of sarcoid-like reactions secondary to SARS-CoV-2 vaccine have been reported [2, 3] but two of these cases were diagnosed clinically as Löfgren syndrome without biopsy [3], making this case the second reported case of biopsy-proven de novo sarcoid reaction in the setting of SARS-CoV-2 vaccine. CONCLUSIONS: Sarcoid-like inflammatory reactions following SARS-CoV-2 vaccine have not been well-reported in the literature. This case, among the other limited cases reported, underscores the need to consider sarcoid on the differential of vaccine-related side effects, especially in those with bilateral hilar lymphadenopathy and cutaneous lesions. Reference #1: Virmani P., Chung E., Marchetti M. A. (2015). Cutaneous adverse drug reaction associated with oral temozolomide presenting as dermal and subcutaneous plaques and nodules. Jaad. Case. Rep. 1, 286–288. 10.1016/j.jdcr.2015.06.012 Reference #2: Bauckneht, M., Aloè, T., Tagliabue, E. et al. Beyond Covid-19 vaccination-associated pitfalls on [18F]Fluorodeoxyglucose (FDG) PET: a case of a concomitant sarcoidosis. Eur J Nucl Med Mol Imaging 48, 2661–2662 (2021). https://doi.org/10.1007/s00259-021-05360-w Reference #3: Rademacher JG, Tampe B, Korsten P. First Report of Two Cases of Löfgren's Syndrome after SARS-CoV-2 Vaccination-Coincidence or Causality? Vaccines (Basel). 2021 Nov 11;9(11):1313. doi: 10.3390/vaccines9111313. PMID: 34835244;PMCID: PMC8619392 DISCLOSURES: no disclosure on file for Alexander Geyer;No relevant relationships by Mustafa Jafri

A RARE CASE OF ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES (ANCA)-ASSOCIATED VASCULITIS IN THE SETTING OF COVID-19 INFECTION

SESSION TITLE: Management of COVID-19-Induced Complications SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Anti-neutrophil cytoplasmic antibody-associated vasculitis (ANCA-AV) is an autoimmune mediated inflammation of small and medium sized vessel walls. The occurrence of this autoimmune vasculitis is typically associated with underlying infection, medications, and genetic predisposition.(1) The objective of this case report is to describe a rare presentation of ANCA-AV in the setting of COVID-19 infection. CASE PRESENTATION: A 67-year-old male presented to the hospital with a three-week history of cough productive of brown sputum, epistaxis, fatigue, decreased appetite, and unintentional weight loss. During the previous week, he experienced worsening dyspnea and bilateral lower extremity swelling. On physical examination, he was hypoxic requiring 4L of supplemental oxygen to maintain saturations greater than 90%. Diffuse and bilateral wheezes were heard on auscultation of his lungs. A tender petechial rash was dispersed over his limbs, trunk, oropharynx, and nasopharynx. A basic metabolic panel revealed a mild, acute renal impairment. Urinalysis showed new onset proteinuria and hemoglobinuria. Nasopharyngeal swab was positive for SARS-COV-2. Contrast-enhanced computed tomography of the chest revealed diffuse, bilateral ground glass opacities and interstitial changes. Therapy with piperacillin-tazobactam was started for presumed superimposed bacterial community acquired pneumonia in the setting of COVID-19 infection. On day three of hospitalization, the petechial rash progressed to hemorrhagic blisters. His oral petechiae were now ulcerated. A punch biopsy of the affected skin showed leukocytoclastic vasculitis. Anti-Proteinase 3 (PR3) antibodies were positive. Subsequent renal biopsy showed pauci-immune focal necrotizing crescentic glomerulonephritis consistent with ANCA-AV. Therapy with intravenous pulse dose corticosteroids led to improvement in his rash and body aches, and he was discharged home on oral steroids ten days after admission. DISCUSSION: This report describes a rare case of ANCA-AV in the setting of recent COVID-19 infection. Differentiation of ANCA-AV, bacterial and COVID-19 pneumonia can be challenging on chest imaging alone.(1) New onset renal impairment, hematuria, proteinuria and the presence of the petechial rash were suspicious for co-existing ANCA-AV in this patient. COVID-19- associated cytokine storm and formation of neutrophil extracellular traps (NETs) is postulated to be the underlying cause.(1-3) NETs present myeloperoxidase (MPO) and PR3 antigens to the immune system. Formation of auto-antibodies to MPO and PR3 lead to the development of ANCA-AV. The findings of NETs on kidney biopsy specimens in patients with ANCA-AV supports this hypothesis.(1,2) CONCLUSIONS: To avoid the misdiagnosis of COVID-19-induced vasculitis, a low threshold to investigate co-existing vasculitis in patients with COVID-19 and associated clinical findings is highly recommended. Reference #1: Izci Duran T, Turkmen E, Dilek M, Sayarlioglu H, Arik N. ANCA-associated vasculitis after COVID-19. Rheumatol Int. 2021;41(8):1523-1529. Reference #2: Uppal NN, Kello N, Shah HH, et al. De Novo ANCA-Associated Vasculitis With Glomerulonephritis in COVID-19. Kidney Int Rep. 2020;5(11):2079-2083. Reference #3: Cobilinschi C, Cobilinschi C, Constantinescu A, Draniceanu I, Ionescu R. New-Onset ANCA-Associated Vasculitis in a Patient with SARS-COV2. Balkan Med J. 2021;38(5):318-320. DISCLOSURES: No relevant relationships by Andrei Hastings No relevant relationships by Jason Lane No relevant relationships by Tanya Marshall No relevant relationships by Palak Rath No relevant relationships by Sterling Shriber No relevant relationships by inderprit Singh No relevant relationships by Samuel Wiles

