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Background/Aims Research has shown nurse-led gout clinics provide better outcomes compared to usual care. This District General Hospital set up a pilot nurse-led gout clinic in autumn 2019. This aimed to improve patients' understanding of their condition, achieve better control of serum uric acid levels (SUA), reduce flares and prevent Emergency Department attendances. Methods A modified clinic protocol, closely modelled on BSR guidance was agreed within the department. With consultant supervision, one nurse specialist provided a mix of in-person and telephone appointments. Targets were set aiming for SUA <360mumol/L for most patients and <300mumol/L for those with erosive change or tophi. All patients were offered prophylaxis. Patients required a rheumatologist's diagnosis of gout or crystal confirmation for enrolment. Exclusion criteria were significant renal or hepatic derangement. Within 3 months of the service starting SARS-CoV-2 impacted the operation of healthcare worldwide and led to the closure of routine outpatient clinics in Northern Ireland. A decision was made to switch the gout clinic to run entirely by telephone. Blood testing was facilitated through primary care and phlebotomy hubs. Results Over a 19-month period, 78 patients were treated and audited through this clinic: 69 men and 9 women. Average age was 57, mean SUA 509 mumol/L at referral and 322 mumol/L on discharge. 69 patients received allopurinol and 9 received febuxostat. No patients required uricosuric drugs. All patients were offered and agreed to take prophylaxis with a majority (85.8%) remaining on it for 3-6 months. Patients required a mean of 3.38 appointments prior to discharge from the clinic. The mean dose of urate lowering therapy on discharge was 315.9mg allopurinol and 93.3mg febuxostat. 95% experienced >=2 flares during their enrolment in the clinic with no patients requiring Emergency Department attendance due to gout flare. Conclusion The nurse-led gout clinic was well received by patients and was effective as a telephone service during the pandemic when so many services were stood down. The clinic was able to continue to provide education, deliver effective reductions in uric acid as well as reduce incidence of flares and Emergency Department attendances. Lower doses of urate lowering therapy than expected were needed to achieve target. A small number of patients were discharged prior to enrolment for initial non-engagement which may have been exacerbated by the lack of face-to-face appointments. Our COVID-19 model did struggle with those patients needing an interpreter. In-person initial appointments have since been restarted;however, a greater proportion of reviews will continue to be offered by telephone given the unexpected success of the model. This audit showed that a nurse-led gout clinic can run successfully, even during a pandemic with a significant reliance on telephone consultations.
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Case Report: Mediastinal masses are rare with an incidence of 1 in 100 000 [1]. While the differential is broad, the risk of malignancy is higher in the pediatric population. Lymphomas account for about 50% of mediastinal masses [2].We present a patient with superior vena cava (SVC) syndrome from a mediastinal mass, concerning for lymphoma. After extensive work up, the mass was determined to be reactive. Case Presentation: A 5-year-old male, presented with one day of left sided face and neck swelling. Review of systemswas positive for a fewweeks of cough but notably negative for night sweats, fatigue, fever, or weight loss. Computed tomography (CT) scan (Figure 1, left) showed a heterogeneous mass, most concerning for lymphoma. Blood work was notable for lymphopenia (640 x 103/uL), elevated lactate dehydrogenase and uric acid (549 U/L and 7.1 mg/dL respectively). He tested positive for SARs- CoV2 RNA on nasopharyngeal PCR. Upon admission, he was started on methylprednisolone and allopurinol. A bone marrow biopsy and a lumbar puncture were unrevealing for immunophenotypic evidence of lymphoid neoplasm. A mediastinal biopsy showed fibrosis with patchy inflammation and inadequate number of viable cells to allow for flow cytometric analysis. A post-biopsy echocardiogram revealed a moderate sized pericardial effusion which eventually resolved. He was discharged with infectious disease and oncology follow up. Later, histoplasma and bartonella antibodies, and T spot were negative. A CT (Figure 1, right), ten days after initial presentation showed significant decrease in size of the mediastinal mass. At one month follow up, he remained clinically well with a normal chest x-ray. [Figure presented] Fig 1: A CT ten days after initial presentation showed significant decrease in size of the mediastinal mass Conclusion(s): This patient presented with SVC syndrome from a mediastinal mass that resolved with 3 days of intravenous steroids. The initial presumed diagnosis of lymphoma was ultimately inconsistent with the extensive workup, and the mass was ultimately deemed reactive. COVID-19 related mediastinal mass is not described in the literature, and although possible, remains unlikely. This case represents the importance of avoiding premature closure and keeping a broad differential diagnosis. 1. Park DR, Vallieres E. The mediastinal mass. Murray and Nadel's Textbook of Respiratory Medicine. 5th edn. Philadelphia, PA: Saunders;2010. pp. 1814-35. 2. Glick R. D., & La Quaglia M. P. (1999). Lymphomas of the anterior mediastinum. Seminars in Pediatric Surgery, 8(2),69-77.Copyright © 2023 Southern Society for Clinical Investigation.
