RESUMEN
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.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma Cutáneo de Células T , Micosis Fungoide , Síndrome de Sézary , Neoplasias Cutáneas , Humanos , Estudios Prospectivos , Síndrome de Sézary/terapia , Síndrome de Sézary/etiología , Puntaje de Propensión , Linfoma Cutáneo de Células T/terapia , Linfoma Cutáneo de Células T/etiología , Trasplante Homólogo , Trasplante de Células Madre Hematopoyéticas/métodos , Micosis Fungoide/etiología , Micosis Fungoide/patología , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/etiologíaRESUMEN
BACKGROUND: Epidermal necrolysis (EN), comprising Stevens Johnson syndrome and toxic epidermal necrolysis is a rare and severe blistering reaction, mainly induced by drugs. Differences have been discussed between pediatric and adult patients regarding incidence, causes, and outcomes, but only based on a limited number of patients, in small case-series. OBJECTIVES: To directly compare incidence, causes and prognosis between adult and pediatric EN patients. METHODS: We used the French Health System Database from January 1st 2013 to December 31st 2022. We included adult and pediatric patients hospitalized for EN using the international classification of diseases, 10th revision codes combined with validated algorithms. The outcomes were incidence of EN; presence of a suspected drug before EN onset, defined by a new drug dispensation from 5 to 56â days before hospitalization; and in-hospital mortality. To estimate the association between pediatric EN and the presence of a suspected drug, we computed a multivariable logistic regression with odd ratios (OR). To estimate the association with mortality, we computed a multivariable Cox proportional hazard ratio (HR) model. RESULTS: A total of 1440 EN patients were included, with 799 (55.5%) females, comprising 219 children and 1221 adults. Among children, EN incidence was 1.5 cases (95%CI: 1.3-1.7) per million people year compared with 2.6 cases (95%CI: 2.5-2.7) in adults. Moreover, children had less chances to have a culprit drug before EN onset (93/219 (42.5%) versus 829/1221 (67.9%)), with an adjusted OR of 0.43 (95%CI: 0.32-0.59), p < 0.0001, together with a better prognosis, with death rates of 1.4% (95%CI: 0.4%-3.7%) in pediatric patients compared with 19.4% (95%CI: 17.3%-21.7%) in adult patients, and an adjusted HR of 0.12 (95%CI: 0.04-0.38), p = 0.0003 for in-hospital mortality. CONCLUSION: Pediatric EN seems to be rarer, with less chances to be caused by drugs, together with a better prognosis than adult EN. These results suggest the existence of different underlying pathophysiological mechanisms and clinical particularities between adult and pediatric patients.
RESUMEN
BACKGROUND: Much has been documented about the physical sequelae of Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN). Whilst less documented, it is recognised that patients can have long lasting psychological sequelae. There is a lack of qualitative research on the quality of life (QoL) experiences of adults who have been diagnosed with SJS/TEN. OBJECTIVES: To explore the experiences of adults who had SJS/TEN and how these experiences relate to their QoL. METHODS: Using an interpretative descriptive qualitative study, a purposive sample of 18 adults with SJS/TEN were interviewed using in depth semi structured interviews. Data were analysed using content analysis. RESULTS: Two themes were constructed, each with two categories. Theme 1, Psychosocial Impacts included the categories 'The Self and Others', and 'A Changed Perspective on Life'. Theme 2, The Chronicity of Sequelae comprised the categories 'Multi Organ Involvement', and 'Further Consequences of TEN'. CONCLUSIONS: Findings highlighted that SJS/TEN had a significant impact on the different quality-of-life experiences of participants including psychological, physical, social, educational and occupational. Many expressed challenges they faced following discharge from hospital, including gaps in psychological care, navigating disjointed care pathways and lack of coordinated care. If SJS/TEN is viewed as a chronic condition, it is important that researchers and clinicians study the long-term effects of SJS/TEN on people's lives to aid in developing a plan of care to enhance the QoL for this cohort. Psychological and quality of life assessments following discharge from hospital require consideration.
