[Spontaneous streptococcal arthritis of the pubic symphysis]. / Arthrites septiques spontanées à streptocoques de la symphyse pubienne.

Septic arthritis of the pubic symphysis is uncommon, and usually occurs in patients with predisposing conditions (female incontinence surgery, sports). Staphylococcus aureus and Pseudomonas aeruginosa are the main bacteria responsible of these infections. Streptococcal infections of the pubic symphysis are uncommon. We report three cases of streptococcal infections of the pubic symphysis that occurred in the absence of predisposing condition such as surgery or endocarditis. The diagnosis of septic arthritis was difficult, particularly in one patient who underwent an orchidopexy for a suspected of spermatic cord torsion before diagnosis was corrected. All three patients had a favourable outcome after an antibiotic treatment combining amoxicillin and rifampicin. Septic arthritis of the pubic symphysis should be suspected in patients with sudden groin pain, pubic tenderness and fever to avoid traumatic treatments and useless investigations.

[Hypereosinophilic syndromes: pathogenic and therapeutic up-to-date]. / Syndromes hyperéosinophiliques : actualités physiopathologiques et thérapeutiques.

The hypereosinophilic syndromes (HES), defined by an unexplained and sustained hypereosinophilia, can be associated with heterogeneous hematological conditions. Several molecular mechanisms underlying the eosinophilia, which remained indeterminate for a long time, have been recently identified. These recent advances allowed a better classification of the various forms of HES and the development of targeted therapies. The role of tyrosine kinases, especially PDGFRA, and the efficacy of tyrosine kinases inhibitors dramatically improved the diagnosis and the treatment of myeloproliferative variant of HES. On the other side, eosinophilia can be driven by IL-5 secreting abnormal and often clonal T cell subsets (lymphocytic variant of HES). The crucial role of this cytokine in eosinophil development, activation and survival leads to the assessment of anti-IL-5 monoclonal antibodies which have recently shown to provide a significant corticosteroid sparing effect in FIP1L1-PDGFRA negative HES patients. Despite these major advances, half of HES remains unexplained (idiopathic HES). Some FIPL1-PDGFRA negative patients respond to imatinib, suggesting the role of other tyrosine kinases (or other partners than FIP1L1 in a fusion gene implicating PDGFRA). Development of new biomarkers is needed to help physicians in the diagnosis, classification of HES and in the choice of a targeted therapy.

[What's new in internal medicine?]. / Quoi de neuf en médecine interne?

Among diagnostic progress over the last three years in internal medicine, Antisynthetase Syndrome is now more easily recognised with the diffusion of laboratory tests for research of antibodies against tRNA synthetases (Anti JO1, anti PL7, Anti PL12). In two third of cases, these antibodies are found despite absence of antinuclear antibodies. Hence, we have to search them specifically in patients with polyarthritis associated with myositis, cutaneous manifestations (Raynaud phenomenom and "mechanic'hands") and interstitial lung disease. Discovery of asymptomatic mutation in the L ferritin coding sequence help us to better understand the "unexplained" hyperferritinemia. Initially described by japonese gastroenterologists, auto immune pancreatitis in fact a part of a systemic sclerosing disease with a biochemical hallmark: in crease of a subclass of immunoglobulins G (IgG4). A new pediatric disease due to a deficiency of the interleukin1 receptor antagonist (multifocal aseptic osteitis, periostitis, stomatitis, disseminated pustulosis) help us to better understand unexplained auto inflammatory diseases. The therapeutic progress is primarily due to an explosion of biological therapies, particularly four of them very useful for internists (in an off label use) : Interleukin 1 inhibitors (anakinra, Canakinumab) to treat some auto inflammatory diseases (cryopirin associated periodic syndromes and deficency of interleukin 1 receptor antagonist), monoclonal antibody against interleukin 5 (mepolizumab) to treat some hypereosinophilic syndromes and Churg and Strauss angiitis, interleukin 6 inhibitiors to treat multifocal Castleman's disease and adult Still disease, a monoclonal antibody against vascular endothelial growth factor (Bevacizumab) to treat hereditary hemorrhagic telangiectasia.

[Usefulness of combined positron emission tomography and computed tomography imaging in Erdheim-Chester disease]. / Intérêt de la tomographie par émission de positons couplée au scanner dans la maladie d'Erdheim-Chester.

