Depression, a major comorbidity of psoriatic disease, is caused by metabolic inflammation.

Psoriatic disease is a chronic, systemic immune-mediated inflammatory disorder comprising three major domains, skin, vascular and bone/joint inflammation. It is known for a long time that psoriatic disease is associated with a number of conditions such as hypertension, dyslipidemia, diabetes (metabolic syndrome) and depression. Up to one out of five people with psoriasis show concomitant depression. In the past, this was attributed to psychological stress of suffering from a chronic condition that is often visible and itchy, leading to stigmatization and adding to a significant burden of disease. Recent data provide evidence that depression associated with psoriatic disease is linked to the specific inflammatory pattern with IL-23, IL-17 family cytokines, TNF, IL-6 and IL-8 causing neuroinflammation and subsequently depression or depressive behaviour and/or anxiety. Psoriatic disease shows a distinct pattern of immune cells (e.g. dendritic cells, Th17 cells, neutrophils), mediators (e.g. IL-17A/F, IL-23, TNF) and tissue-related factors in all major domains that is different from other inflammatory dermatoses. There is a striking similarity between the inflammatory pattern in psoriatic disease and neuroinflammation that leads to depression. A number of risk factors have been identified in psoriatic disease, the most important of which are obesity and tobacco smoking. Obesity is known as a major risk factor for depression and anxiety due to its inflammatory signature. Apart from psychotherapy and anti-depressive medication, targeted treatments for psoriasis, including TNF, IL-17 and IL-23 inhibitors, can improve depression/depressive symptoms. The review summarizes the current knowledge about depression as a comorbidity in psoriatic disease.

Joint Statement (DZK, DGRh, DDG) on the Tuberculosis Risk with Treatment Using Novel Non-TNF-Alpha Biologicals.

BACKGROUND: While the risk of tuberculosis (TB) reactivation is adequately documented in relation to TNF-alpha inhibitors (TNFi), the question of what the tuberculosis risk is for newer, non-TNF biologics (non-TNFi) has not been thoroughly addressed. METHODS: We conducted a systematic review of randomized phase 2 and phase 3 studies, and long-term extensions of same, published through March 2019. Of interest was information pertaining to screening and treating of latent tuberculosis (LTBI) in association with the use of 12 particular non-TNFi. Only rituximab was excluded. We searched MEDLINE and the ClinicalTrial.gov database for any and all candidate studies meeting these criteria. RESULTS: 677 citations were retrieved; 127 studies comprising a total of 34,293 patients who received non-TNFi were eligible for evaluation. Only 80 out of the 127 studies, or 63 %, captured active TB (or at least opportunistic diseases) as potential outcomes and 25 TB cases were reported. More than two thirds of publications (86/127, 68 %) mentioned LTBI screening prior to inclusion of study participants in the respective trial, whereas in only 4 studies LTBI screening was explicitly considered redundant. In 21 studies, patients with LTBI were generally excluded from the trials and in 42 out of the 127 trials, or 33 %, latently infected patients were reported to receive preventive therapy (PT) at least 3 weeks prior to non-TNFi treatment. CONCLUSIONS: The lack of information in many non-TNFi studies on the number of patients with LTBI who were either excluded prior to participating or had been offered PT hampers assessment of the actual TB risk when applying the novel biologics. Therefore, in case of insufficient information about drugs or drug classes, the existing recommendations of the German Central Committee against Tuberculosis should be applied in the same way as is done prior to administering TNFi. Well designed, long-term "real world" register studies on TB progression risk in relation to individual substances for IGRA-positive cases without prior or concomitant PT may help to reduce selection bias and to achieve valid conclusions in the future.

EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris - Part 2: specific clinical and comorbid situations.

