[Cutaneous foreign body granulomas following cervico-facial arterial embolization: Three cases]. / Granulomes cutanés à corps étrangers après embolisation artérielle de la sphère cervico-faciale : trois cas.

BACKGROUND: Foreign body granuloma is an inflammatory tissue reaction to exogenous material. Classically it appears on the face after aesthetic procedures. Herein we report for the first time three cases of facial granulomatous reactions to microbeads after arterial cervico-facial embolization. PATIENTS AND METHODS: Three patients underwent embolization of the facial arteries using Embogold® microbeads in a setting of epistaxis or tumoral hemostasis. Within 10 to 45 days painful, inflammatory, subcutaneous nodules appeared on the homolateral side of the face. Histological samples showed an inflammatory response with giant cells as well as the presence of microbeads in the skin. A favorable outcome was achieved with colchicine in one patient and with surgery in another; the third patient was lost to follow-up. DISCUSSION: The embolizing microspheres produced a local inflammatory reaction, with destruction of the vascular wall and bead migration to facial tissue leading to a granulomatous reaction. The occurrence of three cases within a period of few weeks, with several different operators and batches of products, is surprising considering the long-standing use of the product. There was no common comorbidity in the patients and no suggestion of trauma. Retrospective analysis of the product batches was normal. Gold staining could play a role in severe inflammatory response to Embogold® particles. CONCLUSION: These three cases illustrate the value of discussing potential foreign body granulomatous reaction in cases of facial nodules following cervico-facial embolization. Colchicine may offer a valuable therapeutic alternative.

On demand Gamma-Knife strategy can be safely combined with BRAF inhibitors for the treatment of melanoma brain metastases.

BACKGROUND: Both Gamma-Knife radiosurgery (GKRS) and BRAF inhibitors (BRAF-I) have been shown to be useful in melanoma patients with brain metastases (BMs), thus suggesting that it could be interesting to combine their respective advantages. However, cases of radiosensitization following conventional radiation therapy in BRAF-I treated patients have raised serious concerns about the real feasibility and risk/benefit ratio of this combination. PATIENTS AND METHODS: Review by two independent observers of brain magnetic resonance imaging (MRI) follow-up pictures, and volume and edema quantifications, and survival assessment in all patients who had been treated by GKRS and BRAF-I at a single institution. RESULTS: Among 53 GKRS carried out in 30 patients who ever received BRAF-I and GKRS, 33 GKRS were carried out in 24 patients while under BRAF-I treatment, from which only 4 with an interruption of BRAF-I. The 20 other GKRS were carried out in 15 patients (including 9 of the 24) before initiation of BRAF-I treatment. No case of radiation-induced necrosis and no scalp radiation dermatitis occurred. A >20% increase in volume was observed in 35 of the 263 BM treated by GKRS (13.3%), but only 3 clear-cut edemas and 3 hemorrhages were detected within 2 months after GKRS, and 4 edemas and 7 hemorrhages later. Neither the MRI features nor the incidence of the volume changes, hemorrhage and edema were deemed unexpected for melanoma BM treated by GKRS. Median survival from first GKRS under BRAF-I and first dose of BRAF-I were 24.8 and 48.8 weeks, respectively. CONCLUSION: This series does not show immediate radiotoxicity nor radiation recall, in melanoma patients with BRAF-I whose BMs are treated by GKRS. Interrupting BRAF-I for stereotactic radiosurgery (SRS) of BM seems useless, although it is still advised for other radiation therapies. The potential benefit of combining SRS and BRAF-I can be safely tested.

Evidence-based recommendations on topical treatment and phototherapy of psoriasis: systematic review and expert opinion of a panel of dermatologists.