INTRODUCTION: Erdheim-Chester disease is a rare non-Langerhans form of histiocytosis. We report the use of combined fluorodeoxyglucose positron emission tomography and computed tomography (18F-FDG PET-CT) in this disease. EXEGESIS: Three men, aged from 55 to 74 years with confirmed Erdheim-Chester disease were included. 18F-FDG PET-CT allowed to detect visceral and vascular involvement of the disease which were overlooked with CT-scan or magnetic resonance imaging: left common carotid and ilio-femoral artery in one patient, coronary, femoral and tibia in the second, aortic, common carotid, femoral and mandibula in the remaining patient. Also, sequential 18F-FDG PET-CT was useful to appreciate treatment efficiency (decrease hyperfixation) and decide treatment modification (interferon alpha). CONCLUSION: 18F-FDG PET-CT combined imaging allows to assess the extent of involvement in Erdheim-Chester disease. 18F-FDG PET-CT may be also a useful tool in the management of Erdheim-Chester disease.

Molecular characterization of the idiopathic hypereosinophilic syndrome (HES) in 35 French patients with normal conventional cytogenetics.

Idiopathic hypereosinophilic syndrome (HES) characterized by unexplained and persistent hypereosinophilia is heterogeneous and comprises several entities: a myeloproliferative form where myeloid lineages are involved with the interstitial chromosome 4q12 deletion leading to fusion between FIP1L1 and PDGFRA genes, the latter acquiring increased tyrosine kinase activity. And a lymphocytic variant, where hypereosinophilia is secondary to a primitive T lymphoid disorder demonstrated by the presence of a circulating T-cell clone. We performed molecular characterization of HES in 35 patients with normal karyotype by conventional cytogenetic analysis. TCRgamma gene rearrangements suggesting T clonality were seen in 11 (31%) patients, and FIP1L1-PDGFRA by RT-PCR in six (17%) of 35 patients, who showed no evidence of T-cell clonality. An elevated serum tryptase level was observed in FIP1L1-PDGFRA-positive patients responding to imatinib, whereas serum IL-5 levels were not elevated in T-cell associated hypereosinophilia. Sequencing FIP1L1-PDGFRA revealed scattered breakpoints in FIP1L1-exons (10-13), whereas breakpoints were restricted to exon 12 of PDGFRA. In the 29 patients without FIP1L1-PDGFRA, no activating mutation of PDGFRA/PDGFRB was detected; however; one patient responded to imatinib. FISH analysis of the 4q12 deletion was concordant with FIP1L1-PDGFRA RT-PCR data. Further investigation of the nature of FIP1L1-PDGFRA affected cells will improve the classification of HES.

[Medical practice analysis in internal medicine: a national descriptive study]. / Analyse des pratiques des spécialistes de médecine interne: une enquête transversale descriptive nationale.

PURPOSE: This descriptive and epidemiological study was conducted in Mars 2002 in Internal Medicine in order to (1) participate in elaborating a White Book about the speciality, (2) analyse the post-university formation needs of the specialists in Internal Medicine. METHODS: A questionnaire was sent to all specialists in Internal Medicine listed on the ADELI file (n = 2155). For the first three patients seen in consultation and during hospital stay, questioned specialists had to mention the age, sex, origin, motive of the visit, nature of symptoms, complexity of the problem and the nature of the required abilities. They also had to precise the main diagnosis of all patients seen in the same day. RESULTS: Three hundred and sixty answers have been received. Three hundred and thirty two were exploitable. Five thousand six hundred and eleven main diagnosis were listed. Fifteen percent of the questioned specialists did practise in other specialities than Internal Medicine. Orphaned diseases were the most common pathologies carried out in consultation (17%). Patients seen during their hospital stay suffered more frequently from infectious, haematological and malignant diseases. In 55% of the cases, patients were seen in second or third line after a visit to a general practitioner or another specialist. The abilities of the Internal Medicine specialist alone were sufficient in 70% of the cases to solve the problem. Complexity of the problem was evaluated by the specialists themselves at about 45/100 on an analogical scale. CONCLUSIONS: This study inform the medical community about the type of patients treated by the specialists in Internal Medicine, precise the exact nature of their professional exercise and their real need in medical post-university formation.

[Biological monitoring of autoimmune diseases during pregnancy]. / Surveillance biologique des pathologies auto-immunes pendant la grossesse.

