Jaundice due to suspected statin hepatotoxicity: a case series.

Statin drugs are widely used worldwide and are generally considered safe and well tolerated. Only small proportion of patients receiving statins develop elevations of liver enzymes and an even smaller proportion will have clinically significant hepatitis induced by statins. We describe four patients with jaundice caused by drug-induced liver injury, where the most likely agent was a statin drug, over a period of approximately three year in Iceland. We calculate the risk of jaundice caused by statin drugs, from sale in the whole country of Iceland, to be one in 17,434 users a year. This is a higher risk than has previously been estimated and we challenge the current opinion that statins rarely cause clinically significant drug-induced liver injury and encourage alertness when managing patients with statins with regard to clinical signs of hepatitis before jaundice occurs.

Tissue localization and the establishment of a sensitive immunoassay of the newly discovered human phospholipase B-precursor (PLB-P).

Human phospholipase B-precursor (PLB-P) is a newly identified and purified protein from human neutrophils. The precise function of PLB-P in vivo is not yet known. Its existence in neutrophils and the enzymatic activity against phospholipids imply a role in the defence against invading microorganisms and in the generation of lipid mediators of inflammation. We describe here the generation of specific antibodies against PLB-P, the tissue localizations of PLB-P and the establishment of an accurate, specific, and reproducible radioimmunoassay (RIA). A survey of normal and malignant tissues showed strong immunostaining of PLB-P in neuronal and myeloid cells and in adrenal glands. Elevated levels were found in sera of patients with influenza A infection i.e. >1 microg/L and in gut fluids of patients with inflammatory bowel disease i.e. >20 microg/L. The levels correlated to markers of neutrophil activation, suggesting a neutrophil origin of PLB-P in these conditions. The antibodies and the assay will be useful in the future basic and clinical investigations of PLB-P.

Gluten sensitivity in patients with IgA nephropathy.

BACKGROUND: Coeliac disease is more frequent in IgA nephropathy (IgAN) patients compared to the healthy population. Several hypotheses postulate that food antigens like gluten may be involved in the onset of IgAN. METHODS: In this study, we used a recently developed mucosal patch technique to evaluate the rectal mucosal inflammatory reaction to gluten in patients with IgAN (n = 27) compared to healthy subjects (n = 18). The rectal mucosal production of nitric oxide (NO) and release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured. Serum samples were analysed for IgA and IgG antigliadin antibodies (AGA), IgA antibodies against tissue transglutaminase and IgA endomysium antibodies. RESULTS: Gluten reactivity, defined as increase in MPO and/or NO after gluten exposure, was observed in 8 of 27 IgAN patients. The prevalence of HLA-DQ2 and DQ8 was not increased among gluten-sensitive patients, and the total prevalence among IgAN patients was the same as for the normal population. An elevated serum IgA AGA response was seen in 9 of 27 IgAN patients. The increase in IgA AGA did not correlate with the gluten sensitivity as measured by NO and/or MPO. A specific serum IgG AGA response was seen in one patient only. Antibodies against tissue transglutaminase and endomysium were not observed. CONCLUSION: It is concluded that approximately one-third of our IgAN patients have a rectal mucosal sensitivity to gluten, but without signs of coeliac disease, and we hypothesize that such sub-clinical inflammation to gluten might be involved in the pathogenesis of IgAN in a subgroup of patients.

The prevalence of celiac disease in blood donors in Iceland.

BACKGROUND: Prospective epidemiological studies based on serological methods have shown that celiac disease is more common than previously thought. The aim of this study was to evaluate the prevalence of celiac disease among apparently healthy blood donors in Iceland. METHODS: Plasma samples were obtained from 813 apparently healthy blood donors at the FSA Hospital Blood Bank in Akureyri, Iceland, between December 2004 and January 2007 and screened for human tissue transglutaminase IgA antibodies. Positive samples were retested and, if the test was again positive, the subject was referred to a gastroenterologist for clinical examination and a duodenoscopy with mucosal biopsies. RESULTS: Six subjects tested positive for tissue transglutaminase. The prevalence of biopsy-confirmed celiac disease, according to modified Marsh classification, among apparently healthy blood donors in Iceland was found to be 1:136 (0.74%, 95% confidence interval 1/667-1/75, 0.15-1.33%). CONCLUSION: Prevalence of celiac disease in Iceland is similar to what has been reported in many other countries.

Gluten sensitivity in patients with primary Sjögren's syndrome.

