Association of myelodysplastic syndrome and relapsing polychondritis: further evidence.

We report five patients with both a myelodysplastic syndrome (MDS) and relapsing polychondritis (RP), that represented 0.6% of all MDS and 28% of all RP diagnosed over a period of 14 years. Ten other cases had previously been reported (four in detail), supporting a non-fortuitous association between the two disorders, already suggested for MDS and some other immunological disorders.

POEMS syndrome: report on six patients with unusual clinical signs, elevated levels of cytokines, macrophage involvement and chromosomal aberrations of bone marrow plasma cells.

POEMS syndrome is a multisystemic disorder characterized by the association of polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes and various other systemic clinical signs. The pathophysiology of this syndrome remains largely unknown. In order to gain insight into its pathophysiology, we studied the clinical characteristics and performed serum analysis (auto-antibodies, cytokine levels) and phenotypic and cytogenetic studies of bone marrow plasma cells (BMPC) in six patients with unequivocal POEMS syndrome. Two unusual clinical signs were present in these patients: pulmonary hypertension (two patients) and diffuse cutaneous necrosis (one patient). No auto-antibodies against peripheral nerve (PN) antigens (SGPG and SGLPG glycolipids, GM1, GD1a, GD1b and GT1b gangliosides) were found. Sequential evaluations of serum cytokines (IL-1-beta, IL-6 and TNF-alpha) showed a moderate to marked elevations of IL-6 and TNF-alpha in all patients (up to six-fold for TNF-alpha and 16-fold for IL-6). Using in situ hybridization of these cytokines mRNAs on lymph node specimens of two patients who had an angiofollicular lymph node hyperplasia, a strong positivity was found with the IL-1-beta antisense probe in lymph node macrophages. On skin biopsy a high number of cells expressing TNF-alpha mRNA was observed in the dermis. The biological features of BMPC: phenotype (expression of CD19 and CD56 antigens), kinetics (Ki-67 index), karyotype, DNA content and chromosomal in situ hybridization remained those of BMPC found in monoclonal gammopathy of undetermined significance. We conclude that POEMS syndrome is a hypercytokinemic syndrome in which BMPC are not of malignant type. Macrophages are involved in this syndrome and their role has to be further investigated as well as treatments which act through an anti-cytokine mechanism.

Influence of age on characteristics of polymyositis and dermatomyositis in adults.

In a retrospective study of 79 consecutive patients, we evaluated characteristics of polymyositis (PM) and dermatomyositis (DM) and compared clinical presentation, biochemical findings, histologic changes, evolution, complications, and mortality rate of elderly patients (aged > or = 65 yr) and younger patients (aged < or = 64 yr) at the onset of PM/DM. We found a high prevalence of PM/DM in elderly patients: 23 patients (29%) were aged 65 years or over. We also found that esophageal involvement (34.8% versus 16.1%, respectively) and bacterial pneumonia related to both ventilatory insufficiency and esophageal impairment (21.7% versus 5.4%, respectively) were more common in elderly patients compared with younger patients, resulting in increased morbidity and mortality rates. Moreover, malignancy frequency was higher in elderly patients compared with younger patients (47.8% versus 9.1%, respectively, p = 0.0001), particularly patients with DM (10/11). Fifty percent of malignancies were colon malignancies in elderly patients. Erythrocyte sedimentation rate, C-reactive protein, fibrinogen, and ferritin levels were also higher in the elderly patient group compared with the younger group, and the presence of serum hypoprotidemia, hypoalbuminemia, and anemia was more frequent. Finally, PM/DM complete remission was less frequent (13.6% versus 41.1%) and the mortality rate (47.8% versus 7.3%) was higher in elderly patients than in younger patients. The main causes of death in elderly patients were bacterial pneumonia, due to ventilatory insufficiency and esophageal impairment, and malignancies. Our findings therefore indicate that PM/DM-related esophageal and lung involvement should be systematically searched for in elderly patients. Esophageal manometry and pulmonary function tests should become an integral part of initial evaluation in elderly patients for early detection of impairment. Moreover, as we observed a marked overrepresentation of colon cancer in elderly patients with DM, we suggest that the search for malignancies in elderly patients with DM should include lower gastrointestinal tract investigations.

