the palms, soles, and scalp, with secondary alopecia, although guttate and plaque psoriasis are also described.1-3,5 Smoking and female sex have been proposed as risk factors.1,6
Treatment of infliximab-induced psoriasis should follow a similar treatment ladder as traditional psoriasis, starting with topical therapy. In one study by Malkonen et al, of 84 children with inflammatory bowel disease who developed infliximab-induced psoriasis, most responded well to topical corticosteroids, with only 7 patients requiring discontinuation of infliximab, and none requiring phototherapy or systemic therapy.7 Similar results were seen by Guerra et al., with 78% responding to topical corticosteroids. 6 However, Ko et al examined 127 cases of TNF-induced psoriasis and found topical corticosteroids led to resolution in only 25%.2 In cases unresponsive to topical corticosteroids, systemic therapies such as cyclosporine or methotrexate can be added. In more severe or recalcitrant cases, both discontinuation of the TNF inhibitor and systemic therapy may be required.2 In the Ko et al series, TNF inhibitor discontinuation and initiation of systemic therapy was most effective, leading to resolution of symptoms in 64% of cases. Switching within the anti-TNF family of medications appears to be ineffective, with resolution of 0 to 15% in different case series, indicating a likely class effect.2,3
Ustekinumab is a monoclonal antibody that binds to the p40 subunit of the interleukin 12 and 23 cytokines. It has shown remarkable efficacy in adult psoriasis and was recently approved in October 2017 by the Food and Drug Administration for moderate to severe psoriasis in adolescents aged 12 and older.8 There are a few case reports and case series demonstrating the safety of ustekinumab in younger pediatric patients with psoriasis. In a retrospective case series by Klufas et al., ustekinumab was among the biologics evaluated for efficacy in treating pediatric psoriasis. They evaluated ustekinumab as monotherapy, as well as in combination with methotrexate. Six patients ranging from seven to eighteen years of age were treated with ustekinumab alone in varying doses: 1) four patients were given a fixed dose of 45 mg at weeks 0, 4, and every 12 weeks afterwards; 2) one patient received a fixed dose of 90 mg at weeks 0, 4, and every 12 weeks afterwards; 3) one patient received a fixed dose of 45 mg every 8 weeks. In all groups, Physician Global Assessment measurements decreased from 2.6 at baseline to 1.5 after a seven-month observation period. No significant adverse events were reported at any dosage.7 Min et al. described a two-year old female with refractory psoriasis despite maximum topical therapy and phototherapy treated with ustekinumab. She received half-standard dosage (22.5 mg subcutaneously) ustekinumab at weeks 0 and 4, then every 12 weeks.10
In September 2016, ustekinumab was FDA approved for the treatment of Crohn’s disease in adults 18 years and older. However, there is limited data on the efficacy or safety of ustekinumab in the treatment of pediatric Crohn’s disease. There is one case of a 7-year-old male with refractory Crohn’s disease, diagnosed at 9 months of age, treated successfully with half-dose ustekinumab, after failing azathioprine with steroids, mesalamine, methotrexate, and adalimumab.8 In another retrospective case series of four patients ages 12 to 17 with refractory Crohn’s disease, two of the four demonstrated a clinical response while the others had continued symptoms and disease complications, ultimately requiring discontinuation of therapy.9
Even less is published about treating concomitant psoriasis and Crohn’s disease or TNF-induced psoriasis in patients with Crohn’s disease. In a series of TNF-induced psoriasis in adults with inflammatory bowel disease, seven patients with underlying Crohn’s disease were switched from anti-TNF therapy to ustekinumab with significant improvement in their skin lesions and maintenance of their bowel disease.1 They found that anti- TNF-induced psoriasiform skin lesions were characterized by IL-17/IL-22 expressing Th17 cells and IFN-γ expressing Th1 cells, with increased expression of Th17 cells correlated with more severe skin lesions and a need for ustekinumab therapy.1 There is only one other case in the literature of a pediatric patient with inflammatory bowel disease and TNF inhibitor-induced psoriasis treated with ustekinumab.12 This was a 16 year old female with Crohn’s disease who developed psoriasiform lesions after treatment with infliximab and adalimumab. She failed treatment with topical corticosteroids, was unable to tolerate methotrexate and was ultimately treated with ustekinumab with complete clearance of her skin lesions at 10 months and sustained remission of her Crohn’s disease.
