J Clin Aesthet Dermatol. 2021;14(9):41–44.
by Kathryn Jayne Tan, MD; Maria Rosa Noliza Encarnacion, MD; Olga Marushchak, MA; and Rina Anvekar, MD
Drs. Tan, Encarnacion, and Anvekar and Ms. Marushchak are with the Department of Dermatology, Icahn School of Medicine at Mount Sinai in New York, New York. Ms. Marushchak is also with Touro College of Osteopathic Medicine in New York, New York.
FUNDING: No funding was provided for this article.
DISCLOSURES: The authors report no conflicts of interest relevant to the content of this article.
ABSTRACT: Coronavirus disease 2019 (COVID-19) was first reported in late December 2019 and, since then, has rapidly taken over the globe, with the scientific world furiously working to gather more data on its effect on people with and without concurrent conditions. The dysregulation of the immune system noted in COVID-19 patients is said to be similar to that seen with psoriasis. The pandemic has affected the management of psoriasis, not only for those under treatment but also those about to begin a new therapy. There has been an increasing number of studies in the current literature focusing on the relationship between psoriasis and COVID-19, offering different perspectives. This is a summary of available data in PubMed supplemented by a manual review of reference lists of included articles. There may be lack of robust evidence to drive approaches to the management of psoriasis during the pandemic; however, we hope that the current literature may provide some clues for safety considerations. The conclusion of this article is that each approach to treatment should be personalized, weighing the benefits and risks in each case separately.
Keywords: Psoriasis, COVID-19, biologics, immunosuppressant, treatment
Psoriasis is caused by an inappropriate activation of T-cells and dendritic cells, which eventually results in the upregulation of inflammatory cytokines, such as interleukin (IL)-17, IL-23, and tumor necrosis factor alpha (TNF-alpha).1 Clinically, psoriasis may present with erythematous scaly plaques, pustular eruptions, or generalized cutaneous erythema, with or without nail and joint manifestations.2
Meanwhile, coronavirus disease 2019 (COVID-19) is a disease that rapidly took over the globe only recently, and we have yet to fully understand this condition. It was first reported in late December 2019 and, since then, the scientific world has been working to gather more data on its effect on people with and without concomitant conditions. The immunological abnormalities described in patients with COVID-19 can also be observed in auto-inflammatory or autoimmune conditions such as psoriasis. Several studies have shown that the increase in inflammatory cytokines in psoriasis is similar to that found in COVID-19 patients in a manner corresponding to a hyper-responsive activation of the immune system also known as cytokine storm.3
In this review, we discuss the following: (1) the impact of psoriasis on COVID-19, (2) the impact of COVID-19 on psoriasis, (3) the impact of COVID-19 on the selection of psoriasis therapies, and (4) the impact of COVID-19 therapies such as hydroxychloroquine on psoriasis.
Impact of Psoriasis on COVID-19
As psoriasis is an auto-inflammatory and autoimmune condition that manifests cutaneously, it may weaken the skin barrier, increasing the risk of bacterial, viral or fungal infections.4 Additionally, the dysregulation of cytokine proliferation may have destructive effects by inducing an inflammatory response, leading to more serious infections.4,5 During the pandemic, it was postulated that the risk of contracting the virus and experiencing serious complications is higher than average in patients with psoriasis.5 A study by Kutlu et al.6 revealed that psoriasis has been one of the top concomitant conditions present in patients with COVID-19, which may be due to the stress burden caused by the pandemic leading to frequent consults or the use of immunosuppressive drugs. Many treatment options for psoriasis directly or indirectly affect immune pathways associated with COVID-19.7 While there is no certainty whether the susceptibility is caused by the presence of psoriasis, its severity, or immunomodulator involvement, there is consensus among the experts that many comorbidities associated with psoriasis may be risk factors for increased mortality rates among patients with COVID-19.7
Impact of COVID-19 on Psoriasis
COVID-19 has been thought to worsen chronic inflammatory conditions by driving a negative impact of quarantine on the daily activities of patients, aggravating comorbidities such as obesity, hypertension, and diabetes, which are well-known to be associated with psoriasis.8 Additionally, frequent handwashing and sanitizing predisposes individuals to develop skin cracks, further compromising the skin integrity and increasing the risk of infection in psoriasis.9 Psoriasis is a multifactorial condition; thus, many factors can trigger the disease in genetically predisposed individuals.2,10 During the COVID-19 pandemic, there have been case reports showing that infected patients experience a state of hyperinflammation, which may exacerbate their psoriasis status.6,10 It has also been hypothesized that psoriasis flareups may be induced by therapies in use against COVID-19.6
The bidirectional relationship between psoriasis and COVID-19 has led to numerous studies showing the impact of COVID-19 on patients with inflammatory, immune-mediated conditions like psoriasis and vice versa as well as on the management of psoriasis, specifically the use of immunosuppressive medications.
