Clinical and histological resolution of collagenous sprue following gluten-free diet and discontinuation of non-steroidal anti-inflammatory drugs (NSAIDs).

Collagenous sprue is a rare small bowel enteropathy that has overlapping clinical features with coeliac disease; it is commonly associated with arthritic autoimmune conditions, which often require non-steroidal anti-inflammatory drugs (NSAIDs). In the limited published literature available, there are putative suggestions of a link between NSAID use and collagen deposition in intestinal subepithelia in such patients. The authors present a case of a 43-year-old woman with long-standing NSAID use for autoimmune polyarthropathy and positive coeliac antibodies. However, distal duodenal biopsies revealed a thickened band of subepithelial collagen with villous atrophic appearances consistent with collagenous sprue. The patient was treated with a gluten-free diet and her NSAIDs were discontinued. After 6 months, her gastrointestinal symptoms had resolved with complete histological resolution of the collagenous subepithelial bands and villous atrophy on duodenal biopsy.

Retinal vein thrombosis associated with a herbal phytoestrogen preparation in a susceptible patient.

A 55 year old woman, known to have systemic lupus erythematosus and protein S deficiency, presented with sudden onset of visual loss in the left eye. Three days previously, she took a herbal phytoestrogen preparation for relief of her menopausal symptoms. Ophthalmological assessment showed a left inferior hemiretinal vein thrombosis. The temporal relation between the onset of visual symptoms and ingestion of this herbal preparation suggested that in this patient with a prior non-manifest prothrombotic tendency, there may be an association between the development of retinal vein thrombosis and herbal phytoestrogen use.

Bone turnover in untreated polymyalgia rheumatica.

BACKGROUND: Polymyalgia rheumatica (PMR) is a common condition in the elderly. A previous study demonstrated that it is associated with an increase in bone resorption. This effect was ameliorated by steroids, implying that inflammation is the cause of increased bone resorption and that this can be reduced by steroids. This is in keeping with accumulating evidence that systemic inflammation is associated with bone resorption and bone loss. We studied bone formation and resorption markers in 53 patients with PMR prior to any therapeutic intervention. METHODS: Bone resorption was measured by estimating urinary free pyridinoline (fPYD) and deoxypyridinoline (fDPD). Bone formation was estimated by measuring serum concentrations of procollagen type 1 N-terminal propeptide (P1NP). Disease activity was assessed using inflammatory markers (erythrocyte sedimentation rate and C-reactive protein). Patients had a baseline dual-energy X-ray absorptiometer scan to assess bone mineral density. RESULTS: Bone resorption markers were significantly increased and bone formation markers significantly decreased in PMR patients prior to treatment, compared with a control population matched for gender and age. CONCLUSIONS: This implies that bone turnover is uncoupled in PMR. This may lead to a decrease in skeletal mass in the long term due to the disease process alone. However, no significant loss of bone mineral density was detected. It is possible that, due to the acute onset of PMR, increased bone resorption is not present long enough to result in a detectable decrease in bone mineral density. The effects of steroid treatment on bone metabolism and the subsequent long-term outcome need to be investigated.

Epstein-Barr virus (types 1 and 2) in the tear film in Sjogren's syndrome and HIV infection.

Evidence of Epstein-Barr virus (EBV) shedding in the saliva and tear film has been sought to explain the pathogenesis of the oral and ocular features of Sjogren's syndrome. Patients with human immunodeficiency virus (HIV) infection are purported to have a higher incidence of keratoconjunctivitis sicca. Twenty patients with definite Sjogren's syndrome (primary and secondary), 19 with HIV infection, and 15 normal controls were recruited and studied. Human herpes viruses (EBV 1 and 2, CMV, HZV, and HSV-1) in tear film were detected by polymerase chain reaction of DNA extracted from Schirmer strips. HSV-1, VZV, and CMV were not detected in any tear samples. EBV-1 DNA was found in the tear film of 4 patients with Sjogren's syndrome, which was not significantly different from the control group (P = 0.18). Twelve patients with HIV infection had evidence of EBV-1 in their tears, which was significantly different from controls (P = 0.0002) and patients with Sjogren's syndrome (P = 0.014). EBV-2 was found in 3 patients with HIV and in 1 patient with secondary Sjogren's syndrome, and was always found as a co-infection with EBV-1 (P = 0.01). This represents the first report examining EBV types 1 and 2 in the tear film and also EBV in the tear film of patients with HIV. Shedding of EBV in the tear film was not related to the presence of keratoconjunctivitis sicca in Sjogren's syndrome. EBV-2 co-infection with EBV-1 has not been previously reported in the tear film. EBV infection is abnormally regulated in Sjogren's syndrome and HIV, and it is likely that the presence of EBV in the tear film is related to the patients' altered immune status.

