Correlation of serum level of squamous cell carcinoma antigen with severity of cutaneous psoriasis, assessed using the simplified psoriasis index.

BACKGROUND: Squamous cell carcinoma antigen (SCCA) is a biomarker of disease progression in squamous cell carcinoma but also contributes to the pathogenesis of psoriasis. Eight previous studies have shown a correlation between psoriasis severity, assessed using the Psoriasis Assessment Severity Index or body surface area, and serum level of SCCA, mainly SCCA2, assessed by means of non-commercial tests. We examined the correlation between serum SCCA level, measured with a commercial kit, and psoriasis severity assessed using the Simplified Psoriasis Index (SPI). METHODS: We conducted a prospective, non-interventional, single-centre study at the University Hospital of Tours over 18 months. The primary endpoint was same-day measurement of serum SCCA level and the psoriasis severity score on the professional version of the SPI (proSPI-s) at both baseline and follow-up. Secondary endpoints were same-day measurement of serum SCCA level and the proSPI psychosocial score (proSPI-p), proSPI treatment score, Dermatology Life Quality Index (DLQI), and inflammation parameters (C-reactive protein level, neutrophil-to-lymphocyte ratio). RESULTS: We included 50 psoriasis patients. Serum SCCA level was correlated with the proSPI-s at baseline and follow-up (Spearman r = 0.686 and r = 0.674, p < 0.0001) for both. It was correlated with the proSPI-p and DLQI. Serum SCCA level was not correlated with either neutrophil-to-lymphocyte ratio (r = 0.083) or C-reactive protein level (r = 0.192). CONCLUSION: This study is the first to correlate serum SCCA level with proSPI-s. Moreover, SCCA was measured using a widely available kit. SCCA may be used to assess the severity of psoriasis.

Adcitmer® , a new CD56-targeting monomethyl auristatin E-conjugated antibody, is a potential therapeutic approach in Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive skin cancer, whose tumour cells often express CD56. While immune checkpoint inhibitors constitute a major advance for treating patients with MCC with advanced disease, new therapeutic options are still urgently required. OBJECTIVES: To produce and evaluate the therapeutic performance of a new antibody-drug conjugate (Adcitmer® ) targeting CD56 in preclinical models of MCC. METHODS: CD56 expression was evaluated in a MCC cohort (immunohistochemistry on a tissue microarray of 90 tumour samples) and MCC cell lines. Interaction of an unconjugated CD56-targeting antibody with CD56+ MCC cell lines was investigated by immunohistochemistry and imaging flow cytometry. Adcitmer® product was generated by the bioconjugation of CD56-targeting antibody to a cytotoxic drug (monomethyl auristatin E) using the McSAF Inside® bioconjugation process. The chemical properties and homogeneity of Adcitmer® were characterized by hydrophobic interaction chromatography. Adcitmer® cytotoxicity was evaluated in vitro and in an MCC xenograft mice model. RESULTS: Similar to previous reports, CD56 was expressed by 66% of MCC tumours in our cohort, confirming its relevance as a therapeutic target. Specific binding and internalization of the unconjugated CD56-targeting antibody was validated in MCC cell lines. The high homogeneity of the newly generated Adcitmer® was confirmed by hydrophobic interaction chromatography. The CD56-mediated cytotoxicity of Adcitmer® was demonstrated in vitro in MCC cell lines. Moreover, Adcitmer® significantly reduced tumour growth in a MCC mouse model. CONCLUSIONS: Our study suggests that Adcitmer® should be further assessed as a therapeutic option in patients with MCC, as an alternative therapy or combined with immune checkpoint inhibitors.

Etiological diagnosis of macroglossia: Systematic review and diagnostic algorithm.

BACKGROUND: The objective of this literature review was to list the different etiologies of macroglossia reported in the literature, to identify characteristics that might guide diagnosis, and to create a diagnostic algorithm. METHODS: The bibliographic search was carried out between October 2019 and July 2020 in the PubMed research base using the keywords "macroglossia" (MESH) and/or "tongue enlargement". RESULTS: Of the 1711 references identified, 615 articles were excluded, and 1096 abstracts were reviewed. We classified the different etiologies identified according to their mechanism and whether they were congenital or acquired. The etiologies are divided into the following categories: genetic malformation syndromes, non-syndromic congenital malformations, endocrinopathies, neuromuscular diseases, storage disorders, infectious, inflammatory, traumatic, and iatrogenic diseases. CONCLUSION: Based on this review, we propose a diagnostic algorithm for macroglossia according to the characteristics described. The most common diagnoses among acquired causes were amyloidosis (13.7%), endocrinopathies (8.8%), myopathies (4%) and tongue tumors (6.7%). The most common congenital causes were aneuploidy, lymphatic malformations, and Beckwith-Wiedemann syndrome, which is the main cause of congenital macroglossia, even if it appears isolated.

