Sustained Remission Without Corticosteroids Among Patients With Pemphigus Who Had Rituximab as First-Line Therapy: Follow-Up of the Ritux 3 Trial.

Importance: The Ritux 3 trial demonstrated the short-term efficacy and safety of first-line treatment with rituximab compared with a standard corticosteroid regimen in pemphigus. No data on the long-term follow-up of patients who received rituximab as first line are available. Objective: To assess the long-term efficacy and safety of the Ritux 3 treatment regimen. Design, Setting, and Participants: This 7-year follow-up study of the Ritux 3 trial included patients with pemphigus from 25 dermatology departments in France from January 1, 2010, to December 31, 2015. Exposure: Patients were initially randomized in the rituximab plus prednisone group or prednisone-alone group. Main outcomes and measures: The primary outcome was the 5- and 7-year disease-free survival (DFS) without corticosteroids, assessed by Kaplan-Meier curves. Secondary outcomes were occurrence of relapse, occurrence of severe adverse events (SAEs), and evolution of antidesmoglein (Dsg) antibody enzyme-linked immunosorbent assay values to predict long-term relapse. Results: Of the 90 patients in the Ritux 3 trial, 83 were evaluated at the end of follow-up study visit (44 in the rituximab plus prednisone group; 39 in the prednisone-alone group) with a median (IQR) follow-up of 87.3 (79.1-97.5) months. Forty-three patients (93%) from the rituximab plus prednisone and 17 patients (39%) from the prednisone-alone group had achieved complete remission without corticosteroids at any time during the follow-up. Patients from the rituximab group had much longer 5- and 7-year DFS without corticosteroids than patients from the prednisone-alone group (76.7% and 72.1% vs 35.3% and 35.3%, respectively; P < .001), and had about half the relapses (42.2% vs 83.7%; P < .001). Patients who received rituximab as second-line treatment had shorter DFS than patients treated as first line (P = .007). Fewer SAEs were reported in the rituximab plus prednisone group compared with the prednisone-alone group, 31 vs 58 respectively, corresponding to 0.67 and 1.32 SAEs per patient, respectively (P = .003). The combination of anti-Dsg1 values of 20 or more IU/mL and/or anti-Dsg3 values of 48 or more IU/mL yielded 0.83 positive predictive value and 0.94 negative predictive value to predict long-term relapse. Conclusions and Relevance: In this secondary analysis of the Ritux 3 trail, first-line treatment of patients with pemphigus with the Ritux 3 regimen was associated with long-term sustained complete remission without corticosteroid therapy without any additional maintenance infusion of rituximab.

Elastic fiber alterations and calcifications in calcific uremic arteriolopathy.

Calcific uremic arteriolopathy (CUA) is a severely morbid disease, affecting mostly dialyzed end-stage renal disease (ESRD) patients, associated with calcium deposits in the skin. Calcifications have been identified in ESRD patients without CUA, indicating that their presence is not specific to the disease. The objective of this retrospective multicenter study was to compare elastic fiber structure and skin calcifications in ESRD patients with CUA to those without CUA using innovative structural techniques. Fourteen ESRD patients with CUA were compared to 12 ESRD patients without CUA. Analyses of elastic fiber structure and skin calcifications using multiphoton microscopy followed by machine-learning analysis and field-emission scanning electron microscopy coupled with energy dispersive X-ray were performed. Elastic fibers specifically appeared fragmented in CUA. Quantitative analyses of multiphoton images showed that they were significantly straighter in ESRD patients with CUA than without CUA. Interstitial and vascular calcifications were observed in both groups of ESRD patients, but vascular calcifications specifically appeared massive and circumferential in CUA. Unlike interstitial calcifications, massive circumferential vascular calcifications and elastic fibers straightening appeared specific to CUA. The origins of such specific elastic fiber's alteration are still to be explored and may involve relationships with ischemic vascular or inflammatory processes.

Current characteristics of a population of psoriatic arthritis and gender disparities.

