| 1. |
- Hagforsen, Eva, et al.
(författare)
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Calcium homeostasis and body composition in patients with palmoplantar pustulosis : a case-control study
- 2012
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 166:1, s. 74-81
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Tidskriftsartikel (refereegranskat)abstract
- Background Palmoplantar pustulosis (PPP) is a common disease strongly associated with smoking, autoimmune comorbidities and a deranged calcium homeostasis. It is unclear whether these changes in calcium homeostasis are a consequence of vitamin D status, abnormal dermal vitamin D synthesis or whether they are substantiated in effects on bone mineral density (BMD). Objectives To study the vitamin D status and BMD in patients with PPP. Methods In comparisons with two sets of controls (n = 101 for serum analyses and n = 5123 for BMD analyses), we therefore aimed to investigate whether PPP (59 cases) was associated with serum levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, whether patients with PPP had decreased BMD and finally if the dermal expression of 25-hydroxyvitamin D(3) -1α-hydroxylase (CYP27B1) and the vitamin D receptor (VDR) were affected in PPP skin lesions. Results We found no differences in mean serum 25-hydroxyvitamin D levels between cases and controls, whereas PPP cases displayed 17·8 pmol L(-1) lower (P = 0·04) values in 1,25-dihydroxyvitamin D. BMD at the hip, lumbar spine or of total body did not differ substantially between cases and controls. Finally, patients with PPP had lower dermal expression of CYP27B1 and VDR in affected skin lesions. Conclusions The increase in serum calcium levels and suppressed parathyroid hormone in patients with PPP were not attributable to derangements in vitamin D status and these patients did not have lower BMD.
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| 2. |
- Hagforsen, Eva, et al.
(författare)
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Women with palmoplantar pustulosis have disturbed calcium homeostasis and a high prevalence of diabetes mellitus and psychiatric disorders : a case-control study
- 2005
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 85:3, s. 225-232
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Tidskriftsartikel (refereegranskat)abstract
- Palmoplantar pustulosis is characterized by pustule formation in the acrosyringium. Nearly 50% of palmoplantar pustulosis sera produce immunofluorescence of the palmar papillary endothelium from healthy subjects, but also of the endothelium of normal parathyroid gland. With a case-control design the levels of calcium and parathyroid hormone in serum were measured in 60 women with palmoplantar pustulosis and 154 randomly selected population-based control women. One-third of the controls had been smokers, whereas 95% of the cases were or had been smokers. Mean age-adjusted serum calcium was increased in the patients compared with the controls (2.43 vs 2.36 mmol/l; p<0.0001), whereas the parathyroid hormone concentration was suppressed (23.2 vs 31.1 ng/l; p<0.0001). The plasma levels of parathyroid hormone-related protein were normal in patients but there was a strong expression of this protein in the acrosyringium both in palmoplantar pustulosis and control skin. As even a marginal elevation of serum calcium is associated with an increased risk for diabetes, cardiovascular disease and psychiatric disease, we analysed the risk for these disorders in palmoplantar pustulosis patients compared with that in the control group. Both diabetes mellitus and psychiatric disorders were associated with palmoplantar pustulosis with an odds ratio of 8.7 (95% CI 3.3-22.8) and 5.6 (95% CI 2.2-14.4), respectively. Palmoplantar pustulosis is a complex disease with an increased risk for several non-dermatological disorders. The role of the mildly increased serum calcium for the high risk for diabetes and depression deserves to be studied.
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| 3. |
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| 4. |
- Asumalahti, Kati, et al.
(författare)
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Genetic analysis of PSORS1 distinguishes guttate psoriasis and palmoplantar pustulosis
- 2003
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 120:4, s. 627-632
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Tidskriftsartikel (refereegranskat)abstract
- The PSORS1 locus in the major histocompatibility complex region is the major genetic determinant for psoriasis vulgaris. Within the PSORS1 region reside at least three potential candidate genes for psoriasis susceptibility. Specific allelic variants of the genes HLA-Cw*6, HCR*WWCC, and CDSN*5 are strongly associated with psoriasis vulgaris and are in strong linkage disequilibrium with each other. We have genotyped the three psoriasis vulgaris susceptibility alleles of the PSORS1 locus in two clinical variants of psoriasis (guttate psoriasis and palmoplantar pustulosis) to study whether PSORS1 is also involved in the pathogenesis of these variants. We also asked whether these two clinical subgroups could help us to distinguish the causative gene within the high-risk PSORS1 haplotype. The association of guttate psoriasis with the three PSORS1 susceptibility alleles was similar and even stronger than seen with psoriasis vulgaris. Palmoplantar pustulosis, however, did not show association with any of the three candidate genes at this locus. Finally, no correlation with the age of onset for disease was observed. Our results show conclusively that psoriasis vulgaris and guttate psoriasis have a similar genetic basis for their association to PSORS1, whereas palmoplantar pustulosis appears to be a distinct disorder.
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| 5. |
- Donat-Vargas, Carolina, et al.
(författare)
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Urinary phosphate is associated with cardiovascular disease incidence.
