Spotlight on Etanercept in Plaque Psoriasis and Psoriatic Arthritis

Etanercept (Enbrel), a tumor necrosis factor (TNF)-alpha antagonist produced by recombinant technology, is approved for use in the US as subcutaneous monotherapy in adults with moderate-to-severe psoriasis who are candidates for systemic therapy or phototherapy. The drug is also indicated in patients with psoriatic arthritis, in whom it may be used in combination with methotrexate.In well designed trials in patients with moderate-to-severe psoriasis, short-term etanercept therapy (typically 25 or 50mg twice weekly) significantly increased the proportion of patients achieving a 75% reduction in the Psoriasis Area and Severity Index score compared with placebo. Similarly, in well designed trials in patients with psoriatic arthritis, treatment with short-term etanercept 25mg twice weekly, alone or in combination with methotrexate, improved clinical features of the disease, while radiographic progression of joint damage appeared to be significantly slowed in a nonblind 1-year extension. Short-term etanercept therapy was well tolerated in patients with psoriasis or psoriatic arthritis. Etanercept is thus a valuable new option for the treatment of patients with chronic moderate-to-severe plaque psoriasis (who are candidates for systemic therapy or phototherapy or have failed other systemic therapies) or with psoriatic arthritis.     

The Immunologic Role of IL-17 in Psoriasis and Psoriatic Arthritis Pathogenesis

Psoriasis is a chronic, immune-mediated, inflammatory disease that is pathogenically driven by proinflammatory cytokines. This article reviews the immunologic role of interleukin (IL)-17, the major effector cytokine in the pathogenesis of psoriatic disease, along with the rationale for targeting the IL-17 cytokine family (IL-17A, IL-17F, and IL-17 receptor A) in the treatment of psoriasis and psoriatic arthritis. Emerging evidence indicates that major sources of IL-17A in patients with psoriatic disease are mast cells, γδ T cells, αβ T cells, and innate lymphoid cells in lesional skin and synovial fluid. Within the skin and joints, IL-17A acts on cellular targets, including keratinocytes, neutrophils, endothelial cells, fibroblasts, osteoclasts, chondrocytes, and osteoblasts, to stimulate production of various antimicrobial peptides, chemokines, and proinflammatory and proliferative cytokines, which, in turn, promote tissue inflammation and bone remodeling. The critical importance of the IL-23/IL-17A axis to the pathogenesis of psoriatic disease has resulted in many new biologic treatments targeting these cytokines. These biologics dramatically improve skin and joint symptoms in patients with moderate-to-severe psoriasis and psoriatic arthritis.     

Leflunomide in psoriatic arthritis

Psoriatic arthritis (PsA) is a common unique form of inflammatory arthritis associated with psoriasis. Its exact prevalence is unknown but 5-30% of the 2-3% of subjects of the general population affected with psoriasis are developing PsA. Typically PsA presents as an oligoarticular asymmetrical arthritis with predominant distal finger joint pattern, presence of spinal involvement enthesitis and dactylitis. There is evidence that T-cells play a key role in the immunopathology of PsA as well as Psoriasis. Leflunomide, a selective pyrimidine synthesis inhibitor with the property to inhibit T-cell activation and proliferation has been shown to improve both joint and skin symptoms in patients with PsA. Significant response rates have been observed for Psoriatic Arthritis Response Criteria (PsARC), modified ACR20 and PASI 50 after 24 weeks of treatment with 20 mg/d Leflunomide orally in a randomised, placebo controlled multicenter trial (TOPAS Study). Leflunomide treatment also improved quality of life and showed a favourable safety profile. It is therefore concluded that Leflunomide offers an efficacious, well tolerated, safe, and relatively inexpensive therapeutic option for the treatment of actively inflamed joints and psoriatic skin lesions in patients with PsA.     

Skeletal pattern in subjects with temporomandibular joint disorders

Introduction

To establish the skeletal pattern in subjects with malocclusions and temporomandibular disorders (TMD); to assess the relationship between craniofacial skeletal structures and TMD in subjects with malocclusions.

Material and methods

Sixty-four subjects with malocclusions, over 18 years of age, were included in the study. Temporomandibular disorders were clinically assessed according to the Helkimo Anamnestic Index. Subjects underwent a lateral cephalogram. Subjects were grouped according to the sagittal skeletal pattern (ANB angle) into class I, II and III. Parametric Student tests with equal or unequal variations were used (variations were previously tested with Levene test).