RESUMEN
BACKGROUND: Interest in the use of omalizumab to treat bullous pemphigoid (BP) in the event of resistance or contraindication to conventional therapies is currently based on limited evidence. OBJECTIVES: To assess the effectiveness and safety of omalizumab in BP and to identify predictive factors in response to treatment. METHODS: We conducted a French national multicentre retrospective study including patients with a confirmed diagnosis of BP treated with omalizumab after failure of one or several treatment lines. We excluded patients with clinically atypical BP, as per Vaillant's criteria. The criteria for clinical response to omalizumab were defined according to the 2012 international consensus conference. Anti-BP180-NC16A IgE enzyme-linked immunosorbent assay was performed on sera collected before initiating omalizumab, when available. RESULTS: Between 2014 and 2021, 100 patients treated in 18 expert departments were included. Median age at diagnosis was 77â years (range 20-98). Complete remission (CR) was achieved in 77% of patients, and partial remission in an additional 9%. CR was maintained 'off therapy' in 11.7%, 'on minimal therapy' in 57.1%, and 'on non-minimal therapy' in 31.2%. Median time to CR was 3â months (range 2.2-24.5). Relapse rate was 14%, with a median follow-up time of 12â months (range 6-73). Adverse events occurred in four patients. CR was more frequently observed in patients with an increased serum baseline level of anti-BP180-NC16A IgE (75% vs. 41%; P = 0.011). Conversely, urticarial lesions, blood total IgE concentration or eosinophil count were not predictive of CR. Patients with an omalizumab dosage > 300â mg every 4 weeks showed a similar final outcome to those with a dosage ≤ 300â mg every 4 weeks, but control of disease activity [median 10â days (range 5-30) vs. 15â days (range 10-60); P < 0.001] and CR [median 2.4â months (range 2.2-8.2) vs. 3.9â months (range 2.3-24.5); P < 0.001] were achieved significantly faster. CONCLUSIONS: We report the largest series to date of BP treated by omalizumab and confirm its effectiveness and safety in this indication. Serum baseline level of anti-BP180-NC16A IgE may predict response to treatment.
Asunto(s)
Penfigoide Ampolloso , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Penfigoide Ampolloso/diagnóstico , Colágeno Tipo XVII , Omalizumab/uso terapéutico , Estudios Retrospectivos , Colágenos no Fibrilares , Autoantígenos , Inmunoglobulina E , AutoanticuerposRESUMEN
BACKGROUND: Mycosis fungoides (MF) has usually an indolent course. However, some patients develop a more aggressive disease and few prognostic parameters have been identified. Isolated cases of pustular MF (pMF) suggest an unfavourable prognosis. OBJECTIVES: We aim to describe the clinico-pathological characteristics and prognostic value of pMF. METHODS: We retrospectively collected data of all cases of MF with histological pustules diagnosed from 2009 to 2020. The outcomes and clinico-pathological characteristics of pMF at diagnosis (pMFD) were compared to those of a cohort of non-pustular MF (NpMF). RESULTS: 33 pMF (including 22 pMFD) and 86 NpMF cases were included. The median age at diagnosis of pMF was 61 years [IQR=50-75]. The median follow-up of pMFD was 32 months [IQR=14-49]. Clinically, 33% of pMF had pustules. Large-cell transformation (LCT) occurred in 17 cases. pMFD were at a significantly more advanced-stage and more showed LCT at diagnosis than NpMF (50% vs 7%, p<0.001 and 23% vs 0%, p<0.001, respectively). In multivariate Cox analysis, the presence of histological pustule at diagnostic was associated with shorter OS in all patients (HR=13.90, CI95%[2.43-79]; p=0.003), and in early-stage patients (HR=11.09, CI95%[1.56-78.82]; p=0.02). In multivariate Fine and Gray model analysis, pMFD was associated with a higher cumulative incidence of LCT (SHR=13.90, CI95% [2.43-79]; p=0.003) in all patients. Median OS after the occurrence of histological pustules during follow-up of all pMF patients was 37 months, with a five-year OS of 25% (CI95% [0.06-0.5]). CONCLUSION: pMF often follows an aggressive course, with a high risk of LCT and shorter survival, even for early-stage patients. Histological pustules at diagnostic of MF might represent an independent poor prognostic factor, to be confirmed by further studies. Because pustules are not always clinically identified, histological pustules should be mentioned in pathology reports of MF and prompt discussion of a closer follow-up.
