Inflammatory polyarthritis

Lipid abnormalities are associated with a wide spectrum of pathological conditions. In particular, recent advances have been made in understanding the role of lipoproteins in coronary heart disease (Davies and Woolf, 1993). However, included within the spectrum of diseases associated with perturbations of lipid metabolism are a number of musculoskeletal problems including inflammatory polyarthritis, tenosynovitis, osteoporosis and bone cysts. 

There is a long-standing hypothesis that the microvasculature plays a pathological role in forms of chronic inflammatory polyarthritis, particularly RA (Rothschild and Masi, 1982). One of the proposed mechanisms of vascular damage in connective tissue disease is the direct action of a cytotoxic serum factor inducing endothelial cell damage. Blake et al. (1985) have su ested that the vascular abnormalities associated with RA may be linked to oxidized lipoproteins because they are cytotoxic to endothelial cells. 

Pattison D, Symmons D, Lunt M, Welch A, Birngham S, Day N and Silman A. 2005. Dietary (3-cryptoxanthin and inflammatory polyarthritis results from population-based prospective study. Am J Chn Nutr 82 451 155. 

Creamer et al. (1994) reported cases of breast cancer where the use of tamoxifen was temporally related to the development of an inflammatory polyarthritis resembling rheumatoid arthritis. Cases of cyclical psoriatic arthritis, however, have positively responded to antiestrogen therapy (Stevens et al. 1993). Tsai and Liu (1992) have shown that tamoxifen concurrently injected with estradiol benzoate antagonizes the condrodestructive effects of estradiol at the early stage of knee osteoarthritis in rabbits. 

Creamer P, Lim K, George E, Dieppe P (1994) Acute inflammatory polyarthritis in association with tamoxifen. Br J Rheumatol 33 998... 

An acute inflammatory polyarthritis resembling rheumatoid arthritis has been reported in three women temporally related to the use of tamoxifen (89). 

Thomson W, Harrison B, Ollier B, Wiles N, Payton T, Barrett J, Symmons D, Silman A (1999) Quantifying the exact role of HLA-DRB1 alleles in susceptibility to inflammatory polyarthritis. Arthritis Rheum, 42 757-762. 

In streptococcal cell wall arthritis, an animal model of RA, an inflammatory polyarthritis is induced by injecting streptococcal cell wall into susceptible animals. Treatment with a single course of a non-depleting anti-CD4 mAb, at the time of streptococcal cell wall injection, prevents the development of arthritis. Furthermore, the treated animals acquire a resistance to further attempts at disease induction without repeated treatment with anti-CD4 mAbs. This refractory state appears to be due to the induction of immunological tolerance (67). 

As was already mentioned, piroxicam also is a nonsteroidal, anti-inflammatory drug. It is used in inflammatory and degenerative diseases of the musculoskeletal system that are accompanied by painful symptoms. It is used for rheumatic heart disease, nonspecific infectious polyarthritis, gouty arthritis, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, arthrosis, back pain, nenralgia, myalgia, and other diseases associated with inflammation. Synonyms for piroxicam are feldene, dexicam, roxenan, and others. 

Viral arthritis is rather common and usually selflimited within a few weeks. The most common pathophysiological mechanism is not a direct virus invasion in the synovium but deposition of immune complexes. Viral infections frequently involve multiple joints and produce inflammation without suppuration. The typical clinical presentation is a peripheral and symmetrical polyarthritis, undistin-guishable from other inflammatory arthritis. Virtually all viruses can cause arthritis. There is no specific treatment and simple symptomatic measures are sufficient. 

Fluorination of corticosteroids at C-9 or/and C-6 increases glucocorticoid activity, while mineralocorticoid activity, responsible for sodium retention (the main adverse effect of corticoids), is decreased (cf. Chapter 4). Fluorocorticoster-oids were the first fluorinated compounds to be used clinically. They are still major drugs against many inflammatory disorders rheumatoid polyarthritis, ORL (asthma, rhinitis), brain edema, dermatological, allergies, anaphylactic shock, Quincke s edema). 

Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory joint disease. It is a progressive symmetrical, destructive and deforming polyarthritis affecting proxi-... 

Clinical use Phenylbutazone (Brogden, 1986) is a nonsteroidal anti-inflammatory drug used for the acute treatment of ankylosing spondylitis, chronic polyarthritis and gout. Phenylbutazone on its own shows only weak inhibition of COX-1 and COX-2 with IC50s >30 pM (Brideau et al., 1996) and active metabolites are mainly responsible for its actions. 

Two commonly used models to detect anti-inflammatory activity are carrageenan-induced paw edema and adjuvant-induced polyarthritis in rats. The former represents an acute and the latter a chronic inflammatory process. Non-steroidal anti-inflammatory agents inhibit the formation of carrageenan-induced paw edema. However, to detect activity in the developing and established phases of chronic inflammation, the polyarthritis model is well accepted. In both tests the measured endpoint is volume of the hind paw. This is done by immersing the hind paw in the well of a mercury displacement... 

Systemic lupus erythematosus and rheumatoid arthritis The possible role of interferon alfa in the development of rheumatoid arthritis or systemic lupus erythematosus has been described in isolated cases (363,364), and confirmed cases of systemic lupus erythematosus have very occasionally been reported (SED-13, 1096) (SEDA-20, 330). In most of these cases, the predominance of young patients and female sex, the presence of renal or skin involvement, the findings of positive antibodies to double-stranded DNA, and the rapid onset after the start of treatment, as well as persistence of symptoms after interferon alfa withdrawal, are more in keeping with unmasking by interferon alfa of idiopathic lupus rather than with a new drug-induced illness. The reactivation or appearance of inflammatory rheumatological disorders consistent with rheumatoid arthritis or lupus-like polyarthritis were... 