- 2023
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Ingår i: Journal of Internal Medicine. - 0954-6820 .- 1365-2796. ; 294:3, s. 358-369
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Elevated phosphate (P) in urine may reflect a high intake of inorganic P salts from food additives. Elevated P in plasma is linked to vascular dysfunction and calcification.OBJECTIVE: To explore associations between P in urine as well as in plasma and questionnaire-estimated P intake, and incidence of cardiovascular disease (CVD).METHODS: We used the Swedish Mammography Cohort-Clinical, a population-based cohort study. At baseline (2004-2009), P was measured in urine and plasma in 1625 women. Dietary P was estimated via a food-frequency questionnaire. Incident CVD was ascertained via register-linkage. Associations were assessed using Cox proportional hazards regression.RESULTS: After a median follow-up of 9.4 years, 164 composite CVD cases occurred (63 myocardial infarctions [MIs] and 101 strokes). Median P (percentiles 5-95) in urine and plasma were 2.4 (1.40-3.79) mmol/mmol creatinine and 1.13 (0.92-1.36) mmol/L, respectively, whereas dietary P intake was 1510 (1148-1918) mg/day. No correlations were observed between urinary and plasma P (r = -0.07) or dietary P (r = 0.10). Urinary P was associated with composite CVD and MI. The hazard ratio of CVD comparing extreme tertiles was 1.57 (95% confidence interval 1.05, 2.35; P trend 0.037)-independently of sodium excretion, the estimated glomerular filtration rate, both P and calcium in plasma, and diuretic use. Association with CVD for plasma P was 1.41 (0.96, 2.07; P trend 0.077).CONCLUSION: Higher level of urinary P, likely reflecting a high consumption of highly processed foods, was linked to CVD. Further investigation is needed to evaluate the potential cardiovascular toxicity associated with excessive intake of P beyond nutritional requirements.
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| 6. |
- Eriksson, M.O., et al.
(författare)
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Palmoplantar pustulosis : a clinical and immunohistological study
- 1998
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 138:3, s. 390-398
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Tidskriftsartikel (refereegranskat)abstract
- Pustulosis palmoplantaris (PPP) is a common chronic skin disease, which is very resistant to treatment. It is not known why the lesions are located in the palms and soles. There are few studies of the disease and in particular studies of the histology. Fifty-nine patients with PPP answered a questionnaire concerning their medical history and 39 of them were clinically examined. Biopsy specimens were taken from involved skin in 22 of the 39 patients and studied immunohistologically for tryptase+ mast cells, EG2+ eosinophils, lipocalin+ neutrophils and CD3+ T lymphocytes. The sweat gland and sweat duct were visualized with AE1/AE3 antibody (cytokeratins 1-8, 10, 14/15, 16, 19). In addition to neutrophils in the pustule and lymphocytes in the upper dermis, there were also large numbers of mast cells and eosinophils in the subpustular area. Numerous eosinophils were present in the pustule. The epidermal part of the eccrine duct was not detectable in any of the specimens from patients with PPP but was present in all of the nine control persons (including two smokers). The results indicate that the acrosyringium is involved in the inflammation and also that mast cells and eosinophils participate in a hitherto unknown way. Of the 39 patients clinically examined, two had previously diagnosed thyroid disease and two had gluten hypersensitivity. Seventeen had one or several abnormal serum concentrations of thyroid-stimulating hormone, thyroxin, antibodies against thyroglobulin or thyroperoxidase and 10 had immunoglobulin (Ig) A antibodies to gliadin. The mean +/- SD for serum IgA and for eosinophil cationic protein was increased. From the questionnaire the most notable finding was that 56 of the 59 patients had been or still were smokers, all of whom had started smoking before the first signs of PPP. We hypothesize that the acrosyringium might be the target for the inflammation and that PPP is linked to autoimmune thyroid disease and smoking.
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| 7. |
- Hagforsen, Eva, et al.
(författare)
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Expression of nicotinic receptors in the skin of patients with palmoplanta pustulosis
- 2002
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 146:3, s. 383-391
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A suggested role for nicotine in the pathogenesis of palmoplantar pustulosis (PPP) has been discussed. The target for the inflammation in PPP is the acrosyringium. Nicotine acts as an agonist on nicotinic acetylcholine receptors (nAChRs) and can influence a variety of cellular functions. OBJECTIVES: To study the alpha 3- and alpha 7-nAChR expression in palmar skin of patients with PPP in comparison with that in healthy smoking and non-smoking controls. METHODS: Biopsies from 20 patients with PPP, seven healthy smokers and eight healthy non-smokers were studied by immunohistochemistry with a monoclonal anti-alpha 3 and a polyclonal anti-alpha 7 antibody. RESULTS: In healthy controls both nAChR subtypes showed stronger immunoreactivity in the eccrine glands and ducts than in the epidermis. The papillary endothelium was positive for both subtypes. Epidermal alpha 3 staining was stronger and that of the coil and dermal ducts weaker in healthy smokers than in healthy non-smokers. In involved PPP skin, granulocytes displayed strong alpha 3 immunoreactivity. The normal epidermal alpha 7 staining pattern was abolished in PPP skin and was replaced by strong mesh-like surface staining, most markedly adjacent to the acrosyringium, which in controls was intensely alpha 7 positive at this level. Endothelial alpha 7 staining was stronger in PPP skin than in the controls. CONCLUSIONS: Smoking can influence nAChR expression. The altered nAChR staining pattern in PPP skin may indicate a possible role for nicotine in the pathogenesis of PPP. We hypothesize that there is an abnormal response to nicotine in patients with PPP, resulting in inflammation.