Background and Aim: Psoriatic arthritis (PsA) is a polymorphic disease associated with numerous comorbidities. The objective of this study was to describe the main clinicobiological and imaging characteristics of a population of PsA and to extract any disparities between men and women. Methods: A total of 132 patients in the rheumatology department of Amiens University Hospital with a confirmed diagnosis of PsA according to the CASPAR criteria were included over a period of 4 months. All data were collected retrospectively in this observational and single-center study. Results: The sex ratio was 1 and the average age at inclusion was 54.9 years. Peripheral PsA was the predominant clinical form. Axial PsA represented 12.1% of cases. Enthesitis was noted in 52.3% of cases while dactylitis was identified in 29.5% of cases. Moreover, 12.1% had a joint symptomatology preceding the appearance of cutaneous signs. HLA-B*27 positivity was found in 33.3% of cases. Chronic hyperuricemia accounted for 10% of our population. Sacroiliitis was observed in 41% of cases. The disparities between men and women are multiple and consistent with the literature: Polyarticular form, enthesitis, obesity, more intensive prescription of s-DMARDs, and b-DMARDs are more associated with the female population. Oligoarticular form, psoriatic nail dystrophy, radiological axial involvement, and chronic hyperuricemia are more encountered in the male population. Conclusions: Our study found a very heterogeneous disease, with marked differences between men and women. Peripheral PsA remains predominant but the search for associated axial involvement, which is probably underestimated, seems essential. Relevance for Patients: This work studied the main characteristics of patients with PsA followed in real life, in a regional university reference center. We have highlighted a very heterogeneous disease as well as some gender disparities, not well described in the literature, which should be taken into account in order to optimize therapeutic management.

Allogeneic transplantation in advanced cutaneous T-cell lymphomas (CUTALLO): a propensity score matched controlled prospective study.

BACKGROUND: Advanced-stage cutaneous T-cell lymphomas (CTCLs) are rare, usually refractory, and fatal diseases. Case series have suggested that allogeneic haematopoietic stem cell transplantation (HSCT) might improve the prognosis of advanced-stage CTCLs. The objective of this study was to investigate the effect of allogeneic HSCT compared with non-HSCT therapy on the outcome of individuals with advanced-stage CTCLs. METHODS: In this prospective, multicentre, matched controlled trial, conducted at 30 hospitals, participants with advanced CTCLs were allocated treatment: if they had an available compatible related donor they were assigned to allogeneic HSCT, or if not they were allocated to non-allogeneic HSCT therapy. Key inclusion criteria were participants aged 18-70 years, with advanced stage mycosis fungoides or Sézary syndrome, and at least one poor prognostic criteria. Participants were excluded if they were not in complete or partial remission of the disease. Propensity score 1:1 matching with replacement (ie, that each participant treated with HSCT was matched to the participant with the closest propensity score treated with non-HSCT therapy, even if they had already been matched) was used to handle confounding factors, with the balance of covariate distribution between HSCT and non-HSCT groups assessed using standardised mean differences. The primary endpoint was progression-free survival in the matched intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02520908), and is currently active but not recruiting. FINDINGS: From June 1, 2016, to March 3, 2022, total of 99 participants were enrolled at 17 centres in France. Participants with a sibling or matched unrelated donor were assigned to allogeneic HSCT (HSCT group, n=55 [56%]) and participants without a donor were assigned to non-allogeneic HSCT treatment (non-HSCT group, n=44 [44%]). The median follow-up among survivors was 12·6 months (IQR 11·0-35·2). In the HSCT group, 51 participants (93%) were 1:1 matched to participants from the non-HSCT group. In the intention-to-treat analysis, median progression-free survival was significantly longer in the HSCT group (9·0 months [95% CI 6·6-30·5]) than in the non-HSCT group (3·0 months [2·0-6·3]), with a hazard ratio of 0·38 (95% CI 0·21-0·69; p<0·0001). In the per-protocol population, 40 participants (78%) in the HSCT group had 101 serious events and 29 participants (67%) in the non-HSCT group had 70 serious adverse events. The most common serious adverse event other than graft-versus-host disease in both groups was infections, occurring in 30 participants (59%) in the HSCT group and in 19 participants (44%) in the non-HSCT group. INTERPRETATION: Allogeneic HSCT was associated with significantly longer progression-free survival in participants with advanced-stage CTCLs. These results indicate that allogeneic HSCT treatment should be made available to individuals with high-risk, advanced-stage mycosis fungoides or Sézary syndrome who achieve pre-transplant disease remission. FUNDING: French Ministry of Health, National Cancer Institute, Programme Hospitalier de Recherche Clinique en Cancérologie.

