Management of Adult Patients With Drug Reaction With Eosinophilia and Systemic Symptoms: A Delphi-Based International Consensus.

Importance: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but potentially fatal drug hypersensitivity reaction. To our knowledge, there is no international consensus on its severity assessment and treatment. Objective: To reach an international, Delphi-based multinational expert consensus on the diagnostic workup, severity assessment, and treatment of patients with DRESS. Design, Setting, and Participants: The Delphi method was used to assess 100 statements related to baseline workup, evaluation of severity, acute phase, and postacute management of DRESS. Fifty-seven international experts in DRESS were invited, and 54 participated in the survey, which took place from July to September 2022. Main Outcomes/Measures: The degree of agreement was calculated with the RAND-UCLA Appropriateness Method. Consensus was defined as a statement with a median appropriateness value of 7 or higher (appropriate) and a disagreement index of lower than 1. Results: In the first Delphi round, consensus was reached on 82 statements. Thirteen statements were revised and assessed in a second round. A consensus was reached for 93 statements overall. The experts agreed on a set of basic diagnostic workup procedures as well as severity- and organ-specific further investigations. They reached a consensus on severity assessment (mild, moderate, and severe) based on the extent of liver, kidney, and blood involvement and the damage of other organs. The panel agreed on the main lines of DRESS management according to these severity grades. General recommendations were generated on the postacute phase follow-up of patients with DRESS and the allergological workup. Conclusions and Relevance: This Delphi exercise represents, to our knowledge, the first international expert consensus on diagnostic workup, severity assessment, and management of DRESS. This should support clinicians in the diagnosis and management of DRESS and constitute the basis for development of future guidelines.

Short interruptions of TNF-inhibitor treatment can be associated with treatment failure in patients with immune-mediated diseases.

INTRODUCTION: The prevalence of immune-mediated diseases has increased in the past decades and despite the use of biological treatments all patients do not achieve remission. The aim of this study was to characterise the reasons for short interruptions during treatment with two commonly used TNF-inhibitors infliximab and adalimumab and to analyse the possible effects of the interruptions on immunisation and switching the treatment. MATERIAL AND METHODS: This case-control study was based on retrospective analyses of patient records and a questionnaire survey to clinicians. A total of 370 patients (194 immunised cases and 172 non-immunised controls, 4 excluded) were enrolled from eight hospitals around Finland. Eleven different diagnoses were represented, and the largest patient groups were those with inflammatory bowel or rheumatic diseases. RESULTS: Treatment interruptions were associated with immunisation in patients using infliximab (p < .001) or adalimumab (p < .000001). Patients with treatment interruptions were more likely to have been treated with more than one biological agent compared to those without treatment interruptions. This was particularly prominent among patients with a rheumatic disease (p < .00001). The most frequent reason for a treatment interruption among the cases was an infection, whereas among the control patients it was remission. The median length of one interruption was one month (interquartile range 1-3 months). CONCLUSION: Our results suggest that the interruptions of the treatment with TNF-inhibitors expose patients to immunisation and increase the need for drug switching. These findings stress the importance of careful judgement of the need for a short interruption in the biological treatment in clinical work, especially during non-severe infections.

Guselkumab Treatment Outcomes and Persistence in a Nationwide Real-world Cohort of Patients with Plaque Psoriasis.

Guselkumab treatment outcomes and persistence were assessed in a real-world cohort of Finnish patients with difficult-to-treat plaque psoriasis over a median follow-up of 1 year. Data on 181 patients who initiated guselkumab at the 15 study centres were collected retrospectively from the patient charts. Prior exposure to biologic therapies was common, with 56% and 35% having used at least 1 and 2 biologics, respectively. Median guselkumab treatment duration was 11 months with 21 patients (12%) discontinuing treatment during follow-up. Of 85 patients with a follow-up duration of at least 1 year, 73 (86%) were still on guselkumab at 1 year. Significant improvements during follow-up were seen in the absolute Psoriasis Area and Severity Index (PASI) scores with 32 patients (80%) having absolute PASI ≤ 2 after a 9-14-month treatment. Guselkumab treatment was effective and treatment persistence was high in the nationwide Finnish real-life setting.

[Exemplary cases of individualization of biological therapy]. / Esimerkkitapauksia biologisen hoidon yksilöllistämisestä.

The use of biological drugs consisting of large molecules has in recent years expanded to new indications and new specialties. These drugs are most commonly proteins possessing the structure of an antibody or a receptor, and treatment with them is significantly more expensive than that carried out with conventional small molecule drugs. Determination of drug levels and emerging antibodies form the basis of individualization. They will enable better treatment results with simultaneous avoidance of unnecessary medications, excessive doses--and extra costs. We demonstrate the individualization of TNF-α blocker therapy through patient cases in various situations.

Skin reactions during anti-TNFα therapy for pediatric inflammatory bowel disease: a 2-year prospective study.

