Skin disease and its therapy affect health-related quality of life (HRQoL). The aim of this study was to measure the burden caused by dermatological therapy in 3,846 patients from 13 European countries. Adult outpatients completed questionnaires, including the Dermatology Life Quality Index (DLQI), which has a therapy impact question. Therapy issues were reported by a majority of patients with atopic dermatitis (63.4%), psoriasis (60.7%), prurigo (54.4%), hidradenitis suppurativa (54.3%) and blistering conditions (53%). The largest reduction in HRQoL attributable to therapy, as a percentage of total DLQI, adjusted for confounders, was seen in blistering conditions (10.7%), allergic/drug reactions (10.2%), psoriasis (9.9%), vasculitis/immunological ulcers (8.8%), atopic dermatitis (8.7%), and venous leg ulcers (8.5%). In skin cancer, although it had less impact on HRQoL, the reduction due to therapy was 6.8%. Treatment for skin disease contributes considerably to reducing HRQoL: the burden of dermatological treatment should be considered when planning therapy and designing new dermatological therapies.

Objective: To describe the social status and health-related quality of life of patients with psoriatic arthritis mutilans (PAM) in the Nordic countries. Method: Patients with at least one mutilated joint confirmed by radiology were studied. Disease activity involving joints and skin, physician-assessed disease activity, and patient’s education and work status were recorded. Data from the 36-item Short Form Health Survey, Health Assessment Questionnaire and Dermatology Life Quality Index questionnaire were gathered and correlated with disease duration, pain, and general well-being (visual analogue scale). The controls were 58 Swedish patients with long-standing psoriatic arthritis sine PAM. Results: Sixty-seven patients were included. Patients with PAM had a protracted disease history (33 ± 14 years) and disease onset at a relatively early age (30 ± 12 years). Overall inflammatory activity at inclusion was mild to moderate. The mean number of mutilated joints was 8.2 and gross deformity was found in 16% of patients. Forty per cent were treated with biological and 32% with conventional synthetic disease-modifying anti-rheumatic drugs. Forty-two per cent had retired early or were on sick leave. Impaired functional capacity with little or no ability to perform self-care or everyday tasks was reported by 21% of the patients. Patients between 45 and 60 years of age reported the most impaired quality of life in comparison to the control group. Conclusion: PAM seriously affects social functioning. Whether early recognition of PAM and new forms of therapy can improve disease outcome and quality of life remains to be studied.

BACKGROUND:Fatigue is associated with various chronic inflammatory diseases, but few studies have focused on its occurrence in psoriasis.OBJECTIVES:To describe fatigue prevalence and degree among patients with chronic plaque psoriasis vs. age- and sex-matched healthy subjects, and to examine how fatigue is influenced by essential clinical and demographic factors.METHODS:In 84 patients and 84 healthy subjects, fatigue severity was assessed using three different generic fatigue instruments: the fatigue Visual Analogue Scale (fVAS), the Fatigue Severity Scale (FSS) and the Short Form 36 (SF-36) Vitality scale. Cut-off scores for clinically important fatigue were defined as ≥ 4 for FSS, ≥ 50 for fVAS and ≤ 35 for the SF-36 Vitality scale. Disease activity was evaluated using the Psoriasis Area and Severity Index (PASI), and the impact on quality of life with the Dermatology Life Quality Index (DLQI).RESULTS:Patients and healthy control subjects, respectively, showed median fVAS scores of 51 [interquartile range (IQR) 21-67] and 11 (IQR 3-20); FSS scores of 4 (IQR 2·5-5·3) and 1·6 (IQR 1·1-2·2); and SF-36 Vitality scores of 43 (IQR 25-85) and 73 (IQR 65-85). The rates of clinically important fatigue among patients vs. healthy controls, respectively, were 51% vs. 4% (fVAS); 52% vs. 4% (FSS); and 42% vs. 2% (SF-36 Vitality) (P < 0·001 for all differences). Fatigue was associated with DLQI scores, but not PASI scores, in univariate analysis but not in multivariate analysis.CONCLUSIONS:Nearly 50% of patients with psoriasis suffered from substantial fatigue. Fatigue severity was associated with smoking, pain and depression, but not with psoriasis severity.

