Glenohumeral instability is an important cause of shoulder pain and disability in an active population. An awareness of the prevalence of recurrent instability, either in the form of dislocation or subluxation, is particularly useful in the assessment of the young athlete presenting with shoulder pain. Young adults presenting with rotator cuff tendinitis may have an underlying instability as the primary cause of their problem. A careful clinical examination should determine whether the instability is voluntary or involuntary, of traumatic or atraumatic onset, and the primary direction of the instability, as these factors have important implications with regard to treatment. Anterior glenohumeral instability is most common and the incidence of recurrent instability following on from an initial dislocation is high in the young active patient. An intensive rehabilitation programme is indicated for all initial dislocations or subluxations but surgery may become necessary after failure of conservative treatment. Care must be taken to determine accurately those patients with voluntary or multi-directional instability and a longer trial of conservative treatment is indicated here, as results of operative treatment in those cases are less favourable. Conservative treatment should be directed at strengthening the dynamic stabilizers of the shoulder joint, notably the rotator cuff muscles. Additional X-ray views are needed to demonstrate all the radiological changes associated with recurrent instability and further evaluation with examination under anaesthesia and arthroscopy is beneficial in the assessment of these patients. Arthroscopic surgery also has a role in the treatment of patients with symptomatic labral pathology and is now being used to perform stabilization procedures in selected cases. Many operative procedures have been described for stabilization of the shoulder and these should be directed at correcting the pathology present. Restoration of the patient's flexibility and strength postoperatively is essential, especially in the athlete in order to allow a full return to sporting activity.

Sjögren's syndrome is the result of lymphocyte-mediated destruction of exocrine glands that leads to diminished or absent glandular secretions and mucosal dryness. The manifestations from the alimentary system in patients with Sjögren's syndrome include, within the mouth, mucosal dryness, atrophy, accelerated dental decay and enlargement of the major salivary glands. Dysphagia is a common complaint and is probably secondary to oesophageal dysfunction. The symptoms from gastric involvement are nausea, epigastric pain and dyspepsia which might be attributable to chronic atrophic gastritis. Whether the small bowel is affected in Sjögren's syndrome patients is not clear. However, nutritional deficiencies have been noted in these patients. Pancreatic involvement is perhaps expressed as subclinical, acute or chronic pancreatitis, and finally there have been a large number of studies dealing with liver involvement in Sjögren's syndrome. From these reports it is clear that many patients with Sjögren's syndrome have abnormal biochemical liver function tests and some of them may also have abnormal liver biopsy. The pathogenic process responsible for the hepatic damage and for the salivary gland destruction could be similar.

Although intestinal bypass procedures are no longer performed, important lessons have been learned concerning clinical arthritides resulting from bacterial overgrowth and immune complex deposition. This information is of considerable value in patients who present with the clinical picture of intestinal bypass arthritis on the basis of other bowel abnormalities. Furthermore, the pathogenetic mechanisms involving bacterial overgrowth, release of bacterial antigens, and immune complex deposition may be pertinent to many types of inflammatory arthritis.

Ankylosing spondylitis (AS) is probably produced by repeated episodes of Klebsiella-reactive arthritis, usually in HLA-B27-positive individuals. This concept is based on immunological, microbiological and serological considerations. Immunological studies based on anti-B27 tissue typing sera and anti-B27 monoclonal antibodies indicate that HLA-B27 cross-reacts with antigens found in Klebsiella, Salmonella, Shigella and Yersinia micro-organisms. Salmonella, Shigella and Yersinia gut infections are associated with a reactive arthritis that occurs predominantly in HLA-B27-positive individuals. However, microbiological studies indicate that only Klebsiella, but not Salmonella, Shigella or Yersinia, can be isolated in faecal cultures obtained from AS patients. Furthermore, serological studies involving a number of different techniques demonstrate that only antibodies against Klebsiella, but not against Salmonella, Shigella or Yersinia, can be identified in active AS patients. The evidence is sufficiently extensive to warrant long-term studies involving Klebsiella reduction in the bowel flora of AS patients, in an attempt to reduce the severity and modify the development of the disease. It would appear that Klebsiella-reactive arthritis is the precursor stage occurring in the early and active phases of AS. Only future studies can determine whether this disease will remain a taxonomic curiosity or provide guidelines for therapeutic sequelae which will be of benefit to AS patients.

