Inefficacy of intravenous immunoglobulins and infliximab in Degos' disease.

We report the case of a 60-year-old man who presented with sudden visual loss, a history of postprandial abdominal pain, malabsorption, and skin lesions typical of systemic Degos' disease. Despite anti-aggregants and prednisone the patient's status did not improve. On the basis of the hypothetical dysimmune origin of this disease, we attempted treatment with intravenous immunoglobulins, without success. We then administered infliximab (Remicade), but 2 months after the third injection the patient developed mesenteric infarction and died. We therefore believe that both intravenous immunoglobulins and antiTNFalpha are ineffective for the treatment of Degos' disease.

An atypical case of Whipple's disease: case report and review of the literature.

We report the case of a 57-year-old man, presenting with bilateral panuveitis, bilateral sacroiliitis, intermittent pyrexia and a pulmonary nodule. The patient had been under immunosuppressive treatment for 2 years for Behçet's disease. However, he did not fulfill the diagnostic criteria of Behçet's disease. Blood analysis showed a very high C reactive protein (CRP at 34 mg/dl). In view of severe intra-ocular inflammation, the anterior chamber was punctured. Polymerase chain reaction (PCR) on the aqueous humour and on the blood revealed the presence of Tropheryma whippelii DNA, an agent responsible for Whipple's disease. The patient was treated with ceftriaxone followed by trimethoprim-sulfamethoxazol for 1 year with good clinical and biological evolution. This case illustrates the difficulty to diagnose an atypical Whipple's disease. In cases of uveitis with atypical signs and/or not responding to the treatment, the internist must consider to perform an analysis of the ocular fluids.

Positive octreotide scintigraphy and determination of lanreotide activity in Paget's disease of bone associated with phosphate diabetes: a case report.

A patient with Paget's disease developed phosphate diabetes (phosphate: 1.6 mg/dl (2.5-4.4 mg/dl), with 29 ml/min phosphate clearance (Nl<15ml/min) and a 65% phosphate reabsorption rate (Nl>85%). As previously demonstrated in tumor-induced osteomalacia, we hypothesized that osteoblasts might manifest somatostatin receptor activity. The patient underwent an octreotide scan which demonstrated increased uptake localized in affected bone. Under lanreotide treatment (40 mg i.m.), the patient's bone pain improved with a concomitant decrease in phosphate alkaline level. Phosphate clearance and tubular readsorption rate of phosphate did not change significantly. We reviewed previously reported cases of associated Paget's bone disease and phosphate diabetes.

[Review on hypertrophic osteoarthropathy and digital clubbing]. / Le point sur l'ostéoarthropathie hypertrophique et l'hippocratisme digital.

Clubbing was first described by Hippocrates more than 2.500 years ago. It may be seen alone or as part of an entity called hypertrophic osteoarthropathy which include periostitis, arthritis and sometimes thickening and edema of the skin around the affected joints. Pulmonary diseases such as cancer, abscess, empyema, bronchiectasis and cystic fibrosis are the major diseases known to be associate with hypertrophic osteoarthropathy. Digestive tract cancer, cyanogenic congenital heart disease are well known association. Many theories have attempted to explain the appearance of this sign but few have persisted. In this article, we review characteristics, relation with etiology and the basis of the pathophysiology of hypertrophic osteoarthropathy and particularly of clubbing.

Possible association between deep infection and hypertrophic osteoarthropathy. Report of three cases and review of the literature.

Hypertrophic Osteoarthropathy is classically associated with chronic pulmonary disease, cancer or inflammatory bowel disease. However, deep infection such as vascular graft infection is an etiology important to recognize because of the risk of life-threatening complication (aorto-enteric fistula). In this study, we reported two cases of aortic graft infection and one case of para-anal abscess associated with hypertrophic osteoarthropathy. The previously reported cases are reviewed.

Relationship between red cell mean corpuscular volume and 6-thioguanine nucleotides in patients treated with azathioprine.