Impact of COVID-19 on the Selection of Psoriasis Therapies
Approximately one in six individuals with psoriasis have moderate-to-severe disease that requires systemic treatments, such as biologics or oral medications.11 Some patients chose to discontinue their treatment temporarily due to the fear of increased susceptibility to COVID-19 while on therapy.12 Some case reports show that psoriasis still remains in remission in COVID-19-positive patients who temporarily discontinue their biologics.13 On the other hand, reports of patients who have continued their biologic treatment but who did not develop any COVID-19 symptoms despite exposure to infected individuals suggest that biologic therapy may play a protective role.13 The following are the different available psoriasis medications with accompanying evidence-based findings of their safety during this pandemic.
Cyclosporine (CSA). CSA is a calcineurin inhibitor that binds cellular cyclophilins and blocks the translocation of the nuclear factor of activated T-cells from the cytosol into the nucleus, preventing the transcription of IL-2.14 Several viruses require the same cyclophilins for replication.15 Interestingly, inhibition by CSA can block the replication of all genera of coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).16 In patients treated with CSA, a study revealed that there were no cases of COVID-19-related deaths nor hospitalizations and that there is no evidence to support a preventative discontinuation of CSA during the pandemic.7,17
Methotrexate. Methotrexate is an antifolate agent that significantly decreases IL-6 and TNF-alpha and increases regulatory T-cells, providing the anti-inflammatory effect in treating psoriasis.18 In a retrospective study by Kutlu et al., two of 93 COVID-19 patients with previous dermatologic comorbidities were on methotrexate when infected with SARS-CoV-2. This finding made the authors speculate that the medication may increase one’s vulnerability to COVID-19.6 However, there are studies that also provide a strong rationale for the use, albeit in the context of a clinical trial, of high-dose methotrexate in combination with antiviral medications for the treatment of the COVID-19 cytokine storm due to the aforementioned anti-inflammatory properties.18
Acitretin. Acitretin is an oral retinoid approved by the Food and Drug Administration for the treatment of psoriasis which is both anti-inflammatory and anti-proliferative in nature.19 Unlike cyclosporine and methotrexate, it does not suppress the immune system and has been safely used in psoriasis patients with a history of chronic infection such as hepatitis B or C, human immunodeficiency virus, or malignancy.20 In an observational cohort study, no increase in the rate of overall serious infections was observed among acitretin-treated patients versus methotrexate-treated ones; the medication was concluded to be safe to use during the pandemic.21
Apremilast. Apremilast, an oral phosphodiesterase-4 inhibitor, was suggested to be protective against COVID-19 in a case report by Olisova et al.,22 who described a psoriasis patient treated with apremilast who had significant exposure to symptomatic family members and was expected to have a poor prognosis due to risk factors, yet did not develop any symptoms. A case series by Queiro Silva et al.23 showed that apremilast may be a safe alternative for dermatology patients in cases of clinically active infection; a patient on apremilast infected with COVID-19 and one with an infected spouse presented the mildest symptoms and the best safety profile. The safety of the medication and its probable protection were hypothesized to be due to its mechanism of action whereby the final pathway decreases TNF-alpha expression, which is markedly increased during COVID-19.22
Biologics. Biologic agents have become game-changers and staple medications in psoriatic treatment efforts. However, concerns regarding their safety in the context of viral infection have emerged, with a focus on the possibility of increased infection risk as these agents are considered “immunosuppressive.”11 Since biologics inhibit specific pathways involving cytokines, there is a theoretical risk of increased susceptibility to infection. According to a case-control study performed by Damiani et al.24 on the impact of biologics among psoriatic patients, those who were on biologics were at greater risk for COVID-19 as well as for being hospitalized or self-quarantined at home. However, the risks of being admitted to the intensive care unit and of dying did not differ from those of the general population.
