Le pemphigus paranéoplasique: revue de la littérature, à propos d'un cas associé à une leucémie lymphoïde chronique

In 990, Anhalt et al described a newly autoimmune billious disease: paraneoplastic pemphigus, in five patients. It was characterized by a distinct set of circulating autoantibodies from those in the sera of patients with pemphigus vulgaris and superficial pemphigus. We report a 7 year-old man with chronic lymphocytic leukemia of years duration who developed a severe mucocutaneous eruption with clinical and immunofluorescence findings of pemphigus vulgaris evolving into an oral bullous lichen planus presentation. Evaluation of his serum confirmed the presence of autoantibodies specific for paraneoplastic pemphigus by indirect immunofluorescence on rat-bladder and immunoprécipitation. Subsequently, additional cases have been reported in the literature. All occured in patients with various neoplastic conditions. These patients present with polymorphous skin lesions and severe erosive oral disease. Histologic examination shows interface dermatitis and keratinocyte necrosis in addition to acantolysis. Direct immunofluorescence may reveal deposition of immunoglobulin and/or complement at the basement membrane as well as deposition on epithelial cell surfaces. Circulating IgG anti-cell-surface antibodies are detectable with both stratified and stratified epithelia as substrates. These antibodies immunoprecipitate a complex of four desmosomal proteins, including desmoplakin I (50 kDa), the bullous pemphigoid antigen (0 kDa), desmoplakin II (0 kDa) and a 90 kDa antigen.     

Les syndromes confusionnels du sujet âgé hospitalisé: polymorphisme sémiologique et évolutif. Étude prospective de 183 patients

Using explicit criteria contained in the DSM III R, we collected in a prospective cohort study clinical features, outcome and risk factors from two cohorts of delirium in hospitalized elderly patients: 138 hospitalized in geriatric department and 45 patients admitted to an acute and comprehensive care hospital. The clinical features were assessed using a quantitative scale (developed by Derouesné). Delirium was unrecognized or misdiagnosed by physicians in 34% of the cases. The onset was known only two thirds of cases. The incidence of hyperactive type, prolonged hospital stay, poor outcomes (persistent delirium leading up to dementia) were highest in subjects admitted in comprehensive hospital. The etiology of delirium is complex and multifactorial. An underlying cause was identified in 80% of patients. The length or the worsening of delirium was significantly higher in patients with psychiatric or dementia comorbidity (OR: 0.2; IC 95%: 0.1–0.5). The prognosis was better in patients without psychoactive medications (OR: 0.2; IC 95%: 0.1–0.4) or with metabolic abnormalities or acute diseases and disorders (OR: 3.3; IC 95%: 1.5–7.6). The predisposing factors to the development of dementia were prior use of psychoactive medications and signs of prior cognitive impairment. This article suggests delirium in elderly patients is associated with several outcomes. The prognosis should be improved at admission by specific scale and an evaluation of predisposing and precipitating factors.     

« Sclérose en plaques plus » :les leucoencéphalopathies aux frontièresde la médecine interne“Multiple sclerosis plus”: frontiers between multiple sclerosis and a new nosological entity.

Introduction. – Multiple sclerosis (MS) is an inflammatory, demyelinating and probably autoimmune disease affecting the white matter of the central nervous system (CNS). Due to the absence of specific clinical and laboratory markers, diagnosis remains difficult.Current knowledge and key points. – In particular, no clinical or paraclinical investigation is satisfactory to distinguish definite MS from other autoimmune or inflammatory diseases, especially when they predominantly affect  the CNS. Moreover, previous studies have reported that patients with definite MS could present clinical systemic signs suggestive of other inflammatory or autoimmune diseases, and that MS could be associated with other autoimmune diseases. On the other hand, the presence of biological autoimmune abnormalities, including antinuclear antibodies and antiphospholipid antibodies, has been observed, with a high frequency in patients with MS in comparison to control populations. These clinical and laboratory features could therefore represent a new nosological entity characterized by a systemic immune dysregulation more extensive than the CSN target, or a distinct subgroup of MS patients with a classical course of the disease. Because of the impact of the new therapeutic approach to MS, an important issue concerning this aspect that should be addressed is the use of immunomodulatory therapy, especially with interferon beta. It appears necessary to consider these abnormalities before treating MS patients with preventive therapy, in particular in the perspective of new strategies, such as treatment at an early stage of the disease or combination therapies.     

