M. Viguier

High frequency of cholestasis in generalized pustular psoriasis: Evidence for neutrophilic involvement of the biliary tract

Generalized pustular psoriasis is a rare form of psoriasis that is sometimes associated with extracutaneous manifestations. Evidence for biliary involvement has been suggested in isolated cases. We investigated the prevalence and nature of liver abnormalities occurring in this disease. Twenty‐two patients consecutively admitted for generalized pustular psoriasis who underwent liver biological tests at the time of the attack and during the following weeks were included. Twenty patients (90%) had at least one abnormal biological liver parameter. Eleven patients (50%) had pronounced abnormalities: jaundice (4/22), gammaglutamyl transferase higher than 5 times the normal value (10/22), alkaline phosphatase higher than twice the normal value (7/22), and/or aminotransferases higher than 3 times the normal value (7/22). These abnormalities returned to normal range at the time of remission of pustular psoriasis, suggesting that severe liver abnormalities could be associated with severe cutaneous disease. Neutrophilic cholangitis was observed on liver biopsy. Persistent magnetic resonance cholangiopancreatography features similar to those observed in sclerosing cholangitis were found in 3 of the 4 patients studied. No causal factor other than pustular psoriasis could be identified. In conclusion, our results demonstrate the high frequency of liver abnormalities in patients with generalized pustular psoriasis. Biliary involvement related to neutrophilic cholangitis should be added to the spectrum of extracutaneous manifestations of this disease, and physicians should be aware of such a complication. (HEPATOLOGY 2004;40:452–458.)

Management and outcome of metastatic melanoma during pregnancy

Background  Although metastatic melanoma occurrence during pregnancy challenges the physician in several ways, only a few studies have been published.

Paradoxical adverse effects of anti-TNF-α treatment: onset or exacerbation of cutaneous disorders

TNF-α antagonists have been shown to be very effective for the treatment of various rheumatic and nonrheumatic diseases, including psoriasis, and for off-label use in other inflammatory and immune-mediated disorders. However, the increasing use of these agents has led to the recognition of several paradoxical cutaneous adverse effects. New onset or exacerbation of cutaneous psoriasis, cutaneous vasculitis and sarcoidosis have been described. Further characterization and more precise diagnosis of these adverse events are warranted to provide further insights into the pathogenic mechanisms involved and to optimize their management. Herein, we present a review of the different clinical patterns of these paradoxical cutaneous adverse disorders, and we propose recommendations for their management.

Onset of psoriatic arthritis in patients treated with efalizumab for moderate to severe psoriasis.

OBJECTIVE To investigate the nature of polyarthritis in patients with moderate to severe psoriasis undergoing treatment with efalizumab, a humanized anti-CD11a monoclonal antibody. METHODS In a multicenter study, we retrospectively analyzed patients who developed arthritis during treatment with efalizumab. The relationship between joint manifestations and psoriatic disease was addressed by using different classification criteria for psoriatic arthritis (PsA). The course of arthritis and its response to treatment were also investigated. RESULTS Sixteen patients developed de novo inflammatory rheumatic disease, with a mean delay of 15 weeks following the start of treatment, and with exclusive asymmetric peripheral monarthritis or oligoarthritis (8 patients), inflammatory spinal disease (1 patient), or both (7 patients), associated in some cases with enthesitis and dactylitis. All patients fulfilled at least 2 different sets of classification criteria for PsA. In most of them, an improvement in skin lesions was observed at the onset of PsA, as measured using the Psoriasis Area and Severity Index (mean score 24.88 before efalizumab versus 18.78 at the time of arthritis). Efalizumab treatment was stopped in 11 patients and was followed by the elimination of rheumatologic symptoms in 1 patient, while 8 patients required treatment with nonsteroidal antiinflammatory drugs with or without methotrexate, with 2 later being switched to tumor necrosis factor alpha inhibitors. Reintroduction of efalizumab (2 patients) was followed by a relapse of PsA. CONCLUSION This study questions the role of efalizumab in the induction of PsA. It also emphasizes the discrepancy between the courses of psoriatic skin and joint manifestations under treatment. Prospective case-control studies are needed to accurately investigate the impact of efalizumab on PsA.

Intravenous immunoglobulins in difficult‐to‐treat ulcerated livedoid vasculopathy: five cases and a literature review

Livedoid vasculopathy (LV) is a thrombotic vasculopathy of the skin of unknown origin. No treatment has been validated in this indication, but case reports suggest the successful use of intravenous immunoglobulins (IVIG) in LV.

