Factors influencing the outcomes of dermatoses during the COVID-19 outbreak in China: a retrospective study

Background The coronavirus disease 2019 (COVID-19) pandemic subverted people’s lives and potentially affected the management and prognosis of pre-existing dermatoses. The study aims to identify factors influencing the outcomes of dermatoses during a rapid and widespread Omicron outbreak in China following the adjustment of the COVID-19 policy. Materials and methods This retrospective observational study involved outpatients visiting the dermatology department at a tertiary referral hospital in Beijing, China between December 2022 and February 2023. Demographics, COVID-19 characteristics, treatment modalities, and dermatosis outcomes were subjected to statistical analysis. Results The odds ratio (OR) for vitiligo aggravation during COVID-19 was 0.497 [95% confidence interval (CI): 0.254–0.973, p = 0.038] compared to total patients with various dermatoses. Psoriasis patients with a maximum body temperature (Tmax) over 38.6°C during COVID-19 were 2.833 times more likely to experience dermatosis aggravation (OR: 2.833 [1.029–7.803], p = 0.041). Moreover, autoimmune bullous disease (AIBD) patients receiving biologics treatment exhibited a reduced likelihood of aggravation during the COVID-19 outbreak (OR: 0 [0–0.531], p = 0.011). Conclusion Vitiligo exhibits lower aggravation rates during COVID-19 than other dermatoses. A higher body temperature during COVID-19 infection can increase the risk of psoriasis aggravation. Biologics treatment reduces the risk of AIBD aggravation during the COVID-19 outbreak.


Introduction
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the culprit agent of the coronavirus disease 2019 (COVID-19) pandemic, and the Omicron strain currently prevails as the dominant virus type affecting people worldwide.A range of cutaneous manifestations associated with SARS-CoV-2 have been reported, with chilblain-like and maculopapular lesions being the most frequently observed (1).The pathophysiology of such lesions primarily involves the antiviral inflammatory response mounted by the immune system, rather than a direct cytopathic effect of the virus (2).However, studies on the outcomes of various dermatoses during the COVID-19 outbreak have been limited.Here, we aimed to identify factors influencing the prognosis of pre-existing dermatoses during a rapid and widespread Omicron outbreak in China after the adjustment of the COVID-19 policy.

Materials and methods
We performed a single-center retrospective observational study on consecutive outpatients visiting the dermatology clinic at Peking Union Medical College Hospital in China from 21 December 2022 to 4 February 2023, during the first phase of the Omicron pandemic.The study was approved by the Bioethics Committee of Peking Union Medical College Hospital (No. K23C2463).Inclusion criteria were individuals (1) aged 18 years or older; (2) with a pre-existing diagnosis of eczematous disorders, psoriasis, disorders of pilosebaceous units (including acne, folliculitis, rosacea, and hidradenitis suppurativa), vitiligo, autoimmune bullous diseases (AIBD, including pemphigus, bullous pemphigoid, and mucous membrane pemphigoid), or urticaria based on guideline indicators; and (3) with a disease duration exceeding 6 months.Dermatologists provided in-person guidance on completing a paper-based questionnaire to eligible patients during their dermatology clinic appointments, following the acquisition of informed consent.Data on demographics, COVID-19 characteristics, treatments, and dermatosis outcomes were collected.COVID-19 cases were identified by positive results of SARS-CoV-2 nucleic acid or antigen tests within the past 3 months.Aggravation of the dermatosis was defined as the expansion of pre-existing skin lesions, the occurrence of new skin lesions, or the exacerbation of pruritus or pain after COVID-19 infection or within the past 3 months.Biologics treatment included Ixekizumab, Secukinumab, Ustekinumab, Dupilumab, Rituximab, and Benralizumab.p-values, odds ratios (OR), and 95% confidence intervals (CI) for categorical variables were calculated using Pearson's chi-square test.p-values for the continuous variable (age) were calculated using Student's t-test.A p-value less than 0.05 was considered statistically significant.

Clinicodemographic profile of study participants
We contacted all patients who visited our clinic during the study period (n = 1,175).Among them, 568 patients consented to participate and 516 completed the questionnaire.Table 1 summarizes the clinicodemographic profile of participants with various dermatoses.Out of the 516 participants, 267 (51.7%) were female and the average age was 38.8 ± 19.1 years.Twenty-two (4.3%) patients received biologics treatment prior to the Omicron pandemic.Four hundred and thirty (83.3%) patients suffered from SARS-CoV-2 infection in the past month, among whom 396 (92.1%) developed a fever during infection, with an average maximum body temperature (T max ) of 38.6°C ± 0.7°C and a fever duration of 2.4 ± 1.6 days.Notably, subjects with AIBD exhibited the lowest T max (38.2°C ± 0.8°C), while those with disorders of pilosebaceous units showed the highest (38.8°C ± 0.7°C).The extensive use of systemic corticosteroids in patients with AIBD may partly contribute to this phenomenon.