Postenteric reactive arthritis is one of several syndromes in which arthritis appears to be secondary to gastrointestinal tract pathology. A wide range of microbes may trigger this type of arthritis. On the other hand, there are differences between strains in their arthritogenic potential. Two possible mechanisms, not mutually exclusive, can be forwarded to explain these findings: first, particular characteristics of the infective organisms are necessary to initiate events leading to reactive arthritis and, second, particular anatomical locations and a certain degree of mucosal involvement are needed to initiate the process. Studies on humoral and cellular immune responses have not revealed any unifying feature that could explain the pathogenesis of reactive arthritis. The HLA allele B27 plays some kind of key role. Yet the elucidation of the fine structure of B27 specificity has not led to any immediate breakthrough in the understanding of the pathogenetic pathways. Experience of reactive arthritis associated with acquired immunodeficiency syndrome suggests that helper T cells are not involved. Antigen persistence may be connected with continuation of the inflammation. Recent developments in the serology of enteric bacterial infections will provide additional tools for uncovering the triggering agents in reactive arthritis. 'Idiopathic reactive arthritis' associated with clinically silent terminal ileitis is an interesting disease entity requiring further characterization.

In this chapter we have outlined the seronegative spondarthritides associated with bowel disease, excluding those discussed in separate chapters. Although, traditionally, Crohn's disease and ulcerative colitis have been dealt with separately in any discussion of seronegative arthritides, they have been discussed together here for the following reasons. Despite being pathologically distinct they show remarkable similarity in extraintestinal manifestations including any associated arthritis. Any observed differences in prevalence rates of arthritis may be secondary to the relative difficulty in diagnosing Crohn's disease, and most of the important prevalence studies were done before the more sophisticated techniques to investigate the bowel became available. This may in part explain the dramatic increase in the world-wide incidence of Crohn's disease seen in the last 30 years, particularly through the 1970s, but which has fallen off recently (Miller et al, 1974). It would seem that the body has a limited means of expressing disease processes. The final common pathway of a number of quite distinct disease entities is the concept of the seronegative spondarthritides. Exactly how the microbiological, immunogenetic and molecular factors interact to produce a particular disease end-point is currently not clearly defined, but with the increasingly sophisticated means to investigate the body at a cellular level the explanations may soon be at hand. Further controlled family studies are also needed to define the genetic relationships more precisely. We may then be able to piece the jigsaw puzzle together.

Rheumatological disorders frequently have gastrointestinal manifestations and, conversely, intestinal disorders frequently have rheumatological manifestations. The possibility of altered intestinal permeability in arthritic patients may provide the bridge needed to link the two organ systems. The normal intestine absorbs nutrients and excludes the remaining material. If the intestine were less discriminating or 'leaky' then material normally excluded would be able to cross the intestinal mucosa into the lamina propria. An inflammatory response to these antigens, be they dietary, bacterial, or viral in origin, could produce either local or systemic disease. This would depend upon the type of immunological response and the cross-reactivity between the host's antigens and the absorbed antigens. This theory could account for the postulated relationship between intestinal abnormalities and the pathogenesis of some forms of arthritis.

