Evolution of bone metastases in patients receiving at least three months of checkpoint inhibitors.

BACKGROUND: To investigate the evolution of bone metastases in patients receiving immune checkpoint inhibitors (ICI). METHODS: A single-center retrospective study included cancer patients with bone metastases treated with ICI at our institution between January 2014 and September 2019. Clinical and biological data were collected from medical records and independent expert review of imaging was performed. Target and non-target lesions were identified and followed up to 1 year. Patients were then classified as bone responder or non-responder. Comparisons between groups were performed with Student's t test or Mann-Whitney test. RESULTS: Among 1108 patients screened, 192 patients had bone metastases and 48 patients were included in the final analysis, with lung cancer, renal carcinoma and melanoma as most represented cancer type. Half of the patients experienced stability, condensation or peripheral sclerosis of bone lesions. Initial progression before stabilization with or without sclerosis of bone lesion occurred for 19% of patients (pseudoprogression). There was an association between bone response and global oncological outcomes. Bone responder patients had a significant decrease in morphine and co-analgesic prescription as well as a significant decrease in alkaline phosphatases compared to non-responder patients. CONCLUSION: Bone response was observed in half of patients with available imaging and follow-up after 3 months of ICI treatment, with sclerosis observed in one-third of bone lesions at month 3, in all tumor types. Up to 20% of patients experienced a pseudoprogression of bone lesions such as previously described in primary tumor and other metastatic sites. Bone response was associated with improvement of pain and survival.

Segmental facial infantile haemangiomas in the era of propranolol: evaluation at 6 years of age.

BACKGROUND: The long-term evolution of children with segmental facial infantile haemangioma (SFIH) treated with propranolol remains unstudied. OBJECTIVES: The objective of this study was to evaluate the neurodevelopmental features of children with SFIH treated with propranolol at 6 years of age. METHODS: This retrospective case series study was conducted from January 2008 to June 2020 using data from medical files, patient examinations and appointments spanning 6 years. To be included, patients should present SFIH and have previously received propranolol. A complete physical examination, magnetic resonance imaging (MRI) of the head, echocardiography and ophthalmologic examination should have been performed. Neurodevelopmental features were divided into cognition, audition, vision, orality, motor skills and the occurrence of new symptoms. RESULTS: Thirty children with SFIH were included. Of these, 11 presented criteria of PHACES. Evaluation of neurodevelopmental features of the children at 6 years of age showed learning difficulties in one case but grade skipping in three cases. There were six cases of unilateral hearing loss that had not been diagnosed at birth, two of oral difficulties and one of minor hypotonia. Early headache was primarily reported as the main new outcome. All children were treated with propranolol, with three following oral steroid therapy. No severe adverse effects were reported. The median length of treatment with propranolol was 16 months, and the median age at treatment cessation was 21 months. Analysis based on segment implication showed the median length of treatment to vary from 12 months (if S3 was spared) to 25 months (if at least S3 was involved). Vascular laser therapy was used in 16 patients (53.3%) and surgery in four. CONCLUSION: In this case series, children with SFIH, including patients with PHACES criteria, presented a good tolerance of propranolol, as well as encouraged neurodevelopmental data. Segmental implication appears to have a significant impact on treatment duration and associated complications.

[Impact on quality of life and autonomy of patients aged over 75 years treated with anti-PD-1 for metastatic melanoma: A single-centre prospective study]. / Impact sur la qualité de vie et l'autonomie des patients de plus de 75 ans traités par anti-PD-1 pour un mélanome métastatique : étude prospective monocentrique.

INTRODUCTION: We previously studied anti-PD-1 safety in elderly (≥80 years) patients and reported a retrospective two-centre cohort with a similar safety profile in elderly and in younger patients. Quality-of-life evaluation data is still lacking in this specific population. MATERIALS AND METHODS: A prospective, single-centre study in patients aged over 75 years presenting metastatic melanoma treated with anti-PD-1. The endpoint was monitoring of quality of life (by a specific survey) and onco-geriatric assessment at the beginning of therapy, then at 3 and 6 months (nutritional status, comorbidities, autonomy, thymic and cognitive disorders). RESULTS: Fourteen patients were included of median age 86.5 years [range: 78-94] from March to September 2018. General status was good, with a median Charlson score of 0 [extremes 0-4]. Nine patients were evaluated at 3 months and six patients at 6 months. There was no significant difference in quality-of-life scores obtained at baseline, 3 months and 6 months. DISCUSSION: This study shows that neither quality of life nor autonomy appears to be affected by anti-PD-1 treatment in patients aged over 75 years. However, these results should be interpreted with caution due to the small number of patients included, the short follow-up period and the single-centre data. Nevertheless, the prospective analysis and the complete onco-geriatric evaluation and monitoring yielded unique and original data.