BACKGROUND: Although topical treatments and phototherapy are available for more than 40 years, there is a paucity of evidence-based recommendations regarding their use. OBJECTIVES: The aim of this work was to develop evidence-based recommendations on topical treatments and phototherapy in psoriasis for daily clinical use. METHODS: A scientific committee selected clinically relevant questions on efficacy and safety of topical agents and phototherapy in psoriasis. This selection was made using the Delphi method. A systematic literature search was performed in Medline, Embase and the Cochrane Library. The articles selected for analysis were reviewed and the level of evidence was appraised according to the Oxford Levels of Evidence. An Expert consensus meeting took place in June 2011, including 42 dermatologists. Recommendations for use of topical treatments and phototherapy were made during interactive workshops where the evidence was presented and discussed. Agreement among participants was assessed on a 10-point scale. The participants systematically assessed the impact of the recommendations on clinical practice. RESULTS: A total of 3555 references were identified, among which 312 articles were included in the systematic reviews. Three recommendations were issued on phototherapy including both PUVA and narrow-band UVB. The recommendations related to administration schedule, clearance rate and risk of side-effects. The mean agreement between participants was good varying from 8.5 to 9.5. Six recommendations were issued on topical treatments focusing on administration schedule, clearance rate, risk of side-effects, cost-effectiveness and measures to improve treatment adherence. The mean agreement between participants varied from 7.3 to 9.9. CONCLUSIONS: These recommendations for the use of topical agents and phototherapy in psoriasis are evidence-based and supported by a panel of dermatologists. The next step will be to disseminate these recommendations and assess the opinion of physicians who were not involved in generating the recommendations.

Efficacy of psoralen UV-A therapy vs. narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review.

BACKGROUND: Oral 8-methoxypsoralen-UV-A (PUVA) and Narrowband UV-B (NB-UVB or UVB TL-01) are well established treatments for chronic plaque psoriasis but there is limited evidence regarding their respective efficacy. OBJECTIVES: To prepare for evidence-based recommendations concerning the practical use of oral 8-methoxypsoralen-UV-A and Narrowband UV-B in psoriasis, a systematic review to assess respective response rates, remission duration and predictive factors of efficacy was performed. METHODS: A systematic search was carried out in PubMed, Cochrane and Embase databases, using the key words 'Psoriasis', 'UVB therapy', 'UVA therapy' for the period from 1980 to December 2010. RESULTS: The initial literature search identified 773 articles. The final selection included 29 randomized controlled trials: 18 were about the efficacy of PUVA, eight about the efficacy of NB-UVB and three directly compared PUVA vs. NB-UVB. The response rate defined by 75% or more improvement in PASI was 80% with PUVA vs. 70% with NB-UVB. The meta-analysis of the three comparative studies found a higher probability of remission at 6 months with PUVA than with NB-UVB [OR = 2.73 (95% CI 1.19-6.27), P = 0.02]. The choice of initial dose, according to skin type, the minimal erythemal dose or minimal phototoxic dose, incremental regimen and periodicity of the sessions did not appear to be predictive factors of efficacy for PUVA or NB-UVB. Despite methodological limitations in trials, the number of sessions needed for psoriasis clearance appeared to be lower with PUVA than with NB-UVB (approx. 17 vs. 25, respectively). CONCLUSION: PUVA and NB-UVB are both effective therapies in treatment of psoriasis. Our results suggest that compared with NB-UVB, PUVA tends to clear psoriasis more reliably, with fewer sessions, and provides with longer lasting clearance. However, the long-term safety of PUVA, especially its cutaneous carcinogenic risk, and the easier administration procedure often lead dermatologists to prefer NB-UVB as first line phototherapy treatment in plaque type psoriasis.

Carcinogenic risks of psoralen UV-A therapy and narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review.