French guidelines for the management of oral lichen planus (excluding pharmacological therapy).

INTRODUCTION: Oral lichen is a chronic inflammatory disease for which diagnostic management and follow-up are heterogeneous given the absence of specific guidelines in France. Our objective was to develop French multidisciplinary guidelines for the management of oral lichen. MATERIALS AND METHODS: Working groups from the Groupe d'Etude de la Muqueuse Buccale (GEMUB) formulated a list of research questions and the corresponding recommendations according to the "formal consensus" method for developing practice guidelines. These recommendations were submitted to a group of experts and the degree of agreement for each recommendation was assessed by a scoring group. RESULTS: Twenty-two research questions, divided into 3 themes (nosological classification and initial assessment, induced oral lichenoid lesions, and follow-up) resulted in 22 recommendations. Initial biopsy for histology is recommended in the absence of reticulated lesions. Biopsy for direct immunofluorescence is recommended for ulcerated, erosive, bullous types and for diffuse erythematous gingivitis. Management should include a periodontal and dental check-up, and investigation for extra-oral lesions. Hepatitis C testing is recommended only if risk factors are present. Definitions, triggering factors and the management of "induced oral lichenoid lesions" were clarified. Oral lichen must be monitored by a practitioner familiar with the disease at least once a year, using objective tools. CONCLUSION: This formalised consensus of multidisciplinary experts provides clinical practice guidelines on the management and monitoring of oral lichen.

Most chilblains observed during the COVID-19 outbreak occur in patients who are negative for COVID-19 on polymerase chain reaction and serology testing.

BACKGROUND: Acral lesions, mainly chilblains, are the most frequently reported cutaneous lesions associated with COVID-19. In more than 80% of patients tested, nasopharyngeal swabs were negative on reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 when performed, and serology was generally not performed. METHODS: A national survey was launched on 30 March 2020 by the French Society of Dermatology asking physicians to report cases of skin manifestations in patients with suspected or confirmed COVID-19 by using a standardized questionnaire. We report the results for acral manifestations. RESULTS: We collected 311 cases of acral manifestations [58.5% women, median age 25.7 years (range 18-39)]. The most frequent clinical presentation (65%) was typical chilblains. In total, 93 cases (30%) showed clinical suspicion of COVID-19, 67 (22%) had only less specific infectious symptoms and 151 (49%) had no clinical signs preceding or during the course of acral lesions. Histology of skin biopsies was consistent with chilblains. Overall, 12 patients showed significant immunological abnormalities. Of the 150 (48%) patients who were tested, 10 patients were positive. Seven of 121 (6%) RT-PCR-tested patients were positive for SARS-CoV-2, and five of 75 (7%) serology-tested patients had IgG anti-SARS-CoV-2. Tested/untested patients or those with/without confirmed COVID-19 did not differ in age, sex, history or acral lesion clinical characteristics. CONCLUSIONS: The results of this survey do not rule out that SARS-CoV-2 could be directly responsible for some cases of chilblains, but we found no evidence of SARS-CoV-2 infection in the large majority of patients with acral lesions during the COVID-19 lockdown period in France. What is already known about this topic? About 1000 cases of acral lesions, mainly chilblains, were reported during the COVID-19 outbreak. Chilblains were reported to occur in young people within 2 weeks of infectious signs, which were mild when present. Most cases did not have COVID-19 confirmed by reverse transcription polymerase chain reaction (RT-PCR), and few serology results were available. What does this study add? Among 311 patients with acral lesions, mainly chilblains, during the COVID-19 lockdown period in France, the majority of patients tested had no evidence of SARS-CoV-2 infection. Overall, 70 of 75 patients were seronegative for SARS-Cov-2 serology and 114 of 121 patients were negative for SARS-CoV-2 RT-PCR.

Topical rapamycin versus betamethasone dipropionate ointment for treating oral erosive lichen planus: a randomized, double-blind, controlled study.

