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Vol. 113. Núm. 3.
Páginas T219-T221 (Marzo 2022)
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Vol. 113. Núm. 3.
Páginas T219-T221 (Marzo 2022)
Opinion article
Open Access
[Translated article] Patterns of Head and Neck Dermatitis in Patients Treated With Dupilumab: Differential Diagnosis and Treatment
Patrón de dermatitis de cabeza y cuello en pacientes tratados con Dupilumab: diagnóstico diferencial y tratamiento
F.J. Navarro-Triviño, R. Ruiz-Villaverde
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Corresponding author.
Departamento de Eczema de Contacto e Inmunoalergia, Dermatología, Hospital Universitario San Cecilio, Granada, Spain
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F.J. Navarro-Triviño, R. Ruiz-Villaverde
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Atopic dermatitis is a chronic inflammatory skin disease that is very common in childhood. Among adults it is an increasingly common reason for consultation and is diagnosed with increasing frequency. Dupilumab is a monoclonal antibody that blocks the interleukin 4 (IL-4) receptor subunit α, decreasing activation of cells that express this receptor (mainly Th2 lymphocytes). The decreased polarization of naïve Th to Th2 lymphocytes results in a decrease in the secretion and function of the cytokines IL-4, IL-13, and IL-5. Naive Th lymphocytes are instead polarized to Th1 and Th17 lymphocytes, increasing the secretion of the corresponding cytokines.

Therapeutic blockade of certain cytokines or their receptors causes certain immunological modifications. Beneficial effects have been described for several such therapies, mainly in patients with psoriasis, although paradoxical reactions occur in some patients.

The persistence or de novo appearance of head and neck dermatitis, which is observed in up to 10% of the cases in clinical practice,1 was not reported in the phase 3 clinical trial of dupilumab. Zhu et al.2 reported the appearance or persistence of facial dermatitis in 14 patients treated with dupilumab. In their study of 1000 patients with atopic dermatitis who were treated with dupilumab, Soria et al.3 found that this biological treatment resulted in the appearance of de novo head and neck dermatitis in 10 patients, and aggravation of the same presentation in 32, requiring discontinuation of dupilumab treatment in some cases.

Given these findings, it is important to consider the possibility of dermatosis of the head and neck in dupilumab-treated patients. This requires knowledge of the peculiarities of the corresponding lesions in affected patients.

Malassezia hypersensitivity4 is proposed as the main reason for the de novo appearance or exacerbation of facial dermatitis. Pityriasiform lesions on the scalp (Fig. 1), whether associated or not with localized facial lesions in seborrheic areas, are indicative of seborrheic dermatitis. Detection of specific immunoglobulin (Ig) E against Malassezia species and a culture positive for this fungus can help orient the diagnosis. The underlying etiology is not well defined. Studies, including that of Adalsteinsson et al.,5 have proposed that Th2 lymphocytes are the main adaptive immune system cells responsible for regulating interactions with this commensal fungus. An adequate therapeutic response to oral or topical antifungals has been described in these cases.

Figure 1.

De novo pityriasiform dermatitis that appeared on the scalp of a dupilumab-treated patient 2 months after starting treatment.


Rosacea is another dermatosis that appears to play a key role in head and neck dermatitis in dupilumab-treated patients. Of 94 patients treated with dupilumab, 6.4% showed histologically confirmed inflammatory rosacea with an increase in colonization by the parasite Demodex.6 The proliferation of Demodex after polarization to Th1 and Th17 is proposed as trigger for rosacea. Although flushing episodes were observed in these patients, the main clinical manifestation appears to be basal erythema with inflammatory papules located mainly in the malar area. Histology reveals the abundant presence of Demodex folliculorum, although an adhesive tape test can demonstrate the presence of this parasite less invasively. It is important to remember the utility of the dermoscopy for the detection of Demodex species.7 Topical ivermectin or oral tetracyclines are the treatments of choice in these cases.

The persistence or de novo appearance of eyelid dermatitis may pose the greatest diagnostic and therapeutic challenge in clinical practice. In such cases, it will be necessary to rule out the presence of allergic contact dermatitis (ACD). The main culprits are fragrances and preservatives, although others, such as surfactants (e.g. cocamidopropyl betaine, derived from coconut), are common components of hair cosmetics. Both Raffi et al.8 and Zhu et al.9 reported no interference of continuous dupilumab treatment with patch testing. Another potential cause is ACD resulting from contact between the hands and face. In such cases, acrylates are one of the main allergens responsible, especially in women.