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| 8. |
- Hagforsen, Eva, et al.
(författare)
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Normal and PPP-affected palmoplantar sweat gland express neuroendocrine markers chromogranins and synaptophysin differently
- 2010
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Ingår i: Archives of Dermatological Research. - : Springer Science and Business Media LLC. - 0340-3696 .- 1432-069X. ; 302:9, s. 685-693
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Tidskriftsartikel (refereegranskat)abstract
- Earlier findings indicate the acrosyringium as the target for the inflammation in the chronic and intensely inflammatory skin disease palmoplantar pustulosis (PPP). The sweat gland apparatus seems to be an immune-competent structure that probably contributes to the defence of the skin. Furthermore, the sweat gland and duct may be a hitherto unrecognized neuroendocrine organ because it expresses cholineacetyl-transferase and acetylcholinesterase, nicotinic receptors, beta-adrenergic and angiotensin receptors.The aim of this study was to obtain further information about neuroendocrine properties of the sweat gland apparatus by examining the expression of common neuroendocrine markers synaptophysin and chromogranins A and B in healthy palmar skin and in PPP skin.Synaptophysin and chromogranins were expressed in the sweat glands and ducts with some variation in the pattern and intensity of the expression. In PPP skin the expression differed, being higher and lower, depending on the part of the sweat duct. Chromogranins were further expressed in the epidermis, endothelium and inflammatory cells, but its intensity was weaker in epidermis than in the sweat gland apparatus. In most cases, chromogranins in epidermis in involved PPP were weakly expressed compared to healthy controls. The presence of synaptophysin and chromogranins in palmoplantar skin may have marked neuroendocrine effects, and the palmoplantar skin is likely to have important neuroimmuno-endocrine properties. Moreover, the altered chromogranin expression in PPP skin might influence both the neuroendocrine and neuroimmunologic properties of palmoplantar skin in these patients. These results indicate important neuroendocrine properties of the palmoplantar skin.
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| 9. |
- Hagforsen, Eva, et al.
(författare)
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Novel findings of Langerhans cells and IL-17 expression in relation to the acrosyringium and pustule in palmoplantar pustulosis
- 2010
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Ingår i: British Journal of Dermatology. - : Wiley- Blackwell. - 0007-0963 .- 1365-2133. ; 163:3, s. 572-579
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Tidskriftsartikel (refereegranskat)abstract
- Backgound Palmoplantar pustulosis (PPP) is a chronic and intensely inflammatory skin disease with pustules, erythema and scaling localized to the palms and soles. To date, no specific treatment is known. Earlier findings indicate the acrosyringium as the target for the inflammation.Objectives To identify specific features of the PPP inflammatory cell infiltrate and mediators of inflammation, which might provide insight into the pathogenesis and possible future treatment of the disease.Methods Skin biopsies were taken from 23 patients with typical PPP (23 from involved skin and seven from noninvolved skin) and from 18 healthy controls (10 nonsmokers, eight smokers). Cell infiltrates and inflammation mediators were studied with immunohistochemistry.Results A strong inflammation was observed in lesional skin of PPP. Our main findings of Langerhans cells and interleukin-17 close to or in the acrosyringium differs from findings in psoriasis vulgaris. Other inflammatory cells such as CD4+, CD8+, regulatory T cells and CD11a+ cells were also accumulated close to the sweat duct in epidermis and papillary dermis. More CD4+, CD8+, Langerhans cells, plasmacytoid dendritic cells and a higher proportion of regulatory T cells/CD3+ cells were seen in noninvolved palmar skin from patients with PPP compared with healthy controls.Conclusions Our novel findings indicate that the inflammation in PPP is initiated by the 'stand-by' innate immune system at the acrosyringium.
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| 10. |
- Hagforsen, Eva, et al.
(författare)
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Palmoplantar pustulosis : an autoimmune disease precipitated by smoking
- 2002
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 82:5, s. 341-346
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Tidskriftsartikel (refereegranskat)abstract
- Ninety-five percent of patients with palmoplantar pustulosis are smokers at onset of the disease. The aim of this study was to determine whether these patients have serum antibodies to nicotinic acetylcholine receptors (nAChR ab) and if their sera induce a specific immunofluorescence in normal palmar skin. Sera from 45 patients with palmoplantar pustulosis and 23 patients with chronic hand eczema were analysed for muscle nAChR ab, and immunofluorescence was performed on healthy palmar skin. Forty-two percent of the patients with palmoplantar pustulosis but none of the eczema patients had raised levels of nAChR ab. Immunofluorescence showed staining on endothelial cells in the papillary dermis in 47% of all sera from patients with palmoplantar pustulosis and in those with nAChR ab in 68%. On palmar skin from smokers there was also a staining of the sweat duct. Sera from patients with chronic hand eczema were negative. Our findings indicate that palmoplantar pustulosis is an autoimmune disease, possibly induced by smoking.
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| 11. |
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| 12. |
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| 13. |
- Hagforsen, Eva, et al.
