[Misdiagnosis of hidradenitis suppurativa continues to be a major issue. The R-ENS Verneuil study]. / Errance médicale des patients atteints d'hidradénite suppurée : un problème majeur et persistant. Étude « R-ENS Verneuil ¼.

OBJECTIVE: To provide physicians with an understanding of the factors behind significant delays in the diagnosis of hidradenitis suppurativa (HS) in France. PATIENTS AND METHODS: This prospective multicentre national study conducted from October 2015 to March 2016 included all patients consulting for HS. Patient data were collected by means of a standardized questionnaire. Univariate and multivariate analyses were conducted to collect factors associated with a significant time to diagnosis of at least 5.5years, defined as the period between the onset of initial clinical signs and the time of formal diagnosis. RESULTS: The 16 participating centres enrolled 312 patients (62% women), of average age 35years. The average age at onset of HS was 22years. Before formal diagnosis by a dermatologist (64% of cases), 170 (54%), 114 (37%) and 45 (15%) patients had previously consulted at least 3, 5 and 10 general physicians, respectively. The average time between the initial clinical signs of HS, the first dermatology visit and the definitive diagnosis was 6.2 and 8.4 years, respectively. Active smoking (OR adjusted 1.85; P=0.027) and disease onset at a younger age (adjusted OR 0.92; P<0.001) were both associated with significant delays in diagnosis. CONCLUSION: These results emphasized misdiagnosis among HS patients but did not evidence any association between either sociodemographic or economic characteristics and the existence of significant times to diagnosis.

Active tuberculosis in psoriasis patients treated with TNF antagonists: a French nationwide retrospective study.

BACKGROUND: There is limited information about active tuberculosis (TB) occurring in psoriasis patients treated with Tumor necrosis factor (TNF) antagonists. OBJECTIVE: To describe the clinical characteristics of TB in psoriasis patients treated with TNF antagonists. METHODS: Nationwide retrospective study of psoriasis patients having experienced TB. Cases of TB were collected via three methods: search in the national pharmacosurveillance database, questionnaire to members of the French psoriasis research group, the college of French dermatology professors. We collected demographic data, TNF antagonist used, screening for latent tuberculosis infection, median time between TNF antagonists introduction and first symptoms, tests used for diagnosing TB infection, clinical features of tuberculosis and outcome. RESULTS: Eight centres reported 12 cases of TB between 2006 and 2014. They were nine men and three women with mean age of 49 years. All patients had adequate screening for latent tuberculosis. Three patients had stayed in endemic areas, three reported contact with a patient with TB. Tuberculosis presentation was extrapulmonary in 10 patients. Seven patients were treated with infliximab, four with adalimumab and one with certolizumab. The median time between TNF antagonist introduction and first symptoms of tuberculosis was 23.4 weeks (2-176). Six of the 12 patients had a positive direct examination and/or positive culture for Mycobacterium tuberculosis. Histological samples of affected organs taken from seven patients showed granulomatous inflammation in six, with caseating necrosis in five. Two of the 12 patients died of disseminated TB. CONCLUSION: This study shows tuberculosis in patients treated with TNF antagonists still occurs despite adherence to tuberculosis prevention guidelines. Prophylactic measures do not fully prevent the occurrence of tuberculosis. Rapid initiation of effective anti-tuberculosis treatment is important even in patients with negative mycobacteriological examination presenting with suggestive symptoms and organ involvement.

Metabolic comorbidities and hypertension in psoriasis patients in France. Comparisons with French national databases.