Stay in NICU and infantile haemangioma development.

BACKGROUND: Infantile haemangiomas (IHs) are more frequent in low birth weight babies, especially premature. OBJECTIVE: To compare the characteristics of infants with IHs who stayed in neonatal intensive care unit (NICU) vs. those with IHs who did not. METHODS: Prospective observational multicentric study. Consecutive infants consulting for IHs in two departments of paediatric dermatology were included and a questionnaire specifically designed was filled for each patient. To identify factors associated with hospitalization in NICU vs. no hospitalization in NICU, we conducted univariate logistic regression analyses. RESULTS: A total of 210 infants with 323 IHs were included (56 boys, 154 girls, F/M sex ratio 2.75/1); 27 stayed in NICU, whereas 183 did not. Limbs involvement and multiple IHs were more frequent in NICU infants. Similarly, infants who had stayed in NICU had an earlier onset of their IH. Multiple IH was more frequent in infants with a history of congenital onset of IH. CONCLUSION: Infants staying in NICU and those with congenital lesion are at risk for specific type and involvement of their IH and should be early addressed to a dermatologist in case of suspicion of IH to provide them an early diagnosis and to start a treatment if necessary as soon as possible.

Factors associated with the relapse of infantile haemangiomas in children treated with oral propranolol.

BACKGROUND: Although propranolol has become the first-line therapy for infantile haemangiomas (IHs), no study has yet investigated factors associated with the risk of relapse in children with IH treated with propranolol after cessation of treatment. OBJECTIVES: To compare factors associated with the risk of relapse in children with IH treated with oral propranolol. METHODS: We conducted a single-centre retrospective observational study. All files and photographs of patients with IH aged 5 months or less at the time of treatment initiation, and who were seen between 1 June 2008 and 31 December 2011 at the National Reference Center for rare skin diseases of Bordeaux, were retrospectively reviewed. RESULTS: In total 158 children were included, of whom 118 had not relapsed and 40 had relapsed. Fifty-two patients were boys and 106 were girls (male : female ratio 1 : 2), and 19 had a segmental IH (12%). When conducting multivariate analysis, only IHs with a deep component and those with segmental distribution were independently associated with relapse. CONCLUSIONS: Our study shows that segmental IHs, as well as haemangiomas with a deeper component, are more at risk of relapse and should thus indicate closer follow-up after treatment interruption, and/or longer treatment.

[Photodynamic therapy for the treatment of extramammary Paget's disease]. / Traitement de la maladie de Paget extramammaire par photothérapie dynamique topique.

BACKGROUND: The usual treatment for extramammary Paget's disease (EMPD) is surgery, but this approach may have grave functional and physical consequences, as well as high recurrence rates. Topical photodynamic therapy (PDT) offers an optional approach for EMPD; it has a high complete response rate and there is no dose restriction. The aim of this study was to evaluate the efficacy and safety of PDT in the treatment of EMPD. PATIENTS AND METHODS: This series of patients was seen at a single centre between 1 December 2005 and 31 December 2010. All patients with histologically confirmed EMPD were included. Patients received two courses of PDT 21 days apart: 3 hours after topical application of methyl aminolevulinic acid emulsion, they underwent illumination with red light (570-670 nm) at a dose of 37 J/cm(2) for 10 minutes. In the event of relapse, a further cycle was given at week 6. RESULTS: Eight patients (seven female, one male) of a mean age of 69 years were included. After two series of two illuminations, seven patients were in complete clinical remission at 3 months and one patient was in partial remission. Five patients were still in complete clinical remission at 6 months. All patients had relapsed after a mean 8.4 months (4-14 months). The limiting factor appears to be pain occurring during illumination. Patients reported satisfaction with the disappearance of symptoms and a notable improvement in quality of life. DISCUSSION: The complete clinical response rate to PDT at month 6, after two series of two illuminations, was equivalent to that for surgery. Although the recurrence rate was high, this treatment may be repeated without functional or physical consequences. PDT resulted in disappearance of pain and improved quality of life.

Halo naevi and leukotrichia are strong predictors of the passage to mixed vitiligo in a subgroup of segmental vitiligo.