(författare)
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Skin nerve fibres and their contacts with mast cells in patients with palmoplantar pustulosis
- 2000
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Ingår i: Archives of Dermatological Research. - : Springer Science and Business Media LLC. - 0340-3696 .- 1432-069X. ; 292:6, s. 269-274
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Tidskriftsartikel (refereegranskat)abstract
- Patients with palmoplantar pustulosis (PPP) frequently report that stress worsens their condition. A study was therefore made of the distribution and number of nerve fibres positive for protein gene product (PGP) 9.5 (a general nerve marker) and nerve fibres with substance P- and calcitonin gene-related peptide-like immunoreactivity in involved skin from patients with PPP and in skin from healthy controls. The number of mast cells in the papillary dermis was larger (P = 0.0003) in lesional palmar PPP skin than in control skin, and the number of contacts between mast cells and nerve fibres was significantly larger (P = 0.02) in PPP skin than in control skin. Image analysis of the nerve fibres around the sweat glands showed that the positively stained area as a percentage of the total area of the sweat gland (coil + surrounding nerves) was significantly lower in PPP skin (P = 0.0006). Furthermore, the nerves seemed to be fragmented. Neutrophils within and below the pustules and in the papillary dermis showed positive substance P staining. The increased number of contacts between nerves and mast cells in PPP skin and the intense substance P-like immunoreactivity of the neutrophils indicate that neuromediation may influence the inflammation in PPP, whereas the destruction of the nerve fibres around the sweat glands might be a result of the inflammation.
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| 14. |
- Hagforsen, Eva, et al.
(författare)
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Somatostatin receptors are strongly expresssed in palmoplantar sweat glands and ducts : studies of normal and palmoplantar pustulosis skin
- 2011
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Ingår i: Clincal and Experimental Dermatology. - : Oxford University Press (OUP). - 0307-6938 .- 1365-2230. ; 36:5, s. 521-527
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe acrosyringium is the target for inflammation in the chronic and intensely inflammatory skin disease palmoplantar pustulosis (PPP). The sweat-gland apparatus seems to be an immunocompetent structure that probably contributes to skin defence. Furthermore, the sweat gland and duct may be a hitherto unrecognized neuroendocrine organ.AimTo obtain further information about the neuroendocrine properties of the sweat-gland apparatus by examining expression of the somatostatin receptors (SSTRs) 1-5 in healthy palmar skin and in PPP skin.MethodsBiopsy specimens were taken from 25 patients with PPP and 25 healthy controls. Immunohistochemical analysis was used to investigate expression of SSTRs 1-5.ResultsSSTRs 1-5 were expressed in both epidermal and endothelial structures. The staining intensity of the sweat-gland apparatus was more pronounced than that of the epidermis. Expression differed significantly between lesional PPP and normal plantar skin, with increased expression of SSTRs 3 and 4 in ducts in epidermis, and decreased expression of SSTR 1 in ducts in both papillary and reticular dermis. In specimens with pronounced inflammation, numerous dendritic cells with strong expression of SSTRs 1.. 2 and 4 were seen, especially in the papillary dermis.ConclusionsThe presence of SSTRs in palmoplantar skin, and specifically at high density in the sweat glands and ducts, might be of particular importance in skin neuroimmunoendocrinology. Although the relevance of the changes in SSTR expression in PPP skin compared with normal skin is unclear, our hypothesis is that these differences might influence the function of both the neuroendocrine and neuroimmunological properties of palmoplantar skin, especially in the sweat-gland apparatus.
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| 15. |
- Hagforsen, Eva, et al.
(författare)
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The distribution of choline acetyltransferase- and acetylcholinesterase-like immunoreactivity in the palmar skin of patients with palmoplantar pustulosis
- 2000
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 142:2, s. 234-242
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Tidskriftsartikel (refereegranskat)abstract
- The distribution of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in involved skin in patients with palmoplantar pustulosis (PPP) and in normal palmar skin in healthy non-smokers and smokers has been studied by immunohistochemistry, especially in relation to the sweat gland apparatus. The sweat gland and its duct showed ChAT- and AChE-like immunoreactivity (LI) of varying intensity in all three groups and with stronger reactivity than in the epidermis. ChAT-LI was present in the coil and in the duct except in the corneal layer. Smokers and patients with PPP displayed significantly fewer ChAT+ acrosyringia than non-smokers. In the patients with PPP, the granulocytes in the pustules and in the papillary dermis displayed ChAT-LI. Western blot analysis of granulocytes from peripheral blood from healthy donors confirmed the presence of ChAT-like proteins in large amounts in neutrophils and small amounts in eosinophils. AChE-LI of varying intensity was found in all parts of the sweat gland apparatus in all three groups. The strongest AChE-LI in the acrosyringia was seen in the lowest part of the stratum corneum, where the PPP pustules are located. No significant differences in staining pattern or intensity were found between the coils, nerve fibres surrounding the coils or ducts. The number of mast cells in the papillary dermis was about four times larger in the patients with PPP than in the control subjects. AChE-LI was observed in about 25% of the mast cells in non-smoking control subjects and in patients with PPP, but only in 10% of those in the smoking control subjects. Our findings indicate that the (non-neuronal) cholinergic system may be involved in cutaneous inflammatory processes.
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| 16. |
- Hedstrand, Håkan, et al.