INTRODUCTION: Several studies have shown a high prevalence of cardiovascular and metabolic comorbidities in psoriasis. Our study aimed to evaluate the association of psoriasis with key comorbidities such as smoking, obesity, hypertension, dyslipidaemia and diabetes comparatively with French national data. MATERIAL AND METHODS: This multicentre noninterventional observational study of adults with psoriasis was conducted in 29 dermatology centres in France. A total of 2210 patients were included. The prevalence of comorbidities in psoriatic patients was compared to data from the French national databanks "ObEpi 2012" (obesity, hypertension, dyslipidaemia and diabetes) and "Baromètre Santé 2010" (smoking). RESULTS: We reported a higher prevalence of all metabolic comorbidities and high blood pressure in psoriatic patients. Smoking: 32.5% were active smokers; the age of onset and the prevalence of familial psoriasis were significantly lower in the smoking group but the severity of psoriasis was significantly higher. The frequency of smoking was higher than in the general population, particularly among young female patients. Obesity: 24% of patients with psoriasis were obese. Multivariate analysis showed obesity to be significantly associated with other comorbidities, severity of psoriasis and psoriatic arthritis. The incidence of obesity was higher than in general population, occurring chiefly in subjects aged over 45 years. HYPERTENSION: 26% of patients with psoriasis had hypertension. The age of onset of psoriasis and the prevalence of psoriatic arthritis were significantly higher in the hypertension group, although there was less familial psoriasis. The incidence of hypertension was higher than in general population. Dyslipidaemia: 27.5% of patients with psoriasis had dyslipidaemia. The age of onset in the dyslipidaemia group was higher although there was less familial psoriasis. The incidence of dyslipidaemia was higher than in general population. Diabetes: 11.0% of patients with psoriasis had diabetes. The age of onset of psoriasis was significantly higher in the diabetes group although there was less familial psoriasis. The incidence of diabetes was higher than in general population particularly after the age of 35 years. CONCLUSION: These results confirmed that psoriasis is associated with significant metabolic comorbidities and hypertension compared to the general population in France, with certain epidemiological differences for each.

Psoriasis in the elderly: epidemiological and clinical aspects, and evaluation of patients with very late onset psoriasis.

BACKGROUND: Age of the patients and age of onset of psoriasis may have an impact on the disease. There is little information about psoriasis in elderly patients. OBJECTIVE: We evaluated epidemiological, clinical aspects, comorbidities and treatments of psoriasis in the elderly (>70 years) patients, and in patients with very late onset psoriasis (onset ≥ 70 years). METHODS: This observational multicentre non-interventional study of adults with psoriasis was conducted in 29 departments of dermatology in France. A total of 2210 adults with psoriasis were included. RESULTS: A total of 212 (9.5%) patients were elderly. This group had a higher frequency of females (P = 0.005), a later onset of the disease (P < 0.0001), a lower frequency of familial (P < 0.0001) and plaque psoriasis (P < 0.0001), but higher frequency of guttate and inverse psoriasis (P ≤ 0.005). Hypertension, diabetes, dyslipidaemia, and major cardiovascular events (MACE) were more frequent in this group (P < 0.0001), but not tobacco (P < 0.0001). Systemic and biological therapies were used less frequently in the elderly group (P < 0.0001). Fifty-eight (2.7%) patients had late onset psoriasis. Patients with very late onset psoriasis were more frequently women (P = 0.02) and older (P < 0.0001), among elderly group. They had significantly less frequently familial (P < 0.0001) and plaque psoriasis (P < 0.0001), and were less often on systemic treatment including biological. Frequencies of comorbidities were not statically different but patients with 'early' onset psoriasis have a tendency (P < 0.5) to have higher frequencies of obesity, diabetes, dyslipidaemia, hypertension and MACE. CONCLUSION: This study highlights phenotypic features of psoriasis in elderly and in very late onset psoriasis. The management of these fragile patients remains poorly codified and needs further investigation.

Evaluation of risk factors for body weight increment in psoriatic patients on infliximab: a multicentre, cross-sectional study.

