Comparison of real costs in the French healthcare system in newly diagnosed patients with pemphigus for first-line treatment with rituximab vs. standard corticosteroid regimen: data from a national multicentre trial.

BACKGROUND: Rituximab has been demonstrated to be highly effective as a first-line treatment for moderate-to-severe pemphigus; however, its high cost can be considered a limitation of this treatment. OBJECTIVES: To compare direct costs of two regimens, rituximab + short-term prednisone vs. prednisone alone, tested in the Ritux3 trial. METHODS: Patients were randomly assigned to receive 2 g of rituximab and two 500-mg maintenance infusions at month 12 and month 18 along with low doses of prednisone for 3-6 months, or high doses of prednisone alone tapered over 12-18 months. We estimated the direct costs related to (i) protocol (treatments, consultations, hospitalizations); (ii) unfavourable disease course (relapse); and (iii) adverse events in both treatment groups during a 3-year follow-up. RESULTS: Annual individual cost discrepancies related to drugs decreased from +€3597 to -€1589 from the first to the third year, which corresponded to an initially higher cost in the rituximab group, counterbalanced during follow-up by costs related to treatment of patients with persistent disease activity/relapses in the standard corticosteroid (CS) group. Individual costs relating to treatment of adverse events were higher in the standard CS group (€4352) than in the rituximab group (€2468). Overall, mean individual total cost over the 3 years of follow-up was €13 997 in the standard CS arm vs. €14 818 in the rituximab arm, corresponding to a difference of €821 more per patient (+6%). CONCLUSIONS: First-line treatment of pemphigus with rituximab results in a slightly greater cost compared with a standard CS regimen. What's already known about this topic Rituximab is the most effective treatment for moderate-to-severe pemphigus. Rituximab cost might be considered as a limitation of this treatment. What does this study add? After 3 years of follow-up, mean individual total cost for a patient with first-line treatment with rituximab was €14 818 vs. €13 997 with standard corticosteroids (CS), resulting in a slightly higher cost of €821 (+6%). The initially greater cost of rituximab was counterbalanced by costs related to management of flares/relapses in patients treated with a standard CS regimen.

[Syphilitic osteitis in an HIV-negative patient]. / Ostéite syphilitique chez un patient séronégatif pour le VIH.

BACKGROUND: Secondary syphilis with skeletal involvement is rare; herein we report a case concerning an HIV-negative patient. PATIENTS AND METHODS: During the course of secondary syphilis, a 28-year-old male homosexual, HIV-negative and with no medical history, presented intense and localized headaches persisting despite three weeks of antibiotic therapy. Bone scintigraphy revealed three bone lesions evocative of syphilitic osteitis, for which prolonged antibiotic therapy was instituted. DISCUSSION: Few cases of syphilitic osteitis have been described in the recent literature and these are linked to haematogenous diffusion of Treponema pallidum. Skeletal disease is suggested when febrile bone pain is present. Bone scintigraphy remains the best diagnostic tool and treatment comprises prolonged penicillin G or ceftriaxone.

[Charcot-Marie-Tooth disease associated with periaxin mutations (CMT4F): Clinical, electrophysiological and genetic analysis of 24 patients]. / Maladie de Charcot-Marie-Tooth associée au gène de la périaxine (CMT4F) : description clinique, électrophysiologique et génétique de 24 patients.

Autosomal recessive Charcot-Marie-Tooth disease (AR-CMT) is often characterized by onset in early childhood and severe phenotype compared to the dominant forms. CMT disease associated with periaxin gene (PRX) is rare and characterized by demyelination limited to the major peripheral nerves. Following the discovery of a high frequency of a specific periaxin gene mutation (E1085fsX4 homozygote) in the Reunion Island, we examined all French patients known as carriers of the periaxin gene mutation. There were 24 patients. Eighteen were from the Reunion Island (6 families and 10 sporadic cases). The six remaining patients were in two families, each with two affected individuals, and two sporadic cases. The series included 17 female and seven male patients. Walking was acquired late, on average at 3.4±1.6 years. One patient never learned to walk. The Charcot Marie Tooth Neuropathy Score (CMTNS) averaged 24.5±8.1. Seven patients had been wheelchair-bound since the age of 24±22. Other symptoms were: scoliosis most often observed after the age of 12 years and sometimes complicated by a restrictive respiratory syndrome; foot deformity in 24 patients; strabismus; glaucoma; myopia. When conduction recordings are available, median nerve motor conduction was slow (<10m/s), associated with a major lengthening of distal latencies. Study of the periaxin gene should be considered in patients with severe demyelinating neuropathy associated with early infantile scoliosis. This disease leads to major disability (29% of patients in this series were wheelchair-bound) and to respiratory insufficiency. Genetic counselling is highly recommended for consanguineous families.

