Sezary syndrome cells unlike normal circulating T lymphocytes fail to migrate following engagement of NT1 receptor

Circulating malignant Sezary cells are a clonal proliferation of CD4+CD45RO+ T lymphocytes primarily involving the skin. To study the biology of these malignant T lymphocytes, we tested their ability to migrate in chemotaxis assays. Previously, we had shown that the neuropeptide neurotensin (NT) binds to freshly isolated Sezary malignant cells and induces through NT1 receptors the cell migration of the cutaneous T cell lymphoma cell line Cou-L. Here, we report that peripheral blood Sezary cells as well as the Sezary cell line Pno fail to migrate in response to neurotensin although they are capable of migrating to the chemokine stromal-cell-derived factor 1 alpha. This is in contrast with normal circulating CD4+ or CD8+ lymphocytes, which respond to both types of chemoattractants except after ex vivo short-time anti-CD3 monoclonal antibody activation, which abrogates the neurotensin-induced lymphocyte migration. Furthermore, we demonstrate that neurotensin-responsive T lymphocytes express the functional NT1 receptor responsible for chemotaxis. In these cells, but not in Sezary cells, neurotensin induces recruitment of phosphatidylinositol-3 kinase, and redistribution of phosphorylated cytoplasmic tyrosine kinase focal adhesion kinase and filamentous actin. Taken together, these results, which show functional distinctions between normal circulating lymphocytes and Sezary syndrome cells, contribute to further understanding of the physiopathology of these atypical cells.     

Paraneoplastic acral vascular syndrome: epidemiologic features,clinical manifestations,and disease sequelae

BACKGROUND: Acral vascular syndromes associated with malignancy have rarely been reported. OBJECTIVE: Our purpose was to assess the clinical and evolving features of paraneoplastic acral vascular syndromes. Patients and Methods: Two cases of paraneoplastic gangrene are described and analyzed together with previously reported cases identified by a MEDLINE search. RESULTS: Among the 68 patients identified, 40 had gangrene, 16 had acrocyanosis, and 12 had Raynaud's phenomenon. The male to female ratio was 0.89; median age was 59 years. Fingers were affected in 94%. Adenocarcinomas were the predominant associated malignancies (41%), and metastases were observed in 41%. The acral vascular syndromes in 48% of the patients definitively regressed after tumor treatment. Forty-four percent of the patients died within 2 years. A favorable cutaneous outcome was obtained with prostacyclin infusions in 6 patients. CONCLUSION: A neoplastic origin of acral vascular syndrome should be considered in elderly patients, especially men, in the absence of usual causative conditions.     

Cutaneous CD8+ epidermotropic cytotoxic T-cell lymphoma with aggressive course

BACKGROUND: Cutaneous CD8+ epidermotropic cytotoxic T-cell lymphoma is a recently described rare primary cutaneous lymphoma exhibiting aggressive clinical behavior. Only about twenty cases have been described in the literature. Below we report a case involving unusual association of cutaneous vasculitis and lymphoproliferation. CASE REPORT: A 42-year-old senegalese man was hospitalized for cutaneous nodular lesions, which rapidly spread and became necrotic and ulcerated. he had recent weight loss with fever and multiple enlarged lymph nodes. Cutaneous histological analysis showed epidermotropic dermal infiltrate comprising medium and large cd8+ cytotoxic t-cells of unusual angiocentricity with cutaneous vasculitis and fibrinoid necrosis. the patient died 4 months after initiation of treatment with multi-agent chemotherapy. DISCUSSION: This patient presented the characteristics of primary cutaneous CD8+ epidermotropic cytotoxic T-cell lymphoma described by Berti. The clinical findings in most cases consist of nodular and ulcerative cutaneous lesions. Histologically, the cutaneous infiltrate is composed of pleomorphic lymphocytes with marked and constant epidermotropism. Immunohistochemistry shows lymphocytes expressing a CD8+ phenotype and cytotoxic proteins, which probably accounts for the local and systemic aggressiveness of the disease, as well as the angiodestructive nature of the infiltrate and the necrotic lesions.     