BACKGROUND: A significant weight gain has been reported in patients with psoriasis treated with anti-tumour necrosis factor-alpha agents. Among these patients, there are contradictory results about risk factors for weight gain. OBJECTIVE: Assessing risk factors for weight increment in psoriatic patients on infliximab (IFX). METHODS: This study was a 4-month, non-interventional, cross-sectional, multicentre study on adults with psoriasis performed in 19 French dermatological centres. All the patients who received IFX for at least 1 year were prospectively included, with retrospective analysis of data. Impact of sex, age, severity of the disease, cardiovascular and metabolic comorbidities, and previous and simultaneous systemic treatments on weight changes, was analysed. Weight gain was defined as an increment of more than 2% of baseline weight. RESULTS: Overall, 191 psoriatic patients (males: 68.6%; mean age: 46.9 years) were included. Mean weight gain was 1.6 kg (2.1%) after 1 year of IFX. Half (48.2%) suffered from a weight gain, and 9.9% from a weight increment of 10% or more. Baseline weight and Body Mass Index, and cardiovascular and metabolic comorbidities did not influence weight. Men (P=0.007) and patients with severe psoriasis (BSA, P=0.005) had a tendency to put on weight. Patients with a hospital dietary follow-up (P=0.01; OR=0.36 [0.16-0.79]) and patients on methotrexate (P=0.03; OR=0.41 [0.18-0.93]) during IFX treatment are thinner, in a multivariate analysis. CONCLUSION: Severe weight increment is frequent on IFX treatment, mainly in men, and patients with severe psoriasis. Dietary follow-up or simultaneous use of methotrexate could limit this weight increment.

Childhood-onset psoriasis: association with future cardiovascular and metabolic comorbidities.

BACKGROUND: Psoriasis is associated with higher prevalences of cardiovascular and metabolic comorbidities in adults but the relationship of age at onset and those prevalences is unknown. OBJECTIVE: To evaluate whether the childhood onset of psoriasis (COP) is correlated with the frequency of cardiovascular and metabolic comorbidities in adulthood. METHODS: This noninterventional, cross-sectional, multicentre study of adults with psoriasis was conducted in 29 dermatology centres in France. Data on sex, age at onset of psoriasis and its clinical characteristics, and cardiovascular risk factors, including weight, body mass index, waist circumference, dyslipidaemia, diabetes, hypertension, smoking, and personal/familial major adverse cardiovascular events (MACE) were systematically recorded. RESULTS: Two thousand two hundred and one patients with psoriasis (male: 56%; mean age: 49 years; 25% with COP) were included consecutively in the study. Univariate analysis showed that COP was associated with lower frequencies of obesity, high waist circumference, diabetes, dyslipidaemia, hypertension, familial cardiovascular disease, MACE and metabolic syndrome, but more frequent active smoking. Multivariate analysis retained age as being associated with frequency of cardiovascular and metabolic comorbidities, and sex with smoking, but not age at the onset of psoriasis. Psoriasis severity was associated with higher frequencies of obesity and psoriatic arthritis. CONCLUSION: Our results showed that COP does not seem to be an additional risk factor for higher frequencies of cardiovascular and metabolic comorbidities during adulthood.

Effectiveness of infliximab in pityriasis rubra pilaris is associated with pro-inflammatory cytokine inhibition.

BACKGROUND: Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease. Recently, the use of anti-TNF-α in treating resistant forms of PRP has been reported. OBJECTIVES: To evaluate the clinical efficacy of infliximab in the treatment of PRP along with the evolution of secretion of some serum cytokines during treatment. METHODS: Patients presenting widespread PRP were included consecutively and treated with infliximab. We compared cytokine profiles (notably CXCL-10 and TNF-α) by ELISA in sera from both patients with PRP and controls (healthy/psoriasis) at the time of diagnosis and after clinical remission (PRP). RESULTS: 4 patients were treated with infliximab and achieved complete remission without any recurrence after treatment ending. The serum level of TNF-α and CXCL-10 was increased at the time of inclusion and normalized after treatment. Analysis of the typical component of the T helper cell 1 (Th1) and Th2 cytokine network did not show modification. CONCLUSION: Infliximab is an effective treatment of PRP. The analysis of the cytokine profile is in agreement with an absence of further recurrence of PRP by an early and unique inflammatory mechanism without significant underlying autoimmunity.