A case of nasal‐type NK/T cell lymphoma in a patient with dermatomyositis

The association of malignancy with dermatomyositis is well known, and the frequency is reported to be up to 30%. However, cutaneous lymphoma associated with dermatomyositis has rarely been reported. We experienced a case of nasal‐type NK/T‐cell lymphoma in a 40‐year‐old woman with a 2‐year history of dermatomyositis. To our knowledge, this is the first report of cutaneous involvement of nasal‐type NK/T‐cell lymphoma developing in a dermatomyositis patient. When skin lesions are resistant to aggressive conventional treatment in dermatomyositis patients, we should consider the possibility of malignancy, especially cutaneous lymphoma.     

Analysis of p53 and mdm-2 expression in 18 patients with Sézary syndrome

Sézary syndrome is a leukaemic form of cutaneous T-cell lymphoma which presents with multiple cytogenetic abnormalities and responds poorly to chemotherapy. Because of the importance of the p53 tumour suppressor in maintaining genomic stability and in sensitizing transformed cells to DNA damaging agents, we looked for alterations which may affect p53 functions in 18 patients with Sézary syndrome. Cytogenetic analysis suggested frequent p53 gene inactivation since 6/18 patients had loss of one copy of 17p. However, single-strand conformational polymorphism (SSCP) revealed that p53 gene mutations are relatively rare, occurring in only two of 18 Sézary patients. Neither of these two patients was missing a copy of 17p. Possible abnormalities of p53 pathway function through mdm-2 over-expression were also investigated. Although all 18 patients had normal levels of mdm-2 RNA, 4/18 over-expressed mdm-2 protein. One patient with advanced disease and the highest percentage of malignant cells overexpressed mdm-2 protein and possessed a nonsense p53 gene mutation. The five patients with abnormalities of p53 or mdm-2 were found to have significantly higher absolute lymphocyte counts and higher absolute numbers of Sézary cells (P = 0.021 and 0.027 respectively). In summary, molecular alterations of 17p and potential p53 pathway abnormalities are a common event in Sézary syndrome and appear to be associated with more advanced disease.     

Gamma‐delta t‐cell lymphomas

Gamma‐delta T‐cell lymphomas are aggressive and rare diseases originating from gamma‐delta lymphocytes. These cells, which naturally play a role in the innate, non‐specific immune response, develop from thymic precursor in the bone marrow, lack the major histocompatibility complex restrictions and can be divided into two subpopulations: Vdelta1, mostly represented in the intestine, and Vdelta2, prevalently located in the skin, tonsils and lymph nodes. Chronic immunosuppression such as in solid organ transplanted subjects and prolonged antigenic exposure are probably the strongest risk factors for the triggering of lymphomagenesis. Two entities are recognised by the 2008 WHO Classification: hepatosplenic gamma‐delta T‐cell lymphoma (HSGDTL) and primary cutaneous gamma‐delta T‐cell lymphoma (PCGDTL). The former is more common among young males, presenting with B symptoms, splenomegaly and thrombocytopenia, usually with the absence of nodal involvement. Natural behaviour of HSGDTL is characterised by low response rates, poor treatment tolerability, common early progression of disease and disappointing survival figures. PCGDTL accounts for <1% of all primary cutaneous lymphomas, occurring in adults with relevant comorbidities. Cutaneous lesions may vary, but its clinical behaviour is usually aggressive and long‐term survival is anecdotal. Available literature on gamma‐delta T‐cell lymphomas is fractioned, mostly consisting of case reports or small cumulative series. Therefore, clinical suspicion and diagnosis are usually delayed, and therapeutic management remains to be established. This review critically analyses available evidence on diagnosis, staging and behaviour of gamma‐delta T‐cell lymphomas, provides recommendations for therapeutic management in routine practice and discusses relevant unmet clinical needs for future studies.     

