Vascular expression of annexin A2 in lupus nephritis.

AIMS: To evaluate vascular expression of annexin A2 (ANXA2) and its subunit S100A10 in lupus nephritis (LN). METHODS: The present histological study included 14 patients with LN and 11 controls (patients with non-lupus kidney diseases). Kidney biopsies from patients with lupus were scored for lupus glomerulonephritis (according to the International Society of Nephrology/Renal Pathology Society 2003 classification) and vascular lesions (such as microthrombi and antiphospholipid syndrome nephropathy (APSN)). ANXA2 and S100A10 expression in glomerular and peritubular capillaries was evaluated by immunohistochemistry on tissue sections. The staining intensity score ranged from 0 (no expression) to 4 (intense expression). RESULTS: In patients with LN, the median age (range) at first kidney biopsy was 36 (18-49). Vascular lesions were observed in six patients (including two with APSN). We observed intense expression of ANXA2 in glomerular and peritubular capillaries while expression of S100A10 was weaker. However, one of the patients with APSN showed strong S100A10 expression. Patients with LN and controls differed significantly in terms of S100A10 expression in peritubular capillaries. We also observed a statistical difference between patients who had LN with renal vascular lesions and those without renal vascular lesions in terms of ANXA2 expression in peritubular capillaries. CONCLUSIONS: The presence of vascular lesions in LN appears to be associated with significant differences in the vascular expression of ANXA2. Vascular expression of ANXA2 was somewhat higher in LN. Vascular expression of S100A10 was somewhat lower in LN (except one of the two patients with APSN). Further studies of ANXA2's putative value as a biomarker of active LN or of vascular lesions in LN are required.

Antibodies against the N-terminal domain of annexin A2 in antiphospholipid syndrome.

Annexin A2 (ANXA2, an endothelial cell receptor for plasminogen and tissue plasminogen activator) has been identified as a new autoantigen in antiphospholipid syndrome (APS). The aim of the present study was to evaluate the presence of antibodies against the N-terminal domain of annexin A2 (ANXA2) in primary APS (PAPS). By using a synthetic peptide corresponding to the 31N-terminal amino acids of ANXA2 (ANXA2(N31)) as an antigen, we performed an enzyme-linked immunosorbent assay (ELISA) to measure anti-ANXA2(N31) IgG and IgM antibodies in the serum of PAPS patients (n=19), systemic lupus erythematosus (SLE) patients (n=50) and healthy blood donors (n=106). We did not find any statistically differences between the three groups in terms of IgG and IgM anti-ANXA2(N31) titres. Elevated IgG anti-ANXA2(N31) titres were not observed in the serum of PAPS or SLE patients who had previously tested positive for anti-ANXA2 antibodies. Thus, the ANXA2 N-terminal domain does not appear to be the target antigen for anti-ANXA2 antibodies in APS.

[Adrenal hemorrhage acutised by adrenocorticotropin hormone]. / Hématomes surrénaliens potentialisés par le Synacthène (HSS).

OBJECTIVE: Many spontaneous adrenal hematomas have been observed in patients being treated by Synacthène. The purpose of this study is to define how to take those patients in charge on a short-, mid- and long-term. PATIENTS AND METHODS: From January 2000 to December 2008, five patients (four males and one female), mean age 47, were taken in charge in our service for spontaneous adrenal hematomas. All those patients had been treated with Synacthène for a mid-sciatic pain for 72 hours. We associated a clinical, endocrine and radiologic staging to treat those patients. RESULTS: Four patients underwent a watchful waiting, only one patient needed surgery. No adrenal tumor was ever found during the mean two years follow-up (one to four). Two patients suffered of the condition of the antiphospholipid syndrome. CONCLUSION: Spontaneous adrenal hematomas are a most uncommon pathology. The clinical attitude has thus to be defined clearly. The patient must be under close clinical evaluation. Biological and morphological parameters have to be often repeated. An adrenal tumor has to be excluded by the evaluation, as that tumor could be secreting or could not be secreting. Antiphospholipid syndrome must also be excluded.