Sensitization to pneumoallergens is another potential cause in patients who show a seasonal worsening of head and neck dermatitis. Detection of specific IgE and collaboration with an allergologist is essential to confirm this etiology. Despite antihistamine treatment, skin lesions in these patients do not usually improve, necessitating specific recommendations on environmental exposure and the use of topical calcineurin inhibitors for the period during which the individual is exposed to pneumoallergens.

Obviously, there will be complex cases in which the cause of head and neck dermatitis in a given patient will not be clear. A growing body of evidence on this topic will help further our knowledge. However, the persistence or de novo appearance of head and neck dermatitis in patients taking dupilumab should not be a reason for treatment discontinuation. Clinical peculiarities may aid the dermatologist in selecting the most appropriate adjuvant treatment for each patient. Table 1 shows the clinical characteristics, corresponding additional tests, and recommended treatments in dupilumab-treated patients with head and neck dermatitis.

Table 1.

Possible etiologies of head and neck dermatitis in dupilumab-treated patients.

Bacterial  Clinical manifestations  Complementary test  Treatment 
Seborrheic dermatitis  Pityriasiform lesions (dry whitish scales) over orange erythema in seborrheic areas and on the scalp  Microbiological cultureMalassezia IgEMalassezia spp. prick testSkin biopsy  Oral antifungalsFluconazole 150mg/wk, 2 dosesItraconazole 50–100mg/d, 7–14 daysTopical antifungalsClotrimazoleFenticonazoleKetoconazole 
Rosacea  Flushing (less frequent)Malar erythemaErythematous papulesPustules  Punch biopsyIn vivo study with adhesive test  Topical ivermectin 1%Oral doxycyclineOral isotretinoin 
Allergic contact dermatitis  Localized eczema on the eyelids and hairline  Patch testsStandard seriesFragrance seriesCosmetic seriesOwn cosmetics  Avoid allergenHigh-potency topical corticosteroidsTopical calcineurin inhibitors 
Airborne dermatitis  Facial eczema with involvement of skinfolds such as the eyelids and the retroauricular area  Specific IgE against pneumoallergensSpecific prick tests  Oral antihistaminesHigh-potency topical corticosteroidsTopical calcineurin inhibitors 
R.A. Waldman, M.E. DeWane, B. Sloan, J.M. Grant-Kels.
Characterizing dupilumab facial redness: a multi-institution retrospective medical record review.
J Am Acad Dermatol, 82 (2020), pp. 230-232
G.A. Zhu, J.K. Chen, A. Chiou, J. Ko, G. Honari.
Assessment of the development of new regional dermatoses in patients treated for atopic dermatitis with dupilumab.
JAMA Dermatol, 155 (2019), pp. 850-852
A. Soria, A. Du-Thanh, J. Seneschal, M. Jachiet, D. Staumont-Sallé, S. Barbarot.
GREAT research group development or exacerbation of head and neck dermatitis in patients treated for atopic dermatitis with dupilumab.
JAMA Dermatol, 155 (2019), pp. 1312-1315
K. Darabi, S.G. Hostetler, M.A. Bechtel, M. Zirwas.
The role of Malassezia in atopic dermatitis affecting the head and neck of adults.
J Am Acad Dermatol, 60 (2009), pp. 125-136
J.A. Adalsteinsson, S. Kaushik, S. Muzumdar, E. Guttman-Yassky, J. Ungar.
An update on the microbiology, immunology and genetics of seborrheic dermatitis.
Exp Dermatol, 29 (2020), pp. 481-489
T. Quint, P.M. Brunner, C. Sinz, I. Steiner, R. Ristl, K. Vigl, et al.
Dupilumab for the treatment of atopic dermatitis in an Austrian cohort-real-life data shows rosacea-like folliculitis.
J Clin Med, 9 (2020), pp. 1241
G. Serarslan, Ö. Makbule Kaya, E. Dirican.
Scale and pustule on dermoscopy of rosacea: a diagnostic clue for demodex species.
Dermatol Pract Concept, 11 (2021), pp. e2021139
J. Raffi, R. Suresh, N. Botto, J.E. Murase.
The impact of dupilumab on patch testing and the prevalence of comorbid allergic contact dermatitis in recalcitrant atopic dermatitis: a retrospective chart review.
J Am Acad Dermatol, 82 (2020), pp. 132-138
G.A. Zhu, J.K. Chen, A. Chiou, J. Ko, G. Honari.
Repeat patch testing in a patient with allergic contact dermatitis improved on dupilumab.
JAAD Case Rep, 5 (2019), pp. 336-338
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