SWEET SYNDROME IN ACUTE MYELOGENOUS LEUKEMIA- A CASE REPORT

CASE: Patient is a 63 y/o F with PMH of relapsed AML on treatment with Gilteritinib, Meniere's Disease, asthma, GERD, PRA positive, CKD Stage 3. She was on cycle 1 day + 20 of Gilteritinib when she presented with a neutropenic fever of 101.9. She reported congestion and headache. She was pan cultured and started on empiric Cefepime. Her blood cultures, COVID test and CXR were all negative for sources of infection. Eventually, Cefepime was stopped, and she was transited to PO Cefdinir and Cipro but redeveloped fevers and a maculopapular rash. Repeat pan-cultures were negative. Antibiotics were broadened to Merrem, Linezolid and Cresemba and her fevers improved. However, the rash continued to worsen. There was concern that nodular rash was secondary to infection or possible drug reaction from her antibiotics. Her rash showed no improvement with Benadryl or withholding drugs. She underwent skin punch biopsy before discharge. Biopsy showed florid superficial inflammation with benign ulcer that was highly suggestive of Sweet Syndrome given history of AML. IMPACT/DISCUSSION: Sweet syndrome (SS), or acute febrile neutrophilic dermatosis is a rare inflammatory condition characterized by painful cutaneous nodules and neutrophilic infiltrate in the dermis, in the absence of vasculitis. This syndrome is associated with malignancies with AML and MDS being the most reported. Malignancy associated Sweet Syndrome accounts for 15-20% of cases of SS. The atypical production of both pro-inflammatory cytokines (IL - 6, TNF - alpha) and signaling molecules demonstrated in AML is suspected to affect neutrophil function leasing to dermal clumping of the mature neutrophils. In our patient the fever presented prior to the rash with sudden onset of nodular as it has been commonly reported in literature review. Glucocorticoids, either topical or systemic, together with antibiotics and wound care, represent the mainstays of SS therapy. The rash heals without scarring if no ulcerations are present. The signs and symptoms of Sweet syndrome can mimic infection and be treated inaccurately, thus, it is important to make a correct diagnosis. Our patient's tissue cultures were negative for microorganisms. She was started on glucocorticoid with good response in regards to her rash but did have some scars and hyperpigmentation. Unfortunately due to her aggressive AML and complications patient elected to go to Hospice. CONCLUSION: When SS is established, the physician should keep a high index of suspicion to search underlying malignancies. Sweet Syndrome generally responds promptly to treatment with glucocorticoid.