BACKGROUND: Although superpotent topical corticosteroids are the first-line treatment for oral erosive lichen planus (OELP), topical rapamycin was found efficient in a previous case series. OBJECTIVES: To compare the efficacy and safety of topical rapamycin and betamethasone dipropionate ointment for OELP in a randomized, double-blind trial. METHODS: Patients were randomized to receive treatment with betamethasone dipropionate ointment 0.05% in Orabase® or topical rapamycin solution (1 mg/mL) on lesions twice daily for 3 months, followed by 3 months of observation. The primary outcome was clinical remission after 3 months of treatment. Secondary outcomes were clinical remission after 1 and 2 months, reduced oral pain and reduced impact on food intake after 3 months, clinical recurrence after treatment withdrawal, and adverse events. RESULTS: During a 4-year period, 76 patients were randomized and 75 received treatment (rapamycin, n = 39; betamethasone, n = 36). At 3 months, 39.4% of patients with betamethasone and 27.3% with rapamycin showed clinical remission (odds ratio 0.68, 95% CI [0.24; 1.89]; P = 0.46). Rates of remission after 1 and 2 months, reduction in pain and impact on food intake after 3 months, were higher with betamethasone than rapamycin. Recurrence of oral erosions was similar between groups. Adverse events occurred in 43.6% of patients with rapamycin (mostly burning sensation, impaired taste) and 27.8% with betamethasone (mostly oral candidiasis). CONCLUSION: Although the study was limited by insufficient recruitment, we did not find any superiority of topical rapamycin over betamethasone dipropionate ointment for OELP. Given the rapid remission and pain improvement in the betamethasone group, it appears that superpotent topical corticosteroids should remain the first-line treatment for OELP.

The evolving field of Dermato-oncology and the role of dermatologists: Position Paper of the EADO, EADV and Task Forces, EDF, IDS, EBDV-UEMS and EORTC Cutaneous Lymphoma Task Force.

BACKGROUND: The incidence of skin cancers has been increasing steadily over the last decades. Although there have been significant breakthroughs in the management of skin cancers with the introduction of novel diagnostic tools and innovative therapies, skin cancer mortality, morbidity and costs heavily burden the society. OBJECTIVE: Members of the European Association of Dermato-Oncology, European Academy of Dermatology and Venereology, International Dermoscopy Society, European Dermatology Forum, European Board of Dermatovenereology of the European Union of Medical Specialists and EORTC Cutaneous Lymphoma Task Force have joined this effort to emphasize the fundamental role that the specialist in Dermatology-Venereology has in the diagnosis and management of different types of skin cancer. We review the role of dermatologists in the prevention, diagnosis, treatment and follow-up of patients with melanoma, non-melanoma skin cancers and cutaneous lymphomas, and discuss approaches to optimize their involvement in effectively addressing the current needs and priorities of dermato-oncology. DISCUSSION: Dermatologists play a crucial role in virtually all aspects of skin cancer management including the implementation of primary and secondary prevention, the formation of standardized pathways of care for patients, the establishment of specialized skin cancer treatment centres, the coordination of an efficient multidisciplinary team and the setting up of specific follow-up plans for patients. CONCLUSION: Skin cancers represent an important health issue for modern societies. The role of dermatologists is central to improving patient care and outcomes. In view of the emerging diagnostic methods and treatments for early and advanced skin cancer, and considering the increasingly diverse skills, knowledge and expertise needed for managing this heterogeneous group of diseases, dermato-oncology should be considered as a specific subspecialty of Dermatology-Venereology.

Quality of life measurement in skin cancer patients: literature review and position paper of the European Academy of Dermatology and Venereology Task Forces on Quality of Life and Patient Oriented Outcomes, Melanoma and Non-Melanoma Skin Cancer.

The European Academy of Dermatology and Venereology (EADV) Task Forces (TFs) on Quality of Life (QoL) and Patient Oriented Outcomes, Melanoma and Non-Melanoma Skin Cancer (NMSC) present a review of the literature and position statement on health-related (HR) QoL assessment in skin cancer patients. A literature search was carried out to identify publications since 1980 that included information about the impact of SC on QoL. Generic, dermatology-specific, cancer-specific, SC-specific, facial SC-specific, NMSC-specific, basal cell carcinoma-specific and melanoma-specific QoL questionnaires have been used to assess HRQoL in SC patients. HRQoL was assessed in the context of creation and validation of the HRQoL instruments, clinical trials, comparison of QoL in SC and other cancers, other diseases or controls, HRQoL assessment after treatment, comorbidities, behaviour modification, predictors of QoL and survival, supportive care needs, coping strategies and fear of cancer recurrence. The most widely used instruments for HRQoL assessment in SC patients are the European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30), the Functional Assessment of Cancer Therapy-Melanoma (FACT-M), Skin Cancer Index (SCI), Short Form 36 Item Health Survey (SF-36) and the Dermatology Life Quality Index (DLQI). The TFs recommend the use of the cancer-specific EORTC QLQ-C30, especially in late stages of disease, and the melanoma-specific FACT-M and SC-specific SCI questionnaires. These instruments have been well validated and used in several studies. Other HRQoL instruments, also with good basic validation, are not currently recommended because the experience of their use is too limited. Dermatology-specific HRQoL instruments can be used to assess the impact of skin-related problems in SC. The TFs encourage further studies to validate HRQoL instruments for use in different stages of SC, in order to allow more detailed practical recommendations on HRQoL assessment in SC.

