Mucocutaneous manifestations of inflammatory bowel disease.

Mucocutaneous manifestations can be indicative of a variety of gastrointestinal diseases, and the dermatologist needs to know how to recognize them to refer the right patients to the gastroenterologist. Conversely, the gastroenterologist is often confronted with mucocutaneous lesions that raise the question of a possible association with a known digestive disease. Among the extra-intestinal manifestations of inflammatory bowel disease (IBD), mucocutaneous manifestations are the most common. This review will provide a breakdown by classifying them into 4 groups: 1) reactive manifestations, which include neutrophilic dermatoses, aphthous stomatitis, erythema nodosum, and vasculitis; 2) Crohn's disease-specific granulomatous skin lesions, which are histologically characterized by tuberculoid granulomas similar to those found in the gastrointestinal tract; 3) nutritional deficiency manifestations secondary to anorexia, malabsorption, loss, and drug interactions; and 3) a variety of autonomous autoimmune or inflammatory skin diseases. Dermatologists may also be involved in the management of the adverse effects of IBD treatments, especially the so-called "paradoxical" psoriatic eruptions.

Rituximab is an effective treatment in patients with pemphigus vulgaris and demonstrates a steroid-sparing effect.

BACKGROUND: Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing steroid-related adverse events (AEs) is unproven. OBJECTIVES: To utilize data collected in a French investigator-initiated, phase III, open-label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV. METHODS: This was an independently conducted post hoc analysis of the moderate-to-severe PV subset enrolled in the Ritux 3 study. Patients were randomized to rituximab plus 0·5 or 1·0 mg kg-1 per day prednisone tapered over 3 or 6 months, or 1·0 or 1·5 mg kg-1 per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for ≥ 2 months, and 24-month efficacy and safety results were also reported. RESULTS: At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff ≥ 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one rituximab-plus-prednisone patient withdrew due to pregnancy. Overall, 24 of 36 patients (67%) on prednisone alone experienced a grade 3/4 CS-related AE vs. 13 of 38 patients (34%) on rituximab plus prednisone. CONCLUSIONS: In patients with moderate-to-severe PV, rituximab plus short-term prednisone was more effective than prednisone alone. Patients treated with rituximab had less CS exposure and were less likely to experience severe or life-threatening CS-related AEs. What's already known about this topic? Pemphigus vulgaris (PV) is the most common type of pemphigus. Corticosteroids, a standard first-line treatment for PV, have significant side-effects. Although their effects are unproven, adjuvant corticosteroid-sparing agents are routinely used to minimize steroid exposure and corticosteroid-related side-effects. There is evidence that the anti-CD20 antibody rituximab is effective in the treatment of patients with severe recalcitrant pemphigus and in patients with newly diagnosed pemphigus. What does this study add? This study provides a more detailed analysis of patients with PV enrolled in an investigator-initiated trial. Rituximab plus prednisone had a steroid-sparing effect and more patients achieved complete remission off prednisone. Fewer patients experienced grade 3 or grade 4 steroid-related adverse events than those on prednisone alone. This collaboration between academia and industry, utilizing independent post hoc analyses, led to regulatory authority approvals of rituximab in moderate-to-severe PV.

Heterogeneity of virological suppression in the national antiretroviral programme of Cameroon (ANRS 12288 EVOLCAM).

