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      A case of exacerbation of psoriasis after oseltamivir and hydroxychloroquine in a patient with COVID‐19: Will cases of psoriasis increase after COVID‐19 pandemic?

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      Dermatologic Therapy
      John Wiley & Sons, Inc.

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          Abstract

          Dear Editor, COVID‐19 pandemics have been described in the city of Wuhan in China and spread around the world. 1 The new type of SARS‐Cov2, a mutant novel coronavirus that humans encountered for the first time, binds to ACE receptors cause pneumonia. Researchers have focused on the treatment of the current disease through different pathways, especially this pathophysiological mechanism besides FcR activation. 2 Recent studies have revealed numerous effective therapeutic options including favipiravir, brincidofovir, monoclonal antibodies, hydroxychloroquine, oseltamivir, and antisense RNA.3, 4 Herein, a case of psoriasis exacerbated with hydroxychloroquine and oseltamivir treatment in a patient with COVID‐19 will be presented. A 71‐year‐old woman with no skin lesions was admitted to the pandemic clinic with the diagnosis of COVID‐19. The patient had a history of psoriasis that has been activated occasionally since childhood. The patient was started orally oseltamivir 2 × 75 mg and hydroxychloroquine on 2 × 400 mg on the first day then 2 × 200 mg. On the fourth day of treatment, the patient had an exacerbation of silver‐scaled psoriatic plaques spread quickly all over the body separated from the surrounding tissue with sharp borders. This is the first case of exacerbation of psoriasis during COVID‐19 infection in a patient receiving oseltamivir versus hydroxychloroquine. The exacerbation of psoriasis in this patient can be explained by several conditions. First, it is well known that hydroxychloroquine is an inhibitor of the epidermal trans‐glutaminase, cause to the collection of the epidermal cells. 5 In addition, hydroxychloroquine promotes IL‐17 production through p38‐dependent IL‐23 release resulting in keratinocyte growth and differentiation. 6 Therefore, hydroxychloroquine treatment, which was started as a high dose on the first day, maybe the main factor that exacerbates psoriasis in this patient. To date, we did not find any reports that oseltamivir may affect psoriasis. To be under quarantine and learn the diagnosis of COVID‐19, which is a fatal disease in older patients may have contributed to the triggering of psoriasis by increasing a stress burden in this patient. Finally, infections are known to trigger psoriasis, especially the pustular form. Here, we present for the first time a case of psoriasis potentially triggered by COVID‐19 infection. Although exacerbation of psoriasis may occur after hydroxychloroquine, given severe psoriasis which occurs in a very short time may indicate that the COVID‐19 infection also plays an important role in the etiology of psoriasis. Patients with SARS‐CoV2, that have been reported recently, have increased plasma concentrations of inflammation‐related cytokines, including interleukins 2, 7, and 10, granulocyte‐colony stimulating factor, interferon‐inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1 alpha, and tumor necrosis factor α. 7 The increasing some cytokines in the COVID‐19 that are also accused in the etiopathogenesis of psoriasis may suggest that COVID‐19 may be a new entity that exacerbates psoriasis vulgaris. As a result, it can be speculated that hydroxychloroquine, a commonly used drug for COVID‐19 infection, can lead to a worldwide increase number of psoriasis that is prevalence between 1% and 3%. This condition may lead clinicians to new treatments that do not have immunosuppressive properties. 8 CONFLICT OF INTEREST The authors declare no conflicts of interest.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention

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              The COVID‐19 epidemic

