There is a limited therapeutic armamentarium for recalcitrant cases of childhood rosacea.
We report the case of a 12-year-old girl who presented with severe ocular and cutaneous rosacea unresponsive to oral doxycycline, oral isotretinoin, and topical tacrolimus. A biopsy specimen showed numerous mites within the folliculosebaceous unit. Treatment with a single dose of oral ivermectin achieved resolution of her symptoms.
Conclusions and Relevance
The causative role of Demodex folliculorum should be considered in immunocompetent children with rosacea or rosacea-like refractory eruptions. In such cases, treatment with ivermectin can be beneficial.
An otherwise healthy 12-year-old girl presented with facial lesions including erythema, papules, and pustules of 1-year duration. She also had blepharitis, reddening of the conjunctiva on the left eye, and corneal opacity on the right eye (Supplement [eFigure 1]). She had no history of recurrent infections and, other than these findings, the results of her physical examination, as well as a comprehensive metabolic panel and complete blood cell count, were normal. There were no lesions on other parts of her body, although she eventually had involvement on the neck and anterior chest. The patient reported no worsening of her lesions after sun exposure. She had undergone 3 biopsies in a different center; the results of all were consistent with acne rosacea. The recurrent episodes of blepharoconjunctivitis with corneal opacities were treated with topical corticosteroids and cyclosporine, 0.05%, solution with minor success. The lack of response to treatment prompted a new skin biopsy to confirm the clinical diagnosis. Histologic examination revealed perivascular and perifollicular lymphohistiocytic infiltrates with conspicuous neutrophils and scattered multinucleated histiocytes as well as numerous Demodex mites, in follicular infundibula.
Treatment with doxycycline, 100 mg/d, and topical tacrolimus for 2 months achieved temporary improvement in the skin lesions (Supplement [eFigure 2]); however, the ocular symptoms persisted. Doxycycline was discontinued. The patient had a flare 4 weeks after discontinuing doxycycline; restarting the drug did not result in improvement. A trial of oral isotretinoin, 0.5 mg/kg/d, was administered for 2 months. She continued to use topical tacrolimus. There was some improvement in the skin lesions; however, the blepharoconjunctivitis and corneal opacities were not improved (Figure, A).
A, Before treatment with ivermectin. Oral isotretinoin had been discontinued 1 month ago and the patient was using only topical tacrolimus twice daily. B, Resolution of the lesions after a single dose of oral ivermectin. The photograph was taken at the 6-month follow-up visit.
We thought that Demodex folliculorum might be the underlying cause of the facial and ocular rosacea and sought to eradicate it from her skin. Microbial organisms, such as Helicobacter pylori, Staphylococcus epidermidis, Demodex brevis, and D. folliculorum, have been suggested1- 4 as causative or triggering factors for initiation of the inflammatory response in rosacea. As noted, numerous Demodex mites were demonstrated in our patient’s biopsy specimen. Oral doxycycline and isotretinoin were discontinued 1 month before treatment with a single 12-mg dose of ivermectin (250 µg/kg). This therapy resulted in marked improvement of the lesions at the 1-month follow-up, and resolution was achieved progressively without further topical or oral treatments (Figure, B). There was resolution of the ocular symptoms and, 2 years after ivermectin administration, there was no recurrence.