OBJECTIVES: In terms of HIV infection, western and central Africa is the second most affected region world-wide, and the gap between the regional figures for the testing and treatment cascade and the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets is particularly worrying. We assessed the prevalence of virological suppression in patients routinely treated in 19 hospitals in Cameroon. METHODS: A cross-sectional survey was performed in adult patients receiving antiretroviral therapy (ART) in the Centre and Littoral regions. The prevalences of virological suppression (<1000 HIV-1 RNA copies/mL) were compared among all 19 hospitals using the χ2 test. Potential individual and health care-related determinants of virological suppression were assessed using multivariate logistic regression models. RESULTS: A total of 1700 patients (74% women; median age 41 years; median time on ART 3.7 years) were included in the study. The prevalence of virological suppression was 82.4% overall (95% confidence interval 80.5-84.2%). It ranged from 57.1 to 97.4% according to the individual hospital (P < 0.001). After adjustment, virological suppression was associated with age, CD4 cell count at ART initiation, disclosure of HIV status to family members, interruption of ART for more than two consecutive days, and location of patient's residence and hospital (rural/urban). These factors did not explain the heterogeneity of virological suppression between the study hospitals (P < 0.001). CONCLUSIONS: The overall prevalence of virological suppression was reassuring. Nevertheless, the heterogeneity of virological suppression among hospitals highlights that, in addition to programme-level data, health facility-level data are crucial in order to tailor the national AIDS programme's interventions with a view to achieving the third UNAIDS 90 target.

A single typical trichoscopic feature is predictive of tinea capitis: a prospective multicentre study.

BACKGROUND: Specific trichoscopic signs of tinea capitis (TC) were first described in 2008. The accuracy of this diagnostic tool has not been evaluated. OBJECTIVES: To assess the diagnostic accuracy of trichoscopy. METHODS: A prospective, multicentre study was done between March 2015 and March 2017 at the dermatology departments of four French university medical centres. Patients with a presumed diagnosis of TC were included. Trichoscopy was considered to be positive if at least one specific trichoscopic sign was observed. Trichoscopy results were compared with the gold standard for diagnosis of TC (mycological culture). RESULTS: One hundred patients were included. Culture was positive for 53 patients and negative for 47. The sensitivity of trichoscopy was 94% [95% confidence interval (CI) 88-100], specificity was 83% (95% CI 72-94), positive predictive value was 92% and negative predictive value was 86%. Comma hairs, corkscrew hairs, zigzag hairs, Morse-code-like hairs and whitish sheath were significantly more frequent in patients with a positive mycological culture (P < 0·001). Comma hairs were more frequent in patients with Trichophyton TC (P = 0·026), and zigzag hairs were more frequent in patients with Microsporum TC (P < 0·001). Morse-code-like hair was not observed in any patients with Trichophyton TC and therefore appears to be highly specific for Microsporum TC. CONCLUSIONS: The presence of a single trichoscopic finding is predictive of TC. Trichoscopy is a useful, rapid, painless, highly sensitive tool for the diagnosis of TC - even for dermoscopists with little experience of trichoscopy. It enhances physicians' ability to make treatment decisions. What's already known about this topic? Tinea capitis (TC) must be confirmed by a mycological culture that may take up to 6 weeks, delaying treatment. Specific trichoscopic signs of TC were first described in 2008, but the accuracy of trichoscopy for diagnosing TC has not previously been evaluated. What does this study add? The present series is the largest yet on the use of trichoscopy in the diagnosis of TC. Our results demonstrated that the presence of a single feature (comma hair, corkscrew hair, zigzag hair, Morse-code-like hair or whitish sheath) is predictive of TC. Trichoscopy is painless and highly sensitive. Morse-code-like hair appears to be highly specific for Microsporum TC.

[Nodulocystic eruption induced by sorafenib]. / Éruption nodulo-kystique induite par le sorafénib.

INTRODUCTION: Sorafenib is a multikinase inhibitor used in the treatment of hepatocellular carcinoma, advanced renal cell carcinoma, and differentiated thyroid carcinoma. Cutaneous adverse events are numerous and occur frequently. PATIENTS AND METHODS: We present two cases of nodulocystic lesions associated with comedones in patients treated with sorafenib for hepatocellular carcinoma. In the first patient, a 64-year-old man, lesions appeared on the trunk one year after beginning sorafenib. Histopathological examination revealed a non-granulomatous, perivascular and perisudoral polymorphic cellular infiltrate associated with comedones and microcysts. These lesions progressed via inflammatory episodes interrupted by long periods of spontaneous remission without any specific treatment. In the second patient, a 53-year-old woman, a rash appeared on the buttocks three months after starting sorafenib and then spread to the lumbar region and thighs. Histopathological examination was consistent with granulomatous acne lesions. The initial treatment (oral tetracycline and zinc) given for 3 months proved ineffective. Patient follow-up over 3 years showed gradual regression without the appearance of any further lesions. DISCUSSION: In the literature, several reports discuss acneiform rashes in patients treated with targeted therapy. In most cases, these lesions were papulopustular without retentional lesions. There are few reports of nodulocystic eruptions associated with comedones following sorafenib therapy. The mechanisms of emergence of these lesions seem to involve inhibition of the RAF pathway, C-KIT, and the PDGF signaling pathway.