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[...]a time frame could be set before the Covid-19 epidemic attack in January 2020, owing to the association between Covid-19 infection (ICD-10-CM B34.2, U07.1, U07.2, J12.81, J12.82, B97.29) and new-onset ED, which was recently detected in the same database [6]. According to the National Institute for Health and Care Excellence (NICE) guideline [15], treat-to-target (T2T) approach should be adhered to with serum urate level of at least < 360
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Introduction: Monitoring of patients on immunomodulator therapy for inflammatory bowel disease (IBD) and auto-immune hepatitis (AIH) significantly increases clinical workload in gastroenterology outpatient clinics owing to blood test monitoring requirements. Aim(s): This study conducted at Barnsley Hospital NHS Foundation Trust aimed to determine the clinical impact of a pharmacist-led virtual thiopurine clinic on drug monitoring, safety and quality of service in a cohort of IBD and AIH patients. Method(s): Patients attended an initial face-to-face outpatient consultation and were then followed-up via remote telephone consultations, as part of a virtual clinic, at two-week intervals. Patient biochemical data were analysed alongside anonymous postal questionnaires to provide an assessment of the quality of the service over a three-month period between 1 May and 31 July 2014. A second survey was performed in December 2019 to re-assess patient satisfaction. Result(s): 81 patients were assessed;clinical indications for thiopurines were IBD (n=75) and AIH (n=6). Overall, 39.5% (n=32) patients failed to reach the thiopurine therapeutic target (2mg/kg with normal thiopurine methyltransferase) owing to drug intolerance, lack of clinical response or hepatotoxicity. Thioguanine nucleotide analysis was performed in 29.6% (n=24) of patients who failed initial treatment, to allow dose optimisation. Hepatotoxicity developed in 9.9% (n=8) of patients, which required shunting of thiopurine metabolism with allopurinol. Myelosuppression developed in 6.9% (n=21) of the total number of blood tests performed (n=304), leading to discontinuation of thiopurines in two patients. The questionnaire response rate was 51.9% (n=42);92.9% of respondents (n=39) found the virtual clinic to be convenient;and 95.2% (n=40) were satisfied with the service. The follow-up survey included 373 patients with a 35.9% response rate (n=134);88% (n=118) found the service easily or very easily accessible, and 82% (n=109) found it very helpful or extremely helpful. Overall satisfaction was highly rated (average 4.46/5). Conclusion(s): Pharmacist-led virtual thiopurine clinics were shown to be safe and regarded favourably by patients. The clinics identified patients exposed to the risks of myelosuppression, as well as allowing thiopurine dose optimisation during the three-month period from May to July 2014. The followup survey in 2019 showed patients valued telemedicine as an alternative to face-to-face visits. Virtual clinics offer a viable alternative to traditional outpatient-driven thiopurine monitoring, especially during the ongoing COVID-19 pandemic. Copyright © 2020 Pharmaceutical Press. All rights reserved.
