Combined treatment with low-dose methotrexate and initial short-term superpotent topical steroids in bullous pemphigoid: an open, multicentre, retrospective study.

BACKGROUND: The interest of long-term superpotent topical steroids (STS) in bullous pemphigoid (BP) has been supported by randomized controlled trials. However, inadequate compliance, poor cutaneous tolerance and nursing difficulties are potential drawbacks. Open-label studies on limited series of patients suggested that low-dose methotrexate (MTX) may be useful, permitting long-term maintenance of a clinical remission obtained by initial, short-term STS. OBJECTIVES: Open, clinical records-based retrospective analysis of a multicentre series of patients receiving a combined regimen of initial, short-term STS and MTX followed by long-term MTX alone. The primary objective was evaluation of the clinical efficiency of this strategy based on initial clinical remission and subsequent clinical maintenance. The secondary objective was evaluation of the tolerance (type and rating of adverse events) of this combined regimen. METHODS: Seventy patients with BP (mean age 82·7 years) were included. Treatment consisted of an initial combination of STS and MTX for a mean duration of 12·3 weeks followed by long-term MTX alone for a mean duration of 8·48 months with a mean and median MTX dosage of 10 mg per week. RESULTS: One hundred per cent of the patients showed an initial, complete clinical remission after a mean time interval of 21·9 days. The overall rate of long-term disease control was 76%, whereas 24% of patients experienced at least one relapse during subsequent treatment with MTX alone. Drug-related adverse effects were mainly haematological and gastrointestinal and resulted in treatment discontinuation in 11 patients (16%). Six patients (9%) died during the follow-up period with one death (1%) most likely to be related to treatment. CONCLUSIONS: Long-term low-dose MTX combined with short-term STS may result in protracted control of BP in carefully selected patients. These results should prompt randomized controlled trials comparing this treatment with the more usual regimen of long-term STS alone.

[Tumoral and pilotropic mycosis fongoides without mucin: evolution towards a pustulous erythroderma]. / Mycosis fongoïde tumoral et pilotrope sans mucine: évolution vers une érythrodermie pustuleuse.

INTRODUCTION: Pilotropic mycosis fongoides is a particular form of the disease, because of its clinical and histological aspects, its poor prognosis and its resistance to treatment. We report a case of pilotropic mycosis fongoides without mucinosis, immediately tumoral, the fatal progression of which was marked by the occurrence of pustular erythroderma. OBSERVATION: In 1998 a 69 year-old man presented with infiltrated erythro-squamatous plaques and nodules on the limbs associated with follicular lesions predominating on the cervical-cephalic area. Histological explorations revealed a pilotropic infiltrate with atypical CD4+ CD8 CD30 T-cells, without epidermotrophism or mucinosis. Study of genetic rearrangements found a clone lymphocyte T-cell in the skin. Diagnosis of pilotropic mycosis fongoides at the tumoral stage was made and, despite various treatments, the disease developed towards fatal pustular erythroderma. DISCUSSION: At the onset of its progression, pilotropic mycosis fongoides is sometimes difficult to distinguish from classical mycosis fongoides, during which follicular involvement is often seen. However it is important to differentiate these entities because of the poor prognosis of pilotropic mycosis fongoides. Development of tissue micro dissection techniques and lymphocyte T-cell clones from human skin would help to separate these cutaneous T-cell lymphoma sub-groups. Our case report is original because of the absence of dermal mucinosis combined with an immediately tumoral form and the progression towards generalized pustulosis. It also underlines the poor prognosis and resistance to treatment of pilotropic mycosis fongoides.

The expression of cytotoxic mediators is altered in mononuclear cells of patients with melanoma and increased by interferon-alpha treatment.

