Open Access Case
Report DOI: 10.7759/cureus.7831
Clinical Psoriasiform Dermatitis Following
Dupilumab Use for Autoeczematization
Secondary to Chronic Stasis Dermatitis
Kory P. Schrom 1 , Alison Kobs 1 , Susan Nedorost 1
1. Dermatology, University Hospitals Cleveland Medical Center, Cleveland, USA
Corresponding author: Kory P. Schrom, kory.schrom@gmail.com
Abstract
T helper 2 (Th2) and T helper 1 (Th1) mediated immune processes lie on a spectrum.
Autoeczematization secondary to chronic stasis dermatitis may fall on the Th2 side of the
spectrum due to skin stretch and chronic barrier dysfunction, supporting a primary Th2
response to self-antigen. In our patient, we posited that dupilumab would benefit
autoeczematization secondary to chronic stasis dermatitis given its efficacy in atopic
dermatitis, a Th2-mediated immune process. We report a case of clinical psoriasiform
dermatitis, suggesting a shift toward a Th1-mediated immune process developing during
dupilumab treatment for autoeczematization secondary to chronic stasis dermatitis.
Categories: Dermatology
Keywords: autoeczematization, dupilumab, psoriasiform, th2, th1
Introduction
Patients with chronic venous stasis dermatitis are susceptible to developing
autoeczematization, with an associated 37% lifetime prevalence [1,2]. The cause of
autoeczematization is likely due to chronic skin stretch, skin irritation, and chronic barrier
dysfunction supporting autosensitization to self-antigens [3]. We hypothesize that these
protein self-antigens promote a T helper 2 (Th2) mediated immune response, which is a
phenomenon seen with other protein allergens in disease states such as atopic dermatitis [4].
Therefore, a “skewing” of the immune response to a predominately Th2-mediated immune
process in a patient with autoeczematization secondary to chronic stasis dermatitis is
theoretically possible [5].
Mediators of a Th2-mediated immune process include interleukin (IL)-4 and IL-13, which are
targeted by the monoclonal antibody, dupilumab [6,7]. Given the mechanism of action for
Received 03/26/2020
Review began 03/31/2020
dupilumab and the hypothesized pathogenesis of autoeczematization, it is possible that
Review ended 04/16/2020 dupilumab could be effective in treating autoeczematization. We report here the first case of
Published 04/25/2020 clinically developed psoriasiform dermatitis during dupilumab treatment for
© Copyright 2020
autoeczematization secondary to chronic stasis dermatitis.
Schrom et al. This is an open access
article distributed under the terms of
the Creative Commons Attribution Case Presentation
License CC-BY 4.0., which permits
An 80-year-old male with autoeczematization secondary to chronic stasis dermatitis developed
unrestricted use, distribution, and
clinical psoriasiform dermatitis after treatment with dupilumab. He initially presented with
reproduction in any medium, provided
the original author and source are generalized pruritic papules and eczematous patches on the trunk, arms, and lower extremities
credited. in the setting of previously diagnosed chronic lower extremity swelling and venous stasis
dermatitis. He rated his itch a 10 (i.e. worst possible), and a biopsy of the right upper back
How to cite this article
Schrom K P, Kobs A, Nedorost S (April 25, 2020) Clinical Psoriasiform Dermatitis Following Dupilumab
Use for Autoeczematization Secondary to Chronic Stasis Dermatitis. Cureus 12(4): e7831. DOI
10.7759/cureus.7831
revealed subacute spongiosis with frequent eosinophils. Direct immunofluorescence was
negative for immunoglobulin (Ig) G, IgA, IgM, complement 3, and fibrinogen. Indirect
immunofluorescence was negative for BP230/180 autoantibodies. Extensive patch testing was
performed and was non-contributory as there was no improvement with topical and systemic
avoidance of items producing positive patch test results. A diagnosis of autoeczematization
secondary to chronic stasis dermatitis was made. Unna boots were initiated followed by daily
compression stocking use and triamcinolone 0.1% ointment as needed. With therapy, his skin
improved and his itch was rated a 2. He was instructed to follow-up as needed.
He returned several months later following a prolonged car ride with a similar clinical picture
of generalized pruritic papules and eczematous patches on the trunk, arms, and lower
extremities. He also had pitting edema and rated his itch a 9. Despite adequate compression
with optimal patient compliance, triamcinolone as needed, and several courses of prednisone,
his condition was uncontrolled; therefore, our patient asked if dupilumab might help. We
reasoned that chronic stasis dermatitis might provoke a Th2-skewed immune response to self-
antigen in skin experiencing stretch and that mechanistically dupilumab may help.
The patient was treated with dupilumab 300 mg every two weeks subcutaneously with an initial
loading dose of 600 mg. An “Investigative New Drug” designation and Institutional Review
Board approval were obtained for this off-label use. After 10 weeks, itch decreased to 3 out of 10
and he had significantly reduced lower extremity edema; however, the morphology transitioned
from papules and patches to scaling erythematous plaques more consistent with
clinical psoriasiform dermatitis (Figure 1).