OBJECTIVE: To evaluate the rectal mucosal response to gluten as an indication of gluten sensitivity in patients with primary Sjögren's syndrome (pSS). MATERIAL AND METHODS: Rectal challenges with wheat gluten were performed in 20 patients with pSS and 18 healthy control subjects. Fifteen hours after challenge the mucosal production of nitric oxide (NO) was measured. RESULTS: Five patients with pSS had a significant increase in the luminal release of NO after the rectal gluten challenge, indicating gluten sensitivity. All were HLA-DQ2 and/or -DQ8-positive. Two of the patients with increased NO had antibodies against transglutaminase and a duodenal biopsy showed an absolutely flat mucosa consistent with coeliac disease in one of the patients. Before gluten challenge, 15 of the Sjögren's syndrome (SS) patients reported gastrointestinal symptoms, and 8 reported intolerance to various food products. No correlation was found between gluten sensitivity and self-reported food intolerance or gastrointestinal symptoms. CONCLUSIONS: Rectal mucosal inflammatory response after gluten challenge is often seen in patients with pSS, signifying gluten sensitivity. However, this reactivity is not necessarily linked to coeliac disease.

Patients with psoriatic arthritis have an increased number of lymphocytes in the duodenal mucosa in comparison with patients with psoriasis vulgaris.

OBJECTIVE: To determine if there is evidence of inflammation in the duodenal mucosa in patients with psoriatic arthritis (PsA) and to compare the results with those in patients with psoriasis vulgaris (PsV). METHODS: Nineteen consecutive patients with PsA underwent gastroduodenoscopy, and biopsy specimens were taken from the duodenal and gastric mucosa. In addition to routine processing, the duodenal mucosal specimens were stained for CD3+, CD8+ and CD4+ T lymphocytes, tryptase-positive mast cells, and EG2-positive eosinophil granulocytes. The results were compared with those in duodenal mucosal specimens from patients with PsV and patients with irritable bowel syndrome. RESULTS: Compared with PsV patients (without antibodies against gliadin), patients with PsA had a highly significant increase in intraepithelial CD3+ and CD8+ lymphocytes and also in CD4+ lymphocytes in the lamina propria in the villi. The lymphocyte increase was not related to presence of IgA antibodies against gliadin, endomysium, or transglutaminase, or to concomitant gastritis. Patients with PsA and PsV showed a pronounced increase in mast cells and eosinophil granulocytes. CONCLUSION: The increased lymphocyte infiltration in the duodenal mucosa in PsA, but not in PsV, might indicate different pathogenetic mechanisms in these psoriasis variants.

Kinetics of mucosal granulocyte activation after gluten challenge in coeliac disease.

OBJECTIVE: To elucidate the dynamics of the rectal inflammatory response to rectal gluten challenge in coeliac disease by measuring inflammatory mediators released by activated neutrophils, eosinophils and mast cells/basophils. MATERIAL AND METHODS: The release of myeloperoxidase (MPO), eosinophilic cationic protein (ECP) and histamine was measured continuously during the early challenge period (3-6 h after gluten challenge) in coeliac patients (n = 9) and healthy controls (n = 5). A segmental perfusion technique was used to carry out this part of the study. Another method, the mucosal patch technique, was used to enable studies of the late challenge period (5-48 h after gluten challenge) in coeliac patients (n = 10) and healthy controls (n = 15). RESULTS: During the early challenge period the MPO levels began to increase as early as 3 h after challenge and increased progressively (p < 0.001) during the next 3 h. A decline in MPO levels was seen 15 h after challenge and another phase of increasing levels at 24 h. The MPO values declined 48 h after challenge but still remained significantly increased (p < 0.05). The ECP levels started to increase 4 h after challenge and increased progressively during the next 2 h (p < 0.05). The ECP kinetics during the late challenge period was similar as for MPO but the relative increase in ECP was more modest. No increase in histamine was found except in one patient who had a transient, early increase of histamine (3-5 h after challenge). No signs of inflammatory reaction to gluten were seen in the controls. CONCLUSIONS: There is a pronounced neutrophil activation in coeliac patients after rectal gluten challenge. This activation is apparent 4 h after challenge and remains for at least 48 h. A more modest eosinophil activation defined by ECP levels starts 1-2 h later and also remains for at least 48 h. The biphasic pattern of MPO and ECP after challenge suggests a biphasic inflammatory reaction.