Sarcoidosis and the kidney: not only the granulomatous interstitial nephritis.

Renal involvement in sarcoidosis displays a wide range of manifestations, and kidney dysfunction may involve all three mechanisms of renal failure. We report a new case of systemic sarcoidosis presenting as a severe renal failure due to hypercalcemia, sarcoidosis-related bilateral nephrolithiasis and granulomatous interstitial nephritis. A prostate adenocarcinoma was also diagnosed, but has to be regarded as an unrelated disease.

Drug rash with eosinophilia and systemic symptoms after chlorambucil treatment in chronic lymphocytic leukaemia.

Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous drug reaction with a long duration of eruption and serious organ involvement. The mortality rate has been estimated at about 10%. Aromatic anticonvulsants, sulphamides, minocycline and more rarely carbamazepine are the principal responsible drugs. We report the first case of chlorambucil-induced DRESS syndrome in a 70-year-old man recently diagnosed with chronic lymphocytic leukaemia. He developed recurrent skin rash, fever, hypereosinophilia, and acute renal failure after rechallenge with chlorambucil. The condition improved slowly after stopping medication and systemic steroids. Prompt recognition of a chlorambucil drug reaction is essential in patients receiving chemotherapy.

Anti-annexin II antibodies in systemic autoimmune diseases and antiphospholipid syndrome.

OBJECTIVES: The objective of this study were (1) to evaluate the prevalence of anti-annexin II antibodies in patients with various autoimmune diseases and antiphospholipid syndrome and (2) to correlate anti-annexin II antibodies with anti-phospholipid antibodies. MATERIALS AND METHODS: Anti-annexin II antibodies and anti-phospholipid were detected, using an enzyme-linked immunosorbent assay, in the serum of patients with primary antiphospholipid syndrome (n = 16), systemic lupus erythematosus (n = 53), primary Sjögren syndrome (n = 71), systemic sclerosis (n = 17), systemic vasculitis (n = 18), and rheumatoid arthritis (n = 119). Healthy blood donors (n = 99) were used as controls. RESULTS: Anti-annexin II antibodies were significantly more prevalent in patients with connective tissue diseases (8.5%), especially antiphospholipid syndrome (14.8%) and rheumatoid arthritis (10%), than in controls (2%). An inverse correlation was observed between anti-annexin II antibodies and antiphospholipid antibodies. CONCLUSION: Annexin II can be recognized by antibodies in serum from patients with systemic autoimmune disorders. Further studies are required to determine the clinical significance of anti-annexin II antibodies in rheumatoid arthritis and to determine their diagnostic value in discriminating clinical subgroups of patients with antiphospholipid syndrome.

[Mouth ulcers induced by enteric-coated mycophenolate sodium (Myfortic]. / Ulcérations buccales après prise de mycophénolate de sodium (Myfortic).

BACKGROUND: Mycophenolate sodium (Myfortic) is an enteric-coated formulation of the immunosuppressant therapy mycophenolic acid. We report a case of diffuse mouth ulceration in a patient treated with Myfortic presenting recurrence after another dose of drug. PATIENTS AND METHODS: We report the case of a 26-year-old female patient with systemic lupus erythematosus, initially treated with corticosteroids and mycophenolate mofetil, but which was stopped because of varicella-zoster dissemination and leucopoenia. She consulted for mouth ulcers occurring two weeks after the introduction of Myfortic. There were no signs of opportunist infection or lupus activity. Mucosal ulcerations disappeared when Myfortic was stopped. Several weeks later, the patient presented recurrence of mouth ulcerations after another treatment of Myfortic. DISCUSSION: Myfortic is a new enteric-coated formulation of mycophenolic acid developed to reduce gastrointestinal upset associated with Cellcept. In certain cases, Cellcept toxicity can present as a number of oral ulcerations. Direct toxicity is involved in these cases. This side effect has never been described with Myfortic. In our case, the distinctive characteristic is that the patient was never treated with Cellcept without mucosal toxicity despite equivalent systemic mycophenolic acid exposure.

Retroperitoneal hematoma compressing a single functioning kidney: an unusual cause of obstructive renal failure.

