Patient inclusion
There were 1,783 patients with JIA, 1,424 patients with IBD, 178 patients with CNO identified by initial ICD code search at Seattle Children’s Hospital between January 1, 2005 and July 31, 2015. Among these patients, a total of 1,092 patients met the inclusion criteria as shown in Fig. 1. There were 28 CNO patients, 620 JIA patients, and 450 IBD patients who were treated with TNFi for their primary disease and had at least 1 follow-up visit after initiation of TNFi by the study end date. For patients with both IBD and JIA diagnoses, we excluded patients with prior IBD diagnosis from the JIA cohort. Two patients had both CNO and JIA diagnoses, and four with both CNO and IBD. Family history data was excluded from IBD patients as < 14% had available data.
Prevalence Rate Of Paradoxical Psoriasis And Risk Factors
Psoriasis developed or worsened after exposure to TNFi in 4 out of 28 CNO patients (14%, 95% CI: 2.2–25.8%), 3 out of 620 JIA patients (0.5%, 95% CI: 0.1–1.0%), and 25 out of 450 IBD patients (5.6%, 95% CI: 3.8–7.4%). There was no significant difference in distribution of age, gender, race, family history of psoriasis, or concomitant medications between psoriasis and non-psoriasis subsets within each underlying disease as shown in Table 1. The majority of patients were white, non-Hispanic. The age of the diagnosis of primary disease was younger in children with JIA than those with IBD and CNO. However, the age at which the first TNFi was received was similar among all three populations. Family history of psoriasis was not present in the psoriasis subgroups within JIA and CNO and data were not available within IBD. Given the limited number of patients with CNO and JIA who developed psoriasis, data on antinuclear antibody (ANA) and human leukocyte antigen (HLA)-B27 positivity were descriptive. Lab findings for ANA and HLA-B27 were unavailable within the IBD subgroup. Across all three disease populations, disease modifying anti-rheumatic drugs (DMARDs) such as methotrexate, leflunomide, cyclosporine and prednisone were only used in a portion of patients at the time of initiation of first TNFi. Concurrent use of methotrexate was reported less frequently among IBD patients (34% vs. >70% in the other two disease populations). Within the IBD group, there was no difference in concurrent medication use among those who developed psoriasis versus those who did not.
Table 1. Demographic and Clinical Characteristics
Median follow-up time from initiation of first TNFi was 20 months for CNO patients, 35 months for JIA patients, and 36 months for IBD patients (Table 2). Exposure of > 1 TNFi at the time of psoriasis development was recorded among 11/25 IBD, 2/3 JIA, and 2/4 CNO patients. Psoriasis developed during active administration of a TNFi for 23/25 IBD, 3/3 JIA, and 4/4 CNO patients. Two patients with IBD developed psoriasis while not actively on a TNFi, but after completing a course of infliximab; one developed psoriasis 50 days after a 16-month course of TNFi use, and another developed psoriasis 54 days after a 15-month course of TNFi use.
Table 2. Summary of TNFi Treatment in patient Population
Relationship Of Psoriasis With Specific Tnfi Administered
Among all three primary disease groups, only one patient (JIA) developed psoriasis while taking etanercept. In contrast, 16 patients (1 from CNO, 1 from JIA, and 14 from IBD) and 13 patients (3 from CNO, 1 from JIA, and 9 from IBD) developed psoriasis during exposure to adalimumab or infliximab respectively. No patients developed psoriasis while on certolizumab pegol (n = 22, median of 6.5 [2.6–11.5] months) or golimumab (n = 1, 5.5 months).
Characteristics Of Paradoxical Psoriasis And Outcome
Clinical presentation of psoriasis and treatment of these patients were summarized in Table 3. Among those who developed psoriasis, 88% had plaque psoriasis, 25% had alopecia, and 84% had scalp psoriasis.