Clinical and haemodynamic risk factors associated with discrepancies in lower limb length with capillary malformations: data from the national paediatric French cohort CONAPE.

BACKGROUND: Genetics discoveries have allowed for a better understanding of capillary malformations (CMs) associated with overgrowth syndrome. However, molecular analyses are still not easy to perform or interpret. Other analytical methods are needed. OBJECTIVES: To identify clinical and haemodynamic factors associated with leg length discrepancy (LLD) in children with CMs of the lower limbs. METHODS: Data were obtained from the multicentre French national cohort CONAPE (COhorte Nationale d'enfants atteints d'Angiome Plan de membrE inférieur), from children aged 2-12 years old with CMs of the lower limbs. Clinical characteristics were prospectively collected. Haemodynamic factors were measured by an sonographer who calculated the arterial blood flow (ABF) in both lower limbs. An ABF difference ≥ 50% between the two lower limbs was considered relevant. LLD ≥ 2% was determined by the same radiologist on centralized radiographs. RESULTS: We analysed data at baseline for 96 children. The mean ± SD age was 5·6 ± 3·1 years; 49 (51%) were male; and 14 (15%) showed LLD. In total, 32 patients (33%) had venous anomalies, 13 (14%) lymphatic anomalies and in one child a diagnosis of Parkes Weber syndrome was made. Only an increased circumference above the knee was more frequent with than without LLD (43% vs. 13%, P = 0·02). In all, 10/79 patients (13%) showed a difference in ABF ≥ 50%: four had LLD. The frequency of differences in ABF ≥ 50% was greater with than without LLD [33% (n = 4/12) vs. 9% (n = 6/67), P = 0·04]. CONCLUSIONS: ABF measured by Duplex ultrasonography is a simple, low-cost and noninvasive complementary examination for help in detecting LLD, with a difference of ≥ 50% possibly associated.

Salivary scintigraphy for Sjögren's syndrome in patients with xerostomia: A retrospective study.

OBJECTIVES: The value of salivary gland scintigraphy in the diagnosis of Sjögren's syndrome remains controversial. The primary aim of this study was to estimate the diagnostic accuracy of salivary gland scintigraphy in the diagnosis of Sjögren's syndrome among 237 patients with xerostomia. METHODS: We retrospectively compared eight scintigraphy parameters between 106 Sjögren patients and 131 non-Sjögren patients. RESULTS: Seven of the eight parameters were significantly decreased in patients with Sjögren; however, their diagnostic accuracy was low, with areas under the curves (AUCs) ranging from 0.58 (95% CI 0.50-0.65) to 0.63 (95% CI: 0.55-0.70). The prestimulatory oral activity index allowed discrimination between primary and secondary Sjögren's syndrome (AUC 0.73, 95% CI: 0.62-0.84), and the secretion velocity for parotid glands allowed discrimination between patients with Sjögren and burning mouth syndrome (AUC 0.71, 95% CI 0.59-0.82). CONCLUSION: The accuracy of scintigraphy parameters for the diagnosis of Sjögren's syndrome among patients with xerostomia was low; however, some functional indices appeared to assist discrimination between primary and secondary SS patients and between subgroups of patients with different causes of xerostomia.

[Aphthous mouth ulcers as an initial manifestation of sécukinumab-induced inflammatory bowel disease]. / Ulcérations buccales aphtoïdes inaugurales d'une maladie inflammatoire chronique de l'intestin induite par le sécukinumab.

