Ivermectin therapy for papulopustular rosacea and periorificial dermatitis in children: A series of 15 cases

      To the Editor: Treatment of papulopustular rosacea (PPR) and periorificial dermatitis (POD) can be challenging in children. Demodex mites, although part of the normal-appearing skin fauna, are more numerous in rosacea and POD than in normal-appearing skin.
      • Elston D.M.
      Demodex mites: facts and controversies.
      In 2014, we reported a case of severe oculocutaneous rosacea in a 12-year-old girl treated with a single dose of oral ivermectin
      • Brown M.
      • Hernández-Martín A.
      • Clement A.
      • Colmenero I.
      • Torrelo A.
      Severe demodexfolliculorum-associated oculocutaneous rosacea in a girl successfully treated with ivermectin.
      ; the excellent response encouraged us to use it in subsequent cases. The aim of this retrospective study was to assess the benefit and tolerability of oral and topical ivermectin therapy in pediatric PPR and POD.
      Eight patients with PPR and 7 with POD (mean age 9.8 ± 2.2 years) were treated with either a single dose of 200 to 250 μg/kg of oral ivermectin or a compound of 1% ivermectin in an oil-in-water base cream applied once a day for 3 months. Oral ivermectin was prescribed for 6 children with PPR and 3 with POD. Oral or topical therapy was chosen depending on the severity of the condition. No other medications were allowed.
      To assess disease severity at baseline and after treatment, we applied the Investigator Global Assessment score by retrospectively reviewing clinical charts and photographs. We rated overall severity on a 0-to-4 scale as 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, and 4 = severe. We considered treatment to be successful when lesions cleared or almost cleared. Recurrence was documented when a disease flare required a further course of therapy. Table I summarizes the demographic and clinical data.
      Table IDemographic and clinical data of 15 patients treated with either topical or oral ivermectin for periorificial dermatitis or rosacea
      Case123456789101112131415
      Age, y3121312610115516131115411
      SexMaleFemaleMaleFemaleMaleMaleFemaleFemaleMaleFemaleMaleFemaleFemaleFemaleFemale
      Clinical diagnosisPODPODPODPPRPODPODPPRPODPPRPPRPPRPPRPPRPPRPOD
      IGA score at baseline
      0 = No inflammatory lesions, no erythema; 1 = very few small papules/pustules, very mild erythema; 2 = few small papules/pustules, mild erythema; 3 = several small or large papules/pustules, moderate erythema; 4 = numerous small or large papules/pustules, severe erythema.
      334433323334342
      Prior treatments
      Treatment specifications: erythromycin 2% cream, pimecrolimus 1% cream, tacrolimus 0.1% ointment, doxycycline, 50 mg/d; metronidazole 0,75% gel.
      Erythromycin