Background: Rheumatoid arthritis (RA), a chronic inflammatory polyarthritis, should be treated promptly to improve clinical outcomes and prevent further joint destruction. Reaching the optimal control of RA requires regular evaluation of inflammatory activity with the aim of defined indices, such as the Disease Activity Score in 28 joints (DAS28) (1, 2). Objective: To evaluate the reliability of DAS28 in RA, with focus on a subgroup of patients with DAS28 > 3.2. Method: All RA patients with DAS28 > 3.2 who were registered in the local part of the DANBIO registry were categorized into two groups: (i) patients with at least one swollen joint (SJ) or elevated C-reactive protein (CRP) (the ‘objective group’) and (ii) patients with no swollen joints and normal CRP values (the ‘subjective group’). We defined a new score, the subjective DAS28 (DAS28s), to focus on subjective parameters. Results: Of the 230 included patients, 198 (86.1%) and 32 (13.9%) were in the objective and subjective groups, respectively. Patients in the subjective group had lower mean values of DAS28 (p < 0.001) and evaluator global assessment (p < 0.001), with less frequent IgM RF (p < 0.001) and anti-cyclic citrullinated peptide (anti-CCP) antibody positivity (p = 0.02), but higher mean values of tender joints (p = 0.04) and DAS28s (p = 0.003) compared to the objective group (Table 1). Conclusions: DAS28 should be used cautiously in patients who are considered for treatment intensification.

Psoriatic arthritis mutilans (PAM) is the most severe and rare form of psoriatic arthritis (PsA). We describe radiological development in a typical case of PAM covering three decades in order to elucidate the need for early diagnosis of PAM. Radiographs of hands and feet, taken from 1981 to 2010, were evaluated using the Psoriatic Arthritis Ratingen Score (PARS). When PsA was diagnosed, in 1981, gross deformity was observed in the second PIP joint of the left foot. Several pencil-in-cup deformities and gross osteolysis were present in the feet in the first decade of the disease. Over 10 years, many joints had reached maximum scores. During the follow-up, other joints became involved and the disease developed clinically. Reporting early signs suggestive of PAM, e.g. pencil-in cup deformities and gross osteolysis in any joint, should be mandatory and crucial. This would heighten our awareness of PAM, accelerate the diagnosis, and lead to improved effective treatment in order to minimize joint damages resulting in PAM.

Fatigue is a prevalent and substantial phenomenon in many patients with chronic inflammatory diseases, often rated by patients as the most troublesome symptom and aspect of their disease. It frequently interferes with physical and social functions and may lead to social withdrawal, long-standing sick leave and disability. Although psychological and somatic factors such as depression, sleep disorders, pain and anaemia influence fatigue, the underlying pathophysiological mechanisms by which fatigue is generated and regulated are largely unknown. Increasing evidence points towards a genetic and molecular basis for fatigue as part of the innate immune system and cellular stress responses. Few studies have focused on fatigue in dermatological diseases. Most of these studies describe fatigue as a phenomenon related to psoriatic arthritis and describe the beneficial effects of biological agents on fatigue observed in clinical studies. It is therefore possible that this problem has been underestimated and deserves more attention in the dermatological community. In this review, we provide a definition and explanation for chronic fatigue, describe some commonly used instruments for measuring fatigue, and present hypothetical biological mechanisms with an emphasis on activation of the innate immune system and oxidative stress. An overview of relevant clinical studies covering the theme 'psoriasis and fatigue' is given.

Objective: To determine the prevalence and clinical characteristics of psoriatic arthritis mutilans (PAM) in the Nordic countries.Method: Patients with putative PAM aged ≥ 18 years were recruited. Fifty-nine patients were included after clinical examination.Results: The prevalence of PAM in the adult Nordic population was estimated to be 3.69 per million inhabitants [95% confidence interval (CI) 2.75–4.63]. The female to male ratio was close to 1:1. The mean age of skin disease onset was 25 years and the mean age of onset of joint disease was 30 years. The onset of skin disease was 2 years earlier among female patients. At inclusion, the mean duration of arthritis was 27 ± 11 years for male patients and 33 ± 11 years for female patients. PAM was most frequently seen in the distal interphalangeal (DIP) joints of the toes, followed by the IP joint of the thumb and the DIP joint of the little finger on the left hand. Female and male patients had similar numbers of painful and swollen joints. Enthesitis was found in 19 patients (32%), while 38 patients (64%) had a history of dactylitis. Twenty-three of these 38 patients (61%) had a history of dactylitis in the same finger/toe as they had PAM. At the time of inclusion, 45% of the patients were found to have clear or almost clear skin.Conclusions: PAM in the Nordic countries has a low prevalence, with only three to five cases per million inhabitants. The majority of the patients present with mild skin disease.

