Recent advances in topical treatment for psoriasis: a review

Pathophysiology:

Psoriasis is immune mediated condition which is caused by faulty signals in the body’s immune system. It is believed that psoriasis develops when the immune system tells the body to over-react and accelerate the growth of skin cells. Normally the skin cells mature and are shed from the skin’s surface every 28 to 30 days ^[16]. When psoriasis develops, the skin cells mature in 3 to 6 days and move to skin surface. Instead of being shed, the skin cells pile up, causing the visible lesions. It is also found that genes that cause psoriasis can determine how a person’s immune system reacts ^[17]. There are two main hypotheses about the process that occurs in the development of the disease. The first considers psoriasis as primarily a disorder of excessive growth and reproduction of skin cells. The problem is simply seen as a fault of the epidermis and its keratinocytes. The second hypothesis sees the disease as being an immune-mediated disorder in which the excessive reproduction of skin cells is secondary to factors produced by the immune system ^[18,19].

1.Triggering factors: - Genetic predisposition- psoriasis often runs in families, showing a strong genetic influence. The gene most commonly linked to the disease is HLA-Cw6, especially in people who develop psoriasis at a young age. Other genes affect the immune system and skin cell growth, making some individuals more likely to develop psoriasis when exposed to triggers ^[20,21]. Environmental triggers- In people with a genetic tendency, psoriasis can be triggered or worsened by infections, skin injury, stress, smoking, alcohol, and some medicines. These factors activate the immune system and increase skin inflammation ^[21].

2.Immune Activation: - Dendritic cells become activated in the skin after injury or infection. They process and present antigens to T cells and release inflammatory cytokines such as IL-12 and IL-23. These signals activate and expand Th1 and Th17 T cells, which then migrate to the skin and release cytokines that maintain inflammation and promote psoriasis lesions ^[21,22].

3.Cytokine cascade: - TNF-α, released by immune cells and keratinocytes, drives inflammation in psoriasis by activating more immune cells, promoting keratinocyte growth, and sustaining psoriatic lesions. IL-17A and IL-17F, produced by Th17 cells, trigger keratinocytes to release inflammatory signals, attracting more immune cells and causing skin thickening and psoriasis plaques. IL-23, produced by dendritic cells, helps Th17 cells survive and multiply. This increases the production of IL-17 and IL-22, driving inflammation, keratinocyte overgrowth, and the formation of psoriatic plaques ^[23].

4.Keratinocyte Response: - Hyperproliferation- Keratinocytes grow and divide much faster than normal. This rapid turnover shortens the skin renewal cycle from about 28 days to just a few days, leading to thick, scaly plaques on the skin ^[24]. Abnormal differentiation- Keratinocytes do not mature properly. They retain nuclei in the outer layer (parakeratosis) and fail to form a normal skin barrier, contributing to the thick, scaly appearance of psoriatic plaques ^[25].

5.Inflammatory loop: - Cytokines such as IL-17, IL-22, and TNF-α attract neutrophils and T cells to the skin. This increases inflammation, amplifies the immune response, and contributes to plaque formation and persistence. Munro’s microabscesses form when inflammatory cytokines recruit neutrophils into the epidermis. These neutrophils migrate upward and accumulate in the stratum corneum, resulting in small collections that are characteristic of psoriasis ^[26].

6.Clinical Outcome: - Erythema appears as red skin due to increased blood flow, scaling results from rapid skin cell turnover, and plaques form as thick, raised patches caused by inflammation and excessive skin cell growth due to psoriasis ^[27,28].

Current treatment landscape:

The overall treatment approach for psoriasis begins with evaluation for psoriatic arthritis because regardless of the extent of psoriasis, the presence of active psoriatic arthritis may alter treatment choices in favor of options that are effective for both psoriasis and psoriatic arthritis ^[29]. The goal of psoriasis treatment is to reduce inflammation and lesions, control symptoms and prevent flares ^[30]. Psoriasis requires long-term and individualized treatment. The current treatment landscape includes a wide range of options, from topical therapies and phototherapy for mild disease to systemic agents and targeted biologics for moderate to severe psoriasis ^[29,30]. Advances in understanding disease immunology have led to more effective and selective treatments, improving disease control, safety, and patient quality of life ^[30,31].

