H. Rousset

Whipple Disease: Clinical Review of 52 Cases

: Whipple disease is a rare, multiorgan disease with prominent intestinal manifestations. We report a retrospective clinical study of 52 patients recruited in various parts of France from 1967 to 1994. Seventy-three percent of the patients were male. Clinical manifestations preceding the diagnosis were articular for 35 patients (67%), digestive for 8 patients (15%), general for 7 patients (14%), and neurologic for 2 patients (4%). At a later stage of the disease, 44 patients (85%) presented diarrhea, weight loss, and malabsorption, while 8 patients (15%) did not show any gastrointestinal symptom throughout the development of the disease. Forty-three patients (83%) presented arthralgia or arthritis, and 11 (21%) had prominent neurologic symptoms. In addition, cardiovascular symptoms were present in 9 patients (17%); mucocutaneous symptoms, in 9 patients (17%); pleuropulmonary symptoms, in 7 patients (13%); and ophthalmologic symptoms, in 5 patients (10%). All patients but 1 were given a positive diagnosis on histopathologic criteria: jejunal biopsy for 46 patients (90%), lymph node biopsy for 3 patients (6%), brain biopsy for 1 patient (2%), postmortem jejunal and cerebral biopsy for 1 patient (2%). With treatment, the disease evolved favorably in 47 patients (90%), while 5 patients (10%) had unfavorable outcomes (2 deaths from neurologic involvement, 1 patient with chronic dementia, and 2 patients with digestive symptoms insensitive to antimicrobial therapy). Of the 41 patients initially treated successfully and whose treatment has been completed, clinical evolution after discontinuation of treatment was favorable in 34 cases (83%). Clinical relapses occurred in 7 patients. No relapse was observed after treatment by trimethoprim-sulfamethoxazole, alone or following a combination of penicillin and streptomycin, or after the combination of penicillin and streptomycin, whatever the oral follow-up treatment prescribed. The evolution of patients showing a relapse was favorable in all cases after reintroduction of antibiotic therapy. These results are discussed in the light of previously published series and case reports of Whipple disease. The diagnosis of the disease remains difficult at an early phase or when digestive symptoms are absent. It is noteworthy that proximal enteroscopy is sometimes misleading, considered normal on macroscopic examination and nonspecific on pathologic grounds. A normal erythrocyte sedimentation rate represents another pitfall. Histopathology is the key for positive and differential diagnosis, and may require multiple and repeated biopsies. Findings from molecular biology confirm the central role of an uncultured Gram-positive bacillus which was named in 1992 Tropheryma whippelii. A recent report suggests that polymerase chain reaction (PCR) analysis of peripheral blood might allow the diagnosis of Whipple disease in some cases. However, immunologic or cellular parameters such as macrophagic function may play an important, although not clearly elucidated, role in the pathogeny of the disease. Trimethoprim-sulfamethoxazole should be considered the antimicrobial agent of choice in the treatment of Whipple disease, minimizing the risk of cerebral involvement and relapses.

Neurologic presentation of Whipple disease: report of 12 cases and review of the literature.

We report 12 cases of Whipple disease in patients with prominent neurologic symptoms, along with 122 cases of Whipple disease with nervous system involvement reported in the literature. We analyzed the clinical signs and results of additional examinations in 2 groups: the first group included patients with predominantly but not exclusively neurologic signs, and the second included patients with clinically isolated neurologic presentation of the disease. Whipple disease is a multisystemic infectious disease due to Tropheryma whippelii that may present with prominent or isolated symptoms of either the central or the peripheral nervous system. Recent reports stress the importance of polymerase chain reaction (PCR) analysis of cerebrospinal fluid, magnetic resonance imaging (MRI) during follow-up, and prolonged antibiotic therapy with drugs able to cross the blood-brain barrier.Cerebrospinal fluid should be analyzed repeatedly during follow-up, and treatment should be discontinued only when the results of PCR assay performed on cerebrospinal fluid are negative. Other examinations to be done include searching for gastrointestinal tract involvement with multiple duodenal biopsies and searching for systemic involvement with lymph node biopsies, which should be analyzed with light microscopy, electron microscopy, and PCR. When all examinations are negative, if Whipple disease is suspected and a lesion is found on brain MRI, a stereotactic cerebral biopsy should be performed. Treating Whipple disease with long-term trimethoprim-sulfamethoxazole is usually effective, but the use of third-generation cephalosporins in case of incomplete response deserves further attention.

