G Michaëlsson’s research while affiliated with Uppsala University and other places

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Publications (110)


Calcium homeostasis and body composition in patients with palmoplantar pustulosis: A case-control study
  • Article

September 2011

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54 Reads

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7 Citations

British Journal of Dermatology

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I Pihl-Lundin

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G Michaëlsson

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). To study the vitamin D status and BMD in patients with PPP. 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. 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. 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.


Somatostatin receptors are strongly expresssed in palmoplantar sweat glands and ducts: Studies of normal and palmoplantar pustulosis skin

July 2011

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25 Reads

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6 Citations

Clinical and Experimental Dermatology

The 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. To 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. Biopsy specimens were taken from 25 patients with PPP and 25 healthy controls. Immunohistochemical analysis was used to investigate expression of SSTRs 1-5. SSTRs 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. The 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.


Normal and PPP-affected palmoplantar sweat gland express neuroendocrine markers chromogranins and synaptophysin differently

November 2010

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42 Reads

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15 Citations

Archives of Dermatological Research

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.


Novel findings of Langerhans cells and interleukin-17 expression in relation to the acrosyringium and pustule in palmoplantar pustulosis

September 2010

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81 Reads

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61 Citations

British Journal of Dermatology

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. 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. 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. 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. Our novel findings indicate that the inflammation in PPP is initiated by the 'stand-by' innate immune system at the acrosyringium.



PPP: What's new in the treatment, pathogenesis and terminology?
  • Article
  • Full-text available

February 2008

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12 Reads

Acta Dermato-Venereologica

This article does not have an abstract.

Download


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

July 2007

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66 Reads

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5 Citations

Journal of Investigative Dermatology

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.


Palmoplantar pustulosis and gluten sensitivity: A study of serum antibodies against gliadin and tissue transglutaminase, the duodenal mucosa and effects of gluten-free diet

May 2007

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682 Reads

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64 Citations

British Journal of Dermatology

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. To find out whether any patients with PPP are gluten-sensitive and whether this might be relevant for the PPP activity. 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. 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. 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.


Fig. 1. Immunoreactivity as assessed by indirect immunofluorescence with sera in non-dermal tissues. (a–c) The parathyroid gland: (a) serum from a palmoplantar pustulosis (PPP) patient with endothelial immunoreaction; (b) serum from a healthy non-smoking person, no endothelial staining; (c) double staining (PPP serum and endothelial cell antibodies), yellow colour demonstrates that PPP serum reacts with endothelial cells; (d) thyroid gland – immunoreactivity in the endothelium between the follicles; (e) pancreas – strong staining of the endothelial cells lining the lumen of a larger blood vessel. Scale bars: (a–c) 10 µm; (d) 20 µm; (e) 10 µm.  
Sera from Patients with Palmoplantar Pustulosis Show Immunoreactivity Against Endothelial Cells

February 2007

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40 Reads

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8 Citations

Acta Dermato-Venereologica

This article does not have an abstract.


Citations (78)


... 20 Various studies have reflected role of topical vitamin E in improvement of various skin parameters like acute and chronic dermatitis, erythema, edema, skin hydration, roughness, wrinkling, and sebum production. [21][22][23][24] Colloidal oatmeal strengthens skin barrier and provides benefits for dry and compromised skin and alleviate skin irritation and inflammation. 25 Results of our study are supported by this statement. ...

Reference:

Cetyl alcohol, stearyl alcohol and colloidal oatmeal-based gentle skin cleanser in management of dry and sensitive skin: a cross-sectional study
Erythrocyte glutathione peroxidase activity in acne vulgaris and the effect of selenium and vitamin E treatment
  • Citing Article
  • January 1984

Acta Dermato-Venereologica

... All subtypes share clinical , radiological, and genetic characteristics evidently different from those of other chronic inflammatory joint diseases, for example rheumatoid arthritis. The presence of gut inflammation in psoriatic arthritis has been reported in several stud- ies63646566. In two of these studies it was observed that gut inflammation was only found in the forms of psoriatic arthritis belonging to the SpA concept, not in the polyarticular group. ...