Extensive levamisole-induced vasculitis.

Levamisole (an increasingly frequent contaminant of cocaine) can cause antineutrophil cytoplasmic antibody-associated vasculitis. Dermatologists should consider a diagnosis of cocaine/levamisole-associated cutaneous vasculopathy syndrome in cases of purpura of the ears and/or extensive retiform purpura in drug users. We report a case of particularly severe levamisole-induced necrotic purpura and immunological abnormalities in a 40-year-old woman.

Predictors of long-term drug survival for infliximab in psoriasis.

BACKGROUND: Limited information is available regarding factors associated with long-term drug survival of infliximab for psoriasis in real life. OBJECTIVES: The main aim pf this study was to identify predictors of long-term (>12 months) drug survival among patients treated with infliximab for psoriasis in a real-world clinical setting. METHODS: Retrospectively collected data, relating to disease, patient characteristics and treatment procedures, in a multicentre observational cohort of patients with moderate-to-severe plaque psoriasis treated with infliximab at eight university hospitals, 120 of whom maintained a response to infliximab for more than 12 months, were compared with prospectively collected data in the same centres from 54 patients who experienced secondary loss of response within a 12-month period. RESULTS: Mean duration of drug survival of infliximab in patients with long-term drug survival was 41.12 months ± 20.64 SD vs. 8.5 months ± 2.43 SD in patients with a secondary loss of response. Multivariate analysis identified greater disease severity at treatment onset (PASI score >12) (OR = 5.18, 95% CI: 1.60-16.77, P = 0.006), high levels of initial psoriasis clearance (PASI-90 reduction or equivalent) (OR = 18.50, 95% CI: 4.56-74.45, P = 0.0001) and combination with methotrexate (OR = 13.15, 95% CI: 1.46-118.79, P = 0.022) as independent predictors of long-term drug survival and sustained efficacy of infliximab. CONCLUSION: Positive predictors for long-term drug survival of infliximab in real life were identified. Their impact on treatment management should be addressed in further prospective trials.

Factors associated with the choice of the first biologic in psoriasis: real-life analysis from the Psobioteq cohort.

BACKGROUND: Decision-making is a complex process. The aim of our study was to assess factors associated with the choice of the first biological treatment in patients with moderate-to-severe psoriasis. METHODS: Data on all patients included in the French prospective, observational, cohort, Psobioteq and initiating a first biologic prescription between July 2012 and July 2016 were analysed. Demographic information and clinical features were collected during routine clinical assessments by the dermatology team at the recruiting centres using a standardized case report form. The primary outcome was the nature of the first biologic treatment. Four groups were identified as follows: adalimumab, etanercept, ustekinumab and infliximab groups. Factors associated with the choice of the first biological agent were determined by a multinomial logistic regression model adjusted on year of inclusion. RESULTS: The study population included the 830 biological-naïve patients who initiated a first biological agent. The mean age was 46.6 years (±SD 13.9), and 318 patients (38.3%) were female. The most commonly prescribed biologic was adalimumab: 355 (42.8%) patients, then etanercept (n = 247, 29.8%), ustekinumab (n = 194, 23.4%) and infliximab (n = 34, 4.0%). In the multinomial logistic regression analysis, patients were significantly more likely to receive adalimumab if they had a severe psoriasis as defined by baseline PASI or if they had psoriatic arthritis compared to etanercept (aOR, 0.42; 95% CI, 0.16-1.07) and ustekinumab (aOR, 0.15; 95% CI, 0.04-0.52). Patients were significantly more likely to receive ustekinumab (aOR, 2.39; 95% CI, 1.04-5.50) if they had a positive screening for latent tuberculosis compared to adalimumab. Younger patients were also more likely to receive ustekinumab. Patients with chronic obstructive pulmonary disease were more likely to be prescribed ustekinumab or etanercept compared to adalimumab. There was a trend in favour of etanercept prescription in patients with cardiovascular comorbidities, metabolic syndrome and in patients with a history of cancer. CONCLUSION: We identified patient- and disease-related factors that have important influence on the choice of the first biological agent in clinical practice. Clinicians appear to have a holistic approach to patient characteristics when choosing a biological agent in psoriasis.