Insoluble and soluble immune complexes activate neutrophils by distinct activation mechanisms: changes in functional responses induced by priming with cytokines.

BACKGROUND: Rheumatoid synovial fluid contains both soluble and insoluble immune complexes that can activate infiltrating immune cells such as neutrophils. OBJECTIVES: To determine if these different complexes activate neutrophils through similar or different receptor signalling pathways. In particular, to determine the circumstances which result in the secretion of tissue damaging reactive oxygen metabolites and granule enzymes. METHODS: Blood neutrophils were incubated with synthetic soluble and insoluble immune complexes and the ability to generate reactive oxidants tested by luminescence or spectrophotometric assays that distinguished between intracellular and extracellular production. Degranulation of myeloperoxidase and lactoferrin was determined by western blotting. The roles of FcgammaRII (CD32) and FcgammaRIIIb (CD16) were determined by incubation with Fab/F(ab')(2) fragments before activation. The effect of cytokine priming was determined by incubation with GM-CSF. RESULTS: Insoluble immune complexes activated unprimed neutrophils, but most of the oxidants produced were intracellular. This activation required FcgammaRIIIb, but not FcgammaRII function. Soluble complexes failed to activate unprimed neutrophils but generated a rapid and extensive secretion of reactive oxygen metabolites when the cells were primed with granulocyte-macrophage colony stimulating factor (GM-CSF). This activity required both FcgammaRII and FcgammaRIIIb function. Insoluble immune complexes activated the release of granule enzymes from primed or unprimed neutrophils, but the kinetics of release did not parallel those of secretion of reactive oxygen metabolites. Only primed neutrophils released enzymes in response to soluble complexes. CONCLUSIONS: Soluble and insoluble immune complexes activate neutrophils by separate receptor signalling pathways. Profound changes in neutrophil responsiveness to these complexes occur after cytokine priming.

Fcgamma receptors in autoimmune diseases.

Fcgamma-receptors (Fcgamma-R) recognise the Fc portion of IgG and thus form a link between humoral and cellular immunity. These receptors are expressed by a variety of immune cells, and they function in the binding of immune complexes or IgG-opsonised particles, such as microbial pathogens. The are three major types of Fcgamma-R, namely Fcgamma-RI (CD64), Fcgamma-RII (CD32) and Fcgamma-RIII (CD16), and these differ in their ability to bind IgG and complexes. There are many isoforms of these receptors and a number of recently identified polymorphisms in their structure. This review describes the structure and function of these Fcgamma-Rs, and highlights how gene deficiencies and polymorphisms may contribute to the pathology of human diseases.

Severe hypercalcaemia in B-cell lymphoma: combined effects of PTH-rP, IL-6 and TNF.

Hypercalcaemia as the only manifestation of B-cell lymphoma is seen very rarely. Its pathophysiology is heterogenous and not well understood. We report a 73-year-old man who presented with severe hypercalcaemia before any signs of malignancy became evident. He was diagnosed with a B-cell lymphoma on bone marrow trephine biopsy. The hypercalcaemia was associated with high plasma concentrations of parathyroid-hormone-related protein, interleukin-6 and tumour necrosis factor. Our patient had markedly increased osteoclast and osteoblast activity as a result of synergistic effects between these factors, with consequent severe hypercalcaemia. This is the first reported example of such combined effects of these factors in humans.