Prospective and serial study of primary amyloidosis with serum amyloid P component scintigraphy: from diagnosis to prognosis.

OBJECTIVE: The purpose of this study was to assess the value of the serum amyloid P (SAP) component scintigraphy in patients with primary amyloidosis (AL). MATERIAL AND METHODS: Pure human SAP labeled with iodine-123 (123I-SAP) was given intravenously to 24 patients with biopsy-proven systemic amyloidosis (15 without multiple myeloma = group 1, and 9 with multiple myeloma = group 2) and to 6 patients with multiple myeloma without any clinical or biological signs of amyloidosis (group 3). Whole-body images as well as regional views and tissue retention levels were obtained after 24 hours. Our study was approved by the institutional review committee and all individuals gave informed consent and were prospectively studied (median 13 months, range 1 to 47 from the date of the scintigraphy to May 1995). RESULTS: Organ localization of 123I-SAP, indicating the presence of substantial visceral amyloid deposits, was observed in all patients in group 1 and 2. The organ uptake of 123I-SAP included the spleen (1 patient was splenectomized) in 20 of 23 cases (87%), the liver in 15 of 24 (60%), and the kidneys in 6 of 24 (25%). Myocardial 123I-SAP was never seen although 13 out of the 24 patients had clinical or echographic data for amyloidosis. Twenty-four hour tissue retention was significantly elevated in all patients (group 1 and group 2): 55.66% +/- 19.16% in group 1 and 34.37% +/- 24.92% in group 2, as compared with normal levels < 24%. The sensitivity of the technique was 79% when only organ uptake was considered but reached 100% when tissue retention was also considered. The 24-hour tissue retention might be correlated with the severity of the amyloidosis: mean survival in patients with tissue retention greater than 50% was 11.3 months versus 24.5 months in patients with levels less or equal to 50%. Five of the 6 patients with multiple myeloma without evidence of amyloidosis had abnormal 123I-SAP imaging and 24-hour tissue retention levels. In 2 of them, amyloidosis was secondly detected. In the 9 patients who had two scintigraphies, variations in 24-hour tissue retention values were in accordance with the clinical evaluation. CONCLUSIONS: Spleen and liver distribution of amyloidosis is mostly revealed by 123I-SAP scintigraphy in patients with AL amyloidosis. The uptake of 123I-SAP appeared in proportion to the quantity of amyloidosis present in different tissues, and the relative quantity of amyloid deposits in the myocardium, carpal tunnel, digestive tract, and kidneys was often small and seldom visualized by 123I-SAP scintigraphy. In contrast 24-hour tissue retention levels were abnormal in all cases of known AL amyloidosis. This may be a positive argument for the diagnosis of amyloidosis when histopathological tests are normal. Tissue retention levels appear important as they may be correlated with survival.

'Localized amyloidosis': 123I-labelled SAP component scintigraphy and labial salivary gland biopsy.

In apparently localized amyloidosis, there is no appropriate test to determine whether systemic deposits exist. We studied the value of serum amyloid P component (SAP) scintigraphy and labial salivary gland (LSG) biopsy on patients with apparently localized amyloidosis in 12 patients who had neither clinical nor biological evidence of systemic amyloidosis. All patients had an LSG biopsy and echocardiography. Iodine-123-labelled serum amyloid P component (123I-SAP) scintigraphy was performed in all patients. Whole-body scintigraphy was done, and tissue retention was evaluated at 24 h and 48 h. Of these 12 patients, three had amyloidosis in their LSG and had abnormal 123I-SAP scintigraphy; these three had a secondary clinical history of systemic amyloidosis. Three other patients had abnormal 123I-SAP scintigraphy without detectable systemic amyloid deposits, but one had a previous history of bilateral carpal tunnel syndrome treated with infiltration. 123I-SAP scintigraphy in association with LSG biopsy may be helpful in determining the localized or systemic character of amyloid disease.

