Title of paper: Chronic Hand Eczema and Hepatogenic Pruritus with good response to

Apremilast

Short running head: Hand Eczema and Apremilast

Type of article: Therapeutic Hotline: Short Papers

Keywords: chronic hand eczema, Apremilast, hepatogenic pruritus

Manuscript words: 636

Table: 0

Figure count: 2

Corresponding author: Francisco José Navarro Triviño1.

Address: Hospital Universitario San Cecilio, Granada1. Avenida de la Ilustración, s/n CP 18016,
Granada.

Telephone: 657998758

Email address: fntmed@gmail.com

Names of authors as initial (s) folllowed surnames: Francisco J Navarro-Triviño (1), Cuenca-
Barrales C (1), Vega-Castillo JJ (1) Ricardo Ruiz-Villaverde R (1).

Names of the institutions at wich the research was conducted, clearly linked to respective
authors: Hospital Universitario San Cecilio. Unidad de Gestión Clínica de Dermatología1

A statement of all funding sources that supported the work: No

Conflict of interest: None

This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process which
may lead to differences between this version and the Version of Record. Please cite this
article as doi: 10.1111/dth.12879

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Abstrac

Hand eczema (HE) presents a high prevalence and severe impact on the quality of life of the
patients. HE is a worldwide problem recognized for his high socio-occupational involvement.

Treatment is mainly based on adequate recommendations for hand care together with topical
anti-inflammatory treatments. Frequently, patients require systemic treatments such
Alitretinoin, among others. The comorbidities of the patients and the side effects of the
treatments sometimes require prescribing other treatments off label on the technical data.

This role in immunomodulation has led to the development of new studies that investigate
what role does Apremilast have in eczematous diseases, such as atopic dermatitis.

We present this case for the quick and complete response of HE with Apremilast, and the
effective control of hepatogenic pruritus. These finding open a new possibility and alternative
treatment of this complex and difficult of control with the treatments already described in the
literature.

Dear editor:

A 65-year-old man, farmer, consulted by chronic hand eczema of 5 years of evolution. On the
examination, he presented the hyperkeratotic and fissured plaques on both palms of the
hands, predominantly on the fingers (Fig. 1), that associated the high pain and itching
symptoms. The patient did not associate other lesions on the body. Among the personal
antecedents of the interest, he associated non-alcoholic hepatic steatosis in a pre-cirrhotic
state, with very severe hepatogenic pruritus, limiting the quality of life. There was no personal
or family history of the atopic dermatitis or psoriasis. The skin biopsy showed hyperkeratosis
with the acanthosis and mild spongiosis. The patch test with the TRUE TEST® was negative at
48 and 96 hours. After the results obtained, we ruled out the possibility of the palmar
psoriasis, both by the clinic and histological study. The treatment was started with a clobetasol
propionate 0.05% cream once a day associated to keratolytics agents without an
improvement. Agreed with the digestive specialist, the patient started treatment with
Alitretinoin 30 mg / day, but we suspended due to transaminase elevation and severe
headache. The impossibility of performing phototherapy treatment due to unavailability in our
hospital, and due to the patient's conditions, we decided to start the Apremilast off label
treatment with a psoriasis dosage according to the technical data. One month after start the

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treatment, the patient showed a complete clearance of hand eczema (Fig. 2), as well as the
disappearance of hepatogenic pruritus. The analytical follow-up showed no alterations in the
hepatic profile and hemogram study. Currently the patient is being treated with Apremilast 30
mg/12 hours, with good control of the disease.

Hand eczema (HE) presents a high prevalence and severe impact on the quality of life of the
patients (Antonov D et al, 2015). HE is a worldwide problem recognized for his high socio-
occupational involvement. Multiple articles have been published (Diepgen TL et al, 2015)
trying to classify the different clinical presentations of hand eczema. HE is considered a
multifactorial disease, where certain professions increase the development of it, such as
construction, agriculture, or more specifically, health professionals. Among the differential
diagnosis (Cazzaniga S et al, 2018), psoriasis and infection by dermatophytes are the top of the
long list of diseases that must be taken into account when study these patients. Treatment is
mainly based on adequate recommendations for hand care (emollients, correct use of gloves,
etc.) together with topical anti-inflammatory treatments, such as topical high-potency
corticosteroids. Frequently, patients require systemic treatments, given the refractoriness of
the disease. There are publications that defend the use of classic oral retinoids such as
Acitretin (Song M et al, 2017), and more recently, as the only drug with recommendation
grade IA, Alitretinoin (Blair HA et al, 2016; Al-Dhubaibi MS et al, 2018). Other publications
have reported those therapeutic preferences (Smith IL et al, 2017) by different dermatologists,
which also include phototherapy or methotrexate. The comorbidities of the patients and the
side effects of the treatments sometimes require prescribing other treatments off label on the
technical data. Among them, oral Apremilast was the drug chosen for the profile of our
patient.