1.Topical Therapies:

• Corticosteroids- Topical corticosteroids reduce inflammation, slow excessive skin cell growth, and cause local vasoconstriction by suppressing inflammatory cytokines. Their effectiveness depends on potency, which ranges from class I (superpotent) to class VII (least potent) ^[32]. For lesions on the trunk and limbs, mid- to high-potency corticosteroids are usually effective, while superpotent agents are reserved for thick plaques ^[33]. Low-potency corticosteroids are preferred for sensitive areas such as the face and skin folds to reduce side effects. During active disease, corticosteroids are generally applied twice daily until improvement occurs ^[34,35]. Once lesions settle, intermittent use or combination with agents like vitamin D analogues or calcineurin inhibitors helps maintain remission. Combination formulations offer better results, fewer adverse effects, and longer disease control compared to single-agent therapy ^[36].
• Vitamin D analogues- Topical vitamin D analogues are commonly used in psoriasis for their ability to regulate keratinocyte proliferation and differentiation through activation of vitamin D receptors on skin and immune cells ^[37]. Calcipotriol (calcipotriene) and calcitriol are the most widely used agents, either alone or in combination with topical corticosteroids to enhance efficacy ^[38]. These agents show moderate effectiveness as monotherapy but are particularly useful for long-term maintenance ^[39,40]. They are generally safe when used within recommended limits (≤50 g/week in children and ≤100 g/week in adults) and in the absence of renal impairment. The main adverse effects are mild, transient local irritation and burning, while systemic effects are rare when dosing guidelines are followed ^[40].
• Retinoids- These are vitamin A based agents that help control psoriasis by normalizing skin cell growth and reducing inflammation ^[41]. Topical retinoids, especially tazarotene, are used for localized plaque psoriasis. They can be combined with corticosteroids or vitamin D analogues to improve effectiveness and reduce irritation. Common side effects include redness, burning, and peeling, and application should avoid the face, skin folds, and genitals. Use is contraindicated in pregnancy ^[41,42].
• Calcineurin inhibitors- Tacrolimus and pimecrolimus are topical calcineurin inhibitors that aid in controlling psoriasis by suppressing T-cell activation, as well as, decreasing the inflammatory response (IL-2 and IFN-γ) ^[43]. They are also applicable especially to sensitive regions like the face and folds of the skin since they do not and cannot lead to skin thinning seen in prolonged use of corticosteroids. It has been demonstrated that a maximum of 70 per cent patients can obtain clear or almost clear skin after 8 weeks. The most common side effect is mild local irritation ^[44].

2.Phototherapy: Phototherapy uses either natural sunlight or special UV-emitting equipment to deliver controlled doses, which slow skin cell proliferation and modulate immune responses ^[45].

• UVB- UVB phototherapy treats plaque psoriasis by reducing DNA synthesis, inducing keratinocyte apoptosis, and lowering proinflammatory cytokine production by T cells. It can be delivered as broadband (290–320 nm) or narrowband (311 nm) UVB, with narrowband preferred for greater effectiveness, longer remission, and fewer side effects ^[46]. Treatment usually starts three times per week in clinic or at home, then decreases to twice per week after 2–3 months to maintain results. Side effects include erythema, itching, blistering, photoaging, and long-term skin cancer risk ^[47]. 
• PUVA- PUVA therapy combines a psoralen with UVA light (320–400 nm) to slow keratinocyte proliferation and modulate immune responses in psoriasis ^[48]. It can be administered orally or topically, with treatment typically given 2–3 times per week and adjusted based on response. Side effects include nausea, headache, erythema, burning, and hyperpigmentation, and long-term use increases the risk of skin cancer and photoaging ^[48,49]. PUVA is contraindicated in children, pregnant or lactating women, and patients with severe liver, kidney, or cardiovascular disease, and protective measures like sunglasses are recommended during treatment ^[50].

3.Systemic Therapies: Psoriasis which becomes resistant to topical treatment and phototherapy is treated by medications which can be taken internally by pill or injection.  Patients undergoing systemic treatment are required to have regular blood and liver function tests because of the toxicity of the medication ^[51].