Azathioprine (AZA) is characterized by high interindividual differences in bioavailability and metabolization. The aim of the present study was to analyze, in patients treated with AZA for various immune system disorders, whether the variation in red blood cell mean corpuscular volume (deltaMCV) could be used as an indirect estimation of the level of the active immune modifier metabolite 6-thioguanine nucleotides (6-TGN). In 43 consecutive patients treated with a stable dose of AZA for at least 6 months who were not initially anemic, the erythrocyte 6-TGN levels with routine hematologic parameters were determined two to four times at 1-month intervals. In most patients MCV significantly increased after 3 months of therapy and stabilized after 6 months. The correlation between the daily dose of AZA and the 6-TGN level was mild (r = 0.51; P<.001). A weak correlation was also found between the dose of AZA and the deltaMCV after at least 6 months of therapy (r = 0.36; P<.05). The correlation between deltaMCV and 6-TGN level, however, was much better (r = 0.74; P<.001). The lack of a significant increase in MCV after 3 to 4 months of AZA therapy reflects low 6-TGN levels, sometimes a result of undertreatment. A determination of the 6-TGN level during the first months after AZA therapy is begun will allow more accurate adaptation of the effective dose. We observed that deltaMCV could be used as an indicator of 6-TGN levels after 6 months of AZA treatment. An increase in MCV of at least 6 fL is expected to reflect a 6-TGN level of about 175 pmol/8x10(8) red blood cells (probably being within a therapeutic value).

[Peripheral ulcerative keratitis and a form of limited wegener's granulomatosis]. / Kératite périphérique ulcérative et forme limitée de la granulomatose de Wegener.

A man aged 68 years presents superior limbal infiltrates at his left eye two weeks before a marginal ulcer which quickly perforates. He has no systemic complaint. Clinical, biological, radiologic and histological evaluations disclose superior airways and lungs implications, an inflammatory syndrome, high ANCA (antineutrophiles cytoplamic antibodies) titer and vasculitis. There is no sign of renal involvement. A limited form of Wegener's granulomatosis is diagnosed. The outcome is favorable with a partial penetrating keratoplasty and systemic corticosteroid therapy in association with immunosuppressive drugs. This so called limited form of Wegener's granulomatosis is sight threatening when eye is the initial presentation. The early diagnostic and treatment will be performed by the help of ANCA in cases with subclinical systemic manifestations.

Restoration by corticosteroids of the hyperaldosteronism in hyponatraemic rats with panhypopituitarism.

1. In the syndrome of inappropriate secretion of antidiuretic hormone, hyponatraemia is associated with a normal bicarbonate concentration despite dilution. This normal bicarbonate concentration is related to the development of a hyperaldosteronism, which is attributed to a direct stimulation of the zona glomerulosa by the hyponatraemic state. Some workers have suggested that, to develop this hyperaldosteronism requires the presence of a pituitary factor. To determine whether the pituitary gland plays a role in this hyponatraemia-induced hyperaldosteronism, water intoxication was performed for 24 h in normal and in panhypopituitaric rats. 2. In normal rats, hyponatraemia (108 mmol/l), induced by the administration of 1-desamino-8-D-arginine vasopressin and 2.5% D-glucose-0.45% NaCl by gavage (15% body weight) was associated with a mild increase in bicarbonate concentration, and blood acid-base equilibrium showed a mixed metabolic and respiratory alkalosis (pH 7.57, partial pressure of CO2 29 mmHg, base excess +5.5 mmol/l), and aldosterone concentration was increased 3-fold as compared with the control value. When hyponatraemia (110 mmol/l) was induced in a similar manner in panhypopituitaric rats, we observed a very low aldosterone concentration (< 50 pg/ml) and a compensated respiratory alkalosis (pH 7.45, partial pressure of CO2 30 mmHg, base excess -2.6 mmol/l). The restoration of a hyperaldosteronaemic state in this group of rats was related essentially to corticosteroid intake. 3. These data suggest that corticosteroids play a critical role in the development of hyponatraemia-related hyperaldosteronism, a phenomenon not necessarily dependent on a pituitary factor.

[Chronic fatigue syndrome]. / Le syndrome de fatigue chronique.

The major and minor diagnostic criteria of the chronic fatigue syndrome are described. The stages of the differential diagnosis, the diagnostic strategies and the controversies, while insisting on certain sleeping disorders are discussed. The cause of the syndrome may be a viral infection, and an anxious-depressive state may increase somatic complaints. Patients with chronic fatigue syndrome did not demonstrate a specific response to therapy. Spontaneous remission after a few years is a typical feature of this syndrome.

Uric acid, anion gap and urea concentration in the diagnostic approach to hyponatremia.