Apremilast, an oral inhibitor of Phosphodiesterase 4 (PDE4) (Wittmann M et al, 2013), is

indicated for the treatment of mild to moderate plaque psoriasis and psoriatic arthritis. The
role of PDE4 in inflammatory regulation acts through two mechanisms mainly, increasing IL-10
as an anti-inflammatory cytokine, and decreasing pro-inflammatory cytokines such as IL-2, 5,
13, 17, or TNF alpha, among other molecules.

This role in immunomodulation has led to the development of new studies that investigate
what role does Apremilast have in eczematous diseases, such as atopic dermatitis. In fact,
there are already some publications (Samrao A et al, 2012) that show encouraging results of
the improvement in atopic dermatitis, even in the pediatric age (Saporito RC et al, 2016). So
far, there is only one reported case of chronic hand eczema treated with Apremilast (Michael
Abrouk et al, 2017). It is possible that patients can benefit from this treatment. This fact
should encourage the development of studies that determine the appropriate dosage for other
diseases, as investigated with psoriasis.

We present this case, not only for the quick and complete response of HE, but also because of
the quick and effective control of hepatogenic pruritus. These finding open a new possibility
and alternative treatment of this complex and difficult of control with the treatments already
described in the literature.

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References

Al-Dhubaibi MS, Settin AA. (2018)The effectiveness of alitretinoin for the treatment of chronic
hand eczema: A meta-analysis. Int J Health Sci (Qassim), 12, 70-9.

Antonov D, Schliemann S, Elsner P. (2015) Hand dermatitis: a review of clinical features,

prevention and treatment. Am J Clin Dermatol, 16, 257-70.

Blair HA, Scott LJ. (2016)Alitretinoin: A Review in Severe Chronic Hand Eczema. Drugs, 76,
1271-9.

Cazzaniga S, Apfelbacher C, Diepgen T, Ofenloch RF, Weisshaar E, Molin S, et al (2018).

Patterns of chronic hand eczema: a semantic map analysis of the CARPE registry data. Br J
Dermatol, 178, 229-37.

Diepgen TL, Andersen KE, Chosidow O, Coenraads PJ, Elsner P, English J, et al. (2015)
Guidelines for diagnosis, prevention and treatment of hand eczema. J Dtsch Dermatol Ges. 13,
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(2017) Apremilast treatment of atopic dermatitis and other chronic eczematous dermatoses. J
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Samrao A, Berry TM, Goreshi R, Simpson EL. (2012) A pilot study of an oral phosphodiesterase
inhibitor (apremilast) for atopic dermatitis in adults. Arch Dermatol, 148, 890-7.

Saporito RC, Cohen DJ. (2016) Apremilast Use for Moderate-to-Severe Atopic Dermatitis in
Pediatric Patients. Case Rep Dermatol, 8, 179–84.

Smith IL, Brown S, Nixon J, Cowdell FC, Ersser S, Fernandez C, et al. (2017)Treatment of severe,
chronic hand eczema: results from a UK-wide survey. Clin Exp Dermatol, 42, 185-8.

Song M, Lee HJ, Lee WK, Kim HS, Ko HC, Kim MB, Kim BS. (2017) Acitretin as a Therapeutic
Option for Chronic Hand Eczema. Ann Dermatol, 29, 385-7.

Wittmann M, Helliwell PS. (2013) Phosphodiesterase 4 inhibition in the treatment of psoriasis,

psoriatic arthritis and other chronic inflammatory diseases. Dermatol Ther (Heidelb), 3, 1-15.

Figure

Fig. - 1. Chronic hyperkeratotic and fissured hand eczema, predominantly in the digital area.

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Fig. - 2. Complete cleansing after one month of starting treatment with oral Apremilast.

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This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.