(författare)
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Antibodies against hair follicles are associated with alopecia totalis inautoimmune polyendocrine syndrome type I
- 1999
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 113:6, s. 1054-1058
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Tidskriftsartikel (refereegranskat)abstract
- In the autosomal recessively inherited autoimmune polyendocrine syndrome type I (APS I) patients have autoantibodies directed against several endocrine and nonendocrine organs. Alopecia areata is present in about one-third of the patients and usually in the more severe forms, alopecia universalis or totalis. Sera from 39 patients with APS I, diluted 1:150, were used in indirect immunofluorescence staining of cryo-sections from normal human scalp. Two hair follicle staining patterns were observed. A cytoplasmic staining of the differentiating matrix, cuticle, and cortex keratinocytes in the anagen hair follicle was seen in five (13%) APS I sera. All these five patients had alopecia totalis, representing 63% of the eight patients with alopecia totalis (p < 0.0001). Furthermore, four (10%) of the APS I sera stained the nuclei of the melanocytes in the hair follicle. Two of these patients had vitiligo. None of 20 healthy control sera stained the keratinocyte cells or the melanocyte nuclei. These data show that many patients with APS I have high-titer autoantibodies directed against the anagen matrix, cuticle, and cortex keratinocytes and a melanocyte nuclear antigen, and also that the hair follicle keratinocyte staining is associated with alopecia, especially alopecia totalis. This study emphasizes the role of the differentiating anagen keratinocytes as an important structure in the autoimmune etiology of alopecia, both in APS I and at least in a subgroup of patients with alopecia areata unrelated to APS I.
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| 17. |
- Lindqvist, Ulla, et al.
(författare)
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IgA antibodies to gliadin and coeliac disease in psoriatic arthritis
- 2002
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Ingår i: Rheumatology (Oxford, England). - 1462-0324. ; 41:1, s. 31-37
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To find out whether patients with psoriatic arthritis (PsoA) have an increased prevalence of antibodies to gliadin (AGA) and of coeliac disease. METHODS: One hundred and fourteen PsoA patients with skin disease of 20+/-13 yr and joint disease of 11+/-10 yr duration answered a questionnaire concerning their medical history and underwent clinical examination, including radiology. Serum IgA AGA and IgG AGA, IgA antibodies to endomysium and immunoglobulins, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) concentration were determined. RESULTS: Five of the 114 patients (4.4%) had coeliac disease. After exclusion of these five patients, the mean IgA AGA concentration was significantly higher (P=0.0005) than that in a reference group. None of the patients had IgA antibodies to endomysium. The mean serum IgA concentration was significantly increased and IgM decreased. Patients with a high concentration of IgA AGA had significantly higher ESR and CRP and a longer duration of morning stiffness than those with a low AGA concentration. CONCLUSIONS: Patients with PsoA have an increased prevalence of raised serum IgA AGA and of coeliac disease. Patients with raised IgA AGA seem to have more pronounced inflammation than those with a low IgA AGA concentration.
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| 18. |
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| 19. |
- Lindqvist, Ulla, et al.
(författare)
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Patients with psoriatic arthritis have an increased number of lymphocytes in the duodenal mucosa in comparison with patients with psoriasis vulgaris
- 2006
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Ingår i: Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 33:5, s. 924-927
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 20. |
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| 21. |
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| 22. |
- Michaëlsson, Gerd, et al.
(författare)
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Gluten-free diet in psoriasis patients with antibodies to gliadin results in decreased expression of tissue transglutaminase and fewer Ki67+ cells in the dermis
- 2003
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 83:6, s. 425-429
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have shown that 16% of patients with psoriasis vulgaris have IgA and/or IgG antibodies to gliadin, but few have antibodies to endomysium. The increase in duodenal intraepithelial lymphocytes was mild. Still, highly significant clinical improvement was observed after 3 months on a gluten-free diet. This study surveys certain immunohistological aspects of involved and non-involved skin in 28 AGA-positive psoriasis patients before and after 3 months of a gluten-free diet. Staining was performed for CD4+ T lymphocytes, Langerhans' cells, endothelium, proliferating (Ki67) cells and tissue transglutaminase. In the entire group of patients, as well as in those on a gluten-free diet as the only treatment, Ki67 + cells in involved dermis were highly significantly decreased after the diet. There was a significant decrease in Ki67 + cells even in patients without increased intraepithelial lymphocytes. Tissue transglutaminase was highly overexpressed in involved skin in the papillary endothelium, and decreased by 50% after gluten-free diet. The possible role of tissue transglutaminase in the pathogenesis of psoriasis needs further investigation.
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| 23. |
- Michaëlsson, Gerd, et al.