This evidence- and consensus-based guideline on the treatment of psoriasis vulgaris was developed following the EuroGuiDerm Guideline and Consensus Statement Development Manual. The second part of the guideline provides guidance for specific clinical and comorbid situations such as treating psoriasis vulgaris patient with concomitant psoriatic arthritis, concomitant inflammatory bowel disease, a history of malignancies or a history of depression or suicidal ideation. It further holds recommendations for concomitant diabetes, viral hepatitis, disease affecting the heart or the kidneys as well as concomitant neurological disease. Advice on how to screen for tuberculosis and recommendations on how to manage patients with a positive tuberculosis test result are given. It further covers treatment for pregnant women or patients with a wish for a child in the near future. Information on vaccination, immunogenicity and systemic treatment during the COVID-19 pandemic is also provided.

Adalimumab medium-term dosing strategy in moderate-to-severe hidradenitis suppurativa: integrated results from the phase III randomized placebo-controlled PIONEER trials.

BACKGROUND: Weekly adalimumab (Humira® ) is approved for the treatment of hidradenitis suppurativa (HS) based on the 12-week placebo-controlled periods of the two phase III PIONEER trials. OBJECTIVES: Using PIONEER integrated trial results, we aimed to evaluate the optimal medium-term adalimumab maintenance dosing strategy for moderate-to-severe HS. METHODS: Each trial had two double-blind periods; 12-week Period A and 24-week Period B. Patients randomized to adalimumab 40 mg every week (ADAew) (Period A), were rerandomized in Period B to ADAew (ADAew/ew), ADA every other week (ADAew/eow), or placebo (ADAew/pbo). Placebo-randomized patients were reassigned in Period B to ADAew (PIONEER I) or placebo (PIONEER II). The primary outcome was HS Clinical Response (HiSCR). Patients who lost response during Period B were discontinued from the study and offered an option to enter the open-label extension (OLE) to receive ADAew. Results are reported across the two study periods, and data were combined from the two study periods and the OLE. RESULTS: For week-12 HiSCR achievers, the HiSCR week-36 rate was 48·1% (ADAew/ew) vs. 46·2% (ADAew/eow) and 32·1% (ADAew/pbo). Combining (post hoc) these patients with week-12 partial responders further differentiated outcomes in Period B (ADAew/ew 55·7% vs. ADAew/eow 40·0% and ADAew/pbo 30·1%). Period-B adverse-event rates were ADAew/ew 59·6% vs. ADAew/eow 57·4% and ADAew/pbo 65·0%. One patient (ADAew/ew) reported a serious infection. CONCLUSIONS: Weekly adalimumab treatment, effective throughout 36 weeks, was the optimal maintenance medium-term dosing regimen for this population. At least partial response after 12 weeks with continued weekly dosing had better outcomes than dose reduction or interruption. Patients who do not show at least a partial response to weekly adalimumab by week 12 are unlikely to benefit from continued therapy. No new safety risks were identified. What's already known about this topic? Hidradenitis suppurativa (HS) is a chronic inflammatory disease, commonly misinterpreted as an infection and treated with long-term antibiotic regimens or surgical incisions. Based on the chronicity of HS and the lack of evidence for efficacious and safe long-term HS treatments, it is important to evaluate medium- to long-term therapies for HS. Weekly adalimumab (Humira® ) is approved for the treatment of moderate-to-severe HS based on the two phase III PIONEER trials. What does this study add? This study pooled data from the two PIONEER trials, providing a more robust assessment of outcomes. After at least partial treatment success with weekly adalimumab short-term therapy (12 weeks), continuing weekly dosing during the subsequent 24 weeks had better outcomes than dose reduction or treatment interruption. Patients who do not show at least a partial response to weekly adalimumab by week 12 are unlikely to benefit from continued therapy.

ALIGNed on adherence: subanalysis of adherence in immune-mediated inflammatory diseases in the DACH region of the global ALIGN study.