[Bacillus cereus endocarditis and a probable cutaneous gateway]. / Endocardite à Bacillus cereus avec probable porte d'entrée cutanée.

BACKGROUND: Bacillus cereus is a ubiquitous telluric organism. B. cereus endocarditis is a rare condition seen mostly in prosthetic heart valves and among intravenous drug users. We report a new case of a patient without risk factors and with a good clinical outcome not requiring valve replacement. CASE REPORT: In October 2014, a 50-year-old woman was referred to the dermatology department of Lille University Hospital for lower-limb wounds developing 6 months earlier. She presented fever without clinical signs of infection, except for the lower-limbs wounds. Blood cultures revealed the presence of B. cereus. Transesophageal echocardiography was performed and revealed two foci of aortic valve vegetation with a diameter of 5mm. After bacterial sensitivity testing, rifampicin and levofloxacin treatment was given for six weeks, with complete remission. A skin graft was performed and good improvement was seen. DISCUSSION: Nineteen cases of B. cereus endocarditis have been described previously, only one of which was without risk factors. We described a case of complete remission after a 6-week course of antibiotics. Our case demonstrates that BC should not be considered as a blood culture contamination, and that treatment may be complex due to antibiotic resistance.

Benefits of task-shifting HIV care to nurses in terms of health-related quality of life in patients initiating antiretroviral therapy in rural district hospitals in Cameroon [Stratall Agence Nationale de Recherche sur le SIDA (ANRS) 12110/Ensemble pour une Solidarité Thérapeutique Hospitalière en Réseau (ESTHER) substudy].

OBJECTIVES: The World Health Organization (WHO) recommends task-shifting HIV care to nurses in low-resource settings with limited numbers of physicians. However, the effect of such task-shifting on the health-related quality of life (HRQL) of people living with HIV (PLHIV) has seldom been evaluated. We aimed to investigate the effect of task-shifting HIV care to nurses on HRQL outcomes in PLHIV initiating antiretroviral therapy (ART) in rural district hospitals in Cameroon. METHODS: Outcomes in PLHIV were longitudinally collected in the 2006-2010 Stratall trial. PLHIV were followed up for 24 months by nurses and/or physicians. Six HRQL dimensions were assessed during face-to-face interviews using the WHO Quality of Life (WHOQOL)-HIV BREF scale: physical health; psychological health; independence level; social relationships; environment; and spirituality/religion/personal beliefs. The degree of task-shifting was estimated using a consultant ratio (i.e. the ratio of nurse-led to physician-led visits). The effect of task-shifting and other potential correlates on HRQL dimensions was explored using a Heckman two-stage approach based on linear mixed models to adjust for the potential bias caused by missing data in the outcomes. RESULTS: Of 1424 visits in 440 PLHIV (70.5% female; median age 36 years; median CD4 count 188 cells/µL at enrolment), 423 (29.7%) were task-shifted to nurses. After multiple adjustment, task-shifting was associated with higher HRQL level for four dimensions: physical health [coefficient 0.7; 95% confidence interval (CI) 0.1-1.2; P = 0.01], psychological health (coefficient 0.5; 95% CI 0.0-1.0; P = 0.05), independence level (coefficient 0.6; 95% CI 0.1-1.1; P = 0.01) and environment (coefficient 0.6; 95% CI 0.1-1.0; P = 0.02). CONCLUSIONS: Task-shifting HIV care to nurses benefits the HRQL of PLHIV. Together with the previously demonstrated comparable clinical effectiveness of physician-based and nurse-based models of HIV care, our results support the WHO recommendation for task-shifting.