(författare)
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Increased lymphocyte infiltration in duodenal mucosa from patients with psoriasis and serum IgA antibodies to gliadin
- 1995
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 133:6, s. 896-904
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Tidskriftsartikel (refereegranskat)abstract
- In a screening study concerning IgA and IgG antibodies to gliadin (IgA AGA and IgG AGA, respectively) in psoriasis, raised levels of IgA and AGA were found to be more common than in a reference group. To determine whether elevated AGA levels were associated with an increased number of intraepithelial lymphocytes, 33 patients with IgA AGA (n = 28) or IgG AGA (n = 5) values above 90% of the reference values (> 50 units/ml IgA AGA and < 12 units/ml IgG AGA) underwent gastroduodenoscopy and duodenal biopsy in a prospective study. For comparison, six patients with low levels of both IgA AGA and IgG AGA were included. Five biopsy specimens were taken in each patient. Paraffin-embedded specimens were examined with regard to the degree of intraepithelial lymphocyte infiltration, and scored from 0 to 3. Biopsy specimens with a score of 0 had one mononuclear cell or less per four epithelial cells. The specimens were also examined with regard to the presence of intraepithelial CD3+ T lymphocytes and gamma/delta+ T lymphocytes. In the six patients with low IgA AGA and low IgG AGA, the biopsy score was 0. Fourteen of the 33 patients with raised AGA had a score of > or = 1; of these, 12 had raised IgA AGA and two had slightly raised IgG AGA. Two of the patients with raised IgA AGA had partial villous atrophy, but the majority had normal villous architecture. There was a significant correlation both between the biopsy score and the number of intraepithelial CD3+ cells and between the score and the number of intraepithelial gamma/delta+ positive T lymphocytes. The serum IgA AGA levels were significantly correlated with the duodenal biopsy score, the number of intraepithelial gamma/delta+ T lymphocytes, and the number of CD3+ intraepithelial T lymphocytes. Most patients had no, or only mild, gastrointestinal symptoms. Of the 14 patients with biopsy scores > or = 1, seven had severe psoriasis and five moderately severe psoriasis, whereas only two had mild psoriasis. There was no relationship between the duodenal score and haemoglobin, folate, whole blood selenium or serum zinc levels. Some of these patients improve on a gluten-free diet, but it is still too early to draw any definite conclusions concerning the type of relationship between the skin lesions, the increased number of intraepithelial lymphocytes in the duodenal mucosa and gluten hypersensitivity.
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| 24. |
- Michaëlsson, Gerd, et al.
(författare)
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Palmoplantar pustulosis and gluten sensitivity : A study of serum antibodies against gliadin and tissue transglutaminase, the duodenal mucosa and effects of gluten-free diet
- 2007
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 156:4, s. 659-666
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Tidskriftsartikel (refereegranskat)abstract
- Background: Palmoplantar pustulosis (PPP) is a chronic inflammatory disease affecting mainly smoking women. Some patients also have psoriasis. A subgroup of patients with psoriasis has been shown to have silent gluten sensitivity with relevance for their psoriasis. Nothing is known about gluten sensitivity in PPP. Objectives: To find out whether any patients with PPP are gluten-sensitive and whether this might be relevant for the PPP activity. Patients and methods: One hundred and twenty-three patients (113 women) with PPP participated. Screening for IgA antibodies against gliadin and tissue transglutaminase (tTG) was performed, the duodenal mucosa in patients with and without these antibodies was studied and the effect of a gluten-free diet (GFD) was followed up. Results: Twenty-two patients (18%) had IgA antibodies against gliadin and nine of 94 (10%) against tTG. Twelve patients with antibodies and 11 without underwent gastro-duodenoscopy. Four displayed villous atrophy, whereas all other specimens were judged as essentially normal at routine staining. However, with immunohistochemistry, the numbers of CD3+ and CD8+ lymphocytes in the epithelium were found to be increased in patients with any type of antibody, although they were most numerous in those with both types of antibodies. Seven of 123 patients (6%) had coeliac disease (three previously diagnosed). Patients with antibodies who adhered to the GFD displayed total or nearly total clearance of the skin lesions and normalization of the antibody levels. Conclusions: Patients with PPP should be screened for antibodies against gliadin and tTG. Those with antibodies can be much improved on a GFD regardless of the degree of mucosal abnormalities.
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| 25. |
- Michaëlsson, Gerd, et al.
(författare)
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Patients with psoriasis have elevated levels of serum eosinophil cationic protein and increased numbers of EG2 positive eosinophils in the duodenal stroma
- 1996
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Ingår i: British Journal of Dermatology. - 0007-0963 .- 1365-2133. ; 135:3, s. 371-378
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Tidskriftsartikel (refereegranskat)abstract
- The occurrence of EG2-positive (EG2+) eosinophils and IgE in biopsy specimens of duodenal mucosa and skin from 39 psoriasis patients was studied, with emphasis on the relation to serum eosinophil cationic protein (ECP), serum IgE and the presence or absence of serum IgA and IgG antigliadin antibodies. Psoriasis patients had significantly elevated serum levels of ECP even after exclusion of five of 37 sera which were Phadiatop positive. The elevated serum ECP was not associated with the presence of IgA or IgG antibodies to gliadin. After exclusion of Phadiatop positive sera the serum IgE values did not differ from those of a group of healthy blood donors. Patients with psoriasis had a pronounced increase of EG2+ cells in their duodenal stroma. Patients without antibodies to gliadin tended to have even more EG2+ cells than those with such antibodies and those with increased duodenal intraepithelial lymphocytes. IgE+ cells were present in most duodenal specimens, and in some specimens there were > 100 IgE+ cells/section. The number of EG2+ cells was increased in lesional skin and, in some patients, also in non-involved skin, but there was a more pronounced increase in EG2 reactivity in the duodenal than in the skin specimens. IgE reactivity was increased both in non-involved and involved skin and was significantly related to the number of IgE-positive cells in the duodenal stroma. The results of this study indicate that the gastrointestinal tract and the eosinophil granulocyte might be involved in psoriasis in a hitherto unknown way.