• Methotrexate- Methotrexate is an active and antimetabolic agent that is reserved for severe psoriasis, being administered in a dose of 15 mg once weekly or once every 2 weeks orally or parenterally ^[52]. It is also useful in psoriatic arthritis. A low-dose maintenance treatment may be sustained prior to discontinuation ^[53,54]. The medication is usually well tolerated; the most common side effects are nausea, loss of appetite and pain in the upper abdomen, but occasional monitoring is needed in case of severe toxicity ^[54].
• Cyclosporine- Cyclosporine is a systemic immunomodulatory agent currently used for severe recalcitrant psoriasis. It inhibits T-cell function, with consequent fast resolution of skin lesions. The typical oral dosage is 3 to 5 mg/kg per day given in divided doses, and it is predominantly employed for short-term control. Side effects Incidences of nephrotoxicity and hypertension are significant, and long-term use yields increased susceptibility to infections and neoplasm ^[55].
• Acitretin- Acitretin is a retinoid used systemically to treat moderate to severe psoriasis, including pustular and erythrodermic psoriasis. It treats the disease by “getting skin cell growth back under control,” and can be utilized in conjunction with phototherapy. The dose is usually 25 to 50 mg per day. Side effects tend to be mild, dry skin and lips (cheilitis) and hair loss are common. Since it is highly teratogenic, strict contraception is mandatory and liver functions and lipid profiles should be monitored periodically ^[56].

4.Biologics-

• TNF-α inhibitors- TNF-α inhibitors treat psoriasis by inhibiting a key inflammatory cytokine. In terms of efficacy, infliximab > certolizumab > adalimumab and etanercept has the lowest efficacy ^[57]. These drugs need to be taken more often than IL-17 and IL-23 blockers, and dose escalation is typically accomplished by increasing the dose frequency. Adverse reactions are usually upper respiratory tract infections and injection site reactions ^[58].
• IL-17 inhibitors- IL-17 inhibitors are a class of biologic drugs that inhibit the IL-17 pathway, either by binding to the IL-17 cytokines or to its receptor. Secukinumab and ixekizumab are specific IL-17A inhibitors, bimekizumab is a dual IL-17A and IL-17F inhibitor, and brodalumab binds to the IL-17 receptor A. These agents work quickly and provide potent, long-term control of plaque psoriasis in those who respond. Upper respiratory infections and reactions at the site of injection are common adverse reactions, although mucocutaneous candidiasis and exacerbation of inflammatory bowel disease have been noted ^[59]
• IL-23 inhibitors- IL-23 inhibitors are a class of biologic drugs that bind to the p19 subunit of IL-23, blocking the Th17 inflammatory pathway. The approved drugs for the treatment of plaque psoriasis in adults with this mechanism of action are guselkumab, tildrakizumab, risankizumab and mirikizumab that is under development. While efficacy may differ for each drug, the safety profiles are similar, with no evidence so far of increased rates of serious infections or malignancy ^[60]. Upper respiratory tract infections and reactions at the injection site were the most frequent and generally mild adverse reactions ^[61].