FIGURE 1: Scaling erythematous psoriasiform plaques on the
upper back after 10 weeks of dupilumab therapy.
Dupilumab was discontinued, and a repeat biopsy of the right upper posterior arm was
2020 Schrom et al. Cureus 12(4): e7831. DOI 10.7759/cureus.7831 2 of 5
performed at the time of discontinuation. The biopsy demonstrated non-specific histology with
orthokeratosis overlying parakeratosis, very mild spongiosis, lymphocyte exocytosis, and a mild
superficial perivascular lymphocytic infiltrate. Per the dermatopathologist, early psoriasis
could not be excluded, and the histology needed to be correlated with the clinical picture. The
patient was subsequently started on narrowband ultraviolet B phototherapy and responded
well.
Discussion
Clinical psoriasiform dermatitis developed in our patient after treatment with dupilumab for
autoeczematization secondary to chronic stasis dermatitis. Similar events have been reported
in patients with atopic dermatitis who developed psoriasiform dermatitis after treatment with
dupilumab, but this is the first case related to autoeczematization [8-12].
We treated our patient with dupilumab because we hypothesized that autoeczematization is
driven by a Th2-mediated immune process involving the cytokines IL-4 and IL-13 whose
functions are inhibited by dupilumab [6,13]. Skin stretch in chronic stasis dermatitis results in
chronic barrier dysfunction, which supports an altered epidermal microenvironment that is
primed for induction of a Th2-immune response, as described by Ellenbogen et al. [7,14]. In the
setting of this primed microenvironment, sensitization to autologous skin proteins occurs and
subsequently promotes autoeczematization [3,14]. Thus, dupilumab was considered a
reasonable treatment for our patient. Although his itch improved after 10 weeks of therapy, his
clinical morphology became psoriasis-like.
Although our patient’s biopsy was non-specific for psoriasis, biopsies related to dupilumab-
induced psoriasiform dermatitis may not always demonstrate clear psoriasiform changes even
when the lesions clinically appear psoriasiform. Fowler et al. reported a case that appeared as
psoriasiform dermatitis clinically but histologically as acute spongiotic dermatitis [11]. It is also
possible that clinical presentation may not be psoriasiform in appearance; but histologically,
psoriasiform changes can be present [15]. Providers, therefore, must review the entire clinical
picture when diagnosing and treating this phenomenon.
Psoriasis and atopic dermatitis have been described as sitting on a spectrum between T helper
1 (Th1) cell immunity and Th2 cell immunity. A shift toward Th1 immunity drives psoriasis,
and a shift toward Th2 immunity drives atopic dermatitis [13]. We postulate that dupilumab
shifted our patient along this spectrum toward a more Th1-mediated process through its
inhibition of IL-4 and IL-13 signaling [6]. IL-4 has been shown to enhance Th2 responses and
acts as a negative regulator of Th1 immune responses related to psoriasis through direct action
on T cells, keratinocytes, and dendritic cells [10,16].
Interestingly, a reverse phenomenon has been reported where patients with psoriasis
developed eczematous eruptions after treatment with TNFα (tumor necrosis factor-α)
inhibitors and the anti-IL-17 monoclonal antibody, secukinumab [17,18]. These shifts in
phenotypic presentation between atopic dermatitis and psoriasis are not likely to occur in
every patient, but previous research demonstrates that some patients may be at an increased
risk due to genetic susceptibilities to both atopic dermatitis and psoriasis [19,20].
Conclusions
Chronic stasis dermatitis causes skin stretch, resulting in chronic barrier dysfunction. This
dysfunction subsequently supports a Th2-mediated immune response to autologous skin
proteins and the development of autoeczematization. Dupilumab is effective in treating atopic
dermatitis, a Th2-mediated process, but it may skew the immune response to a Th1-skewed
response in less Th2-dominant processes such as autoeczematization secondary to chronic
2020 Schrom et al. Cureus 12(4): e7831. DOI 10.7759/cureus.7831 3 of 5
stasis dermatitis. Further research is required to better understand this phenomenon.
Additional Information
Disclosures
Human subjects: Consent was obtained by all participants in this study. University Hospitals
Institutional Review Board issued approval STUDY20181262. Conflicts of interest: In
compliance with the ICMJE uniform disclosure form, all authors declare the following:
Payment/services info: All authors have declared that no financial support was received from
any organization for the submitted work. Financial relationships: All authors have declared
that they have no financial relationships at present or within the previous three years with any
organizations that might have an interest in the submitted work. Other relationships:
Regeneron supplied dupilumab at no cost to our patient through their Compassionate Use
Program. We obtained an “Investigative New Drug” designation for this use.
References
1. Parish WE, Champion RH, Rook AJ: A study of auto-allergy in generalized eczema . Br J
Dermatol. 1965, 77:479-526. 10.1111/j.1365-2133.1965.tb14570.x
2. Haxthausen H: Generalized ids (autosensitization) in varicose eczema . Acta Derm Venereol.
1955, 35:271-280.
