CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, M-protein agglutination, disialosyl antibodies) syndrome is a rare polyneuropathy. IgM paraproteins react with ganglioside-containing disialylated epitopes resulting in dorsal root ganglionopathy and B-lymphocyte infiltration of cranial and peripheral nerves. Clinical features include ataxia, slight muscle weakness, areflexia, sensory- and cranial nerve symptoms. Case studies have reported the efficacy of rituximab and intravenous immunoglobulin (IVIg) treatments. We present the case of a 57-year-old man, who had difficulty walking, with numbness and clumsiness in all limbs. He had areflexia, vibratory sensation loss and ataxia. Laboratory tests showed IgM monoclonal components and disialosyl antibodies in the serum. Nerve conduction studies indicated severe sensorimotor demyelinating polyneuroradiculopathy. Despite IVIg and rituximab treatments, the patient’s disease course gradually worsened and he died of respiratory failure. Neuropathological examination revealed dorsal column- and dorsal root atrophy with mixed mononuclear cell infiltration. This article aims to draw attention to this syndrome, and the use of early potent immunosuppressive treatment to improve patients’ quality of life.

[The present review is compiled of two parts, the first part aims to summarize the induction immunosuppressive therapy, the second part delineates the outcome and complications of ANCA-associated vasculitis. ANCA-associated vasculitis is a systemic disease, accompanied with rapidly progressive glomerulonephritis and severe, often life-threatening extrarenal complications. By early diagnosis and immediate initiation of immunosuppressive therapy both patient and renal outcome have been substantially improved. The major aims of modern therapeutic protocols are, besides improving survival, to decrease immunosuppressive drug toxicity and avoid infections. Immunosuppression is based on the combination of large dose of corticosteroid and cyclophosphamide, which is advisable to supplement by plasma exchange. The B-cell depleting anti-CD20 monoclonal antibody rituximab, which has already been available in Hungary, has been proved to be similarly effective in newly diagnosed ANCA-vasculitis, and even more effective in a relapsing disease, compared to cyclophosphamide. Amongst rituximab’s further indications in this disease is the preservation of young women’s fertility, and it also has priority in some other special cases. Early diagnosis and prompt immunosuppressive treatment have resulted that ANCAvasculitis became a treatable disease with reasonably good clinical outcome, yet both the disease and the immunosuppressive medications frequently cause complications, which necessitate continuous alertness of the attending nephrologists.]

[Peripheral neuropathy is caused by structural or functional damage of nervous system. The pathophysiology is not well known. Its clinical features are established but there is a need to standardize CIPN assessment, also considering that health care providers and patients frequently have a different perception of CIPN severity. Neurotoxicity caused by traditional chemotherapy is widely recognized in patients with cancer. The adverse effects of newer therapeutics, such as targeting and immunotherapeutic agents, need more information for the proper management. This review addresses the main neurotoxicities of cancer treatments with a focus on the newer therapeutics. Recognition of these patterns of toxicity is important because drug discontinuation or dose adjustment might prevent further neurological injury. Treatment is symptomatic. For prevention or treatment there is need for further basic research outcomes.]

[AIM: Rheumatoid arthritis (RA) is commonly associated with secondary osteoporosis.The BsmI polymorphism of the vitamin D receptor (VDR) gene has been implicated in the pathogenesis of osteoporosis. However, little data is available on the relationship between rheumatoid arthritis and the BsmI polymorphism. In this study, Hungarian frequencies of BsmI polymorphism genotypes were compared with those found in other countries. METHODS: In this study, 64 RA patients and 40 healthy controls were tested for VDR gene BsmI polymorphism genotypes.The frequencies of the B and b alleles were correlated with densitometric and laboratory markers of bone metabolism as well as with laboratory markers of arthritis. RESULTS: Among control subjects, the frequency of the BB genotype (27,5%) was relatively higher than in other European populations. In RA patients with secondary osteopenia/osteoporosis the BB genotype was rarer, while the bb was more common than in control subjects. Markers of bone metabolism showed that the presence of the B allele in RA patients was associated with a lower bone mineral density and an increased bone loss, while the bb genotype was associated with a higher bone mineral content. An increased osteoclast and osteoblast activity was observed in patients with the B allele, as determined by biochemical markers of bone metabolism. Rheumatoid factor titer, an important laboratory marker of disease progression in RA, was significantly higher in bb patients compared to patients carrying the B allele. CONCLUSION: Our data suggest that the imbalance in B and b allele expression may be involved in the pathogenesis of osteoporosis and perhaps of rheumatoid arthritis.]

[A clear understanding of the pathogenic events and/or environmental conditions that lead to the development of rheumatoid arthritis has not been accomplished. In recent years, some of the most capable therapies have targeted individual proteins, such as proinflammatory cytokines, which contribute to persistent inflammation. The success of these therapies in some patients underscores the importance of having a solid pathophysiologic knowledge of the mechanisms at play in the diseased joint. Targeting the joint therapeutically with proteins or other agents has presented many challenges in the treatment of rheumatoid arthritis. To circumvent these obstacles, the idea of providing transgenes to cells of the synovial lining was born. This use of gene therapy, as a delivery vehicle rather than replacement of a genetic deficit, has had many successes in preclinical animal studies. Preliminary results of the first Phase I clinical trial in humans suggests that an ex vivo approach can be safe and enable transgene expression. This review provides a consolidated overview of many of the successful gene therapy strategies undertaken for the treatment of animal models of arthritis. The focus is on: 1. joint targeting strategies, including discussion on the local and systemic approaches as well as the contralateral joint; 2. the applicability of viral vectors, including comparison of adenoviral, retroviral, adeno-associated, and herpes simplex viruses; 3. timing and dosage of treatment; and 4. targets and candidate proteins that have been examined, including targeting proinflammatory cytokines or the use of anti-inflammatory cytokines.]