Designing an intervention for women with systemic lupus erythematosus from medically underserved areas to improve care: a qualitative study.

OBJECTIVE: Systemic lupus erythematosus (lupus) disproportionately affects women, racial/ethnic minorities and low-income populations. We held focus groups for women from medically underserved communities to discuss interventions to improve care. METHODS: From our Lupus Registry, we invited 282 women, ≥18 years, residing in urban, medically underserved areas. Hospital-based clinics and support groups also recruited participants. Women were randomly assigned to three focus groups. Seventy-five-minute sessions were recorded, transcribed and coded thematically using interpretative phenomenologic analysis and single counting methods. We categorized interventions by benefits, limitations, target populations and implementation questions. RESULTS: Twenty-nine women with lupus participated in three focus groups, (n = 9, 9, 11). 80% were African American and 83% were from medically underserved zip codes. Themes included the desire for lupus education, isolation at the time of diagnosis, emotional and physical barriers to care, and the need for assistance navigating the healthcare system. Twenty of 29 participants (69%) favored a peer support intervention; 17 (59%) also supported a lupus health passport. Newly diagnosed women were optimal intervention targets. Improvements in quality of life and mental health were proposed outcome measures. CONCLUSION: Women with lupus from medically underserved areas have unique needs best addressed with an intervention designed through collaboration between community members and researchers.

Abatacept in the treatment of rheumatoid arthritis.

Over the past decade, biological immunotherapy has revolutionised the treatment of rheumatoid arthritis (RA). The most widely used of these therapies targets tumour necrosis factor-alpha (TNF-alpha). Approximately 20% of patients fail to respond to TNF-alpha antagonism, however, and a significant number of additional patients become refractory to anti-TNF-alpha therapy over time. Thus investigators have sought to target other pathogenic elements of RA using novel biological therapies. Abatacept is the first immunotherapy directed against the process of T-cell costimulation. Abatacept has shown clinical effectiveness in RA by improving disease activity, quality of life measures and radiographic progression of disease. In this article, we review the immunology of T-cell activation and costimulation, define the role of abatacept in this process, and discuss the clinical trials that led to the approval of abatacept as the latest biological therapy in RA in the USA and Canada. We also address the role of abatacept in the greater context of biological therapy for RA.

An atypical population of NK cells that spontaneously secrete IFN-gamma and IL-4 is present in the intraepithelial lymphoid compartment of the rat.

The intestinal lymphoid compartment of the rat is large and diverse, but the phenotype and functions of its constituent cell populations are not fully characterized. Using new methodology for the isolation and purification of rat intestinal intraepithelial lymphocytes (IELs), we previously identified a population of alphabeta- and gammadelta-TCR- NKR-P1A+ NK cells. These cells were almost completely restricted to the CD4-CD8- IEL population, and unlike peripheral NK cells in the rat, they were CD2-. We now report that rat intraepithelial NK (IENK) and peripheral NK cells are similar in morphology, in their ability to lyse NK-sensitive targets, and in their ability to suppress a one-way mixed lymphocyte culture. In contrast, however, intraepithelial and splenic NK cells differ markedly in two respects. First, IENK cells express high levels of ADP-ribosyltransferase 2 (a marker of regulatory T cells in the rat) and CD25, whereas peripheral NK cells do not. Second, unlike splenic NK cells, a substantial fraction of IENK cells appear to spontaneously secrete IL-4 and/or IFN-gamma. We conclude that the rat IEL compartment harbors a large population of NKR-P1A+CD3- cells that function as NK cells but display an activated phenotype and unusual cytokine profile that clearly distinguish them from splenic NK cells. Their phenotypic and functional characteristics suggest that these distinctive IENK cells may participate in the regulation of mucosal immunity.

Concurrent pilomatrix carcinoma and giant pilomatrixoma.

A 52-year-old man presented with a large, fungating mass on the inner aspect of his left thigh and a smaller hard mass on the inner aspect of his left knee with normal overlying skin. Both lesions had first been noted by the patient 1 year previously and for the first 6 months had a similar appearance until the thigh mass rapidly increased in size and fungated. Pathology of the large thigh lesion showed pilomatrix carcinoma while that of the smaller knee lesion was typical of pilomatrixoma. The pilomatrix carcinoma was widely excised and there has been no evidence of recurrence or metastasis after 3 years. The clinical course of the thigh lesion suggested that pilomatrix carcinoma may arise from a pre-existing pilomatrixoma. On review of the literature, pilomatrix carcinoma of the lower limb may be more likely to metastasize than those on other sites.

Molecular genetics of erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) is caused by decreased activity of the enzyme ferrochelatase and is characterized by burning photosensitivity commencing in childhood. From 1-10% of patients develop potentially fatal protoporphyric hepatic failure. The gene for ferrochelatase has been cloned, sequenced and mapped to the long arm of chromosome 18. EPP is genetically very heterogeneous and 24 different mutations in 27 unrelated patients have been published. In the majority of families co-inheritance of a mutant ferrochelatase allele from one parent and a low-output "normal" ferrochelatase allele from the other parent is required for disease expression. The molecular basis, if any, of protoporphyric hepatic failure has not yet been resolved. Gene therapy experiments have been completed in vitro and are in progress in an animal model of EPP. In conclusion, molecular genetic investigation of EPP has increased our understanding of its pathogenesis and inheritance. Why some EPP patients develop hepatic failure is still unanswered. Gene therapy of EPP patients may become possible in the future.

Clinical implications of the molecular biology of erythropoietic protoporphyria.