BACKGROUND: Although the development of therapy-related skin reactions is common along with an increase in the number of adult patients receiving anti-TNFα, there are few studies on pediatric inflammatory bowel disease; hence, this prospective study focuses on skin reactions related to infliximab therapy. METHODS: All pediatric patients with inflammatory bowel disease undergoing infliximab therapy were prospectively screened for the presence of skin manifestations at the time of each infusion between March 1, 2011 and March 31, 2011 at Children's Hospital, Helsinki, Finland. Blood inflammatory markers and fecal calprotectin levels were measured at the time of infusions. RESULTS: During the study period, 84 children with inflammatory bowel disease (Crohn's n = 64) received infliximab infusions (the median duration of therapy 12.2 mo). Almost every other patient (n = 40; 47.6%) presented chronic skin reactions, 23% with lesions considered severe. Most commonly, the patient's ear lobes and scalp were affected with psoriasis-like manifestations, followed by their eyelids, perioral and pubic area, trunk, and the extremities. However, an HLA-Cw*0602 genotype associating with psoriasis was rare. Interestingly, most patients with skin reactions had a low degree of intestinal inflammation based on their fecal calprotectin levels (median level, 133 µg/g versus 589 in unaffected patients; P < 0.016). Seven patients (8.3% of all patients but 17% of those with skin lesions) discontinued the given therapy due to a skin reaction. CONCLUSIONS: Skin reactions are common during maintenance therapy with infliximab in pediatric patients. For most patients, skin reactions seem to correlate with a low level of intestinal inflammation. Although potentially harsh, skin lesions mostly allow continuation of infliximab.

[New biological drugs in the treatment of inflammatory skin diseases]. / Uudet biologiset lääkkeet tulehduksellisten ihosairauksien hoidossa.

Psoriasis in the only skin disease for which biological drug treatments are in use. Three of these are TNFalpha inhibitors and one, ustekinumab, is an inhibitor of the interleukins (IL) 12 and 23. The new IL-17 inhibitors have proven to be highly efficient, and new low molecular weight drugs such as Janus kinase inhibitors and phosphodiesterase 4 inhibitors may provide a competitive oral alternative to monoclonal antibodies. No biological drugs are available for atopic eczema. The pathogenesis of atopic eczema has, however become more precise, providing several interesting therapeutic targets in the future.

Immunosuppression Adversely Affects TST but Not IGRAs in Patients with Psoriasis or Inflammatory Musculoskeletal Diseases.

The performance of the interferon gamma release assays (IGRAs) and tuberculin skin test (TST) was reviewed retrospectively in patients with psoriasis, inflammatory musculoskeletal diseases, or miscellaneous inflammatory conditions. The study was carried out over a 22-month period using 109 records of patients with psoriasis (n = 21), musculoskeletal disease (n = 74), or other inflammatory conditions (n = 14). Forty-four (48%) of 109 patients were on immunosuppressive therapy and 38/109 (35%) on systemic glucocorticoid therapy. The agreement between the IGRAs was substantial (κ = 0.71) whilst that between the IGRAs and TST was low (κ = 0.32). Logistic regression models revealed that IGRAs associated with risk factors for latent tuberculosis infection better than TST. TST was influenced by age, BCG vaccination, sex, and glucocorticoid therapy. We found that IGRAs performed equally well with low level of indeterminate results (1-2%). IGRAs were superior to TST because the latter was influenced by BCG-vaccination status and immunosuppressive therapy.

[What do we know about pathogenesis of psoriasis?]. / Mitä tiedämme psoriaasin tautimekanismeista?

Psoriasis has been considered as a disease of the keratinocytes, or an autoimmune disease. According to the current view, altered interaction of the immune system with epithelial cells and mediators of the skin is essential in psoriasis. In genetically predisposed subjects, psoriasis may appear as a result of external factors, but no antigen or autoantigen triggering the inflammation has been identified. Genetic factors have a particularly strong effect in the so-called type I psoriasis. During the last few years, genome research has revealed a number of new susceptibility genes for psoriasis.

A 6-month follow-up study of 1048 patients diagnosed with an occupational skin disease.

BACKGROUND: Occupational skin diseases (OSDs) often have considerable medical and occupational consequences. Previous data on prognostic factors have been derived from studies with fairly small sample sizes. OBJECTIVES: To determine the medical and occupational outcome in 1048 patients diagnosed with OSD at the Finnish Institute of Occupational Health and to identify the prognostic risk factors for the continuation of OSD. METHODS: Patients examined in 1994-2001 filled out a follow-up questionnaire 6 months after the diagnosis. Data on atopy, contact allergies, and occupation were analysed. RESULTS: Six months after the diagnosis the skin disease had healed in 27% of the patients. The OSD had cleared up in 17% of those with no changes at work, and in 34% of those who had changed their job/occupation. The best clearing had occurred in the patients with contact urticaria (35%), whereas the healing of allergic (27%) and irritant (23%) contact dermatitis was similar. The risk factors for continuing occupational contact dermatitis (OCD) were no changes in work, age > 45 years, food-related occupations, respiratory atopy, and male sex. CONCLUSIONS: The healing of OSD was associated with discontinuation of the causative exposure. A change in work and the presence of easily avoidable work-related allergies were associated with a good prognosis.