NorCal Open Access PublicationsJournal of Dermatologic Surgery, Research and TherapyVolume 2, Issue 2Tampouratzi E, et al.

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Case Report

Eleftheria Tampouratzi1, Theodora Kanni2, Xristina Kapizioni3, Theodora Douvali2 and John Katsantonis1

1Department of Dermatology and Venereology, Tzaneio General Hospital, Piraeus, Greece2Department of Dermatology and Venereology, Andreas Sygros Hospital, Athens, Greece3Department of Gastroenterology, Tzaneio General Hospital, Piraeus, Greece*Corresponding author: Theodora Kanni, Department of Dermatology and Venereology, Andreas Sygros Hospital, Athens, Greece. Tel: +30 210 72 65 100 ; E-mail: kannidora@med.uoa.gr

Received Date: 23 October, 2019; Accepted Date: 28 November, 2019; Published Date: 06 December, 2019

AbstractBackground: Atopic dermatitis is a chronic, relapsing inflammatory disease, characterized by pruritus, eczema, papules and in the late disease lichenification of the skin. Therapeutic approaches for atopic dermatitis have been stagnant for years with treatment options being emollients, general skin care, corticosteroids and calcineurin inhibitors.

Patients and methods: We present 2 cases with atopic dermatitis, resistant in usual treatments, that received omalizumab with a very good response. The dosage regimen was the same as that given in chronic spontaneous urticaria: 300mg by subcutaneously, every 4 weeks.

Results: Pruritus, measured with DLQI (Dermatology Life Quality Index) and VAS (Visual Analogue Scale), was significantly improved after 2 months of treatment, without any of the undesirable effects. Additionally, one month after treatment start no laboratory disturbances were detected with total IgE of the first patient remaining increased. Both patients continue the same treatment one year after with excellent tolerance. They are under follow-up of three months with their symptoms fully controlled and with significant improvement of their quality of life.

Conclusion: Omalizumab represents to our opinion another good alternative therapeutic option in difficult cases of adult atopic dermatitis where conventional medications have failed. Our clinical experience suggests excellent efficacy of omalizumab without any undesirable effects on 1 year follow up in two elderly patients. Further evidence in the

form of randomized controlled trials is needed to elucidate the role of omalizumab in refractory atopic dermatitis.

Keywords: Anti-IgE, Atopic dermatitis, Omalizumab.

IntroductionAtopic dermatitis is a chronic, relapsing inflammatory

disease, characterized by pruritus, eczema, papules and in late stages lichenification of the skin. It is accompanied by intense itching with negative impact on patient’s quality of life [1]. Therapeutic advances have been stagnant for years with treatment options being emollients, general skin care, corticosteroids and calcineurin inhibitors. In patients who fail conventional topical therapy or phototherapy are used systemic immunomodulating drugs: cyclosporine (150-300mg/day), methotrexate (7.5-25mg/week), azathioprine (1-3mg/kg/day) or mycophenolate mofetil (1-1.5gr orally twice daily) but these medications have been associated with significant side effects [2]. Over the past decades there has been remarkable development of biological agents, result of an increase in the knowledge of specific immune cascades essential in the development of monoclonal antibodies against key perpetrators.

Dupilumab, a human IgG4 monoclonal antibody inhibits IL-4 receptor who block IL-4 and IL-13 release and is the first targeted biologic therapy for moderate to severe atopic dermatitis [3]. Omalizumab, a monoclonal antibody that prevents binding of IgE to the surface of mast cells by forming complexes with free IgE in serum, is officially used for chronic urticaria [4]. It is the first drug approved for

Resistant Atopic Dermatitis Successfully Treated with Omalizumab: Report of 2 Cases

Citation: Tampouratzi E, Kanni T, Kapizioni X, Douvali T, Katsantonis J (2019) Resistant Atopic Dermatitis Successfully Treated with Omalizumab: Report of 2 Cases. J Dermatol Surg Res Ther 2019: 81-83.

J Dermatol Surg Res Ther 2019: 81-83. 02

patients with chronic spontaneous urticaria who remain symptomatic despite H1-antihistamine therapy. Several randomized clinical trials have confirmed its efficacy, safety and tolerability, showing significant improvement in terms of reducing symptoms and mitigating signs of the disease [5].

We herein present 2 cases with atopic dermatitis resistant in usual regimens that received omalizumab with a very good response without side effects on 12 months follow up. Written informed consent was undertaken for both patients.

Case reportsThe first patient, a 72-year old man, was referred to us

for pruritic red macules located on his arms, legs, chest and back first occurring 7 years ago. Itching was under control with antihistamines and corticosteroid treatments until 6 months before the referral when symptoms recurred despite continuing therapy (Figure 1). His medical history was free of any underlying disease and the laboratory tests were unremarkable (table 1) except for total IgE which was increased (1000 iu/ml). Skin biopsy demonstrated chronic dermatitis with hyperkeratosis, parakeratosis, hyper-

granulosis, acanthosis and vertically oriented collagen bundles in the papillary dermis (Figure 2).

The second patient, an 80-year old woman, presented with whole body pruritic hyperkeratotic papules more prominent in arms and legs, first presenting 5 years ago. She temporarily improved with antihistamines and corticosteroids in the past but shortly after therapy discontinuation she relapsed. The last 2 months of topical treatment with corticosteroids and antihistamines (4 times per day) there was no improvement of the disease. Her medical history included only hypertension under medical therapy with b-blockers (metoprolol 100mg/day). Laboratory tests were normal (Table 1). Skin biopsy revealed hyperplastic epidermis with elongation of the rete ridges, prominent hyperkeratosis and minimal spongiosis, with no intercellular edema. In addition, dyskeratosis and scale crust were noted. Dermal changes included papillary fibrosis and a moderate perivascular and intervascular lymphohistiocytic infiltrate in the upper dermis. Due to patients’ age and taking into consideration possible side effects of cyclosporine, omalizumab was selected as the best treatment option. The dosage regimen

Figure 1: a) Patient 1 with pruritic red macules on legs, before treatment, b) Patient 1, one month after treatment.

