Phosphodiesterase-4 Enzyme Inhibitors
The mechanisms by which phosphodiesterase-4 (PED4) inhibitors elicit anti-inflammatory effects are not completely understood. Unlike biologics that neutralize inflammatory mediators at the protein level, apremilast modulates mediator production at the level of mRNA expression.
Apremilast (Otezla)
Apremilast is a phosphodiesterase-4 inhibitor specific for cAMP, resulting in increased intracellular cAMP levels. It may affect cytokines and chemokine synthesis, leading to anti-inflammatory effects. It is indicated for moderate-to-severe plaque psoriasis in adults who are candidates for phototherapy or systemic therapy.
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Huynh N, Cervantes-Castaneda RA, Bhat P, Gallagher MJ, Foster CS. Biologic response modifier therapy for psoriatic ocular inflammatory disease. Ocul Immunol Inflamm. 2008 May-Jun. 16(3):89-93. [Medline].
Papp KA, Griffiths CE, Gordon K, Lebwohl M, et al. Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from five years of follow-up. Br J Dermatol. 2013 Jan 10. [Medline].
Kimball AB, Gordon KB, Fakharzadeh S, Yeilding N, Szapary PO, Schenkel B, et al. Long-term efficacy of ustekinumab in patients with moderate-to-severe psoriasis: results from the PHOENIX 1 trial through up to 3 years. Br J Dermatol. 2012 Feb 22. [Medline].
Lebwohl M, Strober B, Menter A, Gordon K, Weglowska J, Puig L, et al. Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis. N Engl J Med. 2015 Oct. 373 (14):1318-28. [Medline]. [Full Text].
Gordon KB, Strober B, Lebwohl M, Augustin M, Blauvelt A, Poulin Y, et al. Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. Lancet. 2018 Aug 25. 392 (10148):650-661. [Medline].
[Guideline] Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol. 2009 Sep. 61(3):451-85. [Medline].
Mrowietz U, de Jong EM, Kragballe K, Langley R, Nast A, Puig L, et al. A consensus report on appropriate treatment optimization and transitioning in the management of moderate-to-severe plaque psoriasis. J Eur Acad Dermatol Venereol. 2013 Feb 26. [Medline].
Gulliver W. Long-term prognosis in patients with psoriasis. Br J Dermatol. 2008 Aug. 159 Suppl 2:2-9. [Medline].
Krueger JG, Bowcock A. Psoriasis pathophysiology: current concepts of pathogenesis. Ann Rheum Dis. 2005 Mar. 64 Suppl 2:ii30-6. [Medline]. [Full Text].
Keaney TC, Kirsner RS. New insights into the mechanism of narrow-band UVB therapy for psoriasis. J Invest Dermatol. 2010 Nov. 130(11):2534. [Medline].
Pietrzak AT, Zalewska A, Chodorowska G, Krasowska D, Michalak-Stoma A, Nockowski P, et al. Cytokines and anticytokines in psoriasis. Clin Chim Acta. 2008 Aug. 394(1-2):7-21. [Medline].
Keller JJ, Lin HC. The Effects of Chronic Periodontitis and Its Treatment on the Subsequent Risk of Psoriasis. Br J Dermatol. 2012 Jul 3. [Medline].
Woodrow JC, Ilchysyn A. HLA antigens in psoriasis and psoriatic arthritis. J Med Genet. 1985 Dec. 22 (6):492-5. [Medline].
Riveira-Munoz E, He SM, Escaramís G, et al. Meta-Analysis Confirms the LCE3C_LCE3B Deletion as a Risk Factor for Psoriasis in Several Ethnic Groups and Finds Interaction with HLA-Cw6. J Invest Dermatol. 2011 May. 131(5):1105-9. [Medline].
Gelfand JM, Stern RS, Nijsten T, Feldman SR, Thomas J, Kist J, et al. The prevalence of psoriasis in African Americans: results from a population-based study. J Am Acad Dermatol. 2005 Jan. 52(1):23-6. [Medline].