Among the different classes of biologics, TNF-alpha inhibitors play an important role in the immune response against pathogens and granuloma formation, which increases the risk for serious infections such as pneumonia, upper respiratory infections, hepatitis, and tuberculosis.25,26 IL-12 and IL-23 are involved in the activation of interferon-gamma and are crucial in immunity against bacteria, viruses, fungi, and parasites.27 IL-17 plays a role in mucosal immunity and, hence, biologics targeting IL-17 are postulated to increase the risk for respiratory tract infections (RTIs).28 A meta-analysis was performed from the placebo-controlled period of a phase III pivotal IL-17 inhibitor trials in terms of consistency with RTIs of secukinumab, ixekizumab, and brodalumab. An increased risk of RTIs was found in the IL-17 group as compared to the placebo one.28 However, because there was no objective testing and because of the substantial variation in the rates of RTIs across trials, it is difficult to fully evaluate the risk. The meta-analysis recommended that clinicians use their clinical judgment in deciding whether continue or discontinue biologics in asymptomatic patients or those who have not tested positive and to discontinue them in patients who test positive for SARS-CoV-2.28 Due to the suboptimal data available at this time, there is fear among patients with regards to continuing these medications during a pandemic. In two tertiary hospitals in Toronto, Canada, it was observed that seven (0.5%) of 1,390 patients on a biologic agent for psoriasis discontinued treatment due to COVID-19 concerns, and a contributing factor to the low rates of biologic discontinuation was because providers offered telephone visits to patients who had concerns regarding their medication.12
On the other hand, the management of psoriasis with selective immunosuppressants or immunomodulatory drugs appears to be useful in controlling the exaggerated immune response against COVID-19. Biologic therapies do not seem to increase the severity of COVID-19 or its complications.29 In northern Italy, a retrospective multicenter observational study revealed that there were no deaths from COVID-19-related disease in the study population, which included 5,206 psoriatic patients being treated with biologic therapy.30 A retrospective observational study in Verona, Italy, showed that patients on biologics showed no early signals of increased hospitalization or death rates.31
TNF-alpha inhibitors decrease the penetration of SARS-COV-2 into the cell by reducing the TNF-alpha-converting enzyme-dependent shedding of the ACE2 ectodomain.32 Anti-TNF-alpha medications may be a promising therapy for COVID-19 infection as there was a case report wherein concomitant adalimumab therapy did not lead to any respiratory distress or COVID-19 complications in a 57-year-old male psoriatic patient who was infected with the SARS-CoV-2 virus.33 IL-17 inhibitors may also play a role in suppressing the cytokine storm responsible for tissue damage and pulmonary edema.34 Hence, it may be beneficial for patients with psoriasis to continue their treatment, even during the COVID-19 pandemic. In addition, continuing these medications is beneficial in controlling disease flares and related sequelae. However, clinical judgment should be used by clinicians regarding whether or not to continue using these medications in patients who have not tested positive or who are symptomatic for COVID-19.35 IL-23 inhibitors also inhibit the IL-17 pathway rather indirectly.36 These medications may actually play a role in controlling the hyperinflammatory state, resulting in severe symptoms. There is a reported case of a 40-year-old female with psoriasis on guselkumab, an IL-23 inhibitor, who eventually contracted COVID-19 virus, presenting with severe cough associated with myalgia, fatigue, and fever.37 The patient reported a major improvement in her respiratory condition, normalization of her temperature, and relief from myalgia and fatigue the day after she administered her guselkumab injection. This shows that IL-23 may play a role in the hyperinflammatory state of COVID-19 leading to severe symptoms.37