RESUMEN
BACKGROUND AND PURPOSE: Peripheral neuropathy is a frequent complication of brentuximab vedotin (BV), used in CD30+ lymphoma treatment. Classic BV-induced neuropathy (BV-CN) is a mild distal sensory axonal polyneuropathy. Severe BV-induced inflammatory neuropathies (BV-IN) have been described. BV-IN contribute to lymphoma-associated morbidity but might be immunotherapy-responsive. Our primary objective was to evaluate the rate of BV-IN. Our secondary objectives were to determine risk factors and warning signs. METHODS: We conducted a retrospective cohort study on all patients treated with BV at our center between April 2014 and September 2021. Clinical, biological, and electrophysiological data were collected. BV-induced neuropathy was defined as the occurrence of neuropathy up to 3 months after BV discontinuation. BV-IN was defined with criteria adapted from European Academy of Neurology/Peripheral Nerve Society 2021 electrodiagnostic criteria for chronic inflammatory demyelinating polyradiculoneuropathy. Other neuropathies were classified as BV-CN. RESULTS: Among 83 patients, 41 (49%) developed neuropathy: 35 BV-CN and 6 BV-IN. Thus, the rate of BV-IN was 7.2%. Compared to patients with BV-CN, no predisposing factor was identified. However, patients with BV-IN more frequently presented muscle weakness (67% vs. 5.7%, p < 0.05), gait disorders (83% vs. 20%, p < 0.05), or acute or subacute onset (67% vs. 14%, p < 0.05). BV-IN was frequently more severe (Common Terminology Criteria for Adverse Events grade ≥3; 50% vs. 0%, p < 0.05). Four patients were treated with immunotherapy. CONCLUSIONS: Brentuximab vedotin-induced neuropathy is an overlooked complication. Based on four easily identifiable "red flags", we provide an algorithm to help non-neurologist physicians that care for BV-treated patients to detect BV-IN. The aim of the algorithm is to decrease the diagnostic and management delay of this disabling neuropathy.
Asunto(s)
Antineoplásicos Inmunológicos , Brentuximab Vedotina , Enfermedades del Sistema Nervioso Periférico , Humanos , Masculino , Brentuximab Vedotina/efectos adversos , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Antineoplásicos Inmunológicos/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Adulto , Linfoma/tratamiento farmacológicoRESUMEN
BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare life-threatening mucocutaneous reactions most often induced by drugs. To date, no large pharmacovigilance study has been conducted in the paediatric population. OBJECTIVES: To describe the spectrum of drugs associated with SJS-TEN in children through the analysis of cases reported in the WHO pharmacovigilance database (VigiBase). METHODS: Disproportionality study using data from VigiBase. All paediatric (age under 18 years) cases reported between January 1, 1967, and July 6, 2022, were included. For each molecule, a case-non-case study was performed to assess a potential pharmacovigilance signal by computing the lower end of the 95% credibility interval for the information component (IC025). We performed sensitivity analyses, (i) taking into account only cases reported by physicians and (ii) taking into account only cases reported in the last 10 years. RESULTS: Among 31,376,783 adverse drug reactions reported in VigiBase, 2,248,727 were paediatric cases and 7342 were encoded as paediatric SJS-TEN. Significant statistical pharmacovigilance signals were observed for 165 drugs. The two most represented drug classes were antiepileptics and anti-infectious drugs. The five drugs with the highest IC025 were lamotrigine (IC025 4.99), carbamazepine (IC025 4.88), phenobarbital (IC025 4.67), phenytoin (IC025 4.52) and nimesulide (IC025 4.23). Acetaminophen was significantly associated with paediatric SJS-TEN (IC025 2.85) and we also described various new suspected drugs. Vaccines had no significant pharmacovigilance signal. These results were confirmed with the sensitivity analyses. CONCLUSIONS: This study updates the spectrum of drugs potentially associated with paediatric SJS-TEN.
