Use of rituximab as an induction therapy in anti-glomerular basement-membrane disease.

BACKGROUND: Anti-glomerular basement-membrane (anti-GBM) disease (or Goodpasture disease) is characterized by severe kidney and lung involvement. Prognoses have improved with treatments that combine plasma exchange and immunosuppressive drugs. However, patients with severe renal involvement can have poor renal outcomes and cyclophosphamide can cause significant complications. Anti-GBM antibodies have a direct pathogenic effect on the disease: thus, therapeutics that can decrease their production, such as rituximab, could be a good alternative. METHODS: The medical files of five patients that had received rituximab as a first-line therapy (instead of cyclophosphamide), plus plasma exchange and steroids, were reviewed. All patients had severe disease manifestations. RESULTS: Four patients required dialysis at diagnosis and remained dialysis-dependent over the mean follow-up of 15 months. Three patients had pulmonary involvement, but recovered even though mechanical ventilation was required. Anti-GBM antibodies became rapidly undetectable in all patients. One infectious and two hematological complications were observed. CONCLUSIONS: We report the outcomes of five patients with Goodpasture disease and treated with rituximab as a first-line treatment. This strategy was effective at treating pulmonary manifestations and was associated with a good biological response with no major serious adverse events. However, renal outcomes were not significantly improved.

[Granulomatous periocular eruption]. / Dermatite périoculaire granulomateuse.

BACKGROUND: Herein, we report a case of atypical periorificial dermatitis in a patient that had been receiving treatment for some time for atopic dermatitis. The specific feature of this rash was its periocular predominance with no perioral involvement, its clinical aspect and its histological picture evocative of sarcoidosis. PATIENTS AND METHODS: A 33-year-old man was being treated for a atopic dermatitis limited to the face and poorly responsive to dermal corticosteroids. Treatment was initiated with topical tacrolimus 0.1%. After 4 years, dependence on this treatment was noted, with daily application being needed to control the lesions. One year later, symmetric lesions were seen on the eyelids and periorbital regions; these were erythematous, micropapular and poorly delineated in a setting of oedema. Biopsy revealed epithelioid granulomatous inflammation, and, to a lesser degree, sarcoidal giant-cell features without caseous necrosis. Staging tests to identify systemic sarcoidosis were negative. Treatment with hydroxychloroquine at 400mg per day and discontinuation of topical tacrolimus resulted in complete remission of the lesions within 2 months. Hydroxychloroquine was discontinued after 6 months, and no relapses had occurred after 2 years of follow-up. DISCUSSION: Three diagnostic hypotheses may be posited for these granulomatous facial lesions. We opted for a diagnosis of granulomatous periorificial dermatitis despite the fact that exclusively periorbital involvement is rare (this condition is generally associated with perioral dermatitis). The second was that of pure cutaneous sarcoidosis, but the topography and clinical appearance of the lesions did not correspond to any of the cutaneous forms classically described. The third was that of tacrolimus-induced granulomatous rosacea, but the histological picture is different. CONCLUSION: The present case underscores the fact that a histological appearance of sarcoidosis on skin biopsy may be associated with perioral dermatitis.

[Lethal Lyell's syndrome induced by fusidic acid]. / Syndrome de Lyell à l'acide fusidique oral d'évolution fatale.

BACKGROUND: Herein, we report the first case of toxic epidermal necrosis due to oral fusidic acid having a fatal outcome. PATIENTS AND METHODS: An 82-year-old woman was referred to our dermatology department for generalized bullous skin eruption. Clinical examination showed fever, oral and ocular ulcerations, and epidermal detachment involving more than 70 % of her body surface area together with a positive Nikolsky sign. Lyell's syndrome was diagnosed. Cutaneous histology showed total epidermal necrosis and a normal dermis. Oral fusidic acid had been prescribed 12 days earlier for a chronic sacral pressure sore. No other treatment had been introduced during the previous two months. The outcome was fatal within 24 hours. DISCUSSION: Fusidic acid is commonly used topically by dermatologists for limited staphylococcal skin infections. Oral treatment is rare and is recommended only for skin, bone or joint infections. This is the first reported case of toxic epidermal necrolysis due to oral fusidic acid. The French national drug safety monitoring register contains only one case in which fusidic acid was a possible culprit. CONCLUSION: Fusidic acid must be considered a potential source of serious cutaneous adverse reactions, particularly toxic epidermal necrolysis.