REFERENCES

1. Reid, C.; Griffiths, C.E.M. Psoriasis and Treatment: Past, Present and Future Aspects. Acta Derm.-Venereol. 2020, 100, adv00032.
2. Singh, A.; Easwari, T.S. Recent Advances in Psoriasis Therapy: Trends and Future Prospects. Curr. Drug Targets 2021, 22, 1760–1771.
3. Gyldenløve, M.; Alinaghi, F.; Zachariae, C.; Skov, L.; Egeberg, A. Combination Therapy with Apremilast and Biologics for Psoriasis: A Systematic Review. Am. J. Clin. Dermatol. 2022, 23, 605–613.
4. Hsieh, T.S.; Tsai, T.F. Combination Therapy for Psoriasis with Methotrexate and Other Oral Disease-Modifying Antirheumatic Drugs: A Systematic Review. Dermatol. Ther. 2023, 13, 891–909.
5. Pourani, M.R.; Abdollahimajd, F.; Zargari, O.; Shahidi Dadras, M. Soluble biomarkers for diagnosis, monitoring, and therapeutic response assessment in psoriasis. J. Dermatol. Treat. 2022, 33, 1967–1974.
6. Lwin, S.M.; Snowden, J.A.; Griffiths, C.E.M. The promise and challenges of cell therapy for psoriasis. Br. J. Dermatol. 2021, 185, 887–898.
7. Salgado-Boquete, L.; Carrascosa, J.M.; Llamas-Velasco, M.; Ruiz-Villaverde, R.; de la Cueva, P.; Belinchón, I. A New Classification of the Severity of Psoriasis: What’s Moderate Psoriasis? Life 2021, 11, 627.
8. Mrowietz, U.; Kragballe, K.; Reich, K.; Spuls, P.; Griffiths, C.E.; Nast, A.; Franke, J.; Antoniou, C.; Arenberger, P.; Balieva, F.; et al. Definition of treatment goals for moderate to severe psoriasis: A European consensus. Arch. Dermatol. Res. 2011, 303, 1–10.
9. Oranje, A.P.; Marcoux, D.; Svensson, A.; Prendiville, J.; Krafchik, B.; Toole, J.; Rosenthal, D.; de Waard-van der Spek, F.B.; Molin, L.; Axelsen, M. Topical calcipotriol in childhood psoriasis. J. Am. Acad. Dermatol. 1997, 36, 203–208.
10. Maul, J.T.; Anzengruber, F.; Conrad, C.; Cozzio, A.; Häusermann, P.; Jalili, A.; Kolios, A.G.A.; Laffitte, E.; Lapointe, A.K.; Mainetti, C.; et al. Topical Treatment of Psoriasis Vulgaris: The Swiss Treatment Pathway. Dermatology 2021, 237, 166–178.
11. Elmets, C.A.; Korman, N.J.; Prater, E.F.; Wong, E.B.; Rupani, R.N.; Kivelevitch, D.; Armstrong, A.W.; Connor, C.; Cordoro, K.M.; Davis, D.M.R.; et al. Joint AAD-NPF Guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures. J. Am. Acad. Dermatol. 2021, 84, 432–470.
12. Blauvelt, A.; Leonardi, C.L.; Gooderham, M.; Papp, K.A.; Philipp, S.; Wu, J.J.; Igarashi, A.; Flack, M.; Geng, Z.; Wu, T.; et al. Efficacy and Safety of Continuous Risankizumab Therapy vs Treatment Withdrawal in Patients With Moderate to Severe Plaque Psoriasis: A Phase 3 Randomized Clinical Trial. JAMA Dermatol. 2020, 156, 649–658.
13. Gold, L.S.; Lebwohl, M.G.; Sugarman, J.L.; Pariser, D.M.; Lin, T.; Martin, G.; Pillai, R.; Israel, R.; Ramakrishna, T. Safety and efficacy of a fixed combination of halobetasol and tazarotene in the treatment of moderate-to-severe plaque psoriasis: Results of 2 phase 3 randomized controlled trials. J. Am. Acad. Dermatol. 2018, 79, 287–293.
14. Lis-?wi?ty, A.; Fr?tczak, A. Proactive therapy: New perspectives for long-term topical treatment of psoriasis. Dermatol. Ther. 2022, 35, e15364.
15. Soleymani, T.; Hung, T.; Soung, J. The role of vitamin D in psoriasis: A review. Int. J. Dermatol. 2015, 54, 383–392.
16. Amiri, D.; Schwarz, C.W.; Gether, L.; Skov, L. Safety and Efficacy of Topical Calcineurin Inhibitors in the Treatment of Facial and Genital Psoriasis: A Systematic Review. Acta Derm.-Venereol. 2023, 103, adv00890.
17. Fritz, K.; Salavastru, C. The 308 nm Excimer laser for the treatment of psoriasis and inflammatory skin diseases. Der Hautarzt Z. Dermatol. Venerol. Verwandte Geb. 2018, 69, 35–37