AIM: To review our present knowledge about the molecular genetics of erythropoietic protoporphyria. METHODS: Literature review. RESULTS: Erythropoietic protoporphyria (EPP) is caused by decreased activity of the enzyme ferrochelatase and is characterized by distressing photosensitivity commencing in childhood. For reasons that are not yet fully understood, some patients develop potentially fatal acute hepatic failure. The gene for ferrochelatase has been cloned, sequenced and mapped to the long arm of chromosome 18. Subsequent molecular analysis has shown EPP to be very genetically heterogeneous, and 28 different mutations in 31 unrelated patients have been published. No mutation(s) in the ferrochelatase gene or elsewhere in the genome, or environmental factors have been conclusively associated with the development of protoporphyric hepatic failure. The complex inheritance of EPP has now been partially resolved. In the majority of families co-inheritance of a mutant ferrochelatase allele from one parent and a low-output 'normal' ferrochelatase allele from the other parent is required for disease expression. Gene therapy experiments have been completed in-vitro and are in progress in an animal model of EPP. CONCLUSION: EPP is a good example of how advances in molecular biology have led to a greater understanding of the pathogenesis and inheritance of disease. The most urgent need is to discover why some EPP patients develop hepatic failure. Gene therapy of EPP patients should become possible in the future.

Day 4 is better than day 3 for a single patch test reading.

Readings were performed on day (D) 2, D3 and D4 after application of patch tests in 88 patients. 90 patch test reactions in 49 patients were interpreted as allergic and of past or present relevance. A single D2 reading detected 58 of the allergic reactions with 32 false-negatives and 23 false-positives. A single D3 reading detected 77 allergic reactions, with 13 false-negatives and 17 false-positives. A single D4 reading detected 85 allergic reactions, with 5 false-negatives and 9 false-positives. Therefore, if only a single reading is feasible, it is better performed on D4 than on D3.

Erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) is an inherited inborn error of porphyrin metabolism caused by decreased activity of the enzyme ferrochelatase, the terminal enzyme of the haem biosynthetic pathway, which catalyses the insertion of iron into protoporphyrin to form haem. EPP is characterized clinically by photosensitivity to visible light commencing in childhood, and biochemically by elevated red cell protoporphyrin levels. Although the majority of papers and reviews have classified EPP as an autosomal dominant disorder, the inheritance has now been shown to be more complex, and both autosomal dominant and recessive patterns of inheritance have been demonstrated using ferrochelatase activity. Further molecular studies should clarify the exact mode of inheritance. It seems likely that in the majority of families a defective allele from the apparently normal parent will be required for disease expression, but another possibility is autosomal dominant inheritance with low clinical penetrance. Exposure to bright sunlight, for as little as a few minutes in the worst affected patients, causes burning pain in exposed skin, which may be so severe and persistent that it prevents sleep for several nights. Patients usually attempt to relieve the pain by cold water or cold compresses. Apart from sun avoidance, the mainstay of prophylactic treatment has been beta-carotene. Although the published evidence for the effectiveness of beta-carotene is impressive, no controlled trials using adequate doses have been performed to unequivocally confirm its usefulness. The most serious complication of EPP is acute hepatic failure, which is due to accumulation of protoporphyrin in the liver. If jaundice develops, a rapidly fatal outcome often follows, unless liver transplantation is undertaken. Regular monitoring of liver function and red cell porphyrin levels is advisable, but this does not always identify patients before serious liver damage has occurred. Even when patients are identified at an early stage in the development of liver disease the therapeutic options available to prevent further damage are limited, and have not been fully evaluated. The gene for ferrochelatase has been cloned, sequenced and mapped to the long arm of chromosome 18. As mutations continue to be identified, phenotype/genotype correlations should become apparent, and it may eventually be possible to identify those patients at risk of developing hepatic failure. In addition, as the basic enzymatic defect in EPP is at the level of the bone marrow stem cells, which are the target cells of choice in the development of retroviral-mediated gene transfer, definitive treatment of EPP by gene therapy is a distinct hope for the future.(ABSTRACT TRUNCATED AT 400 WORDS)

Erythrodermic psoriasis. Report of a case associated with symptomatic hypophosphataemia.

We describe a patient with a long history of psoriasis who developed severe erythrodermic psoriasis associated with lethargy, muscular weakness and collapse. Serum biochemical screening at the time revealed severe hypophosphataemia, and when this was corrected by intravenous phosphate replacement her symptoms resolved and her psoriasis improved. Hypophosphataemia may therefore be another metabolic complication of erythrodermic psoriasis.

Erythropoietic protoporphyria, transfusion therapy and liver disease.

A 28-year-old man who had suffered from erythropoietic protoporphyria since infancy was referred because of worsening photosensitivity. Conventional therapy with beta-carotene, terfenadine and topical sunscreens was ineffective or not tolerated, and he was treated with transfusions of washed packed cells. Unexpectedly, his photosensitivity deteriorated further, his whole blood protoporphyrin levels doubled and he developed abnormal liver function tests. This is the first report of such an adverse response to blood transfusion therapy for erythropoietic protoporphyria and may have been related to subclinical hepatitis or the increased iron load associated with blood transfusion.

Patch testing with pure palladium metal in patients with sensitivity to palladium chloride.

During a 15-month period, 536 patients being investigated for suspected contact dermatitis were patch tested with the European standard series and palladium chloride 1% pet. 13 patients (2.4%) had a positive allergic response to palladium chloride and all 13 were also allergic to nickel. 12 of these 13 patients consented to further patch testing with discs of pure palladium metal foil, and none reacted. We have shown previously that palladium chloride patch test material contains traces of nickel, and propose an explanation for these results in terms of the additive effect of allergens when tested in combination.