Elodie Regnier-Rosencher

Acute kidney injury in patients with severe rash on vemurafenib treatment for metastatic melanomas

Vemurafenib, a selective BRAF (v‐raf murine sarcoma viral oncogene homologue B1) kinase inhibitor, is a new targeted biotherapy that improves survival in patients with metastatic melanomas harbouring the BRAF V600E mutation. However, this drug has significant dermatological adverse effects. We report a new severe cutaneous reaction to this drug associated with acute kidney injury (AKI). Four patients presented a generalized grade 3 (Common Terminology Criteria for Adverse Events) erythematous eruption with hyperkeratosis pilaris, 5–14 days after the introduction of vemurafenib. These symptoms were associated with AKI in all cases and transitory hypereosinophilia in two cases. Vemurafenib treatment was stopped in three patients and the dose was reduced in the fourth, leading to a gradual improvement of skin symptoms and renal function. Positron‐emission tomography scans showed a complete response in three cases and a major response in one case. Vemurafenib was reintroduced at a lower dose, without a relapse of the rash, but renal function again deteriorated. Thus, we report a cluster of four cases of AKI associated with similar, severe, grade 3 cutaneous drug reactions related to vemurafenib.

Subacute Cutaneous Lupus Erythematosus Induced and Exacerbated by Proton Pump Inhibitors

Background: Subacute cutaneous lupus erythematosus (SCLE) can be induced by numerous drugs. We report 3 cases of SCLE induced by proton pump inhibitors (PPIs). Objective: To highlight a rare cutaneous side effect induced by a frequently prescribed drug such as a PPI. Case Reports: Case 1 was a 30-year-old man who developed multiple annular plaques over the trunk and lower limbs 1 month after the initiation of pantoprazole. Antinuclear antibodies (ANA) were positive with anti-Ro/SSA and anti-La/SSB antibodies, and histology confirmed the diagnosis. Clinical improvement was achieved 8 weeks after the discontinuation of pantoprazole and the introduction of a treatment combining topical steroids and hydroxychloroquine. Lesions relapsed when pantoprazole was accidentally rechallenged. The second case was a 31-year-old woman, 28 weeks pregnant, who presented erythematous annular plaques over the trunk 7 weeks after starting esomeprazole. ANA and anti-Ro/SSA antibodies were positive, and the histology was compatible with SCLE. Fetal ultrasound was normal. She was treated with topical and oral steroids and hydroxychloroquine. Clinical improvement was achieved 4 weeks after the discontinuation of esomeprazole. The third case was a 57-year-old woman with systemic erythematosus lupus presenting annular and psoriasiform lesions on the trunk for 15 months. She was treated successively with hydroxychloroquine, azathioprine, mycophenolate mofetil and methotrexate with prednisone. A review of her drug history revealed the introduction of omeprazole a few weeks before the first appearance of skin lesions and omeprazole was contraindicated. Conclusion: SCLE should systematically be suspected in case of eruption after the introduction of PPI. The risk of fetal cardiac complications is important in pregnant women.

Age and clear eyes are associated with an increased risk of cutaneous squamous cell carcinomas in vemurafenib-treated melanoma patients.

Cutaneous squamous cell carcinoma (cSCC) is a frequent side-effect of vemurafenib treatment. The main aim of this study was to identify the clinical risk factors associated with the development of cSCC in melanoma patients treated with vemurafenib. We carried out a retrospective study, including 63 consecutive melanoma patients treated with vemurafenib for BRAF-mutant metastatic melanoma in an oncodermatological department. Clinical and follow-up data were collected and analysed, and a comparison of the subgroups who did and did not develop cSCC was performed. A total of 42.9% of patients (n=27) treated with vemurafenib developed one or more cSCC. Patients with cSCC were significantly older (P=0.01). Clear eyes were also associated with a higher risk of developing cSCC (odds ratio=3.50; 95% confidence interval: 1.08–12.43). Three patients developed cSCC more than 1 year after the initiation of treatment (12, 16 and 18 months, respectively). Clinicians should be vigilant in older patients undergoing vemurafenib therapy as well as patients with clear eyes as they seem to be at increased risk of developing cSCC, even late after the initiation of treatment.