Serum amyloid A concentrations in giant-cell arteritis and polymyalgia rheumatica: a useful test in the management of the disease.

A prospective clinical study of 23 patients with giant-cell arteritis (GCA) and/or polymyalgia rheumatica (PMR) was undertaken in order to assess the behaviour of the non-specific markers of the disease activity, the erythrocyte sedimentation rate (ESR) and other acute phase markers, particularly the C-reactive protein (CPR) and serum amyloid A apolipoprotein (apo SAA) levels during induction of disease remission by prednisone therapy, and possible further recurrence of GCA and/or PMR. The apo SAA measurement is more sensitive than the CRP measurement in determining disease activity (97% and 61%, respectively). The specificity of apo SAA is greater than ESR in the determination of inactive disease (86% and 77%, respectively). In some cases with clinically active disease the ESR and CRP were normal, whereas the apo SAA was always elevated. We conclude that the apo SAA measurement in combination with clinical data and other laboratory parameters may be useful in the management of GCA and/or PMR.

Prognostic factors and long-term evolution in a cohort of 133 patients with giant cell arteritis.

OBJECTIVE: Survival in patients with giant cell arteritis (GCA) has generally been found to be similar to that of the general population. The aim of our study was to assess outcome and survival of different subgroups of patients with GCA in relation to clinical, biological data or treatment modalities. METHODS: From 1977 and 1995, 176 patients were treated in the Department of Internal Medicine for GCA. The patient, family or local practitioner were contacted prior to the study (July-October 1995). Treatment modalities and follow-up were obtained for 133 patients. All patients (except 11) had 3 or more 1990 ACR classification criteria for GCA. The 11 patients with 2 criteria had a positive temporal biopsy and were included in the study. RESULTS: Relapse during corticosteroid tapering treatment was observed in 83 patients (62.4%) with a mean 1.57 relapses per patient. No correlation was found in age, sex, initial dose or type of steroid used (i.e. prednisone or prednisolone). Only a slight correlation in the initial erythrocyte sedimentation rate (ESR) was observed (p < 0.01, r = 0.23). In 56 patients free of treatment (mean treatment duration: 40 months), 27 (48%) developed a relapse of the disease 1 to 25 months later. No correlation was found in age, sex, initial dose of steroid, number of relapses during treatment, or initial ESR. Survival analysis was performed using the Kaplan-Meier and Mantel-Menszel methods for comparison of groups. At the time of the study, 41 patients had died (30.7%). A significant reduction of survival was found with the presence of permanent visual loss vs absence (p = 0.04), in patients who required more than 10 mg/d of glucocorticoid (p < 0.001) at 6 months treatment and in patients treated with prednisone (vs prednisolone) (p < 0.01). However, these factors were not independently associated with survival in the multivariate analysis. CONCLUSION: Relapse was observed in 62.4% of the patients during corticosteroid tapering (correlated with initial ESR). A relapse of the disease was also observed in 48% of patients 1 to 25 months after the end of the treatment and was associated with prednisolone use. Long term survival was better in patients with no initial ocular manifestations, in patients who took less than 10 mg/day of corticosteroids at 6 months of the treatment and in patients treated with prednisolone.

Percutaneous vertebroplasty with acrylic cement in the treatment of a Langerhans cell vertebral histiocytosis.

A 25-year-old man developed multiple eosinophilic granuloma of bone including vertebral and sacral localization. Radiotherapy was initially administered. One year later, a relapse occurred in another vertebrae which was previously irradiated. Percutaneous vertebroplasty was, for the first time to our knowledge performed, in this indication, with a good clinical result with follow-up now for one year. We emphasize that such treatment is permissible only in symptomatic, progressive lesions, with threatened decompensation of spinal stability. This technique should be used only on an adult.

Cannabis arteritis revisited--ten new case reports.