BACKGROUND: Non-adherence to medication is a challenging problem in daily clinical practice. OBJECTIVE: To assess reasons for non-adherence in patients with chronic immune-mediated inflammatory diseases (IMIDs) in a direct comparison including evaluation of treatment necessity and concerns. METHODS: ALIGN was a non-interventional, multicountry, multicentre, self-administered, cross-sectional, epidemiologic survey study. Here, we investigate the German, Austrian and Swiss (DACH) cohort. Six hundred thirty-one patients with different IMIDs (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn's disease and ulcerative colitis) under systemic therapies were evaluated concerning adherence, beliefs of necessity and concerns towards treatment in patients with IMIDs. RESULTS: The DACH cohort had significantly different levels of adherence depending on the IMID (P < 0.05) and the type of therapy (P < 0.05). Based on the significant influence of concerns on treatment adherence (P < 0.05) and the high belief of treatment necessity, patients could be classified in four attitudinal segments, which were unequally distributed throughout various IMIDs. High concerns had a significant influence on non-adherence, whereas necessity did not. Older age, female sex, TNFi mono-, conventional combination and TNFi combination therapy are positively associated with adherence. CONCLUSIONS: In the DACH region, patients are less concerned about medication and believe in the necessity of treatment. Therefore, we suggest adapting the communication in the various patient groups.

Small dense LDL cholesterol in human subjects with different chronic inflammatory diseases.

BACKGROUND AND AIMS: Chronic inflammatory diseases (CID) are associated with a profound increase in cardiovascular (CV) risk resulting in reduced life expectancy. However, LDL-cholesterol is reported to be low in CID patients which is referred to as the "LDL paradoxon". The aim of the present study was to investigate whether LDL-particles in CID exhibit an increased content of the highly atherogenic small-dense LDL subfraction (sdLDL). METHODS AND RESULTS: In this prospective, single center, observational study we enrolled 141 patients with CID (RA n = 59, inflammatory bowel disease (IBD) n = 35, ankylosing spondylitis (SpA) n = 25, Psoriasis n = 22) in 2011 through 2013 to evaluate sdLDL levels before as well as 6 and 26 weeks after initiation of different anti-cytokine therapies (anti-TNFα, anti-IL-6R antibodies). sdLDL levels were compared to 141 healthy individuals in a case control design. Compared to healthy controls, all CID patients displayed a significantly higher sdLDL content within the LDL cholesterol fraction: RA 35.0 ± 9.2% (p < 0.001), SpA 42.5 ± 10.5% (p < 0.001), IBD 37.5 ± 7.1% (p < 0.001), Psoriasis 33.6 ± 4.6% (p < 0.01). Furthermore, the sdLDL/LDL ratio was significantly higher in male compared to female RA subjects (p < 0.05). Neither anti-TNFα nor anti-IL6R medication altered sdLDL levels despite a significant improvement of disease activity. CONCLUSION: In several different chronic inflammatory disease entities, LDL-cholesterol is shifted toward a pro-atherogenic phenotype due to an increased sdLDL content which might in part explain the LDL paradoxon. Since premature CV disease is a major burden of affected patients, specifically targeting lipid metabolism should be considered routinely in clinical patient care. CLINICAL TRIALS: Registration at German Clinical Trial Register (DRKS): DRKS00005285.

The German National Program on Psoriasis Health Care 2005-2015: results and experiences.

In 2005, the first national psoriasis survey in Germany revealed large deficits in health care particularly in patients with moderate to severe disease. The consecutive goal was to improve health care for psoriasis countrywide. For this, a large-scale national program was initiated starting with a comprehensive analysis of structures and processes of care for psoriasis. Patient burden, economic impact and barriers to care were systematically analyzed. In order to optimize routine care, a S3 guideline, a set of outcomes measures and treatment goals, were developed. Implementation was enforced by the German Psoriasis Networks (PsoNet) connecting the most dedicated dermatologists. The annual National Conference on Health Care in Psoriasis established in 2009 consented National Health Care Goals in Psoriasis 2010-2015 and defined a set of quality indicators, which are monitored on a regular basis. Currently 28 regional networks including more than 800 dermatologists are active. Between 2005 and 2014 7 out of 8 quality indicators have markedly improved, and regional disparities were resolved. e.g., mean PASI (Psoriasis Area Severity Index) dropped from 11.4 to 8.1 and DLQI (Dermatology Life Quality Index) from 8.6 to 5.9. A decade of experience indicates that a coordinated nationwide psoriasis program based on goal orientation can contribute to better quality of care and optimized outcomes.