Single-center study under a French Temporary Authorization for Use (TAU) protocol for ipilimumab in metastatic melanoma: negative impact of baseline corticosteroids

AbstractIpilimumab is an anti-CTLA-4 antibody which has recently been approved in Europe as a monotherapy in the treatment of metastatic melanoma.We report a single-center study among patients treated within a Temporary Authorization for Use (TAU) protocol.We also performed a review of the literature involving expanded access program studies with a focus on factors associated with overall survival (OS).Patients and methodsThis retrospective, observational study included patients between June 2010 and July 2011 with a diagnosis of non-resectable stage III or IV melanoma with at least one previous line of chemotherapy. Treatment consisted of four courses of ipilimumab at a dose of 3mg/kg every three weeks.Results45 patients were included, among whom23 (51%) had brain metastases. 33 (71%) of the patients completed the induction phase. The best overall response rate (BORR) was 13% and median overall survival (OS) was 8 months (95%CI: 7 to 12). OS was not different between patients with brain metastases at baseline and those without (p = 0.10), regardless of BRAF V600E status (p = 0.61). OS was poorer in patients who were being treated with corticoids at baseline (p<0.001) or with LDH at baseline > 500 UI/ml (p = 0.008).ConclusionA subset of patients most likely to benefit from ipilimumab should be defined. In our series we found a negative association of baseline corticosteroids with OS. Unlike high LDH levels, BRAF V600 E status and brain metastases should not be barriers to the initiation of treatment.

A first case report of a patient with paraneoplastic dermatomyositis developing diffuse alveolar haemorrhage

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La photochimiothérapie extracorporelle

Photopheresis or extracorporeal photochemotherapy (ECP) is a cellular therapy which combines a leukapheresis followed by ex vivo treatment using psoralen and ultraviolet A irradiation before reinfusion into the patient. Its mechanisms of action remain unclear and selective photodestruction of leukocytes cannot explain the long-lasting immunomodulatory effects. Recent studies demonstrated that ECP down regulates the immune response and induces tolerance through the maturation of dendritic cells and the production of regulatory T cells. Based on these effects, ECP is mainly used for treatment of Sezary syndrome, graft-versus-host disease, organ graft rejection and autoimmune diseases. However, it is still not clear how ECP both activates tumor immunity against cutaneous T-cell lymphoma and induces tolerance in autoreactive disorders. In addition, the use of adjuvant therapies, the long-term effects and various treatment protocols remain to be investigated along with the specific indications.

Linear immunoglobulin-A bullous dermatosis complicating multi-organ tuberculosis at early-stage treatment.

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Patients longs survivants sous inhibiteur de B-Raf

Mots clés : Inhibiteur de BRAF ; Longs répondeurs ; Mélanome métastatique Introduction.— Le vemurafenib, inhibiteur de B-Raf (iBRAF), a obtenu l’AMM en première ligne de traitement des mélanomes métastatiques mutés BRAF. Ce traitement permet d’obtenir une réponse dans plus de 50 % des cas. Cependant elles sont rarement durables avec un échappement en moyenne à 8 mois de traitement. Nous rapportons une série de 8 patients longs survivants (plus de 18 mois) sous iBRAF. Patients et méthodes.— Nous avons inclus les patients suivis dans le service pour un mélanome avancé et ayant été traités par iBRAF (vemurafenib ou dabrafenib en protocole ou ATU) pendant au moins 18 mois. Les patients traités par chirurgie ou radiothérapie au cours du traitement étaient inclus. Les patients étaient considérés comme répondeurs lorsqu’ils présentaient une maladie stable, une rémission partielle (RP : > 30 % de réponse) ou une rémission complète (RC). Résultats.— Nous avons inclus 8 patients sur 67 ; un stade IIIB, deux stade IIIC et cinq stades IV. Tous les patients avaient une mutation V600E. Un patient seulement avait reçu auparavant une cure de déticène et un protocole adjuvant comparant l’ipilimumab vs placebo (aveugle non levé). Les autres étaient naïfs de traitement. Au T0, les LDH étaient normaux chez six patients, deux avaient des LDH à 1,5 X la normale (stade IIC et stade IV). On notait six RC, deux patients stables et une RP à M2. Trois patients ont eu une chirurgie pour l’apparition de nouvelles lésions. Une patiente a eu de la radiothérapie stéréotaxique pour une métastase cérébrale. À ce jour, quatre patients sur 8 sont toujours en RC avec un recul de 18 à 30 mois et pour deux d’entre eux, le traitement a été arrêté à M18 et M30. Un patient en RC initiale a présenté pendant un arrêt temporaire du traitement des métastases cérébrales qui ont répondu partiellement à la réintroduction de l’iBRAF. Les trois patients qui n’ont pas eu de RC initiale ont progressé après 23, 26 et 31 mois, deux selon des modes rapidement progressifs. Discussion.— Les iBRAF sont une avancée spectaculaire dans la prise ne charge du mélanome à un stade avancé Cependant, bien qu’il existe peu de résistance primaire, la majorité des patients acquiert une résistance secondaire et échappent au traitement au bout de 6 à 8 mois. Nos patients présentent quelques caractéristiques telles qu’un âge jeune, ainsi que des taux de LDH majoritairement normaux signant une masse tumorale limitée. Par ailleurs, 6/8, soit 75 %, ont eu une rémission complète alors qu’environ 5 % seulement des patients ont une RC dans les essais. Conclusion.— De petits groupes de patients répondent de façon prolongée aux iBRAF. Dans notre cohorte, ce sont des patients plus jeunes (âge moyen : 46 ans) avec une masse tumorale faible et peu de comorbidités. Chez les patients en rémission complète durable, de nombreuses questions restent en suspens, notamment le temps de poursuite du traitement après la rémission complète et l’intérêt d’une prise séquentielle du traitement. Déclaration d’intérêt.— Aucun.