[Acantholytic dermatosis in patients treated by vemurafenib: 2 cases]. / Deux cas de dermatose acantholytique sous vémurafénib.

BACKGROUND: Acantholytic dyskeratosis under BRAF inhibitors are dermatological diseases rarely reported to date. PATIENTS AND METHODS: We report 2 cases of acantholytic dyskeratosis, reaching the trunk and the seborrheic zones, not itchy, appeared one month after the introduction of vemurafenib. The histological analysis was typical of a "Grover-like rash" for the 2 patients. DISCUSSION: The appearance of acantholytic dyskeratosis under vemurafenib, a BRAF inhibitor, seems related with a paradoxical activation of the MAP-kinases pathway and with a growth acceleration of lesions in which RAS mutations of keratinocytes. Theses dermatoses seem also to occur with dabrafenib. CONCLUSION: The patients treated by BRAF inhibitors (vemurafenib and dabrafenib) can present acantholytic dyskeratosis. The arisen of this mild dermatosis does not question, of course, the continuation of the treatment. These cutaneous manifestations can be managed with emollients.

Nitrosopumilus maritimus genome reveals unique mechanisms for nitrification and autotrophy in globally distributed marine crenarchaea.

Ammonia-oxidizing archaea are ubiquitous in marine and terrestrial environments and now thought to be significant contributors to carbon and nitrogen cycling. The isolation of Candidatus "Nitrosopumilus maritimus" strain SCM1 provided the opportunity for linking its chemolithotrophic physiology with a genomic inventory of the globally distributed archaea. Here we report the 1,645,259-bp closed genome of strain SCM1, revealing highly copper-dependent systems for ammonia oxidation and electron transport that are distinctly different from known ammonia-oxidizing bacteria. Consistent with in situ isotopic studies of marine archaea, the genome sequence indicates N. maritimus grows autotrophically using a variant of the 3-hydroxypropionate/4-hydroxybutryrate pathway for carbon assimilation, while maintaining limited capacity for assimilation of organic carbon. This unique instance of archaeal biosynthesis of the osmoprotectant ectoine and an unprecedented enrichment of multicopper oxidases, thioredoxin-like proteins, and transcriptional regulators points to an organism responsive to environmental cues and adapted to handling reactive copper and nitrogen species that likely derive from its distinctive biochemistry. The conservation of N. maritimus gene content and organization within marine metagenomes indicates that the unique physiology of these specialized oligophiles may play a significant role in the biogeochemical cycles of carbon and nitrogen.

[Dermatologic follow-up and evaluation of skin tumours in renal transplant patients]. / Evaluation du suivi dermatologique et des tumeurs cutanées chez les greffés rénaux.

BACKGROUND: Renal transplant patients are at increased risk for warts, actinic keratoses and carcinomas. A descriptive study was conducted to investigate the number and frequency of dermatologic examinations in renal transplant patients with a functional graft. The incidence and clinical factors for skin tumours were also assessed. PATIENTS AND METHODS: We sent an initial questionnaire to 686 renal transplant patients asking whether they had consulted a dermatologist since the time of transplantation. A second questionnaire was then sent to private dermatologists in order to evaluate dermatologic follow-up and the frequency and anatomic distribution of warts and cancerous skin lesions. At the same time, the patients' medical records at the hospital were studied. RESULTS: About two thirds of the 436 patients included in the study have seen a dermatologist at least once since the time of transplantation. Only 31.2% are being followed up regularly by a dermatologist. The incidence of warts and actinic keratoses is 48.8% and 20.6% respectively, and increases with the duration of immunosuppressive therapy. The incidence of carcinomas is 20.2%, with basal cell carcinomas being seen more frequently than other carcinomas. Risk factors identified for carcinomas are older age at transplantation, duration of immunosuppressive therapy, fair skin, presence of warts and actinic keratoses. All these skin lesions arise predominantly on highly sun-exposed surfaces. Nevertheless, squamous cell carcinomas are more often confined to sun-exposed skin than Bowen's diseases and basal cell carcinomas. DISCUSSION: Dermatologic follow-up of transplant recipients has rarely been investigated and our study shows that monitoring of skin cancer is probably inadequate. It also confirms the high incidence of carcinomas among renal-transplant recipients in a temperate climate, although basal cell carcinomas are more frequent than squamous cell carcinomas.