This review focuses on auto-immune diseases which frequently affect women and can have interactions with pregnancy: lupus erythematosus (LES), antiphospholipide syndrome (SAPL), Sjögren's syndrome (GS), rheumatoid arthritis (PR) and auto-immune thyroiditis. LES may flare at the end of a pregnancy and during post-partum. Its biological monitoring during pregnancy is well established. SAPL is at risk of sterility, prematurity, Hellp syndrome, eclampsia and retroplacental hematoma. The main risk, actually risk is foetal loss by placental ischemia, which has to be well known as 2 randomised studies have proven the efficacy of treatments with aspirin +/- subcutaneous heparin. LES, GS and PR can both be associated with anti SS-A +/- anti SS-B antibodies linked to a risk of congenital auriculo-ventricular block, which is fortunately low (less than 5% of the cases). Auto-immune thyroiditis are often revealed during pregnancy and may be enhanced during the six first months of post-partum.

[Do the interferons have an antifibrotic action? The internist's point of view]. / Les interférons ont-ils une action antifibrosante? Le point de vue de l'interniste.

PURPOSE: The antifibrotic action of interferon alpha on the liver is now established in hepatitis C (cf. article by T. Poynard). Numerous in vitro experimental evidences may lead people into believing in the efficacy of interferon gamma in patients with mucous membrane and pulmonary fibrosis. CURRENT KNOWLEDGE AND KEY POINTS: A randomized study has confirmed the efficacy of interferon gamma in the idiopathic pulmonary fibrosis, probably by an anti TGF beta action. Several open studies have shown the efficacy of interferon gamma in patients with post-radiation cutaneous fibrosis (Chernobyl survivors, sequelae of radiotherapy for cancer). In systemic sclerosis, several teams have shown that interferon gamma reduced collagen synthesis by sclerodermic fibroblasts in vitro. Four open studies have also confirmed the efficacy of interferon gamma in systemic sclerosis. In our experience concerning 20 patients with diffuse systemic sclerosis, the five years survival with long term therapy was 85% and we observed an improvement in the cutaneous suppleness in 40% of these cases. There was no serious side effect. FUTURE PROSPECTS AND PROJECTS: These encouraging results need to be confirmed by large randomized studies in pulmonary fibrosis and systemic sclerosis. Other indications should be assessed, particularly extra-cutaneous radiation sequelae and in systemic fibrosis (retroperitoneal, mediastinal and cervical).

Spontaneous resolution of hemophagocytic syndrome associated with acute parvovirus B19 infection and concomitant Epstein-Barr virus reactivation in an otherwise healthy adult.

Reported here is the case of a patient who spontaneously recovered from hemophagocytic syndrome associated with acute B19 infection and concomitant Epstein-Barr virus reactivation. The previously healthy 37-year-old-man was hospitalized after 10 days of high fever, arthralgia and arthritis and was determined to have hemophagocytic syndrome. Immunoglobulin (Ig) M antibodies to Epstein-Barr virus (EBV) capsid antigen, early antigen and parvovirus B19 (B19) were found. B19 DNA and low-level EBV DNA were detected in bone marrow, serum and peripheral blood mononuclear cells. The patient recovered spontaneously without any treatment. Two months later anti-B19 IgG antibodies were detected, while at 9-month follow-up, anti-B19 IgM antibodies were no longer detectable and B19 DNA had disappeared from serum. To the best of our knowledge, this is the first report of spontaneous resolution of hemophagocytic syndrome associated with acute B19 infection and concomitant EBV reactivation in an otherwise healthy adult.

[Castleman's disease in patients infected with HIV]. / Maladie de Castleman chez les patients infectés par le VIH.

PURPOSE: Castleman's disease is a polyclonal lymphoplasmacytic and vascular proliferation prominant in lymphoid tissues. It is associated with lymph node enlargement, hepatosplenomegaly and fever. This manifestations could be secondary to hyperproduction of interleukin 6. The prognosis is poor. The opportunistic infections which are characteristic of severe HIV infection worsen the prognosis. Prolonged monochemotherapy with vinblastine or etoposide can control Castleman's disease. CURRENT KNOWLEDGE AND KEY POINTS: Recent advances in human herpesvirus 8 (HHV8) knowledge and its predominance in the forms which are linked to the HIV seropositivity have partly explained the clinical manifestations of Castleman's disease. Indeed, HHV8 produce an homologous interleukin 6, the vIL-6, responsible for lymphoplasmacytic proliferation. The presence of other homologues of human cytokines produced by HHV8 could contribute to lymphoplasmacytosis and to endothelial proliferation. FUTURE AND PROSPECTS: Taking into account this viral origin, alpha interferon could be an alternative in forms which are less progressive. However, antiviral therapy against HHV8 or HIV and the immunitary restoration do not have any influence on the evolution of Castleman's disease, contrary to opportunistic infections.

