Human immunodeficiency virus (HIV) infection and arthritis

A variety of inflammatory arthritic conditions are observed in the setting of HIV infection. The epidemiology of these disorders is a point of current controversy, although it appears that several unique syndromes are clinically associated. The pathogenesis of these disorders remains unclear, but we hope that further work in this area will lend important insights into the mechanisms of both HIV-associated and non-HIV associated rheumatic disease. The overall management of such patients is based on recognizing the underlying HIV infection and the judicious use of antirheumatic drug therapy. Rheumatologists need to be aware of the natural history of HIV infection and its clinical manifestations.     

Noninfectious canine arthritis: rheumatoid arthritis

Chronic unremitting, generally symmetric, erosive polyarthritis was studied in 8 dogs. The disease had clinical, serologic, radiographic, and pathologic changes similar to those of rheumatoid arthritis of man. The condition occurred mainly in smaller breeds of dogs, with time of onset from 8 months to 8 years of age, Characteristic radiographic changes were seen in the joints several weeks to several months after the appearance of the initial lameness. Synovial fluid contained an increased number of neutrophils, and synovial fluid and synovial tissues were sterile for anaerobic and aerobic bacteria, mycoplasma, chlamydia, and viruses. Corticosteroids were therapeutically ineffective in all of the cases; however, corticosteroids, cyclophosphamide, and azathioprine were effective when used in combination in several dogs.     

Psoriatic arthritis

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. It is classified with the human leukocyte antigen B27 seronegative spondyloarthropathies because it shares certain features with other conditions included in that group. Specific features of PsA, however, distinguish it from both rheumatoid arthritis and other spondyloarthropathies. Although the cause and pathogenesis of PsA are not known, genetic, immunologic, and environmental factors are thought to play a role, and provide a rationale from therapeutic modalities.     

Rheumatoid arthritis

Angiogenesis is essential for the growth of solid tumors. Antiangiogenic therapy has therefore attracted considerable interest as a novel therapy for various tumors including colorectal carcinoma. We experimentally investigated the therapeutic effect of TNP-470, a nonspecific inhibitor of angiogenic factors, and vascular endothelial growth factor (VEGF)-neutralizing antibody (VEGFAb), was a VEGF-specific inhibitor, on liver metastases of colon carcinoma using a murine orthotopic transplantation model. TK-4 and TK-13 are moderately differentiated adenocarcinoma strains established in our department which express VEGF mRNA and protein. Administration of TNP-470 30 mg/kg significantly inhibited the liver metastases of both strains, as did administration of VEGFAb 100 micrograms/mouse. The therapeutic effect on liver metastases was more dominant with antiangiogenic therapy than with chemotherapy (mitomycin C). Furthermore, the sustained effect of TNP-470 induced tumor dormancy and consequently improved the survival of the animals. These results suggest that antiangiogenic treatment will be a potent therapy for liver metastases of human colorectal carcinoma in the future.     

Psoriatic arthritis

Psoriatic arthritis and its associated enthesopathy appear to be another immune-mediated manifestation of the genetic predisposition to develop psoriasis. The occurrence of psoriatic arthritis in the setting of the selective immune deficiency of advanced HIV infection, especially in the association with HLA-B27, points to a role of the CD8 T cell in disease pathogenesis. The relationship of Reiter's syndrome to psoriatic arthritis is emphasized.     

Corticosteroid prescribing in rheumatoid arthritis and psoriatic arthritis

Embryos from certain mouse strains are arrested at the 2-cell stage in cell culture ('2-cell block'), whereas those from other strains develop to the blastocyst stage under the same conditions. It was previously shown that blocking embryos can be rescued in culture by aggregation with an excess of 2-cell stages of a non-blocking strain such as CBA x C57BL/6 F2. Here we have employed a LacZ transgene in a blocking strain (NMRI) to follow the fate of rescued blastomeres up to the blastocyst stage. We found that rescued blastomeres can participate in both inner cell mass and trophoblast formation, thus completely overcoming the 2-cell block.     

Management of arthritis

Over the last 25 years the diagnostic approaches and therapeutic strategies of breast cancer have dramatically changed. The relationship between diagnosis and therapy has gradually become more complex due to the ever more sophisticated diagnostic tools (mammographic screening, digital mammography, magnetic resonance, SPECT scan and FDG-PET), which have improved resolution limits and accuracy, and also due to the different therapeutic planning applied to breast cancer in these years (conservative surgery, neo-adjuvant chemotherapy, axillary dissection or not). Thus, in this paper, we have briefly analyzed the many open questions in breast cancer management and the clinical challenges of present diagnostic tools in relation to pre-, peri- and postoperative phases, and to therapeutic strategies in general. The main goal of mammographic screening is to detect early invasive cancers and to treat them at the first useful moment. However, at which age should one begin screening, and what is the impact on overall survival, the cost-effectiveness, and, most of all, the best operative approach to suspect lesions? Can digital mammography give a better quality of imaging with respect to conventional mammography? Does unexpected multicentricity and/or multifocality, which is sometimes showed by magnetic resonance, have any clinical relevance? Is this technique really better than traditional methods for the identification of local recurrence? Is scintimammography able to improve the low diagnostic accuracy of mammography on non-palpable breast lesions? Moreover, at present, the need for axillary dissection and its therapeutic and staging value is deeply debated: however, clinical detection of axillary metastases is not a reliable diagnostic tool and there are no conventional radiologic techniques to be used: recently nuclear medicine imaging has provided various approaches, such as SPECT scan with different tracers, FDG-PET, or lymphoscintigraphy with gamma probe sentinel biopsy: there are not only methodologic but also phylosophic differences in using these techniques. Neo-adjuvant chemotherapy has allowed a dramatic reduction of primary breast cancer with a replanning of the surgical approach to large breast tumours but, at the same time, has posed new questions such as the adequacy of diagnostic pre- and perioperative revaluation. Finally, does postoperative follow-up take advantage of intensive diagnostic programs and are there therapeutic margins which would improve survival of patients with metastatic disease? This paper is an attempt to analyze the answers given in the literature. Nevertheless, at present, this matter is globally in progress and a scientific debate will provide, in the near future, a new promising scenario for breast cancer management.     

Syndromes and arthritis

There are many questions and no clear answers raised by these children. These syndromes, however, seem to be biologic experiments of nature and present unique opportunities to study the various elements involved in the pathogenesis of arthritis. Pediatric rheumatologists are in a unique position to study these syndromes.