Neutrophils from the synovial fluid of patients with rheumatoid arthritis express the high affinity immunoglobulin G receptor, Fc gamma RI (CD64): role of immune complexes and cytokines in induction of receptor expression.

Neutrophils isolated from the synovial fluid of 16/24 patients with rheumatoid arthritis expressed Fc gamma RI (CD64), the high-affinity receptor for monomeric immunoglobulin G (IgG), on their cell surface. Receptor expression ranged from 17% to 168% of the level of expression obtained after incubation of control blood neutrophils with 100 U/ml interferon-gamma (IFN-gamma) for 24 hr in vitro. Similarly, mRNA for Fc gamma RI was detected in synovial fluid neutrophils from 12/15 patients and transcript levels ranged from 5% to 200% of the values obtained after treatment of blood neutrophils with IFN-gamma for 4 hr in vitro. No surface expression nor mRNA were detected in freshly isolated blood neutrophils from either patients or from healthy controls. Addition of cell-free synovial fluid to control blood neutrophils induced both mRNA and surface expression of Fc gamma RI to levels that were comparable to those achieved after addition of IFN-gamma. Neither soluble nor insoluble immune complexes appeared to be involved in induction of Fc gamma RI expression in spite of the ability of these complexes to induce protein biosynthesis. Synovial fluid-induced expression of Fc gamma RI was partially blocked by incubation with neutralizing IFN-gamma antibodies, whilst neutralizing interleukin (IL)-6 antibodies had little effect. Levels of IFN-gamma measured within these synovial fluids ranged from 0 to 2.7 U/ml, well within the range known to induce neutrophil Fc gamma RI expression. These data thus indicate that gene expression in synovial fluid neutrophils is selectively activated as the cells enter the diseased joint. Furthermore, these data indicate that induced expression of Fc gamma RI may alter the ability of infiltrating neutrophils to respond to IgG-containing immune complexes present in these joints.

The establishment of a xerostomia clinic: a prospective study.

The study investigated the aetiological factors and management of patients who have xerostomia. The subjects were 100 consecutive patients referred to the Oral Medicine Unit for investigation of oral dryness. A detailed case history was recorded and patients underwent a systematic examination together with sialometry, haematological, biochemical and immunological investigations. Suspected cases of Sjögren's syndrome (SS) were referred for assessment by a rheumatologist and ophthalmologist. Objective evidence of salivary gland hypofunction was found in 39 patients. A definite diagnosis of primary and secondary SS was made in 24 and 15 patients respectively, a further five cases had possible primary SS. Other causes of xerostomia were: undiagnosed diabetes (3); drug-induced (11); therapeutic radiation (3); alcohol-related (3); psychogenic (15) and idiopathic (21). Patients complaining of a dry mouth should be questioned about non-oral symptoms. In total, 40% of patients attending the dry mouth clinic had a diagnosis of SS.

Signs and symptoms in patients with salivary gland hypofunction.

Salivary gland hypofunction can have a devastating effect on oral health and may be an indicator of systemic disease such as Sjögren's syndrome. This prospective study investigates the oral and non-oral signs and symptoms in 120 patients with objective evidence of salivary gland hypofunction (ie, an unstimulated whole salivary flow of < 0.2 ml/min). Patients were questioned about symptoms associated with decreased oral function; non-oral symptoms were also noted. The underlying cause of salivary gland hypofunction was established on the basis of clinical and laboratory findings and further investigations. Eighty-five per cent of patients reported symptoms of decreased oral function in addition to oral dryness. Non-oral signs and symptoms were reported by 106 patients. Fifty-three per cent of patients were diagnosed as having Sjögren's syndrome. The prevalence of the following non-oral signs and symptoms were significantly higher in patients with Sjögren's syndrome, than in those without; a history of dry/irritated eyes, salivary gland swelling, dry skin and reduced lacrimal flow. Salivary gland hypofunction is associated with a wide range of oral and non-oral signs and symptoms. Several of these are of potential value as triggers for the clinician to identify patients with Sjögren's syndrome, and should serve to prompt referral for specialist investigation.