Survey on the management of skin toxicity associated with EGFR inhibitors amongst French physicians.

BACKGROUND: Epidermal growth factor receptor (EGFR) inhibitors are part of the therapeutic arsenal available for advanced cancer. However, they are frequently associated with cutaneous side-effects, which can hamper compliance, lead to treatment refusal and impair quality of life. OBJECTIVE: To know the attitudes of French oncologists who deal with this skin toxicity. This work is one of the steps to build a therapeutic algorithm of side-effects induced by EGFR inhibitors taking both evidence-based medicine and standard practices into account. METHODS: Physicians completed a questionnaire as part of regional meetings, before any discussion. Questions concerned the management of 11 clinical situations in the context of EGFR inhibitor prescription. RESULTS: Sixty-seven questionnaires were analysed. The collaboration with dermatologists was especially planned for persisting or worsening lesions beyond 2 weeks, but never considered at the time of the introduction of targeted therapy. The results demonstrated the difficulties encountered in diagnosing and grading skin lesions. Attitudes of oncologists were uniform for preventive care and management of mild lesions for which moisturizing and cyclines were widely prescribed. Significant differences appeared in the treatment of less typical cases such as the involvement of skin appendages, secondary infections of folliculitis or cases associated with radiodermatitis. Discrepancies existed also for what to do in relation with maintenance or interruption of EGFR inhibitor mainly if they were responsible for severe lesions. CONCLUSION: This original survey emphasizes the interest of greater multidisciplinary collaboration and the necessity to harmonize practice.

Management of cutaneous adverse events induced by anti-EGFR (epidermal growth factor receptor): a French interdisciplinary therapeutic algorithm.

PURPOSE: Cutaneous adverse events induced by epidermal growth factor receptor (EGFR) inhibitors can hamper the patients' quality of life. The aim of our work was to draft an algorithm for the optimised management of this skin toxicity. METHODS: This algorithm was built in three steps under the responsibility of a steering committee. Step I: a systematic literature analysis (SLA) has been performed. Step II: the collection of information about practices was performed through a questionnaire.These questions were asked during regional meetings to which oncologists, gastro-enterologists, radiotherapists, and dermatologists were invited. Step III: a final meeting was organised involving the bibliography group and the steering committee and regional scientific committees for proposing a final algorithm. RESULTS: Step I: 14 publications were selected to evaluate the use of cyclines as curative or prophylactic treatment of the folliculitis induced by EGFR inhibitors. Nineteen publications were retained for the topical treatment of the folliculitis. Forty-six articles were selected for the management of the cutaneous lesions in link with appendages and 12 for xerosis and pruritus. Step II: 96 delegates attended the seven regional meetings and 67 questionnaires were analysed. Step III: a final algorithm was proposed on the basis of the conclusions of the first two steps and expert opinions present at this final meeting. The different propositions were unanimously approved by the 14 experts who voted. CONCLUSIONS: This multidisciplinary study summarising published data and current practices produced a therapeutic algorithm, which should facilitate the standardised, optimised management of skin toxicity associated with EGFR inhibitors in France.

Semiology of skin toxicity associated with epidermal growth factor receptor (EGFR) inhibitors.