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| 26. |
- Michaëlsson, Gerd, et al.
(författare)
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Psoriasis patients have highly increased numbers of tryptase-positive mast cell in the duodenal stroma
- 1997
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Ingår i: British Journal of Dermatology. - 0007-0963 .- 1365-2133. ; 136:6, s. 866-870
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Tidskriftsartikel (refereegranskat)abstract
- We have shown that the number of tryptase-positive mast cells in the duodenal mucosa in psoriasis is increased and that a subgroup of psoriasis patients showed elevated levels of antibodies to gliadin (some of whom also had increased lymphocytes in the duodenal epithelium). Duodenal biopsy specimens from 37 patients with psoriasis (eight mild, 13 moderate and 16 severe) and 22 patients with irritable bowel syndrome (IBS) were examined regarding the presence of tryptase + mast cells. Intraepithelial infiltration by lymphocytes was evaluated and scored from 0 to 3. Patients with psoriasis had 131 +/- 58 mast cells/mm2 (mean +/- SD) and those with IBS 28 +/- 18. Only in four of the 37 psoriasis patients was the number within the range of that in the IBS group. There were no signs of stromal inflammation except in one psoriasis patient. No relationship was found between degree of severity of psoriasis and number of mast cells. In 25 of the 37 specimens from psoriasis patients there was no increase in intraepithelial lymphocytes, whereas seven showed a slight increase (score 1-2) and five a moderate increase (score > or = 2-3). The number of tryptase + mast cells was similar in patients with or without increased intraepithelial lymphocytes. The number of mast cells showed no relation to the presence or absence of antibodies to gliadin. We hypothesize that there are at least two types of abnormalities in the duodenal mucosa in psoriasis, one type that is present in most psoriasis patients and characterized by an increase in mast cells and eosinophils, and another that is present in a subgroup of patients with antibodies to gliadin and an increased number of duodenal intraepithelial lymphocytes. The mechanisms underlying the increase in the number of mast cells and its relevance are not yet known.
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| 27. |
- Michaëlsson, Gerd, et al.
(författare)
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Psoriasis patients with antibodies to gliadin can be improved by a gluten-free diet
- 2000
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 142:1, s. 44-51
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Tidskriftsartikel (refereegranskat)abstract
- In a previous screening study, 16% of patients with psoriasis had IgA and/or IgG antibodies to gliadin (AGA). The aim of the present study was to evaluate the effect of a gluten-free diet (GFD) in 33 AGA-positive and six AGA-negative psoriasis patients. Of the 33 AGA-positive patients, two had IgA antibodies to endomysium (EmA) and 15 an increased number of lymphocytes in the duodenal epithelium, but in some this increase was slight. Two patients had villous atrophy. A 3-month period on a GFD was followed by 3 months on the patient's ordinary diet. The severity of psoriasis was evaluated with the psoriasis area and severity index (PASI). The examining dermatologists were unaware of the EmA and duodenal biopsy results throughout the study. Thirty of the 33 patients with AGA completed the GFD period, after which they showed a highly significant decrease in mean PASI. This included a significant decrease in the 16 AGA-positive patients with normal routine histology in duodenal biopsy specimens. The AGA-negative patients were not improved. After GFD, the AGA values were lower in 82% of those who improved. There was a highly significant decrease in serum eosinophil cationic protein in patients with elevated AGA. When the ordinary diet was resumed, the psoriasis deteriorated in 18 of the 30 patients with AGA who had completed the GFD period. In conclusion, psoriasis patients with raised AGA might improve on a GFD even if they have no EmA or if the increase in duodenal intraepithelial lymphocytes is slight or seemingly absent.
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| 28. |
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| 29. |
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| 30. |
- Michaëlsson, Gerd, et al.
(författare)
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The skin and the gut in psoriasis : the number of mast cells and CD3+ lymphocytes is increased in non-involved skin and correlated to the number of intraepithelial lymphocytes and mast cells in the duodenum
- 1997
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Ingår i: Acta Dermato-Venereologica. - 0001-5555 .- 1651-2057. ; 77:5, s. 343-346
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this work was to study tryptase+ mast cells and CD3+ T lymphocytes in non-involved skin in psoriasis and their possible relation to mast cells and lymphocytes in the duodenal mucosa. Skin biopsy specimens were obtained from 43 patients with psoriasis of variable severity and from 10 healthy subjects. Compared with the reference subjects, the number of mast cells in non-involved skin was clearly increased, most markedly in the papillary dermis. The increase was present both in mild, moderate and severe psoriasis. CD3+ lymphocytes were increased in non-involved skin in moderate and severe psoriasis. Patients with an increased number of duodenal intraepithelial lymphocytes had significantly more mast cells in non-involved skin than those without such an increase, and there was a significant correlation between the number of mast cells in non-involved skin and score for intraepithelial lymphocytes. However, when the 14 patients with increased intraepithelial duodenal lymphocytes were excluded-as they may represent a separate type of psoriasis-another type of correlation between the skin and the duodenal mucosa was found, namely a highly significant inverse correlation between the number of CD3+ lymphocytes in non-involved skin and the number of duodenal mast cells, which is highly elevated in psoriasis. The results might indicate an interplay between skin and intestinal mast cells and lymphocytes in a hitherto unknown way.