BACKGROUND: Oral 8-methoxypsoralen-UV-A (PUVA) and narrowband UV-B (NB-UVB or UVB TL-01) are effective and widely used treatments for chronic plaque psoriasis. Although the role of PUVA therapy in skin carcinogenesis in humans with psoriasis has been clearly demonstrated, there is still controversy regarding the risk of skin cancer with NB-UVB. Furthermore, there is no clear evidence about the maximum cumulative number of sessions not to be exceeded in a lifetime. OBJECTIVES: To assess the respective cutaneous carcinogenic risks of PUVA or NB-UVB in psoriasis; to estimate the respective dose-relationship between skin cancers and PUVA or NB-UVB; to estimate a maximum number of sessions for PUVA or NB-UVB not to be exceeded in a lifetime. METHODS: A systematic literature search was carried out in Medline, Embase and Cochrane Library databases from1980 to December 2010 in English and French, with the keywords 'Psoriasis' AND 'UVB therapy' AND 'UVA therapy' AND 'cancer' AND 'skin' OR 'neoplasm' OR 'cutaneous carcinoma' OR 'melanoma'. RESULTS: Of 243 identified references, 49 published studies were included. Most of them (45/49) concerned PUVA therapy, with 41 assessing the risk of non-melanoma skin cancers (NMSC) following PUVA. All publications referring to the US prospective PUVA follow-up study revealed an increased risk of NMSC with the following characteristics: risk most pronounced for squamous cell carcinomas developing even with low exposures and increasing linearly with the number of sessions, tumors occurring also on non-exposed skin including invasive penile tumors, risk persisting after cessation of treatment. An increased risk of basal cell carcinomas was observed in patients receiving more than hundred PUVA sessions. The four prospective European studies selected in our review and most of the pre-1990 European and US retrospective studies failed to find a link between exposure to PUVA and skin cancer. Only the most recent cohorts, including three large long-term retrospective European studies comparing records with their respective national cancer registries reported on an independent increased risk of NMSC with PUVA, The risk was lower as compared to the US prospective PUVA follow-up study. Six studies assessed the risk of melanoma following PUVA therapy: two of the three US publications coming from the same PUVA prospective follow-up study revealed an increased risk with more than doubled incidence of both invasive and in situ melanoma among patients exposed to at least 200 PUVA treatments compared with patients exposed to lower doses, whereas the three retrospectives European studies, comparing the incidence of melanoma in PUVA users with national cancer registers, did not find any increased risk of melanoma. No increased risk of skin cancer was evidenced in the four studies specifically assessing the potential carcinogenic risk of NB-UVB. CONCLUSION: There is an increased risk of skin cancer following PUVA, shown by both US and European studies. The greater risk measured by the US studies may be at least partly explained by high UVA dose exposure and the lighter phototypes of the treated patients. The lack of prospective studies in psoriasis patients treated with NB-UVB constitutes a barrier to the robust assessment of carcinogenic risk of this phototherapy technique.

Topical corticosteroids in plaque psoriasis: a systematic review of efficacy and treatment modalities.

INTRODUCTION: Topical steroids are used for more than 50 years to treat mild-to-moderate plaque psoriasis. The purpose of this systematic review was to evaluate the efficacy but also the optimal modalities of administration of topical corticosteroids in psoriasis i.e. influence of steroid potency on clinical response, putative impact of topical formulation, occlusion procedure, rate of application to control the initial response and the potential interest of a maintenance treatment to prolong psoriasis clearance. MATERIAL AND METHODS: A systematic search was performed between 1980 and January 2011 in Medline, Embase and Cochrane databases (English and French language, adults), using the keywords 'psoriasis'/exp/mj AND 'corticosteroid'/exp/mj. To analyse response across studies, three levels of response were categorized depending on the data available in studies: percentage of patients who achieved more than 50%, 75% or 90% improvement of initial psoriasis severity. RESULTS: From an initial selection of 1269 references, 1166 references were excluded on reading the title or the abstract and 32 on reading the article and 71 were finally retained and analysed. Fifty randomized controlled trials (RCT) assessing topical steroids in the initial treatment of mild-to-severe psoriasis body plaque psoriasis were retained: 40 were parallel-group studies and 10 were within-patient studies. Treatment duration was mostly 4 weeks. Sample size varied from 30 to 1 603 patients. Outcome measures to assess efficacy were highly variable. A total of 30-90% patients across parallel group studies experienced more than 50% of initial mild-to-severe psoriasis improvement while from 7% to 85% experienced more than 75% improvement and from 5% to 85% experienced at least 90% of improvement. The success rate in the within-patient studies varied from 10% to 70%. Eighteen RCT were performed in scalp psoriasis: 16 were parallel-group and two were within-patient studies, with a treatment follow-up time from 2 weeks to 6 months, enrolling 42-1417 patients. A total from 40% to 75% patients across studies experienced more than 75% of initial scalp psoriasis improvement and from 43% to 90% experienced more than 90% initial psoriasis improvement. Only three RCT studies evaluated topical steroids as a maintenance treatment for body psoriasis and one for scalp lesions. Despite heterogeneity in treatment schedule, topical steroid intermittent maintenance treatment was shown to prolong remission. The literature analysis did not provide with high evidence-based quality data on the role of formulation, topical steroid potency, number of applications per day to obtain the highest rate of success excepting occlusion dressing which provided with additional benefit. CONCLUSION: The clinical development of topical steroids in psoriasis did not follow state of the art modern methodology. Treatment success appears to be highly variable across studies. Maintenance intermittent treatment appears to be useful to prolong remission. Recommendations concerning topical steroids treatment modalities in plaque psoriasis should be mostly based on expert opinion.