In contradistinction to the various types of chemically-induced and anaphylactic arthritis which have been mentioned above, adjuvant arthritis appears to simulate closely the inflammatory reactions seen in rheumatoid arthritis in humans. Stoerk, Bielinski and Budzilovitch first reported the development of a chronic polyarthritis in rats, and this work was later elaborated by a number of other workers " . The reaction seems to be a type of delayed hypersensitivity response , although recent work suggests that this may not be so. ... 

Table 6.3. Cu(II)2(acetate)4 was found to be active in the initial test (carrageenan paw oedema) for anti-inflammatory activity, but inactive in the two follow-up anti-inflammatory screens (cotton wad granuloma and polyarthritis). Cupric chloride had no activity in any of these models of inflammation. Ligands such as anthranilic acid and 3,5-diisopropylsalicylic acid (3,5-DIPS) which were anticipated to be inactive were found to be so. However, their copper complexes were found to be potent anti-inflammatory agents in all three models of inflammation. These observations supported the notion that complexed copper is a more active anti-inflammatory form of copper and led to the suggestion that copper complexes of active anti-inflammatory agents might be more active than their parent anti-inflammatory drugs.

The observation that copper complexes have anti-inflammatory activity has been confirmed and extended by many others with reports that the same and additional copper complexes listed in Table 6.4 have anti-inflammatory activity in an even greater variety of animal models of inflammation carrageenan, kaolin, dextran, hydroxyapatite and concanavolin A (Con A) paw oedemas, cotton wad granuloma, polyarthritis and ultraviolet erythema. Data presented for copper complexes and their parent ligands in all subsequent reports when compared on a molar basis also show marked increases in anti-inflammatory... 

A number of new copper complexes have also been found to have antiinflammatory activity. Copper(II)(j8-oxo-2-thiophenepropionitrile) is effective in treating rat polyarthritis [175]. The copper complex of glycyl-L-histidyl-L-lysine, Cu(II)(GHL), is claimed to have anti-inflammatory activity and increase the rate of wound healing [176, 177] consistent with earlier reports of increased gastric wound healing rates associated with Cu(II)(aspirinate)4 and Cu(II)(tryptophanate)2 treatment [178]. Copper(II)(L-histidinate)2, Cu(II)-... 

In a large study, many ligands were mixed with Cu(OH)2 or Cu2(acetate)4 in glycerol-ethanol or dimethylsulphoxide and studied in the carrageenan, hydroxyapatite and polyarthritis models of inflammation to determine antiinflammatory activity following topical application [183], Many of these mixtures were found to have anti-inflammatory activity and comparisons of Cu(ll)(salicylate)2, Cu(ll)2(niflumate)4 and Cu(II)(phenylbutazone)2 with their parent ligand in the polyarthritis model revealed that these complexes were more effective than their parent ligands, which were inactive or much... 

To evaluate the time-course of analgesia associated with a non-steroidal anti-inflammatory agent and its copper complex, salicylic acid and its complex were compared in the polyarthritis pain model following oral administration in 5 % gum arabic. Data presented in Figure 6.4 show that analgesic activity increased in a dose-related manner and that Cu(II))(salicylate)2 was 7- to... 

Some empirical uses of S. sclarea as a cure for cold ailments of the respiratory apparatus as well as nervous polyarthritis and acute rheumatism [8] led to the hypothesis of an anti-inflammatory action of certain components, in particular the essential oil. With the aim of determining antiinflammatory and anti-nociceptive properties of S. sclarea essential oil, studies were conducted on experimental models of inflammation and pain [35, 46]. 

Prior to 1950, the anti-inflammatory activities of Cu complexes had been exclusively studied in humans for the treatment of tuberculosis and rheumatic diseases. In 1950 Kuzell and Gardner [78] reported that the i.m. administration of allocupreide (1) favourably influenced polyarthritis produced in rats with a pleuropneumonia-like organism. However, in 1951, using this same model of experimental arthritis, Kuzell, Schaffarzick, Mankle and Gardner [63] reported... 

Miscellaneous - Specific amino acids have been studied for anti-inflammatory activity. Thus, the combination of calcium D,L-aspartate/indometha-cin has been repor gd to be effective in primary chronic polyarthritis Dilauroyl-L-lyslne and trans U-aminomethyl-cyclohexane-l-carboxylic acid (tranexamic acid) have anti-inflammatory properties. The activity of tranexamic acid was not attributed to anti-plasmin action. Detailed pharmacology on SKF 17,910-A (X) has been published. This anti-inflammatory and diuretic agent shares some biological properties with glucocorticoids. 

Several small uncontrolled pilot studies have indicated that most patients with psoriatic arthritis improve when treated with etretinate at 0.5-1 mg/kg/day (Brackertz and Muller, 1979 Rosenthal 1979 Stollenwerk et al., 1981 Kaplan etal., 1983). In one report the etretinate-induced improvement allowed patients to decrease or discontinue their use of nonsteroidal anti-inflammatory agents. In another report patients with chronic polyarthritis similarly improved. RePUVA also led to improvement in five of six patients with psoriatic arthritis. However, because healing of cutaneous lesions of psoriasis with PUVA is associated with an improvement in joint disease, controlled studies are needed to confirm that etretinate is effective in psoriatic arthritis and that the effect is not secondary to cutaneous improvement. 

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