|
| |
 |
|
| ORIGINAL ARTICLE |
|
| Year : 2021 | Volume
: 39
| Issue : 2 | Page : 74-78 |
|
Cutaneous manifestations of coronavirus disease in Turkey: A prospective study
Yeniay Yildiray, Pekdemir Sen Ayse
Department of Dermatology, Golcuk Public Hospital, Kocaeli, Turkey
| Date of Submission | 28-Oct-2020 |
| Date of Decision | 11-Mar-2021 |
| Date of Acceptance | 30-Mar-2021 |
| Date of Web Publication | 23-Jun-2021 |
Correspondence Address:
Dr. Yeniay Yildiray
Department of Dermatology, Golcuk Public Hospital, Kocael
Turkey
 Source of Support: None, Conflict of Interest: None  | 3 |
DOI: 10.4103/ds.ds_17_21
Background: Although the clinical features of coronavirus disease 2019 (COVID-19) infection are mainly based on respiratory system symptoms, different types of skin manifestations have been described in the literature. Objectives: We investigated COVID-19 cases in Kocaeli, Turkey, in a period of 3 months to identify and figure out the real burden of skin lesions associated with COVID-19 infection. Methods: A total of 266 patients who had positive results on reverse transcription–polymerase chain reaction analysis of nasopharyngeal swab for severe acute respiratory syndrome coronavirus type 2 between March 2020 and June 2020 at our region were investigated for the study. Results: A total of 266 patients was included in this study, 92 (34.6%) patients were male and 174 (65.4%) were female. The mean ± standard deviation age of the patients was 49.2 ± 18.69 (range: 18–96 years). During clinical examination, 5 (1.9%) patients demonstrated skin lesions that might be associated with COVID-19 infection. These lesions consisted of urticaria in three patients and vesicular eruption in two patients. Conclusion: Although the incidence of cutaneous manifestations was lower than expected, these symptoms are valuable clues to identify patients or asymptomatic individuals in high-risk populations. Further prospective studies in larger populations are needed to better define the real cutaneous aspect of the disease.
Keywords: Coronavirus disease 2019, coronavirus, eruption, severe acute respiratory syndrome coronavirus type 2, skin, urticaria, vesicles
How to cite this article:
Yildiray Y, Ayse PS. Cutaneous manifestations of coronavirus disease in Turkey: A prospective study. Dermatol Sin 2021;39:74-8 |
| Introduction | |  |
Coronavirus disease 2019 (COVID-19) is a viral infection caused by recently identified severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) that has been quickly spread worldwide since its first appearance in December 2019 in Wuhan, China. Despite tight lockdown restrictions imposed in Wuhan, the World Health Organization declared a pandemic condition in March due to an increasing number of cases in lots of countries around the world.
Currently, by September 2020, more than 30 million confirmed cases have been reported worldwide. Although clinical features of COVID-19 infection are mainly based on respiratory impairment, different types of skin manifestations including urticariform, maculopapular, papulovesicular, erythematous, petechial, purpuric, livedoid, and perniosis-like lesions have been described in case reports and series.[1],[2]
In this prospective study, we investigated COVID-19 cases in our hospital in a period of 3 months to identify and figure out the real burden of skin lesions associated with COVID-19 infection.
| Materials and Methods | | |
The study was designed in a prospective fashion, and the study protocol was submitted to the Regional Ethics Committee approval (approval number: 2020-50). Due to pandemic preventions, protocol approval was also received from the Turkish Ministry of Health. Written informed consent was obtained from all participants to minimize contamination risk.
We included all adult patients (aged ≥18 years) who had a positive result on reverse transcription–polymerase chain reaction (PCR) analysis of nasopharyngeal swab for SARS-CoV-2 between March 2020 and June 2020 at Golcuk Public Hospital that serves as a pandemic hospital during pandemic outbreak. A total of 266 consecutive patients met the inclusion criteria.