Characteristics and prognosis of KI-1 positive anaplastic large cell lymphoma in Asians

Background : Ki-1 positive anaplastic large cell lymphoma is a rare type of non-Hodgkin's lymphoma (NHL), and has not been extensively described in Asian patients.
Aim : To evaluate the clinical characteristics, prognostic factors and treatment outcome of Ki-1 positive lymphoma in an Asian community.
Methods : A retrospective analysis of all patients with CD30 antigen positive anaplastic large cell lymphoma from 1987 to 1996 in a single institution.
Results : Of 218 patients with NHL, ten (5%) were identified with Ki-1 positive anaplastic large cell lymphoma. Eight were Chinese, two Indians. The male: female ratio was 1.5:1, and the median age was 32 years. Seven patients presented with B-symptoms, and five had stage III/IV disease. The majority (seven of ten) was low-or low-intermediate risk according to the International Prognostic Index (IPI). Four out of five cases immunophenotyped showed a T-cell origin. Five out of eight patients who received first-line combination chemotherapy achieved a complete remission. Two relapsed, with one being re-induced into a durable second remission. One patient with recurrent cutaneous lymphoma received solely radiotherapy and was disease-free at 20+ years from diagnosis. At analysis, two patients had died, five were disease-free at four, 27, 78, 89 months and 20 years respectively, and three were alive with disease. The IPI appears to have prognostic significance.
Conclusion : Incidence and clinical characteristics in our Asian patients were similar to those described in Western populations. The IPI appears to have prognostic relevance. In approximately one-third of patients, long term survival can be achieved with standard treatment.     

Hodgkin's lymphoma initially presenting with polymyalgic symptoms: a case report

The association of polymyalgic symptoms and lymphoma is a rare event whose pathogenesis remains to be clarified. Here, we describe a case of a 75-year old man with Hodgkin's lymphoma, who had presented with polymyalgic symptoms suggesting polymyalgia rheumatica. An intensive investigation with respect to malignancy was initially negative. Corticosteroid treatment was administered first and a dramatic clinical improvement was achieved. Four months later, when the corticosteroid treatment was tapered off, the initial manifestations reappeared. After the development of lymph node enlargement, the patient was diagnosed by lymph node biopsy as having Hodgkin's lymphoma. The lymphadenopathy and musculoskeletal manifestations all responded well to chemotherapy. Hodgkin's lymphoma should be considered in the differential diagnosis of PMR. These musculoskeletal syndromes should alert the physician to possible paraneoplastic manifestations of an evolving neoplasm.     

Photosensibilité du lupus érythémateux

Photosensitivity is one of the ARA diagnostic criteria of systemic lupus erythematosus. Sun exposure can also induce extracutaneous manifestations of the disease. Photosensitivity may be difficult to prove by history taking in lupus patients, as the delay between sun exposure and the onset of specific skin lesions is rather long. Photo-induction of lupus can occur by ultraviolet A (UVA) radiation in the shadow or behind window glass, so that the relationship between radiation exposure and exacerbation of the disease may not seem obvious to the patient. Phototesting procedures for lupus erythematosus have been described, but they are not used in routine practice. Both UVB and UVA play a role in the pathogenesis of lupus erythematosus: in the epidermis they induce DNA damage, they expose nuclear antigens and photo-induced neo-antigens at the cell surface, they lead to an accumulation of apoptotic material, and they induce several pro-inflammatory cytokines. In the dermis, UV radiation triggers skin infiltration by inflammatory cells by modulation of microvascular flow rates and by upregulation of white blood cell migration from dermal capillaries to the skin. Photodistribution of skin lesions and a delay of their onset of more than 48 hours after sun exposure are clinical hallmarks of cutaneous lupus erythematosus that are usually completed by histological confirmation. Photoprotection is essential in the treatment of lupus patients: it comprises sun avoidance suitable for both UVB and UVA radiation, protective clothing, and topical broad-spectrum filters.     