Differential expression of antimicrobial peptides in psoriasis and psoriatic arthritis as a novel contributory mechanism for skin and joint disease heterogeneity.

OBJECTIVES: This study tested the hypothesis that a differential innate immune antimicrobial peptide (AMP) profile was evident between the skin and joints in psoriasis and psoriatic arthritis (PsA) and that PsA synovitis may have a distinct AMP pattern compared to other arthropathies. METHOD: Twenty-two cases had knee biopsies [10 PsA, eight rheumatoid arthritis (RA), and four osteoarthritis (OA)]. Lesional and non-lesional skin biopsies in psoriasis and control tissue were also obtained (n = 4 each). Immunohistochemistry with semi-quantitative scoring of both synovium and skin was performed using the following panel of AMPs: S100 A8, S100 A9, human neutrophil peptides 1-3 (HNP1-3), human ß-defensins 2 and 3 (hBD-2 and hBD-3), cathelicidin LL-37, psoriasin (S100 A7), and ribonuclease 7 (RNase 7). RESULTS: Similar expression of S100 A8, S100 A9, and HNP1-3 was detectable in PsA and RA synovium but only in the synovium sublining layer (SSL). No expression of psoriasin, RNase 7, hBD-2, and hBD-3 could be detected in the synovial tissue of PsA, RA, or OA. All psoriasis skin samples exhibited broad expression of all investigated AMPs, with strong keratinocyte expression. CONCLUSIONS: Given that some AMPs, especially hBD-2, are genetically linked to psoriasis and are only expressed in the skin, these findings show how differential AMP expression in innate immune responses may contribute to disease heterogeneity between PsA and psoriasis and provides a genetic basis for the non-progression of psoriasis subgroups to PsA.

TNF-α: a treatment target or cause of sarcoidosis?

Sarcoidosis is a systemic granulomatous disease that affects numerous organs, commonly manifesting at the lungs and skin. While corticosteroids remain the first line of treatment, tumour necrosis factor alpha (TNF-α) inhibitors have been investigated as one potential steroid sparing treatment for sarcoidosis. TNF-α is one of many components involved in the formation of granulomas in sarcoidosis. While there have been larger scale studies of biologic TNF-α inhibition in systemic sarcoidosis, studies in cutaneous disease are limited. Paradoxically, in some patients treated with biologic TNF-α inhibitors for other diseases, treatment can induce the development of sarcoidosis. In the light of this complexity, we discuss the role of TNF-α in granuloma formation, the therapeutic role of TNF-α inhibition and immunologic abnormalities following treatment with these TNF-α inhibitors including drug-specific alterations involving interferon-γ, lymphotoxin-α, TNF receptor 2 (TNFR2) and T-regulatory cells.

Drug safety of systemic treatments for psoriasis: results from The German Psoriasis Registry PsoBest.