SKH-1 mouse skin painting: a short-term assay to evaluate the tumorigenic activity of cigarette smoke condensate.

The hairless mouse strain SKH-1 was investigated in a short-term assay to assess the tumorigenic activity of mainstream cigarette smoke condensate (CSC). The design chosen was the two-stage dermal tumorigenicity assay (skin painting), with tumor initiation using a single dermal application of the carcinogen/mutagen dimethylbenz(a)anthracene applied to the back at a non-tumorigenic dose and tumor promotion by repeated dermal applications of CSC at the same site. The mice reproducibly developed skin tumors at the application site after 15 weeks at a frequency that allowed comparison of the treatment groups. The histopathological examination revealed the benign nature of the tumors (keratotic papillomas). Prolongation of the application period to 25 weeks resulted in the development of malignant tumors (carcinomas), indicating that the benign tumors after 15 weeks can be taken as surrogate endpoints for malignancies progressing after further treatment. After 15 weeks, tumor incidence (the percentage of tumor-bearing mice), tumor multiplicity (the number of tumors per mouse), and tumor-onset (the duration of the application period that resulted in a meaningful tumor incidence) were positively correlated with the initiating and promoting dose. The reproducibility of this assay was at least comparable to that described for other skin painting models in the literature. When the assay system was used to compare CSCs to which different concentrations of benzo(a)pyrene were added, its ability to distinguish these different condensate preparations was comparable to that of other models. The results obtained with the SKH-1 mouse strain suggest its usefulness in the short-term skin painting assay for the comparative investigation of the tumorigenic activity of different CSCs.

Chromosome 15-linked limb-girdle muscular dystrophy: clinical phenotypes in Reunion Island and French metropolitan communities.

Erb's type limb-girdle muscular dystrophy (LGMD) was identified and clinically studied in detail in a small community living in the Reunion Island (RI). It was linked to chromosome 15q and related to mutations in the muscle specific calpain 3 gene. A series of cases were afterwards clinically and genetically identified in the French metropolitan community. The phenotype was identical to the RI type in the great majority of cases, although clinical differences were noticed in a few cases. Six different mutations were identified in the RI families, whereas a series of 39 mutations were detected in the French metropolitan families, all different from those present in the RI patients. Phenotype-genotype correlations were attempted in both communities.

Clinical and genetic abnormalities in patients with Friedreich's ataxia.

BACKGROUND: Friedreich's ataxia, the most common inherited ataxia, is associated with a mutation that consists of an unstable expansion of GAA repeats in the first intron of the frataxin gene on chromosome 9, which encodes a protein of unknown function. METHODS: We studied 187 patients with autosomal recessive ataxia, determined the size of the GAA expansions, and analyzed the clinical manifestations in relation to the number of GAA repeats and the duration of disease. RESULTS: One hundred forty of the 187 patients, with ages at onset ranging from 2 to 51 years, were homozygous for a GAA expansion that had 120 to 1700 repeats of the trinucleotides. About one quarter of the patients, despite being homozygous, had atypical Friedreich's ataxia; they were older at presentation and had intact tendon reflexes. Larger GAA expansions correlated with earlier age at onset and shorter times to loss of ambulation. The size of the GAA expansions (and particularly that of the smaller of each pair) was associated with the frequency of cardiomyopathy and loss of reflexes in the upper limbs. The GAA repeats were unstable during transmission. CONCLUSIONS: The clinical spectrum of Friedreich's ataxia is broader than previously recognized, and the direct molecular test for the GAA expansion on chromosome 9 is useful for diagnosis, determination of prognosis, and genetic counseling.

Juvenile limb-girdle muscular dystrophy. Clinical, histopathological and genetic data from a small community living in the Reunion Island.

A series of patients affected by a muscular dystrophy, similar to the original description of a juvenile scapulo-humeral form by Erb in 1884 and fitting with the criteria used to define limb-girdle muscular dystrophies, was discovered in a small community living in the southern part of Reunion Island in the Indian Ocean. A detailed clinical analysis was conducted over 5 years on a cohort of 20 patients. This community presented a high degree of consanguinity as it was segregated from the majority of the island population for more than a century. In previous molecular genetic studies, the disease locus has been mapped to chromosome 15p. Mutations were recently identified in a gene located in this region encoding for muscle-specific calcium activated neutral protease (CANP3). Clinical, pathological, genetic and complete identification of the mutations are presented here, establishing, for the first time, precise clinico-genetic correlations in this form of autosomal recessive, juvenile, limb-girdle muscular dystrophy (LGMD).

