This is a technical review of scientific literature
Several recent studies suggest the possibility of a skin rash being a clinical presentation of coronavirus disease 2019 (COVID-19). The purpose of this case report is to bring attention to skin manifestations in the early stage of COVID-19 in order to support frontline physicians in their crucial activity of case identification.
In light of recent studies, this case report suggests that skin manifestations, when taken into account with other situational factors (such as profession and patient history) should be taken into proper consideration by frontline physicians as possibly being caused by SARS-CoV-2. Early identification of COVID-19 is a key part of the strategy of case detection and case isolation. To enhance this activity, further research is needed to establish frequency, symptoms, signs, and pathogenesis of skin manifestations in patients with COVID-19.
During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, the sudden appearance of a skin rash in a patient with no other etiology to explain its clinical presentation should encourage physicians to consider a possible coronavirus disease 2019 (COVID-19) diagnosis. This is particularly true for high-risk populations, even if, to the best of current knowledge, no specific cutaneous manifestation should be considered pathognomonic for COVID-19. The probability of a skin rash being an early sign of an underlying SARS-CoV-2 infection should be evaluated in light of the patient's epidemiological risk profile and the local epidemiological situation. To this end, it is important to note that skin manifestations are currently reported as rare signs of the disease.
Further research is needed to improve current knowledge about epidemiology, clinical presentation, and pathogenesis of COVID-19 skin manifestations. This is necessary in order to understand if the sudden appearance of an isolated skin rash could justify the routine prescription of home isolation and/or further patient testing to determine the presence or not of a SARS-CoV-2 infection, especially in primary care settings.
Excluding asymptomatic cases, clinical presentations of COVID-19 can range from a mild respiratory infection (common coldlike illness, 80%) to severe pneumonia (14%). In a percentage of these cases, the patient's pneumonia can degenerate to potentially lethal acute respiratory distress syndrome (5%). The most commonly reported clinical manifestations of SARS-CoV-2 infection include fever (8399%), cough (5982%), fatigue (4470%), anorexia (4084%), shortness of breath (3140%), and myalgias (1135%). Other, less specific symptoms include sore throat, nasal congestion, headaches, conjunctivitis, and gastrointestinal manifestations, such as nausea and diarrhoea. Additionally, according to a recent metanalysis, olfactory and taste disorders have been reported in 4453% of patients with COVID-19. These symptoms have assumed increasing importance in the identification of COVID-19 possible cases: the presence of an isolated anosmia, in the United Kingdom, is sufficient to identify the patient as a suspect case and prescribe home isolation and an oropharyngeal swab for the detection of SARS-CoV-2.
The Use Case
Seven days after the onset of the skin rash, the patient developed a fever (37.5 C, axillary) and watery diarrhoea (three to four episodes per day). As a result of these developments, she called her general practitioner (GP), who performed a comprehensive remote telephone assessment and identified her as a suspected COVID-19 case. This diagnosis was based on the presence of fever, a typical and well-known symptom of COVID-19, and due to her epidemiological high-risk profile (being a healthcare professional exposed to several patients with known COVID-19).
It should be noted that the patient did not have any chronic disease and had no personal or family history of autoimmune illness, atopy, or other skin problems. She did not smoke or consume alcohol. Furthermore, she did not have any ongoing chronic treatments, nor had she taken any new drugs in the weeks before the symptoms' onset.
The GP evaluated the patient's skin rash during this first remote consultation via pictures the patient took herself. The patient was told to quarantine at home, ensure an appropriate fluid intake, and self-medicate with paracetamol 500 mg if needed to manage the symptoms. To treat the skin rash, her GP prescribed an oral H1-antihistamine (cetirizine 10 mg once per day). As the patient was living alone (she was already living in self-isolation in order to reduce the possibility of infecting her family members), her GP started telemonitoring her case via scheduled follow-up calls at 3-day intervals.
During the first week of her remote monitoring, the patient began gradually experiencing a dry cough. The fever showed an intermittent trend during the day, higher in the evening but never higher than 37.5 C. Her diarrhoea gradually improved (from watery diarrhoea to occasional episodes of unformed stool rushes). The itchy rash improved with the administration of oral H1- antihistamine, disappearing after 10 days.
Thirteen days after the onset of symptoms and 7 days after the appearance of fever, the patient was tested for SARS-CoV-2 infection with an oropharyngeal swab (real-time polymerase chain reaction [RT-PCR]), and her results were positive. During the whole period of remote monitoring, the vital signs of the patient remained stable, and she never reported dyspnoea.