BACKGROUND: Until now, segmental vitiligo has been considered as a stable entity and mixed vitiligo, the association of segmental and nonsegmental vitiligo, has been reported rarely. OBJECTIVES: The aim of this study was to search for factors associated with the generalization of vitiligo in patients with segmental vitiligo. PATIENTS AND METHODS: This was a prospective observational study conducted in the vitiligo clinic of the Department of Dermatology of Bordeaux, France. The Vitiligo European Task Force questionnaire was completed for each patient attending the clinic with a confirmed diagnosis of segmental vitiligo after exclusion of other forms of vitiligo (focal, mucosal, not classifiable.) Thyroid function and antithyroid antibodies were screened if not obtained in the previous year. RESULTS: One hundred and twenty-seven patients were recruited: 101 had segmental vitiligo and 26 had segmental vitiligo that evolved into mixed vitiligo; 56 were male and 71 were female. Most patients had onset of segmental vitiligo before the age of 18. When conducting multivariate analysis, we found the following to be independent factors associated with the evolution of patients' disease from segmental vitiligo to mixed vitiligo: initial percentage of body surface involvement of the segment >1% [odds ratio (OR) 15·14, P=0·002], the presence of halo naevi (OR 24·82, P=0·0001) and leukotrichia (OR 25·73, P=0·0009). CONCLUSIONS: Halo naevi association and leukotrichia at first consultation in segmental vitiligo are risk factors for the progression of segmental vitiligo to mixed vitiligo. In addition, this progression of segmental vitiligo to mixed vitiligo carries a stronger link if initial segmental involvement is situated on the trunk.

[Anti-p200 pemphigoid: a spectacular response to dapsone]. / Pemphigoïde anti-p200 : réponse spectaculaire à la dapsone.

BACKGROUND: Types of subepidermal autoimmune bullous dermatosis (AIBD) are classified by anatomoclinical picture and target antigen. A new entity has recently been identified: anti-p200 pemphigoid. PATIENTS AND METHODS: An 82-year-old man consulted for a profuse pruritic bullous eruption refractory to the standard treatments for bullous pemphigoid (BP). Direct immunofluorescence examination of a skin biopsy revealed linear deposits of IgG and of C3 at the dermal-epidermal junction, but Elisa screening for circulating anti-BP180 and anti-BP230 antibodies was negative. Indirect immunofluorescence (IIF) testing of cleaved skin revealed a deposit of IgG4 antibodies on the dermal side. Immunoblotting was negative for a dermal extract but showed an antibody directed against a 200-kD epidermal antigen. A diagnosis of anti-p200 pemphigoid was eventually made and the patient was successfully treated with dapsone. DISCUSSION: The diagnosis of anti-p200 pemphigoid was made in this case in spite of discrepancy between the IIF and immunoblotting results, and despite the fact that the target antigen in this disease is considered as being restricted to dermal sites. Anti-p200 pemphigoid usually begins in the second part of life and differs from standard bullous pemphigoid in terms of more frequent mucous membrane and cephalic involvement, as well as a greater degree of miliary scarring. This disease appears more prominent in males and is associated with psoriasis in around one third of cases. Autoantibodies recognize laminin gamma-1, an extra-desmosomal protein that contributes to dermal-epidermal adhesion. CONCLUSION: This recently described disease as probably under-diagnosed in France. It should be considered in atypical presentations of bullous disease. Diagnosis is confirmed by immunoblotting detection of autoantibodies directed against a 200-kD antigen normally present in the extract. Dapsone appears to be the most effective treatment.

Infantile haemangioma: part I. Pathophysiology, epidemiology, clinical features, life cycle and associated structural abnormalities.

Infantile haemangioma (IH) is the most common tumour of infancy. Its typical natural history is characterized by an early rapid growth following birth and a slow spontaneous regression phase within a period of 3 to 7 years. The exact aetiopathogeny underlying IH is still to be fully understood, but the role of fetal hypoxic stress is strongly suggested as a triggering signal in epidemiological studies. IH are composed of a complex mixture of cells including multipotent stem cells, a majority of immature endothelial cells, pericytes, dendritic cells and in the late stage, adipocytes. Most of IH are nodular and are not associated with malformations. However, in some cases, IH referred to as segmental may be associated with developmental abnormalities such as PHACES and PELVIS/SACRAL syndromes.

Infantile haemangioma: part II. Risks, complications and treatment.

Because of their spontaneous involution, most infantile haemangiomas (IH) do not require therapeutic intervention. However, in 10 to 15% of cases such as segmental and multifocal IH, locations in the periocular, airway and perineal areas, or complications of ulceration, treatment is necessary. Moreover, the risk of permanent scarring and disfigurement associated with IH, even if involution is complete, has been increasingly recognized as a rationale for treatment. Treatments for IH currently include topical, intralesional, systemic therapies, laser and surgical modalities depending on the clinical scenario. However, clinicians must carefully weigh the risks and benefits for each treatment. Recently, the efficacy of propranolol, a non-cardioselective beta-blocker, was reported and has been revolutionary in the management of IH.

Cardiovascular risk factors in patients with plaque psoriasis: a systematic review of epidemiological studies.

