Relapsing polychondritis with p-ANCA associated vasculitis: Which triggers the other?

Relapsing polychondritis (RP) is a rare autoimmune disease with chronic inflammatory/destructive lesions of the cartilaginous tissues. In one third of the cases it is associated with other autoimmune disorders, mostly with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). We report three cases of RP with p-ANCA positive AAV. In the first patient RP developed 1.5 years after the onset of AAV. In the others the signs of RP were present before the onset of severe crescent glomerulonephritis. Patients responded well on steroid and cyclophosphamide. In dialysis dependent cases plasmapheresis was also used successfully. During the 2 and 1.5 years of follow up, they were symptom-free, and had stable glomerular filtration rate. The first patient died after four years of follow-up due to the complications of sudden unset pancytopenia, which raises the possibility of associated hemophagocytic syndrome. In the setting of RP or AAV physicians should always be aware of the possibility of sudden or insidious appearance of the other disease.

[Clinical consequence and significance of anti-neutrophil cytoplasmic antibody positivity in anti-glomerular basement membrane disease]. / Antiglomeruláris bazálmembrán betegségben észlelt antineutrofil citoplazmatikus antitest pozitivitás klinikuma, jelentosége.

INTRODUCTION: Patients with renopulmonary syndrome who have both anti-neutrophil cytoplasmic and anti-glomerular basement membrane antibodies have been described since 1989. AIM: The aim of the authors was to analyse the data of "double positive" patients diagnosed in their department, and compare these with previous studies. METHOD: During the last 16 years, 87 anti-neutrophil cytoplasmic antibody positive and 11 anti-glomerular basement membrane antibody positive patients were diagnosed. Four patients with anti-glomerular basement membrane antibodies (36%) had detectable anti-neutrophil cytoplasmic antibodies, 2 patients were positive for anti-myeloperoxidase and 2 patients for anti-proteinase 3. RESULTS: In comparison with patients having anti-glomerular basement membrane antibodies, the double-positive patients were characterized by older age (median of 46 vs. 24 years), lack of male dominance (50% vs. 71%), more frequent presence of previous extrarenal symptoms (50% vs. 0%), and lower anti-glomerular basement membrane antibody levels (<100EU/ml: 100% vs. 29%). The double-positive patients had more favourable 1-year survival (100% vs. 71%), despite their older age and similar treatment regimen (immunosuppression 100% in both groups, plasmapheresis in 75% vs. 86%), but 1-year renal survival was not different (25% vs. 14%). CONCLUSIONS: In agreement with literature data, about one third of patients with anti-glomerular basement membrane antibodies had detectable anti-neutrophil cytoplasmic antibodies, and the coexistence of the two antibodies may have clinical consequences.

[Amyloidosis]. / Amyloidosis.

The term amyloidosis refers to the extracellular deposition of fibrils composed of different types of plasma proteins. Various clinical symptoms are caused by the tissue damage related to the deposited fibrillary material. Except of the brain, all organs can be affected: kidney, liver, spleen, lung, gastrointestinal tract, endocrine organs, skin, heart and autonomous nervous system. Diagnosis is confirmed by specific histological methods (congo red stain, polarized and electron microscopy, immunohistochemistry) and genetic testing. Scintigraphy with radioisotope labeled serum amyloid P-component is helpful in the localization of the process and in the assessment of therapeutic effect. In the majority of cases the underlying disease is a plasma cell disorder, light chains aggregate to amyloid fibrils. Therefore chemotherapy and - in selected patients - stem cell transplantation is the choice of treatment. Another common type of amyloidosis is caused by chronic inflammatory diseases (amyloid fibrils are composed of elevated serum amyloid A being related to C reactive protein), or by some hereditary fever syndromes. Treatment of the underlying disorder may bring resolution of the amyloid burden. In 10% of the cases, amyloid fibrils are composed of genetically modified proteins. Depending on the source of the mutant protein liver transplantation, hepatorenal or cardiorenal transplantation may cure the disease.

[Molecular pathology and clinical manifestations of Fabry disease]. / A Fabry-kór molekuláris patológiája és klinikai megjelenési formái.

Fabry disease is a rare, progressive lysosomal storage disorder caused by mutation in the GAL gene and an impaired function of the alpha-galactosidase A enzyme. The enzymatic defect results in the progressive accumulation of glycosphingolipids in endothelial cells, smooth muscle cells, leucocytes and fibroblasts leading to organ damage in the skin, eye, nervous system, kidney and heart. Major clinical manifestations include acroparesthesis, angiokeratoma, corneal opacities, vascular diseases of the heart, kidney, and the central nervous system. Enzyme replacement therapy has recently become available for the treatment of Fabry patients. In this review the authors describe clinical features of Fabry disease in 31 Hungarian patients. At the time of this analysis the database consisted of 31 cases (15 males, 16 females) of whom 5 have died (4 males, 1 female). The most common disease-specific manifestation was angiokeratoma in males, and eye symptoms in females. 25% of female subjects were symptom free. Genotyping was performed in all cases and disease-causing mutations were found in all families. Three new mutations were identified. Twelve patients (8 males and 4 females) are currently receiving enzyme replacement therapy.