PURPOSE: Advances in the understanding of the mechanisms involved in oncogenesis have led to the development of so-called targeted therapies such as epidermal growth factor receptor (EGFR) inhibitors, which take on an increasingly important role in the management of cancer. These treatments have the advantage not to trigger the adverse effects traditionally encountered with chemotherapy, such as nausea, vomiting or haematological toxicity. However, they do cause new forms of toxicity: the most common one is skin toxicity. It is important to be aware of it because it can be debilitating, adversely impacting patients' quality of life and altering treatment compliance, although it appears to be correlated with treatment response in certain series. Non-specialists can have difficulty in recognising this unusual skin toxicity. METHODS: The dermatologic side effects most frequently triggered by EGFR inhibitors are discussed in this article. RESULTS: They are divided into three categories depending on their target: inflammation of the pilo-sebaceous follicle, represented by EGFR inhibitor-associated folliculitis, which occurs at an early stage and is frequent; alteration in the skin barrier, primarily responsible for xerosis, fissures and pruritus, which are frequent and delayed; and lesions of the skin appendages (paronychia, pyogenic granuloma, hair changes), which are delayed and less frequent. CONCLUSION: It is essential for all practitioners concerned to know about these dermatologic side effects in order to ensure better global management of patients, particularly in terms of quality of life.

[Squamous cell carcinoma in a patient receiving sorafenib]. / Survenue d'un carcinome spinocellulaire chez un patient traité par sorafenib.

BACKGROUND: Sorafenib is a multikinase inhibitor approved for the treatment of renal cell carcinoma and hepatocellular carcinoma. Associated short-term cutaneous adverse events are well known. Regarding long-term adverse events, keratoacanthoma has been reported more recently and, more rarely, invasive squamous cell carcinoma. PATIENTS AND METHODS: A 56-year-old man was treated with sorafenib in December 2008 for renal cell carcinoma with cutaneous metastases. The patient had a skin phototype IV and no history of intense sun exposure. Within five months of starting sorafenib, he developed deeply invasive well-differentiated retroauricular squamous cell carcinoma. DISCUSSION: Sorafenib modifies the immunostimulatory capacity of dendritic cells by reducing cytokine secretion and CD1a expression. Blockade of autocrine vascular endothelial growth factor (VEGF) signalling in keratinocytes can also select tumoural clones with increased oncogenic Ras mutation, increased activation of phospholipase D and modulation of the Ras/Raf/MAP kinase signalling pathway involved in cutaneous squamous cell carcinogenesis. CONCLUSION: Cases of keratoacanthomas and deeply invasive squamous cell carcinomas reported in patients on sorafenib emphasise the need for multidisciplinary follow-up of this population and the important role of dermatologists in managing the short and long-term adverse effects of multitarget tyrosine inhibitors.

[Efficacy of rituximab in a case of refractory bullous pemphigoid]. / Efficacité du rituximab dans une pemphigoïde bulleuse en échec thérapeutique.

BACKGROUND: The mainstay in the treatment of bullous pemphigoid (BP) is corticosteroids. Immunosuppressive agents might be used for steroid-sparing effect. We report the case of a patient with refractory BP successfully treated with rituximab. PATIENTS AND METHODS: An 83-year-old woman was hospitalized in January 2005 for severe BP. She was initially treated with 30 g/day of clobetasol propionate 0.05% and methotrexate (20 mg/week), with partial remission. However, every attempt to reduce topical corticosteroids resulted in a relapse of the patient's BP. Subsequently, mycophenolate mofetil, azathioprine, dapsone, intravenous immunoglobulins, topical tacrolimus and systemic glucocorticoids (steroid-dependency at 20 mg/day) failed to induce complete remission. In December 2005, we decided to treat the patient with four infusions of rituximab 375 mg/m(2) at 1-week intervals, and this led to a dramatic reduction of the severity of BP. In May 2006, a second course of rituximab was given. One month later, for the first time in 18 months, complete clinical and immunological remission of BP was noted. The patient remains in complete remission, without treatment, 2 years after the last infusion of rituximab. DISCUSSION: The B cell-modulating effect of rituximab has encouraged its use in a variety of autoimmune diseases including pemphigus. Only five cases of refractory BP, treated with rituximab (including two paediatric cases), have so far been reported. In three of these cases, follow-up was too short to allow detection of any relapse and the other two patients had lymphocytic leukaemia requiring rituximab infusions every 2 months. In our case, the two courses of rituximab were well tolerated, induced complete clinical and immunological remission and enabled discontinuation of local and systemic corticosteroids. CONCLUSION: Rituximab could offer a safe and effective therapeutic alternative for refractory BP.