Clostridium difficile infection and immune checkpoint inhibitor-induced colitis in melanoma: 18 cases and a review of the literature.

Immunotherapy has become the standard of care for several types of cancer, such as melanoma. However, it can induce toxicity, including immune checkpoint inhibitor-induced colitis (CIC). CIC shares several clinical, histological, biological, and therapeutic features with inflammatory bowel disease (IBD). Clostridium difficile infection (CDI) can complicate the evolution of IBD. We aimed to characterize the association between CDI and CIC in patients treated with anti-CTLA-4 and anti-PD-1 for melanoma. Patients from nine centers treated with anti-CTLA-4 and anti-PD-1 for melanoma and presenting with CDI from 2010 to 2021 were included in this retrospective cohort. The primary endpoint was the occurrence of CIC. The secondary endpoints were findings allowing us to characterize CDI. Eighteen patients were included. Eleven were treated with anti-PD-1, four with anti-CTLA-4, and three with anti-PD-1 in combination with anti-CTLA-4. Among the 18 patients, six had isolated CDI and 12 had CIC and CDI. Among these 12 patients, eight had CIC complicated by CDI, three had concurrent CIC and CDI, and one had CDI followed by CIC. CDI was fulminant in three patients. Endoscopic and histological features did not specifically differentiate CDI from CIC. Nine of 11 patients required immunosuppressive therapy when CDI was associated with CIC. In nine cases, immunotherapy was discontinued due to digestive toxicity. CDI can be isolated or can complicate or reveal CIC. CDI in patients treated with immunotherapy shares many characteristics with CDI complicating IBD. Stool tests for Clostridium difficile should be carried out for all patients with diarrhea who are being treated with immunotherapy.

Primary cutaneous peripheral T-cell lymphomas with a T-follicular helper phenotype: an integrative clinical, pathological and molecular case series study.

BACKGROUND: Primary cutaneous peripheral T-cell lymphomas with a T-follicular helper phenotype (pcTFH-PTCL) are poorly characterized, and often compared to, but not corresponding with, mycosis fungoides (MF), Sézary syndrome, primary cutaneous CD4+ lymphoproliferative disorder, and skin manifestations of angioimmunoblastic T-cell lymphomas (AITL). OBJECTIVES: We describe the clinicopathological features of pcTFH-PTCL in this original series of 23 patients, and also characterize these cases molecularly. METHODS: Clinical and histopathological data of the selected patients were reviewed. Patient biopsy samples were also analysed by targeted next-generation sequencing. RESULTS: All patients (15 men, eight women; median age 66 years) presented with skin lesions, without systemic disease. Most were stage T3b, with nodular (n = 16), papular (n = 6) or plaque (atypical for MF, n = 1) lesions. Three (13%) developed systemic disease and died of lymphoma. Nine (39%) patients received more than one line of chemotherapy. Histologically, the lymphomas were CD4+ T-cell proliferations, usually dense and located in the deep dermis (n = 14, 61%), with the expression of at least two TFH markers (CD10, CXCL13, PD1, ICOS, BCL6), including three markers in 16 cases (70%). They were associated with a variable proportion of B cells. Eight patients were diagnosed with an associated B-cell lymphoproliferative disorder (LPD) on biopsy, including Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (n = 3), EBV+ LPD (n = 1) and monotypic plasma cell LPD (n = 4). Targeted sequencing showed four patients to have a mutated TET2-RHOAG17V association (as frequently seen in AITL) and another a TET2/DNMT3A/PLCG1/SETD2 mutational profile. The latter patient, one with a TET2-RHOA association, and one with no detected mutations, developed systemic disease and died. Five other patients showed isolated mutations in TET2 (n = 1), PLCG1 (n = 2), SETD2 (n = 1) or STAT5B (n = 1). CONCLUSIONS: Patients with pcTFH-PTCL have pathological and genetic features that overlap with those of systemic lymphoma of TFH derivation. Clinically, most remained confined to the skin, with only three patients showing systemic spread and death. Whether pcTFH-PTCL should be integrated as a new subgroup of TFH lymphomas in future classifications is still a matter of debate. What is already known about this topic? There is a group of cutaneous lymphomas that express T-follicular helper (TFH) markers that do not appear to correspond to existing World Health Organization diagnostic entities. These include mycosis fungoides, Sézary syndrome, or primary cutaneous CD4+ small/medium-sized T-cell lymphoproliferative disorder or cutaneous extensions of systemic peripheral T-cell lymphomas (PTCL) with TFH phenotype. What does this study add? This is the first large original series of patients with a diagnosis of primary cutaneous PTCL with a TFH phenotype (pcTFH-PTCL) to be molecularly characterized. pcTFH-PTCL may be a standalone group of cutaneous lymphomas with clinicopathological and molecular characteristics that overlap with those of systemic TFH lymphomas, such as angioimmunoblastic T-cell lymphoma, and does not belong to known diagnostic groups of cutaneous lymphoma. This has an impact on the treatment and follow-up of patients; the clinical behaviour needs to be better clarified in further studies to tailor patient management.

