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Disponible online el 23 de Enero de 2023
Erythrodermic Psoriasis Has Become Less Frequent: Results From the Biobadaderm Registry
La psoriasis eritrodérmica es cada vez menos frecuente: resultados del registro Biobadaderm
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R. Rivera-Diaza,
Autor para correspondencia
rriveradiaz@hotmail.com

Corresponding author.
, G. Carreterob, J.M. Carrascosac, I. García-Dovald
a Dermatology Department, University Hospital 12 de Octubre & Universidad Complutense, Madrid, Spain
b Dermatology Department, Universitary Hospital Gran Canaria Doctor Negrin, Gran Canaria, Spain
c Dermatology Department, H. Germans Trias i Pujol, Spain
d Academia Española de Dermatología y Venereología, Research Unit, Fundación Piel Sana & Complexo Hospitalario Universitario de Vigo, Servicio de Dermatologia, Spain
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Dear Editor,

Erythrodermic psoriasis (EP) is a rare and severe form of psoriasis characterized by erythema in 75–90% of the body surface1,2 with high morbidity and increased mortality and considered a dermatological emergency.

EP's prevalence is less than 3% of all cases of psoriasis.3 Although, its pathophysiology is largely unknown, it is thought to differ from that of plaque psoriasis (PP). EP may have a certain TH2 activation with Ig E, IL13, IL4 and IL10, while sharing TNF and IL-17A pathways with PP and genetics with pustular psoriasis, having found family mutations of CARD14 gene in EP.4 Alternatively, EP could represent a worsening of the other types of psoriasis (such as plaque or generalized pustular psoriasis).

EP patients can present systemic symptoms, such as fever, CHILLS, dehydration, arthralgia, asthenia and lymphadenopathy. Environmental triggers often precipitate erythrodermic flares, including steroid withdrawal, systemic infections, drug exposure such as lithium, and emotional stress.1

Treatment of EP is challenging and usually based on clinical experience, in part due to its low incidence and need for urgent management. Conventional treatments, such as glucocorticoid, cyclosporine, acitretin, and methotrexate are frequently ineffective and their discontinuation may cause flares. Recommendations for biologic therapy have limited evidence, but it seems to be well-tolerated and with positive results.5 Due to the need to obtain a rapid clinical response, the best therapies will be those with a faster onset of action, avoiding the more immunosuppressive agents given the high frequency of bacteraemia and sepsis in EP.4 Biologics as infliximab or IL-17 antagonist could be the first line, followed by IL-23 antagonist, anti-IL12/23 or other anti TNF.6 Interestingly, Th17 was found to be the second-most predominant T-cell type after Th2 in EP lesions, supporting the use of anti-IL-17 agents when rapid control is needed.1

We aimed to evaluate and compare the demographic characteristics, comorbidities and treatment prescription for EP with PP. To achieve this, we extracted data from the Biobadaderm from October 2008 to December 2021. The characteristics of the registry have been previously described.7

68 patients with inclusion diagnosis of EP were compared with 3930 patients with plaque psoriasis (PP). EP patients were older, had higher PASI and higher use of CsA when entering the cohort. No differences in comorbidities were observed, even when considering cancer and infection (Table 1).

Table 1.

Demographic characteristics, comorbidities and previous therapies in plaque psoriasis, vs erythrodermic psoriasis and first drug used after entry in the cohort and all drugs used over follow-up.

