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Non Commercial Use Only Dermatology Reports 2016; volume 8:6599 Erythrodermic psoriasis treated novel oral small-molecule phosphodiesterase-4 inhibitor apremilast. Correspondence: Navin Jaipaul, VA Loma Linda with apremilast Healthcare System, 11201 Benton St. 111N, Loma Linda, CA 92357, USA. John Arcilla,1 Daniel Joe,1 Tel.: +1.909.583.6090 - Fax: +1.909.777.3858. Johnathan Kim,1 Yohanan Kim,1 Case Report E-mail: [email protected] VuAnh N. Truong,1 Navin Jaipaul1,2 Key words: Erythroderma; Psoriasis; 1 Department of Medicine, Loma Linda A 79-year-old man with hypertension and Erythrodermic psoriasis; Apremilast. University School of Medicine and psoriasis was hospitalized for severe sepsis 2Department of Medicine, VA Loma Linda associated with a generalized and painful ery- Contributions: the authors contributed equally. Healthcare System, Loma Linda, CA, USA thematous rash. He had been diagnosed with psoriasis affecting <1% body surface area Conflict of interest: the authors declare no poten- (BSA) three months before this presentation tial conflict of interest. and was treated with topical ketoconazole and Received for publication: 13 May 2016. Abstract fluocinolone. Two weeks before hospitaliza- Accepted for publication: 17 August 2016. tion, he received a five day oral prednisone taper prescribed by a family physician for skin This work is licensed under a Creative Commons Erythroderma is a rare potentially deadly rash. Following this, he developed a confluent, Attribution-NonCommercial 4.0 International exfoliative dermatitis characterized by diffuse erythematous, scaling rash covering >50% License (CC BY-NC 4.0). cutaneous erythema which may be associated BSA. Methotrexate was started for presumed ©Copyright J. Arcilla et al., 2016 with multi-organ dysfunction. Therefore, it is psoriatic erythroderma; however, his symp- Licensee PAGEPress, Italy imperative to recognize and treat it promptly. toms worsened to include progressive skin Erythrodermic psoriasis is the most common Dermatology Reports 2016; 8:6599 involvement, fever, and hypotension which led doi:10.4081/dr.2016.6599 form of erythroderma. Management of this to hospitalization.Physical exam revealed ten- condition is largely based on aggressive sup- der erythematous plaque with scale from head only portive care and the use of anti-inflammatory to toe, most prominently involving the head, unchanged, psoriasis plaques demonstrated immunosuppressive and biologic agents. We neck, chest, back, upper arms, abdomen, but- reduced erythema and scaling with marked describe a case of psoriatic erythroderma tocks, groin, and proximal thighs (Figure 1). improvement in cutaneous pain symptoms which was triggered by withdrawal from sys- Laboratory evaluation was remarkable for (Figure 3). As a result, Psoriasis Area and temic steroids and successfully treated with use leukocytosis of 23.8×103/µL and pre-renala- Severity Index score improved from 44.0 on apremilast and cyclosporine. Apremilast zotemia. Intravenous fluids, empiric antibi- induced atrial fibrillation limited its continued admission to 26.4 after initiating apremilast otics, topical steroids, and emollient moisturiz- treatment. However, the patient subsequently use after the initial response period. er were started. Infectious work-up was nega- developed new-onset atrial fibrillation attrib- tive; yet fevers, leukocytosis, and cutaneous uted to apremilast which was discontinued and pain symptoms persisted. Dermatology per- formed a punch biopsy which demonstrated switched to cyclosporine. The patient contin- Introduction evolving pustular psoriasis (Figure 2). ued to improve and was discharged on Apremilast was started for treatment of ery- cyclosporine. We report a case of a 79 year old man with throdermic psoriasis. The patient’s rash and erythrodermic psoriasis successfully treated systemic features began to improve by day 10. during the initial response phase with the Thoughcommercial BSA involvement was essentially Non Figure 1. Skin findings on day one of hospitalization demonstrating (A) well defined generalized erythema and scaling most promi- nently involving the head, neck, chest, back, upper arms, abdomen, buttocks, groin, and proximal thighs and (B) magnified view of the erythema and scaling. [page 8] [Dermatology Reports 2016; 8:6599] Case Report ing anti-inflammatory cytokines.8 It is reduction versus placebo in the baseline Discussion approved for treatment of psoriatic arthritris Psoriasis Area and Severity Index score in and moderate to severe plaque psoriasis. The patients with moderate to severe plaque psori- Erythroderma is a rare potentially deadly efficacy of apremilast was demonstrated in a asis.9 However, a search of the published liter- exfoliative dermatitis which may result from