Measurement Properties of the Psoriasis Symptom Inventory Electronic Daily Diary in Patients with Moderate to Severe Plaque Psoriasis.

OBJECTIVES: The Psoriasis Symptom Inventory (PSI) is a patient-reported outcome instrument that measures the severity of psoriasis signs and symptoms. This study evaluated measurement properties of the PSI in patients with moderate to severe plaque psoriasis. METHODS: This secondary analysis used pooled data from a phase 3 brodalumab clinical trial (AMAGINE-1). Outcome measures included the PSI, Psoriasis Area and Severity Index (PASI), static Physician's Global Assessment (sPGA), psoriasis-affected body surface area, 36-item Short-Form Health Survey version 2, and the Dermatology Life Quality Index (DLQI). The PSI was evaluated for dimensionality, item performance, reliability (internal consistency and test-retest), construct validity, ability to detect change, and agreement between PSI response and response measures based on the PASI, sPGA, and DLQI. RESULTS: Results supported unidimensionality, good item fit, ordered responses, and PSI scoring. The PSI demonstrated reliability: baseline Cronbach's alpha ≥ 0.92 and intraclass correlation coefficients ≥ 0.95. Correlations between PSI total score and DLQI item 1 (r = 0.86), DLQI symptoms and feelings (r = 0.87), and 36-item Short-Form Health Survey version 2 bodily pain (r = -0.61) supported convergent validity. PSI scores differed significantly (P < 0.001) among severity groups based on the PASI (< 12/≥ 12), sPGA (0-1/2-3/4-5), body surface area (< 5%/5%-10%/> 10%), and DLQI (≤ 5/> 5) at weeks 8 and 12. At week 12, the PSI detected significant changes in severity based on PASI responses (< 50/50- < 75/≥ 75) and sPGA (0-1/≥ 2), and showed good agreement (k ≥ 0.66) between PSI response and PASI, sPGA, and DLQI responses. CONCLUSION: The PSI demonstrated excellent validity, reliability, and ability to detect change in the severity of psoriasis signs and symptoms.

Differences in psoriasis signs and symptom severity between patients with clear and almost clear skin in clinical practice.

INTRODUCTION: In psoriasis clinical trials, treatment success is often defined as achieving a static Physician Global Assessment (sPGA) score of 0 (clear) or 1 (almost clear). Patients with clear versus almost clear skin may experience psoriasis differently. This study assessed whether aggregating these patients underestimates subjective improvements associated with total skin clearance. METHODS: Patients with plaque psoriasis with stable sPGA 0 or 1 currently treated with adalimumab, etanercept, infliximab, or ustekinumab reported Psoriasis Symptom Inventory (PSI) scores for seven days and Dermatology Life Quality Index (DLQI) scores on day 8. The PSI measures psoriasis signs and symptom severity; the DLQI measures the impact of skin disease on quality of life. This analysis compared PSI and DLQI outcomes between patients with sPGA 0 and 1. RESULTS: This study assessed 230 patients: 79 sPGA 0 and 151 sPGA 1. A greater percentage with sPGA 0 than sPGA 1 achieved a total PSI score of 0 ("best"; 61% vs. 5%, p < 0.0001) and DLQI 0 ("no effect"; 79% vs. 24%, p < 0.001). Patients with sPGA 0 reported better scores than sPGA 1 on all other PSI and DLQI assessments. CONCLUSIONS: Achieving total skin clearance, compared with almost clear skin, provides clinically meaningful improvements in psoriasis.

Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8alpha+ conventional dendritic cells.

Although CD103-expressing dendritic cells (DCs) are widely present in nonlymphoid tissues, the transcription factors controlling their development and their relationship to other DC subsets remain unclear. Mice lacking the transcription factor Batf3 have a defect in the development of CD8alpha+ conventional DCs (cDCs) within lymphoid tissues. We demonstrate that Batf3(-/-) mice also lack CD103+CD11b- DCs in the lung, intestine, mesenteric lymph nodes (MLNs), dermis, and skin-draining lymph nodes. Notably, Batf3(-/-) mice displayed reduced priming of CD8 T cells after pulmonary Sendai virus infection, with increased pulmonary inflammation. In the MLNs and intestine, Batf3 deficiency resulted in the specific lack of CD103+CD11b- DCs, with the population of CD103+CD11b+ DCs remaining intact. Batf3(-/-) mice showed no evidence of spontaneous gastrointestinal inflammation and had a normal contact hypersensitivity (CHS) response, despite previous suggestions that CD103+ DCs were required for immune homeostasis in the gut and CHS. The relationship between CD8alpha+ cDCs and nonlymphoid CD103+ DCs implied by their shared dependence on Batf3 was further supported by similar patterns of gene expression and their shared developmental dependence on the transcription factor Irf8. These data provide evidence for a developmental relationship between lymphoid organ-resident CD8alpha+ cDCs and nonlymphoid CD103+ DCs.

Contrasting roles of the IL-1 and IL-18 receptors in MyD88-dependent contact hypersensitivity.

Contact hypersensitivity (CHS) requires activation of the innate immune system, and results in an adaptive immune response. Many cells of the innate immune system use Toll-like receptors (TLRs), which signal through the adaptor protein, MyD88, to initiate an immune response. MyD88 is also required for signaling downstream of the IL-1 and Il-18 receptors (IL-1R and IL-18R, respectively). Herein, we studied the MyD88 signaling pathway in the CHS response to DNFB. Mice deficient in MyD88 were unable to mount a CHS response to DNFB. In contrast, mice deficient in Toll/IL-1R-containing adaptor-inducing IFN-beta, TLR2, TLR4, TLR6, and TLR9 had no defect in their ability to respond to DNFB. Although both IL-1R and IL-18R-deficient mice showed a reduced CHS response to DNFB, in bone marrow chimera and adoptive transfer experiments, we found that MyD88 and the IL-18R were required in a radioresistant cell in the sensitization phase of the CHS response. In contrast, similar strategies revealed that the IL-1R was required in a radiosensitive cell in the sensitization phase of the CHS response. Taken together, these data indicate that the IL-1R and IL-18R/MyD88 pathways are required in distinctly different cells during the sensitization phase of CHS.

Seasonal variation of Stevens-Johnson syndrome and toxic epidermal necrolysis associated with trimethoprim-sulfamethoxazole.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and severe cutaneous adverse reactions to medications and infections. OBJECTIVE: We sought to determine whether a seasonal variation to SJS and TEN exists and to define the characteristics in our tertiary referral hospital. METHODS: A retrospective chart review of 50 patients from 1995 through 2007 was performed and statistically analyzed. RESULTS: The most common medication implicated as a cause of SJS/TEN was trimethoprim-sulfamethoxazole (TMX) (26%). A seasonal trend, favoring springtime, was observed for the total number of cases of SJS and TEN (P = .34). There was a significant increase in cases due to TMX (53%) occurring in spring compared to other seasons (P = .002). These patients were significantly younger (37.8 +/- 13.7) than other patients with SJS and TEN (53.7 +/- 16.4) (P = .003). Their overall mortality (1 death) and average SCORTEN value (1.62 +/- 1.6) was also significantly lower (P = .04 and 0.03, respectively). Based on outpatient pharmacy records, there was no increase in TMX prescriptions filled during the spring. LIMITATIONS: The study was limited by reliance on chart data, the use of inpatient records, and number of patients. CONCLUSIONS: A seasonal variation in SJS and TEN caused by TMX affecting younger patients may exist.