TNF +489 polymorphism does not contribute to susceptibility to rheumatoid arthritis.

OBJECTIVES: To determine if a tumour necrosis factor (TNF +489) polymorphism is associated with susceptibility to rheumatoid arthritis (RA). METHODS: Two European populations were studied: 217 controls and 238 patients from the north of England and 145 controls and 179 patients from Spain. HLA-DRB1 and TNF +489 markers were typed using polymerase chain reaction based methods. RESULTS: Strong associations were demonstrated with shared epitope (SE) encoding HLA-DRB1 alleles in the English (OR = 2.9 [2.2-3.9]) and Spanish (OR = 2.3 [1.6-3.3]) populations, however no association was found with TNF +489 alleles. Furthermore carriage of TNF +489A was not associated with the presence of radiological erosions, rheumatoid nodules or rheumatoid factor. CONCLUSION: The role of the TNF locus in the genetic background of RA is unclear, however, our data does not support the previous reported association of the TNF +489A allele with RA susceptibility or severity.

Peripheral ulcerative keratitis 'corneal melt' and rheumatoid arthritis: a case series.

OBJECTIVES: (1) To review the visual and systemic outcomes of patients who developed rheumatoid arthritis (RA)-associated peripheral ulcerative keratitis (PUK). (2) To describe the clinical and serological characteristics of the patients' arthropathy at the time of presentation of this rare condition. (3) To review the aetiology and management of RA-associated PUK. Patients and methods. A case series is given of all nine patients within our unit who have developed RA-associated PUK since 1996. Details of the patients' arthropathy and the serological characteristics of the RA at presentation of PUK were noted. The patients' visual outcomes and the development of any significant systemic complications were recorded. RESULTS: All patients had long-standing seropositive, erosive RA. PUK was associated with a poor visual outcome in most patients, five requiring emergency corneal surgery to prevent perforation of the globe. Two patients developed systemic vasculitis within 1 month of PUK onset, one of whom died. CONCLUSION: RA-associated PUK often has a poor visual outcome and its appearance may herald the transformation of a patient's RA into the systemic vasculitic phase. RA-associated PUK should be managed with aggressive immunosuppression if the associated morbidity and mortality are to be avoided. Cell-mediated mechanisms appear to be important in the aetiopathogenesis of PUK and a combination of corticosteroids and cyclosporin is therefore probably the regimen of choice.

Long-term follow-up of juvenile-onset cutaneous polyarteritis nodosa associated with streptococcal infection.

Polyarteritis nodosa (PAN) is a multisystem inflammatory disease associated with necrotizing vasculitis of small and medium arteries. Although predominantly an adult disease, PAN is well described in children. It can occur in a systemic form with manifestations in skin, joints, heart, nervous system, gastrointestinal tract, lungs and kidneys, and a limited form in which disease is confined to the skin, muscles, joints and peripheral nerves. In either case, streptococcal infection has been implicated by a positive throat swab or a significant increase in either antistreptolysin O (ASOT) or antihyaluronidase titres. The limited form is thought to run a benign course, but little has been written about its long-term outcome. We describe two patients who developed a cutaneous vasculitis following a probable streptococcal infection. Both have run a relapsing and remitting course with significant elevations of ASOT and in one, at least, prophylactic penicillin has had a strikingly beneficial effect. In both patients, the disease seems to have receded during childhood, only to recur, retaining its original form, in adult life. Their current ages are 22 and 19 yr, respectively.

Neurofibromatosis masquerading as monoarticular juvenile arthritis.

A 3-yr-old boy presented with a monoarthritis. Persistence of the condition and some unusual features led to re-evaluation of the original investigations, when a diagnosis of extensive plexiform neurofibroma involving his right leg was made. This previously unreported presentation of neurofibromatosis is discussed.

Infertility may sometimes be associated with NSAID consumption.

Non-steroidal anti-inflammatory drugs are widely used in the treatment of inflammatory joint diseases. Many patients suffering from these disorders are young women during their childbearing years. We report three cases of infertility where the cause may have been NSAID-induced 'luteinized unruptured follicle' syndrome. This phenomenon is well recognized in obstetric circles, and we would like to bring it to the attention of rheumatologists since it is not documented in the rheumatological literature.

The history of the use of sulphasalazine in rheumatology.

Sulphasalazine was initially used more than 50 yr ago to treat inflammatory arthritis but fell into disuse, only to be revived 25 yr ago for rheumatoid arthritis. Since then its place as a second-line agent has been established and its toxicity profile has been outlined. Subsequently, its use has been widened to include other inflammatory rheumatic diseases, with strong suggestions that it may be useful for several indications. The history of its initial use, its reintroduction and the establishment of its place in modern rheumatology are reviewed.