We report a case of a retroperitoneal hematoma occurring in a patient under anticoagulation therapy for deep-venous thrombosis and presenting as an anuric acute renal failure. A coexisting polycythemia vera led to misdiagnosis that could have been life-threatening. A woman, known for polycythemia vera and a single functioning right kidney, was admitted with mild abdominal pain in a context of recent deep venous thrombosis under low-molecular weight heparin. Clinical examination revealed hepatomegaly associated with polycythemia vera. Biochemical evaluation disclosed an acute renal failure, and renal ultrasonography showed no dilation of the renal pelvis. Retroperitoneal hematoma resulted in shock, progressive anemia and obstructive renal failure, related to renal pelvic compression. A right renal indwelling catheter was introduced to restore urine flow after one hemodialysis session, and an inferior vena cava filter was placed because of anti-coagulation contra-indication. However, pulmonary embolism occurred, so that oral anticoagulants were introduced. The hematoma resorbed spontaneously, and a year after this episode, the patient is still alive and well. Retroperitoneal hematoma is a rare cause of obstructive acute renal failure and a life-threatening complication of anti-coagulation therapy.

[Muscular haematoma in Henoch-Schönlein purpura]. / Hématome intramusculaire sévère au cours du purpura rhumatoïde.

INTRODUCTION: Henoch-Schonlein purpura is one of the most frequent systemic vasculitis in children. In adults, muscle involvement is extremely rare and not very well characterized. We report a case of Henoch-Schonlein purpura with severe skin and renal involvement in witch multiple intramuscular haematoma leaded to severe anaemia. Histological examination confirms the muscle localization of the disease. EXEGESIS: A 68 years old man treated by oral anticoagulation for multiple venous thrombosis, was admitted with necrotic vasculitis of the skin, abdominal pain and segmental IgA glomerulopathy. The diagnosis of Henoch-Schonlein purpura was rapidly made and intensive steroid therapy started. After rapid improvement, a haemorrhagic shock due to voluminous intramuscular haematoma was diagnosed by MRI. Histological examination of the muscle, confirms the localization of the disease. CONCLUSION: Intramuscular haematomas are very uncommon in Henoch-Schonlein purpura. There are usually a consequence of muscular immune complex vasculitis. In our patient, high dose corticosteroid was not unable to control the disease.

[Inaugural unilateral adrenal hematoma of an antiphospholipid syndrome]. / Hématome surrénalien unilatéral inaugural d'un syndrome des antiphospholipides.

INTRODUCTION: A primary antiphospholipid syndrome is a very rare cause of adrenal haemorrhage. OBSERVATION: A 51 year-old man presented with a unilateral adrenal haemorrhage, enhanced by the prescription of Synacthène during the 4 days that preceded. There was no adrenal deficiency but the immunological control revealed the presence of anti-phospholipid antibodies. After 2 years of follow-up, adrenal controls have not shown any underlying tumour or endocrine insufficiency. COMMENTS: Adrenal involvement is described in the anti-phospholipid syndrome and may present in the form of adrenal deficiency in the case of occasionally only microscopic bilateral haemorrhages. Furthermore, Synacthène is known to induce adrenal haemorrhages although this complication remains rare. Moreover, any unilateral adrenal haemorrhage requires subsequent follow-up for several months or even years in order to eliminate any underlying tumour and to control the absence of any adrenal deficiency if the involvement is bilateral.

[Amyloidosis and pleural calcification]. / Amylose et calcinose pleurale.

INTRODUCTION: Pulmonary diseases during the course of generalised amyloidosis are principally represented by tracheobronchial involvement and diffuse parenchymal localizations. CASE REPORT: The authors report the case of a 66-year-old woman presenting with pleural amyloidosis in the context of generalised amyloidosis. Thoracoscopy performed in the investigation of recurrent transudative pleural effusions found evidence of an inflamed parietal pleura with areas of calcification. Pleural biopsies confirmed amyloid infiltration pleural ossification. Talc pleurodesis was performed. CONCLUSIONS: The authors' conclusion is that, meeting an unexplained pleural effusion even transudative during the course of a generalised amyloidosis, the thoracoscopy is the diagnosis key test as it allows moreover a pleural pleurodesis to be performed.