BACKGROUND: The role of cytotoxic cells in the control of cancer is now well established. OBJECTIVES: To evaluate the expression of perforin and granzyme A in cytotoxic cells of patients with melanoma and to look for a link between this expression and natural tumour progression; to check if interferon (IFN)-alpha administration increased expression of cytotoxic mediators; and to evaluate if this increase was correlated with the antitumoral effect of IFN-alpha. METHODS: To determine in patients with melanoma the expression of the cytotoxic mediators perforin and granzyme A in peripheral blood natural killer (NK) and T cells, we used flow cytometry before and after IFN-alpha administration. RESULTS: Compared with healthy volunteers, we observed in 82 patients a low percentage of NK cells harbouring perforin [75% (95% confidence interval (CI) 70-79) vs. 92% (95% CI 89-95), P < 0.001] and granzyme A [48% (95% CI 41-55) vs. 73% (95% CI 66-81), P < 0.001]. By contrast, a high percentage of T cells, and particularly of CD56+ T cells, expressed perforin [56% (95% CI 41-71) vs. 28% (95% CI 18-38), P < 0.001], whereas a low percentage of CD56+ T cells expressed granzyme A [30% (95% CI 24-36) vs. 54% (95% CI 43-65), P < 0.001]. In untreated patients, the percentage of CD56+ T cells expressing granzyme A was higher in progressors than in nonprogressors [49% (95% CI 39-58) vs. 16% (95% CI 0-33), P = 0.003]. We followed cytotoxic mediator expression in 17 patients treated with IFN-alpha. IFN-alpha administration increased granzyme A expression in NK cells [44% (95% CI 27-61) and 65% (95% CI 54-76) before and after treatment, respectively, P = 0.010], rather than perforin expression, whereas expression of both perforin [46% (95% CI 30-62), and 58% (95% CI 44-73), P = 0.112] and especially granzyme A [27% (95% CI 14-40) vs. 45% (95% CI 26-64), P = 0.016] was increased in CD56+ T cells after IFN-alpha administration. Yet, this effect was not correlated with the clinical response to IFN-alpha. CONCLUSIONS: Thus, the expression of cytotoxic mediators is altered in cytotoxic cells of patients with melanoma, and increased under IFN-alpha administration.

[Loss of motivation and frontal dysfunctions in old patients]. / Démotivation et dysfonctionnements frontaux chez le sujet âgé

UNLABELLED: Loss of motivation and frontal dysfunction are frequent in old people. Motivation refers to what drives acts and relationships. The loss of motivation has some spécific characteristics from depression: loss of sens of meaning, loss of commitment for others, disinterest for daily activities. The frontal function is related to speed of acting, emotional system, anticipating of the future. All these points are altered in demotivated patients. For these reasons we assayed to analyse the possible links between loss of motivation and frontal dysfunctions. METHODS: The focus of this assay was to determine and to precise the functional links between frontal brain and loss of motivation in old people; 45 old patients cared in a day care hospital were proposed to participate to neuropsychologic evaluation. After their agreement and their family acceptation if they were demented, they were assessed by a practitioner, then by 2 different psychologists. They were evaluated for cognition (MMS), depression (Cornell's scale), apathy (Marin's scale), age and scholarships level. In a other time, they were tested with different frontal tests: Trail making A and B, Wisconsin, BREF (frontal battery of psychological tests) ana-lyse concerned speeds, number and natures of errors, habilities for matching categories. Loss of demotivation was scored on EAD scale. Statistical analysis was done with Systat 10 and Statview software. RESULTS: It could be notice the significant negative links between EAD scores and the BREF scales, or with the number of categories found with the Wisconsin test. The more motivated the patients are the best results they have with their frontal tests. There are positive and significant links between EAD score and the number of errors at the Wisconsin test, and especially with repetitive errors either with this test or with BREF test. Repetitive errors and the number of errors, pointing some frontal dysfunctions are associated with a loss of motivation. Considering BREF sub-items, it could be shown the negative links between EAD scores and programmation or inhibition sub-items. All these points persist in a statistical model including pathology, cognitive levels, depression level at the Cornell's scale, age or scholarship level. We do not find a link between EAD scores and the time obtained with the Trail making test. CONCLUSION: Loss of motivation is associated with some frontal impairment responsible for numerous errors in tasks. A good motivation of old people is associated with good frontal habilities especially in complex tasks or in programming capacities of old patients. There is no links between the speeds of tasks and the level of motivation. Motivation could be so related with orbito-frontal brain activities.