Cutaneous presentation of disseminated cytomegalovirus infection in a non-transplant patient with hematological malignancy: A case report

Rationale:Cytomegalovirus (CMV) disease is relatively uncommon in nontransplant hematological patients. Moreover, cutaneous manifestations of CMV diseases have scarcely been reported and are probably under-recognized.Patient concerns:We describe a patient with large B-cell lymphoma who developed a band-form, erythematous lesion over his left abdomen soon after the second course of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone chemotherapy.Diagnoses:The lesion was initially mistaken for bacterial cellulitis or herpes zoster and was histologically confirmed as cutaneous CMV infection. Subsequent work-up also detected CMV viremia and the presence of CMV meningoencephalitis.Interventions:The patient was treated with ganciclovir plus CMV immune globulin followed by foscarnet.Outcomes:Although the patient''s cutaneous lesion resolved, his cognitive impairment did not recover, and he developed a fatal multi-organ failure 1 month later.Lessons:Cutaneous CMV disease can herald multisystem involvement and an unfavorable prognosis in immunocompromised hosts. It should be ruled out with biopsy in patients with hematological malignancy who have cutaneous lesions refractory to antibacterial therapy.     

Efficacité clinique de l’enzymothérapie dans la maladie de Fabry. Analyse critique

Fabry disease is a X-linked lysosomal storage disorder. Two preparations of the enzyme α-galactosidase A are available in Europe since 2001: agalsidase alpha and agalsidase beta. Clinical evidence of efficacy are mandatory considering the absence of a robust biomarker. A literature review was performed to assess the clinical efficacy of these two enzyme replacement therapies. Only open or randomised controlled trials were considered. No unflawed direct comparison exists between the two drugs. Significant clinical benefits have been demonstrated with enzyme replacement therapy (ERT), mainly at an early phase of the disease, with positive effects on heart, kidneys, pain, and quality of life. Further prospective studies are required to confirm the long term clinical benefits of ERT. More specific studies are also needed in women or with ERT earlier in the course of Fabry disease to assess prevention of organ damage.     

Favorable outcome of primary cutaneous marginal zone lymphoma treated with intralesional rituximab

Primary cutaneous marginal zone lymphoma (PCMZL) is an indolent disease. Treatment options include excision, local irradiation, interferon-alpha or chemotherapy. We present two patients with PCMZL and multiple skin lesions successfully treated with intralesional administration of the anti-CD20 monoclonal antibody rituximab. The first presented with four red skin lesions and the second with two. Biopsy of the largest lesion revealed marginal zone B-cell lymphoma in both patients. There was no evidence of systemic involvement in either patient. Both patients were treated with intralesional rituximab for 18 consecutive weeks. Skin lesions gradually regressed. Apart from mild local pain during the injection, no other adverse effects were observed. In conclusion, rituximab can be safely administered intralesionally in patients with PCMZL and can produce disease remission.     

Sarcoïdose au cours du traitement de l’hépatite C par interféron alpha et ribavirine : deux casSarcoidosis during the treatment of hepatitis C by interferon-alpha and ribavirin: two cases.