Systemic medium-sized vessel vasculitis associated with chronic myelomonocytic leukemia.

OBJECTIVE: To determine the clinical aspects of systemic vasculitis associated with chronic myelomonocytic leukemia (CMML). METHODS: In this retrospective study, 8 patients suffering from systemic vasculitis associated with CMML are described. The French and English literature on systemic vasculitis associated with myelodysplasia was reviewed. RESULTS: All 8 patients had a systemic medium-sized vessel vasculitis which fulfilled the American College of Rheumatology criteria for polyarteritis nodosa in the setting of active CMML. Antineutrophil cytoplasmic antibodies (ANCA) were negative in 7 patients. One patient had cytoplasmic ANCA by indirect immunofluorescence without antiproteinase 3 or antimyeloperoxydase antibodies on the enzyme-linked immunosorbent assay. At presentation, 6 patients had fever of unknown origin, 5 had polymyalgia rheumatica, 3 had sensory hearing loss, and 4 had eosinophilia. None had viral infection or drug-associated vasculitis. Diagnostic procedures included renal or hepatic angiography in 6 patients which showed microaneurysms in 4, skin and temporal artery biopsy in 2 which showed vasculitis, and 1 postmortem examination which showed gastroduodenal arteritis. All patients were treated with corticosteroids, and 7 received immunosuppressive drugs. Death was attributable to vasculitis in 2 cases, infection in 3, and other vasculitis-related causes in 2. In a review of the French-English literature, we found 11 similar cases of ANCA-negative systemic vasculitis, generally associated with refractory anemia, with or without blast excess. CONCLUSIONS: Systemic ANCA-negative polyarteritis nodosa-type vasculitis seems closely associated to CMML. Clinical presentation is nonspecific, and systemic vasculitis should be suspected when a patient with myelodysplasia develops atypical manifestations. Renal, gastrointestinal, or hepatic angiography are useful diagnostic procedures when more invasive biopsies should be avoided because of low platelet count. The prognosis of CMML-associated systemic vasculitis is poor.

Intracranial aneurysm associated with relapsing polychondritis.

We describe a 50-year-old man with relapsing polychondritis (RP) involving auricular cartilage, uveitis and hearing loss, who had an aneurysm of the anterior cerebral artery. Intracranial aneurysm is a rare manifestation of RP.

[Fabry disease in adulthood: clinical aspects and therapeutic progress]. / La maladie de Fabry chez l'adulte: aspects cliniques et progrès thérapeutiques.

INTRODUCTION: Fabry disease is an X-linked recessive abnormality of glycosphingolipid metabolism that is due to deficiency of the lysosomal enzyme alpha-galactosidase A. CURRENT KNOWLEDGE AND KEY POINTS: A majority of hemizygous men develop severe multisystemic disease (classic form), dominated by renal failure, progressive neurological and cardiac involvement. Nevertheless, some affected men retain sufficient enzyme activity and long remain asymptomatic (atypical form); their main manifestation is hypertrophic cardiomyopathy. Female heterozygous carriers are usually asymptomatic; 15% of them, however, have severe involvement of one or several organs. Laboratory, histologic and molecular diagnosis identifies 100% of hemizygous and over 80% of heterozygous subjects. FUTURE PROSPECTS AND PROJECTS: With developments in molecular genetics, it is now possible to produce the human recombinant enzyme alpha-galactosidase A. Two recent studies had proven that this therapeutic approach was able to be clinically and histologically effective in men. In addition, the results of a trial of gene therapy in a Fabry gene knocked-out mouse appear promising.

[Idiopathic hypereosinophilic syndrome]. / Hyperéosinophilies dites essentielles.

The idiopathic hypereosinophilic syndrome is defined by the combination of prolonged eosinophilia and evidence of tissue damage including heart and nervous system. Cardiac disease is the major cause of mortality. The idiopathic hypereosinophilic syndrome is a heterogeneous collection of disorders. Products of activated eosinophils could exert toxicities on specific organs; it is a diagnosis of exclusion. There is no specific tests diagnostics. The development of a comprehensive diagnosis and therapeutic approach ensure from a better understanding of the pathogenesis.

De novo systemic sclerosis after radiotherapy: a report of 3 cases.

We describe 3 patients in whom the onset of systemic scleroderma occurred shortly after ionizing irradiation for nasopharyngeal or breast carcinoma. This relationship has been described rarely as has the exacerbation of a preexisting scleroderma after irradiation. This gives indications for direction of studies.