[Contribution of enzyme-linked immuno-electrotransfer blot assay for the diagnosis of human neurocysticercosis]. / Apport de l'enzyme-linked immunoelectrotransfer blot assay au diagnostic de la neurocysticercose humaine.

An enzyme-linked immunoelectrotransfer blot (EITB) is developed for immunodiagnosing human neurocysticercosis. The assay's efficacy is evaluated in 71 neurocysticercotic patients whose diagnosis of the disease and evaluation of disease activity is based on CT scan findings. We identified eight bands (molecular weigh less than 35 000) that evaluate the disease activity: active disease, calcification in progress, inactive disease. All samples patients with active disease recognized 14 000 band. This band is missing in the others parasitic diseases and in serum of the patients with inactive diseases or calcification in progress. The enzyme-linked immunoelectrotransfer blot is simple to perform and may be used in sero-epidemiology.

[Immunologic diagnosis of the cerebrospinal fluid and serum in developing brain cysticercosis]. / Diagnostic immunologique dans le liquide céphalo-rachidien et le sérum de la cysticercose encéphalique évolutive.

ELISA detection of specific antibodies in the serum (IgG) and cerebrospinal fluid (IgG, IgM and IgA) was evaluated in 28 patients. Diagnosis of cerebral cysticercosis and evaluation of disease activity was based on CT scan findings. Specific IgG antibodies were found in the serum in 83.3% of patients with active disease and 10% of those with inactive disease. Cerebrospinal fluid tests evidenced specific antibodies in all patients with active disease and none of the patients with inactive disease. The specific CSF antibodies were IgG (94.4%), IgM (66.6%) or IgA (66.6%). Antibody titers were significantly higher in patients with an intraventricular vesicle or cyst.

[Racemous cysticercosis of the cauda equina and cystic arachnoiditis. Apropos of 2 cases]. / Cysticercose racemeuse de la queue de cheval et arachnoidite kystique. A propos de deux cas.

Central nervous system infection by the larval form of the pork tapeworm, taenia solium is a major public health problem in view of its prevalence. The high incidence of neurocysticercosis in Reunion Island has been precised by computerized tomography and Elisa test. Spinal involvement is an uncommon form of cysticercosis, occurring with a frequency of less than 1% in large series. The types of involvement that are most common are subarachnoid cysts which appear as intradural extramedullary masses and meningeal reaction with appearance of arachnoiditis at myelography. Intramedullary involvement is less frequent. Epidural and subpial masses have been reported very rarely. The authors report the two first cases of spinal cysticercosis in Reunion Island which are both extramedullary leptomeningeal forms. A radicular syndrome was present in both cases; incontinence and sacral hemihypoesthesia in one case. Myelography showed lumbosacral arachnoid cysts. Immunodiagnostic tests were positive in blood and C.S.F. in the two cases. Laminectomy was performed and the arachnoid membrane appeared opaque and thickened; the cysts were removed. Microscopically the cystic wall had a thin and curved cuticle, no scolex was found. Treatment was completed with the anti-helminthic agent Praziquantel. Full recovery was observed in one case. In the other case low back pain spread out to the lower extremities with a non radicular distribution and was associated with lumbosacral spinal fibrosis.

[Epidemiologic survey of the cysticercosis endemic on Réunion Island]. / Enquête épidémiologique sur l'endémie cysticerquienne à la Réunion.

The high incidence of cysticercosis was underestimated in Reunion Island before computed tomography (January, 1984). In 1974, Soulayrolles et Boyer-Vidal found that cysticercosis was responsible for 0.5 p. 100 of the cases of epilepsy. In hospitalized people, routine cranial and muscles radiographies detected: 1/among 242 epileptics: 183 men: 36 positive (19.67 p. 100); 59 women: 9 positive (15.25 p. 100), 2/among 166 non epileptic-related neurological disorders: 106 men, 6 positive (5.66 p. 100), 60 women: 6 positive (8.33 p. 100); 3/among 219 hospitalized patients with no neurological diseases: 124 men: 18 positive (14.5 p. 100), 95 women: 2 positive (2.10 p. 100). The clinical features of cysticercosis are so various that it appears impossible to define a typical clinical presentation. On the other hand the diagnosis is easy with CT scan and a serodiagnostic test (Elisa). In 98 patients, clinical symptoms and signs, CT scan and serology (Elisa) have been evaluated. Praziquantel was introduced in 1984 with good results as judged by serial CT scans. A human and animal investigation has been set up to define more clearly the relationship between the human parasitosis and rearing of domestic pigs to try to eradicate human and animal cysticercosis in Reunion Island.