Growth factors and proinflammatory cytokines in the renal involvement of POEMS syndrome.

The POEMS syndrome is a multisystemic syndrome associated with plasma cell dyscrasia, characterized by the combination of polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes. Renal involvement in POEMS syndrome is rare (26 reported cases). It has been described as membranoproliferative glomerulonephritis-like lesions (MPGN-like), mesangiolytic glomerulonephritis, or thrombotic microangiopathy. Proinflammatory cytokines (TNF-alpha, IL-1, IL-6) have been implicated in the physiopathogenesis of POEMS syndrome, particularly when there is renal involvement. Growth factors (FGF-beta, TGF-beta, PDGF) have been implicated in renal lesions of the same histological type but of different origins. An increase in serum vascular endothelial growth factor (VEGF) has been reported in POEMS syndrome (20 of 22 cases). Circulating levels of these factors were determined in 4 patients with POEMS and renal involvement (3 MPGN-like, 1 MPGN-like, and mesangiolysis) and compared with those obtained in 4 patients with POEMS without clinical renal involvement and in 4 patients with primitive membranoproliferative glomerulonephritis (MPGN). TNF-alpha, IL-1beta, and IL-6 were determined with an immunoradiometric assay, and VEGF, PDGF, FGF-beta, and TGF-beta with an enzyme-linked immunosorbent assay. Among the patients with POEMS syndrome, there was no difference in proinflammatory cytokines and growth factors between those with or without renal involvement. VEGF is the only growth factor that differentiates MPGN in POEMS syndrome from primitive MPGN.

Exogenous oestrogen as an alternative to food allergy in the aetiology of angioneurotic oedema.

Although frequently reported as an aetiology for chronic angioneurotic oedema or urticaria, food allergy is often a diagnosis proposed in the absence of more convincing evidence, as illustrated by the disappointing results of eviction regimens. We report a series of women with an initial diagnosis of food allergy, but in whom the role of oral contraceptives was subsequently demonstrated. Detailed medical history was obtained from 26 young women presenting with chronic angioneurotic oedema or urticaria initially attributed to food allergy, but in whom C1-esterase inhibitor (C1 INH) deficiency was demonstrated. We investigated the effects of oral contraception on C1 INH levels, C1 INH activity and clinical symptoms of these patients. Discontinuation of oral contraception induced an increase in C1 INH levels and C1 INH activity, associated with recovery or marked improvement of the clinical symptoms formerly attributed to food allergy. The relatively high frequency of women taking cyproterone acetate in this population appeared to be a remarkable finding. Replacement of the initial contraception containing ethinylestradiol by a progestogen maintained or even accentuated these good therapeutic results. Exogenous oestrogens, such as those contained in most oral contraceptives, may play an iatrogenic role in the aetiology of chronic angioneurotic oedema or urticaria.

Abcès splénique à Coxiella burnetii en l'absence d'endocardite

— Spleen abcess due to Coxiella burnetii in the absence of endocarditis. Introduction. — The most frequent clinical expression of chronic Q fever is culture-negative endocarditis. Other localizations are rare. Exegesis. — We report a documented case of chronic Q fever that occurred in a 47-year-old immunocompetent man and was associated with spleen abcess, in the absence of detectable endocarditis. The spleen abcess was a complication of either a preexisting cyst or a calcified hematoma. Splenic infection with Coxiella burnetii was documented with cultures, polymerase chain reaction and immunohistochemistry. The outcome was favorable after splenectomy and a a 21-month antibiotherapty. Conclusion. — Chronic Q fever may develop in the absence of endocarditis, when a preexisting vascular lesion such as aortic aneurysm exists. A splenic cyst may have played a similar role for this patient.

Méningites puriformes aseptiques chez l’adulte: Étude rétrospective de 32 cas

Resume Objectif L’objectif de cette etude etait d’analyser les caracteristiques d’une serie de meningites puriformes aseptiques (MPA) (definies par un liquide cephalorachidien [LCR] sterile avec plus de 10 leucocytes par mm 3 et une formule riche en polynucleaires neutrophiles) : prise en charge initiale, decision d’antibiotherapie et/ou traitement antiviral, etiologies, interet d’une ponction lombaire de controle, evolution, etc. Methode Nous avons analyse retrospectivement 32 cas de MPA (sur un total de 130 dossiers de meningite) issus de 2 services de medecine interne de Lyon, diagnostiques entre janvier 1996 et janvier 2003. Seuls les dossiers repondant aux criteres de MPA ont ete retenus en choisissant un taux minimal de polynucleaires neutrophiles (PNN) de 30 % dans le LCR. Resultats L’âge moyen etait de 32,6 ans (extremes :18-75) avec une predominance masculine (59 %). A l’entree, 87 % des patients etaient febriles, 9 % le restant a 72 heures. On notait un syndrome viral prealable (59 %) et une predilection saisonniere (ete : 39 %, hiver : 35 %). Les indications de la ponction lombaire (PL) etaient un syndrome meninge franc (44 %), des cephalees (94 %), des vomissements (47 %). Il n’y avait aucun cas de meningoencephalite. Le taux moyen des PNN dans le LCR a J1 etait de 63 % (extremes : 30-96). Une ponction lombaire de controle a J3 fut realisee 16 fois (50 %) : taux moyen de PNN a 18 % (extremes : 0-80), taux de lymphocytes a 68 % (extremes : 20-95). La plupart des patients (77,4 %) avaient une proteine C reactive (CRP) inferieure a 50 mg/L a l’entree (extremes : 5-320). Une imagerie cerebrale realisee 10 fois etait anormale 2 fois (abces cerebraux multiples, hypertension intracrânienne probable). Un traitement antibiotique (84 %) et/ou antiviral (34 %) etait instaure. L’evolution a J3 etait favorable (87,5 %) : apyrexie, regression du syndrome meninge, avec en moyenne 8,3 jours d’hospitalisation (extremes : 1-60). Une recherche d’herpes et d’ Enterovirus par PCR etait entreprise dans 20 cas (62,5 %) : aucune positivite pour l’herpes mais 9 pour l’ Enterovirus . Les hemocultures systematiques etaient positives une seule fois (endocardite infectieuse a staphylocoque avec abces cerebraux). Le diagnostic de meningite decapitee etait evoque 3 fois (antibiotherapie prealable). Conclusion La frequence des MPA a Enterovirus incite a entreprendre cette recherche pour arreter rapidement le traitement anti-infectieux souvent initie et eviter une deuxieme ponction lombaire.OBJECTIVE The objective of this study was to analyze the characteristics of a series of acute aseptic meningitis (AAM) (defined by sterile cerebrospinal fluid (CSF) with more than 10 leucocytes per mm3 and a neutrophilic polynuclear-rich formula). We analysed the initial management, the reasons for antibiotic and/or antiviral treatment, the aetiologies, the need for lumbar puncture and the progression... METHOD We retrospectively analyzed 32 cases of AAM (out of a total of 130 cases of meningitis) from two departments of internal medicine in Lyon, diagnosed between January 1996 and January 2003. Only the files fulfilling the AAM criteria were retained, selecting those with a minimum neutrophilic polynuclear level of 30% in the CSF. RESULTS The mean age was 32.6 years (range: 18-75) and predominantly male patients (59%). On admission, 87% of the patients exhibited fever, but only 9% remaining so for 72 hours. Viral syndrome before admission was noted in 59% of cases, with seasonal predilection (summer: 39%, winter: 35%). The motivation for lumbar puncture (LP) was meningeal syndrome (44%), headache (94%) and vomiting (47%). The average rate of neutrophils in the CSF on admission was 63% (range: 30-96). A control LP on Day 3 was performed 16 times (50%): mean PNN rate at 18% (range: 0-80), lymphocyte rate=68% (range: 20-95). Most of the patients (77.4%) had a C reactive protein (CRP) lower than 50 mg/l on admission (range: 5-320). A cerebral scan was performed 10 times (31%) and was abnormal 2 times (multiple cerebral abscesses, possible intracranial hypertension). An antibiotic (84%) and/or antiviral (34%) treatment was initiated. The evolution on Day 3 was favourable (87.5%): no fever, regression of the meningeal syndrome, with a mean duration of hospitalisation of 8.3 days (range: 1-60). Search for Herpes simplex virus and Enterovirus was made with PCR analysis in 20 cases (62.5%): no positivity for the herpes, but 9 for the Enterovirus. The systematic blood cultures were positive only once (staphylococcal infective endocarditis with cerebral abscesses). The diagnosis of bacterial meningitis was evoked 3 times (prior antibiotic treatment). DISCUSSION The frequency of Enterovirus AAM should encourage this type of investigation in order to withdraw the often initiated anti-infectious treatment rapidly, and hence avoid a second lumbar puncture.

Anticoagulants circulants en dehors de l'hémophilie: Enquête multicentrique conduite par le secrétariat à la recherche de la SNFMI à propos de 207 observations

A retrospective multicentre study, undertaken under the aegis of the French National Society of Internal Medicine, involved 200 subjects with acquired circulating anticoagulants; 130 were female and 77 were male; mean age was 45 +/- 23 years (range: 10 months to 80 years). Mean duration of follow-up was 23 months. In 130 subjects the anticoagulants were detected as a result of a systematic screening examination. The main overt clinical manifestations were haemorrhages, venous or arterial thrombosis and spontaneous abortion. Typing of the anticoagulant, performed in 166 cases, showed the presence of an antiprothrombinase in 141; this enzyme is not responsible for severe bleeding unless it is associated with other disorders of coagulation; less frequent were an anti-factor VIIIc (n = 16) and an anti-factor V (n = 2) anticoagulants. An underlying pathology was found in 172 subjects, including systemic lupus erythematosus (n = 60), induced lupus (n = 11), discoid lupus (n = 3), infection (n = 23), blood disease (n = 19), cancer (n = 15) and vasculitis (n = 15); other factors were pregnancy (n = 5) and medicines (n = 6). The anticoagulant disappeared spontaneously in 10 cases and in 33 of the 115 subjects treated. In subjects with lupus and in children under twelve years of age, an antiprothrombinase was regularly identified at typing.

Amyloses localisées de découverte forfuite: analyse de 12 observations

Authors report ten cases of localized amyloidosis exposed by surgery. Three patients have developped later a systemic amyloidosis. The others patients have a local disease (2 larynx, 1 heart valves, 1 urinary bladder, 1 sciatic nerve, 1 eyelid, 1 Fallopian tube) with an excellent pronostic.

Tuberculose chez les sujets corticothérapés pour maladie inflammatoire : à propos de neuf cas, et revue de la littérature

Objectives – The authors wanted to describe the clinical presentation and outcome of tuberculosis in patients receiving corticosteroids for an inflammatory disease, determine the means for diagnosis, evaluate risk factors, and suggest a rationale for empiric antituberculous treatment in high risk patients. Methods – A retrospective analysis was made of nine bacteriologically proven tuberculosis cases occurring under corticosteroid treatment for inflammatory or immune disorders, over a six-year period, in three French university hospitals. Results – Eight patients out of nine were over 60. The inflammatory disease had started from two months to 22 years before, cumulated and mean daily corticosteroid doses were heterogeneous. More than one organ was affected by tuberculosis in eight cases. Lungs or pleura were involved in seven cases, central nervous system in three cases, and bones or joints in three cases. Delay for diagnosis was important, because of atypical clinical presentations and rarity of positive smears (1/9). Three deaths and three cases of major sequels were noted. In five cases, a history of tuberculosis could have been suspected at the onset of corticosteroid therapy. No relapse of the inflammatory disease was observed during the treatment for tuberculosis. Conclusion – Tuberculosis can be devastating in patients receiving corticosteroids for an inflammatory disease. Usual diagnostic means are not reliable and early antituberculous treatment should be initiated in high-risk patients. When a corticosteroid treatment is prescribed, risk factors for tuberculosis (old age, emigration from a high-prevalence country, radiological sequels of pulmonary tuberculosis) should be carefully assessed, and prophylactic treatment should be systematically given.

Infection pulmonaire à Mycobacterium Avium intracellulaire avec déficit en CD4 + sans infection HIV

We report the case of a patient with pulmonary Mycobacterium Avium intracellular infection and CD4 + T lymphocytopenia which may have resolved after treatment of vitamin and trace mineral deficiencies.