ACUTE HEPATITIS AND RASH LINKED THROUGH EPSTEIN-BARR VIRUS

Epstein-Barr virus (EBV) hepatitis is well established, and most cases involves asymptomatic liver enzyme abnormalities. Albeit rare, viruses such as EBV have been reported to induce generalized pustular psoriasis (GPP);and exanthems such as GPP have been associated with acute hepatitis. This case describes a unique case of cholestatic hepatitis due to EBV, followed by a diffuse pustular rash suggestive of GPP. After complete resolution of the cholestatic hepatitis, the patient returned over a year later with concurrent hepatitis and diffuse pustular rash. Case: An obese 26 year-old African-American female presented to the hospital on three separate occasions over a 15 month span with slightly varying symptoms. At the index hospitalization she presented with fatigue and jaundice. Liver chemistries revlead a mixed pattern liver injury, see Table 1. Extensive serological evaluation was unremarkable, though antinuclear antibody and anti-smooth muscle antibody were mildly and non-specifically elevated, but IgG was normal. A liver biopsy was performed revealing portal and lobular inflammation with predominantly lymphocytic moderate micro-vesicular steatosis (Figure 1). EBV PCR returned positive at 20,737 IU/mL yielding a diagnoses of EBV-induced hepatitis. She returned to the hospital one week later due to a diffuse pruritic and painful rash. She had scleral icterus and diffuse erythematous plaques with tiny pustules dispersed over the body sparing the palms, soles, and mucosal surfaces. Laboratory values were overall improved as noted in Table 1. Punch biopsy of the right arm was suggestive of EBV induced GPP. She rapidly stabilized and was discharged the following day with triamcinolone 0.1% ointment. The patient had an uneventful convalescence and liver chemistries returned to normal. Approximately 15 months after her initial hospitalization, she presented with both recurrent hepatitis and a pustular, pruritic, erythematous rash with perioral and periorbital swelling. She denied taking any new medications or supplements. Labs revealed recurrent, though now primarily cholestatic liver injury, see Table 1. Results of a repeat thorough serological evaluation were negative, including for EBV-PCR and COVID-19. Abdominal ultrasound revealed a 16 cm hepatic length. Pustules, spongiosis, and edema were found on repeat skin biopsy, suggestive of GPP. She recovered quickly with systemic steroids. Awareness of GPP induced hepatitis can guide a judicious assessment of abnormal liver chemistries. Furthermore, unnecessary healthcare utilization can be avoided by providing appropriate and timely pharmacotherapy (i.e., corticosteroid taper) for on demand flares. (Figure Presented) (Table Presented) (Figure Presented)

LESIONS MIMICKING KAPOSI SARCOMA IN A WOMAN LIVING WITH HIV FOLLOWING PFIZER-BIONTECH COVID- 19 VACCINATION

Introduction A spectrum of skin reactions following mRNA COVID vaccinations have been reported that can mimic dermatological manifestations of Human Immunodeficiency Virus (HIV) infection. Case Description A 47-year-old Zimbabwean female living with HIV since 2011 (nadir CD4 366 cells/mm3) was seen in our HIV clinic with a widespread rash and raised, itchy lesions over her body measuring approximately 5-7mm which appeared three weeks after her first Pfizer-BioNTech COVID-19 vaccine. There was no systemic involvement. Her CD4 count was 641 cells/mm3 (44%) with a fully suppressed viral load on antiretroviral therapy since June 2015 with no other pertinent medical history. There was no response to topical anti-fungal therapy but symptomatic relief with anti-pruritic and anti-histamine was noted. Treatment with oral erythromycin 500mg four times a day for two weeks decreased the size of the lesions and improved the rash. A punch biopsy of pale brown skin at this time was performed with appearances in keeping with those of a lichenoid pattern of inflammation. Our patient continues to improve with erythromycin.Topical or systemic corticosteroid therapy can be considered to further ameliorate her condition. Discussion Lichenoid drug eruptions are well recognized. Our case demonstrates such a reaction to the Pfizer-BioNTech COVID-19 vaccination which adds to cases described in the contemporary medical literature. It is vital to recognize this complication in our specialty as lesions may mimic lichen planus clinically and histologically and may be mistaken for dermatological manifestations associated with HIV, including Kaposi Sarcoma (KS) and bacillary angiomatosis, which can manifest regardless of immune status.

Cutaneous thrombosis associated with skin necrosis following Oxford/AstraZeneca COVID-19 vaccination: a case report