Each patient was visited at his or her private room with personal protective equipment in terms of avoiding infection. Two trained dermatologists recorded the clinical and demographic features of the patients and performed skin examination to detect any visible skin lesions that might be associated with COVID-19 infection on the 1st day that they were hospitalized and followed up by daily visits for any new symptoms. Patients were also asked if they have any skin symptoms during prodromal periods that have been diminished at the time of examination. Clinical and demographic features are analyzed by descriptive statistics in order to define the frequencies of these variables. Statistical analyses were performed using SPSS (IBM Corp. Released 2011. IBM SPSS Statistics for Macintosh, version 20.0. Armonk, NY, USA).
| Results | | |
In a total of 266 patients included in this study, 92 (34.6%) patients were male and 174 (65.4%) were female. The mean ± standard deviation age of the patients was 49.2 ± 18.69 (range: 18–96 years). Twenty-three patients had treatment in the intensive care unit, 141 patients had treatment in the inpatient clinic, and 102 patients had treatment in the quarantine facility. During clinical examination, 5 (1.9%) patients demonstrated skin lesions that might be associated with COVID-19 infection. These lesions consisted of urticaria in three patients and vesicular eruption in two patients [Figure 1]. The demographic and clinical features of the patients and characteristics of the lesions are summarized in [Table 1]. | Table 1: Demographic and clinical features of the patients and characteristics of the lesions
Click here to view |
All patients with cutaneous manifestations presented with systemic symptoms during the course of the infection including fatigue, myalgia, fever, diarrhea, sore throat, respiratory distress, and cough. The timeline relation between the systemic symptoms and cutaneous manifestations varies according to the cases. Urticarial lesions were observed 2–4 days before or after the systemic symptoms, whereas vesicular lesions developed 1–3 days before the symptoms.
According to the national guideline, all patients received hydroxychloroquine and/or favipiravir treatment for COVID-19 infection. Three patients with urticarial lesions were treated with oral antihistamines and topical steroids, and the lesions resolved within a few days. One of the patients with urticarial lesions has a partial response with reduced flares after the treatment. The patient with scattered vesicular lesions on the trunk was also treated with topical steroids in a few days. On the other hand, localized vesicular lesions of the other patient progressed quickly to erosion and ulceration that need weeks to recover by topical antibiotics and occlusive dressing.
| Discussion | | |
By the end of 2019, humankind faced the greatest challenge, COVID-19 pandemic, in which modern medicine struggles with it globally. Currently, by September 2020, more than 30 million confirmed cases have been reported worldwide, and more than 300 thousand cases have been reported in Turkey.[3] Regardless of specialty, doctors tried their best to ameliorate public health in the COVID-19 pandemic.
Patients with COVID-19 mainly present with flu-like symptoms including sore throat, cough, dyspnea, fatigue, rhinorrhea, headache, conjunctivitis, and fever.[4] In addition to this, isolated anosmia has been reported frequently.[5] Less frequent cases with dysgeusia and diarrhea also presented in the literature. During the pandemic period, clinicians have observed that some of the COVID-19-infected patients presented with cutaneous manifestations. Cases with urticariform, maculopapular, papulovesicular, erythematous, petechial, purpuric, livedoid, and perniosis-like lesions that are associated with COVID-19 infection have been reported.[6],[7],[8],[9]
According to the literature, the first report that identifies the incidence of previously described skin manifestations of COVID-19 infection published from Italy, where the pandemic hits hard, demonstrated that 18 (20.4%) out of 88 patients had skin lesions including urticaria and erythematous and vesicular rashes.[6] To date, there has been only one published prospective study that aims to investigate the cutaneous manifestations of COVID-19 infection, which showed that 5 (4.9%) out of 103 patients in France presented with cutaneous lesions associated with the infection.[10] Here, our study demonstrated the incidence of skin manifestations due to the COVID-19 infection as 5 (1.9%) out of 266 patients in our region, which is lower than other European countries. The varying incidence of skin manifestations of COVID-19 infection raised the questions to identify possible factors that lead to these differences.
During the study period, our country has adopted strict measures to fight COVID-19 infection. All patients with a positive nasopharyngeal swab for SARS-CoV-2 were hospitalized for the treatment and transferred to the quarantine facilities after the treatment until full recovery. Even if a patient had mild systemic symptoms or asymptomatic, all positive cases were treated according to this protocol. As a result of this protocol, we are able to demonstrate the incidence of skin manifestations in COVID-19 cases more accurately by including all cases. While Hedou et al. reported a higher incidence of skin manifestations (4.9%) in COVID-19 infection, they emphasized that they could only include patients with respiratory illness or requiring hospitalization. Thus, patients who have systemic symptoms tend to have skin manifestations which may influence the study result via selection bias.[11] In our study, strict measures for coronavirus pandemic minimize this selection bias risk by including all positive patients.