Asunto(s)
Bases de Datos Factuales , Farmacovigilancia , Síndrome de Stevens-Johnson , Organización Mundial de la Salud , Humanos , Síndrome de Stevens-Johnson/etiología , Síndrome de Stevens-Johnson/epidemiología , Niño , Adolescente , Preescolar , Lactante , Masculino , Femenino , Anticonvulsivantes/efectos adversos , Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricosRESUMEN
BACKGROUND: Patch tests (PTs) are recommended to identify the culprit drug in non-immediate cutaneous adverse drug reactions (NICADRs). We recently reported that, in patients with NICADRs, a unique reading of PTs at day (D)2 compared with an additional second late reading at D4 missed almost half (45.3%) of the positive PTs. OBJECTIVES: To assess the change in sensitivity of the PT reading on D4 compared with the reading on D3. METHODS: We performed a retrospective (July 2020-June 2023) monocentric study of patients who had PTs with two readings for a NICADR. We compared reading on D3 and the second reading on D4 for the suspected drug (primary outcome) and for the related drugs tested simultaneously (secondary outcome). RESULTS: During the study period, 249 patients underwent patch testing with D3 and D4 readings. Regarding the primary outcome, the first reading at D3 was positive for 13.7% of patients, and the reading at D4 for 24.9% of patients (p < 0.0001). Regarding the secondary outcome, only 9.6% of patients had all their positive PT at D3 compared with 24.9% of patients at D4 (p < 0.0001). Considering the evaluated drug classes, no statistical difference was observed. However, we highlight that D3 reading detected all positive carbamazepine PTs (n = 3) while positive clindamycin PTs (n = 4) were identified only with the help of the second reading on D4. CONCLUSION: This study showed that, an additional D4 reading compared with a single D3 reading enhanced the sensitivity of PTs to identify culprit drugs and related. Further studies should replicate these findings and evaluate the medico-economic balance and safety of a single reading of PTs on D4.
RESUMEN
BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but potentially life-threatening cutaneous adverse reactions. There is still no consensus on adjuvant treatments, and little is known about their effects on systemic inflammation in SJS/TEN. Our aim was to characterize the systemic and cutaneous immune profiles of SJS/TEN patients and to investigate whether/how intravenous immunoglobulins (IVIG), cyclosporine A (CSA), and best supportive care only (BSCO) affected the systemic immune signature and clinical outcome (6 week-mortality, complications, hospitalization stay). METHODS: We included 16 patients with SJS/TEN, treated with high-dose IVIG (n = 8), CSA (n = 4) or BSCO (n = 4). Serial serum samples were obtained prior-, 5-7 days, and 21 days after treatment onset. Serum levels of inflammation-/immune response-associated proteins were measured by high-throughput proteomics assay (OLINK) and cytotoxic molecules by ELISA. RNA extracted from skin biopsies collected prior treatment was analyzed by Nanostring. RESULTS: Serum inflammatory profiles in SJS/TEN patients were notably characterized by massive upregulation of type 1 immune response and proinflammatory markers. Surprisingly, there was limited overlap between cutaneous and serum immune profiles. Serial serological measurements of immune response markers showed very diverse dynamics between the different treatment groups. IVIG-treated patients showed completely different dynamics and most significant proteomic changes in an early phase (Day 5-7). In all treatment groups, type 1-/inflammatory response markers were dampened at day 21. Clinically, there were no outcome differences. CONCLUSION: Our study demonstrates that BSCO, CSA, and IVIG have very diverse biological effects on the systemic inflammatory response in SJS/TEN, which may not correlate with clinical outcome differences.