The purpose of this paper was to revisit the old concept of cannabis arteritis first described in the 1960s and report 10 new cases. Ten male patients, with a median age of 23.7 years developed subacute distal ischemia of lower or upper limbs, leading to necrosis in the toes and/or fingers and sometimes to distal limb gangrene. Two of the patients also presented with venous thrombosis and three patients were suffering from a recent Raynaud's phenomenon. Biological test results did not show evidence of the classical vascular risk factors for thrombosis. Arteriographic evaluation in all cases revealed distal abnormalities in the arteries of feet, legs, forearms, and hands resembling those of Buerger's disease. A collateral circulation sometimes with opacification of the vasa nervorum was noted. In some cases, arterial proximal atherosclerotic lesions and venous thrombosis were observed. All patients were moderate tobacco smokers and regular cannabis users. Despite treatment with ilomedine and heparin in all cases, five amputations were necessary in four patients. The vasoconstrictor effect of cannabis on the vascular system has been known for a long time. It has been shown that delta-8- and delta-9-tetrahydrocanabinols may induce peripheral vasoconstrictor activity. Cannabis arteritis resembles Buerger's disease, but patients were moderate tobacco smokers and regular cannabis users. These cases show that prolonged use of cannabis could be an additive risk factor for juvenile and young adult arteritis. Cannabis arteritis is a forgotten and severe occlusive vascular disease occurring in young adults. Search for cannabis use may be an important tool for a better knowledge of arteritis in young smokers.

Lymphocytes T and pharmacokinetics after a single oral dose of levamisole in healthy and cancer subjects.

Levamisole, an anthelmintic drug with immunopotentiating activity, is shown to have variable effects on cell-mediated immunity. We have studied the effect of a single oral dose (2.5 mg/kg or 5 mg/kg) on early and spontaneous E rosettes percentages in healthy and cancer patients. Pharmacokinetic study of this compound was conducted in parallel. The results indicated that single administration of levamisole (2.5 mg/kg) in healthy men can promote an increase of early E rosettes with mean peak plasma level of 0.8 micrograms. ml-1. On the other hand, there was no change in the proportion of early E rosettes in cancer patients and in the proportion of spontaneous E rosettes in healthy and cancer subjects.

[Effects of a high dose of vitamin A on experimental immunologic arthritis]. / Effets d'une dose élevée de vitamine A sur les arthrites immunitaires expérimentales.

Vitamin A, a good adjuvant to immunologic reactions, has in this aspect an interesting therapeutic effect, especially in immunotherapy. On the other hand, in diseases caused by circulating immunocomplexes or in auto-immune diseases, vitamin A can prolong the pathologic immunologic process. This experimental study shows that vitamin A in high doses has an adjuvant effect, that is aggravating considerably the immunologic arthritis induced in the Wistar rat.

[Value of transcutaneous staged dynamic oximetry of stage II arteritis of the leg]. / Intérêt de l'oxymétrie transcutanée dynamique étagée dans l'artérite des membres inférieurs de stade II.

The clinical and prognostic value of transcutaneous oxygen pressure measurements at rest has been established in Leriche Stage III and IV occlusive peripheral arterial disease but is controversial in Stage II because there is an overlap of transcutaneous pO2 (Tc pO2) values with those of normal subjects. The authors report the results of Tc pO2 measurements during exercise testing in a group of patients with Stage II occlusive arterial disease of the lower limbs. Seventy-eight patients with an average age of 53 years (range 40 to 65 years) whose claudication perimeter and site of pain had been carefully assessed and who had also recently undergone Doppler arterial examination and arteriography and 35 control subjects with an average age of 54 years (range 45 to 70 years) were studied. The Tc pO2 was continuously measured with a multimodular Kontron Supermon at 4 different sites simultaneously: precordium (reference probe), thigh, calf and foot in the dorsal recumbent position after 30 minutes rest, during a standardised exercise stress test at 50 watts and during the recovery phase. The results were expressed as ratio of tissue oxygenation (RTO): thigh, calf or foot Tc pO2/precordial Tc pO2 X 100 in order to take into account the patients cardiorespiratory status and adaptation to exercise. The RTO in normal subjects remained at the upper limits of the resting value throughout exercise and then returned slowly to basal values during the recovery phase.(ABSTRACT TRUNCATED AT 250 WORDS)

[Significance of arterial Doppler in Horton's disease. Prospective study of 59 case reports]. / Intérêt du Doppler artériel dans la maladie de Horton. Etude prospective de 59 observations.

