Compared burden of psoriasis, atopic dermatitis, hidradenitis suppurativa and chronic urticaria: baseline characteristics of the patients included in the OMCCI cohort, a French, prospective multicentre study of chronic inflammatory dermatoses.

INTRODUCTION: Chronic inflammatory dermatoses (CIDs) can significantly affect patients' lives. The Observatory of Chronic Inflammatory Skin Diseases (OMCCI) cohort was initiated to quantify the impact and disease evolution of four CID over 4 years' follow-up; at least 1,000 patients per CID are planned to be enrolled. To present baseline characteristics of patients included in the OMCCI cohort between December 2020 and September 2022. METHODS: This French, prospective, multicentre registry included adult patients treated in daily practice for moderate-to-severe psoriasis (PS), atopic dermatitis (AD), hidradenitis suppurativa (HS) or chronic urticaria (CU) starting or modifying a systemic treatment. At the inclusion visit and then every 6 months during 4 years, patient-reported outcomes and data on these diseases and their treatments are recorded. RESULTS: A total of 2,058 patients from 24 centers were included: 1,137 PS, 413 AD, 301 HS, and 207 CU. Of these, 1,950 patients started or changed systemic treatment and 108 reduced the dose of existing systemic treatment. Disease impact was qualified as debilitating by 80.1% (PS), 90.5% (AD), 90.5% (HS), and 89.4% (CU), affecting daily, family, and professional life. According to the SF-12 Survey, the impact of all four diseases was borderline pathological for physical health and severe for mental health. At inclusion, 20.4% of patients were receiving a conventional systemic or biologic treatment. After the first visit this percentage raised to 83.3%. During the 6 months preceding study inclusion, 17.7% (PS), 27.9% (AD), 43.1% (HS), and 43.6% (CU) of patients missed work due to their illness, and 26.3% of patients with HS had been admitted to hospital (vs. 8.1%, 5.8%, and 13% of patients with PS, AD, or CU, respectively). CONCLUSION: These CIDs (especially HS) had a major impact on all aspects of patients' quality of life. The low baseline use of systemic drugs and the high burden of these CIDs suggests that these agents are underused. Long-term and dynamic evaluation of the changes brought by the initiation or optimization of these treatments on the evolution of patients' lives will be studied prospectively during the 4-year follow-up of the OMCCI.

Evolution of dupilumab-associated conjunctivitis in patients with atopic dermatitis after switching dupilumab to tralokinumab or Janus kinase inhibitors (RESO-ADOC study).

BACKGROUND: Clinical trials and real-life data have reported an increased incidence of conjunctivitis in patients treated with dupilumab for their atopic dermatitis (AD). Although mostly mild in severity, in some cases conjunctivitis will appear or increase after dupilumab initiation, which can lead to dupilumab discontinuation. OBJECTIVES: (1) To describe the characteristics of patients developing conjunctivitis requiring discontinuation of dupilumab; and (2) to analyse the factors associated with a complete conjunctivitis improvement after dupilumab discontinuation and a switch to tralokinumab or Janus kinase inhibitors. METHODS: This was a multicentre retrospective cohort study that included all patients with AD treated with dupilumab who developed conjunctivitis leading to dupilumab discontinuation and switching to tralokinumab or Janus kinase inhibitors in daily practice. Data on patients, their AD and conjunctivitis were analysed at the inclusion visit (corresponding to discontinuation of dupilumab and the institution of new AD treatment), at visit 2 (3-6 months after inclusion) and at visit 3 (corresponding to the last medical visit). RESULTS: After multivariate analysis, the only factors associated with a complete resolution of dupilumab-associated conjunctivitis at visit 2 and/or visit 3 were conjunctivitis duration (OR 8.98, 95% CI 1.47-55) (p = 0.018), personal history of asthma (OR 10.66, 95% CI 1.82-62.63) (p = 0.009) and switching from dupilumab to Janus kinase inhibitors (OR 17.11, 95% CI 2.94-99.66) (p = 0.002). CONCLUSIONS: Although uncommon, severe dupilumab-associated conjunctivitis is more frequent in daily life compared to its incidence in the dupilumab pivotal trials. In these cases, our study suggests that a rapid switch to another molecule, particularly a Janus kinase inhibitor, should be considered.

Impact of Baricitinib on Patients' Quality of Life after One Year of Treatment for Atopic Dermatitis in Real-World Practice: Results of the Observatory of Chronic Inflammatory Skin Diseases Registry.