BACKGROUND: Secukinumab, a humanized monoclonal antibody targeting interleukin 17A, has been associated with the development of inflammatory bowel diseases. We report a case of a female patient developing recurrent oral ulcers prior to inflammatory bowel disease induced by secukinumab. The patient had developed similar oral ulcers 6 years earlier while on tocilizumab (targeting IL6R), suggesting an immunological link between the two episodes. PATIENTS AND METHODS: A 36-year-old female patient had refractory spondylarthrosis. In 2010, she had presented oral aphthous ulcers during treatment with tocilizumab. In 2011, tocilizumab was stopped and the ulcers resolved. In 2016, secukinumab was introduced and led to recurrence of oral aphthous ulcers followed by ileitis-pancolitis. Corticosteroids and ustekinumab resulted in partial remission. DISCUSSION: The patient developed inflammatory bowel disease during treatment with secukinumab, preceded by recurrent oral aphthous ulcers. She had presented similar oral ulcers 6 years earlier while on a treatment targeting IL6R. IL6 is a pleiotropic cytokine that may activate the Th17 pathway. Thus, tocilizumab could have induced an "anti-IL17-like" effect, accounting for the occurrence of oral aphthous ulcers, possibly related to mild inflammatory bowel disease. CONCLUSION: The occurrence of oral ulcers during treatment with secukinumab may herald inflammatory bowel disease. In patients with a previous history of recurrent aphthous stomatitis, especially where induced by previous biologics, consideration must be given to the risk-benefit ratio of prescribing an anti-IL17 antibody.

[Reversible posterior leukoencephalopathy syndrome in a patient presenting granulomatosis with polyangiitis]. / Syndrome d'encéphalopathie postérieure réversible au cours d'une granulomatose avec polyangéite.

BACKGROUND: Reversible posterior leukoencephalopathy syndrome (RPLS) is characterised by clinical neurological features of sudden onset and brain MRI findings such as T2/Flair white matter hyperintensities. RPLS can occur in autoimmune diseases, and rarely in systemic vasculitis. We report a case of RPLS in a woman presenting granulomatosis with polyangiitis (Wegener's granulomatosis). PATIENTS AND METHODS: A 22-year-old female patient was treated with methylprednisolone pulses for granulomatosis with polyangiitis and neurological impairment. A few hours after the second pulse, the patient had seizures, blindness and confusion associated with high blood pressure and acute renal failure. MRI revealed a high-intensity area on T2-Flair weighted images of the occipital-temporal lobes. The patient was treated with antiepileptic and antihypertensive medications, oral steroids and cyclophosphamide; the clinical and radiological findings proved reversible over the ensuing days. DISCUSSION: The occurrence of RPLS in systemic vasculitis is rare. Six cases of RPLS associated with granulomatosis and polyangiitis have been reported. It appears important to screen for high blood pressure in patients recently treated with corticosteroids for vasculitis as this condition may represent a precipitating factor for RPLS.

Prognostic value of antibodies to Merkel cell polyomavirus T antigens and VP1 protein in patients with Merkel cell carcinoma.

BACKGROUND: Merkel cell polyomavirus (MCPyV) is the main aetiological agent of Merkel cell carcinoma (MCC). Serum antibodies against the major MCPyV capsid protein (VP1) are detected in the general population, whereas antibodies against MCPyV oncoproteins (T antigens) have been reported specifically in patients with MCC. OBJECTIVES: The primary aim was to assess whether detection of serum antibodies against MCPyV proteins at baseline was associated with disease outcome in patients with MCC. The secondary aim was to establish whether evolution of these antibodies during follow-up was associated with the course of the disease. METHODS: Serum T-antigen and VP1 antibodies were assessed by enzyme-linked immunosorbent assay using recombinant proteins in a cohort of 143 patients with MCC, including 84 patients with serum samples available at baseline. RESULTS: Low titres of VP1 antibodies at baseline (< 10 000) were significantly and independently associated with increased risk of recurrence [hazard ratio (HR) 2·71, 95% confidence interval (CI) 1·13-6·53, P = 0·026] and death (HR 3·74, 95% CI 1·53-9·18, P = 0·004), whereas T-antigen antibodies were not found to be associated with outcome. VP1 antibodies did not differ between patients in remission and those with recurrence or progression during follow-up. However, T-antigen antibodies were more frequently detected in patients with recurrence or progression at 12 months (P = 0·020) and 24 months (P = 0·016) after diagnosis. CONCLUSIONS: VP1 antibodies constitute a prognostic marker at baseline, whereas T-antigen antibodies constitute a marker of disease recurrence or progression if detected > 12 months after diagnosis.