Table 3
Clinical Presentation and Treatment of Patients Who Developed Psoriasis
|
CNO*
N = 4
|
JIA
N = 3
|
IBD*
N = 25
|
Morphology
|
|
|
|
Plaque
|
4 (100.0%)
|
2 (66.7%)
|
23 (92.0%)
|
Guttate
|
1 (25.0%)
|
0 (0.0%)
|
3 (12.0%)
|
Pustular
|
0 (0.0%)
|
1 (33.3%)
|
1 (4.0%)
|
Erythrodermic
|
0 (0.0%)
|
0 (0.0%)
|
0 (0.0%)
|
Palmoplantar
|
2 (50.0%)
|
0 (0.0%)
|
0 (0.0%)
|
Other
|
1 (25.0%)
|
0 (0.0%)
|
3 (12.0%)
|
Alopecia
|
3 (75.0%)
|
0 (0.0%
|
6 (24.0%)
|
Areas Affected
|
|
|
|
Scalp
|
4 (100.0%)
|
2 (66.7%)
|
22 (88.0%)
|
Face
|
0 (0.0%)
|
3 (33.3%)
|
3 (12.0%)
|
Trunk
|
3 (75.0%)
|
0 (0.0%)
|
17 (68.0%)
|
Extremities
|
3 (75.0%)
|
1 (33.3%)
|
18 (72.0%)
|
Intertriginous locations
|
2 (50.0%)
|
0 (0.0%)
|
7 (28.0%)
|
Nails
|
1 (25.0%)
|
0 (0.0%)
|
4 (16.0%)
|
Palms
|
3 (75.0%)
|
1 (33.3%)
|
3 (12.0%)
|
Soles
|
2 (50.0%)
|
1 (33.3%)
|
4 (16.0%)
|
%BSA
|
10 (5.0–30.0)
|
5.0 (1.0–10.0)
|
12.5 (5.8–40.0)
|
Symptoms
|
|
|
|
Pain
|
1 (25.0%)
|
0 (0.0%)
|
2 (8.0%)
|
Pruritis
|
4 (100.0%)
|
2 (66.7%)
|
13 (52.0%)
|
Bleeding
|
0 (0.0%)
|
0 (0.0%)
|
1 (4.0%)
|
Severity
|
|
|
|
Mild
|
2 (50.0%)
|
3 (100.0%)
|
13 (52.0%)
|
Moderate
|
2 (50.0%)
|
0 (0.0%)
|
11 (44.0%)
|
Severe
|
0 (0.0%)
|
0 (0.0%)
|
0 (0.0%)
|
Unknown
|
0 (0.0%)
|
0 (0.0%)
|
1 (4.0%)
|
Topical treatment/Phototherapy
|
|
|
|
Topical Steroids
|
4 (100.0%)
|
3 (100.0%)
|
24 (96.0%)
|
Topical Retinoid
|
0 (0.0%)
|
0 (0.0%)
|
0 (0.0%)
|
Vitamin D Analogue
|
1 (25.0%)
|
2 (66.7%)
|
12 (48.0%)
|
Coal Tar
|
3 (75.0%)
|
0 (0.0%)
|
10 (40.0%)
|
Phototherapy
|
0 (0.0%)
|
0 (0.0%)
|
0 (0.0%)
|
Systemic Medications
|
|
|
|
Cyclosporine
|
0 (0.0%)
|
0 (0.0%)
|
0 (0.0%)
|
Methotrexate
|
0 (0.0%)
|
3 (100.0%)
|
2 (8.0%)
|
Isotretinoin
|
0 (0.0%)
|
0 (0.0%)
|
0 (0.0%)
|
Azathioprine
|
0 (0.0%)
|
0 (0.0%)
|
0 (0.0%)
|
Prednisone/Prednisolone
|
0 (0.0%)
|
0 (0.0%)
|
1 (4.0%)
|
Ustekinumab
|
0 (0.0%)
|
0 (0.0%)
|
1 (4.0%)
|
Other
|
0 (0.0%)
|
0 (0.0%)
|
1 (4.0%
|
Response to Topical/Phototherapy
|
|
|
|
Worsened or Unchanged
|
0 (0.0%)
|
0 (0.0%)
|
2 (8.0%)
|
Partial Response
|
3 (75.0%)
|
1 (33.3%)
|
9 (36.0%)
|
Complete Response
|
1 (25.0%)
|
2 (66.7%)
|
12 (48.0%)
|
Unknown
|
0 (0.0%)
|
0 (0.0%)
|
2 (8.0%)
|
*1 patient is included in both groups
|
|
|
|
Within the CNO group, 4 out of the 4 patients developed psoriasis while on TNFi treatment characterized by plaque, guttate, palmoplantar, and pustular presentation. Areas affected included the scalp, trunk, extremities, intertriginous locations, nails, palms, and soles. The reported psoriatic lesions were rated from mild to moderate severity with associated pain and pruritis.
Within the JIA group (n = 3), psoriasis presented as pruritic plaques on scalp, face, palms and soles covering approximately 5% body surface area (BSA). These patients were documented to have mild presentations of psoriasis.
Within the IBD group (n = 25), psoriasis was described as pruritic, and/or painful. They presented as plaques, guttate lesions, pustules that affected the scalp, face, trunk, extremities, intertriginous locations, nails, palms, and soles. The lesions on average covered approximately 12.5% BSA. Out of the 25 IBD patients, 6 developed alopecia ranging from mild to moderate in severity.
Treatment And Outcomes
Treatments included topical glucocorticoids, topical retinoids, vitamin D analogues, coal tar, phototherapy, methotrexate, systemic glucocorticoids, ustekinumab, discontinuing the inciting TNFi or switching to another TNFi. Eleven patients (35%) discontinued, none (0%) switched and twenty (65%) continued TNFi therapies. Of all patients who developed psoriasis after exposure to TNFi, 38% had partial and 47% had complete responses to comprehensive management.