  Erythrodermic psoriasisn=68  Plaque psoriasisn=3930  P value for the difference 
Sex, male (n, (%))  47 (69.1%)  2352 (59.8%)  0.1218 
Current age (mean (sd))  62.8 (19.1)  53.6 (14.9)  0.0000 
Age at entry in the cohort (mean (sd))  54.1 (16.9)  46.8 (14.5)  0.0000 
Disease duration at entry in the cohort, years (mean (sd))  21 (13.9)  17 (13.4)  0.0137 
PASI at entry in the cohort (mean (sd))  19.4 (13.7)  11.3 (7.4)  0.0000 
Toxic habits
Current or previous smoker (n, (%))  36 (63.2%)  1948 (63.1%)  0.9907 
Current or previous alcohol drinking (n, (%))  33 (63.5%)  2143 (73.8%)  0.0947 
  n (%)  n (%)   
Comorbidities
Body mass index0.5767 
Normal (<25)  16 (31.4%)  1006 (32.7%)   
Overweight (25–29.9)  21 (41.2%)  1063 (34.5%)   
Obesity (>30)  14 (27.5%)  1009 (32.8%)   
Ischemic heart disease  2 (3.4%)  107 (3.1%)  0.8908 
Heart failure  0 (0%)  35 (1%)  0.4339 
Hypertension  22 (36.1%)  859 (24%)  0.0297 
Diabetes  14 (23.3%)  447 (12.7%)  0.0144 
Hypercholesterolemia  22 (35.5%)  1028 (28.9%)  0.2575 
COPD  3 (5%)  115 (3.3%)  0.4717 
Chronic haepatic disease  7 (11.1%)  318 (9.1%)  0.5918 
Chronic renal failure  3 (5.1%)  50 (1.4%)  0.0227 
Previous and current cancer  3 (5.2%)  147 (4.2%)  0.7245 
Previous and current lymphoma  1 (1.7%)  11 (0.3%)  0.0765 
HBV infection  3 (5.6%)  147 (4.6%)  0.7107 
HCV infection  2 (3.6%)  70 (2.2%)  0.5750 
HIV infection  1 (2.1%)  29 (1%)  0.7227 
Psoriatic arthritis  12(17.6%)  559 (14.2%)  0.4238 
  n (%)  n (%)   
Previous therapies
Previous PUVA therapy  16 (23.5%)  711 (18.1%)  0.2491 
Previous narrow band UVB therapy  7 (10.3%)  806 (20.5%)  0.0380 
Previous therapy with methotrexate  32 (47.1%)  1523 (38.8%)  0.1637 
Previous therapy with cyclosporine  39 (57.4%)  934 (23.8%)  0.0000 
Previous therapy with acitretin  25 (36.8%)  867 (22.1%)  0.0039 
  n (%)  n (%) 
First drug used after entry in the cohort
Cyclosporine  14 (20.6%)  337 (8.6%) 
Etanercept  14 (20.6%)  390 (9.9%) 
Adalimumab  8 (11.8%)  613 (15.6%) 
Ustekinumab  7 (10.3%)  353 (9%) 
Acitretine  7 (10.3%)  411 (10.5%) 
Ixekizumab  2 (2.9%)  111 (2.8%) 
Methotrexate  7 (10.3%)  986 (25.1%) 
Secukinumab  1 (1.5%)  176 (4.5%) 
Apremilast  1 (1.5%)  190 (4.8%) 
Risankizumab  1 (1.5%)  40 (1%) 
Tildrakizumab  0 (0%)  19 (0.5%) 
Certolizumab pegol  0 (0%)  12 (0.3%) 
Golimumab  0 (0%)  1 (0%) 
Brodalumab  0 (0%)  26 (0.7%) 
Dimethyl fumarate  0 (0%)  47 (1.2%) 
Guselkumab  0 (0%)  64 (1.6%) 
All drugs used over follow-up
Methrotrexate  50 (19.3%)  2248 (22.7%) 
Cyclosporine  37 (14.3%)  706 (7.1%) 
Adalimumab  30 (11.6%)  1602 (16.2%) 
Etanercept  29 (11.2%)  977 (9.9%) 
Ustekinumab  27 (10.4%)  1158 (11.7%) 
Acitretine  24 (9.3%)  855 (8.6%) 
Secukinumab  13 (5%)  511 (5.2%) 
Infliximab  13 (5%)  207 (2.1%) 
Ixekizumab  10 (3.9%)  419 (4.2%) 
Guselkumab  8 (3.1%)  277 (2.8%) 
Apremilast  5 (1.9%)  366 (3.7%) 
Risankizumab  5 (1.9%)  167 (1.7%) 
Dimethyl fumarate  2 (0.8%)  101 (1%) 
Efalizumab  2 (0.8%)  86 (0.9%) 
Golimumab  2 (0.8%)  20 (0.2%) 
Brodalumab  1 (0.4%)  84 (0.8%) 
Certolizumab pegol  1 (0.4%)  50 (0.5%) 
Tildrakizumab  0 (0%)  62 (0.6%) 

P values have been calculated using t-student or chi square. P values in bold are significant after Bonferroni correction for multiple testing (30 tests).

Our most interesting finding has been a gradual reduction of EP cases included in the registry through the follow up time (Table 2). This may reflect the better disease control achieved recently in psoriatic patients due to advances in treatment. And it supports the idea that EP in some patients is a severe stage of other types of psoriasis, thus a greater control would result in a reduction of EP frequency.

Table 2.

Percentage of erythrodermic patients at entry in the cohort in consecutive periods.

  2008–2012  2013–2017  2018–2021 
Plaque psoriasis  1511 (97.6%)  906(97.5%)  1513(99.5%) 
Erythroderma  37 (2.4%)  23 (2.5%)  8 (0.5%) 

Changes over time are statistically significant (P<0.0001).

When analysing the first treatment after entry in the cohort we found that the most prescribed treatments in EP compared with PP were Cyclosporine, Etanercept, Ustekinumab, Ixekizumab and Risankizumab (Table 1). When analysing all treatments used during follow up, the most frequently used in EP where Cyclosporine and anti-TNF due to their longer time of availability and that the majority of EP patients analyzed were included in the first eight years of the registry.

The limitation of our study is that in Biobadaderm, patients are classified with the diagnosis at the moment of inclusion, thus patients who developed EP after their inclusion in the registry were not analyzed. Moreover, treatment options changed during follow up period, which explains why the first treatment in several patients is no longer the current option for management of EP, as etanercept.

In conclusion, our study confirms that EP patients have a higher mean age, greater disease severity (higher base PASI and more frequent previous use of cyclosporine), and the decreasing frequency of this type of psoriasis.

Funding

Biobadaderm received funding from “Agencia Española del Medicamento” and Pharmaceutical companies (Abbott/AbbVie, Almirall, Amgen, Janssen, Leo Pharma, Lilly, MSD, Novartis, Pfizer and UCB). Funding industry has not participated in study design, data collection or management, nor manuscript writing or decisions about publication.

Conflict of interest

Dr. Rivera-Diaz acted as a consultant and/or speaker for and/or participated in clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis, including Janssen Pharmaceuticals Inc., Almirall SA, Boehringer, Lilly, AbbVie, Novartis, Leo-Pharma, and UCB.

The rest of authors do not declare any conflict of interest for this article.

Acknowledgements

We would like to thank Drs. Sahuquillo-Torralba, Antonio; Dauden, Esteban; de la Cueva Dobao, Pablo; Baniandrés, Ofelia; Belinchón, Isabel; Ruiz-Genao, Diana; Ferran Farrés, Marta; Flórez Menéndez, Ángeles and other members of the Biobadaderm registry for their collaboration.

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