The German Psoriasis Registry PsoBest was conducted in 2008 in order to investigate the long-term outcomes and safety of systemic treatments for moderate-to-severe psoriasis. Safety analysis of antipsoriatic drugs with special focus on serious adverse events (SAE) for infections, malignancies and major cardiac events (MACE) was done. Nationwide non-interventional patient treatment registry conducted in 251 active dermatology centers. Until June 2012, n = 2444 patients [40 % female; mean age 47.3 (SD 14.1) years; mean duration of disease 18.2 (SD 14.7) years] were recruited, including n = 1791 patients (3842 patient years) with conventional systemic drugs and n = 908 (3442 patient years) with biological drugs. Mean PASI (Psoriasis Area and Severity Index) at inclusion was 14.7, mean DLQI (Dermatology Life Quality Index) 11.1, mean BMI (Body Mass Index) 28.2. The overall rate of SAE per 100 patient years were 1.3 (SD 0.9) per 100 patient years in conventional systemic and 1.5 (SD 1.2) in biologics (p > 0.5, no significant difference). The rates per 100 patient years for single severe adverse events were as follows (systemic/biologics): serious infections, 0.33/0.65 [CI (confidence interval) 0.13-0.54/0.35-0.98]; MACE, 0.56/0.77 (CI 0.29-0.97/0.41-1.31); malignancies (except non-melanoma skin cancer), 0.46/0.49 (CI 0.22-0.84/0.21-0.97). There were no significant differences between single drugs in any of the safety parameters. The conventional systemic and biologic drugs for psoriasis show satisfying safety under routine psoriasis care in Germany with respect to infections, MACE and malignancies.

[Evolution of biologicals in inflammation medicine--biosimilars in gastroenterology, rheumatology and dermatology]. / Evolution der Biologika in der Entzündungsmedizin--Biosimilars in Gastroenterologie, Rheumatologie und Dermatologie.

Biologicals revolutionized the therapy of chronic inflammatory diseases in gastroenterology, rheumatology and dermatology in the last decade. The first generation biologicals mainly targeted against the pro-inflammatory cytokine TNF-α. The evolution of these therapies in the last years led to the development of new antibodies and to the admission of first generation "generic" biologics - the biosimilars. Biosimilars are not a fundamental new pharmacological development for existing substances, however they have the potential to lead to enormous cost savings in healthcare without reducing the level of care for patients. Biosimilars are not identical with the originator, but in an extensive biosimilarity exercise including analytical, preclinical and comparative clinical studies it was shown that the biosimilars could demonstrate comparability in all relevant aspects with the originator.In September 2013, the Infliximab biosimilars (Inflectra(®), Remsina(®)) were the first biosimilars for monoclonal antibodies to be authorized by the EMA for use in the European Union. By demonstrating the therapeutic similarity only in one indication (rheumatoid arthritis) the EMA agreed with an extrapolation also to all approved indications of the originator. This could be a relevant problem in clinical practice. Therefore, comparative studies with the originator are required in all approved indications.After expiration of the national patent protection in beginning of 2015, the infliximab biosimilars will be launched on the market in Germany and will be part of the therapeutic arsenal in gastroenterology, rheumatology and dermatology. Interchangeability (Switching) of biosimilars with the originator will be subject of an important discussion with the health care providers. Regardless of the biosimilars EMA-approval, several potential problems (efficacy, extrapolation, switching, long-term safety) should be the topic of intensive long-term registries in the future.

Psoriasis: rationale for targeting interleukin-17.

The exact pathogenesis of plaque psoriasis remains to be fully determined, but it is thought to depend on environmental and genetic factors that stimulate dysregulated innate and adaptive immune responses in the skin. The cytokine interleukin (IL)-17A plays a key role in host defence against extracellular bacteria and fungi. An increasing body of evidence suggests that IL-17A is also important in psoriasis pathogenesis. While IL-17A is a key product of Th17 cells, it is also produced by neutrophils, mast cells and Tc17 cells. Each of these cell types is found in psoriatic lesions. IL-17A acts on keratinocytes to increase expression of chemokines (e.g. CCL20, CXCL1, CXCL3, CXCL5, CXCL6 and CXCL8) involved in recruiting myeloid dendritic cells, Th17 cells and neutrophils to the lesion site. IL-17A induces production of antimicrobial peptides and proinflammatory cytokines that, in turn, may help sustain immune responses in the skin. Blocking IL-17A improved psoriasis-like pathology in experimental models, and reductions in IL-17 signalling have been associated with response to tumour necrosis factor-α blockers in patients with psoriasis. Agents that inhibit IL-17 are in development and preliminary clinical results for IL-17 inhibitors indicate the importance of IL-17A in psoriasis pathophysiology. In a proof-of-concept and two phase II trials, three agents markedly reduced disease severity in patients with moderate-to-severe plaque psoriasis. One agent downregulated cytokines, chemokines and proteins associated with inflammatory responses in lesional skin. In summary, IL-17A is an attractive therapeutic target, which may allow selective intervention to address the dysregulated immune system in plaque psoriasis.