There have been studies showing that immunosuppressed patients, as compared with the general population, are not at an increased risk for severe disease and complications.38 There is no available evidence that supports the discontinuation of biologic medications due to possible risk of infection. Galluzzo et al.39 reported that in their practice, no evidence favoring the discontinuation of secukinumab in patients with moderate-to-severe plaque psoriasis and that it does not appear to increase the risk of secondary infections even during COVID-19. However, discontinuing biologics during the time of COVID-19 only causes mild to moderate exacerbation of psoriasis.35 Hence, dermatologic societies recommend that treatment with immunosuppressive or biologic therapy in COVID-19-positive patients be postponed until the patient recovers from the infection.6
Impact of COVID-19 Therapies Such a Hydroxychloroquine (HCQ) on Psoriasis
HCQ is an epidermal transglutaminase inhibitor as well as promoter of IL-17 production through p38-dependent IL-23 release resulting in keratinocyte growth and differentiation.40 There have been reports about the role of HCQ in decreasing viral load in patients with COVID-19 infection.41 However, the medication has been reported to trigger psoriatic flares.10
According to a systematic review done by Sachdeva et al. on the correlation of psoriasis and HCQ treatment, it was found that HCQ may result in induction, exacerbation or relapse of psoriasis.42 In a case report by Kutlu and Metin, a patient with COVID-19 has developed an exacerbation of psoriasis after being treated with oseltamivir and HCQ. It was postulated that such a reaction was mainly due to the high dose intake of HCQ which promoted IL-17 production thereby causing the exacerbation.40 Hence, it is suggested that monitoring for adverse effects of HCQ treatment is necessary. Further clinical trials with a larger population are needed to characterize the safety profile of this medication in psoriatic patients with COVID-19 infection.
It is important to note that there is no difference in the management of COVID-19 in patients with or without psoriasis. Patients with dermatologic disorders, as compared to the normal population, do not have increased severity of the disease nor a greater need for hospitalization.34 Despite the studies showing the safety of these therapies for psoriasis patients in the era of COVID-19, the decision is still based on the combined judgment of the physician and his or her patient. We know that a lot of factors affect treatment decision making and this includes age, presence of other comorbidities and being in a high-risk environment for infection, among others. Patients should continue to be educated and well-informed about their condition in order to maintain or even improve treatment adherence during these times.
- Hawkes, J, Chan, T, Krueger, J. Psoriasis pathogenesis and the development of novel targeted immune therapies. J Allergy Clin Imunol. 2017;140(3):645–653.
- Kimmel GW, Lebwohl M. Psoriasis: overview and diagnosis. In: Bhutani T., Liao W, Nakamura M, eds. Evidence-Based Psoriasis. Updates in Clinical Dermatology. New York, NY: Springer, 2018: 1–16.
- Zeng F, Huang Y, Guo, Y et al. Association of inflammatory markers with the severity of COVID-19: A meta-analysis. Int J Infect Dis. 2020;96,467–474.
- Samotij D, Nedoszytko B, Bartosinska, J, et al. Pathogenesis of psoriasis in the “omic” era. Part I. Epidemiology, clinical manifestation, immunological and neuroendocrine disturbances. Postepy Dermatol Alergol. 2020;37(2):135–153.
- Naldi L. Risk of infections in psoriasis. a lesson to learn during the SARS-CoV-2 pandemic. Br J Dermatol. 2021;184(1):6.