Asunto(s)
Inmunoglobulinas Intravenosas , Síndrome de Stevens-Johnson , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Síndrome de Stevens-Johnson/tratamiento farmacológico , Síndrome de Stevens-Johnson/etiología , Ciclosporina/uso terapéutico , Proteómica , Piel , Estudios RetrospectivosRESUMEN
BACKGROUND: No study has assessed the risk factors of progression from discoid lupus erythematosus (DLE) to severe systemic lupus erythematosus (sSLE) (defined as requiring hospitalization and specific treatment). OBJECTIVE: To identify the risks factors of and generate a predicting score for progression to sSLE among patients with isolated DLE or associated with systemic lupus erythematosus with mild biological abnormalities. METHODS: In this registry-based cohort study, multivariable analysis was performed using risk factors identified from literature and pruned by backward selection to identify relevant variables. The number of points was weighted proportionally to the odds ratio (OR). RESULTS: We included 30 patients with DLE who developed sSLE and 134 patients who did not. In multivariable analysis, among 12 selected variables, an age of <25 years at the time of DLE diagnosis (OR, 2.8; 95% CI, 1.1-7.0; 1 point), phototype V to VI (OR, 2.7; 95% CI, 1.1-7.0; 1 point), and antinuclear antibody titers of ≥1:320 (OR, 15; 95% CI, 3.3-67.3; 5 points) were selected to generate the score. Among the 54 patients with a score of 0 at baseline, none progressed to sSLE, whereas a score of ≥6 was associated with a risk of approximately 40%. LIMITATIONS: Retrospective design. CONCLUSION: In our cohort, an age of <25 years at the time of DLE diagnosis, phototype V to VI, and antinuclear antibody titers of ≥1:320 were risk factors for developing sSLE.
Asunto(s)
Lupus Eritematoso Discoide , Lupus Eritematoso Sistémico , Humanos , Adulto , Estudios de Cohortes , Estudios Retrospectivos , Anticuerpos Antinucleares , Lupus Eritematoso Sistémico/diagnóstico , Factores de RiesgoRESUMEN
BACKGROUND: Our objective was to describe the clinical, histological characteristics, and disease outcome of a cohort of mycosis fungoides (MF) diagnosed during childhood including disease status at adulthood. METHODS: This is a retrospective multicentre survey of patients aged under 18 years at diagnosis with histologically confirmed MF. Patients' clinical and histological characteristics, treatments, and disease outcome (for patients followed for more than 12 months) were analysed. RESULTS: Forty-six patients were included (median age at diagnosis: 11 years; M:F sex ratio: 3:1) with 39 (85%) followed for at least 12 months. Thirty-nine patients (85%) had stage I MF. Hypopigmented patches were observed in 48% and folliculotropism in 43% patients. Immunophenotype of the skin infiltrate was predominantly CD8+ in 17% of patients. Initial management included a wait-and-see strategy in 6/39 (15%), skin-directed treatment in 27 (69%), and systemic treatment in 6 (15%) patients, respectively, with partial or complete clinical response (PR or CR) observed in 28 patients (72%). 14/39 patients (36%) relapsed after initial response. After a median follow-up period of 54 months, disease status at last news was PR or CR in 31/39 (79%), stable disease in 6 (15%), and progression in 2 (5%) patients. Histological transformation was observed in 3/39 (8%). Of the 15 patients followed until adulthood, 13 (87%) had persistent MF. DISCUSSION: This survey confirms the high frequency of hypopigmented and folliculotropic lesions and of CD8+ immunophenotype compared to adult MF patients. The long-term course is usually indolent but transformation may occur sometimes long after disease onset and the disease may persist during adulthood.
Asunto(s)
Hipopigmentación , Micosis Fungoide , Neoplasias Cutáneas , Adulto , Humanos , Niño , Adolescente , Anciano , Neoplasias Cutáneas/diagnóstico , Micosis Fungoide/diagnóstico , Estudios Retrospectivos , Hipopigmentación/tratamiento farmacológico , Hipopigmentación/patología , Administración CutáneaRESUMEN
Primary cutaneous diffuse large B-cell lymphoma, leg-type (PCDLBCL-LT) is an aggressive cutaneous lymphoma. Bone involvement is rare and poorly described. We present five cases of PCDLBCL-LT with bone localization. In four cases, the bone involvement was diagnosed during the initial staging with positron emission tomography (PET) or computed tomography (CT) scan, and in the fifth case after tibial fracture during treatment with rituximab (RTX) and polychemotherapy (PCT). PCDLBCL-LT can be asymptomatic and involve bone sites distant from cutaneous lesions. None had other extracutaneous involvement. In our series, all patients received RTX-PCT as first-line chemotherapy and all had early relapses or progression. Second-line treatments had poor efficacy. Our series shows that bone involvement seems to be associated with poor prognosis in PCDLBCL-LT. Bone localization is not diagnosed with initial thoracic-abdominal-pelvic CT when asymptomatic and affecting the limbs only. If there is a suspicion of PCDLBCL-LT, patients should undergo systematic investigation with alternative imaging techniques, including PET, both at baseline and if there is any concern during follow-up.