Efficacy, safety and medication cost implications of adalimumab 40 mg weekly dosing in patients with psoriasis with suboptimal response to 40 mg every other week dosing: results from an open-label study.

BACKGROUND: The clinical utility of increasing to weekly adalimumab therapy in patients with psoriasis with inadequate response to every other week (eow) dosing is unknown. OBJECTIVES: (i) To determine the effectiveness of escalating adalimumab dosage from 40 mg eow to 40 mg weekly in patients with < PASI 50 response following ≥ 24 weeks treatment. (ii) To identify retrospectively characteristics of patients likely to benefit from dose escalation using classification and regression tree analysis. (iii) To assess cost implications for allowing dose escalation from the private payers' perspective. METHODS: Patients with moderate-to-severe psoriasis who had received blinded adalimumab 40 mg eow or placebo in antecedent phase II/III studies could enrol in an open-label extension (OLE) and initially receive open-label adalimumab 40 mg eow (EOW population). On/after week 24 (OLE), patients with < PASI 50 response relative to baseline of antecedent study could increase to 40 mg weekly. The dosage escalation population continued on weekly dosing until achieving PASI 75 response, then resumed eow dosing. Study visits were 6/12 weeks after dosage escalation, and every 12 weeks thereafter. The percentage of patients who achieved PASI 75 response following dosage escalation was determined (missing PASI scores imputed as nonresponse). Safety was assessed for the dosage escalation population and for all adalimumab exposure that did not follow dosage escalation in the EOW set. RESULTS: In total, 349/1256 (27·8%) patients underwent dosage escalation (OLE). At 12/24 weeks after dosage escalation, 93/349 (26·6%)/133/349 (38·1%) were PASI 75 responders or resumed eow dosing. Secondary nonresponders, patients weighing ≤ 102 kg, and those with disease duration < 8·3 years were most likely to benefit from dose escalation. Rates of serious/serious infectious/malignant (excluding nonmelanoma skin cancers or lymphoma) adverse events were 6·8/0·9/1·4 events per 100 patient-years (dosage escalation population); comparable rates in the EOW set were 6·5/1·2/0·5 events per 100 patient-years. CONCLUSIONS: Most patients did not require dose escalation. By 12 weeks after dose escalation, one-quarter achieved substantial clinical improvement. Safety results were similar between patients who dosage-escalated and those who did not.

[Comorbidities and psoriasis. Impact on clinical practice]. / Komorbiditäten und Psoriasis. Konsequenzen für die Praxis.

Psoriasis is a genetically determined, chronic inflammatory systemic disease. Besides skin symptoms, patients with moderate to severe forms of psoriasis show an association with other diseases, referred to as comorbidities. Metabolic disorders (e.g. diabetes mellitus, insulin resistance, dyslipidemia mainly in obese patients) and cardiovascular diseases (e.g. arterial hypertension, coronary artery disease, myocardial infarction and stroke) are of importance as they can increase patients' mortality. In addition, psychiatric diseases are more frequent in psoriasis patients and influence the therapeutic approach. The dermatologist in most cases is the primarily consulted physician for patients with psoriasis and therefore plays the role as a gatekeeper managing therapy. He is responsible for the early diagnosis of comorbidities and insuring their appropriate management. The anti-psoriatic treatment has to be adapted to existing comorbidities and their systemic treatments. The following article provides information on psoriatic comorbidities and their consequences for daily practice.

Management of palmoplantar pustulosis: do we need to change?