Another possible factor might be variation in the viral genome. Mutation of viral genome is the most important mechanism for virus evolution in nature. These mutations could be advantageous or disadvantageous for the virus that results in changes in its virulence, antigenicity, host tropism, and transmission behaviors. In a recent report, genetic analyses of 86 genomes of SARS-CoV-2 from different countries revealed a total of 93 mutations and 3 deletions on coding and noncoding regions in the genome.[12] It is important that three of these mutations were discovered in the spike surface glycoprotein receptor-binding domain. The spike surface glycoprotein is a structural protein that has a crucial role in binding to receptors on the host cell to modify host tropism.[13] These variations in the virus genome lead to alteration of the antigenicity, which might result in diversity at skin manifestations.
Urticarial eruptions are common dermatologic conditions that a wide spectrum of infectious agents can cause its initiation.[14] In the literature, urticarial eruption associated with COVID-19 infection has been reported frequently.[15],[16] Galván Casas et al. collected a large group of COVID-19-infected patients with skin manifestations and reported that 19% of the 375 patients presented with urticarial eruption.[7] From another aspect, Recalcati S. investigated all COVID-19 cases and reported that 3 of 88 patients had urticarial eruptions which are not correlated by the severity of the disease.[6] Similar to this study, Hedou et al. reported that 2 of 104 patients with COVID-19 infection had urticarial eruption.[10] Urticarial eruption might be confined to the trunk or distributed to the extremities, and the time of onset of the lesions might be at prodromal phase or later.[7],[10] In our study, 3 of 266 patients had an urticarial eruption on the trunk and extremities that started at the prodromal and illness phase of the disease.
Viral infections of the human body can be presented with vesicular eruptions. In particular virus infections, these skin lesions are documented as pathognomonic that could lead to a quicker and earlier diagnosis.[17] Vesicular eruptions associated with COVID-19 infection have been reported in previous studies.[8],[18] According to the literature, these vesicular lesions might be localized or widespread.[8],[18] Marzano et al. described varicella-like eruption in 12 of 22 patients with COVID-19 infection.[8] In addition to this, Galván Casas et al. also reported that 9% of the 375 patients with cutaneous manifestations presented with vesicular eruption on the trunk that consisted of small monomorphic vesicles.[7] They also emphasized that these vesicles may have hemorrhagic content and become larger and diffuse. In our study, we observed that 2 of 266 patients had vesicular eruption whereas one of our patients had scattered vesicular eruption on his back and the other one had localized vesicles that become confluent, hemorrhagic, and infected. Although we assumed these vesicular eruptions as a part of COVID-19 infection, no distinct features to identify these vesicular lesions to address COVID-19 infections have been described yet.
In the literature, chilblains-like lesions have been described in COVID-19-infected patients.[10] Galván Casas et al. reported that 19% of the 375 patients with cutaneous manifestations presented with erythema–edema with some vesicles or pustules in acral areas.[7] During clinical examination, patients informed about this type of skin lesion and asked if they had any during prodromal period of the infection. Unfortunately, we could not observe any erythematous lesion that may associate with chilblains or perniosis. We could not conclude any reason for the absence of this skin manifestation.
Skin manifestations of COVID-19 disease are reported in case series and review articles to raise the awareness of physicians for early recognition of the disease. It is still questionable if the skin manifestations might be a clue for early diagnosis. In our prospective study, a 57-year-old female patient with urticaria complaint was admitted to our dermatology outpatient clinic. While performing a clinical examination and taking her medical history, we learned that she was also complaining about mild fever, diarrhea, myalgia, and sore throat. The patient was quickly transferred to the COVID-19 care unit for chest computed tomography (CT), laboratory tests, and nasopharyngeal swab for SARS-CoV-2. Chest CT reported that the patient had bilateral ground-glass opacity, which is related to COVID-19 infection. Hydroxychloroquine and favipiravir medications initiated before the swap result in order to avoid the progression of the disease. The patient had a positive result on PCR analysis of nasopharyngeal swab for SARS-CoV-2. By monitoring this patient, we had an experience that cutaneous manifestation of COVID-19 disease might be an important clue for early diagnosis. Physicians should be aware of the spectrum of cutaneous manifestations of COVID-19 disease in order to avoid missing or delayed diagnosis.