Asunto(s)
Neoplasias Óseas , Linfoma de Células B Grandes Difuso , Neoplasias Cutáneas , Humanos , Pierna/patología , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Extremidad Inferior/patología , Rituximab/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but potentially fatal drug hypersensitivity reaction. OBJECTIVE: To explore treatment approaches across Europe and their impact on the disease course, as well as prognostic factors and culprit drugs. METHODS: In this retrospective European multicentric study, we included patients with probable or certain DRESS (RegiSCAR score ≥ 4) between January 2016 and December 2020. Independent associations between clinical parameters and the risk of intensive care unit admission and mortality at three months were assessed using a multivariable-adjusted logistic regression model. RESULTS: A total of 141 patients from 8 tertiary centres were included. Morbilliform exanthem was the most frequent cutaneous manifestation (78.0%). The mean affected body surface area (BSA) was 67%, 42% of the patients presented with erythroderma, and 24.8% had mucosal involvement. Based on systemic involvement, 31.9% of the patients had a severe DRESS. Anticonvulsants (24.1%) and sulphonamides (22.0%) were the most frequent causative agents. In all, 73% of the patients were treated with systemic glucocorticoids, and 25.5% received topical corticosteroids as monotherapy. Few patients received antiviral drugs or anti-IL5. No patients received intravenous immunoglobulins. The overall mortality was 7.1%. Independent predictors of mortality were older age (≥57.0 years; fully adjusted OR, 9.80; 95% CI, 1.20-79.93; p = 0.033), kidney involvement (fully adjusted OR, 4.70; 95% CI, 1.00-24.12; p = 0.049), and admission in intensive care unit (fully adjusted OR, 8.12; 95% CI, 1.90-34.67; p = 0.005). Relapse of DRESS and delayed autoimmune sequelae occurred in 8.5% and 12.1% of patients, respectively. CONCLUSIONS: This study underlines the need for diagnostic and prognostic scores/markers as well as for prospective clinical trials of drugs with the potential to reduce mortality and complications of DRESS.
Asunto(s)
Síndrome de Hipersensibilidad a Medicamentos , Eosinofilia , Humanos , Estudios Retrospectivos , Síndrome de Hipersensibilidad a Medicamentos/tratamiento farmacológico , Síndrome de Hipersensibilidad a Medicamentos/etiología , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Estudios Prospectivos , Eosinofilia/complicaciones , Resultado del Tratamiento , Glucocorticoides/uso terapéuticoRESUMEN
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.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Linfadenopatía Inmunoblástica , Linfoma de Células B , Linfoma Cutáneo de Células T , Linfoma de Células T Periférico , Micosis Fungoide , Síndrome de Sézary , Neoplasias Cutáneas , Femenino , Humanos , Linfoma de Células T Periférico/genética , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/patología , Síndrome de Sézary/genética , Síndrome de Sézary/patología , Infecciones por Virus de Epstein-Barr/metabolismo , Infecciones por Virus de Epstein-Barr/patología , Linfocitos T Colaboradores-Inductores/metabolismo , Herpesvirus Humano 4 , Fenotipo , Micosis Fungoide/diagnóstico , Micosis Fungoide/genética , Neoplasias Cutáneas/patología , Linfoma de Células B/patología , Linfoma Cutáneo de Células T/genética , Linfoma Cutáneo de Células T/patologíaRESUMEN
BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disorder. Its presentation is polymorphic. OBJECTIVE: To investigate different clinical and biological profiles of BP. METHODS: We conducted a retrospective 2-center study including all BP patients seen between January 1, 2015, and February 28, 2021. We performed hierarchical clustering on principal components. RESULTS: Three clusters were identified. Patients in cluster 1 (n = 155) were older than those in clusters 2 (n = 89) and 3 (n = 35; P < .0001), more frequently presented pauci-bullous BP (n = 63 [41%] vs 14 [16%] and 2 [6%], respectively; P < .0001) and had anti-BP230 antibodies in 87% of cases. More than 100 blisters were observed in 14 patients (40%) from cluster 3, versus 3 (2%) from cluster 1 and 0 (0%) from cluster 2 (P < .0001). Frequency of mucosal involvement was higher in cluster 3 (n = 32 [91%, including epiglottis in 40%] vs 11 [7%] and 34 [38%]; P < .0001). In clusters 2 and 3, 70% and 74% of patients had antibodies targeting only BP180. Those in cluster 3 received more lines of systemic treatment and experienced more relapses. LIMITATIONS: Retrospective study without immunoelectron microscopy. CONCLUSION: We identified 3 different BP clusters, including one corresponding to severe BP180+ BP230- BP with features common to mucous membrane pemphigoid.