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Introduction: In Lombardy and Piedmont (Northern Italy, about 14 million people) the GRESIF pharmacovigilance network project, aimed to collect, assess, treat and prevent severe systemic drug reactions was activated in 2021, supported by the Italian Medicines Agency (AIFA). GRESIF involves regional and hospital pharmacovigilance centers, and several hospital wards: burn, dermatology, allergology, internal medicine, infectivology and intensive care departments. The registry collects in the National Pharmacovigilance Network all reports of suspected adverse drug reactions (ADRs) concerning Toxic Epidermal Necrolysis (TEN), Stevens-Johnson Syndrome (SJS), Drug reaction with eosinophilia and systemic symptoms (DRESS) and Acute Generalized Exanthematous Pustulosis (AGEP). Objective: The specific objectives of the study are to early detect severe systemic ADRs, evaluate their incidence, morbidity and mortality rates, focus on new generation drugs such as RNA antivirals and oncological drugs, implement and optimize guidelines, manage long-term sequelae by follow-up and create a consultable web-based database. Methods: We have drawn up the guidelines [1,2], through a multidisciplinary approach in order to improve the management of very complex patients even in facilities that are not habitually involved in the treatment of these pathologies. This document aims to support professionals in standardizing diagnostic criteria and methods of therapeutic approach. Its useful to inform the general practitioner about responsible drugs and give some information about risk /benefit on the riexposure. Results: In 2021, 27 cases of SJS/TEN, 18 cases of DRESS and no cases of AGEP were collected. There is a female prevalence (25 cases out 44);the age range is from 20 to 93 years. The median age of patients in Lombardy and in Piedmont is respectively 55 and 66 for females, 47 and 63 for males. The total mortality for cases of SJS/ TEN is about 19% and for DRESS we have no deaths. More frequent suspected drugs are antibiotics, followed by allopurinol and anticonvulsants. Noteworthy is the presence of 4 cases of severe ADR related to anti Covid19 RNA vaccines. In all cases, according to the guidelines, the timely discontinuation of the responsible drug was fundamental as the general management. Furthermore we started a study for the HLA typing of these patients. We enrolled 18 cases and the results showed that 6 patients who received allopurinol were all positive to HLA B 58:01. Conclusion: Despite being extremely rare but serious reactions, the absolute need to implement shared diagnostic and therapeutic protocols to be applied promptly is highlighted, in order to reduce both patient mortality and long-term sequelae.
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Introduction: Covid-19 infection has been spreading worldwide since December 2019. Skin manifestations are common as 60% of patients had skin involvement such as rashes, chilblains, urticaria, purpura and vasculitis (1). Toxic Epidermal Necrolysis (TEN) is a life-threatening dermatological disease with > 30% of body surface area involved. TEN pathophysiology is linked to immune system activation triggered by drugs or infections or unknown causes (2). We are reporting a case of biopsy confirmed TEN in pediatrics patient with history of recent Covid19 infection. Case Description: A 6-year-old boy with history of mild Covid 19 infection two weeks ago presented with fever, oral ulcers and maculopapular rash on the trunk and extremities for 2 days. He was admitted for supportive care. His skin rash was progressing to violaceous targetoid lesions on the trunk and extremities with genital erosion, Nickolsky sign was positive. He had purulent conjunctivitis and crusted lips lesions with deepithelization of the oral mucosa. SCROTEN score was 2 for detachment more than 30%, low bicarbonate of 19. All virology tests came out negative including respiratory and blood PCR testing. A 4-mm punch skin biopsy histopathology was consistent with TEN. He was treated with supportive care, IVIG 1 g/Kg daily for 5 days, IV dexamethasone shifted later to oral Prednisolone, Cyclosporin 3 mg/kg/day. His rash and oral mucositis improved within 1 week and he was discharged in stable condition. He was seen in the clinic after 1 month of discharge and recovery of the skin, oral and eye mucosa was observed. Discussion: This report presented a case of a child with TEN and history of recent Covid-19 infection. Most cases of TEN are triggered by drugs and some by infections (3)(4). There were case reports of TEN associated with Covid 19 infection in adults with probable association with drugs such as hydroxychloroquine (3), Allopurinol (5), Lamotrigine (6), one case with no history of drug exposure (7). In a report of more than 5000 pediatrics patients with Covid-19 infection only one patient had SJS (8). Another case of 8-year-old boy with Covid-19 infection who developed SJS rash was reported (9). Both pediatrics cases had history of Amoxicillin- Clavulanate use. In our case the relationship between Covid-19 infection and TEN is not clear as the child had a history of Ibuprofen use that could be the culprit trigger. However, Covid-19 could still be the trigger in this case. It is worth reporting this case to keep in mind the wide spectrum of dermatological presentation in Covid-19 patients. Conclusion: Whether Covid 19 infection can trigger TEN in pediatrics patient is an important question that needs larger studies, yet it is worth reporting this case of possible correlation between Covid 19 and TEN in pediatrics.
