# Inflammation Causes Exacerbation of COVID-19: How about Skin Inflammation?
## 3 Inflammation Exacerbates COVID-19 Infection
### COVID-19 and Inflammatory Skin Disease  
#### 3.3.1. Psoriasis  
Psoriasis is one of the major inflammatory skin diseases which affects 2-3% of Western people and 0.2-0.3% of Japanese people. The pathogenesis of psoriasis has been increasingly elucidated due to the rapid development of biological treatments under the recent advancement in immunology, molecular biology, and biomedical techniques. Psoriasis is known for the increased expression of antimicrobial peptides, elevated Th17 and Th1 response, which may cause an increased defense against infectious attacks, including COVID-19. Psoriasis has also been known recently for its association with metabolic syndromes, such as obesity, diabetes mellitus (DM), hypertension, hyperglycemia, and cardiovascular diseases (CVD), as well as with other inflammatory conditions, such as inflammatory bowel disease (IBD), uveitis, arthritis, and psychomotor disorders [20]. These systemic conditions are related to upregulated inflammation and an increased risk of hospitalization caused by COVID-19 in the general population. However, the cohort of psoriasis patients suffering from COVID-19 did not show an increased risk of hospitalization as the above metabolic conditions in the population without skin diseases shows [21; 22; 23; 24; 25; 26; 27]. It could be because the number of patients has been small and the statistical significance is not obvious so far, but could be because of any unknown factors, such as genetic background, causing psoriasis patients to be less susceptible to severe infection. Another explanation could be that psoriasis patients are well-treated with anti-inflammatory agents, such as anti-TNF antibodies and other biologists and immunosuppressive agents, and that they are not at a higher risk of severe infection with COVID-19 [28]. Rebutanoid arthritis is another inflammatory condition often treated with biologics commonly used in psoriasis and psoriatic arthritis treatment. A Danish cohort study on immune-mediated inflammatory diseases (IMIDs) showed an increased risk of COVID-19-related hospitalization and mortality with rheumatoid disease, while those with dermatologic disease and gastrointestinal disease showed a decreased risk [27]. It may be due to the difference in genetic background of these diseases, treatment history, comorbidities, and concomitant treatments, but may be due to an unknown pathophysiological status of these diseases. Several independent studies showed that psoriasis patients under a biologics treatment did not show an increased risk of COVID-19 infection [27; 28; 29; 30; 31; 32; 33; 34; 35; 36], or showed a decreased risk of severe COVID-19 infection [37], although an early study suggested an increased risk of mild-to-moderate COVID-19 infection in biologics-treated psoriasis patients [23]. TNF inhibitors plus MTX in psoriasis patients showed no difference in severe COVID-19 infection, but in certain cohorts [38; 39], this treatment showed a decreased risk of COVID-19 infection and COVID-19-related mortality among IMD patients. Recent studies showed that non-biologics- or biologics-treated psoriasis patients with positive COVID-19 showed a decreased risk of severe COVID-19 infection [39; 40; 41]. These results suggest that IMIDs other than psoriasis treated with non-biologics may have an increased risk of severe COVID-19, while psoriasis patients are not at a higher risk of severe COVID-19 infection when treated either with biologics or non-biologics. In rheumatoid arthritis (RA), biologic DMARDs (bDMARDs), especially TNF inhibitors, decrease the risk of hospitalization, while rituximab and systemic corticosteroids increase the hospitalization risk; thus, the risk of severe COVID-19 infection also depends largely on treatment modalities. Appremilast, one of the phosphodiesteraseerase 4 inhibitors, increases the cellular concentration of cAMP by suppressing the phosphodiesteraseerase activity, thus resulting in the suppression of inflammation.