Several preliminary studies drew attention to the value of Doppler examination in temporal arteritis. This study involving 59 cases aimed to define the value of Doppler examination in the diagnosis of the disease, evaluation of ophthalmic risk and in the monitoring of treatment. The study involved 59 patients and 47 controls with no evidence of temporal arteritis, but of comparable mean age. The following arteries were investigated before treatment: arteries of limbs, subclavian, vertebral, carotid, temporal, occipital, facial and ophthalmic recorded via the internal nasal branch and also transocularly. The results were expressed in the form of a score from 0 to 3 describing the degree of deterioration of the curves. A mean score corresponding to the mean of the scores of the cephalic arteries was calculated for each patient and each control. The specificity and sensitivity of the investigation were studied, based on this mean score by ROC analysis. The progression under treatment was monitored for more than 24 months in 20 patients divided into 3 groups: group I: 6 patients cured; group II: 6 patients with late recurrence of temporal arteritis after steroid withdrawal; group III: 8 patients with progressive disease. 81.5% of temporal arteries were pathological, including 60% with tight stenosis (score 2 and 3). Morphological anomalies in the curves were also noted at the level of the occipital arteries (69%), facial arteries (80%), as well as the ophthalmic artery at both recording sites (internal nasal: 84.5%, transocular: (73%) (table I).(ABSTRACT TRUNCATED AT 250 WORDS)

[Chorea and systemic lupus erythematosus with circulating anticoagulant. 3 cases]. / Chorée et lupus érythémateux disséminé avec anticoagulant circulant. Trois cas.

Circulating anticoagulant was detected during the course of choreic manifestations in three young women with systemic lupus erythematosus, associated in two cases with false syphilitic serology due to the presence of antiphospholipid antibodies. The high prevalence of the presence of these antibodies in lupic chorea was confirmed by reports of 41 cases in the literature. These findings could suggest a possible pathogenic role for these antibodies in choreic manifestations by either a thrombotic or auto-immune encephalitis mechanism.

[Calcium antagonists and Raynaud's phenomenon]. / Antagonistes calciques et phénomène de Raynaud.

Epidemiologic studies indicate that episodic vasospasm of arterioles (Raynaud's phenomenon) is a common finding in the general population. The prevalence has been estimated at approximately 10%. Raynaud's phenomenon follows a benign course in most cases and may improve or even disappear in time. Occasionally, Raynaud's phenomenon may be induced by some drugs (beta-blockers, ergot, vinblastine...) or some occupations (pneumatic hammer operators, hand-arm vibration syndrome...) or may be a sign of connective tissue disease (systemic sclerosis, systemic lupus erythematosus, Sjögren's syndrome...). Several different physiologic mechanisms may be responsible for vasospasm: hyperactivity of the sympathetic nervous system and abnormal adrenergic receptor function appear to be most important. Calcium channel blockers have been studied extensively for the treatment of primary and secondary Raynaud's phenomenon. There have been shown to be particularly effective for inhibiting vascular responses evoked by alpha 2-adrenoceptor activity. Calcium channel blockers have been mostly effective in Raynaud's phenomenon.

[Arteriopathies as occupational diseases]. / Artériopathies des maladies professionnelles.

Arteriopathies of occupational diseases predominate in the upper limbs and are usually expressed as Raynaud's phenomenon ("white finger"), sometimes complicated by digital gangrene. Hand-arm vibration disease, hypothenar hammer syndrome, exposure to silica even without silicosis and vinyl chloride intoxication are the principal causes of occupational diseases acknowledged as such by the laws. In a personal series of 60 patients with complicated upper limb arteriopathies, 25% had a recognized occupational disease. Since December 1992, Erasmus' syndrome and systemic scleroderma due to silica without silicosis have been accepted in France as being occupational diseases. The therapeutic problems are discussed, notably the surgical indications in hypothenar hammer syndrome, the possible medical treatments of finger necrosis occurring in Erasmus' syndrome and, in particular, the role played by spinal cord neurostimulation.