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CASE: A 72 year old male presented to the outpatient clinic with a “vaccine reaction” after he developed a left arm rash following his Moderna COVID-19 booster. He had received the Moderna vaccines in March & April with the only side effect being arm soreness. On 10/30/2021, he received his booster in his lateral left upper arm. Three days later, he reported arm soreness that progressed in intensity by day 6 and developed a rash. Patient had no prior history of shingles and had received the SHINGRIX vaccine. Medical history was remarkable for subtotal colectomy with ileostomy 2/2 to Crohn's disease, stage III CKD, hypertension, HLD, amputations of the right big toe and left metatarsal 2/2 to osteomyelitis. Home medications included daily allopurinol 100mg, amlodipine 5mg, mesalamine 1,000 mg and octreotide 200 mcg/mL injection 0.5mL SQ BID. Presenting vital signs were normal. A physical exam revealed vesicles on an erythematous base in a C5 dermatome distribution. Incidentally, there was a concentration of vesicles located at the Moderna Booster vaccine site. Rash collected in groups of vesicles on the anterior forearm. Due to delay in presentation and stage III CKD, antivirals were not prescribed. Patient was prescribed Gabapentin 300mg nightly for pain and instructed to continue OTC Tylenol. After several weeks the rash resolved and pain subsided. IMPACT/DISCUSSION: Approximately 4% of patients with a history of Varicella develop a recurrent episode later in life with people who are immunosuppressed most affected. Possible triggers of zoster (HZ) include external reexposure to the virus, acute or chronic diseases such as malignancies or infections (i.e COVID-19), medications and stress. As of 12/5/21, the Vaccine Adverse Event Report System (VAERS) reported shingles in 1200 patients after receiving Pfizer vaccine, 1201 Moderna, and 1203 in Janssen vaccine recipients. While these reports are unable to be validated, it is important for clinicians to recognize the suggested relationship. Hypotheses of why our patient developed shingles include: 1) the immune activation from the vaccine activated dormant varicella, 2) the patient being older & immunocompromised puts him at a higher risk of developing HZ in general, and 3) the vaccine triggers a transient lymphopenia similar to being infected with COVID-19 and lymphopenia causes reactivation. As we continue to reach higher percentages of individuals receiving vaccines, we likely will continue to encounter cases such as described. CONCLUSION: It is important for clinicians to be aware of HZ reaction post COVID vaccination and to have this in their differential when a patient complains of a “reaction” to the vaccine. We regret that the patient being mis-triaged as an “allergic reaction” led to the patient being evaluated outside of the possible window of acute treatment of HZ. By describing this case we hope clinicians will be more aware of this relationship and prevent delay to treatment or misdiagnosis.
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A 51-year-old woman presented acutely to dermatology with an 8-week history of painful, purple discolouration of her toes, which started on her left foot but progressed to involve all of her toes. She was noted to have a positive COVID-19 polymerase chain reaction test after her symptoms began. There was some superficial ulceration of two of her toes. The episode lasted for 5 weeks;however, after 6 weeks her toes had flared again. No triggers were indentified;in particular, her symptoms were not related to the cold. There were no other rashes. She has a past medical history of endometriosis and gout. She takes desogestrel and allopurinol, which she had been on for 2 years. Vasculitis screen was negative. She was treated initially with clobetasol propionate and nifedipine. On follow-up 6 weeks later, the patient reported hypersensitivity of her toes, with severe pain reported from socks rubbing against her toes. The toes had normal appearances and cool peripheries. We suspect that the increased sensitivity and pain is a reflex sympathetic response secondary to 'COVID toes' and have treated with it gabapentin. It is thought that reflex sympathetic dystrophy occurs because inflammation causes damage to the nerves;however, the exact mechanism behind reflex sympathetic dystrophy is yet to be elucidated.