- Kutlu Ö, Metin A. Dermatological diseases presented before COVID-19: are patients with psoriasis and superficial fungal infections more vulnerable to the COVID-19? Dermatol Ther. 2020;33(4):e13509.
- Gelfand JM, Armstrong AW, Bell S, et al. National Psoriasis Foundation COVID-19 Task Force guidance for management of psoriatic disease during the pandemic: version 1. J Am Acad Dermatol. 2020;83(6):1704–1716.
- Marasca C, Ruggiero A, Napolitano M, et al. May COVID-19 outbreaks lead to a worsening of skin chronic inflammatory conditions?. Med Hypotheses. 2020;143:109853.
- Medical News Today. Hand washing: wxpert advice for people with skin Available at: https://www.medicalnewstoday.com/articles/hand-washing-advice-for-people-with-skin-conditions. Accessed December 14, 2020.
- Ozaras R, Berk A, Ucar D, et al. COVID-19 and exacerbation of psoriasis. Dermatol Thera. 2020;33(4):e13632.
- Yeung H, Takeshita J, Mehta NN, et al. Psoriasis severity and the prevalence of major medical comorbidity: a population-based study. JAMA Dermatol. 2013;149(10):1173–1179.
- Georgakopoulos JR, Yeung J. Rate of patient-driven biologic treatment discontinuation during the COVID-19 pandemic in 2 academic hospital clinics at the University of Toronto. J Cutan Med Surg. 2020;24(4):424–425.
- Conti A, Lasagni C, Bigi L, Pellacani G. Evolution of COVID-19 infection in four psoriatic patients treated with biological drugs. J Eur Acad Dermatol Venereol. 2020;34(8):e360–e361.
- Lee JU, Kim LK, Choi JM. Revisiting the concept of targeting NFAT to control T cell immunity and autoimmune diseases. Front Immunol. 2018;9:2747.
- Tanaka Y, Sato Y, Sasaki T. Suppression of coronavirus replication by cyclophilin inhibitors. Viruses. 2013;5(5):1250–1260.
- Lai Q, Spoletini G, Bianco G et al. SARS-CoV2 and immunosuppression: a double-edged sword. Transpl Infect Dis. 2020;22(6):e13404.
- Di Lernia V, Goldust M, Feliciani C. COVID-19 infection in psoriasis patients treated with cyclosporin. Dermatol Ther. 2020;33(4):e13739.
- Safavi F, Nath A. Silencing of immune activation with methotrexate in patients with COVID-19. J Neurol Sci. 2020;415:116942.
- Zito PM, Mazzoni T. Acitretin. [Updated 2020 Sep 29]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2020.
- Lee CS, Li K. A review of acitretin for the treatment of psoriasis. Expert Opin Drug Saf. 2009;8(6):769–779.
- Ricardo JW, Lipner SR. Considerations for safety in the use of systemic medications for psoriasis and atopic dermatitis during the COVID-19 pandemic. Dermatol Ther. 2020;33(5):e13687.
- Olisova OY, Anpilogova EM, Svistunova DA. Apremilast as a potential treatment option for COVID-19: no symptoms of infection in a psoriatic patient. Dermatol Ther. 2020;33(4):e13668.
- Queiro Silva R, Armesto S, González Vela C, et al. COVID-19 patients with psoriasis and psoriatic arthritis on biologic immunosuppressant therapy vs apremilast in North Spain. Dermatol Ther. 2020;33(6):e13961.
- Damiani G, Pacifico A, Bragazzi NL, Malagoli P. Biologics increase the risk of SARS-CoV-2 infection and hospitalization, but not ICU admission and death: real-life data from a large cohort during red-zone declaration. Dermatol Ther. 2020;33(5):e13475.
- Warren RB, Smith CH, Yiu ZZN, et al. Differential drug survival of biologic therapies for the treatment of psoriasis: a prospective observational cohort study from the British association of dermatologists biologic interventions register (BADBIR). J Invest Dermatol. 2015;135(11):2632–2640.