[Massive panniculectomy and bilateral subtotal mastectomy in a case of calciphylaxis: A case report and up date]. / Dermolipectomie abdominale et mastectomie bilatérale subtotale dans le cadre d'une calciphylaxie: à propos d'un cas et mise au point.

Calciphylaxis or calcific arteriolopathy is a rare, life-threatening obstructive pathology of the small cutaneous and subcutaneous vessels. It mainly affects patients with chronic renal failure but it also has been described in patients with normal renal function. The principal risks factors apart from renal failure and phosphocalcic metabolism imbalance are: the female sex, obesity, peripheral vascular disease, diabetes and oral anti-coagulation. We present a very rare case of abdominal, mammarian and upper thighs calciphylaxis in a patient with normal renal function. She presented a severe obesity with a recent important loss of weight and had been treated by oral anticoagulants for a long time. She benefited of a multidisciplinary approach with dermatologists, plastic surgeons and anesthesists permitting a recovery in fourteen weeks. Multidisciplinary approach is necessary but the place of the surgery is not well defined. We report a case in which early and wide surgical approach permitted to obtain a favourable evolution of the pathology. Then, we propose a therapeutic strategy after review of the literature.

Patterns of adherence to antiretroviral therapy and HIV drug resistance over time in the Stratall ANRS 12110/ESTHER trial in Cameroon.

OBJECTIVES: The emergence of HIV drug resistance is a crucial issue in Africa, where second-line antiretroviral therapy (ART) is limited, expensive and complex. We assessed the association between adherence patterns and resistance emergence over time, using an adherence measure that distinguishes low adherence from treatment interruptions, in rural Cameroon. METHODS: We performed a cohort study among patients receiving nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART in nine district hospitals, using data from the Stratall trial (2006-2010). Genotypic mutations associated with antiretroviral drug resistance were assessed when 6-monthly HIV viral loads were > 5000 HIV-1 RNA copies/mL. ART adherence data were collected using face-to-face questionnaires. Combined indicators of early (1-3 months) and late (6 months to t - 1; t is the time point when the resistance had been detected) adherence were constructed. Multivariate logistic regression and Cox models were used to assess the association between adherence patterns and early (at 6 months) and late (after 6 months) resistance emergence, respectively. RESULTS: Among 456 participants (71% women; median age 37 years), 45 developed HIV drug resistance (18 early and 27 late). Early low adherence (< 80%) and treatment interruptions (> 2 days) were associated with early resistance [adjusted odds ratio (95% confidence interval) 8.51 (1.30-55.61) and 5.25 (1.45-18.95), respectively]. Early treatment interruptions were also associated with late resistance [adjusted hazard ratio (95% confidence interval) 3.72 (1.27-10.92)]. CONCLUSIONS: The emergence of HIV drug resistance on first-line NNRTI-based regimens was associated with different patterns of adherence over time. Ensuring optimal early adherence through specific interventions, adequate management of drug stocks, and viral load monitoring is a clinical and public health priority in Africa.

Severe acute generalized exanthematous pustulosis with blistering mimicking toxic epidermal necrolysis, associated with a primary mumps infection.

Acute generalized exanthematous pustulosis (AGEP) is a severe adverse cutaneous reaction, which is mostly due to drugs, but which has also been described as occurring after infections. We report a case of severe AGEP with extensive blistering mimicking toxic epidermal necrolysis (TEN) in a 47-year-old woman. This was associated with a life-threatening primary mumps infection, complicated by perimyocarditis and encephalitis. The recent increase in the incidence of mumps should lead physicians to be aware of the uncommon clinical features and complications of this disease.