Klufas DM, Wald JM, Strober BE. Treatment of Moderate to Severe Pediatric Psoriasis: A Retrospective Case Series. Pediatr Dermatol. 2016 Feb 12. [Medline].
Gelfand JM, Troxel AB, Lewis JD, Kurd SK, Shin DB, Wang X, et al. The risk of mortality in patients with psoriasis: results from a population-based study. Arch Dermatol. 2007 Dec. 143(12):1493-9. [Medline].
Harding A. Extent of psoriasis tied to risk of comorbidities. Reuters Health Information. August 15, 2013. [Full Text].
Yeung H, Takeshita J, Mehta NN, et al. Psoriasis Severity and the Prevalence of Major Medical Comorbidity: A Population-Based Study. JAMA Dermatol. 2013 Aug 7. [Medline].
Patel RV, Shelling ML, Prodanovich S, Federman DG, Kirsner RS. Psoriasis and vascular disease-risk factors and outcomes: a systematic review of the literature. J Gen Intern Med. 2011 Sep. 26(9):1036-49. [Medline].
Li WQ, Han JL, Manson JE, Rimm EB, Rexrode KM, Curhan GC, et al. Psoriasis and risk of nonfatal cardiovascular disease in U.S. women: a cohort study. Br J Dermatol. 2012 Apr. 166(4):811-8. [Medline].
Henderson D. Psoriasis severity linked to uncontrolled hypertension. Medscape Medical News. October 27, 2014. [Full Text].
Takeshita J, Wang S, Shin DB, Mehta NN, Kimmel SE, Margolis DJ, et al. Effect of Psoriasis Severity on Hypertension Control: A Population-Based Study in the United Kingdom. JAMA Dermatol. 2014 Oct 15. [Medline].
Wan J, Wang S, Haynes K, Denburg MR, Shin DB, Gelfand JM. Risk of moderate to advanced kidney disease in patients with psoriasis: population based cohort study. BMJ. 2013 Oct 15. 347:f5961. [Medline].
Laidman J. Moderate and Severe Psoriasis Linked to Higher Kidney Risks. Medscape [serial online]. Available at https://www.medscape.com/viewarticle/812730. Accessed: October 21, 2013.
Kurd SK, Troxel AB, Crits-Christoph P, Gelfand JM. The risk of depression, anxiety, and suicidality in patients with psoriasis: a population-based cohort study. Arch Dermatol. 2010 Aug. 146(8):891-5. [Medline]. [Full Text].
Oostveen AM, de Jager ME, van de Kerkhof PC, Donders AR, de Jong EM, Seyger MM. The influence of treatments in daily clinical practice on the Children's Dermatology Life Quality Index in juvenile psoriasis: a longitudinal study from the Child-CAPTURE patient registry. Br J Dermatol. 2012 May 23. [Medline].
Lucka TC, Pathirana D, Sammain A, Bachmann F, Rosumeck S, Erdmann R, et al. Efficacy of systemic therapies for moderate-to-severe psoriasis: a systematic review and meta-analysis of long-term treatment. J Eur Acad Dermatol Venereol. 2012 Mar 9. [Medline].
Pettey AA, Balkrishnan R, Rapp SR, Fleischer AB, Feldman SR. Patients with palmoplantar psoriasis have more physical disability and discomfort than patients with other forms of psoriasis: implications for clinical practice. J Am Acad Dermatol. 2003 Aug. 49(2):271-5. [Medline].
Sampogna F, Tabolli S, Soderfeldt B, Axtelius B, Aparo U, Abeni D. Measuring quality of life of patients with different clinical types of psoriasis using the SF-36. Br J Dermatol. 2006 May. 154(5):844-9. [Medline].