The efficacy and safety of baricitinib for treatment of atopic dermatitis have been demonstrated in clinical trials; however, very few real-life studies have been published to date. The Observatory of Chronic Inflammatory Skin Diseases (OMCCI) registry was initiated to prospectively determine the long-term impairment caused by chronic inflammatory dermatoses on patients' lives. The study included 88 patients starting baricitinib for treatment of atopic dermatitis. Clinical evaluation and patient-reported outcomes were recorded at baseline and after 6 and 12 months. After 6 months and 1 year of follow-up, 65 and 47 patients, respectively, were still being treated with baricitinib. Treatment failure was the main reason for discontinuation. Only 1 patient stopped baricitinib because of a side-effect. After 1 year of follow-up, the mean Eczema Area and Severity Index score decreased significantly from 20.7 to 6.4; the percentage of patients with severe atopic dermatitis decreased from 42.9% to 6.5% and a significant improvement in most patient-reported outcomes was noted. There was no difference in terms of efficacy whether or not patients were previously treated with dupilumab. The results remained stable after 6 and 12 months of treatment, which suggests a sustained efficacy of the treatment in patients who initially responded well.

Prevalence of ocular disease during dupilumab treatment for atopic dermatitis: a bicentric retrospective comparative cohort study.

BACKGROUND: Dupilumab is the first human monoclonal antibody approved for the treatment of atopic dermatitis (AD). Clinical trials have reported an increase of ocular side effects in patients who receive dupilumab, with a prevalence of 5-37%. OBJECTIVE: To compare the prevalence of ocular disease between AD patients receiving dupilumab treatment and AD reference group and to study the profile of the patients who developed ocular disease secondary to dupilumab treatment. METHODS: Efficacy outcomes were collected both at baseline and at month 4 (M4). Presence of ocular disease was recorded at M4. RESULTS: Data from 100 patients were examined. At M4, ocular disease was significantly more frequent in the dupilumab group (36% vs. 10%, P = 0.002). Severe allergic conjunctivitis and blepharitis were significantly more frequent in the dupilumab group (30% vs. 4%, P < 0.001, and 22% vs. 2%, P = 0.004, respectively). Six of 18 patients permanently discontinued therapy. CONCLUSION: This study observed a prevalence of 36% of ocular disease in AD patients treated with dupilumab. Additional studies are required to confirm the risk factors we found for dupilumab-associated ocular disease and to identify new ones. Consultation with an ophthalmologist before the introduction of dupilumab might limit the occurrence of complications.

Development of monoclonal gammopathy under biotherapy in psoriasis: a French multicenter retrospective study.

BACKGROUND: Biotherapies or targeted therapies are fairly new treatments indicated for moderate to severe psoriasis. The side effects appear to be mainly infectious or cancerous. The role of biotherapies in the development of a pre-cancerous condition, monoclonal gammopathy of undetermined significance (MGUS), has recently been debated in the literature. OBJECTIVES: To evaluate the incidence of MGUS in psoriasis patients treated with biotherapy. MATERIALS AND METHODS: This study was a French multicenter retrospective study carried out through the French multicenter study group RESOPSO. Data on the results of serum protein electrophoreses performed before and within at least six months after the start of the biotherapy were collected. Demographic data, medical history, and psoriasis treatment history were specified. RESULTS: Four hundred and forty three patients were eligible for inclusion. Of these, three presented with monoclonal gammopathy for which the assessment was in favor of MGUS. The average treatment period was 19.7 months. Six patients presented with MGUS prior to the treatment. These patients' immunoglobulin levels remained stable, with an average remission of 24 months. Only psoriatic rheumatism appeared to be statistically linked to MGUS. CONCLUSION: The incidence and frequency of MGUS in psoriasis patients treated with biotherapy do not appear to increase relative to the general population.

Occupational protein contact dermatitis.

Occupational contact dermatitis is generally caused by haptens but can also be induced by proteins causing mainly immunological contact urticaria (ICU); chronic hand eczema in the context of protein contact dermatitis (PCD). In a monocentric retrospective study, from our database, only 31 (0.41%) of patients with contact dermatitis had positive skin tests with proteins: 22 had occupational PCD, 3 had non-occupational PCD, 5 occupational ICU and 1 cook had a neutrophilic fixed food eruption (NFFE) due to fish. From these results and analysis of literature, the characteristics of PCD can be summarized as follows. It is a chronic eczematous dermatitis, possibly exacerbated by work, suggestive if associated with inflammatory perionyxix and immediate erythema with pruritis, to be investigated when the patient resumes work after a period of interruption. Prick tests with the suspected protein-containing material are essential, as patch tests have negative results. In case of multisensitisation revealed by prick tests, it is advisable to analyse IgE against recombinant allergens. A history of atopy, found in 56 to 68% of the patients, has to be checked for. Most of the cases are observed among food-handlers but PCD can also be due to non-edible plants, latex, hydrolysed proteins or animal proteins. Occupational exposure to proteins can thus lead to the development of ICU. Reflecting hypersensitivity to very low concentrations of allergens, investigating ICU therefore requires caution and prick tests should be performed with a diluted form of the causative protein-containing product. Causes are food, especially fruit peel, non-edible plants, cosmetic products, latex, animals.