Patient 1 Patient 1 Patient 2 Patient 2Before Treatment One month after treatment Before Treatment One month after treatment

HCT(%) 47.4 44.1 38.1 38.7HGB(gr/dL) 16.2 14.7 12.9 12.7RBC(M/μl) 5.45 4.91 4.41 4.30WBC(K/ μl) 8.1 7.3 7.1 7.7NEUT(%) 55.4 49.5 60 56.7LYM(%) 34.6 40.8 30 38

MONO(%) 7 6.8 7 3.7EOS(%) 3 4 3 0.9

BASO(%) 0 0 0 0.7PLT(K/ μl) 160 165 191 188

GLU(mg/dL) 92 97 97 86UREA(mg/dL) 40 42 35 39

CREAT(mg/dL) 1.4 1.4 0.71 0.9CHOL(mg/dL) 206 200 187 194TRIGL(mg/dL) 180 193 88 82SGOT(mg/dL) 37 35 28 24SGPT(mg/dL) 34 30 16 20ALP(mg/dL) 90 103 85 82IgE(iu/ml) 1000 923 154 150

Table 1: Patients’ laboratory tests.

Citation: Tampouratzi E, Kanni T, Kapizioni X, Douvali T, Katsantonis J (2019) Resistant Atopic Dermatitis Successfully Treated with Omalizumab: Report of 2 Cases. J Dermatol Surg Res Ther 2019: 81-83.

J Dermatol Surg Res Ther 2019: 81-83. 03

was the same as that given in chronic spontaneous urticaria: 300mg by subcutaneous administration, every 4 weeks. Pruritus, measured with DLQI (Dermatology Life Quality Index) and VAS (Visual Analogue Scale), was significantly improved after 2 months of treatment, without any of the undesirable effects mentioned in the revised summary of product characteristics of the drug released in 2018 [6].

Additionally, one month after treatment start no laboratory disturbances were detected with total IgE of the first patient remaining increased (table 1) and also his clinical profile was significantly improved (Figure 2).Second patient increased IgE three months after initiating treatment with omalizumab (IgE: 180iu/ml), as it happens in “slow responders” in chronic urticaria that need more time to response to treatment [7]. One year after, both patients continue the same treatment with excellent tolerance. They both have elevated total IgE (the first patient:825iu/ml and the second 303iu/ml) indicating good response in medicine. They are under 3-month follow-up with their symptoms fully controlled and with significant improvement of their quality of life.

DiscussionTo our knowledge this is the first description of omalizumab

use as a treatment option for atopic dermatitis. According to current knowledge, atopic dermatitis frequently persists as an itch-scratch cycle who do not respond to antihistamines but improves with anti-inflammatory (corticosteroid and calcineurin inhibitors) treatments. Our patients had initial partial response to conventional therapy but efficacy weaned off over time. Although only one patient had increased levels of IgE, correlating with atopic predisposition, they both responded successfully to omalizumab. The underlying pathophysiologic mechanism of chronic itching has not yet been fully elucidated but is believed to be a complicated interaction among skin keratinocytes, cutaneous nerve fibers, pruritogenic molecules and their effect on peripheral

and central nervous system [8]. The mechanism of action of omalizumab could explain its beneficial effect in the down-regulation of mast cell activation implicated in atopic dermatitis [4], even though the exact mechanism is still elusive.

Omalizumab represents to our opinion a good alternative therapeutic option in difficult cases of atopic dermatitis where conventional medications have failed and other treatments as systemic immunosuppressors were not advisable. Our clinical experience with these two patients suggests excellent efficacy of omalizumab without any undesirable effects on 1 year follow up in elderly patients. Further evidence in the form of randomized controlled trials is needed to elucidate the role of omalizumab in refractory adult atopic dermatitis.

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2. Sidbury R, Davis DM, Cohen DE, Cordoro KM, Berger TG et al (2014) Guideliness of care for the management of atopic dermatitis. J Am Acad Dermatol 71: 327-349

3. Eshtiaghi P, Gooderham MJ (2018) Dupilumab: an evidence-based review of its potential in the treatment of atopic dermatitis. Core Evid 13: 13-20.

4. Beck LA, Marcotte GV, MacGlashan D, Togias A, Saini S (2004) Omalizumab induced reductions in mast cell Fcepsillon RI expression and function. J Allergy Clin Immunol 114: 527-530.

5. Deza G, Bertolín-Colilla M, Pujol RM, Curto-Barredo L, Soto D, et al. (2017) Basophil FcεRI Expression in Chronic Spontaneous Urticaria: A Potential Immunological Predictor of Response to Omalizumab Therapy. Acta Derm Venereol 97: 698-704.

6. Revision summary of product characteristics of the drug released 2018.

7. Ghezanfar MN, Thomsen SF (2018) Predicting response to omalizumab in chronic urticaria based on biomarkers. EMJ Dermatol 6: 124-130

8. Mollanazar NK, Smith PK, Yosiporitch G. (2016) Mediators of chronic pruritus in atopic dermatitis: getting the itch out? Clin Rev Allergy Immunol 51: 263-292.

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