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With the outbreak of the emergent coronavirus, there have been sparse reports of severe cutaneous adverse reactions in some severely ill patients (Chen XY, Yan BX, Man XY. TNFα inhibitor may be effective for severe COVID-19: learning from toxic epidermal necrolysis. Ther Adv Respir Dis 2020;14: 1753466620926800). It is thought that this is due to clonal expansion of CD8+ cytotoxic T lymphocytes and natural killer cells that occurs during the cytokine storm elicited by the virus or the use of unconventional drugs to treat patients (Rossi CM, Beretta FN, Traverso G et al. A case report of toxic epidermal necrolysis (TEN) in a patient with COVID-19 treated with hydroxychloroquine: are these two partners in crime? Clin Mol Allergy 2020;18: 19;Saha M, D'Cruz A, Paul N et al. Toxic epidermal necrolysis and co-existent SARS-CoV-2 (COVID-19) treated with intravenous immunoglobulin:'Killing 2 birds with one stone'. J Eur Acad Dermatol Venereol 2020;35: e97-8). In a minority of cases, viral or autoimmune forms of toxic epidermal necrolysis (TEN) may be implicated (Chen et al.;Rossi et al.). However, very little research, has been done to decipher the association or pathogenesis with TEN and the novel virus. We report an interesting case of a 51-year-old woman who developed a rash on her face, flanks and periumbilical area immediately after an intensive care admission with respiratory failure secondary to confirmed COVID-19 pneumonitis. The patient had a background of gout on allopurinol and type 2 diabetes. There were no changes in medications. While admitted, she was started on broad spectrum antibiotics. On examination, there were large, confluent patches of erythema with a targetoid appearance on the face, upper limbs and trunk, and tense blistering over the forearms. Biopsy showed full thickness epidermal necrosis and subepidermal bullous formation. An autoimmune and bullous screen was negative. Prognosis was poor with the critical care team considering end-of-life management. However, with the diagnosis of a reversible condition, supportive therapy was continued. With continued intensive care intervention, steroids and barrier protection, her TEN gradually resolved as she recovered from COVID-19, and she had a favourable outcome with only residual milia and signs of re-epithelialization.
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Mycophenolate rapidly substituted azathioprine (AZA) in transplant immunosuppression regimens since the 1990s, when early clinical trials indicated better outcomes, although opposite results were also observed. However, none of these trials used the well-established optimization methods for AZA dosing, namely, thiopurine methyltransferase pharmacogenetics combined with monitoring of the thiopurine metabolites 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP). Resistance to optimize AZA therapy remains today in transplant therapy, despite the fact that thiopurine metabolite testing is being used by other medical disciplines with evident improvement in clinical results. In a previous analysis, we found that active 6-TGN metabolites were not detectable in about 30% of kidney transplant patients under continuous use of apparently adequate azathioprine dosage, which demonstrates the need to monitor these metabolites for therapeutic optimization. Two of four case studies presented here exemplifies this fact. On the other hand, some patients have toxic 6-TGN levels with a theoretically appropriate dose, as seen in the other two case studies in this presentation, constituting one more important reason to monitor the AZA dose administered by its metabolites. This analysis is not intended to prove the superiority of one immunosuppressant over another, but to draw attention to a fact: there are thousands of patients around the world receiving an inadequate dose of azathioprine and, therefore, with inappropriate immunosuppression. This report is also intended to draw attention, to clinicians using thiopurines, that allopurinol co-therapy with AZA is a useful therapeutic pathway for those patients who do not adequately form active thioguanine metabolites.