Impact of Mogamulizumab in Real-Life Advanced Cutaneous T-Cell Lymphomas: A Multicentric Retrospective Cohort Study.

BACKGROUND: Advanced mycosis fungoides (MF) and Sézary syndrome (SS) are rare, aggressive cutaneous T-cell lymphomas that may be difficult to treat. Mogamulizumab is a recent monoclonal antibody targeting the CCR4 receptor expressed on the surface of Sézary cells. It can be prescribed in MF/SS stages III to IV in the second line after systemic therapy or in stages IB-II after two unsuccessful systemic therapies. We lack data on long-term efficiency and potential side effects in real-life conditions. Our study aims to determine efficacy considering the median PFS of advanced CTCL with mogamulizumab. Secondary objectives were to consider tolerance and estimate delay until side effects appeared. METHODS: Data on patients with advanced cutaneous T-cell lymphomas were collected since French Authorization, in six French university hospitals. Patients were followed until they stopped mogamulizumab because of relapse or toxicity. For those still treated by mogamulizumab, the end point was 1 September 2021. We excluded 3 patients as they had already been included in the MAVORIC study and data was not available. RESULTS: The median time of follow-up was 11.6 months. Of the 21 patients included, we reported four full-response patients, eight in partial response, one in stability, three in progression, and five were deceased. One patient had visceral progression, and seven had new lymphadenopathy. Progression-free survival was estimated at 22 months. Twenty patients presented adverse events, of which 10 were severe, i.e., grade III-IV. The median time between the introduction of mogamulizumab and the first adverse event was 21 days. CONCLUSIONS: Our study suggests that mogamulizumab can give patients with advanced refractory CTCL a consequent PFS, estimated at 22 months. The long-term safety of mogamulizumab was determined to be acceptable since we reported few grade III-IV AEs, comparable with other studies. No other study using real-life data has been performed to investigate the AEs of mogamulizumab.

Biological Therapies or Apremilast in the Treatment of Psoriasis in Patients with a History of Hematologic Malignancy: Results from a Retrospective Study in 21 Patients.

