Two adolescent boys presented with acute acneiform eruptions in the setting of recent dupilumab administration. Subsequent investigation via direct scraping of pustules revealed live Demodex mite colonization of the face. These adolescent patients represent a population not commonly associated with Demodex folliculitis, and we theorize their baseline commensal Demodex mite population may have increased as a consequence of dupilumab-induced, focused immunomodulation. We recommend that pediatricians consider Demodex potentially etiologic in patients presenting with new onset acneiform or rosacea-like dermatoses in patients treated with dupilumab.
Case Report
Infestation by Demodex folliculorum, an obligate ectoparasite mite found in or near the pilosebaceous follicle and sebaceous glands, usually remains clinically asymptomatic. However, the skin of rosacea patients tends to have an increased density of Demodex mites, the presence of which has been correlated to an amplified release of interleukin (IL)-17, possibly playing a role in this inflammatory skin condition.1,2 Dupilumab, a monoclonal antibody targeting the α chain of the IL-4 receptor, carries with it a prescriber warning that it “will influence the immune response against helminth infections.”3 There has been at least 1 report of an adult patient who experienced recurrent episodic flares of rosacea temporarily associated with her dupilumab injections that resolved after dupilumab discontinuation,4 and it has been recently postulated that dupilumab’s inhibition of IL-4 and IL-13 may permit a proliferation of Demodex mite density, leading to ocular rosacea-like symptoms with an attendant conjunctivitis.5 To date, a specific increased incidence of Demodex folliculitis has not been reported among dupilumab patients, either because such a relationship does not truly exist or because it remains underrecognized. In this article, we present the case of 2 adolescent boys who developed Demodex folliculitis in the setting of recent dupilumab administration.
The index patient is a >60-kg, 15-year-old boy with long-standing moderate-severe atopic dermatitis who had completed 4 consecutive months of dupilumab 300 mg every other week before discontinuing the medication 3 months earlier because of anxiety around performing self-injections. He denied history of conjunctivitis but reported regular use of olopatadine 0.2% drops for the relief of “itchy eyes” secondary to environmental allergies. The second patient is a 44-kg, 12-year-old boy with a lifelong history of moderate-severe atopic dermatitis on dupilumab for 4 months at a dose of 200 mg every other week with excellent results. Neither patient had used any topical or oral medication since starting dupilumab (Figs 1 and 2).
Index patient with acute, spreading acneiform eruption on forehead (A), cheeks (B), nose, and chin.
Index patient with acute, spreading acneiform eruption on forehead (A), cheeks (B), nose, and chin.
Second patient with agminated, monomorphic, slightly scaly, pustules on right cheek (A) greater than left cheek (B). An area ∼1 cm2 on the right cheek selected for direct skin scraping has been delineated in blue surgical marker.
Second patient with agminated, monomorphic, slightly scaly, pustules on right cheek (A) greater than left cheek (B). An area ∼1 cm2 on the right cheek selected for direct skin scraping has been delineated in blue surgical marker.
Demodex mite obtained from second patient by direct skin scraping of an individual pustule. Viewed at original magnification 10×. Note the fleck of blue surgical marker in the field of view, correlating with the delineated area from which the skin scraping was performed.
Demodex mite obtained from second patient by direct skin scraping of an individual pustule. Viewed at original magnification 10×. Note the fleck of blue surgical marker in the field of view, correlating with the delineated area from which the skin scraping was performed.
Both patients presented with sudden onset (<2 weeks) of a “spreading,” acneiform eruption consisting of monomorphic, slightly scaly, inflammatory papules and pustules on the face. Comedones and cysts were notably absent. An area on the face, ∼1 cm2 in size, was delineated for direct skin scraping and microscopic examination. Expressed contents from the index patient demonstrated at least 8 live Demodex folliculorum mites, whereas the second patient revealed live Demodex folliculorum mites in each expressed pustule (Fig 3). Both patients were treated with topical ivermectin 1% cream twice a day for 4 weeks, and no posttreatment microscopic examination was performed because the lesions clinically resolved.
As adolescents, these patients represent a population not commonly associated with Demodex folliculitis.6 It is entirely possible that their acute pustular eruptions were caused by an etiology unrelated to administration of dupilumab (eg, stress, sun exposure, etc). We theorize, however, that the patients’ baseline commensal Demodex mite populations may have increased as a consequence of their dupilumab-induced, focused immunomodulation. Why the index patient flared ∼3 months after discontinuing dupilumab is unclear. Perhaps the inflammatory nature of the Demodex folliculitis was masked until dupilumab had been sufficiently eliminated; the timing correlates with the reported duration of 10 to 12 weeks to reach nondetectable concentrations.3 Alternatively, that amount of time may have been required for the Demodex mite population to reach a “critical mass” necessary to cause clinically relevant symptoms.
Although a case series of 2 patients does not establish causation, the documentation of Demodex folliculitis in the setting of recent dupilumab administration establishes a potential link between the drug and dermatosis. We recommend that pediatricians consider Demodex as potentially etiologic in patients presenting with new onset acneiform or rosacea-like dermatoses in patients treated with dupilumab.
Dr Krakowski conceptualized and designed the case report and acquired data from primary sources, patient interactions, and procedures; Drs Senft and Heymann helped to conceptualize the case report and helped to draft the initial manuscript; and all authors reviewed and revised the manuscript and approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
FUNDING: No external funding.
References
Competing Interests
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
Comments