              The current outbreak of the novel coronavirus SARS‐CoV‐2 (coronavirus disease 2019; previously 2019‐nCoV), epi‐centred in Hubei Province of the People’s Republic of China, has spread to many other countries. On 30. January 2020, the WHO Emergency Committee declared a global health emergency based on growing case notification rates at Chinese and international locations. The case detection rate is changing daily and can be tracked in almost real time on the website provided by Johns Hopkins University 1 and other forums. As of midst of February 2020, China bears the large burden of morbidity and mortality, whereas the incidence in other Asian countries, in Europe and North America remains low so far. Coronaviruses are enveloped, positive single‐stranded large RNA viruses that infect humans, but also a wide range of animals. Coronaviruses were first described in 1966 by Tyrell and Bynoe, who cultivated the viruses from patients with common colds 2. Based on their morphology as spherical virions with a core shell and surface projections resembling a solar corona, they were termed coronaviruses (Latin: corona = crown). Four subfamilies, namely alpha‐, beta‐, gamma‐ and delta‐coronaviruses exist. While alpha‐ and beta‐coronaviruses apparently originate from mammals, in particular from bats, gamma‐ and delta‐viruses originate from pigs and birds. The genome size varies between 26 kb and 32 kb. Among the seven subtypes of coronaviruses that can infect humans, the beta‐coronaviruses may cause severe disease and fatalities, whereas alpha‐coronaviruses cause asymptomatic or mildly symptomatic infections. SARS‐CoV‐2 belongs to the B lineage of the beta‐coronaviruses and is closely related to the SARS‐CoV virus 3, 4. The major four structural genes encode the nucleocapsid protein (N), the spike protein (S), a small membrane protein (SM) and the membrane glycoprotein (M) with an additional membrane glycoprotein (HE) occurring in the HCoV‐OC43 and HKU1 beta‐coronaviruses 5. SARS‐CoV‐2 is 96% identical at the whole‐genome level to a bat coronavirus 4. SARS‐CoV‐2 apparently succeeded in making its transition from animals to humans on the Huanan seafood market in Wuhan, China. However, endeavours to identify potential intermediate hosts seem to have been neglected in Wuhan and the exact route of transmission urgently needs to be clarified. The initial clinical sign of the SARS‐CoV‐2‐related disease COVID‐19 which allowed case detection was pneumonia. More recent reports also describe gastrointestinal symptoms and asymptomatic infections, especially among young children 6. Observations so far suggest a mean incubation period of five days 7 and a median incubation period of 3 days (range: 0–24 days) 8. The proportion of individuals infected by SARS‐CoV‐2 who remain asymptomatic throughout the course of infection has not yet been definitely assessed. In symptomatic patients, the clinical manifestations of the disease usually start after less than a week, consisting of fever, cough, nasal congestion, fatigue and other signs of upper respiratory tract infections. The infection can progress to severe disease with dyspnoea and severe chest symptoms corresponding to pneumonia in approximately 75% of patients, as seen by computed tomography on admission 8. Pneumonia mostly occurs in the second or third week of a symptomatic infection. Prominent signs of viral pneumonia include decreased oxygen saturation, blood gas deviations, changes visible through chest X‐rays and other imaging techniques, with ground glass abnormalities, patchy consolidation, alveolar exudates and interlobular involvement, eventually indicating deterioration. Lymphopenia appears to be common, and inflammatory markers (C‐reactive protein and proinflammatory cytokines) are elevated. Recent investigations of 425 confirmed cases demonstrate that the current epidemic may double in the number of affected individuals every seven days and that each patient spreads infection to 2.2 other individuals on average (R0) 6. Estimates from the SARS‐CoV outbreak in 2003 reported an R0 of 3 9. A recent data‐driven analysis from the early phase of the outbreak estimates a mean R0 range from 2.2 to 3.58 10. Dense communities are at particular risk and the most vulnerable region certainly is Africa, due to dense traffic between China and Africa. Very few African countries have sufficient and appropriate diagnostic capacities and obvious challenges exist to handle such outbreaks. Indeed, the virus might soon affect Africa. WHO has identified 13 top‐priority countries (Algeria, Angola, Cote d’Ivoire, the Democratic Republic of the Congo, Ethiopia, Ghana, Kenya, Mauritius, Nigeria, South