- Kalb RE, Fiorentino DF, Lebwohl MG, et al. Risk of serious infection with biologic and systemic treatment of psoriasis: results from the psoriasis longitudinal assessment and registry (PSOLAR). JAMA Dermatol. 2015;151(9): 961–969.
- Watford W, Hissong B, Bream J, et al. Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4. Immunol Rev. 2004;202(1):139–156.
- Wan MT, Shin DB, Winthrop KL, Gelfand JM. The risk of respiratory tract infections and symptoms in psoriasis patients treated with interleukin 17 pathway-inhibiting biologics: a meta-estimate of pivotal trials relevant to decision making during the COVID-19 pandemic. J Am Acad Dermatol. 2020;83(2):677–679.
- Strippoli D, Barbagallo T, Prestinari F, et al. Biologic agents in psoriasis: our experience during coronavirus infection. Int J Dermatol. 2020;59(8):e266–e267.
- Gisondi P, Facheris P, Dapavo P, et al. The impact of the COVID-19 pandemic on patients with chronic plaque psoriasis being treated with biological therapy: the Northern Italy experience. Br J Dermatol. 2020;183(2): 373–374.
- Gisondi P, Zaza G, Del Giglio M, et al. Risk of hospitalization and death from COVID-19 infection in patients with chronic plaque psoriasis receiving a biologic treatment and renal transplant recipients in maintenance immunosuppressive treatment. J Am Acad Dermatol. 2020;83(1):285–287.
- Wu J, Deng W, Li S, Yang X. Advances in research on ACE2 as a receptor for 2019-nCoV. Cell Mol Life Sci. 2021;78(2):531–544.
- Valenti M, Facheris P, Pavia G, et al. Non-complicated evolution of COVID-19 infection in a patient with psoriasis and psoriatic arthritis during treatment with adalimumab. Dermatol Ther. 2020;33(4):e13708.
- Nobari NN, Goodarzi A. Patients with specific skin disorders who are affected by COVID-19: What do experiences say about management strategies? A systematic review. Dermatol Ther. 2020;33(6):e13867.
- Torres T, Puig L. Managing cutaneous immune-mediated diseases during the COVID-19 pandemic. Am J Clin Dermatol. 2020;21(3): 307–311.
- Hawkes JE, Yan BY, Chan TC, Krueger JG. Discovery of the IL-23/IL-17 signaling pathway and the treatment of psoriasis. J Immunol. 2018;201(6):1605–1613.
- Benhadou F, Del Marmol V. Improvement of SARS-CoV-2 symptoms following guselkumab injection in a psoriatic patient. J Eur Acad Dermatol Venereol. 2020;34(8):e363–e364.
- Magnano M, Balestri R, Bardazzi F, et al. Psoriasis, COVID-19, and acute respiratory distress syndrome: focusing on the risk of concomitant biological treatment. Dermatol Ther. 2020;33(4):e13706.
- Galluzzo M, Tofani L, Bianchi L, Talamonti M. Status of a real-life cohort of patients with moderate-to-severe plaque psoriasis treated with secukinumab and considerations on the use of biological agents in the COVID-19 era. Expert Opin Biol Ther. 2020;20(8):829–830.
- Kutlu Ö, Metin A. A case of exacerbation of psoriasis after oseltamivir and hydroxychloroquine in a patient with COVID-19: will cases of psoriasis increase after COVID-19 pandemic? Dermatol Ther. 2020;33(4):e13383.
- Liu WD, Chang SY, Lan TY, Lin YC, et al. Experience of the use of hydroxychloroquine on patients with COVID-19: a perspective on viral load and cytokine kinetics. J Formos Med Assoc. 2021;120(5):1269–1273.
- Sachdeva M, Mufti A, Maliyar K, et al. Hydroxychloroquine effects on psoriasis: a systematic review and a cautionary note for COVID-19 treatment. J Am Acad Dermatol. 2020;83(2):579–586.