We analyzed the serum anion gap (AG = sodium plus potassium minus chloride plus bicarbonate, N = 11-21 mEq/l), serum uric acid and urea concentrations in hyponatremia of various origins. We found that characteristic chemical patterns emerged in association with different hypotonic states: Low uric acid concentration was typically observed in the SIADH and in hyponatremia related to hypopituitarism. The same observation was also frequently noted in hyponatremia secondary to diuretics or to polydypsia. In the SIADH, we observed a decrease in the AG but to a greater extent (-26%) than one would expect from the simple dilutional effect (-16%). Fifty percent of the patients presented an AG lower than 11 mEq/l. In patients with diuretic-related hyponatremia, one group presented an hypouricemia and a low AG as in SIADH (reflecting volume expansion), in the other group the AG was normal or increased as was uric acid concentration (reflecting volume depletion). In adrenocorticotropin deficiency, hyponatremia was typically associated with a low bicarbonate concentration, a normal AG and hypouricemia. In polydypsic patients with hyponatremia, the AG was usually normal or increased despite sometimes very low sodium levels. Uric acid levels were highly variable, most often decreased. We also noted in these patients that the serum urea levels were correlated with urine osmolality (R = +0.8; p < 0.001), and in 40% of them we observed very low blood urea concentration (0.5-2 mmol/l) at the admission time. In hyponatremia related to cardiac failure or cirrhosis, the AG was usually normal despite mild hypoproteinemia.

Hyperferritinemia in adult onset Still's disease and the hemophagocytic syndrome.

Increments in serum ferritin levels in adult onset Still's disease (AOSD) were reported to be higher than one could expect for a simple inflammatory state. When we analyzed the scores of 40 patients with various severe inflammatory diseases aside from AOSD, we recorded no serum ferritin values higher than 3,300 ng/ml (N less than 200 ng/ml). In 3 of 10 consecutive patients with AOSD, the ferritin levels were higher than 3,500. Among these 3 patients, one case had a ferritin value of 3,600 ng/ml and bone marrow aspirate showed a marked hyperplasia of mature appearing histiocytes, and the 2 other patients (serum ferritin levels of 65,000 ng/ml and 250,000 ng/ml) displayed the features of a hemophagocytic syndrome. In 2 patients with normal or mildly increased levels of ferritin, the bone marrow examination was normal. We suggest that very high serum ferritin levels encountered in AOSD reflect the presence of histiocytic hyperactivity that sometimes leads to a hemophagocytic syndrome.

[Corticosteroid therapy of various systemic diseases (non-neoplastic, noninfectious)]. / A propos de la corticothérapie de certaines maladies de système (non néoplasiques, non infectieuses).

The authors evoke how the corticosteroids work (as antiinflammatory and immunosuppressive agents) and how to prescribe them, orally, intravenously, in association with an antimitotic drug. They insist on the suspended and non curative effects of corticotherapy, its side effects and the additive effect of the antimitotic drugs. They suggest different therapeutic programs against rheumatoid arthritis, Still's disease, lupus, dermatomyositis, Behçet's disease, Horton's disease and polymyalgia rheumatica.

Treatment of the syndrome of inappropriate secretion of antidiuretic hormone by urea.

Recent data have shown the role of urea in the urinary concentrating mechanism. We studied the effects of exogenous urea administration in hyponatremia associated with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). In 20 patients with SIADH, we observed a positive correlation between serum sodium and blood urea levels (r = 0.65; p less than 0.01). In one patient with an oat cell carcinoma and SIADH-induced hyponatremia, we observed the same positive correlation (r = 0.80; p less than 0.01) but also a negative one between the excreted fraction of filtered sodium and urinary urea (r = -0.67; p less than 0.001). The short-term administration of low doses of urea (4 to 10 g) resulted in correcting the "salt-losing" tendency of this patient. Longer term administration of high doses of urea (30 g/day) was attempted with the same patient as well as with a healthy volunteer subject with Pitressin-induced SIADH. in both patients, urea treatment lowered urinary sodium excretion as long as hyponatremia was significant (less than 130 meq/liter). Urea treatment also induced a persistent osmotic diuresis, allowing a normal daily intake of water despite SIADH. This was clearly shown during the long-term treatment of a third patient with SIADH who was taking 30 g urea/day during 11 weeks. It is concluded that urea is a good alternative in the treatment of patients with SIADH who presented with persistent hyponatremia despite the restriction of water intake.