A 73-year-old man presented with left shin ulceration two weeks after receiving his first dose of the Oxford-AstraZeneca vaccine. Within 24 h of vaccination, the patient became generally unwell with fever and headache. On the third day after vaccination, he developed left shin erythema and blistering, which rapidly ulcerated. This formed two superficial ulcers with a necrotic base and a violaceous edge on the lateral aspect of his left shin, measuring approximately 2 cm × 3 cm. He had a background of atrial fibrillation and ischemic cardiomyopathy, and had been on several longstanding medications including apixaban. Blood tests revealed normal clotting, full blood count, liver and renal function. The differential diagnosis included pyoderma gangrenosum, vasculitic ulceration, and a cutaneous adverse drug reaction to vaccination. A punch biopsy was obtained from the edge of an ulcer, which revealed microthrombi within blood vessels, an ischemic epidermis, and fat necrosis of subcutaneous tissue. The patient experienced slow healing of ulceration with topical clobetasol propionate 0.05%, neomycin sulphate and nystatin ointment, and compression bandaging treatment. To our knowledge, this is the first reported case of cutaneous thrombosis associated with skin necrosis following Oxford/AstraZeneca vaccination. Recently there have been concerns related to reports of thrombotic events at atypical sites (including cerebral and splanchnic vascular beds) associated with thrombocytopenia following Oxford/ AstraZeneca vaccination (Greinacher A, Thiele T, Warkentin TE et al. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med 2021;384: 2092-101). These findings extend the range of atypically located thromboses associated with COVID-19 vaccination and reinforce the necessity for physicians to be vigilant for signs and symptoms related to thromboses at atypical sites in recently vaccinated patients.

A case of cutaneous vasculitis following third dose of SARS-CoV-2 vaccine in an immunocompromised patient

A 58-year-old man known to dermatology services, established on guselkumab for psoriasis and methotrexate for psoriatic arthritis, attended with an acute onset purpuric rash distributed over both his lower limbs, one day after his third dose of SARS-CoV-2 Pfizer-BioNTech vaccine (booster). He had received his initial vaccinations 6 months prior with no reported reactions. He denied any previous SARS-CoV-2 infection or recent symptoms suggestive of COVID-19. There had been no new recent medications and no systemic symptoms were reported. Examination revealed a nonblanching, palpable, purpuric rash distributed over both lower limbs, clinically in keeping with cutaneous vasculitis. Baseline observations were satisfactory including blood pressure and temperature. Bedside investigations included a urinalysis which revealed no proteinuria or haematuria. Punch biopsies were taken and were consistent with a leucocytoclastic vasculitis (LCV). He was managed symptomatically with potent topical steroids with good clinical response. LCV is classified as a cutaneous, small vessel vasculitis, exclusively characterized by deposition of immune complexes in the dermal capillaries and venules (Baigrie D, Bansal P, Goyal A, Crane JS. Leukocytoclastic vasculitis. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing, 2021). LCV following both first and second SARS-CoV-2 vaccinations has been documented in recent literature with a few reports following a third booster dose, and in particular within an immunocompromised population. This particular case has raised questions regarding delayed immune response following SARS-CoV-2 vaccine in this subgroup. The pathophysiology of SARS-CoV-2 vaccine-induced LCV has not been extensively researched;however, it is felt to be caused by offtarget immune activation after the vaccination (Dicks AB, Gray BH. Images in vascular medicine: leukocytoclastic vasculitis after COVID-19 vaccine booster. Vasc Med 2022;27: 100-1).

Leukocytoclastic vasculitis secondary to COVID-19 vaccine

We present the case of a severe cutaneous reaction following COVID-19 vaccination. A 60-year-old white woman presented to our service with an extensive painful, pruritic rash affecting her bilateral lower limbs. This was on a background of psoriasis, psoriatic arthritis and notably inoculation against COVID-19 with the Johnson & Johnson vaccine hours prior to onset. There was no history of new medications, illicit drug use or infections. On examination, extensive palpable purpura was noted circumferentially at both lower limbs from the knee distally. Tense bullae were described at her bilateral ankles. She was apyrexial. Her cardiopulmonary and gastrointestinal examinations were normal. A punch biopsy taken from her right lower limb demonstrated findings consistent with leucocytoclastic vasculitis (LCV). Direct immunofluorescence demonstrated IgA deposits within the vasculature. IgA LCV secondary to COVID-19 vaccination was proposed on the basis of histological and clinical findings. Treatment consisted of oral steroids, oral antibiotics for secondary infection and wound dressings. Opioid analgesia and nitrous oxide were implemented for severe pain associated with dressing changes. As her urinary protein creatinine ratio was in excess of 100 mg dL-1 and microscopic haematuria was noted on urine microscopy, she was referred to nephrology. We note case reports of patients diagnosed with LCV up to 2 weeks following COVID-19 vaccination (Cavalli G, Colafrancesco, De Luca G et al. Cutaneous vasculitis following COVID- 19 vaccination. Lancet Rheumatol 2021;3: E743-4). In this case, onset of symptoms occurred within hours. While this presentation may have been coincidental, the relationship between immune complex vasculitis, COVID-19 infection (Iraji F, Galehdari H, Siadat AH, Bokaei Jazi S. Cutaneous leukocytoclastic vasculitis secondary to COVID-19 infection: a case report. Clin Case Rep 2020;9: 830-4) and vaccination (Cavalli et al.) has been reported in the literature and represents the most likely diagnosis.