[Acute tubulointerstitial nephritis following adenovirus and respiratory syncytial virus infection]. / Néphrite tubulo-interstitielle aiguë au cours d'une virose respiratoire à adénovirus et virus respiratoire syncytial.

Acute tubulointerstitial nephritis (TIN) is responsible for nearly 10% of acute renal failure (ARF) cases in children. It is mostly drug-induced, but in a few cases viruses are involved, probably by an indirect mechanism. An immune-competent 13-month-old boy was admitted to the intensive care unit for severe ARF with anuria in a context of fever, cough, and rhinorrhea lasting 1 week. The kidney biopsy performed early brought out tubulointerstitial damage with mild infiltrate of lymphocytes, without any signs of necrosis. There were no virus inclusion bodies, no interstitial hemorrhage, and no glomerular or vascular damage. Other causes of TIN were excluded: there was no biological argument for an immunological, immune, or drug-induced cause. Adenovirus (ADV) and respiratory syncytial virus (RSV) were positive in respiratory multiplex polymerase chain reaction (PCR) in nasal aspirate but not in blood, urine, and renal tissue. The patient underwent dialysis for 10 days but the response to corticosteroid therapy was quickly observed within 48 h. The mechanism of TIN associated with virus infection is unknown. However, it may be immune-mediated to be able to link severe renal dysfunction and ADV and/or RSV invasion of the respiratory tract.

Thymolipoma in association with myasthenia gravis.

A 52-year-old male presented with an anterior mediastinal tumor associated with a 2-year history of myasthenia gravis. The patient underwent thymectomy and a 185-g, 10 X 8 X 3.5 cm, well-delineated tumor was resected. On histologic examination the tumor proved to be a thymolipoma composed of mature adipose elements containing cords and nests of thymic tissue. The latter consisted mainly of cortical areas, the thymocytes of which displayed an immunohistochemical profile of cortical cells, i.e., CD 1+, CD 4+, CD 8+, and frequently Ki 67+. Ultrastructural study confirmed the predominant cortical differentiation of the thymic component. No germinal centers, dendritic reticulum cells, or myoid cells were detected by histologic, immunohistochemical, and ultrastructural studies. The association of thymolipoma with myasthenia gravis is rare; this case is the 10th reported. Our findings lead us to believe that (a) the cortical differentiation of the thymic component and the active thymocyte proliferation could represent a factor leading to myasthenia gravis; and (b) thymolipoma could be a peculiar form of thymoma rather than a mixed tumor of mesenchymal and entodermal origin, a lipoma, or a hamartoma of the thymic gland. The reported association of thymolipomas with other immune disturbances or with neoplastic conditions usually associated with true thymomas support these findings.

Ultrastructural localization of the major components of the extracellular matrix in normal rat nerve.

In this study we determined the ultrastructural distribution of the various components of the extracellular matrix (laminin, fibronectin, Type I, III, and IV collagens) of the normal peripheral nerve in adult rat. The localization of these macromolecules was investigated in basement membranes as well as in different areas of epi-, peri-, and endoneurium, by use of a pre-embedding immunoperoxidase method.

Schwannoma of the bulbar conjunctiva.

We describe a conjunctival tumor that occurred in the limbic region of the left eye in a 37-year-old man. The mass was located beneath the conjunctival epithelium. It consisted of a well-demarcated proliferation of fusiform cells arranged in bundles in a fibrous stroma. Tumor cells strongly expressed S-100 protein. On ultrastructural analysis, the tumor was composed of Schwann cells surrounded by a continuous basal lamina. These data led to the rare diagnosis of conjunctival schwannoma.

Human herpesvirus 8 and Epstein Barr-virus in a cutaneous B-cell lymphoma and a malignant cell line established from the blood of an AIDS patient.

Human Herpesvirus 8 (HHV-8) has been consistently associated with Primary Effusion Lymphoma (PEL or body-cavity-based lymphoma) but not with other lymphomas. This paper reports on an AIDS patient without obvious malignant effusion in body cavities but with a cutaneous lymphoma where HHV-8 and Epstein-Barr virus (EBV) were detected by PCR and electron microscopy. Both viruses were also detected in all the cells of a malignant cell line (BBG1) established from the patient's peripheral blood mononuclear cells. As in PEL and PEL-derived cell lines, both the tumor and the lines lacked B-antigen expression in immunological studies but were of the same B origin as shown by clonal immunoglobulin gene rearrangements. In contrast to other co-infected cell lines, BBG1 and subclones spontaneously expressed the HHV-8 lytic antigens p40, p27, p60 and the EBV transforming latent antigen EBNA2. These data suggest that the clinical and biological features of HHV-8-and EBV-associated lymphomas could be wider than has been described to date in PEL particularly with the in vivo presence of circulating malignant dually-infected cells engaged in a spontaneous HHV-8 lytic infection.