Recently the knemometer, a lower leg length measuring device, has been introduced for sensitive assessment of systemic activity of exogeneous glucocorticoids in children. The aim of this study was to assess by means of knemometry whether the topical glucocorticoid budesonide affects short-term growth in children with atopic dermatitis. Fourteen children 5 to 12 years old were studied in an open longitudinal trial with three periods of 2 weeks duration. In periods 1 (run-in) and 3 (run-out), the children were treated with emollient. In period 2, budesonide cream 0.025% was followed by emollient twice daily to all of the body except the face. Eczema was evaluated according to a score based on extent and activity. Knemometry was performed twice weekly. Compared to the run-in and run-out periods the mean growth rate during budesonide treatment was reduced by 0.11 mm/wk (p > .05) and 0.40 mm/wk (p < .05), respectively. The mean growth rate during run-out was increased by 0.29 mm/wk as compared to run-in (p < .05). Compared to run-in the mean severity indices during budesonide treatment and run-out were reduced by 1.55 (p < .05) and 1.55 points (p <.05), respectively. The concomitant variations in lower leg growth rate and disease activity suggest that short-term treatment with topical glucocorticoids may provide a better growth potential during the weeks after withdrawal of the treatment. Whether this is due to improved disease control needs further study. Being a noninvasive method, knemometry may be useful for comparing different topical glucocorticoids and administration regimens in children in whom vasoconstrictor assays are difficult.

Background: Topical glucocorticosteroids are widely used in the treatment of children with atopic dermatitis. Due to percutaneous absorption, these agents may become systemically available and cause inhibition of growth in children. However, the mechanisms responsible for the growth-suppressive effect are not fully understood. Objective: To evaluate whether treatment with topical budesonide has any adverse effects on growth-hormone-dependent serum levels of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3), and on the serum markers of bone and collagen turnover osteocalcin, the carboxy-terminal propeptide of type I collagen (PICP), the carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) and the amino-terminal propeptide of type III procollagen (PIIINP). Methods: 13 children (mean age 9.5 years) with atopic dermatitis were studied in an open longitudinal trial with run-in and budesonide treatment periods of 2 weeks' duration. During the run-in, only emollient was used. During the treatment period, budesonide cream 0.025% followed by emollient were applied twice daily all over the body except on the face. At day 14 of each period, blood samples were taken and eczema was scored according to a severity index based on extent and activity of the disease. Results: Compared to the run-in, budesonide treatment was associated with a statistically significant reduction in mean severity index (p=0.002), No statistically significant effects on serum levels of IGF-I IGFBP-3, osteocalcin or ICTP were observed, The serum concentrations of PICP and PIIINP were reduced with (mean +/- 1 SD) 43 +/- 64 mu g/l (95% confidence interval 3.5-80 mu g/l, p=0.03, t=2.4, d.f.=12) and 1.2 +/- 1.5 mu g/l (95% confidence interval 0.3-2.1 mu g/l, p=0.01, t=3.0, d.f.=12), respectively. Conclusion: Type I and III collagen turnover may be suppressed during short-term treatment with topical budesonide in children with atopic eczema. Clinical implications need further study.

Tannins of natural or synthetic origin are well-known adjuvants in topical anti-inflammatory therapy of skin diseases. In this study, the influence of synthetic tannin on neutrophil accumulation, enzyme release, and on the proinflammatory activity of neutrophil-derived enzymes was investigated. The results show that synthetic tannin (Tamol) specifically inhibits the neutrophil serine protease human leukocyte elastase (HLE) in an irreversible manner with a half-maximal inhibitory concentration (IC50) of 0.3 microgram/ml. Exogenous protein partially abolished the tannin-dependent HLE inhibition (IC50 of Tamol at 1% protein-concentration:1.0 microgram/ml). Synthetic tannin did not influence the activities of other neutrophil enzymes like Cathepsin G, beta-glucuronidase, and myeloperoxidase. The specificity of Tamol for HLE was further substantiated by the lack of inhibition of other serine proteases. Additionally, Tamol had no effect on f-met-leu-phe-induced neutrophil chemotaxis and did not alter enzyme degranulation of neutrophils in response to f-met-leu-phe and opsonized zymosan. We conclude from our results that the anti-inflammatory properties of synthetic tannin may at least in part be due to inactivation of the proinflammatory protease HLE.