3. González-Amaro R, Baranda L, Abud-Mendoza C, Delgado SP, Moncada B:
Autoeczematization is associated with abnormal immune recognition of autologous skin
antigens. J Am Acad Dermatol. 1993, 28:56-60. 10.1016/0190-9622(93)70009-i
4. Strid J, Hourihane J, Kimber I, Callard R, Strobel S: Disruption of the stratum corneum allows
potent epicutaneous immunization with protein antigens resulting in a dominant systemic
Th2 response. Eur J Immunol. 2004, 34:2100-2109. 10.1002/eji.200425196
5. Brandt EB, Sivaprasad U: Th2 cytokines and atopic dermatitis. J Clin Cell Immunol. 2011,
2:110. 10.4172/2155-9899.1000110
6. Thaçi D, L Simpson E, Deleuran M, et al.: Efficacy and safety of dupilumab monotherapy in
adults with moderate-to-severe atopic dermatitis: a pooled analysis of two phase 3
randomized trials (LIBERTY AD SOLO 1 and LIBERTY AD SOLO 2). 2019, 94:266-275.
10.1016/j.jdermsci.2019.02.002
7. Angelova-Fischer I, Wuthe D, Zillikens D, Kahle B: Noninvasive bioengineering assessment of
the skin barrier function in patients with chronic venous insufficiency. Br J Dermatol. 2010,
162:1071-1075. 10.1111/j.1365-2133.2010.09641.x
8. Tracey EH, Elston C, Feasel P, Piliang M, Michael M, Vij A: Erythrodermic presentation of
psoriasis in a patient treated with dupilumab. JAAD Case Rep. 2018, 4:708-710. Accessed:
April 16, 2020: 10.1016/j.jdcr.2018.05.014
9. Stout M, Guitart J, Tan T, Silverberg JI: Psoriasis-like dermatitis developing in an atopic
dermatitis patient treated with dupilumab. Dermatitis. 2019, 30:376-378.
10.1097/DER.0000000000000509
10. Safa G, Paumier V: Psoriasis induced by dupilumab therapy . Clin Exp Dermatol. 2019, 44:49-
50. 10.1111/ced.13901
11. Fowler E, Silverberg JI, Fox JD, Yosipovitch G: Psoriasiform dermatitis after initiation of
treatment with dupilumab for atopic dermatitis. Dermatitis. 2019, 30:234-236.
10.1097/DER.0000000000000481
12. Napolitano M, Scalvenzi M, Fabbrocini G, Cinelli E, Patruno C: Occurrence of psoriasiform
eruption during dupilumab therapy for adult atopic dermatitis: a case series. Dermatol Ther.
2019, 32:e13142. 10.1111/dth.13142
13. Guttman-Yassky E, Krueger JG: Atopic dermatitis and psoriasis: two different immune
diseases or one spectrum?. Curr Opin Immunol. 2017, 48:68-73. 10.1016/j.coi.2017.08.008
14. Ellenbogen Y, Jiménez-Saiz R, Spill P, Chu DK, Waserman S, Jordana M: The initiation of Th2
immunity towards food allergens. Int J Mol Sci. 2018, 16:1447. Accessed: March 31, 2020:
10.3390/ijms19051447
15. de Wijs LEM, Nguyen NT, Kunkeler ACM, Nijsten T, Damman J, Hijnen DJ: Clinical and
2020 Schrom et al. Cureus 12(4): e7831. DOI 10.7759/cureus.7831 4 of 5
histopathological characterization of paradoxical head and neck erythema in patients with
atopic dermatitis treated with dupilumab: a case series [Online ahead of print]. Br J Dermatol.
2019, Accessed: April 16, 2020: 10.1111/bjd.18730
16. Guenova E, Skabytskaa Y, Hoetzeneckera W, et al.: IL-4 abrogates T(H)17 cell-mediated
inflammation by selective silencing of IL-23 in antigen-presenting cells. Proc Natl Acad Sci
USA. 2015, 112:2163-2168. 10.1073/pnas.1416922112
17. Nakamura M, Lee K, Singh R, et al.: Eczema as an adverse effect of anti-TNFa therapy in
psoriasis and other Th1-mediated diseases: a review. J Dermatol Treat. 2017, 28:237-241.
10.1080/09546634.2016.1230173
18. Lai FYX, Higgins E, Smith CH, Barker JN, Pink A: Morphologic switch from psoriasiform to
eczematous dermatitis after anti-IL-17 therapy: a case series. JAMA Dermatol. 2019,
155:1082-1084. 10.1001/jamadermatol.2019.1268
19. Guttman-Yassky E, Krueger JG, Lebwohl MG: Systemic immune mechanisms in atopic
dermatitis and psoriasis with implications for treatment. Exp Dermatol. 2018, 27:409-417.
10.1111/exd.13336
20. Weidinger S, Willis-Owen SA, Kamatani Y, et al.: A genome-wide association study of atopic
dermatitis identifies loci with overlapping effects on asthma and psoriasis. Hum Mol Genet.
2013, 22:4841-4856. 10.1093/hmg/ddt317
2020 Schrom et al. Cureus 12(4): e7831. DOI 10.7759/cureus.7831 5 of 5