[Primary synovial sarcoma of the mediastinum. A case report with immunohistochemistry, ultrastructural and cytogenetic study]. / Synovialosarcome primitif du médiastin. Une observation anatomoclinique avec étude immunohistochimique, ultrastructurale et cytogénétique.

A biphasic synovial sarcoma occurring in the anterior and inferior mediastinum in a 19-year-old woman is reported. A biopsy showed a mesenchymal proliferation and the tumor was first misdiagnosed as a hemangiopericytoma. Inefficacy of chemotherapy led to a tumorectomy. Histologic and immunohistochemical studies on multiple samples showed a biphasic tumor. Ultrastructural study confirmed the presence of epithelial elements and cytogenetic analysis disclosed a translocation t(X;18) (p11;q11), leading to a diagnosis of synovial sarcoma. Synovial sarcoma of the mediastinum is very rare and to our knowledge has not been previously studied with the help of cytogenetics. Given the biphasic pattern of the tumor and its mediastinal location, it can be confused with mesothelioma. This stresses the interest of chromosome analysis in the study of tumors histologically difficult to classify.

[Heterogeneity of nephropathies in type 2 diabetes]. / Hétérogénéité de la néphropathie chez les diabétiques de type 2.

DIVERSE KIDNEY DISORDERS: Patients with type 2 diabetes mellitus who develop nephropathy can have various types of disorders capable of progressively destroying the kidneys. It is now clear that the same type of diffuse or nodular glomerulosclerosis develops irrespective of the type of diabetes, i.e. the pathophysiology of hyperglycemia. HETEROGENEITY: There is however a certain degree of heterogeneity in terms of clinical presentation, clinical course and response to treatment. Heterogeneity is due to age, the number of different accumulated risk factors and disease states, genetic factors that are in the process of being identified, and finally, lesions to the urologic apparatus, the arteries, and the renal parenchyma itself that are not directly caused by diabetes. PRACTICAL IMPACT: Mixed lesions, due to both diabetic and non-diabetic causes, may therefore exist in the same kidney. These different possibilities should be systematically considered in order to adopt an individualized investigative and therapeutic attitude for each new patient.

[Fluindione-induced acute exanthematous pustulosis with renal involvement]. / Pustulose exanthématique aiguë généralisée à la fluindione avec atteinte rénale.

INTRODUCTION: Fluindione (Previscan) is an oral anti-vitamin K anticoagulant, widely prescribed in France. Contrary to phenindione, which is also an indanedione derivative, very few cases of immunoallergic reactions have been described. CASE REPORT: A 68 year-old man, treated with fluindione for cardiac arrhythmia, presented with a pustular eruption and erythema twenty days after initiation of treatment. The eruption was associated with hyperthermia, arthralgia, neutrophilia (11,000/mm2), hepatic cytolysis and renal involvement including acute renal failure, hematuria and proteinuria. In view of the absence of any earlier case in the literature, we did not impute fluindione and the drug was reintroduced and led to the rapid recurrence of all the same manifestations. DISCUSSION: These manifestations were consistent with an immunoallergic reaction to fluindione (probable intrinsic imputability I3) and acute interstitial nephritis (probable intrinsic imputability I3). We believe this is the first case of acute generalized exanthematous pustulosis induced by fluindione (intrinsic imputability Bo). A few rare cases of fluindione-induced hypersensitivity reactions and acute interstitial nephritis, however, have been described.

Hunter's syndrome and associated sleep apnoea cured by CPAP and surgery.

A 42-yr-old male with Hunter's syndrome presented with severe obstructive sleep apnoea syndrome (OSAS) and daytime respiratory failure. Continuous positive airway pressure (CPAP) therapy was initially ineffective and produced acute respiratory distress. Extensive Hunter's disease infiltration of the upper airway with a myxoma was confirmed. Following surgery to remove the myxoma at the level of the vocal cords, CPAP therapy was highly effective and well tolerated. This report demonstrates the necessity of evaluating fully the upper airway in patients with unusual variants of OSAS, particularly where the disease is not adequately controlled by CPAP.