IgE antibodies and skin tests in immediate hypersensitivity reactions to infliximab in inflammatory bowel disease: impact on infliximab retreatment.

BACKGROUND: Infliximab (IFX) is used for the treatment of inflammatory bowel diseases (IBD). Immediate hypersensitivity reactions (HR) to IFX are frequently reported. OBJECTIVES: We investigated immunoglobulin E (IgE)-mediated mechanisms underlying immediate HR to IFX. We also evaluated the clinical utility of allergological tests as well as the tolerability of IFX retreatment in these patients. METHODS: This was a prospective single-center study including IBD patients with previous immediate HR to IFX. Skin tests to IFX, including prick tests and intradermal tests, and measurement of anti-IFX IgE antibodies were performed at least 4 weeks after HR. In case of negative skin tests and absence of IgE antibodies, readministration of IFX was performed with a twice-reduced infusion rate. In case of positive tests or recurrence of HR during readministration of IFX, a 12-step desensitization or induction of tolerance protocol was proposed. RESULTS: A total of 24 IBD patients were included (Crohn's disease: n=20). Prick tests to IFX were all negative. Intradermal test was positive in one patient. Anti-IFX IgE antibodies were not detected in 21 patients and were detected in three patients (significant level in one patient and intermediate level in two patients). No relationship was observed between positive skin tests and the presence of anti-IFX IgE antibodies. Switch to adalimumab was well tolerated in 10/11 patients. The readministration of IFX was well tolerated in 4/11 patients. Desensitization to IFX was successful in three out of four patients. CONCLUSION: The vast majority of immediate HR to IFX is not IgE-mediated. Allergological tests are of poor clinical utility. Desensitization or induction of tolerance protocol may allow continuation of IFX therapy in IBD patients with a history of immediate HR.

Non-irritant concentrations and amounts of active ingredient in drug patch tests.

BACKGROUND: Drug patch tests (DPTs) with medicaments suspected of causing an allergic reaction represent a method of diagnostic testing that is low risk; DPTs can reproduce delayed hypersensitivity to drugs, and entail only a moderate re-exposure of patients to potential offending drugs. We assessed the non-irritating concentrations of DPTs and determined the amounts of active ingredient (AI) contained in the drugs used in the tests. OBJECTIVES: The objectives were to assess the non-irritating concentration of DPTs and determine the amounts of active ingredient (AI) contained in the drugs used in the tests. METHODS: From a retrospective, single-centre study of all patients investigated during a 6-year period with a drug eruption, each potentially responsible drug was tested with the commercially available preparation diluted to 30% in water, petrolatum, or alcohol. Data collection was performed with a customized computer database. For each type of DPT studied, the numbers of positive and negative test results were recorded. The amount of AI contained in the DPT (as a percentage) was then calculated after weighing of each tablet. RESULTS: Of the 5558 DPTs studied, all were non-irritant. The average concentration of AI was 9.8%; 25% of DPTs had an AI concentration of < 2%, and 25% had an AI concentration of > 16%. The AI concentration ranged from 0.05% (digoxin) to 30% (paracetamol lyophilisate). CONCLUSION: These data provide thresholds for the non-irritating concentration of AI of 68 different drugs, and thresholds for the non-irritating dilution for 82 drugs, and will help to standardize DPT methods.

How to manage hypersensitivity reactions to biological agents?

Biological agents induce cutaneous adverse drug reactions (CADR) different from those observed with xenobiotics. Type alpha is the cytokine release syndrome, type beta are hypersensitivity reactions and type gamma is a cytokine imbalance syndrome. Infusion-reactions, anaphylactoid reactions occur with various biological agents administered intravenously. In non-severe cases the infusion rate has to be reduced, in severe reactions, the treatment must be stopped and resuscitation carried out with corticosteroids and epinephrine. Reactions may be due to an alpha syndrome but a true allergy could be involved as demonstrated in some patients with IgE antibodies to the galactose-alpha-1,3-galactose portion of the cetuximab or anti infliximab-IgE. Some desensitisation protocols have been published. Non allergic itching and eczema-like lesions are frequent with epidermal growth factor receptor inhibitors. Rash or desquamation was observed in 40% of cases with antiangiogenic agents, 90% of patients treated with imatinib have rashes, oedema or pruritus and a non-allergic periorbital oedema. Severe CADR, such as Stevens-Johnson syndrome, can be provoked. Delayed readings of intradermal tests could be of value in managing patients with a maculopapular rash due to interferon. Anaphylaxis attributed to omalizumab seems to be rare (0.2%) and skin rashes occur in 7% of cases. Anaphylactoid reactions occur in 1% of patients treated with natalizumab. In the case of anti-natalizumab antibody-mediated reactions, treatment should be stopped. These allergic-like side effects of new biological agents must be known and reported to Pharmacovigilance agency networks.