Methotrexate and sulphasalazine as combination therapy in rheumatoid arthritis.

Sulphasalazine (SASP) and methotrexate (MTX) are well-established treatments for RA but the use of these drugs in combination has been avoided as both have antifolate activity. In this paper we report our experience with 32 patients treated with the combination MTX/SASP and compare the toxicity and tolerability of the combination with 63 patients treated with MTX alone. The median duration of exposure to the combination was 23 months. Nineteen patients have continued this regime for over 18 months. Five patients on MTX/SASP combination discontinued MTX, in four cases due to toxicity and in one because MTX/SASP was ineffective. In 17 patients on MTX alone, the drug was withdrawn permanently. In seven cases the cause was toxicity including two patients with severe reactions. In patients known to tolerate SASP alone, the combination of MTX/SASP is also well tolerated. In our experience of 48 patient-years of such combination therapy, there is no increase in toxicity compared to therapy with MTX alone in RA.

Arthritis artefacta: factitious disease in rheumatology.

Self-induced disease can be difficult to diagnose and costly of time and money to investigate. The key is to think of the possibility. Five patients in whom the evidence for factitious rheumatological illness was strong are discussed and their histories, physical signs and family backgrounds are explored in relationship to factitious disease presenting in other fields. Young immature individuals seem most at risk and the discrepancy between physical signs and understandable pathological mechanisms may suggest the diagnosis. The outlook seems frequently poor.

Leucopenia in rheumatoid arthritis: relationship to gold or sulphasalazine therapy.

Leucopenia is one of the most worrying of the many toxic effects of second-line drug therapy for rheumatoid arthritis, and much time and energy is expended in screening for it. Sulphasalazine (SASP) is generally claimed to be safer than some alternative second-line drugs but the reported incidence of leucopenia has varied widely. We have examined, retrospectively, all records of blood counts before, during and after treatment in 326 SASP treated patients and in 213 on gold. Leucopenia on at least one occasion occurred in up to 10% of patients on both drugs but usually recovered spontaneously in spite of continued therapy. 'Serious' leucopenia leading directly to drug withdrawal was a rare event occurring in only one SASP patient and in two patients receiving gold treatment. Most episodes of leucopenia do not require drug withdrawal and may not be drug related.

[Experiences in long-term therapy of rheumatoid arthritis with sulfasalazine tablets]. / Erfahrungen bei der Langzeittherapie der rheumatoiden Arthritis mit Sulphasalazin-Dragées.

To demonstrate the efficacy and compatibility of sulphasalazine as a long term treatment of rheumatoid arthritis, use of the substance (known in Britain as Salazopyrin EN and in Germany as Azulfidine RA) has been compared with that of intramuscular gold. Using very stringent and novel criteria for success--a patient must have no more than one swollen joint after a minimum of 2 years treatment, with less than 30 min of early morning stiffness and still be receiving the drug--the cumulative efficacy of each drug was very similar (32% with sulphasalazine vs 44% with gold). Toxic events leading to drug withdrawal, however, were twice as frequent with gold, and the type of toxic event encountered was considered to be potentially much more serious than those with sulphasalazine (96% of the toxic events on gold fell into the mucocutaneous, renal or haematological groups).

Sulphasalazine for rheumatoid arthritis: toxicity in 774 patients monitored for one to 11 years.

Sulphasalazine is being used increasingly to treat rheumatoid arthritis, though its long term safety profile has not been established in this condition. The incidence and nature of adverse effects occurring in 774 patients with rheumatoid arthritis treated with sulphasalazine for periods ranging from one to 11 years were therefore noted. Altogether 205 of the patients stopped treatment permanently due to an adverse effect. One hundred and fifty six (76%) of these events occurred within three months and few beyond the first year. Most events were trivial and were self limiting after withdrawal of the drug; of the potentially more serious adverse effects, 33 (66%) occurred within three months of treatment. None of the patients died or suffered lasting ill effects. It is concluded that adverse effects of treatment with sulphasalazine are generally seen within three months; though regular monitoring is desirable during that period, thereafter few worrying problems occur.

Sulphasalazine for rheumatoid arthritis: relationship between dose, acetylator phenotype and response to treatment.

Sulphasalazine is an effective treatment for rheumatoid arthritis but the response in any individual is unpredictable. We have sought to establish a relationship between dose (in mg/kg body weight) and metabolism of the drug in 79 patients selected for an extremely good response (43) or no response (36) to treatment with sulphasalazine. The dose of sulphasalazine in relationship to body weight showed no difference between the two treatment outcome groups. The distribution of acetylator phenotype showed only a trend for slow acetylators to occur more frequently in the group of good responders to treatment. There is no advantage in the routine assessment of acetylator phenotype as a predictor of response to treatment with sulphasalazine.