[Tumoral calcinosis at an unusual site in a haemodialysis patient]. / Calcinose pseudotumorale de localisation inhabituelle chez un patient hémodialysé.

BACKGROUND: Tumour-like calcinosis is a rare cause of tissue calcification in patients on maintenance haemodialysis for chronic renal failure. Its estimated incidence is between 0.5 and 7% of haemodialysis patients. PATIENTS AND METHODS: A 29-year-old male patient was referred to our department with a large cervical mass lesion increasing in size for two months. The patient had been on maintenance haemodialysis for one year for chronic renal failure during which time he reported multiple episodes of cervical trauma. Cervical MRI demonstrated a 11 x 9 cm calcified tumoral mass extending to the cervical muscles and the lower cervical spine (C6, C7, T1), accompanied by C6 osteolysis. Laboratory studies revealed secondary hyperparathyroidism with elevated calcium-phosphorus product. The patient underwent parathyroidectomy and several weeks later, there was a dramatic regression of the tumoral calcinosis. Renal transplantation was performed secondarily with no recurrence of the tumoral calcification after six years of follow-up. DISCUSSION: Tumour-like calcinosis of the lower cervical spine with osteolysis of the cervical vertebrae is very rare. The principal contributing factors are hyperparathyroidism, elevation of calcium-phosphorus product and local trauma. Optimal treatment of these calcifications remains controversial. While surgical resection of the mass is commonly recommended, in our case report, despite the initial aggressiveness of the lesion, surgery was not performed and treatment of hyperparathyroidism alone was sufficient to ensure dramatic improvement with complete resolution of the calcinosis within few weeks.

[Bullous amyloïdis revealing a light chains lambda myeloma]. / Amylose bulleuse révélant un myélome à chaînes légères lambda.

INTRODUCTION: Although rare, skin lesions are regularly reported in patients with systemic amyloidosis. The existence of bullous skin lesions however is very rare; only thirty cases have been previously reported. We report a new case of bullous amyloidosis revealing a light chains lambda myeloma, and underline the usual characteristics of this type of systemic amyloidosis. EXEGESIS: An 85-year-old man was hospitalised for a bullous eruption associated with a general asthenia. Bullous amyloidosis revealing a light chains lambda myeloma was diagnosed and confirmed by histopathological examination of a skin biopsy specimen. The patient died of a severe congestive heart failure, 15 days later, due to cardiac involvement of the amyloidosis. CONCLUSION: Bullous amyloidosis lesions can be an early manifestation of occult dysglobulinemia. Early diagnosis would allow rapid treatment, before onset of systemic amyloidosis, which is often lethal.

Multiple spreading epidermolytic acanthomas of the genital and perigenital skin.

Epidermolytic acanthoma is an uncommon benign tumour mainly characterized histologically by a prominent epidermolytic degeneration of the keratinocytes of the upper layers of the stratum spinosum and of the stratum granulosum. The absence of desmosome involvement allows to differentiate this condition from others such as acantholytic acanthoma. We report the first case, to our knowledge, of a 54-year-old male patient exhibiting disseminated scrotal, gluteal, inguinal and perineal epidermolytic acanthomas.

[Drug induced linear IgA bullous dermatosis]. / Dermatoses bulleuses à IgA linéaire d'origine médicamenteuse.

Linear IgA disease is an autoimmune subepidermal bullous disease in which linear IgA deposits are found at the basement membrane zone. It is classically idiopathic but a drug-induced variant seems to be individualized in which cutaneous lesions resolve spontaneously after cessation of responsible treatment. Among the commonly implicated drugs, vancomycin is the most frequently reported. One should not however ignore other precipitating events sometimes associated, particularly infectious diseases and non-lymphoid or lymphoproliferative malignancies. Authors present here clinical and histological features of this disease as well as drugs that have been implicated.