BACKGROUND: Few studies addressing the safety and efficacy of biological therapy (BT) or apremilast (APR) in patients with psoriasis with a history of hematologic malignancy (HM) exist. AIM: To describe the tolerance and efficacy of BT and APR in moderate-to-severe psoriasis in patients with a history of in-remission or evolving HM. METHODOLOGY: A retrospective, multicenter chart review of the tolerance and efficacy of BT or APR in patients with moderate-to-severe psoriasis and a clinical history of in-remission or evolving HM. RESULTS: Twenty-one patients with severe psoriasis and a history of HM were included in France by the GEM Resopso study group. Of the 16 patients treated with one or more BT lines, none showed recurrence of their HM which was considered as stable or in remission, and only 2 patients showed an evolution of their HM which had been considered as stable at the beginning of treatment. In the 10 patients treated with APR, the HM of one patient who also received BT worsened. The 3 evolutions did not impact the treatment with BT or APR. Tolerance was very satisfactory, with a low occurrence of infections. Regarding efficacy, only one patient treated with APR did not achieve any notable clinical improvement. CONCLUSION: Despite supportive data regarding tolerance, the heterogeneity of the analyzed population and limited available data, BT and APR should be used with caution in this patient population and investigations on larger cohorts should be conducted to further assess their tolerance in this patient population.

Impact of the corticosteroid indication and administration route on overall survival and the tumor response after immune checkpoint inhibitor initiation.

BACKGROUND: Based on their indications, systemic corticosteroids appear to negatively affect clinical outcomes in immune checkpoint inhibitor (ICI)-treated patients. There are few data on the influence of topical and inhaled corticosteroids on the ICIs' effectiveness. METHODS: In a single-center study, we retrospectively investigated the impact of systemic corticosteroids according to their indication [an immune-related adverse event (irAE) or another indication] on overall survival (OS) and the tumor response in all consecutive patients after initiation of ipilimumab, nivolumab or pembrolizumab over a 9-year period. The impacts of topical and inhaled corticosteroids were also examined. RESULTS: Three hundred and seventy-two patients were included. The mean ± standard deviation age was 64.0 ± 12.1 years. The most frequently prescribed ICI was nivolumab (in 58.3% of the patients) and the most frequent indications were lung cancer (44.6%) and melanoma (29.6%). Systemic corticosteroid use for an irAE did not have a negative impact on OS [adjusted hazard ratio (HR) [95% confidence interval (CI)] 1.04 (0.56-1.95), p = 0.902] or the best overall tumor response [adjusted odds ratio (OR) (95% CI) 1.69 (0.52-6.56), p = 0.413], while systemic corticosteroid use for another indication was associated with shorter OS [adjusted HR (95% CI) 1.34 (1.05-2.03), p = 0.046] and a poor best overall tumor response [adjusted OR (95% CI) 2.04 (1.07-5.80), p = 0.039] with a cumulative dose cut-off of 3215 mg prednisolone equivalent (specificity 71.4%; sensitivity 65.3%) and a time cut-off of 132 days (specificity 71.4%; sensitivity 89.8%). The use of topical corticosteroids was associated with a longer OS; this was probably due to dermatological irAEs. Inhaled corticosteroid use did not influence OS. CONCLUSION: Systemic corticosteroid use for an irAE does not impact OS or the tumor response, whereas use for other indications (themselves often associated with a worse prognosis) does. Topical and inhaled steroids do not have a negative impact on OS.

Psychometric validation of a patient-reported outcome questionnaire (Qualipsosex) assessing the impact of psoriasis and psoriatic arthritis on patient perception of sexuality.

ABSTRACT: Psoriasis (Pso) and psoriatic arthritis (PsA) frequently have a negative impact on patients' sexual health. We have developed a specific questionnaire assessing the impact of Pso and PsA on patient perception of sexuality: the QualipsoSex Questionnaire (QSQ). The aim of the present study was to further validate this questionnaire by checking its psychometric properties including validity, reliability, and responsiveness.A cross sectional observational study with a longitudinal component for responsiveness and test-retest reliability was performed in 12 centers in France including 7 dermatologists and 5 rheumatologists. Psychometric properties were examined according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) check-list.At baseline, 114 patients had Pso and 35 patients had PsA including 17 peripheral arthritis, 4 axial disease, 13 patients with both axial disease and peripheral arthritis and one patient with an undifferentiated phenotype. The mean Pso Area and Severity Index score was 12.5. Genital organs were involved in 44.7% of Pso cases. Internal consistency, construct validity, and reliability were good with Cronbach's α coefficient, measure of sampling adequacy and intraclass correlation coefficient respectively at 0.87, 0.84, and 0.93. The QSQ also demonstrated acceptable sensitivity to change.The QSQ has demonstrated good psychometric properties fulfilling the validation process relative to the recommendations of the COSMIN check list. The QSQ is simple to score and may hopefully be valuable in clinical practice and in clinical trials.