Introduction. – Interferon-alpha (IFNα) used to treat chronic hepatitis C can be responsible for some side effects. We report two cases of sarcoidosis which appeared in patients treated with IFNα and ribavirin for chronic hepatitis C.Exegesis. – A first patient, treated for 5 months with IFNα and ribavirin because of chronic hepatitis C, after the failure of a first treatment with IFNα alone, was hospitalized for dyspnea. The chest X-ray and scanner revealed an interstitial syndrome and mediastinal adenopathies. Biopsies of bronchial spurs revealed epithelioid and giganto-cellular granuloma. After discontinuation of antiviral treatment and starting corticosteroid therapy, the evolution was favourable but viremia reappeared. A second patient with IFNα and ribavirin for 4 months because of chronic hepatitis C (after the failure of a first treatment with IFNα alone) was hospitalized for fever, arthralgias, erythema nodosa and modification of previous skin scars. The biopsy of a scar showed an epithelioid and giganto-cellular granuloma. After discontinuation of antiviral therapy and starting corticosteroid treatment, the evolution was favourable.Conclusion. – Some publications mention occurrence of sarcoidosis during IFNα therapy, occasionally associated with ribavirin, disappearing after discontinuation of the treatment, though sometimes corticotherapy is necessary. The roles of IFNα and ribavirin are discussed.     

经支气管镜治疗支气管肿瘤

经支气管镜治疗支气管肿瘤张保金，赵忠忱近十几年来经气管镜治疗的方法已有多种，技术亦日益提高，特别对气管支气管肿瘤的治疗更逐步普及，这是重新打开大气道的阻塞和狭窄，迅速缓解患者呼吸困难和濒临窒息的有效方法。一、适应症的选择：支气管肺癌开始均在支气管粘膜...     

恶性淋巴瘤误诊结核病27例分析

目的　探讨误诊为结核病的淋巴瘤的临床特征和误诊原因。方法 回顾分析1990—2003年27例误诊为结核的恶性淋巴瘤病人的临床特征、影像学特点、病理结果、诊断和治疗。结果 其临床特征无特异性,约8例(29%)无症状,发热19例(70%),咳嗽8例(29%),咯血1例(0.4%),淋巴结肿大22例,其中单一部位6例,多部位16例,其影像学特点是肿块结节样病变10例,弥漫性病变5例,肺门增大11例,胸腔积液10例。误诊淋巴结核6例,误诊肺结核5例,误诊肺结核并淋巴结核10例,误诊肺结核并结核性多浆膜腔积液4例,误诊结核性多浆膜腔积液2例。确诊方式:淋巴结摘除病理活检22例,经纤支镜肺活检2例,经皮肺活检3例。病理结合免疫组化诊断霍奇金病7例,非霍奇金病20例。治疗以放化疗为主,预后差。结论 因二者临床特征相似,易误诊,及时早期获得组织病理标本是早期诊断的关键。     

High frequency of primary cutaneous lymphomas associated with lymphoproliferative disorders of different lineage

In patients suffering from primary cutaneous lymphomas, secondary malignancies of various origin may develop. However, the frequency of a second neoplasm deriving from another lymphoid lineage is still unclear and may be underestimated. We screened all our patients with primary cutaneous lymphomas from a 4-year recruitment period for a coexisting secondary lymphoproliferative disorder. The cohort comprised of a total of 82 patients with primary cutaneous lymphomas, 62 with primary cutaneous T-cell lymphoma (CTCL), 18 with primary cutaneous B-cell lymphomas, and two with CD4+/CD56+ hematodermic neoplasm/blastic lymphomas. Seven patients (8.5%) were identified with a coexisting lymphoma of a different lymphoid lineage. Four patients with Sézary syndrome (SS) suffered from systemic B-cell lymphoma. Two of these developed SS after chemotherapy of their B-cell lymphoma. The other three patients with various types of skin lymphomas (SS, Mycosis fungoides [MF], primary cutaneous marginal zone lymphoma) developed Hodgkin’s disease (hairy cell leukemia). Our data indicate that patients with primary cutaneous lymphomas have an elevated risk for the development of a secondary lymphoproliferative disorder even without previous chemotherapy. Possible explanations for this association include a genetic predisposition, alterations in early progenitor cells, underlying viral infections, and/or stimulation of a B-cell clone by the malignant helper T cells of the primary CTCL and vice versa.     