Langenbruch A, Radtke MA, Krensel M, Jacobi A, Reich K, Augustin M. Nail involvement as a predictor of concomitant psoriatic arthritis in patients with psoriasis. Br J Dermatol. 2014 Nov. 171(5):1123-8. [Medline].
Moadel K, Perry HD, Donnenfeld ED, Zagelbaum B, Ingraham HJ. Psoriatic corneal abscess. Am J Ophthalmol. 1995 Jun. 119(6):800-1. [Medline].
Durrani K, Foster CS. Psoriatic uveitis: a distinct clinical entity?. Am J Ophthalmol. 2005 Jan. 139(1):106-11. [Medline].
Takahashi H, Sugita S, Shimizu N, Mochizuki M. A high viral load of Epstein-Barr virus DNA in ocular fluids in an HLA-B27-negative acute anterior uveitis patient with psoriasis. Jpn J Ophthalmol. 2008 Mar-Apr. 52(2):136-8. [Medline].
Lipper GM. Psoriasis and IBD: Is This Comorbidity for Real?. Medscape Dermatology. Available at https://www.medscape.com/viewarticle/907240. January 11, 2019; Accessed: January 15, 2019.
Fu Y, Lee CH, Chi CC. Association of Psoriasis With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. JAMA Dermatol. 2018 Dec 1. 154 (12):1417-1423. [Medline].
Tsai TF, Wang TS, Hung ST, Tsai PI, Schenkel B, Zhang M, et al. Epidemiology and comorbidities of psoriasis patients in a national database in Taiwan. J Dermatol Sci. 2011 Jul. 63 (1):40-6. [Medline].
Elston DM, Ferringer T, Ko C, Peckham S, High W, DiCaudo D. Dermatopathology. 2nd ed. Philadelphia, Pa: Elsevier Saunders; 2013.
[Guideline] Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi CL, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008 May. 58(5):826-50. [Medline].
[Guideline] Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol. 2009 Apr. 60(4):643-59. [Medline].
[Guideline] Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 5. Guidelines of care for the treatment of psoriasis with phototherapy and photochemotherapy. J Am Acad Dermatol. 2010 Jan. 62(1):114-35. [Medline].
[Guideline] Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis Section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: Case-based presentations and evidence-based conclusions. J Am Acad Dermatol. 2011 Feb 7. [Medline].
Mason AR, Mason J, Cork M, Dooley G, Edwards G. Topical treatments for chronic plaque psoriasis. Cochrane Database Syst Rev. 2009 Apr 15. CD005028. [Medline].
Stern RS. The risk of squamous cell and basal cell cancer associated with psoralen and ultraviolet A therapy: A 30-year prospective study. J Am Acad Dermatol. 2012 Jan 18. [Medline].
Carrascosa JM, Plana A, Ferrandiz C. Effectiveness and Safety of Psoralen-UVA (PUVA) Topical Therapy in Palmoplantar Psoriasis: A Report on 48 Patients. Actas Dermosifiliogr. 2013 Mar 6. [Medline].
Mehta D, Lim HW. Ultraviolet B Phototherapy for Psoriasis: Review of Practical Guidelines. Am J Clin Dermatol. 2016 Feb 12. [Medline].
Stern DK, Creasey AA, Quijije J, Lebwohl MG. UV-A and UV-B Penetration of Normal Human Cadaveric Fingernail Plate. Arch Dermatol. 2011 Apr. 147(4):439-41. [Medline].
Brown T. Fingernail Psoriasis Data Added to Humira Prescribing Info. Medscape News & Perspective. Available at https://www.medscape.com/viewarticle/877985?src=soc_fb_170405_mscpedt_news_pharm_humira. March 30, 2017; Accessed: April 6, 2017.
Mantovani A, Gisondi P, Lonardo A, Targher G. Relationship between Non-Alcoholic Fatty Liver Disease and Psoriasis: A Novel Hepato-Dermal Axis?. Int J Mol Sci. 2016 Feb 5. 17 (2):[Medline].