Prostaglandins are long-chain, saturated, oxygenated fatty acids. Relatively large quantities of prostaglandins have been found in gut mucosa, suggesting that these substances play an important role in gastrointestinal physiology. Non-steroidal anti-inflammatory drugs (NSAIDs) cause damage to the gastric, intestinal, and colonic mucosa in experimental animals and in humans. Prostaglandins protect the gastric mucosa against injury induced by NSAIDs, and this property has been labelled cytoprotection. The mechanisms of cytoprotection have been extensively evaluated and are probably multifactorial, including effects on the gastric mucosal barrier, gastric blood flow, mucus, bicarbonate, and fluid section, ionic transport, cyclic AMP, and surface-active phospholipids. Prostaglandins may also prevent NSAID-induced injury in the small intestine and colon. The mechanisms responsible for prostaglandin protection in the lower gut against injurious agents are unknown. Further studies of the role of prostaglandins in the gut and their relationship to the effects of NSAIDs are needed. The results of these investigations may lead to a better understanding of the importance of prostaglandins in the physiology of the gastrointestinal tract, and may provide information regarding actions of NSAIDs on the functional integrity of the gastric, intestinal, and colonic mucosa.

The distal intestine contains bacterial cell wall polymers capable of inducing acute and chronic polyarthritis if systemically distributed. Parenteral injection of peptidoglycan-polysaccharide (PG-PS) polymers from certain bacterial species produces spontaneously relapsing erosive synovitis in susceptible rat strains, and normally subarthropathic amounts of PG-PS and lipopolysaccharide (endotoxin) can reactivate arthritis initially induced by PG-PS. These experimental results illustrate the inflammatory potential of luminal bacterial products and the importance of genetically determined host susceptibility factors in the pathogenesis of arthritis. Normally, luminal complexing by secretory IgA and an intact epithelial barrier limits uptake of luminal antigen; however, intestinal inflammation enhances mucosal uptake and systemic distribution of potentially injurious macromolecules, including PG-PS and lipopolysaccharide. Occult intestinal inflammation, which may be related to non-steroidal anti-inflammatory drugs or may be disease-associated, occurs in approximately two thirds of patients with rheumatoid arthritis, idiopathic reactive arthritis and ankylosing spondylitis. Enhanced mucosal permeability to macromolecules occurs in rheumatoid arthritis, enteric infections and idiopathic inflammatory bowel disease. Intestinal inflammation is associated with increased mucosal IgG production and circulating immune complexes. Hyperactive IgA synthesis occurs in many types of inflammatory joint disease. Polyclonal IgA is increased in rheumatoid arthritis, Sjögren's syndrome, ankylosing spondylitis, Reiter's syndrome, and reactive arthritis following Yersinia infection. Anti-Klebsiella IgA cross-reacts with HLA-B27 antigen, and antibodies to enteric bacteria are able to lyse lymphocytes from HLA-B27 patients with ankylosing spondylitis. Anti-Yersinia IgA is produced at the mucosa in increased quantities in patients who develop arthritis following Yersinia enteritis, possibly as a consequence of defective cellular immunity. Serum concentrations of IgA correlate with activity of rheumatoid arthritis and ankylosing spondylitis, and serum IgA immune complexes are associated with rheumatoid vasculitis, suggesting that IgA contributes to the pathogenesis of arthritis. We speculate that intestinal injury may also induce or perpetuate arthritis by systemic distribution of inflammatory mediators produced by intestinal immune effector cells.

Damage to bones and/or joints caused by occupational exposure to electrical current, heat, cold, and ionizing radiations remains a relatively little known entity among rheumatologists. Radiologically only a few typical changes may be seen. Bone demineralization, reflex dystrophy, periostitis, osteomyelitis, osteonecrosis, pathological fractures, degenerative joint disease and, in radiation-induced damage, malignancies, do not differ from those occurring from other causes or arising spontaneously. Correct interpretation of the radiological changes often rests on a history of past exposure. Because of the time lapse between exposure and evidence of damage, patients frequently omit to inform their doctors. Only by taking a careful history and elucidating such exposure can a proper diagnosis be made.