INTRODUCTION: Many epidemiological studies have associated psoriasis with an increased risk of coronary artery disease, resulting from a higher prevalence of cardiovascular risk factors in psoriasis patients compared with unmatched controls. However, the results of epidemiological studies vary depending upon the populations studied. The aim of this systemic review was to evaluate the risk of diabetes, hypertension, dyslipidaemia and obesity in adults with plaque psoriasis. In addition, we assessed the relationship between the risk of cardiovascular risk factors and psoriasis severity. METHODS: A systematic search was performed on Pubmed, Cochrane and Embase databases, using the key-words 'psoriasis', 'diabetes', 'hypertension', 'high blood pressure', 'dyslipidaemia', 'metabolic syndrome' and 'obesity', during the period from 1980 to June 2009. RESULTS: The initial literature search identified 353 articles. The final selection included 18 cross-sectional case-control studies. An increased risk of metabolic syndrome was observed in psoriatic patients (OR = 1.3-5.92), and a trend for a higher risk of obesity (OR = 1.18-5.49), especially in patients with severe psoriasis. For hypertension, hypertriglyceridaemia, and diabetes, the association was not significant in all studies. DISCUSSION: There was important heterogeneity in study design preventing from pooling results. Most often lifestyle factors such as smoking, alcohol consumption, physical activities were not taken into account. CONCLUSION: There is an increased risk of obesity and metabolic syndrome in psoriasis. For hypertension, diabetes and dyslipidaemia no consistency was found across studies. Prospective epidemiological studies with thorough recording of cardiovascular risk factors are required in psoriasis patients.

Assessment of risk of psoriatic arthritis in patients with plaque psoriasis: a systematic review of the literature.

OBJECTIVE: The aim of this study was to determine the prevalence of psoriatic arthritis (PsA) in the patients with plaque psoriasis and to give recommendation for the diagnosis of PsA for dermatologists. METHODS: A systematic search was performed in Pubmed, Cochrane and Embase databases. The key-words used from the Medical Searching Heading (MeSH) were: 'Psoriasis', 'Arthritis, Psoriatic', 'Uveitis' and 'Dactylitis'. We selected cross-sectional epidemiological studies written in English or French between January 1980 and October 2009. RESULTS: The initial literature search identified 2171 references. Based on abstract reading and exclusion of studies not written in English or French, and without control group, the final selection included 20 epidemiological studies. With the eight studies using rheumatologically validated criteria, the prevalence of PsA among psoriasis patient spanned a wide range from 7% to 26%. CONCLUSION: Psoriasis arthritis may affect up to 24% of psoriasis patients. Dermatologist should be aware of main clinical sign of PsA to promote earlier recognition and treatment of PsA.

Blastic plasmacytoid dendritic cell neoplasm: is transplantation the treatment of choice?

Background Blastic plasmacytoid dendritic cell neoplasm (BPDCN) represents the malignant counterpart derived from plasmacytoid dendritic cells. This rare entity is usually revealed and diagnosed on cutaneous lesions associated or not with a leukaemic component. The prognosis associated with BPDCN is very poor. Objectives To perform a retrospective review of BPDCN cases registered in the French Study Group on Cutaneous Lymphoma database from June 1995 to May 2008. Methods Forty-seven patients were included. Demographic data, initial staging, therapeutic management and outcome were recorded. Results The mean survival was 16.7 months (95% confidence interval 12.6-20.8). Only eight (17%) and one (2%) patients reached respectively 2 and 5 years of survival. Initial spreading of the disease did not represent, in this cohort, a reliable prognosis factor. The outcome was overall influenced by treatment provided. While radiation therapy, monochemotherapy or even polychemotherapy regimens did not significantly affect the course of the disease, the survival of bone marrow transplanted patients was significantly higher. Conclusions Despite the fact that BPDCN is often initially limited to the skin, only an aggressive initial therapy may improve the patients' prognosis. Local treatments, such radiation therapy, are definitively useless. Regardless of the initial extension of the disease, in our experience only bone marrow transplantation significantly improved the outcome.

[Calciphylaxis treated by cinacalcet: a medical alternative to parathyroidectomy]. / Le traitement de la calciphylaxie par cinacalcet: une alternative médicale à la parathyroïdectomie.

Calciphylaxis is a rare necrotizing calcifying arteriolopathy, with a poor prognosis, for which there is currently no effective treatment. One of the major challenges of the therapy is normalizing the calcium-phosphate balance. Therefore, cinacalcet, which inhibit the production of parathormone by negative feedback, was considered a treatment option to control the evolution of calciphylaxis in a dialysed patient suffering from cholangiocarcinoma.