18. Menter, A.; Strober, B.E.; Kaplan, D.H.; Kivelevitch, D.; Prater, E.F.; Stoff, B.; Armstrong, A.W.; Connor, C.; Cordoro, K.M.; Davis, D.M.R.; et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. J. Am. Acad. Dermatol. 2019, 80, 1029–1072.
19. Menter, A.; Gelfand, J.M.; Connor, C.; Armstrong, A.W.; Cordoro, K.M.; Davis, D.M.R.; Elewski, B.E.; Gordon, K.B.; Gottlieb, A.B.; Kaplan, D.H.; et al. Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies. J. Am. Acad. Dermatol. 2020, 82, 1445–1486.
20. Elmets, C.A.; Lim, H.W.; Stoff, B.; Connor, C.; Cordoro, K.M.; Lebwohl, M.; Armstrong, A.W.; Davis, D.M.R.; Elewski, B.E.; Gelfand, J.M.; et al. Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis with phototherapy. J. Am. Acad. Dermatol. 2019, 81, 775–804.
21. Lambert, J.L.W.; Segaert, S.; Ghislain, P.D.; Hillary, T.; Nikkels, A.; Willaert, F.; Lambert, J.; Speeckaert, R. Practical recommendations for systemic treatment in psoriasis according to age, pregnancy, metabolic syndrome, mental health, psoriasis subtype and treatment history (BETA-PSO: Belgian Evidence-based Treatment Advice in Psoriasis; part 1). J. Eur. Acad. Dermatol. Venereol. JEADV 2020, 34, 1654–1665.
22. Armstrong, A.W.; Puig, L.; Joshi, A.; Skup, M.; Williams, D.; Li, J.; Betts, K.A.; Augustin, M. Comparison of Biologics and Oral Treatments for Plaque Psoriasis: A Meta-analysis. JAMA Dermatol. 2020, 156, 258–269.
23. Kimball, A.B.; Rothman, K.J.; Kricorian, G.; Pariser, D.; Yamauchi, P.S.; Menter, A.; Teller, C.F.; Aras, G.; Accortt, N.A.; Hooper, M.; et al. OBSERVE-5: Observational postmarketing safety surveillance registry of etanercept for the treatment of psoriasis final 5-year results. J. Am. Acad. Dermatol. 2015, 72, 115–122.
24. Menter, A.; Thaçi, D.; Wu, J.J.; Abramovits, W.; Kerdel, F.; Arikan, D.; Guo, D.; Ganguli, A.; Bereswill, M.; Camez, A.; et al. Long-Term Safety and Effectiveness of Adalimumab for Moderate to Severe Psoriasis: Results from 7-Year Interim Analysis of the ESPRIT Registry. Dermatol. Ther. 2017, 7, 365–381.
25. Kalb, R.E.; Fiorentino, D.F.; Lebwohl, M.G.; Toole, J.; Poulin, Y.; Cohen, A.D.; Goyal, K.; Fakharzadeh, S.; Calabro, S.; Chevrier, M.; 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, 961–969.
26. Poulin, Y.; Thérien, G. Drug-induced hepatitis and lupus during infliximab treatment for psoriasis: Case report and literature review. J. Cutan. Med. Surg. 2010, 14, 100–104.
27. López-Ferrer, A.; Vilarrasa, E.; Puig, L. Secukinumab (AIN457) for the treatment of psoriasis. Expert Rev. Clin. Immunol. 2015, 11, 1177–1188.
28. Papp, K.A.; Leonardi, C.L.; Blauvelt, A.; Reich, K.; Korman, N.J.; Ohtsuki, M.; Paul, C.; Ball, S.; Cameron, G.S.; Erickson, J.; et al. Ixekizumab treatment for psoriasis: Integrated efficacy analysis of three double-blinded, controlled studies (UNCOVER-1, UNCOVER-2, UNCOVER-3). Br. J. Dermatol. 2018, 178, 674–681.
29. Foulkes, A.C.; Warren, R.B. Brodalumab in psoriasis: Evidence to date and clinical potential. Drugs Context 2019, 8, 212570.
30. Reich, K.; Leonardi, C.; Langley, R.G.; Warren, R.B.; Bachelez, H.; Romiti, R.; Ohtsuki, M.; Xu, W.; Acharya, N.; Solotkin, K.; et al. Inflammatory bowel disease among patients with psoriasis treated with ixekizumab: A presentation of adjudicated data from an integrated database of 7 randomized controlled and uncontrolled trials. J. Am. Acad. Dermatol. 2017, 76, 441–448.E2.