Subject(s)
Azathioprine , Kidney Transplantation , Enzyme Inhibitors , Humans , Immunosuppressive Agents/adverse effects , Thioguanine/therapeutic useABSTRACT
Background In this study, we aimed to study the frequency of hypertension in Sudanese patients with gouty arthritis attending the largest three tertiary hospitals in Khartoum and correlate it with serum uric acid levels. Methodology An observational, descriptive, cross-sectional, hospital-based study was conducted in rheumatology clinics in Khartoum state, Sudan, from August 2020 to January 2021 involving 100 participants. Data were collected, prepared, and analyzed using SPSS version 25.0 (IBM Corp., Armonk, NY, USA). Results In this study, 100 participants were enrolled. The majority were males (79%), with 45% of the participants in the age group of 61-75 years. Overall, 89% of participants had symptoms of gouty arthritis, with the knee being the most common joint affected in 27% of participants. Most participants had a uric acid level above the target (6 mg/dL). The most frequently used uric acid lowering agent was found to be allopurinol in 85% of the patients. Furthermore, among those with gouty arthritis, 51% had hypertension with nearly half being insufficiently controlled. The frequency of undiagnosed hypertension among the participants was found to be 19%, which was statistically significant among gouty arthritis patients (p-value < 0.0001). Upon further analysis of our hypertensive participants, 79.5% of males (n = 35) had high blood pressure levels, which was statistically significant as well (p-value = 0.005), with the highest prevalence being among the age group of 61-75 years. Of those who were hypertensive, 51% had a history of concomitant comorbidity. Overall, 90% of the hypertensive participants (n = 40) had joint symptoms. Moreover, serum uric acid level was above the target in 93% of the participants. Conclusions Hypertension was found to be the most frequently recognized comorbidity in gouty arthritic patients, with more than a third remaining undiagnosed. Moreover, the male gender was a significant risk factor for hypertension among the gouty arthritis participants. Nevertheless, most patients with high blood pressure levels had concurrent elevated uric acid levels.
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Objetivo: Demonstrar caso de paciente com Leucemia Linfocítica Crônica (LLC) tratado com Ibrutinibe em 1ªlinha. Material e método: Relato de caso, através de consulta de prontuário e revisão de literatura. Relato de caso: Homem, 77 anos, encaminhado para hematologista devido a linfocitose, já conhecida há mais de 10 anos, porém sem desejo de investigação, uma vez acreditando ser obrigatório a realização de estudo medular. Após cerca de um ano e meio, paciente apresentou anemia e progressão linfocitária em mais de duas vezes e em período menor de 6 meses (inicialmente com 28.224 linfócitos/mm3 e após, um máximo de 273.263/mm3). Exame de FISH evidenciou IGVH não mutado, ausência de deleção do cromossomo 17 (del17) e presença de trissomia do 12. Ao exame físico, ele não apresentou alterações, bem como linfonodomegalias, em nenhum momento do seguimento. Sintoma de astenia surgiu concomitantemente ao quadro de anemia e após constatada progressão da doença, foi optado pelo tratamento do paciente. Uma vez considerando paciente idoso e com alta carga linfoproliferativa, foi prescrito inicialmente prednisona 60 mg, alopurinol enquanto foi realizado o processo de solicitação de Ibrutinibe 420 mg diário com base no protocolo ALLIANCE A041202, levando cerca de 2 meses para ser liberado pelo convênio. Com o início do tratamento específico, o paciente apresentou resposta completa em cerca de 7 meses, sem desenvolver sinais de toxicidade ou efeitos colaterais, bem como diarreia, fibrilação atrial, infecções, eventos hemorrágicos ou artralgias. Paciente se encontra em seguimento com retornos a cada 3 meses, sem recidiva e apresentou contagem de linfócitos menor de 5000/mm3, fato que nos levou a solicitar exame de pesquisa de DRM, mesmo não sendo o objetivo deste medicamento (aguardamos este resultado). Discussão e conclusão: A LLC é uma desordem linfoproliferativa caracterizada pelo acúmulo progressivo de linfócitos que são monoclonais, sendo que os linfócitos B CD5+ sofrem transformação maligna. Acomete em maior prevalência pessoas idosas e do sexo masculino, como o paciente deste caso. O início da doença costuma ser insidioso e com sintomas não específicos, com pacientes assintomáticos. Com uma sobrevida variável, entre cerca de 2 e 20 anos, com uma taxa média de 10 anos, existem critérios bem estabelecidos para indicar o início de tratamento, dentre eles, podemos citar a duplicação de linfócitos com tempo inferior a 6 meses ou sintomas relacionados à doença. Existem diversas opções terapêuticas, dentre elas, o Ibrutinibe, uma droga oral, inibidora da tirosina quinase de Bruton, bloqueando a via de sinalização do receptor de células B, importante para a sobrevivência e proliferação dos linfócitos clonais, atualmente, em geral, com indicação em primeira linha para paciente com del17, porém conforme estudo recente, Ibrutinibe demonstrou ser superior à quimioterapia em pacientes idosos com LLC. No caso em discussão, foi optado pelo Ibrutinibe em primeira linha, pois, além de ser um paciente idoso, na ocasião da progressão da doença estávamos no início da pandemia de SARS-CoV2, momento em que havia um grande receio quanto aos possíveis eventos adversos relacionados a uma quimioterapia padrão, em especial do ponto de vista infeccioso, num paciente idoso nesse contexto da pandemia. Apesar do Ibrutinibe representar um grande avanço terapêutico, deve-se considerar a questão de custos e toxicidades possíveis, uma vez que é um tratamento contínuo a longo prazo.