      Pimecrolimus
      Tacrolimus

      Pimecrolimus

      Doxycycline

      Erythromycin

      Tacrolimus

      Doxycycline

      Isotretinoin
      Erythromycin

      Tacrolimus

      Topical metronidazole

      Doxycycline

      Isotretinoin
      NoneTacrolimus

      Pimecrolimus

      Doxycycline
      Tacrolimus

      Doxycycline

      Topical metronidazole
      TacrolimusTacrolimusDoxycyclineTacrolimus

      Doxycycline
      PimecrolimusDoxycyclineTopical steroidsTopical steroids
      Oral/topical ivermectinOralOralOralOralTopicalTopicalOralTopicalTopicalTopicalOralOralOralOralTopical
      Side effectsTransient mild desquamationNoTransient mild desquamationTransient mild desquamationTransient mild desquamationNoNoTransient mild desquamationNoNoNoNoNoNoNo
      IGA score after therapy
      0 = No inflammatory lesions, no erythema; 1 = very few small papules/pustules, very mild erythema; 2 = few small papules/pustules, mild erythema; 3 = several small or large papules/pustules, moderate erythema; 4 = numerous small or large papules/pustules, severe erythema.
      100111301110110
      Time to relapse, mo12No relapseNo relapseNo relapseNo relapseNo relapseImmediateNo relapseNo relapseNo relapseNo relapseNo relapseNo relapse2No relapse
      Follow-up, mo-141642860-12418146-2
      IGA, Investigator Global Assessment; POD, periorificial dermatitis; PPR, papulopustular rosacea.
      0 = No inflammatory lesions, no erythema; 1 = very few small papules/pustules, very mild erythema; 2 = few small papules/pustules, mild erythema; 3 = several small or large papules/pustules, moderate erythema; 4 = numerous small or large papules/pustules, severe erythema.
      Treatment specifications: erythromycin 2% cream, pimecrolimus 1% cream, tacrolimus 0.1% ointment, doxycycline, 50 mg/d; metronidazole 0,75% gel.
      Complete or almost complete clearance (Investigator Global Assessment score 0-1) was achieved in 8 patients treated orally and in 6 children treated with topical ivermectin. One patient did not improve after oral therapy. The overall response to topical or oral ivermectin was excellent: 14 of 15 (93%) patients achieved complete or almost complete clearance of lesions (Fig 1); 3 of 14 patients experienced relapses (21%) and 11 of 14 remained disease-free for a prolonged period. Mean follow-up was 11.9 ± 7.1 (range 2-42) months. The only adverse event observed was mild, transient desquamation of the affected skin in 3 patients receiving oral ivermectin and in 2 patients using topical ivermectin.
      Figure thumbnail gr1
      Fig 1A 13-year-old boy with severe rosacea before (A) and 1 month (B) and 4 months (C) after receiving oral therapy with a single dose of 250 μg/kg ivermectin (case 3). Note the facial desquamation after the first weeks of therapy, not attributable to any concurrent topical therapy. A 5-year-old boy with periorificial dermatitis before (D) and 1 month (E) and 4 months (F) after starting topical ivermectin therapy (case 5).
      In 2014, the US Food and Drug Administration approved 1% ivermectin cream for treatment of rosacea in adults. Oral ivermectin is licensed for treatment of filariasis in children weighing more than 15 kg and has been used off-label in refractory cases of rosacea.
      • Brown M.
      • Hernández-Martín A.
      • Clement A.
      • Colmenero I.
      • Torrelo A.
      Severe demodexfolliculorum-associated oculocutaneous rosacea in a girl successfully treated with ivermectin.
      • Kircik L.H.
      • Del Rosso J.Q.
      • Layton A.M.
      • Schauber J.
      Over 25 years of clinical experience with ivermectin: an overview of safety for an increasing number of indications.
      Topical ivermectin may produce a burning sensation, pruritus, and dry skin in 0.7% to 1.8% of patients.
      • Stein L.
      • Kircik L.
      • Fowler J.
      • et al.
      Efficacy and safety of ivermectin 1% cream in treatment of papulopustular rosacea: results of two randomized, double-blind, vehicle-controlled pivotal studies.
      The only adverse event in our series was transient, mild desquamation in 5 patients. This was observed in patients receiving either topical or oral therapy. We hypothesize the desquamation may be a result of a Mazzotti-like reaction resulting from an immunologic reaction to dying mites, as observed in systemic parasitoses after ivermectin therapy.
      • Mackenzie C.D.
      • Geary T.G.
      • Gerlach J.A.
      Possible pathogenic pathways in the adverse clinical events seen following ivermectin administration to onchocerciasis patients.
      In conclusion, both oral and topical ivermectin were well tolerated and beneficial for treatment of both PPR and POD in this small group of children. A well-designed prospective study with a larger number of patients is necessary to confirm our results.

      References

        • Elston D.M.
        Demodex mites: facts and controversies.
        Clin Dermatol. 2010; 28: 502-504
        • Brown M.
        • Hernández-Martín A.
        • Clement A.
        • Colmenero I.
        • Torrelo A.
        Severe demodexfolliculorum-associated oculocutaneous rosacea in a girl successfully treated with ivermectin.
        JAMA Dermatology. 2014; 150: 61-63
        • Kircik L.H.
        • Del Rosso J.Q.
        • Layton A.M.
        • Schauber J.
        Over 25 years of clinical experience with ivermectin: an overview of safety for an increasing number of indications.
        J Drugs Dermatol. 2016; 15: 325-332
        • Stein L.
        • Kircik L.
        • Fowler J.
        • et al.
        Efficacy and safety of ivermectin 1% cream in treatment of papulopustular rosacea: results of two randomized, double-blind, vehicle-controlled pivotal studies.
        J Drugs Dermatol. 2014; 13: 316-323
        • Mackenzie C.D.
        • Geary T.G.
        • Gerlach J.A.
        Possible pathogenic pathways in the adverse clinical events seen following ivermectin administration to onchocerciasis patients.
        Filaria J. 2003; : S5