Preparations of recombinant human tumor necrosis factor α (rhuTNFα) free of aminoterminal methionine were tested for human neutrophil granulocyte (PMN) and monocyte (MO) chemotactic activity using the Boyden chamber system. Over a wide range of concentrations (10−7 − 10−15 M) rhuTNF α of two different sources failed to elicit chemotactic responses in PMN or MO, whereas strong PMN and MO chemotactic activity could be detected using the tripeptide N-formyl-methionyl-leucyl-phenylalanine (FMLP). In addition, rhuTNFα containing 62% aminoterminal methionine failed to induce PMN and MO chemotaxis. It is concluded that rhuTNFα may not be a chemotaxin for human PMN and MO in vitro.

15-Hydroxyeicosatetraenoic acid (15-HETE), a 15-lipoxygenase product of arachidonic acid, inhibits leukotriene B4 (LTB4)-induced chemotaxis of polymorphonuclear leukocytes (PMNs) in vitro. In this study the effects of intradermal injections of LTB4 were determined in the absence or presence of 15-HETE. For comparison intradermal injections of purified human complement split product C5a were performed in the absence or presence of 15-HETE. The skin response was evaluated by measuring the diameter of the wheal, the area of the flare and by intensity of the erythema (erythema index). LTB4 and C5a were injected at the concentration of 200 ng/ml. At this concentration the maximal skin response of LTB4 and C5a were equivalent. In contrast to C5a reaction, which resolved within 1 h, LTB4-induced skin response lasted up to 18 h. In all subjects the skin response was significantly decreased when LTB4 was injected together with 300 ng of 15-HETE. The decrease of wheal, flare, and erythema index averaged 81.9%, 56.6%, 53.6%, respectively, when all parameters were obtained at the maximal skin response. In contrast, the C5a-induced skin response was not affected by addition of 15-HETE, even when the final dose of 15-HETE was increased 10 times to 3 μg. The LTB4-induced reaction could last up to 18 h after injection. After the addition of 300 ng of 15-HETE the skin response resolved after 1 h. The present results demonstrate that 15-HETE is a specific inhibitor of the LTB4-induced skin response and brings additional evidence in support of the ability of 15-HETE to regulate the proinflammatory effects of LTB4 in vivo.

Annals of the New York Academy of SciencesVolume 548, Issue 1 p. 348-349 Epidermal-Derived Lymphokines and Their Presence in Allergic and Irritant Skin Reactions KRISTIAN THESTRUP-PEDERSEN, KRISTIAN THESTRUP-PEDERSEN University ofAarhus Department of Dermatology Marselisborg Hospital 8000 Aarhus C. DenmarkSearch for more papers by this authorCHRISTIAN GRøNHøJ LARSEN, CHRISTIAN GRøNHøJ LARSEN University ofAarhus Department of Dermatology Marselisborg Hospital 8000 Aarhus C. DenmarkSearch for more papers by this authorTHOMAS TERNOWITZ, THOMAS TERNOWITZ University ofAarhus Department of Dermatology Marselisborg Hospital 8000 Aarhus C. DenmarkSearch for more papers by this authorCLAUS ZACHARIAE, CLAUS ZACHARIAE University ofAarhus Department of Dermatology Marselisborg Hospital 8000 Aarhus C. DenmarkSearch for more papers by this author KRISTIAN THESTRUP-PEDERSEN, KRISTIAN THESTRUP-PEDERSEN University ofAarhus Department of Dermatology Marselisborg Hospital 8000 Aarhus C. DenmarkSearch for more papers by this authorCHRISTIAN GRøNHøJ LARSEN, CHRISTIAN GRøNHøJ LARSEN University ofAarhus Department of Dermatology Marselisborg Hospital 8000 Aarhus C. DenmarkSearch for more papers by this authorTHOMAS TERNOWITZ, THOMAS TERNOWITZ University ofAarhus Department of Dermatology Marselisborg Hospital 8000 Aarhus C. DenmarkSearch for more papers by this authorCLAUS ZACHARIAE, CLAUS ZACHARIAE University ofAarhus Department of Dermatology Marselisborg Hospital 8000 Aarhus C. DenmarkSearch for more papers by this author First published: December 1988 https://doi.org/10.1111/j.1749-6632.1988.tb18827.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume548, Issue1Endocrine, Metabolic and Immunological Functions of KeratinocytesDecember 1988Pages 348-349 RelatedInformation