[Acute renal insufficiency secondary to interferon]. / Insuffisance rénale aiguë secondaire à l'interféron.

Alpha interferon is increasingly used in the treatment of malignancies and viral hepatitis. Renal involvement after its use consist in more cases on proteinuria. We report one case of acute renal failure without nephrotic syndrome but with tubulointerstitiel infiltration by mononuclear cells in 65 old man who had before interferon therapy 151 mumol/l of serum creatinine. Interferon was administrated for digestive carcinoid neoplasia and bone and liver metastasis. Outcome was improvement of renal function after withdrawn of interferon, dialysis and steroid treatment.

[Chronic interstitial nephritis induced by 5-aminosalicylic acid: a new case report]. / Néphrite interstitielle chronique au 5-ASA: mise au point à partir d'un nouveau cas.

5-aminosalicylic acid (5-ASA) used for the treatment of inflammatory bowel disease is known to induce chronic interstitial nephritis (CIN). However, the frequency of occurrence and the spectrum of severity of 5-ASA-induced CIN are not known. In this paper, we report a new case of CIN induced by 5-ASA in a patient treated for about 7 years for a Crohn disease. After that 5-ASA was discontinued and prednisone therapy started, renal function improved partially. About 30 observations of CIN induced by the use of 5-ASA in patients treated for inflammatory bowel disease have already been published. None were published in patients treated for other diseases such as arthritis rheumatism. The review of the literature suggests that the prognosis is poor and correlates with the duration of treatment, the cumulative dose and the level of renal impairment at diagnostic. We believe that the control of the renal function in patients treated by 5-ASA must be regular and prolonged.

[Collapsing glomerulopathy and cytomegalovirus, what are the links?]. / Glomérulopathie avec collapsus du floculus et cytomégalovirus, quels liens?

BACKGROUND: Collapsing glomerulopathy is a form of focal and segmental glomerulosclerosis which occurs preferentially in black people. It causes severe nephrotic syndrome and quickly progresses towards end-stage renal failure. CASE REPORT: We report the case of a 16-year-old black girl from Guadeloupe who was admitted for tetanus and edema in 1996. She had hypoparathyroidism, renal failure and a nephrotic syndrome as well as cytomegalovirus infection. Renal biopsy showed collapsing glomerulopathy. The renal function improved on glucocorticoid and ganciclovir therapy and her serum creatinine stabilized around 250 mumol/l for two years. DISCUSSION: Collapsing nephropathy is the cellular type of focal and segmental glomerulosclerosis. The main etiology is the human immunodeficiency virus. A viral infection may be involved in its pathogenesis. Other viruses could be linked with this nephropathy. This case report relates a case associated with a cytomegalovirus viruria. The clinical course might be related with the antiviral treatment.

Adult Fanconi syndrome secondary to light chain gammopathy. Clinicopathologic heterogeneity and unusual features in 11 patients.