COVID-Long Haulers Can Develop POTS (Postural Orthostatic Tachycardia Syndrome) with Small Fiber Neuropathy and Abnormal Autonomic Testing

Objective: A substantial number of COVID long-haulers have developed POTS, which warrants further investigation. This study is intended as a first look at a new and growing patient population that is bringing greater attention to the prevalent autonomic disease of POTS. Background: POTS (Postural Orthostatic Tachycardia Syndrome) is a disorder of autonomic dysregulation involving overactive compensation for postural blood pressure changes. This debilitating syndrome can be associated with small fiber neuropathy and a broad spectrum of autonomic symptoms including palpitations, changes in sweating, and gastrointestinal problems like constipation. Respiratory and gastrointestinal viruses have been known to cause onset of POTS pathophysiology. In approximately 10% of COVID cases, patients experience long-term health effects after the conclusion of their COVID infection. These patients are called COVID “long-haulers.” Design/Methods: We conducted a chart review of 25 Cleveland Clinic post-COVID POTS patients who are mostly female (84%) to learn about this patient population's distribution of top symptoms, comorbidities, autonomic testing, and autonomic questionnaire scores. Top three symptoms were determined based on the physician's note from the patients' initial visit to the Cleveland Clinic Neurology Department. Results: Our chart review revealed a high occurrence of excitatory comorbidities such as chronic migraine (44%) and irritable bowel syndrome (24%). In addition, when assessing patients' top three POTS symptoms, we found that palpitations, fatigue, and dyspnea were affecting patients most. As with POTS in general, autonomic testing outside of tilt table testing (85.7%) shows variable results with QSART (50%), skin punch biopsy (37.5%), deep breathing (14.3%), and Valsalva testing (0%) all showing positivity rates of 50% or less for our patient sample. Conclusions: Post-COVID POTS could be an excitatory process with hyperadrenergic signaling based on the symptoms and comorbidities. We hope that this chart review will be the launching point for future studies aimed at achieving greater understanding of the post-COVID POTS phenomenon.

Small Fiber Neuropathy Associated with SARCoV-2 Infection

Objective: The development and persistence of neurological symptoms following SARS-CoV-2 infection is referred to as “long-haul” syndrome. Here, we aim to study the role of small fiber neuropathy (SFN) underlying neuropathic symptoms associated with COVID-19 infection. Background: Post COVID-19 “long-haul” syndrome include chronic fatigue, brain fog, sleep disturbance and paraesthesias. These symptoms can overlap with those seen in SFN, which have not been investigated given the recent wave of pandemic and patients who developed new onset of symptoms following infection. Design/Methods: Using retrospective study between May 2020 - May 2021, we screened the skin biopsy database of patients who were referred from the Center of Post-COVID Care at the Mount Sinai Hospital. Thirteen patients were identified and undergone routine nerve conduction studies and electromyography which ruled out evidence of a large fiber neuropathy. Patients were then clinically evaluated and consented for skin punch biopsy. All specimens were processed using PGP9.5 immunostaining for evaluating intraepidermal nerve fiber density (IENFD) to confirm SFN. Results: We identified 13 patients, 8 women and 5 men (age 38-67 years) with follow-up duration between 8-12 months. All had negative neuropathy blood profile including HbA1c, ANA, B12, TSH, free T4, and serum immunofixation. Three patients had pre-existing but controlled neuropathy risk factors. None had neurological symptoms prior to the SARS-CoV-2 infection. All patients developed new-onset paresthesias within 2 months following infection, with an acute onset in 7 and co-existing autonomic symptoms in 7. Six patients had biopsyconfirmed SFN, all of whom showed both neuropathy symptoms and signs, with 2 showing autonomic dysfunction. Of the remaining 7 patients with negative skin biopsies, 6 showed no clinical neuropathy signs, and 1 exhibited signs with abnormal autonomic function testing. Conclusions: Our findings support that symptoms of SFN may develop during or shortly after COVID-19 illness. SFN may underlie the paresthesias associated with long-haul post-COVID-19 symptoms.