Salvi M, Macaluso L, Luci C, Mattozzi C, Paolino G, Aprea Y, et al. Safety and efficacy of anti-tumor necrosis factors α in patients with psoriasis and chronic hepatitis C. World J Clin Cases. 2016 Feb 16. 4 (2):49-55. [Medline].
Komrokji RS, Kulasekararaj A, Al Ali NH, Kordasti S, Bart-Smith E, Craig BM, et al. Autoimmune Diseases and Myelodysplastic Syndromes. Am J Hematol. 2016 Feb 13. [Medline].
Sorensen EP, Algzlan H, Au SC, Garber C, Fanucci K, Nguyen MB, et al. Lower Socioeconomic Status is Associated With Decreased Therapeutic Response to the Biologic Agents in Psoriasis Patients. J Drugs Dermatol. 2016 Feb 1. 15 (2):147-53. [Medline].
Castaldo G, Galdo G, Rotondi Aufiero F, Cereda E. Very low-calorie ketogenic diet may allow restoring response to systemic therapy in relapsing plaque psoriasis. Obes Res Clin Pract. 2015 Nov 8. [Medline].
Barrea L, Balato N, Di Somma C, Macchia PE, Napolitano M, Savanelli MC, et al. Nutrition and psoriasis: is there any association between the severity of the disease and adherence to the Mediterranean diet?. J Transl Med. 2015 Jan 27. 13:18. [Medline].
Millsop JW, Bhatia BK, Debbaneh M, Koo J, Liao W. Diet and psoriasis, part III: role of nutritional supplements. J Am Acad Dermatol. 2014 Sep. 71 (3):561-9. [Medline].
Finamor DC, Sinigaglia-Coimbra R, Neves LC, Gutierrez M, Silva JJ, Torres LD, et al. A pilot study assessing the effect of prolonged administration of high daily doses of vitamin D on the clinical course of vitiligo and psoriasis. Dermatoendocrinol. 2013 Jan 1. 5 (1):222-34. [Medline].
Hackethal V. Guidelines on Psoriasis Comorbidity Screening in Kids Issued. Medscape News & Perspective. Available at https://www.medscape.com/viewarticle/880462?nlid=115307_1584&src=WNL_mdplsfeat_170530_mscpedit_derm&uac=106950CX&spon=33&impID=1357759&faf=1#vp_1. May 23, 2017; Accessed: May 31, 2017.
[Guideline] Elmets CA, Korman NJ, Prater EF, 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 Feb. 84 (2):432-470. [Medline]. [Full Text].
[Guideline] Smith CH, Yiu ZZN, Bale T, et al. British Association of Dermatologists guidelines for biologic therapy for psoriasis 2020: a rapid update. Br J Dermatol. 2020 Oct. 183 (4):628-637. [Medline]. [Full Text].
[Guideline] Menter A, Strober BE, Kaplan DH, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. J Am Acad Dermatol. 2019 Apr. 80 (4):1029-1072. [Medline].
[Guideline] Berth-Jones J, Exton LS, Ladoyanni E, Mohd Mustapa MF, Tebbs VM, Yesudian PD, et al. British Association of Dermatologists guidelines for the safe and effective prescribing of oral ciclosporin in dermatology 2018. Br J Dermatol. 2019 Jun. 180 (6):1312-1338. [Medline]. [Full Text].
[Guideline] Elmets CA, Lim HW, Stoff B, 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 Sep. 81 (3):775-804. [Medline]. [Full Text].
Kui R, Gál B, Gaál M, Kiss M, Kemény L, Gyulai R. Presence of antidrug antibodies correlates inversely with the plasma tumor necrosis factor (TNF)-α level and the efficacy of TNF-inhibitor therapy in psoriasis. J Dermatol. 2016 Feb 19. [Medline].
Di Lernia V, Bardazzi F. Profile of tofacitinib citrate and its potential in the treatment of moderate-to-severe chronic plaque psoriasis. Drug Des Devel Ther. 2016. 10:533-9. [Medline].