Iatrogenic cutaneous graft versus host disease.

A 65-year-old man with acute myeloid leukemia 6 was treated by bone marrow allograft, developed a systemic classic chronic graft versus host disease with hepatic, rheumatologic, ophthalmic, and muco-cutaneous involvement. He received systemic corticosteroid, ruxolitinib and extracorporeal photopheresis which resulted in complete remission. During follow-up the patient presented with viral cutaneous warts on his neck and submandibular area. After various subsequent topical treatments, he developed localized cutaneous GVHD without any general GVHD reactivation symptoms. To the best of our knowledge, there has been no description in the literature of a graft versus host disease developing after local immunomodulatory or cytotoxic treatments. Topical therapies are commonly used by dermatologists for superficial skin cancers and some viral skin lesions, in high risk populations such as organ transplant patients with regular follow-up.Practitioners should be made aware of a possible localized cutaneous GVHD reactivation induced by Koebner phenomenon after local therapy.

Two cases of pneumonitis induced by targeted therapy.

Interstitial pneumonitis is a rare drug adverse effect. We report two cases of cobimetinib-induced and vemurafenib-induced reversible interstitial pneumonitis. Two patients presenting a BRAF-mutated metastatic melanoma were treated with cobimetinib and vemurafenib. After 3 months, they developed severe feverish dyspnea. Thoracic imaging showed a pattern of organizing pneumonia in one case and a pattern of hypersensitivity pneumonitis in the other case. Infectious and cardiogenic causes were eliminated. An improvement was noted after discontinuation of cobimetinib, vemurafenib, and introducing steroids. Treatment was switched to dabrafenib (a BRAF inhibitor) with no recurrence of drug pneumonitis. To the best of our knowledge, it appears that cases of targeted-therapy-induced pneumonitis are predominantly an MEK-inhibitor effect. We, therefore, propose a management strategy of discontinuing targeted therapy, introducing steroid treatment and switching to dabrafenib.

Localization, Morphologic Features, and Chemical Composition of Calciphylaxis-Related Skin Deposits in Patients With Calcific Uremic Arteriolopathy.

Importance: Calcific uremic arteriolopathy (CUA), a rare, potentially fatal, disease with calcium deposits in skin, mostly affects patients with end-stage renal disease who are receiving dialysis. Chemical composition and structure of CUA calcifications have been poorly described. Objectives: To describe the localization and morphologic features and determine the precise chemical composition of CUA-related calcium deposits in skin, and identify any mortality-associated factors. Design, Setting, and Participants: A retrospective, multicenter cohort study was conducted at 7 French hospitals including consecutive adults diagnosed with CUA between January 1, 2006, and January 1, 2017, confirmed according to Hayashi clinical and histologic criteria. Patients with normal renal function were excluded. For comparison, 5 skin samples from patients with arteriolosclerosis and 5 others from the negative margins of skin-carcinoma resection specimens were also analyzed. Main Outcomes and Measures: Localization and morphologic features of the CUA-related cutaneous calcium deposits were assessed with optical microscopy and field-emission-scanning electron microscopy, and the chemical compositions of those deposits were evaluated with µ Fourier transform infrared spectroscopy, Raman spectroscopy, and energy dispersive radiographs. Results: Thirty-six patients (median [range] age, 64 [33-89] years; 26 [72%] female) were included, and 29 cutaneous biopsies were analyzed. Calcific uremic arteriolopathy and arteriolosclerosis skin calcifications were composed of pure calcium-phosphate apatite. Calcific uremic arteriolopathy vascular calcifications were always circumferential, found in small to medium-sized vessels, with interstitial deposits in 22 (76%) of the samples. A thrombosis, most often in noncalcified capillary lumens in the superficial dermis, was seen in 5 samples from patients with CUA. Except for calcium deposits, the vessel structure of patients with CUA appeared normal, unlike thickened arteriolosclerotic vessel walls. Twelve (33%) patients died of CUA. Conclusions and Relevance: Calcific uremic arteriolopathy-related skin calcifications were exclusively composed of pure calcium-phosphate apatite, localized circumferentially in small to medium-sized vessels and often associated with interstitial deposits, suggesting its pathogenesis differs from that of arteriolosclerosis. Although the chemical compositions of CUA and arteriolosclerosis calcifications were similar, the vessels' appearances and deposit localizations differed, suggesting different pathogenetic mechanisms.