Outcomes of pre-existing dermatoses during COVID-19 outbreak
Out of the 516 patients, 139 (26.9%) experienced aggravation of their pre-existing dermatoses, while 377 (73.1%) did not (Table 2).The number of patients with a recent SARS-CoV-2 infection is 118 (84.9%) for the aggravation group, and 312 (82.8%) for the non-aggravation group.No significant difference was detected in age, sex, biologics treatment, SARS-CoV-2 infection, and COVID-19 characteristics between the aggravation and non-aggravation groups.On univariate analysis, the OR of vitiligo aggravation was 0.497 (95% CI: 0.254-0.973,p = 0.038) compared to the total participants, with no significant OR detected for other dermatoses.Psoriasis patients (Table 3) with a T max over 38.6°C (the average T max of total participants) during COVID-19 were 2.833 times more likely to experience dermatosis aggravation (OR: 2.833 [1.029-7.803],p = 0.041).AIBD patients receiving biologics treatment were less likely to aggravate during the COVID-19 outbreak (OR: 0 [0-0.531],p = 0.011).Meanwhile, biologics treatment did not increase the risk of aggravation for psoriasis patients (OR: 0.977 [0.194-4.156],p = 1).Other factors, including age, sex, SARS-CoV-2 infection, fever, and fever duration, had no significant impacts on outcomes of psoriasis or AIBD.Results for other dermatoses are shown in Supplementary Table 1, with no significant risk factors detected.

Discussion
This study was initiated during a critical period when Omicron was rapidly spreading across China.Stringent COVID-19 regulations have been implemented in China since early 2020, effectively preventing widespread infection among the population.Following the relaxation of these restrictions in December 2022, a significant number of people contracted their first SARS-CoV-2 infection within a relatively short timeframe.
SARS-CoV-2 was known to invade pulmonary cells through angiotensin-converting enzyme 2 (ACE2) receptors.While ACE2 receptors predominantly expressed on pulmonary cells, their nonnegligible expression in epidermal keratinocytes could account for various cutaneous manifestations associated with COVID-19 (3).Moreover, management of patients with chronic dermatological conditions became increasingly challenging during the pandemic, largely due to disruptions in dermatology clinic operations (4).SARS-CoV-2 infection can potentially exert a negative effect on clinical outcomes of pre-existing dermatoses.
Our study provided a novel insight into dermatosis outcomes during the COVID-19 outbreak, revealing that vitiligo, compared to other common dermatoses, exhibited a lower likelihood of aggravation in the COVID-19 era.Vitiligo is a depigmentation cutaneous disorder primarily caused by the destruction of melanocytes, which is mediated by the skin-infiltration of melanocyte-specific CD8+ T cells (5).While cases of de novo or flares of vitiligo triggered by the COVID-19 vaccines have been reported (6), they are generally rare and mild.A retrospective study conducted in China identified treatment delays as the most important risk factor for vitiligo progression and recurrence during the pandemic (7).However, during our study period, treatment delays were no longer a predominant concern, given the relaxation of COVID-19 regulations.The inflammatory response triggered by COVID-19 appeared to have a relatively weaker impact on the prognosis of vitiligo compared to other dermatoses.
Psoriasis is a chronic inflammatory skin condition that can be exacerbated by hyperinflammation and cytokine storm associated with COVID-19.Temporary exacerbation of pre-existing psoriasis following COVID-19 booster vaccination (8) and worsening of psoriasis due to COVID-19 (9) have been reported.Our results showed that a higher T max during COVID-19 could elevate the risk of psoriasis aggravation.The underlying mechanism is likely to involve a more intense cytokine storm, relying on further investigation to be explored.Previous studies have revealed that the use of biologics was not associated with an elevated risk of contracting COVID-19 or with a more severe COVID-19 disease course (10,11).In line with previous reports, our study suggested that biologics treatment did not aggravate the outcomes of pre-existing psoriasis, which may be explained by the suppression of cytokine storm by biologics therapies.
Furthermore, biologics treatment was related to a reduced risk of AIBD aggravation during the COVID-19 outbreak.In our study, seven AIBD patients received biologics treatment and none of them experienced aggravation.However, an association between Rituximab use in AIBD and a higher probability of COVID-19 has recently been reported (12).Dermatologists must carefully weigh the benefits and risks when prescribing biologics in the context of the COVID-19 pandemic.
This observational study provides a snapshot of the clinical outcomes of pre-existing dermatoses during the first phase of the Omicron outbreak in China, following the easing of restrictions.With

Conclusion
In conclusion, this study reveals a lower propensity for vitiligo to aggravate during the COVID-19 outbreak compared to other dermatoses.Furthermore, a higher body temperature during COVID-19 infection can increase the risk of aggravation for psoriasis.Biologics treatment emerges as a protective factor against the aggravation of AIBD during the COVID-19 outbreak.To assess the long-term effects of the Omicron pandemic on the prognosis of major dermatological diseases, larger worldwide studies are anticipated.

TABLE 1
Demographic and clinical features of patients with different dermatological conditions.

TABLE 2
Comparison between patients with aggravation and non-aggravation outcomes of pre-existing dermatoses.

TABLE 3
Comparison between patients with aggravation and non-aggravation outcomes of psoriasis and autoimmune bullous diseases.