Patients with psoriatic arthritis have an increased number of lymphocytes in the duodenal mucosa in comparison with patients with psoriasis vulgaris
  • Citing Conference Paper
  • July 2007

Journal of Investigative Dermatology

... It was hypothesised that the migration of MSCs into skin lesions and their immunomodulatory, anti-autoimmune, and paracrine effects were the primary causes of the ameliorative effects. Other recent preclinical research has demonstrated that stem cell-derived conditioned media (CM) promotes psoriasis-like wound healing, making CM a viable option for many cell-based therapies [10][11][12]. ...

Genetic análisis of PSORS1 distinguishes guttate psoriasis and palmoplantar pustulosis
  • Citing Article
  • January 2003

Journal of Investigative Dermatology

... People with intense Psoriasis were experiencing a large diversity of Neutrophil in contrasted with moderate and mild types [22]. In extreme presence of Neutrophil could contribute to an expeditious proliferation and differentiation on keratinocyte [23]. ...

Increased chemotactic activity of neutrophil leukocytes in psoriasis
  • Citing Article
  • October 1980

British Journal of Dermatology

... The skin condition known as psoriasis is characterized histologically by cutaneous inflammation, increased epidermal proliferation, hyperkeratosis, angiogenesis, abnormal keratinization, shortened maturation time, and parakeratosis (Gisondi et al., 2012;Hagforsen et al., 2012). Around 2-3% of the world's population is impacted. ...

Calcium homeostasis and body composition in patients with palmoplantar pustulosis: A case-control study
  • Citing Article
  • September 2011

British Journal of Dermatology

... Sleeping problems were most common, followed by 30.6% anxiety and 29.4% mood disorders [4]. Many causes have been suggested as possible triggers, but the etiology remains unknown [5] Furthermore, food allergies, defined as immune-mediated responses to specific food proteins that manifest as a wide range of symptoms, including urticaria., are possible triggers to CIU [6]. For example, food additive hypersensitivity reactions occurred in a few patients. ...

Urticaria induced by preservative and dye additives in food and drugs
  • Citing Article
  • June 1973

British Journal of Dermatology

... Direct immunofluorescence analysis of regional skin showed linear deposition of IgG and C3 at the DEJ. The serum anti-BP180 antibody level was elevated to 88 (normal range: , 9). The patient was started on 20 mg daily of oral prednisone, which was gradually increased to 30 mg and minocycline at 200 mg. ...

Abnormal reactions to a nicotinic acid ester

Acta Dermato-Venereologica

... In pustular palmoplantar psoriasis biopsies, there is an increased expression of SSTR3 and SSTR4 in the epidermal ducts, and decreased expression of the SSTR1 in the ducts of both the papillary and reticular dermis. In addition, in marked inflammation, dendritic cells in the papillary dermis increase the expression of SSTR1, SSTR2 and SSTR4 receptors (Hagforsen et al., 2011). However, in biopsies of the lesions with inverted and guttate psoriasis, no SSTRs were observed when analyzed by autoradiograms (Reubi and Hunziker, 1990). ...

Somatostatin receptors are strongly expresssed in palmoplantar sweat glands and ducts: Studies of normal and palmoplantar pustulosis skin
  • Citing Article
  • July 2011

Clinical and Experimental Dermatology

... Hagforsen et al. 1 proved that PPP patients showed a higher intensity of α-3-nAChR staining in the epidermis than healthy control. Additionally, cholinergic materials, such as nicotine, can cause keratinocytes to proliferate and release cytokines that sustain the chronic inflammatory process, suggesting the involvement of the eccrine glands in the pathogenesis of PPP [10][11][12][13] . ...

Normal and PPP-affected palmoplantar sweat gland express neuroendocrine markers chromogranins and synaptophysin differently
  • Citing Article
  • November 2010

Archives of Dermatological Research

... Studies have shown that PPP is the type of pustular psoriasis most affected by smoking status, whereas GPP and ACH were more likely to carry IL36RN mutations than PPP (24). Nicotine seems to play a role in the causation as it produces IL-8 in neutrophils (25). The expression of nicotinic acetyl choline receptor (nAchR) is also increased in smokers (26). ...

Novel findings of Langerhans cells and interleukin-17 expression in relation to the acrosyringium and pustule in palmoplantar pustulosis
  • Citing Article
  • September 2010

British Journal of Dermatology