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Plaque psoriasis is raised, roughened, and covered with white or silver scale with underlying erythema. Contributed by Randy Park, MD.
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Guttate psoriasis erupted in this patient after topical steroid therapy was withdrawn during a pregnancy. Contributed by Randy Park, MD.
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Plaque psoriasis is most common on the extensor surfaces of the knees and elbows. Contributed by Randy Park, MD.
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Nail psoriasis. Pits, distal onycholysis (nail separation), and brownish staining ("oil spots") are classic nail findings
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Inverse psoriasis. Occurring in skin folds, this will often lack the scale seen in other locations.
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Pustular psoriasis of the soles. This may be confined to the hands and feet (Acrodermatitis Continua of Hallepeau) or may be part of a generalized pustular psoriasis (Von Zumbusch disease)
Tables
Jacquiline Habashy, DO, MSc Resident Physician, Department of Dermatology, Western University of Health Sciences College of Osteopathic Medicine of the Pacific
Jacquiline Habashy, DO, MSc is a member of the following medical societies: American Osteopathic College of Dermatology
Disclosure: Nothing to disclose.
David T Robles, MD, PhD, FAAD Director, Dermatology Division, Chaparral Medical Group
David T Robles, MD, PhD, FAAD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.
William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine
William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology
Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD.
Jeffrey Meffert, MD † Former Associate Clinical Professor of Dermatology, University of Texas School of Medicine at San Antonio
Jeffrey Meffert, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists, Texas Dermatological Society
Disclosure: Nothing to disclose.
Robert Arffa, MD Clinical Assistant Professor, University of Pittsburgh School of Medicine
Robert Arffa, MD is a member of the following medical societies: American Academy of Ophthalmology
Disclosure: Nothing to disclose.
Richard Gordon Jr, MD Staff Physician, Department of Emergency Medicine, Detroit Receiving Hospital University Health Center
Richard Gordon Jr, MD is a member of the following medical societies: American College of Emergency Physicians, American College of Physicians, American Medical Student Association/Foundation, Emergency Medicine Residents Association, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.
Ryan I Huffman, MD Resident Physician, Department of Ophthalmology, Yale-New Haven Hospital
Disclosure: Nothing to disclose.
Simon K Law, MD, PharmD Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine
Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.
Randy Park, MD Chair, Associate Professor, Department of Emergency Medicine, Denton Regional Medical Center
Disclosure: Nothing to disclose.
Brian A Phillpotts, MD Former Vitreo-Retinal Service Director, Former Program Director, Clinical Assistant Professor, Department of Ophthalmology, Howard University College of Medicine
Brian A Phillpotts, MD is a member of the following medical societies: American Academy of Ophthalmology, American Diabetes Association, American Medical Association, and National Medical Association
Disclosure: Nothing to disclose.
Christopher J Rapuano, MD Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Institute
Christopher J Rapuano, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Cornea Society, Eye Bank Association of America, and International Society of Refractive Surgery
Disclosure: Allergan Honoraria Speaking and teaching; Allergan Consulting fee Consulting; Alcon Honoraria Speaking and teaching; RPS Ownership interest Other; Bausch & Lomb Honoraria Speaking and teaching; Merck Consulting fee Consulting; Bausch & Lomb Consulting; Merck Honoraria Speaking and teaching
Adam J Rosh, MD Assistant Professor, Program Director, Emergency Medicine Residency, Department of Emergency Medicine, Detroit Receiving Hospital, Wayne State University School of Medicine
Adam J Rosh, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.
Hampton Roy Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.
Dana A Stearns, MD Assistant Director of Undergraduate Education, Department of Emergency Medicine, Massachusetts General Hospital; Assistant Professor of Surgery, Harvard Medical School
Dana A Stearns, MD is a member of the following medical societies: American College of Emergency Physicians
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment