Systemic lupus erythematosus-associated acute transverse myelitis: manifestations, treatments, outcomes, and prognostic factors in 20 patients.

BACKGROUND: Transverse myelitis is a rare complication of systemic lupus erythematosus (SLE). This retrospective multicentre study identifies the prognostic factors in a relatively large patient series. PATIENTS AND METHODS: Twenty patients fulfilled the SLE criteria of the ACR classification and the Transverse Myelitis Consortium Working Group. A severe neurological flare was defined as muscle strength grade <3/5 in more than half the muscle groups at the motor neurological level. Inability to run or another significant ambulation-unrelated disability was considered as 'unfavourable neurological outcome'. RESULTS: Myelitis was the first SLE symptom in 12 patients; in the eight others, it occurred 8.6 years (median delay) after SLE onset. Eleven patients presented severe neurological impairments. The treatment included corticosteroids in all patients associated with intravenous cyclophosphamide in 11 and/or hydroxychloroquine in 14. Unfavourable outcomes were observed in 53% of the patients at six months and in 28% at end of follow-up (median: 5.9 years). An initial severe neurological impairment and no cyclophosphamide use were associated with unfavourable neurological outcomes at six months and at end of follow-up, respectively. CONCLUSION: Transverse myelitis may reveal SLE or occur more than 10 years after SLE diagnosis. The initial severity of the neurological flare (with paraplegia) is the main prognostic marker. The study provides arguments for cyclophosphamide use.

[Exercise-induced muscle pain due to phosphofrutokinase deficiency: Diagnostic contribution of metabolic explorations (exercise tests, 31P-nuclear magnetic resonance spectroscopy)]. / Intolérance musculaire à l'effort par déficit en phosphofructokinase : apport au diagnostic du bilan métabolique musculaire (tests d'effort, spectroscopie RMN du P31).

INTRODUCTION: Muscle phosphofructokinase deficiency, the seventh member of the glycogen storage diseases family, is also called Tarui's disease (GSD VII). METHODS: We studied two patients in two unrelated families with Tarui's disease, analyzing clinical features, CK level, EMG, muscle biopsy findings and molecular genetics features. Metabolic muscle explorations (forearm ischemic exercise test [FIET]; bicycle ergometer exercise test [EE]; 31P-nuclear magnetic resonance spectroscopy of calf muscle [31P-NMR-S]) are performed as appropriate. RESULTS: Two patients, a 47-year-old man and a 38-year-old woman, complained of exercise-induced fatigue since childhood. The neurological examination was normal or showed light weakness. Laboratory studies showed increased CPK, serum uric acid and reticulocyte count without anemia. There was no increase in the blood lactate level during the FIET or the EE although there was a light increase in the respiratory exchange ratio during the EE. 31P-NMR-S revealed no intracellular acidification or accumulated intermediates such as phosphorylated monoesters (PME) known to be pathognomic for GSD VII. Two new mutations were identified. DISCUSSION: FIET and EE were non-contributive to diagnosis, but 31P-NMR provided a characteristic spectra of Tarui's disease, in agreement with phosphofructokinase activity level in erythrocytes. Muscle biopsy does not always provide useful information for diagnosis. In these two cases, genetic studies failed to establish a genotype-phenotype correlation. CONCLUSION: The search for phosphofructokinase deficiency should be continued throughout life in adults experiencing fatigability or weakness because of the severe disability for daily life activities caused by the late onset form.

[Unexplained, subclinical chronically elevated transaminases]. / Élévation modérée, persistante et inexpliquée des transaminases.

Unexplained, subclinical chronically elevated transaminases is mainly a marker of non-alcoholic fatty liver disease, metabolic syndrome, alcoholism and diabetes, which are very common situations but viral hepatitis and iatrogenic origin must also be considered. Before looking for hepatic or genetic rare diseases, it is worth considering hypertransaminasemia as a clue for muscular disease, particularly in paediatric settings, and creatine phosphokinase is a specific marker. Then, patient history, examination and appropriate biologic requests can permit the identification of less frequent disorders where isolated hypertransaminasemia is possibly the unique marker of the disease for a long while: hemochromatosis, celiac disease, autoimmune hepatitis, Wilson's disease, α1-anti-trypsine deficiency, thyroid dysfunctions, Addison's disease. Liver biopsy should be performed only in patients with aspartate aminotransferases upper the normal range or alanine aminotransferases higher than twice the normal range after 6 months delay with dietetic corrections.

[Abnormal hemoglobins with high oxygen affinity in the differential diagnosis of polycythemia]. / Polyglobulies : penser aux hémoglobines hyperaffines pour l'oxygène.

Hemoglobin variant with high oxygen affinity is an uncommon, often misdiagnosed, etiology of erythrocytosis. We report two cases of erythrocytosis. Their hemoglobin-oxygen dissociation curve showed a P50 value (the oxygen tension at which hemoglobin is 50% saturated) below the normal range. Globin chains electrophoresis and DNA analysis evidenced hemoglobin Olympia and hemoglobin Malmö, respectively. More than 200 variants of hemoglobin with increased oxygen affinity have been described, that are in about one-third responsible of secondary erythocytosis because of tissular hypoxia. Such abnormal haemoglobin identification should be routinely included in the diagnostic work-up of unexplained erythocytosis, particularly in young people.

Paediatric systemic lupus erythematosus: prognostic impact of antiphospholipid antibodies.

OBJECTIVES: The aim of our study was to investigate the prognostic impact of aPL in paediatric onset systemic lupus erythematosus (p-SLE). METHODS: This retrospective study included 56 patients with p-SLE. Chi2-test, Fisher's exact test, incidence rate ratio and Kaplan-Meier survival curves were used to compare aPL-positive and aPL-negative patients considering the value of SDI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for SLE) at the end of follow-up, the occurrence of thromboses, organ system involvements and need for immunosuppressive treatment in addition to corticosteroids. RESULTS: Anti-cardiolipin antibodies and lupus anticoagulants were detected in 27 (49%) and 19 (35%) patients, respectively. These aPL were frequently transient or intermittent (10 and 15 cases, respectively), and only rarely persistent over time (five cases). The risk of thrombosis was significantly higher (odds ratio = 6.42) and occurred earlier in the presence of aPL, especially if aPL were persistent (P < 0.05). The association between aPL and neurological, renal, haematological manifestations or need for immunosuppressive treatment was not statistically significant. After a mean follow-up of 7.2 yrs, 30 patients (54.5%) had an SDI score > or = 1. The risk of damage (SDI > or = 1) in aPL-positive patients was three times higher than in aPL-negative patients (P < 0.05). Four of the six fatal cases occurred in the aPL-positive group. CONCLUSIONS: The presence of aPL in p-SLE could represent not only a risk factor for thrombosis but also a poor prognostic factor overall.

[Toxic or drug-induced granulomatous reactions]. / Granulomatoses d'origine médicamenteuse ou toxique.

PURPOSE: To review the current concepts in toxic and drug-induced granulomatous reactions. CURRENT KNOWLEDGE AND KEY POINTS: Granulomatous reactions are induced by various chemical agents, treatments or foreign bodies. According to the breaking way into the organism, the lungs, the liver, the kidneys or the skin are mainly concerned, but systemic granulomatosis mimicking sarcoidosis is possible. Therefore systematic analysis of environmental, occupational and leisure exposures and quest for medical or illicit drugs is mandatory to identify the responsible agent. Over the recent period, chronic beryllium disease, interferon-alpha therapy, BCG immunotherapy and allopurinol have been more frequently involved. FUTURE PROSPECTS AND PROJECTS: Literature review uncovers a variety of potential toxic exposures and highlights the necessity of a clear sighted research to identify them.

[Haemochromatosis screening in 120 patients complaining with persistant fatigue]. / Dépistage de l'hémochromatose chez 120 sujets consultant pour une asthénie chronique.

AIM: Chronic fatigue is the more frequent symptom identified in the course of hereditary haemochromatosis. A screening for this disorder was carried out in 120 primary care patients consulting for unexplained chronic fatigue. SUBJECTS AND METHODS: Transferrin saturation and serum ferritin were determined in all patients. If transferrin saturation was >or= 45% and serum ferritin >or= 300 microg/l, HFE1 genotyping for mutations C282Y and H63D was completed. RESULTS: One hundred and twenty patients were recruited, 19-86 years old, including 62 males and 58 females. 45 patients (38%) presented with serum ferritin >or= 300 microg/l. Thirty two patients (27%) presented with transferrin saturation >or= 45%. Twenty two patients (18%) presented with these two pathological values. Four C282Y/H63D compound heterozygous, one H63D/H63D homozygous, and eight simplex heterozygous (6 H63D and 2 C282Y) genotypes were found. Patients with serum ferritin >or= 300 microg/l were predominantly male (89%), older (57 year) and plethoric (BMI: 26.4) corresponding mainly to dysmetabolic hyperferritinemia. CONCLUSION: None of these 120 patients consulting for unexplained chronic fatigue was found with hereditary haemochromatosis. Therefore observed prevalence is 0, with upper limit of 95% confidence interval at 2.5%. But the high prevalence (38%) of serum ferritin >or= 300 microg/l must be emphasized, corresponding usually to dysmetabolic hyperferritinemia.

Phenotype and genotype of French cystic fibrosis patients with long survival and follow-up.

Background: The aim of this study was to assess the clinical features and the genotype characteristics of French patients diagnosed with cystic fibrosis (CF) before their fifth year and who were still alive after 30 years. It is the first descriptive study of 114 CF patients with long survival and follow-up. We compared this subgroup of French CF patients with the overall French CF population and with French adult (> 18 years) CF patients regardless of their age at diagnosis. Methods: Data were obtained from the French CF registry. Results: The 67 men and 47 women studied were 30-59 years old. Some 56% of the patients had DeltaF508 homozygous genotype, 90% had a pancreatic insufficiency, and 81% were colonized with Pseudomonas aeruginosa. The mean body mass index (BMI) was 19.5 for both female and male patients. Mean forced expiratory volume in 1 s was 46% (S.D. 29.2) of the predicted value for men and 53% (S.D. 20.6) for women. Eleven patients underwent a lung transplantation. Conclusions: The data on the patients with long survival and long follow-up were very similar to the data of the overall CF adult population in terms of clinical status. Therefore, criteria such as DeltaF508 homozygous genotype, pancreatic insufficiency, and P. aeruginosa colonization are not sufficient to serve as prognostic criteria for life expectancy in CF patients.

[MRI of central nervous system in a series of 58 systemic lupus erythematosus (SLE) patients with or without overt neuropsychiatric manifestations]. / Apport de l'IRM cérébrale dans une série de 58 cas de malade lupique avec ou sans manifestations neuropsychiatriques.

PURPOSE: Central nervous (CNS) involvement in SLE is common and can be evaluated with MRI. The primary goal of this study was to evaluate with high-field MRI the CNS involvement in a series of SLE patients with or without neuropsychiatric symptoms. The secondary goal was to detect a possible relationship between MRI and clinical or biological parameters in SLE. MATERIALS AND METHODS: We correlated the clinical and biological parameters of 58 patients with a lupus defined according to the American College of Rheumatology criteria, including 30 with neuropsychiatric manifestations with conventional and modern MRI (including diffusion weighted-images, high-resolution 3D T1 weighted-images). The population studied was compared to a group of 18 normal controls. RESULTS: In 69% of cases, MRI demonstrated involvement of the CNS both in asymptomatic patients (64.3%) and in patients with neuropsychiatric manifestations (73.3%): microembolic signals, cerebral infarctions (associated with the anti-phospholipid syndrome), atrophy, basal ganglia involvement, posterior leucoencephalopathy, subcortical calcification or hemosiderin deposits (T2*), dilated perivascular spaces. CONCLUSION: MRI with adapted sequences clearly demonstrated the cerebral involvement in approximately 70% of SLE patients with or without neuropsychiatric symptoms.

[Analysis of 12 cases of McArdle's disease diagnosed after 30 years]. / Maladie de MacArdle diagnostiquée après 30 ans : à propos de 12 cas.

PURPOSE: McArdle's disease (MAD) or glycogen storage disease type V, usually starts in childhood or adolescence. Generally diagnosis is made before the early adulthood because patients present well defined syndrome and are constrained. METHOD: We retrospectively investigated all MAD cases diagnosed in the biochemical laboratory from Debrousse Hospital in Lyon, during 40 years (1962-2002). We then selected patients whose diagnosis had been made after 30 years. RESULTS: Fifteen patients answered our criteria but only 11 files could be analysed. A twelfth patient (service of internal medicine--Royan) supplemented the series. We sought the reasons of a late diagnosis: early age of beginning but few symptoms (7 cases), age of beginning higher than 20 years (5 cases including 3 after 45 years). The principal symptoms were muscular deficit and muscular pains (8 cases) and second wind phenomenon (7 cases). Creatinine phosphokinase level was constantly high. Ischemic effort test when it was carried out was constantly abnormal. Conversely electromyogram was often normal (5 cases). Several biopsies were necessary in a third of the cases to evoke the diagnosis, particularly among the patients with late onset symptoms. CONCLUSION: Diagnosis of metabolic MAD is generally easy if the interrogation finds inaugural symptoms in childhood or adolescence even if the patient consults very late in the life. The diagnosis can become much more difficult if it begins late in life (atypical symptoms, need for several muscular biopsy).

Mucosal ulcerations revealing primitive hypereosinophilic syndrome.

We report the case of a 27 year-old man developing recurrent oral aphtosis associated with fever and 8 kg of weight loss. Moderate splenomegaly was observed on physical examination and neurological and cardiac examination were normal. Laboratory findings included marked eosinophilia at 3280 giga/l. Bone marrow (BM) examination revealed a myeloproliferative syndrome with mature eosinophils. Splenectomy was performed because of a suspected nodule on the BM, the histopathology revealed a myeloid metaplasia. The diagnosis of myeloproliferative form of hypereosinophilic syndrome (HES) was made. He was treated with interferon-alfa and hydroxyurea. After two years of treatment he had no ulcer recurrence and eosinophil count was at 180 giga/l. Mucosal manifestations as a prodromal symptom of HES are rare. The histology of the lesions shows numerous eosinophils; immunohistochemical analysis confirms the presence of eosinophil peroxydase, major basic protein and eosinophil derived neurotoxin. A few cases have been described. Death occurs 11 months to 5 years after the diagnosis of oral ulcerations. The treatment consists of interferon-alfa and hydroxyurea.

[Neurological manifestations of Whipple disease]. / L'atteinte neurologique dans la maladie de Whipple.

Whipple disease is an uncommon chronic bacterial infection due to Tropheryma whipplei. Clinical manifestations are protean (joint pain, fever, weight loss, abdominal pain, lymphadenopathies), and the diagnosis is often delayed. Although previously considered a late manifestation of Whipple disease, neurological involvement is now frequently the initial clinical manifestation and represents the greatest risk for long-term disability. All patients should be treated and monitored as if they had central nervous system disease even if they are asymptomatic. Neurological manifestations include dementia (56 percent), abnormalities of eye movements (33p. cent), involuntary movements (28 percent), seizures, hypothalamic dysfunction, myelopathy, ataxia and psychiatric manifestations. Uveitis, retinitis, optic neuritis and papilloedema may be found. 80 percent of the reported cases of neuro-Whipple had associated systemic symptoms or signs but many patients are presenting without concurrent intestinal manifestation. Thus, the disease may remain undiagnosed or misdiagnosed, as rheumatoid arthritis or sarcoidosis. Traditionally, the diagnostic procedure of choice is biopsy of the duodenal mucosa by demonstrating PAS-positive foamy macrophages. However, not all cases have small bowel infiltration and tissue obtained from sites clinically affected may be helpful. CT and MR images of the central nervous system are normal or not specific: atrophic changes, mass lesions, focal abnormalities and hydrocephalus. The application of a PCR assay against Tropheryma whipplei has transformed the diagnosis. Positive results have been obtained from several tissues and from CSF and PCR is more sensitive than other techniques. All patients must be treated with antibiotics which cross the blood-brain barrier. Most agree that initial treatment with a combination of parenteral penicillin and streptomycin for at least 14 days is appropriate, thereafter cotrimoxazole orally 3 times a day for at least one and probably for two years. Third generation cephalosporins, rifampicin and chloramphenicol have been used successfully. PCR is recognized to be a useful tool for monitoring progress but it is sometimes difficult to reverse established neurological defects.

[Inaugural symptoms of Horton's disease in a series of 260 patients]. / Symptômes inauguraux de la maladie de Horton sur une série de 260 patients.