[Sarcoidosis of the upper respiratory tract. Review of the literature apropos of 2 cases]. / Sarcoïdose des voies aériennes supérieures. Revue de la littérature à propos de deux observations.

We describe two cases with sarcoidosis affecting upper respiratory tract. This uncommon localization, may occur in patients with previously diagnosed sarcoidosis, but it may be the first or the only manifestation of the disease. A severe upper airway obstruction can occur, necessitating urgent tracheostomy. Systemic corticosteroid therapy is the treatment of choice in most cases.

[Silicosis and primary Gougerot-Sjögren syndrome]. / Silicose et syndrome de Gougerot-Sjögren primitif.

We report three cases of primary Sjögren's syndrome in silicotic coal miners. All patients fulfilled the diagnostic criteria for Sjögren's syndrome recently established by the European Community study group. One patient had cryoglobulinemia and polynevritis. Another had Raynaud's phenomenon, arthralgia, purpura and polynevritis. Capillary microscopy was normal in all the three patients. Antinuclear antibodies were detected only in one patient, who had also anti-SSa and anti-SSb antibodies. The prevalence of systemic sclerosis, rheumatoid arthritis and probably systemic lupus erythematosus is significantly higher after longstanding occupational exposure to silica. On the contrary, any case of Sjögren's syndrome was till now described in the course of pulmonary silicosis. The physiopathological mechanisms of these associations are misunderstood.

[Comparison of the efficacy between simvastatin and gemfibrozil in primary hypercholesterolemia]. / Comparaison de l'efficacité de la simvastatine et du gemfibrozil dans l'hypercholestérolémie primaire. Groupe d'Etude Français.

The efficacy on plasma lipids, apo A1 and B of a HMG Co A Reductase inhibitor, simvastatin, and a fibrate derivative, gemfibrozil, were compared in 136 hypercholesterolemic patients. The study was randomized, double-blinded and the active drug was given after a 4 week period of placebo. Gemfibrozil (n = 69) was given at 900 mg q.p.m. during the entire study. The primary dose of simvastatin was 10 mg q.p.m. during the first 6-weeks of treatment. At the end of this period, the dose was doubled if the cholesterol level was above 2 g/l (5,16 mmol/l). The same modification was carried out 12 weeks after the beginning active drug treatment with the same criteria. The baselines of total cholesterol were 3.24 +/- 0.69 g/l (8.38 +/- 1.78 mmol/l) 3.21 +/- 0.72 g/l (8.31 +/- 1.87 mmol/l) for patients with simvastatin and those with gemfibrozil respectively. So, at the end of active treatment, 64% of patients in the simvastatin group (n = 67) received 40 mg q.p.m. After 18 weeks of treatment, 89% of patients treated with Simvastatin and 37% with gemfibrozil had more than 20% reduction in LDL cholesterol. Simvastatin was more efficient on total cholesterol, LDL-C and apo B. The increase of HDL-C is similar in both groups of patients. In contrast, the level of triglycerides was further decreased by gemfibrozil. The tolerance was good in the two groups of patients and no difference in the frequency of side effects was observed.

[Digital arteritis, thrombosis and hypereosinophilic syndrome: an uncommon complication]. / Artérite digitale, thrombose et syndrome hyperéosinophilique: une complication exceptionnelle.

Digital necrosis has been exceptionally described in association with the hypereosinophilic syndrome. We report a case of a smoking patient with idiopathic hypereosinophilic syndrome who developed digital arteritis with necrosis. A radial artery biopsy confirmed the vasculitis with inflammatory infiltrates which were predominantly eosinophilic granulocytes. The eosinophils may have an active role in the development of the vasculitis.