# Inflammation Causes Exacerbation of COVID-19: How about Skin Inflammation?
## 3 Inflammation Exacerbates COVID-19 Infection
### COVID-19 and Inflammatory Skin Disease
#### 3.3.2. Atopic Dermatitis  
Atopic dermatitis is another major chronic inflammatory skin disease, whose treatment has been changing according to the recent developments in immunology, molecular biology, and biomedical techniques as seen in psoriasis. Atopic dermatitis is considered a Th2-balanced disease often associated with bronchial asthma, allergic rhinitis, allergic conjunctivitis, and food allergy [55]. Atopic dermatitis has been reported to be associated with an increased risk of COVID-19 in some research [56; 57; 58] and with decreased risk [59; 60; 61] or no difference in other studies [60; 61; 62].  
Dupilumab, the antibody against IL-4 receptor \(\alpha\), which blocks IL-13 and IL-4 signaling, brings back Th2-balanced immunity to the Th1-balanced direction and normalizes the immune status [63]. Th2 immunity usually tethers the immune defense against viral or bacterial infections, and the atopic dermatitis patients are vulnerable to infections such as herpes simplex and staphylococcus or streptococcus species, and bringing back to the Th1-balanced direction by dupilumab may theoretically strengthen the defensive action against infectious insults in atopic dermatitis patients [46]. Dupilumab has been shown to reduce the risk of serious infection, including skin infections and herpes simplex infection, by pooled analysis of double-blind placebo-controlled studies [64], and may thus result in reduced infection in COVID-19. Dupilumab has been shown in several cohort studies to reduce the risk of COVID-19 infection [61], although another report did not show a decreased risk [62]. A large retrospective study demonstrated a slightly increased risk of COVID-19 infection in adult AD patients, and dupilumab decreased it [55]. Dupilumab also reduced the risk of COVID-19 infection in asthma patients [62; 65].  
Asthma patients express an increased level of TMPRSS2, enzymes needed for SARS-CoV-2 entry to cells, in their nasal mucosa, and are thus considered vulnerable to its infections; on the other hand, the level of the ACE2 expression, the receptor for SARS-CoV-2, has been reported decreased according to the increased exposure to environmental allergens, which may protect them from SARS-CoV-2 infection. Asthma patients present similar symptoms as COVID-19, such as recalcitrant cough and dyspnea; thus, caution is needed to carefully distinguish the symptoms of exacerbation of asthma from COVID-19 [66]. In addition, virus infection, including COVID-19, can exacerbate asthma and other allergic disease symptoms, and telemedicine is recommended for those who do not need face-to-face medical examination during the COVID-19 pandemic [66].  
Systemic corticosteroids are sometimes used in acute exacerbation in atopic dermatitis patients, but prolonged use of systemic corticosteroids has been reported to be associated with an increased risk of severe COVID-19 infection [67]. Acute exacerbation of atopic dermatitis makes patients susceptible to percutaneous infections. [PERSON] et al. reported that moderate-to-severe AD patients are at a higher risk of COVID-19 infection and of having a more severe course. They are also at a higher risk of discontinuation of treatment and at higher anxiety levels [68]. As reported in psoriasis, atopic dermatitis patients are also recommended to continue their treatment, whether it is systemic or topical, to avoid acute exacerbation due to cessation of the treatment [69; 70].