The main limitation of our study was that histological findings or viral particles cannot be investigated in the skin lesions due to lack of laboratory capacity and financial support. Differentiation of the viral eruption from drug eruption is a problematic issue, whereas the eruption of a particular viral infection had not been identified adequately. In this point of view, two of our patients who did not have any history of drug allergy had skin lesions after the hydroxychloroquine treatment. On the other hand, other patients had skin lesions before the diagnosis that increased our suspicion for COVID-19 disease. In the literature, the time of onset of the skin manifestations of COVID-19 disease varies which was compatible with our study.
| Conclusion | | |
We investigated the prevalence and types of cutaneous manifestations of COVID-19 infection in our region to identify the burden of the disease. Although the incidence of cutaneous manifestations was lower than expected, these symptoms are valuable clues to identify patients or asymptomatic individuals in high-risk populations. Further prospective studies in larger populations are needed to better define the real cutaneous aspect and burden of the disease.
Acknowledgments
I would like to thank all health-care professions around the world who are battling coronavirus pandemic.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Tang K, Wang Y, Zhang H, Zheng Q, Fang R, Sun Q. Cutaneous manifestations of the coronavirus disease 2019 (COVID-19): A brief review. Dermatol Ther 2020;33:e13528.  |
| 2. | Elmas ÖF, Demirbaş A, Özyurt K, Atasoy M, Türsen Ü. Cutaneous manifestations of COVID-19: A review of the published literature. Dermatol Ther 2020;33:e13696. |
| 3. | |
| 4. | Pascarella G, Strumia A, Piliego C, Bruno F, Del Buono R, Costa F, et al. COVID-19 diagnosis and management: A comprehensive review. J Intern Med 2020;288:192-206. |
| 5. | Gane SB, Kelly C, Hopkins C. Isolated sudden onset anosmia in COVID-19 infection. A novel syndrome? Rhinology 2020;58:299-301. |
| 6. | Recalcati S. Cutaneous manifestations in COVID-19: A first perspective. J Eur Acad Dermatol Venereol 2020;34:e212-3. |
| 7. | Galván Casas C, Català A, Carretero Hernández G, Rodríguez-Jiménez P, Fernández-Nieto D, Rodríguez-Villa Lario A, et al. Classification of the cutaneous manifestations of COVID-19: A rapid prospective nationwide consensus study in Spain with 375 cases. Br J Dermatol 2020;183:71-7. |
| 8. | Marzano AV, Genovese G, Fabbrocini G, Pigatto P, Monfrecola G, Piraccini BM, et al. Varicella-like exanthem as a specific COVID-19-associated skin manifestation: Multicenter case series of 22 patients. J Am Acad Dermatol 2020;83:280-5. |
| 9. | Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J, et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases. Transl Res 2020;220:1-3. |
| 10. | Hedou M, Carsuzaa F, Chary E, Hainaut E, Cazenave-Roblot F, Masson Regnault M. Comment on 'cutaneous manifestations in COVID-19: A first perspective' by Recalcati S. J Eur Acad Dermatol Venereol 2020;34:e299-300. |
| 11. | Sachdeva M, Gianotti R, Shah M, Bradanini L, Tosi D, Veraldi S, et al. Cutaneous manifestations of COVID-19: Report of three cases and a review of literature. J Dermatol Sci 2020;98:75-81. |
| 12. | Phan T. Genetic diversity and evolution of SARS-CoV-2. Infect Genet Evol 2020;81:104260. |
| 13. | Fung TS, Liu DX. Human coronavirus: Host-pathogen interaction. Annu Rev Microbiol 2019;73:529-57. |
| 14. | Imbalzano E, Casciaro M, Quartuccio S, Minciullo PL, Cascio A, Calapai G, et al. Association between urticaria and virus infections: A systematic review. Allergy Asthma Proc 2016;37:18-22. |
| 15. | Marzano AV, Cassano N, Genovese G, Moltrasio C, Vena GA. Cutaneous manifestations in patients with COVID-19: A preliminary review of an emerging issue. Br J Dermatol 2020;183:431-42. |
| 16. | Henry D, Ackerman M, Sancelme E, Finon A, Esteve E. Urticarial eruption in COVID-19 infection. J Eur Acad Dermatol Venereol 2020;34:e244-5. |
| 17. | Strommen GL, Pucino F, Tight RR, Beck CL. Human infection with herpes zoster: Etiology, pathophysiology, diagnosis, clinical course, and treatment. Pharmacotherapy 1988;8:52-68. |
| 18. | Tammaro A, Adebanjo GA, Parisella FR, Pezzuto A, Rello J. Cutaneous manifestations in COVID-19: The experiences of Barcelona and Rome. J Eur Acad Dermatol Venereol 2020;34:e306-7. |
[Figure 1]
[Table 1]
|
Search Pubmed for