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We report two consecutive cases of toxic epidermal necrolysis presented to our emergency department in the past 5 months. Both patients had history of fever prior to the onset of skin manifestations and showed radiological findings suggestive of COVID-19 pneumonia and elevated D dimers. ALDEN score was used to assess the drug causality, which showed probable and possible associations, respectively. In this report, along with brief review of literature, we highlight the possible role of viral etiology, that is SARS-Cov2, in triggering toxic epidermal necrolysis.
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SARS-CoV-2 by the direct cytopathic effect or indirectly through the propagation of pro-inflammatory cytokines could cause endothelial dysfunction (ED) and oxidative stress (OS). It has been reported that OS is triggered by various types of viral infections, including SARS-CoV-2. Into the bargain, allopurinol is regarded as a potent antioxidant that acts through inhibition of xanthine oxidase (XO), which is an essential enzyme of purine metabolism. Herein, the present study aimed to find the potential protective effects of allopurinol on the biomarkers of OS and ED in patients with severe Covid-19. This single-center cohort study recruited 39 patients with mild-moderate Covid-19 compared with 41 patients with severe Covid-19. Nineteen patients with severe Covid-19 were on the allopurinol treatment because of underlying chronic gout 3 years ago compared with 22 Covid-19 patients not on this treatment. The recruited patients were allocated into three groups: group I, mild-moderate Covid-19 on the standard therapy (n = 39); group II, severe Covid-19 patients on the standard therapy only (n = 22); and group III, severe Covid-19 patients on the standard therapy plus allopurinol (n = 19). The duration of the study was 3 weeks from the time of hospitalization till the time of recovery. In addition, inflammatory biomarkers (D-dimer, LDH, ferritin, CRP, procalcitonin), neutrophil-lymphocyte ratio (NLR), endothelin-1 (ET-1), uric acid and oxidative stress index (OSI), CT scan score, and clinical score were evaluated at the time of admission and discharge regarding the effect of allopurinol treatment adds to the standard treatment of Covid-19. Allopurinol plus standard treatment reduced LDH, ferritin, CRP, procalcitonin, and ET-1 serum level significantly (P < 0.05) compared with Covid-19 patients on standard treatment. Besides, neutrophil (%), lymphocyte (%), and neutrophil-lymphocyte ratio (NLR) were reduced in patients with severe Covid-19 on standard treatment plus allopurinol compared with Covid-19 patients on standard treatment alone (P < 0.01). OSI was higher in patients with severe Covid-19 than mild-moderate Covid-19 patients (P = 0.00001) at admission. At the time of discharge, the oxidative status of Covid-19 patients was significantly improved compared with that at admission (P = 0.01). In conclusion, Covid-19 severity is linked with high OS and inflammatory reaction with ED development. High uric acid in patients with severe Covid-19 is correlated with high OS and inflammatory biomarkers. Allopurinol with standard treatment in patients with severe Covid-19 reduced oxidative and inflammatory disorders with significant amelioration of ED and clinical outcomes.