Africa, Tanzania, Uganda, Zambia) which either maintain direct links to China or a high volume of travel to China. Recent studies indicate that patients ≥60 years of age are at higher risk than children who might be less likely to become infected or, if so, may show milder symptoms or even asymptomatic infection 7. As of 13. February 2020, the case fatality rate of COVID‐19 infections has been approximately 2.2% (1370/60363; 13. February 2020, 06:53 PM CET); it was 9.6% (774/8096) in the SARS‐CoV epidemic 11 and 34.4% (858/2494) in the MERS‐CoV outbreak since 2012 12. Like other viruses, SARS‐CoV‐2 infects lung alveolar epithelial cells using receptor‐mediated endocytosis via the angiotensin‐converting enzyme II (ACE2) as an entry receptor 4. Artificial intelligence predicts that drugs associated with AP2‐associated protein kinase 1 (AAK1) disrupting these proteins may inhibit viral entry into the target cells 13. Baricitinib, used in the treatment of rheumatoid arthritis, is an AAK1 and Janus kinase inhibitor and suggested for controlling viral replication 13. Moreover, one in vitro and a clinical study indicate that remdesivir, an adenosine analogue that acts as a viral protein inhibitor, has improved the condition in one patient 14, 15. Chloroquine, by increasing the endosomal pH required for virus‐cell fusion, has the potential of blocking viral infection 15 and was shown to affect activation of p38 mitogen‐activated protein kinase (MAPK), which is involved in replication of HCoV‐229E 16. A combination of the antiretroviral drugs lopinavir and ritonavir significantly improved the clinical condition of SARS‐CoV patients 17 and might be an option in COVID‐19 infections. Further possibilities include leronlimab, a humanised monoclonal antibody (CCR5 antagonist), and galidesivir, a nucleoside RNA polymerase inhibitor, both of which have shown survival benefits in several deadly virus infections and are being considered as potential treatment candidates 18. Repurposing these available drugs for immediate use in treatment in SARS‐CoV‐2 infections could improve the currently available clinical management. Clinical trials presently registered at ClinicalTrials.gov focus on the efficacy of remdesivir, immunoglobulins, arbidol hydrochloride combined with interferon atomisation, ASC09F+Oseltamivir, ritonavir plus oseltamivir, lopinavir plus ritonavir, mesenchymal stem cell treatment, darunavir plus cobicistat, hydroxychloroquine, methylprednisolone and washed microbiota transplantation 19. Given the fragile health systems in most sub‐Saharan African countries, new and re‐emerging disease outbreaks such as the current COVID‐19 epidemic can potentially paralyse health systems at the expense of primary healthcare requirements. The impact of the Ebola epidemic on the economy and healthcare structures is still felt five years later in those countries which were affected. Effective outbreak responses and preparedness during emergencies of such magnitude are challenging across African and other lower‐middle‐income countries. Such situations can partly only be mitigated by supporting existing regional and sub‐Saharan African health structures.
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                Author and article information

                Contributors
                omerkutlu22@gmail.com
                Journal
                Dermatol Ther
                Dermatol Ther
                10.1111/(ISSN)1529-8019
                DTH
                Dermatologic Therapy
                John Wiley & Sons, Inc. (Hoboken, USA )
                1396-0296
                1529-8019
                24 April 2020
                : e13383
                Affiliations
                [ 1 ] Department of Dermatology and Venereology, School of Medicine Uşak University Uşak Turkey
                Author notes
                [*] [* ] Correspondence

                Ömer Kutlu, MD, MRCP, Department of Dermatology and Venereology, School of Medicine, Uşak University, Uşak, Turkey.

                Email: omerkutlu22@ 123456gmail.com

                Author information
                https://orcid.org/0000-0002-9665-015X
                https://orcid.org/0000-0002-6512-4990
                Article
                DTH13383
                10.1111/dth.13383
                7235511
                32259878
                dde5b859-074d-4976-98f5-e1df8b3622f7
                © 2020 Wiley Periodicals LLC

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 02 April 2020
                : 03 April 2020
                Page count
                Figures: 0, Tables: 0, Pages: 2, Words: 874
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