Asunto(s)
Penfigoide Ampolloso , Autoanticuerpos , Autoantígenos , Vesícula , Distonina , Humanos , Colágenos no Fibrilares , Estudios RetrospectivosRESUMEN
BACKGROUND: A high level of anti-BP180 antibodies on enzyme-linked immunosorbent assay and a persistent positive direct immunofluorescence at the end of treatment (immunologic tests, [ITs]) are predictors of relapse after treatment cessation (TC) in patients with bullous pemphigoid. OBJECTIVE: To evaluate the real-life impact of the immunologic-based decision of TC on the 3- and 6-month relapse rates after TC in bullous pemphigoid. METHODS: Retrospective multicentric study included patients followed almost 6 months after TC. Patients were classified according to whether the TC decision was in accordance with the results of ITs performed during the 3 months before TC, despite the results of ITs or without ITs performed. RESULTS: We included 238 patients. Three months after TC, 36 patients showed relapse: 14 of 95 patients with TC in accordance with IT results (14.7%); 5 of 21 with TC despite ITs (23.8%); and 17 of 122 with TC without ITs (13.9%; P = .5). Six months after TC, the relapse rate was 18.9%, 28.6%, and 18.9% (P = .56), respectively, in the 3 groups. LIMITATIONS: The retrospective design and the limited follow up. CONCLUSION: In real-life practice, in bullous pemphigoid, the 3- and 6-month relapse rates were not significantly reduced with TC decision based on results of ITs as compared with a classic clinical-based decision.
Asunto(s)
Penfigoide Ampolloso , Autoanticuerpos , Autoantígenos , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Pruebas Inmunológicas , Colágenos no Fibrilares , Penfigoide Ampolloso/tratamiento farmacológico , Recurrencia , Estudios Retrospectivos , Privación de TratamientoRESUMEN
BACKGROUND: Possible biases in pharmacovigilance reporting may impact epidermal necrolysis (EN) and drugs associations. OBJECTIVES: To assess biases associated with EN-reporting. METHODS: Using VigiBase, the World Health Organization-pharmacovigilance database, among drugs associated with EN between 2016 and 2020, we used an unsupervised clustering including reports characteristics, that is, reporter quality, time from drug intake to EN onset, and only one suspected drug in the report. RESULTS: Among 152 drugs, three clusters were identified. Cluster 1 (n = 41) exhibited drugs frequently reported within a time from intake to onset longer than 4 days, in 57 ± 13% of reports. It corresponded to well-reported drugs and was composed mainly of antivirals and antiepileptics. Cluster 2 (n = 42) exhibited drugs frequently reported within a time from drug intake to onset shorter than 4 days, in 31 ± 12% of reports. It corresponded to drugs with a high risk of protopathic bias and was composed of nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics, and antibiotics. Cluster 3 (n = 69) exhibited drugs frequently reported with an unavailable time from drug intake to reaction, in 66 ± 11% of reports, and reported by a high frequency of consumers (9 ± 9%). It corresponded to drugs reported with a high risk of classification bias, and was composed of anticancer therapies and cardiovascular drugs. CONCLUSION: Protopathic and classification biases impact EN-reporting and should be considered regarding associations with antibiotics, NSAIDs, analgesics, anticancer therapies, and cardiovascular drugs.