Topical corticosteroids in plaque psoriasis: a systematic review of risk of adrenal axis suppression and skin atrophy.

BACKGROUND: Topical steroids have been used for more than 50 years in mild-to-moderate plaque psoriasis and carry a theoretical risk of adverse events. OBJECTIVES: The aim of this systematic literature review was to evaluate the risk of hypothalamo-pituitary-adrenal (HPA) axis suppression and the risk of skin atrophy with topical steroids in the treatment of plaque psoriasis. METHODS: A systematic search between 1980 and January 2011 in Medline, Embase and Cochrane databases (English, French language, adults), using the keywords 'psoriasis'/exp/mj AND 'corticosteroid'/exp/mj, RESULTS: Altogether 1269 references were found. Of these 1124 articles were excluded by reading the abstract and 123 by reading the article. A total of 22 randomized trials were selected. Effects on HPA axis: Thirteen studies, with a sample size varying from 7 to 341 patients, were selected. The effect on HPA axis was evaluated by the morning cortisol level (11 studies), the 24 h urine steroid levels (five studies) and/or by the Synacthen test (three studies). Reduction of morning cortisol was observed in 0-25% of patients in 10 short-term studies (two in scalp psoriasis, eight in body psoriasis) and in 48% of patients in the remaining short-term study (body psoriasis). Only four of these studies with three on body psoriasis evaluated the effect of long-term treatment defined as 6-month treatment duration or longer and did not identify HPA axis suppression by cortisol level measurement. The Synacthen test, considered as the gold standard to assess HPA axis, was always normal. There was no evidence of clinically significant HPA axis suppression due to absorption of topical steroids even when treating the scalp or in patients with extensive disease. Risk of skin atrophy: Thirteen studies with topical steroid evaluating treatment durations from 4 weeks to 1 year were analysed. The frequency of skin atrophy assessed clinically, varied from 0% to 5% of patients. CONCLUSIONS: The literature analysis on topical steroids in psoriasis is reassuring although the quality of safety studies is limited with a majority of short-term studies. Although short-term biological effects of topical steroids on the HPA axis were observed in several clinical studies, they were not associated with clinical signs. Adequately designed long-term studies would be necessary to better determine the risk of skin atrophy using modern methods of evaluation such as dermoscopy and echography.

Topical vitamin D analogues alone or in association with topical steroids for psoriasis: a systematic review.

OBJECTIVE: The objective of this systematic review was to prepare for evidence-based recommendations on the use of vitamin D analogues, and their combination with topical steroids in psoriasis. METHODS: Literature systematic review performed in May 2011. The Cochrane, PubMed and Embase databases were systematically searched with different combinations: including Psoriasis AND calcipotriol expanded to all vitamin D analogues. To assess efficacy across studies, we used two predefined criteria to account for the numerous endpoints found in the literature, 'Treatment success' corresponding to 90% improvement in severity and 'Satisfactory response' corresponding to 75% improvement. We conducted a meta-analysis comparing the efficacy of vitamin D analogues plus topical steroids (VDS) vs. vitamin D analogues alone (VD). To determine the relative cost-efficacy of the topical drugs available on the market, cost/efficacy ratios were calculated for each product according to the approved therapeutic regimen. RESULTS: 51 articles were selected. The application duration varied between three to 52 weeks across studies. VD as monotherapy had a satisfactory response rate between 22% to 96% and a treatment success rate ranging from 4% to 40%. VDS had a satisfactory response rate between 35% to 86% and a treatment success rate ranging from 27% to 53%. A meta-analysis found a probability of success twice higher with VDS than with VD in adult plaque psoriasis. The cost/efficacy ratio was evaluated as 1.2-1.8 times higher for VDS than for VD. CONCLUSION: VDS is twice more effective than VD and displays a better cost per success. Additional studies are needed to clarify maintenance treatment, impact on quality of life, treatment of non-plaque psoriasis. It will be important to harmonize outcome measures in future studies with topical agents in psoriasis to better appraise their efficacy.