phase III randomized controlled trial that ature resulted in no reports describing the use systemic infection, drug hypersensitivity, showed a statistically and clinically significant of apremilast in erythrodermic psoriasis. Our malignancy (e.g. cutaneous T cell lymphoma), and inflammatory conditions such as Stevens Johnson syndrome, pityriasis rubra pilaris, and erythrodermic psoriasis.1 Initial manage- ment for severe cases includes fluid resuscita- tion, empiric antibiotics, and diligent diagnos- tic evaluation. Erythrodermic psoriasis is the most com- mon form of erythroderma and accounts for 25% of all cases.2 When associated with psori- asis, the erythrodermic variant represents less than 1.5% of cases and manifests with well- defined erythematous plaques and overlying silvery scale.3 It generally affects the entire body and may be associated with life-threaten- ing complications such as sepsis, hypovolemic shock, and acute kidney injury secondary to cutaneous fluid loss.2 Erythrodermic psoriasis may result from uncontrolled dermatosis, abrupt withdrawal of anti-psoriatic drugs such only as steroids or methotrexate, drug reaction, sys- temic infection, ultraviolet burns, alcoholism, and emotional stress.2 Our patient’s withdraw- al from oral steroids likely triggered his ery- use throderma. Skin biopsy may be helpful in diag- nosis as erythroderma may develop acutely or gradually from any variant of psoriasis.2 Figure 2. Skin biopsy demonstrating mild psoriasiform hyperplasia and rare intracorneal Treatment is largely based on aggressive sup- pustules with mild superficial perivascular mixed inflammation consistent with evolving portive care and the use of anti-inflammatory pustular psoriasis. immunosuppressive and biologic agents. High quality evidence-based treatment recommen- dations for erythordermic psoriasis are lacking due to the rarity of the condition. Most ran- domized clinical trials on psoriasis treatments have excluded less common variants such as the erythrodermic and pustular subtypes.4 In commercial light of this, first-line agents that have been used with variable efficacy include cyclosporine, infliximab, acitretin, and methotrexate.5 Etanercept and combination therapies are second-line alternatives.Non5 Recently, biologics including ustekinumab and golimumab have also been used with reported efficacy in the treatment of erythrodermic pso- riasis.6,7 Systemic corticosteroids and ultravio- let light therapy are not recommended due to risks of disease exacerbation and photosensi- tivity.5 Choice of therapy should be based on disease severity and patient comorbidities. For example, we chose to treat our patient with apremilast due to the presence of pre-renal acute kidney injury which is a relative con- traindication to use of the other aforemen- tioned first-line agents. Apremilast is a novel small-molecule oral medication which selec- tively inhibits phosphodiesterase 4 and has been shown to downregulate the production of Figure 3. Skin findings on day ten of hospitalization demonstrating reduced intensity of pro-inflammatory cytokines while upregulat- erythema and scaling in response to apremilast treatment. [Dermatology Reports 2016; 8:6599] [page 9] Case Report patient improved on apremilast; however, he patient, however, was limited after the initial 5. Rosenbach M, Hsu S, Korman NJ, et al. developed new-onset atrial fibrillation which response period by the development of atrial Treatment of erythrodermic psoriasis: was attributed to the medication so it was dis- fibrillation which was attributed to the medica- from the medical board of the National continued. When compared with placebo, tion. Psoriasis Foundation. J Am Acad Dermatol apremilast treatment has been associated with 2010;62:655-62. an increased, albeit low, incidence of tach- 6. Kim YS, Kim JH, Lee S, et al. yarrhythmia, most frequently atrial References Erythrodermic psoriasis improved by 9 fibrillation. Once the patient’s renal function ustekinumab: a report of two cases. Ann improved, he was started on cyclosporine and 1. Rothe MJ, Bernstein ML, Grant-Kels JM. Dermatol 2016;28:121-2. his erythroderma eventually resolved. Life-threatening erythroderma: diagnos- 7. Lee WK, Kim GW, Cho HH, et al. ing and treating the red man. Clin Erythrodermic psoriasis treated with goli- Dermatol 2005;23:206-17. Conclusions mumab: a case report. Ann Dermatol 2. Stinco G, Errichetti E. Erythrodermic pso- 2015;27:446-9. riasis: current and future role of biologi- 8. Kelly JB, Foley P, Strober BE. Current and Erythroderma associated with psoriasis may cals. Bio Drugs 2015;29:91-101. future oral systemic therapies for psoria- be triggered by withdrawal from systemic 3. Raychaudhuri SK, Maverakis E, sis. Dermatol Clin 2015;33:91-109. steroids. It is a
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