B-cell depletion induces a shift in self antigen specific B-cell repertoire and cytokine pattern in patients with bullous pemphigoid.

Bullous Pemphigoid is the most common auto-immune bullous skin disease. It is characterized by the production of auto-antibodies directed against 2 proteins of the hemi-desmosome (BP180 and BP230). We assessed the efficacy and mechanisms of action of rituximab, an anti-CD20 monoclonal antibody, in 17 patients with severe and relapsing type of bullous pemphigoid. The phenotype, cytokine gene expression, and rearrangement of BP180-specific B-cell receptor genes were performed over 2 years following treatment. At the end of the study, 5 patients had died, 3 had withdrawn from the study, and 9 patients were in complete remission. The one- and two-year relapse rates were 44.1% (95% Confidence Interval (CI): 21.0-76.0%) and 66.5%, (95% CI: 38.4-91.4%), respectively. Phenotypic analyses confirmed dramatic B-cell depletion, which lasted for 9 to 12 months. The ELISA values of serum anti-BP180 antibodies and the frequency of BP180-specific circulating B cells decreased dramatically following treatment, which paralleled the improvement of skin lesions. During B-cell reconstitution, a polyclonal IgM repertoire appeared and a shift in the rearrangement of the B-cell receptor genes of BP180-specific circulating B cells was observed. Concurrently, we observed a decrease of IL-15, IL-6 and TNFα expressing BP180-specific B cells, and the emergence of IL-10 and IL-1RA-expressing BP180-specific IgM+ B cells in patients in complete remission off therapy, suggesting the functional plasticity of BP180-specific auto-immune B cells after rituximab treatment.

Subacute cutaneous lupus erythematosus induced by nivolumab: two case reports and a literature review.

Nivolumab is widely used to treat several late-stage malignancies such as melanoma and non-small-cell lung cancer by inhibiting the interaction between the programmed cell death protein-1 and its ligand. By stimulating an antitumor immune response, it also leads to immune adverse events. Here. we report two cases of subacute cutaneous lupus erythematosus (SCLE) induced by nivolumab. Case 1: a 72-year-old woman with a stage IV melanoma. Two months after nivolumab discontinuation because of autoimmune hepatitis, the patient was in complete remission and pruritic nummular erythematous plaques appeared on the back and arms. Case 2: a 43-year-old man put under nivolumab for a metastatic non-small-cell lung cancer. After two cycles, an annular erythematous eruption appeared on the hands, arms, and chest. The hypothesis of SCLE was confirmed by biopsies showing lymphoid perivascular inflammatory infiltrates, with scarce C3 deposits along the basal layer of the epidermis in patient 2. Both patients tested positive for antinuclear antibodies and anti-SSA antibodies. Lesions were regressive under topical corticosteroids and hydroxychloroquine for the first patient and oral prednisone for the second patient. No systemic involvement was observed. The occurrence of SCLE 2 months after nivolumab discontinuation is evidence that the drug effect is prolonged because of the maintenance of programmed cell death protein-1 reception saturation for months. A causal relationship between SCLE and nivolumab is suggested by (i) the occurrence of SCLE after at least two cycles, (ii) the regression of lesions following treatment with corticosteroids and hydroxychloroquine, and (iii) the fact that it appeared after remission in our first patient.