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| 31. |
- Nilsson-Ekdahl, Kristina, et al.
(författare)
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Impairments in complement receptor-and Fc receptor-mediated functions in vivo in patients with psoriasis
- 1995
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Ingår i: Archives of Dermatological Research. - 0340-3696 .- 1432-069X. ; 287:3-4, s. 225-230
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Tidskriftsartikel (refereegranskat)abstract
- The function of the fixed macrophage system in 18 psoriasis patients was evaluated by measuring the elimination rate of injected autologous erythrocytes coated with iC3b or IgG. The mean half-life of iC3b-coated erythrocytes was significantly prolonged in patients with psoriasis compared with healthy controls (4.7 +/- 0.8 vs 2.7 +/- 0.2 min, P = 0.01). There was also a decrease in the total number of cells eliminated from the circulation (2.5 +/- 0.2 x 10(8) vs 3.3 +/- 0.2 x 10(8), P = 0.01). There was an even more pronounced increase in the half-life of IgG-coated erythrocytes (85 +/- 18 vs 20 +/- 5 min, P < 0.001), with normal values in only 5 of 15 patients, and 4 of these 5 patients were receiving systemic treatment. The slow elimination was interpreted as being caused by primary or secondary defects in receptor function rather than by blocking of the receptors by immune complexes, since patients with psoriasis show normal levels of circulating immune complexes. Further studies are needed to elucidate the nature of these defects.
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| 32. |
- Törmä, Hans, et al.
(författare)
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Decreased mRNA Levels of Retinoic Acid Receptor alpha, Retinoid X Receptor alpha and Thyroid Hormone Receptor alpha in Lesional Psoriatic Skin
- 2000
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 80:1, s. 4-9
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Tidskriftsartikel (refereegranskat)abstract
- Retinoic acid, vitamin D3 and triiodothyronine regulate keratinocyte proliferation and differentiation--processes that are disturbed in psoriatic skin--via binding to nuclear receptors for retinoic acid (RAR-alpha,-gamma), vitamin D3 (VDR), thyroid hormone (TR-alpha,-beta) plus the common heterodimer partners, the 9-cis-retinoic acid receptors (RXR-alpha,-beta). By using a new quantitative real-time polymerase chain reaction assay, the expression of these receptors and three housekeeping genes (cyclophilin, GAPDH and beta-actin) was studied in psoriatic skin. The expression of housekeeping genes was consistently 2.7-4.3 times higher in lesional than in non-lesional skin. When the beta-actin expression was used to normalize the receptor mRNA values, the RARalpha, RXRalpha and TRalpha transcripts were found to be 58-75% lower in lesional vs. non-lesional skin and the RXRalpha:RARgamma ratio was reduced from 3.2 to 1.5. Topical treatment for 4 days with 0.025% all-trans-retinoic acid or calcipotriol under occlusion did not normalize the altered mRNA expression of RARs, RXR and VDR in lesional skin. The results suggest that retinoid and thyroid hormone signalling is abnormal in lesional psoriatic skin, but how this relates to the pathogenesis of the disease is still unclear.
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| 33. |
- Törmä, Hans, et al.
(författare)
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Vitamin D analogs affect the uptake and metabolism of retinol by human epidermal keratinocytes in culture
- 1996
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Ingår i: Journal of Investigative Dermatology Symposium Proceedings. - 1087-0024 .- 1529-1774. ; 1:1, s. 49-53
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Tidskriftsartikel (refereegranskat)abstract
- Human epidermis utilizes retinol as precursor for local production of a range of bioactive vitamin A metabolites including 3,4-didehydroretinol, retinoic acid, and 3,4-didehydroretinoic acid. These endogenously formed retinoids bind to nuclear retinoic acid receptors (RARs), thereby altering gene transcription. Because 9-cis-retinoic acid receptors (RXRs) form heterodimers both with RARs and the vitamin D3 receptor (VDR), it is plausible that vitamin D3 may affect retinol metabolism if altered transcription is involved in the regulation of vitamin A-metabolizing enzymes. To investigate the potential effect of vitamin D on retinol metabolism in human skin keratinocytes, HaCaT cells were preincubated with various vitamin D3-analogs at 10(-7)M for 24 h followed by the addition of [3H]retinol for another 24 h period. The uptake and metabolism of the radioactive tracer was monitored by HPLC-radiochromatography. It was found that all synthetic vitamin D-analogs tested (MC903, KH1060, EB1089, and EB1213) reduced the amount of cell-associated [3H]retinoid activity by 35-50% as compared to the vehicle. More specifically, the appearance of the parent substrate and two of its main metabolites, e.g., 3,4-didehydroretinol (ddROH) and 3,4-didehydroretinoic acid (ddRA), was inhibited by the synthetic vitamin D-analogs. The effects on retinol metabolism were not potentiated by coincubation of cells with vitamin D-analogs plus retinoic acid (RA) or 9-cis-RA. This study demonstrates that synthetic vitamin D3 interferes with both the uptake and the metabolism of retinol by human epidermal keratinocytes. Whether the effects are due to direct inhibition of cellular retinol uptake and metabolism or involve VDR-mediated transcriptional alteration of vitamin A metabolizing enzymes remains to be clarified.
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