Adherence to topical treatment in psoriasis: a systematic literature review.

BACKGROUND: Treatment adherence has been recognized as an important issue in the management of chronic diseases such as psoriasis. OBJECTIVE: The aim of this work was to analyse data about topical treatment adherence in psoriasis. METHODS: Systematic literature review (62 references) between 1980 and 2011 (database: PubMed, Embase and Cochrane; Mesh keywords: Patient Compliance [Mesh] OR Medication Adherence [Mesh] AND Psoriasis [Mesh]; limits: date of publication >1980, humans subjects, written in French or English, aged ≥ 19 years). Two parameters were evaluated: (i) the ratio of number of product applications performed vs. number of applications expected according to physician recommendations, (ii) the ratio of amount of product used vs. amount of product prescribed. RESULTS: A total of 22 studies were selected. Nine studies reported on the frequency of topical treatment application in a real world setting. Five studies showed a frequency of applications varying between 50% and 60% of those expected. Because of the high variability in medication adherence assessment methods, the data could not be combined. Twelve articles reported on the frequency of topical treatment application in randomized controlled trials with adherence varying between 55% and 100%. Concerning the amount of product use, four studies showed patients applied between 35% and 72% of the recommended dose during a treatment period of 14 days to 8 weeks. The most frequently mentioned reasons for non-adherence to topical treatment were low efficacy, time consumption and poor cosmetic characteristics of topical agents. Patients experiencing adherence issues were significant younger, were men, had younger age at onset of psoriasis and had a higher self-assessed severity. To improve adherence, the following strategies were suggested: to give patients information about psoriasis, to recognize social impact, to give written instructions for use such as a care plan, to explain side effects of topical therapies, to choose treatment and its cosmetic properties in agreement with the patient. CONCLUSIONS: Literature data about topical treatment adherence are heterogeneous and scarce. They confirm the limited topical treatment adherence in psoriasis in real life, much lower than what is reported in randomized controlled trials. Therapeutic education and clear instructions on the use of topical agents are necessary to improve adherence. Studies are needed to identify predictors of limited adherence and to identify interventions improving adherence to topical medications in psoriasis.

[Morel-Lavallee syndrome of the lower leg]. / Syndrome de Morel-Lavallée du membre inférieur.

BACKGROUND: Morel-Lavallée syndrome, which appears after tangential trauma of highly vascularised tissues, is characterized by closed internal degloving injuries resulting in subcutaneous fluid collection. It can cause many complications. A 42-year-old man presented with open wounds after a violent right lower extremity trauma; the wounds were sutured. One month after the trauma, the patient complained of painful edema of the lower limb and fluid discharge from the previously sutured wounds. Local examination showed fluctuating fluid collection. Serum inflammatory markers were within the normal range. Ultrasound investigation of the right lower limb confirmed an extended fluid collection from the lower third of the thigh to the upper third of the leg, and CT scan delineated a surrounding capsule. The clinical and radiological data supported a diagnosis of post-traumatic Morel-Lavallée syndrome. Local surgical debridement and drainage associated with systemic antibiotic therapy (the fluid was found to be infected with oxacillin-resistant Staphylococcus epidermidis) resulted in rapid improvement. DISCUSSION: Morel-Lavallée syndrome commonly appear after tangential trauma of highly vascularised tissues. The skin and the subcutaneous fat tissue are abruptly torn from the underlying muscle fascia, shearing the lymphatic vessels, rendering lymphostasis impossible. The local inflammatory reaction can cause the formation of a fibrous capsule resulting in a fluid collection. The clinical signs are not specific. When examining a soft-tissue collection or slow-healing wounds, the dermatologist should always rule out previous soft-tissue trauma; simple imaging studies will confirm the diagnosis if Morel-Lavallée injuries are suspected. CONCLUSION: All dermatologists consulted by young patients without vascular disease for an unusual swelling and/or for slow-healing wounds should be mindful of this syndrome.