Annals of the New York Academy of SciencesVolume 548, Issue 1 p. 350-351 Description of an Epidermal Lymphocyte Chemotactic Factor Which Specifically Attracts OKT4-Positive Lymphocytes CLAUS ZACHARIAE, CLAUS ZACHARIAE Department of Dermatology Marselisborg Hospital University of Aarhus DK-8000 Aarhus C. DenmarkSearch for more papers by this authorTHOMAS TERNOWITZ, THOMAS TERNOWITZ Department of Dermatology Marselisborg Hospital University of Aarhus DK-8000 Aarhus C. DenmarkSearch for more papers by this authorCHRISTIAN GRØNHØJ LARSEN, CHRISTIAN GRØNHØJ LARSEN Department of Dermatology Marselisborg Hospital University of Aarhus DK-8000 Aarhus C. DenmarkSearch for more papers by this authorKRISTIAN THESTRUP-PEDERSEN, KRISTIAN THESTRUP-PEDERSEN Department of Dermatology Marselisborg Hospital University of Aarhus DK-8000 Aarhus C. DenmarkSearch for more papers by this author CLAUS ZACHARIAE, CLAUS ZACHARIAE Department of Dermatology Marselisborg Hospital University of Aarhus DK-8000 Aarhus C. DenmarkSearch for more papers by this authorTHOMAS TERNOWITZ, THOMAS TERNOWITZ Department of Dermatology Marselisborg Hospital University of Aarhus DK-8000 Aarhus C. DenmarkSearch for more papers by this authorCHRISTIAN GRØNHØJ LARSEN, CHRISTIAN GRØNHØJ LARSEN Department of Dermatology Marselisborg Hospital University of Aarhus DK-8000 Aarhus C. DenmarkSearch for more papers by this authorKRISTIAN THESTRUP-PEDERSEN, KRISTIAN THESTRUP-PEDERSEN Department of Dermatology Marselisborg Hospital University of Aarhus DK-8000 Aarhus C. DenmarkSearch for more papers by this author First published: December 1988 https://doi.org/10.1111/j.1749-6632.1988.tb18828.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume548, Issue1Endocrine, Metabolic and Immunological Functions of KeratinocytesDecember 1988Pages 350-351 RelatedInformation

Recently, we have found an increased activity of epidermal-derived thymocyte-activating factor (ETAF/IL-1) and epidermal lymphocyte chemotactic factor (ELCF) in epidermis overlying a positive tuberculin skin reaction. In the present study, we investigated 20 patients with confirmed or suspected allergic contact dermatitis by using the suction blister technique before and during patch testing. The ETAF/IL-1 was found in epidermis before patch testing. Its presence increased 2.8-fold in epidermis overlying a positive patch test compared with pretesting values. This increase was statistically significant. Interestingly, nontested skin also showed a significant increase of ETAF/IL-1, which was 1.9-fold higher than pretest values. The ETAF/IL-1 activity in patch test areas was significantly correlated with the clinical response. ELCF is not present in epidermis from noneczematous persons. We observed a significant content of ELCF in three of seven patients with eczema prior to patch testing. After patch testing, all patients showed ELCF in epidermis. Nontested skin showed a 1.5-fold higher content of ELCF compared with pretest values, and in the test area ELCF was 1.8-fold higher. The increases were statistically significant. We performed mixed skin lymphocyte reactions in seven patients using epidermal cells from the patch test area. All patients with a positive patch test had an increased mixed skin lymphocyte reactivity compared with epidermis coming from a negative reaction.

Forty-one persons were tested for tuberculin skin reactivity. Epidermal cells (ECs) were isolated from the tuberculin reaction and from a contra lateral, non injected skin area. We found a significant increase of epidermal thymocyte activating factor (ETAF) in epidermis overlying a positive tuberculin reaction together with an increase of OKT6 and class II (HLA-DR) positive cells. Allogeneic lymphocytes proliferated significantly more when mixed with ECs from a positive tuberculin skin test. Injection of tuberculin per se or a negative reaction did not induce similar changes. The described model seems useful for functional studies of ECs and lymphocytes in patients with contact dermatitis.