Asunto(s)
Farmacovigilancia , Síndrome de Stevens-Johnson , Sistemas de Registro de Reacción Adversa a Medicamentos , Anticonvulsivantes , Sesgo , Humanos , Síndrome de Stevens-Johnson/epidemiología , Síndrome de Stevens-Johnson/etiología , Organización Mundial de la SaludRESUMEN
ABSTRACT: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare but well-defined entity, often associated with autoimmune manifestations, generally with a good prognosis unless associated with hemophagocytic syndrome. Typically, the lymphoma cells rim the adipocytes and are characterized by a CD8 + cytotoxic phenotype. We report 2 cases of SPTCL where the first biopsies only showed subcutaneous fat necrosis without any lymphoma cell visible. The diagnoses were allowed by immunophenotypic markers which characterized necrotic neoplastic T cells and confirmed on further biopsies with a typical pattern of SPTCL. These observations should prompt dermatologists to perform as large biopsies as possible, and pathologists to perform immunophenotyping in all suspected cases even if only lobular necrosis is seen morphologically.
Asunto(s)
Linfoma de Células T , Paniculitis , Humanos , Inmunofenotipificación , Linfoma de Células T/patología , Necrosis , Paniculitis/patologíaRESUMEN
BACKGROUND: Patch tests (PTs) with two readings have been used for decades to identify the culprit drug in nonimmediate cutaneous adverse drug reactions (NICADRs), followed more recently by late reading of intradermal tests (IDTs). Some teams tend to perform PTs with only one reading before IDTs or even directly perform IDTs. OBJECTIVES: To evaluate the relevance of a late PT reading on day 4 (D4) in NICADRs. METHODS: We retrospectively selected patients who had a PT for an NICADR between July 2014 and March 2020. RESULTS: During the study period, 328 patients had a PT with available results. Among the 75 positive-PT patients with available data for the two readings, 41 (54.7%) had positive results on D2 and D4 and 34 (45.3%) had negative results on D2 but positive results on D4. No patient had positive results on D2 and negative results on D4. CONCLUSION: This study shows that a D4 reading enhanced the PT-positive results. A positive PT result allows for reducing the number of IDTs, which are more difficult and costly to perform. Our series suggests that a late PT reading at D4 should be performed for exploring NICADRs.
Asunto(s)
Hipersensibilidad a las Drogas/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Hipersensibilidad Tardía/diagnóstico , Pruebas del Parche/métodos , Femenino , Humanos , Masculino , Preparaciones Farmacéuticas , Estudios RetrospectivosRESUMEN
BACKGROUND: Chronic erosive gingivitis, also called desquamative gingivitis, defines a clinical picture that can be generated by several inflammatory and immune diseases. Pathology is therefore essential for the differential diagnosis. However, when the gingival lesion is initial, exclusive or predominant, selecting the biopsy site and protocol may be problematic due to tissue fragility. Especially since there are few studies on the subject, the aim of our study was to assess the protocol, diagnostic relevance and tolerance of an original protocol using interdental papilla biopsy. METHODS: We conducted a retrospective bicentric study, from October 2011 to July 2019, including all patients with a chronic erosive gingivitis who had received, for diagnostic purposes, a interdental papilla biopsy. RESULTS: The contribution levels for the two hospital departments were 94.7% and 97.1%, respectively. No postoperative complication was recorded in the short or long term. CONCLUSION: The interdental papilla biopsy protocol is perfectly adapted to the anatomopathological examinations required to establish differential diagnosis of chronic erosive gingivitis. This surgical protocol is simple to perform, non iatrogenic with a very good tolerance and and accessible to all clinicians. It is highly efficient with an excellent contribution level. ClinicalTrials NCT04293718 (March 3, 2020). Health Data Hub N° F20201109083211 (November 9, 2020).