Treatment of infliximab-induced psoriasis should follow a similar treatment ladder as traditional psoriasis, starting with topical therapy. In one study by Malkonen et al, of 84 children with inflammatory bowel disease who developed infliximab-induced psoriasis, most responded well to topical corticosteroids, with only 7 patients requiring discontinuation of infliximab, and none requiring phototherapy or systemic therapy.7 Similar results were seen by Guerra et al., with 78% responding to topical corticosteroids. 6 However, Ko et al examined 127 cases of TNF-induced psoriasis and found topical corticosteroids led to resolution in only 25%.2 In cases unresponsive to topical corticosteroids, systemic therapies such as cyclosporine or methotrexate can be added. In more severe or recalcitrant cases, both discontinuation of the TNF inhibitor and systemic therapy may be required.2 In the Ko et al series, TNF inhibitor discontinuation and initiation of systemic therapy was most effective, leading to resolution of symptoms in 64% of cases. Switching within the anti-TNF family of medications appears to be ineffective, with resolution of 0 to 15% in different case series, indicating a likely class effect.2,3
Ustekinumab is a monoclonal antibody that binds to the p40 subunit of the interleukin 12 and 23 cytokines. It has shown remarkable efficacy in adult psoriasis and was recently approved in October 2017 by the Food and Drug Administration for moderate to severe psoriasis in adolescents aged 12 and older.8 There are a few case reports and case series demonstrating the safety of ustekinumab in younger pediatric patients with psoriasis. In a retrospective case series by Klufas et al., ustekinumab was among the biologics evaluated for efficacy in treating pediatric psoriasis. They evaluated ustekinumab as monotherapy, as well as in combination with methotrexate. Six patients ranging from seven to eighteen years of age were treated with ustekinumab alone in varying doses: 1) four patients were given a fixed dose of 45 mg at weeks 0, 4, and every 12 weeks afterwards; 2) one patient received a fixed dose of 90 mg at weeks 0, 4, and every 12 weeks afterwards; 3) one patient received a fixed dose of 45 mg every 8 weeks. In all groups, Physician Global Assessment measurements decreased from 2.6 at baseline to 1.5 after a seven-month observation period. No significant adverse events were reported at any dosage.7 Min et al. described a two-year old female with refractory psoriasis despite maximum topical therapy and phototherapy treated with ustekinumab. She received half-standard dosage (22.5 mg subcutaneously) ustekinumab at weeks 0 and 4, then every 12 weeks.10
In September 2016, ustekinumab was FDA approved for the treatment of Crohn’s disease in adults 18 years and older. However, there is limited data on the efficacy or safety of ustekinumab in the treatment of pediatric Crohn’s disease. There is one case of a 7-year-old male with refractory Crohn’s disease, diagnosed at 9 months of age, treated successfully with half-dose ustekinumab, after failing azathioprine with steroids, mesalamine, methotrexate, and adalimumab.8 In another retrospective case series of four patients ages 12 to 17 with refractory Crohn’s disease, two of the four demonstrated a clinical response while the others had continued symptoms and disease complications, ultimately requiring discontinuation of therapy.9
Even less is published about treating concomitant psoriasis and Crohn’s disease or TNF-induced psoriasis in patients with Crohn’s disease. In a series of TNF-induced psoriasis in adults with inflammatory bowel disease, seven patients with underlying Crohn’s disease were switched from anti-TNF therapy to ustekinumab with significant improvement in their skin lesions and maintenance of their bowel disease.1 They found that anti- TNF-induced psoriasiform skin lesions were characterized by IL-17/IL-22 expressing Th17 cells and IFN-γ expressing Th1 cells, with increased expression of Th17 cells correlated with more severe skin lesions and a need for ustekinumab therapy.1 There is only one other case in the literature of a pediatric patient with inflammatory bowel disease and TNF inhibitor-induced psoriasis treated with ustekinumab.12 This was a 16 year old female with Crohn’s disease who developed psoriasiform lesions after treatment with infliximab and adalimumab. She failed treatment with topical corticosteroids, was unable to tolerate methotrexate and was ultimately treated with ustekinumab with complete clearance of her skin lesions at 10 months and sustained remission of her Crohn’s disease.
CONCLUSION
We present the first case of a school-age pediatric patient with
TNF inhibitor-induced psoriasis treated with ustekinumab. She
achieved complete clearance of her psoriasis, her alopecia resolved,
and she has had maintenance of remission of her Crohn’s
disease with complete mucosal healing. We recommend consideration
of treatment with ustekinumab in pediatric patients with
inflammatory bowel disease and TNF inhibitor-induced psoriasis
recalcitrant to other therapies. However, controlled and blinded
studies are needed to elucidate the long-term efficacy and safety
of this medication in the pediatric population, and its use remains
unlabeled until such data is obtained.
DISCLOSURES
None of the authors have any perceived potential conflicts of
interest and/or relationships with industry.
REFERENCES
1. Tillack, C., et al., Anti-TNF antibody-induced psoriasiform skin lesions in patients with inflammatory bowel disease are characterised by interferon-gamma- expressing Th1 cells and IL-17A/IL-22-expressing Th17 cells and respond to anti-IL-12/IL-23 antibody treatment. Gut. 2014; 63(4):567-77.
2. Ko, J.M., A.B. Gottlieb, and J.F. Kerbleski, Induction and exacerbation of psoriasis with TNF-blockade therapy: a review and analysis of 127 cases. J Dermatolog Treat. 2009;20(2):100-8
2. Ko, J.M., A.B. Gottlieb, and J.F. Kerbleski, Induction and exacerbation of psoriasis with TNF-blockade therapy: a review and analysis of 127 cases. J Dermatolog Treat. 2009;20(2):100-8