31. Dávila-Seijo, P.; Dauden, E.; Descalzo, M.A.; Carretero, G.; Carrascosa, J.M.; Vanaclocha, F.; Gómez-García, F.J.; De la Cueva-Dobao, P.; Herrera-Ceballos, E.; Belinchón, I.; et al. Infections in Moderate to Severe Psoriasis Patients Treated with Biological Drugs Compared to Classic Systemic Drugs: Findings from the Biobadaderm Registry. J. Investig. Dermatol. 2017, 137, 313–321.
32. Beck, K.M.; Koo, J. Brodalumab for the treatment of plaque psoriasis: Up-to-date. Expert Opin. Biol. Ther. 2019, 19, 287–292.
33. Puig, L. Induction phase, primary endpoint, time to decide on primary failure, and therapeutic goals in biologic treatment of psoriasis. J. Eur. Acad. Dermatol. Venereol. JEADV 2013, 27, e257–e260.
34. Hazlewood, G.S.; Barnabe, C.; Tomlinson, G.; Marshall, D.; Devoe, D.J.; Bombardier, C. Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying anti-rheumatic drugs for rheumatoid arthritis: A network meta-analysis. Cochrane Database Syst. Rev. 2016, 2016, Cd010227.
35. Cather, J.C.; Crowley, J.J. Use of biologic agents in combination with other therapies for the treatment of psoriasis. Am. J. Clin. Dermatol. 2014, 15, 467–478.
36. Ormerod, A.D. Switching biologics for psoriasis. Br. J. Dermatol. 2010, 163, 667–669
37. Özkur, E.; K?vanç Altunay, ?.; O?uz Topal, ?.; Aytekin, S.; Topalo?lu Demir, F.; Özkök Akbulut, T.; Kara Polat, A.; Karada?, A.S. Switching Biologics in the Treatment of Psoriasis: A Multicenter Experience. Dermatology 2021, 237, 22–30.
38. Honda, H.; Umezawa, Y.; Kikuchi, S.; Yanaba, K.; Fukuchi, O.; Ito, T.; Nobeyama, Y.; Asahina, A.; Nakagawa, H. Switching of biologics in psoriasis: Reasons and results. J. Dermatol. 2017, 44, 1015–1019.
39. Armstrong, A.W.; Patel, M.; Li, C.; Garg, V.; Mandava, M.R.; Wu, J.J. Real-world switching patterns and associated characteristics in patients with psoriasis treated with biologics in the United States. J. Dermatol. Treat. 2023, 34, 2200870.
40. Shin, J.O.; Seok Shin, B.; Bae, K.N.; Shin, K.; Kim, H.S.; Ko, H.C.; Kim, M.B.; Kim, B. Review of the reasons for and effectiveness of switching biologics for psoriasis treatment in Korea. Indian J. Dermatol. Venereol. Leprol. 2023, 28, 1–6.
41. Porter, C.; Woods, A.; Mendelow, M.; Purvis, C.; Feldman, S. Unmet Needs in Psoriasis Patients. J. Drugs Dermatol. JDD 2022, 21, 839–844.
42. Egeberg, A.; Ottosen, M.B.; Gniadecki, R.; Broesby-Olsen, S.; Dam, T.N.; Bryld, L.E.; Rasmussen, M.K.; Skov, L. Safety, efficacy and drug survival of biologics and biosimilars for moderate-to-severe plaque psoriasis. Br. J. Dermatol. 2018, 178, 509–519.
43. García-Beloso, N.; Altabás-González, I.; Samartín-Ucha, M.; Gayoso-Rey, M.; De Castro-Parga, M.L.; Salgado-Barreira, Á.; Cibeira-Badia, A.; Piñeiro-Corrales, M.G.; González-Vilas, D.; Pego-Reigosa, J.M.; et al. Switching between reference adalimumab and biosimilars in chronic immune-mediated inflammatory diseases: A systematic literature review. Br. J. Clin. Pharmacol. 2022, 88, 1529–1550.
44. Ghafoor, R.; Patil, A.; Yamauchi, P.; Weinberg, J.; Kircik, L.; Grabbe, S.; Goldust, M. Treatment of Scalp Psoriasis. J. Drugs Dermatol. JDD 2022, 21, 833–837.
45. Thomas, L.; Azad, J.; Takwale, A. Management of nail psoriasis. Clin. Exp. Dermatol. 2021, 46, 3–8.
46. Kelly, A.; Ryan, C. Genital Psoriasis: Impact on Quality of Life and Treatment Options. Am. J. Clin. Dermatol. 2019, 20, 639–646.
47. Misiak-Galazka, M.; Zozula, J.; Rudnicka, L. Palmoplantar Pustulosis: Recent Advances in Etiopathogenesis and Emerging Treatments. Am. J. Clin. Dermatol. 2020, 21, 355–370.