PURPOSE: Horton disease or 'giant cell arteritis' is a known entity in its typical form; the difficulty in diagnosis is due to the atypical signs and symptoms. METHODS: We review 260 medical files presenting Horton disease between 1979 and 1999 in five different departments: three internal medicine departments, one rheumatology department and one geriatric department. RESULTS: The study shows a female domination with a mean age of 75 years. Temporal artery biopsy was done on all patients. Ten patients presented a vascular manifestation. The neurological manifestation was the first symptom in four patients. Five patients had cutaneous symptomatology, with positive temporal artery in three cases. Renal manifestation was present in two patients. Two symptoms are important to discuss because of their frequency: the cough and the peripheral arthritis. We found nine observations with arthritis affecting large joints and responding to nonsteroidal antiinflammatories with positive temporal artery biopsy in seven patients, and 21 observations manifesting by cough without radiological signs; in 57% of cases the temporal artery biopsy was positive, and the cough regressed with corticoids. CONCLUSION: These atypical symptoms have to be known to make a diagnosis and to begin a corticotherapy as soon as possible.

Duration of the antihistaminic effect after discontinuation of ebastine.

BACKGROUND: The inhibitory effect of antihistamines on allergen-induced skin reactions can impair the results of allergen skin testing, which are necessary for the diagnosis of atopic diseases. This study was designed to determine the time period required for the inhibitory effect of ebastine on allergen-induced skin reactivity to disappear completely. METHODS: This was a double-blind, placebo-controlled, parallel-group study including 23 out of 27 randomized patients. They received either ebastine 20 mg or placebo once daily for 7 days. At the end of treatment, allergen challenge was performed daily for 7 days. Histamine challenge was performed on day 1 (6 and 24 h) and day 5 after treatment. The wheal and flare surface areas were measured and analyzed. RESULTS: Highly significant inhibition of the wheal and flare response induced by allergen was observed after ebastine treatment on days 1 and 2 as compared with placebo (P < 0.01 for both). The inhibition was reduced, although still significant, by day 3 (P < 0.05). No significant difference was observed by day 4 between the ebastine and the placebo groups. The effects of histamine challenge were significantly reduced in the ebastine compared with the placebo group at day 1 (6 and 24 h), and were similar at day 5 after treatment. CONCLUSION: Our results show that the wheal and flare response to allergen after ebastine discontinuation returns to placebo values after 4 days. Therefore, patients using ebastine need to be antihistamine-free for 4 days before the skin prick test. This is valuable information for the allergologist seeking to diagnose allergen sensitivity.

[Hereditary hemochromatosis]. / L'hémochromatose génétique.

INTRODUCTION: Hereditary hemochromatosis is a fairly common disease in the Caucasian population, with a prevalence estimated at between 1.5 to 3/1,000 inhabitants. Over the past few years, its symptomatology has altered; at present, its clinical aspect with diabetes mellitus, cirrhosis, and darker skin pigmentation only constitutes 10% of new cases of this disease. CURRENT KNOWLEDGE AND KEY POINTS: In 1996, the discovery of the C282Y mutation in the HFE gene radically altered the diagnostic approach to hereditary hemochromatosis. At present, any patient admitted with an isolated case of asthenia, or with arthralgia or hypertransaminasemia should be examined via transferrin-saturation testing: if the transferrin saturation coefficient is > 45%, then the presence of the C282Y mutation should be investigated to confirm the diagnosis of hemochromatosis. A liver biopsy is no longer necessary to establish the diagnosis, but this is still useful in cases of possible cirrhosis, which is the main risk factor for hepatocellular carcinoma. Phlebotomy remains the sole recommended treatment, and should be undertaken in a case-specific manner. Family screening should be carried out for all first-degree relatives for every new case that is diagnosed. FUTURE PROSPECTS AND PROJECTS: The discovery of the HFE gene has permitted hereditary hemochromatosis to be easily differentiated from other forms of hepatic iron overload including a new syndrome, dysmotabolic hepatosiderosis. Casos of homozygotic C282Y without hepatic iron overload have been described, but the clinical outcome of some of these cases requires further study, and adds to the controversy on whether systematic population screening should be made available.