Fifty-seven cases of Ig light chain-associated Fanconi syndrome (FS) have been reported so far, mostly as isolated reports. The pioneering work by Maldonado and associates (35), who reviewed the first 17 cases in 1975, led to the unifying concept that patients with FS and Bence Jones proteinuria have a special form of plasma cell dyscrasia characterized by slow progression of the tumor and by prominent crystal formation in proximal tubule cells, in the absence of myeloma casts in the distal tubule. We carefully reappraised these characteristics in a series of 11 patients. Ten renal biopsy specimens were available for electron microscopy, adding to the 15 previously reported cases with ultrastructural studies. Moreover, 10 of the kappa light chains could be entirely or partially sequenced and tested for their resistance to cathepsin B, a lysosomal protease present in proximal tubule cells. Our series showed an unexpected clinicopathologic heterogeneity. Seven patients presented with the typical clinical and pathologic features of FS and low-mass myeloma or monoclonal gammopathy of undetermined significance (MGUS), in keeping with Maldonado et al's description. Crystals in bone marrow cells were detected in patients of this group, only. Three patients who presented with full-blown FS exhibited, however, the characteristic features of myeloma cast nephropathy in the setting of high-mass myeloma. One patient of this group also had numerous crystals in proximal tubule cells. The eleventh patient had complete FS with MGUS, but no crystals in proximal tubule cells even after electron microscopy. Contrasting with the clinicopathologic heterogeneity, genetic and biochemical analyses of the light chains showed a striking homogeneity. First, they all were of the kappa type. Second, 8 of 9 belonged to the V kappa I variability subgroup, which indicates that FS light chains are related by the sequence of their variable regions. Third, the 8 V kappa I light chain sequences most likely originated from only 2 germline genes, LCO2/012 and LCO8/018. Fourth, all 5 LCO2/012-derived sequences presented an unusual hydrophobic or nonpolar residue at position 30. These sequence peculiarities may account for unusual physicochemical properties of the light chains including the resistance of their variable domain V kappa to proteolysis by cathepsin B, observed in 7 of 9 patients in our series, while light chains isolated from patients with myeloma cast nephropathy are completely digested. Resistance of V kappa to proteolysis in FS patients can explain the accumulation of the light chain in the endocytotic compartment of the proximal tubule cells, leading to impairment of proximal tubule functions.

Risk factors of renal failure progression two years prior to dialysis.

AIM: The respective contribution of sex, type of nephropathy, degree of proteinuria, blood pressure, protein and sodium daily intakes, blood lipid profile, protidemia, hemoglobinemia, acidosis and CaPO4 product on the rate of renal failure progression is debated. PATIENTS AND METHODS: The link between these parameters and the decrease of creatinine clearance, deltaCcr (according to Cockroft) was assessed in uni- and multivariate analysis in a population of 49 patients (26 women; age 60+/-15 years, weight 79+/-15 kg) selected out of 173 presently treated hemodialysis patients on the basis of availability of a quarterly follow-up for 2 years before starting dialysis. The patients were advised a moderate protein and salt restriction which could be retrospectively assessed (on urinary excretion of urea and sodium) at, respectively, 0.82 g/kg/day and 6.5 g/day. RESULTS: The 2-year deltaCcr was 14+/-14 ml/min. It was not different in men and women. This decrease in Ccr was neither significantly different in gomerular disease (17+/-8, n = 14), diabetic nephropathy (12+/-6, n = 7), nephroangiosclerosis (15+/-8, n = 5), interstitial nephritis (12+/-10, n = 14), and PKD (11 +/-12, n = 9). Patients with antihypertensive drugs (n = 42) had a faster progression than those without drugs (n = 7): deltaCcr = 15+/-14 vs 7+/-7 ml/min (p < 0.05) in spite of comparable blood pressure but with higher proteinuria. Linear regression of deltaCcr with the initial and 2-year averaged values of the quantitative parameters showed a significant positive link for both values with cholesterol, hemoglobine and proteinuria and a negative one with protidemia. A positive link was observed with the initial value of bicarbonate and the 2-year mean of diastolic and mean blood pressures. No link at all was observed with urea and Na excretion, CaPO4 product and triglycerides. Multiple regression disclosed a significant link only for protidemia (negative with both initial and 2-year averaged value), diastolic BP (only for the 2-year averaged value and hemoglobinemia (for the initial value). When the patients were classified according to a threshold value of their protidemia, DBP, hemoglobinemia, and cholesterolemia those with the combination of 2 risk factors of progression (protidemia > or = 66 g/l, DBP > or = 90 mmHg, hemoglobinemia > 11 g/dl, proteinuria > or = 3 g/d, CT > 5 mmol/l) had a significantly greater decrease of Ccr than those with the 3 other combinations at the exception of the association of low protidemia with DBP. CONCLUSION: Diastolic hypertension and low protidemia are the 2 most important factors predicting progression of renal failure. A predictive synergy was furthermore pointed out between low protidemia or diastolic hypertension with proteinuria and cholesterol. On the contrary anemia attenuates progression linked to low protidemia, diastolic hypertension, proteinuria and high cholesterol.