Performance of the SCORTEN during the first five days of hospitalization to predict the prognosis of epidermal necrolysis

The SCORTEN, calculated within 24 hours of admission, is a severity-of-illness score validated for toxic epidermal necrolysis and Stevens-Johnson syndrome. Our purpose was to assess the performance of successive SCORTEN during the first 5 days of hospitalization and to determine the influence of admission delay. Charts of 144 patients aged 46.8 years (+/-19.7), admitted to our department (1993-2003) with Stevens-Johnson syndrome or toxic epidermal necrolysis, were reviewed. Successive SCORTEN were compared between deceased patients (n = 28, 19.4%) and survivors (n = 116). The performance of the score (calibration, discrimination) was assessed on days 1-5. All seven SCORTEN variables, on days 1-5, were associated with a higher mortality rate. The SCORTEN rose slightly during hospitalization, with a significant difference between days 1 and 4 (<0.05). Performance of the SCORTEN was good on each day, but slightly better on day 3. The areas under the receiver-operating characteristic curves were above 80%. The admission delay did not differ between deceased patients and survivors. Delay-adjusted SCORTEN was close to the crude SCORTEN. The SCORTEN performance during the first 5 days of hospitalization was excellent, and at its best on day 3. We recommend to compute again the SCORTEN on day 3. The admission delay did not influence prognosis or SCORTEN.     

Acute generalized exanthematous pustulosis induced by drugs with low-digestive absorption: acarbose and nystatin

INTRODUCTION: Acarbose and nystatin are usually well-tolerated drugs because of their minimal intestinal absorption. We report herein two cases of acute generalized exanthematous pustulosis induced by these two molecules. CASES REPORT: A 43 year-old man with a history of insulin-deficient diabetes was admitted to our department for a febrile generalized cutaneous pustular erythema, that had appeared 48 hours after acarbose (Glucor) introduction. Acarbose was discontinued and the eruption resolved in one week. A 29 year-old man developed a flexural erythema twenty four hours after nystatin (Mycostatin) treatment, progressing towards a febrile pustular erythroderma, with elevated neutrophilic and eosinophilic counts. The lesions regressed rapidly with topical steroid treatment. The patch tests performed a few months later with Mycostatin and nystatin were positive. DISCUSSION: The clinical presentation of these two patients was typical of acute generalized exanthematous pustulosis, according to the EuroSCAR group criteria and acarbose and nystatin were the most likely factors that caused the disease according to the French unexpected or toxic drug reaction assessment. The minimal intestinal absorption of these two molecules explains their usual good tolerance. However, some cases of toxiderma have already been reported. There is the first described case of acute generalized exanthematous pustulosis with acarbose. Our two observations underline the possibility of severe toxiderma induced by low-absorbed and low-blood concentration molecules and focus on the need to take them in account in the toxiderma anamnesis.     

Severe necrotic and haemorrhagic edema of the upper limbs revealing remitting seronegative symmetrical synovitis with pitting edema

BACKGROUND: RS3PE (Remitting Seronegative Symmetrical Synovitis with Pitting Edema) syndrome is characterized by bilateral and symmetrical tenosynovitis of the distal extremities. It occurs with acute onset in older patients aged over 50 years. This heterogeneous entity can be isolated or can reveal various rheumatic diseases and neoplastic conditions. We report a case of RS3PE syndrome associated with unusually severe cutaneous necrotic and haemorrhagic lesions, and revealing malignant monoclonal IgM proliferation. CASE REPORT: A 62-year-old man was admitted for acute and symmetrical synovitis of both hands and forearms associated with fever and increased acute phase reactants. Severe necrotic and haemorrhagic edema developed simultaneously. Laboratory tests ruled out infectious disease and collagen vascular disorder. Clinical symptoms responded promptly to corticosteroids to reveal severe erosive arthropathy of both wrists. The monoclonal IgM proliferation discovered during the acute phase evolved into a malignant medullary plasmocytosis. After adequate treatment of this proliferation, no haematological, cutaneous or articular relapse occurred during the two-year follow-up period. DISCUSSION: This type of cutaneous symptoms has never been reported during the course of RS3PE syndrome. It may be supposed that the severity of the initial clinical picture was linked in this patient to the paraneoplastic nature of this.     

CD158k/KIR3DL2 is a new phenotypic marker of Sezary cells: relevance for the diagnosis and follow-up of Sezary syndrome

CD158k molecules belong to the family of killer cell immunoglobulin-like receptors (KIR) that are expressed on a minor population of circulating NK and CD8+ T lymphocytes. Here, we report a strong positive correlation between the percentage of CD158k+ blood lymphocytes analyzed by flow cytometry and the percentage of atypical circulating cells (Sezary cells) determined by cytomorphology in a large group of patients with Sezary syndrome. Moreover, we show that circulating CD4+CD158k+ lymphocytes correspond to the malignant clonal cell population. Our findings suggest that the CD158k marker could be a useful tool for the evaluation of the circulating tumoral burden and the follow-up of patients with Sezary syndrome.