Spondylolysis and spondylolisthesis are not uncommon causes of low back pain and sciatica among the general population. Symptoms from these complaints also appear to be increasing in frequency among those who participate in competitive sports, especially those resulting in heavy pressures on the lumbar spine. Neural arch dysplasia is often a predisposing factor and there is evidence that genetic factors may play a role. Isthmic spondylolysis and mild spondylolisthesis not exceeding 10 mm can be satisfactorily cured by a simple operation involving screwing of the defect. Younger patients have better results and the operation permits the patient to withstand double loading on the lumbar spine so that most can return to work, including heavy manual labour, and to their previous sporting activities.

A 20-30 years' occupational and/or environmental exposure to fluorine may cause osteosclerosis, especially of the spine and pelvic bones, and calcification of spinal ligaments. The radiological picture may mimic many other diseases, especially ankylosing spondylitis, diffuse idiopathic hyperostosis, and rare bone diseases, such as Albers-Schönberg disease. As clinical findings are often not characteristic, early diagnosis is based on the history of occupational exposure, examination of urinary fluoride excretion (over 8 mg F-/litre in 24 hours) and radiological signs. It is also useful to monitor the concentration of atmospheric fluoride.

Interaction of the host immune system with certain substances found in the environment will, in the presence of other unknown factors such as genetic susceptibility, lead to aberrant immune responses manifested as disease. In most of the conditions discussed above, simple removal from exposure to the offending agent does not lead to resolution. This suggests that an ongoing response has been triggered which cannot immediately be turned off, perhaps due to continued presence of the substance such as in human adjuvant disease where paraffin or silicone has been found in lymphoid tissue. Scleroderma remains a disease of uncertain cause for which our present treatment is inadequate. Illnesses presented in this chapter resemble the natural form of the disease in many ways and may provide useful insight into its pathogenesis. In the short term, recognition of exposure to environmental hazards which appear to pose risk will prevent additional cases of disabling illness. Study of chemically induced forms of scleroderma may, in the future, allow us to predict potential toxicity of chemically similar compounds. If we could learn how they trigger disease, researchers might be able to apply the information to understanding the pathogenesis of naturally-occurring scleroderma.

The history of saturnine gout is almost as old as civilization itself. Studies carried out in recent decades explain the development of hyperuricaemia and gout, with the inhibiting effect of lead on the tubular urate transport causing decreased urate excretion. In the case of lead intoxication these effects are often associated with renal failure but may occur without clinical features of lead toxicity and renal damage. The clinical features of saturnine gout are essentially similar to those of primary gout; however, acute attacks tend to occur in the knee more frequently than the first metatarsophalangeal joint. Acute attacks in saturnine gout are frequently polyarticular and tophi rarely develop. The diagnosis of saturnine gout rests on the history of exposure to lead, clinical features of lead toxicity, biochemical confirmation of high serum lead levels and other biochemical abnormalities, and the exclusion of other forms of gout. Treatment consists of excluding the patient from further exposure to lead, the use of chelating agents to remove lead, and control of acute gouty arthritis and hyperuricaemia.

Today, in this age of technology, vibration caused by machinery is an almost universal hazard. Vibration transferred from a machine to the human body may cause discomfort, a reduction of performance, and even injury. Vibratory manual tools may cause damage to the circulatory system of the upper extremities (Raynaud's syndrome), to the peripheral nerves (peripheral neuropathy), and to the bones and joints (aseptic necrosis, fatigue fractures, degenerative joint disease). Vehicles and machines causing floor vibration cause degenerative disc disease of the lumbar spine. The pathogenesis of vibration injuries is still not completely clear and there is no effective treatment. Some of the abnormalities are irreversible and may cause permanent decrease of working ability, and even unemployment. This is why prevention is so important. Prevention is complex, including technical and organizational measures, use of individual protective clothing and footwear, and medical supervision both before and during employment. Workers who are exposed to vibration should be protected against other aggravating factors such as cold and noise, etc. Vibration-induced injuries are recognized in law in many countries as grounds for financial compensation. Their cost to industry is rising and, unless a means of prevention or cure is found, will continue to do so in the foreseeable future.