48. Hoegler, K.M.; John, A.M.; Handler, M.Z.; Schwartz, R.A. Generalized pustular psoriasis: A review and update on treatment. J. Eur. Acad. Dermatol. Venereol. JEADV 2018, 32, 1645–1651.
49. Blauvelt, A.; Kimball, A.B.; Augustin, M.; Okubo, Y.; Witte, M.M.; Capriles, C.R.; Sontag, A.; Arora, V.; Osuntokun, O.; Strober, B. Efficacy and safety of mirikizumab in psoriasis: Results from a 52-week, double-blind, placebo-controlled, randomized withdrawal, phase III trial (OASIS-1). Br. J. Dermatol. 2022, 187, 866–877.
50. Krueger, J.G.; McInnes, I.B.; Blauvelt, A. Tyrosine kinase 2 and Janus kinase–signal transducer and activator of transcription signaling and inhibition in plaque psoriasis. J. Am. Acad. Dermatol. 2022, 86, 148–157.
51. Zhang, L.; Guo, L.; Wang, L.; Jiang, X. The efficacy and safety of tofacitinib, peficitinib, solcitinib, baricitinib, abrocitinib and deucravacitinib in plaque psoriasis—A network meta-analysis. J. Eur. Acad. Dermatol. Venereol. JEADV 2022, 36, 1937–1946.
52. Strober, B.; Thaçi, D.; Sofen, H.; Kircik, L.; Gordon, K.B.; Foley, P.; Rich, P.; Paul, C.; Bagel, J.; Colston, E.; et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: Efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 Program for Evaluation of TYK2 inhibitor psoriasis second trial. J. Am. Acad. Dermatol. 2023, 88, 40–51.
53. Madonna, S.; Girolomoni, G.; Dinarello, C.A.; Albanesi, C. The Significance of IL-36 Hyperactivation and IL-36R Targeting in Psoriasis. Int. J. Mol. Sci. 2019, 20, 3318.
54. Hussain, S.; Berki, D.M.; Choon, S.E.; Burden, A.D.; Allen, M.H.; Arostegui, J.I.; Chaves, A.; Duckworth, M.; Irvine, A.D.; Mockenhaupt, M.; et al. IL36RN mutations define a severe autoinflammatory phenotype of generalized pustular psoriasis. J. Allergy Clin. Immunol. 2015, 135, 1067–1070.e1069.
55. Todorovi?, V.; Su, Z.; Putman, C.B.; Kakavas, S.J.; Salte, K.M.; McDonald, H.A.; Wetter, J.B.; Paulsboe, S.E.; Sun, Q.; Gerstein, C.E.; et al. Small Molecule IL-36γ Antagonist as a Novel Therapeutic Approach for Plaque Psoriasis. Sci. Rep. 2019, 9, 9089.
56. Ali, F.; Smith, C.H.; Mahil, S.K. Spesolimab in the treatment of generalized pustular psoriasis: A critically appraised research paper. Br. J. Dermatol. 2023, 188, 328–329.
57. Conti, P.; Pregliasco, F.E.; Bellomo, R.G.; Gallenga, C.E.; Caraffa, A.; Kritas, S.K.; Lauritano, D.; Ronconi, G. Mast Cell Cytokines IL-1, IL-33, and IL-36 Mediate Skin Inflammation in Psoriasis: A Novel Therapeutic Approach with the Anti-Inflammatory Cytokines IL-37, IL-38, and IL-1Ra. Int. J. Mol. Sci. 2021, 22, 8076.
58. Tang, L.; Yang, X.; Liang, Y.; Xie, H.; Dai, Z.; Zheng, G. Transcription Factor Retinoid-Related Orphan Receptor γt: A Promising Target for the Treatment of Psoriasis. Front. Immunol. 2018, 9, 1210.
59. Pandya, V.B.; Kumar, S.; Sachchidanand; Sharma, R.; Desai, R.C. Combating Autoimmune Diseases with Retinoic Acid Receptor-Related Orphan Receptor-γ (RORγ or RORc) Inhibitors: Hits and Misses. J. Med. Chem. 2018, 61, 10976–10995.
60. Zanin-Zhorov, A.; Weiss, J.M.; Trzeciak, A.; Chen, W.; Zhang, J.; Nyuydzefe, M.S.; Arencibia, C.; Polimera, S.; Schueller, O.; Fuentes-Duculan, J.; et al. Cutting Edge: Selective Oral ROCK2 Inhibitor Reduces Clinical Scores in Patients with Psoriasis Vulgaris and Normalizes Skin Pathology via Concurrent Regulation of IL-17 and IL-10. J. Immunol. 2017, 198, 3809–3814.
61. Chen, A.; Luo, Y.; Xu, J.; Guan, X.; He, H.; Xuan, X.; Wu, J. Latest on biomaterial-based therapies for topical treatment of psoriasis. J. Mater. Chem. B 2022, 10, 7397–7417.