Palmoplantar pustulosis (PPP) is difficult to treat. There is little hard evidence for the efficacy of any treatment and no published guidelines for its management. A number of exacerbating factors are well documented and there is some evidence for the importance of others. Smoking is the most recognized environmental trigger and recent research has concentrated on the role of eccrine sweat glands in this regard. Other factors, including tonsillar streptococcal infection and gluten sensitivity, may be important in selected cases. The aim of this review is to challenge dermatologists to consider alternative management strategies for PPP and design clinical trials that will enable the development of useful therapeutic guidelines.

Smoking and alcohol intake in severely affected patients with psoriasis in Germany.

BACKGROUND: Smoking and alcohol may contribute as triggering factors for psoriasis and are substantial for managing severely affected psoriasis patients. OBJECTIVES: To evaluate the general state of smoking and alcohol intake in a group of hospitalized, severely affected patients with psoriasis in comparison with the general population of Germany. METHODS: A retrospective, multicentre study analysing data from 1,203 patients with severe psoriasis was performed. RESULTS: 43.3% of all patients were found to be active smokers (males: 46.6%; females: 39.2%) with a higher likelihood as the control group (odds ratio, OR, 2.08, 95% confidence interval, CI, 1.81-2.39; p < 0.0001). 14.9% of all patients were found to be excessive drinkers (female patients: 5.5%; male patients: 22.3%), more likely than the control group (OR 3.10, 95% CI 2.53-3.80; p < 0.0001); males had an OR of 2.86 (95% CI 2.29-3.56; p < 0.0001) and females an OR of 5.12 (95% CI 3.12-8.39; p < 0.0001). CONCLUSION: Smoking and alcohol intake are independently associated with severe forms of psoriasis. Disease severity is correlated with smoking in both genders as well as with alcohol intake in female patients.

["TRECID", TNFalpha related chronic inflammatory diseases - a new multiple diseases bridging concept]. / "TRECID": TNFalpha-assoziierte chronisch entzündliche Erkrankungen - Eine neue Krankheits-übergreifende Sichtweise.

The pro-inflammatory cytokine TNF alpha (TNF) has a key position in the pathogenesis of various infectious and inflammatory diseases. Clarification of its pivotal role in the pathogenesis of rheumatoid arthritis, spondyloarthritis, uveitis, psoriasis and inflammatory bowel disease has resulted in the successful development of TNF- blocking therapies, which have disease-modifying properties that exceed the effects of conventional therapeutic options. For this reason data on the concurrence of several chronic inflammatory diseases have led to the hypothesis of common pathogenetic processes of cytokine dysregulation. The acronym TRECID describes this concept of "TNF RElated Chronic Inflammatory Diseases". Physicians of different specialties have integrated new therapeutic options with TNF-blocking therapies into their strategies for the management of the affected patients. Thus the concept of TRECID can be regarded as a role model for a dynamic, interdisciplinary cooperation based on shared pathophysiological aspects.

European S3-guidelines on the systemic treatment of psoriasis vulgaris.

Of the 131 studies on monotherapy or combination therapy assessed, 56 studies on the different forms of phototherapy fulfilled the criteria for inclusion in the guidelines. Approximately three-quarters of all patients treated with phototherapy attained at least a PASI 75 response after 4 to 6 weeks, and clearance was frequently achieved (levels of evidence 2 and 3). Phototherapy represents a safe and very effective treatment option for moderate to severe forms of psoriasis vulgaris. The onset of clinical effects occurs within 2 weeks. Of the unwanted side effects, UV erythema from overexposure is by far the most common and is observed frequently. With repeated or long-term use, the consequences of high, cumulative UV doses (such as premature aging of the skin) must be taken into consideration. In addition, carcinogenic risk is associated with oral PUVA and is probable for local PUVA and UVB. The practicability of the therapy is limited by spatial, financial, human, and time constraints on the part of the physician, as well as by the amount of time required by the patient. From the perspective of the cost-bearing institution, phototherapy has a good cost-benefit ratio. However, the potentially significant costs for, and time required of, the patient must be considered.