Late occurrence of Histoplasma duboisii cutaneous and pulmonary infection 18 years after exposure

We report an imported case of Histoplasma capsulatum var. duboisii (H. duboisii) infection in a white French woman revealed by cutaneous lesions of the scalp, 18 years after her last stay in West and Central Africa. Asymptomatic bilateral pulmonary infiltrates were discovered on thoracic computed tomography. Skin biopsy allowed the positive diagnosis showing the typical yeasts; culture of biopsy specimens was positive for H. capsulatum. In the absence of criteria of severity, the patient was treated for one year with oral itraconazole 400mg/day. The outcome was favourable, skin and pulmonary lesions resolved slowly. The follow up is 5 years without relapse after the end of treatment. This case illustrates the possibility of late occurrence of H. duboisii infection, many years after exposure and the major importance of asking any patient for travelling or residency in tropical countries.

Factors Associated with Severe Skin Infections in Patients Treated with Biologic Therapies for Inflammatory Rheumatic Diseases

Background: The incidence of severe infections is increased under biologic therapies and the skin is the second localization. Objective: To appraise the factors associated with severe skin infections (SSI) in patients under biologic therapies for inflammatory rheumatic diseases (IRD). Methods: We performed a case-control (ratio 1:3) study nested in a prospective cohort of patients with IRD. SSI was defined as requiring hospitalization or intravenous anti-infectious therapy. We defined two imbedded periods: period A was the time window between the first biologic therapy and the SSI; period B was the last 3 or 12 months (for tumor necrosis factor blockers or rituximab, respectively) before the SSI. Results: Among 4,361 patients with IRD, 29 had a SSI under biologic therapy. In multivariate analyses, SSI were significantly associated with smoking, baseline C-reactive protein and gammaglobulinemia, non-steroidal anti-inflammatory drugs before biologic therapy, cumulative dose of steroids, concomitant steroids during period A, number of different biologic therapies during period A, treatment with infliximab during period A, period B or as first biologic therapy and treatment at high dose during period B. Conclusion: In patients under biologic therapies for IRD, the risk of SSI is associated with several factors including tobacco, treatment with infliximab or high dose range.

BRAFV600 inhibitor discontinuation after complete response in advanced melanoma. A retrospective analysis of 16 patients

BRAF inhibitors (BRAFi) improve progression-free survival and overall survival in patients with advanced melanoma (1,2), with 3 to 6% of patients experiencing complete remission (CR)(1,3). Nevertheless, this efficacy comes at a cost with 90% of patients experiencing at least one adverse event and 45% grade 3 or 4 adverse events (4). Management of long-term responders is not yet well delineated: safety argues for treatment continuation, because evolution after discontinuation is unknown. This article is protected by copyright. All rights reserved.

Do anti‐hypertensive renin‐angiotensin system inhibitors contribute to the development of classical Kaposi sarcoma?

forms of IBD, such as UC; and PPARc agonists have been successfully used in the treatment of both IBD and PCA. In fact, treatment strategies in general for both IBD and PCA are similar, predominantly taking an immunosuppressive approach. Finally, separate associations of IBD and PCAs with other autoimmune conditions are suggested, although robust case–control or genome-wide association data are not currently available for PCAs. The prevalence of IBD in the UK is 240 000 (400 patients/ 100 000 population). Thus, the higher than expected co-existence of IBD in our cohort of patients with PCA, supported by observed associations with other autoimmune conditions, similarities in the proposed pathogenic mechanisms and common immunosuppressive treatment strategies may suggest a link between these inflammatory entities. The possibility of similar pathologic pathways may open novel avenues for shared research and identification of new treatment strategies.