Rosacea in children is uncommon and not as well described as in adults.1 Childhood rosacea generally presents as papulopustular or granulomatous rosacea subtype.1,2 Ocular rosacea is also uncommon in children.1,2 The most common presenting sign of ocular rosacea is meibomian gland dysfunction, but it may also present as blepharitis, papillary hypertrophy, conjunctival hyperemia, or corneal opacities.2 Childhood rosacea is usually treated with oral antibiotics. Erythromycin and metronidazole are most commonly used, as well as tetracyclines in children older than 8 years.1,3 Macrolides, oral isotretinoin, and topical treatments, such as metronidazole, azelaic acid, or niacinamide, have also proved useful.1,3,5 Therapies for ocular rosacea include eyelid hygiene, the oral antibiotics mentioned above, and ophthalmic metronidazole, erythromycin gel, and cyclosporine, 0.05%, solution.2Demodex mites are a common ectoparasite of the pilosebaceous unit in humans and have been implicated in rosacea, folliculitis, dermatitis, and blepharitis.3,4 These mites are thought to play a role in the inflammatory process and are generally absent in childhood, with increasing incidence throughout adulthood.2- 4 Although an infrequent case of skin disease in children, they have been implicated in childhood ocular rosacea and rosacea-like eruptions in children.1,2,4 The cause and pathogenesis of rosacea are not fully understood. Not all patients with rosacea have a large Demodex burden, and not all patients with a large mite burden have rosacea.4 However, when childhood rosacea is refractory to conventional treatment, a skin biopsy or scraping may be useful in evaluation of the Demodex mite burden because eliminating them has successfully treated rosacea in a subset of patients.1,4,5 It is hypothesized that local immunosuppression at the level of the pilosebaceous unit, elevated levels of serine proteases and kallikrein, and commensal bacteria interacting with the mites all contribute to the disfiguring lesions in demodicosis.4 The hypothesized pathogenesis of ocular lesions is similar to that of skin lesions.2,4 Children with rosacea usually have limited ocular involvement, and few patients present with severe forms, such as corneal ulcers or extensive blepharoconjunctivitis.2 The reported cases of pediatric patients with demodicosis are usually children who are immunocompromised,6 but there are also reports of demodicosis in immunocompetent children.5,7 Ivermectin is an antiparasitic drug that likely leads to parasite paralysis and death by interfering with neurotransmission.8 Single-dose ivermectin has primarily been reported as a means of treating demodicosis in immunosuppressed patients,6,9 although there are reports of its success in immunocompetent patients.7 As with other treatments for rosacea, complete response time will depend on the degree of inflammatory changes, so our patient may have had delayed benefit resulting from earlier treatments. For most patients, the recovery period is approximately 2 to 8 weeks following ivermectin administration (as measured by clinical improvement and skin scrapings negative for mites).6,7,9 Immunocompromised patients may have especially refractory cases that may take weeks to months to show resolution.9,10 Combination therapies with metronidazole, topical corticosteroids, or permethrin have been used in addition to ivermectin in these cases.
To our knowledge, this is the first reported case of an immunocompetent adolescent in whom conventional treatments failed and single-dose ivermectin was required to treat severe oculocutaneous rosacea. The causative role of Demodex mites should be considered in recurrent rosacea or recalcitrant rosacea-like eruptions on the face of children unresponsive to conventional treatments.
Accepted for Publication: August 22, 2013.
Corresponding Author: Angela Hernández-Martín, MD, Department of Dermatology, Hospital Infantil del Niño Jesús, Avda. Menendez Pelayo, 65, 28009 Madrid, Spain (firstname.lastname@example.org).
Published Online: November 27, 2013. doi:10.1001/jamadermatol.2013.7688.
Author Contributions: Drs Brown and Hernández-Martín had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Brown, Hernández-Martín.
Acquisition of data: Hernández-Martín, Clement, Colmenero.
Analysis and interpretation of data: Hernández-Martín, Colmenero, Torrelo.
Drafting of the manuscript: Hernández-Martín, Brown.
Critical revision of the manuscript for important intellectual content: All authors.
Administrative, technical, and material support: Brown, Colmenero.
Study supervision: Hernández-Martín, Clement, Torrelo.
Conflict of Interest Disclosures: None reported.
eFigure 1. Clinical findings before treatment
eFigure 2. Noticeable improvement of the skin lesions with doxycycline, 100 mg/d
Brown M, Hernández-Martín A, Clement A, Colmenero I, Torrelo A. Severe Demodexfolliculorum–Associated Oculocutaneous Rosacea in a Girl Successfully Treated With Ivermectin. JAMA Dermatol. 2014;150(1):61-63. doi:10.1001/jamadermatol.2013.7688