Large mucosa‐associated lymphoid tissue lymphoma simulating multiple polypoid lesions at the cecum and rectum

Herein we describe a case of mucosa‐associated lymphoid tissue (MALT) lymphoma of the cecum and rectum with the Leser–Trélat sign. A 76‐year‐old Japanese woman was admitted to the Harima Hospital of Ishikawajima‐harima Heavy Industries, Health Insurance Society for hematochezia. Colonoscopy showed two large elevated tumors, one in the cecum and the other in the rectum. Biopsy was not diagnostic. Endoscopic snare loop biopsy specimens from both tumors were diagnosed as MALT lymphoma. After staging to IIE, the patient underwent surgery. Macroscopically, the cecal tumor was elevated with a large and deep depressed region, measuring 40 × 35 mm. The rectal lesion was a large elevated tumor, measuring 80 × 70 mm. Histologically, both tumors were diagnosed as MALT lymphoma and there was no lymph node metastasis. The patient received chemotherapy and there is no evidence of recurrence 1 year after surgery. We present this case to show that colorectal MALT lymphoma can present as a large tumor, even in early clinical stages, that multiple lesions should be anticipated and that surgical treatment is needed in these cases.     

Cutaneous presentation of progressive disseminated histoplasmosis nine years after renal transplantation

Initial presentation of invasive fungal infections such as histoplasmosis can include non‐specific clinical manifestations, especially in immunocompromised patients. A high index of suspicion is required to identify atypical manifestations of these diseases, which carry a high risk of mortality, if the diagnosis is delayed or missed. We describe a case of a kidney transplant recipient with cutaneous lesions as initial manifestation of progressive disseminated histoplasmosis where a skin biopsy was crucial to an early diagnosis.     

Les gammapathies monoclonales de signification indéterminéeMonoclonal gammopathy of undetermined significance.

Introduction. – Monoclonal gammopathy of undetermined significance is an asymptomatic disorder associated with serum monoclonal immunoglobulin spike. Its incidence is about 1% in patients of 50 years of age, and rapidly increases in elderly patients.Current knowledge and key points. – Within the 20 years following diagnosis, about 25% of patients will evolve towards either multiple myeloma (for patients with IgG or Ig A) or malignant lymphoproliferative disorder (for patients with IgM). Definition, circumstances associated with a transient monoclonal spike, and currently available parameters used for differential diagnosis with either multiple myeloma or malignant lymphoproliferative disorder are successively discussed. One part of the most usual biological parameters is of prognostic value, and is reviewed in more detail. Recent data concerning immunophenotype, cytogenetics and molecular biology of plasma cells reinforce the link between the asymptomatic condition and multiple myeloma. In monoclonal gammopathy of undetermined significance, some plasma cells resemble normal or reactive plasma cells, whereas others mimic those found in multiple myeloma.Future prospects and projects. – The most recent biological data are also discussed in order to evaluate whether some would help to discriminate those patients who will remain asymptomatic lifelong from those who will evolve towards multiple myeloma.     

胃镜在胃原发性恶性淋巴瘤诊断中的价值

为近一步探讨胃原发性恶性淋巴瘤的发病机制．提高对胃原发性恶性淋巴瘤胃镜及病理表现的认识，对１０年间经胃镜活检诊断为胃恶性淋巴瘤的１９例，可疑胃恶性淋巴瘤、低分化癌、未分化癌、溃疡及淋巴组织明显增生的１２１例病理标本、临床资料进行回顾复习，最后确认有３８例符合胃恶性淋巴瘤的诊断标准。，胃镜下多形性、多灶性、弥漫性、范围广是其特征表现，而组织学上粘膜相关淋巴组织的特点对确诊本病有重要意义。