At the onset of her illness, the patient reported a severe itchy skin rash with pruritus that worsened during the night, making it difficult for her to rest. Scabies, a skin infestation caused by the mite Sarcoptes scabiei, is a frequent cause of severe pruritus, where pruritus is due to a delayed hypersensitivity response to the mite proteins. The patient had no history indicating an increased likelihood to contract scabies or the disease-specific linear skin burrows. As a result, scabies was quickly excluded as a diagnosis. Another frequent cause of pruritus is an adverse drug reaction. Almost any drug may induce pruritus by various pathogenic mechanisms. Drug-induced skin manifestations represent a challenging differential diagnosis in patients with COVID-19 with skin manifestations. In fact, different medications have been used to treat COVID-19 in both hospital and outpatient settings, and many of them are known to cause cutaneous side effects. For this reason, it can be hard to establish causation between COVID-19 infection and skin eruptions when dealing with patients who have received these medications. In this case, we can exclude an adverse drug reaction due to the fact that the patient did not receive a COVID-19specific drug treatment. Moreover, the skin rash was the first manifestation of the disease while the patient had no history of recent or chronic drug intake.
Other common causes of itchy skin rashes could also be reasonably excluded: the patient did not have any chronic physical or mental illnesses, lived in good hygienic conditions, did not use aggressive soaps or cosmetics, was not pregnant, and had no personal or family history of autoimmune illness, atopy, or other skin problems.
The occurrence of erythematous and itchy skin lesions linked to COVID-19, like those in our patient's case, has been reported by several studies. Sachdeva et al. highlighted that cutaneous manifestations of COVID-19 can range from maculopapular exanthem (as in our patient's case) to papulovesicular rash, urticaria, painful acral red-purple papules, livedo reticularis lesions, and petechiae. In some cases, these lesions occurred prior to the onset of respiratory symptoms.
The occurrence of erythematous and itchy skin lesions linked to COVID-19 have been reported by several studies, supporting our hypothesis of an association between a COVID-19 infection and our patient's skin rash. The period of communicability of an individual infected with SARS-CoV-2 is still uncertain, as is the relationship between viral load, disease severity, and transmission rate. However, some studies suggest that the viral load is highest shortly after the onset of symptoms. This means that the transmission rate of the infection could be higher in the early stages of the disease, making the early identification of possible cases even more important. Early identification of COVID-19 symptoms and possible cases is part of the evolving strategy of case detection and isolation that, in the current phases of coexistence with SARS- CoV-2, is a crucial part of the activity of primary care providers.
Strengths and limitations
Nevertheless, some limitations should be mentioned. To begin with, the patient is a healthcare professional and thus part of a professional group under enormous social and mental strain due to the pandemic. Being part of a professional group that in a health emergency has the duty to care for ill people and is therefore responsible for public well-being is likely to generate stress and stress-related clinical manifestations. In light of the above-mentioned points, we cannot exclude the possibility that the patient's psychological stress could have had an influence on the subjective perception of pruritus, worsening it. However, we believe that in the case of our patient, the role of stress in exacerbating her symptoms was limited, and an alternative diagnosis, such as psychogenic itch, is extremely unlikely. The patient did not have any personal or family history of mental illness, and the screening questionnaire performed during the follow up period for major depressive disorder showed only borderline results.
Second, the absence of a comprehensive physical examination, due to the shortage of personal protective equipment and the massive move to telemedicine for primary care services, could have limited the diagnostic accuracy of the skin rash. However, teledermatology has been shown to be as effective as in- person care, even if the studies thus far have been focused on those done in a dermatology specialist setting. Further studies are needed to compare remote dermatologic assessment with in-person care in a primary care setting performed by GPs.
Finally, since the patient was in close contact with multiple patients with COVID-19, it has not been possible to establish her exact incubation period. She developed the skin rash a few days after many patients she took care of during her shifts began to experience COVID-19 symptoms and then had a positive test result for SARS-CoV-2. The onset of her symptoms is therefore consistent with the mean incubation period of 5.2 days (95% confidence interval, 4.1 to 7.0) described by Li et al..
This study is, to the best of our knowledge, the first primary care case report of a female patient who developed a skin rash as the first clinical manifestation of COVID-19. No cutaneous sign can be considered pathognomonic for SARS-CoV-2 infection, and further studies involving larger patient samples are needed to better understand several aspects of the cutaneous involvement of COVID-19. Areas that merit further study include the causal relationship between the infection and skin lesions, the role of pathogenic mechanisms, the absolute frequency and the frequency of skin lesions at the onset, as well as the disease course, the severity, and the transmission rate when skin involvement is the unique manifestation of the COVID-19. More in general, our knowledge regarding the diagnostic accuracy of signs and symptoms to determine if a patient is affected by SARS-CoV-2 infection is still limited at the point that a recent Cochrane review concluded that, based on currently available data, neither absence nor presence of signs or symptoms are accurate enough to rule in or rule out disease.
This said, the sudden appearance of a skin rash for which other causes could be reasonably excluded should encourage primary care and frontline physicians to consider SARS-COV-2 as a possible underlying diagnosis.