Results

Twenty-four patients with TMD (experimental sample); 40 patients without TMD (control group); interincisal angle was higher in class I and II (p < 0.05) experimental subjects; overjet was larger in experimental subjects; midline shift and Wits appraisal were broader in the experimental group in all three classes. In class III subjects, the SNB angle was higher in the experimental group (p = 0.01). Joint noises followed by reduced mandible mobility, muscular pain and temporomandibular joint (TMJ) pain were the most frequent symptoms in subjects with TMD and malocclusions.

Conclusions

Temporomandibular joint status is an important factor to consider when planning orthodontic treatment in patients with severe malocclusions; midline shift, large overjet and deep overbite have been associated with signs and symptoms of TMD.     

Ustekinumab

? Ustekinumab is a fully human monoclonal antibody that binds with high specificity and affinity to the cytokines interleukin (IL)-12 and IL-23, thereby suppressing IL-12- and IL-23-mediated inflammation associated with psoriasis. ? In two large, phase III trials in patients with moderate to severe plaque psoriasis, significantly more subcutaneous ustekinumab 45 or 90 mg recipients (administered as two injections 4 weeks apart) than placebo recipients achieved a 75% improvement on the Psoriasis Area and Severity Index (PASI 75) score at 12 weeks. ? Other efficacy measures, including the physician’s global assessment of clinical response at week 12, also favored ustekinumab over placebo. Psoriatic symptom control was maintained during ustekinumab maintenance therapy (administered once every 12 weeks) for up to 76 weeks. ? In a phase II trial in patients with active plaque psoriasis and psoriatic arthritis, signs and symptoms of arthritis and psoriatic symptom control were improved to a greater extent with ustekinumab than with placebo at 12 weeks, based on the proportion of patients achieving a 20% improvement in American College of Rheumatology response criteria (arthritis) or PASI 75 (skin symptoms). ? Health-related quality of life, assessed using the Dermatology Life Quality Index and the Health Assessment Questionnaire disability index, was improved to a significantly greater extent with ustekinumab than with placebo at week 12. ? Subcutaneous ustekinumab was generally well tolerated in clinical trials, with most treatment-emergent adverse events being of mild severity.     

Psycho-education programme for temporomandibular disorders: a pilot study

Background  

Temporomandibular disorders (TMDs) are by far the most predominant condition affecting the temporomandibular joint (TMJ), however many patients have mild self-limiting symptoms and should not be referred for specialist care.     

Periodontitis: a newly identified comorbidity in psoriasis and psoriatic arthritis

ABSTRACT

Introduction: Psoriasis is a chronic autoimmune skin disease with strong genetic background and environmental triggers. Patients with psoriasis and psoriatic arthritis are at greater risk of developing other chronic and potentially severe comorbidities, such as psoriatic arthritis, hyperlipidemia, type 2 diabetes mellitus, obesity, metabolic syndrome, cardiovascular diseases or depression. Recently, accumulating epidemiologic, genetic and pathogenetic evidence indicates that psoriasis is also associated with periodontitis, a chronic progressive inflammatory disease, which may result in tooth loss without early and adequate therapy.

Areas covered: In this review article we summarize and discuss in detail the available epidemiologic, genetic, microbiological and immunological links between psoriasis and periodontitis.

Expert opinion: Periodontitis, via the immunomodulatory effect of the oral microbiota, may play both a direct and indirect role in the development or exacerbation of psoriasis, and may influence the efficacy of antipsoriatic therapy. These new findings indicate a need for increased awareness, early recognition and focus on prevention of periodontitis for patients with psoriasis.     

Role of magnetic resonance imaging in the clinical diagnosis of the temporomandibular joint

Temporomandibular joint (TMJ) abnormalities cannot be reliably assessed by a clinical examination. Magnetic resonance imaging (MRI) may depict joint abnormalities not seen with any other imaging method and thus is the best method to make a diagnostic assessment of the TMJ status. In patients with temporomandibular joint disorder (TMD) referred for diagnostic imaging the predominant TMJ finding is internal derangement related to disc displacement. This finding is significantly more frequent than in asymptomatic volunteers, and occurs in up to 80% of patients consecutively referred for TMJ imaging. Moreover, certain types of disc displacement seem to occur almost exclusively in TMD patients, namely complete disc displacements that do not reduce on mouth opening. Other intra-articular abnormalities may additionally be associated with the disc displacement, predominantly joint effusion (which means more fluid than seen in any asymptomatic volunteer) and mandibular condyle marrow abnormalities (which are not seen in volunteers). These conditions seem to be closely related. Nearly 15% of TMD patients consecutively referred for TMJ MRI will have joint effusion, of whom about 30% will show bone marrow abnormalities. In a surgically selected material of joints with histologically documented bone marrow abnormalities nearly 40% showed joint effusion. Disc displacement is mostly bilateral, but joint effusion seems to be unilateral or with a lesser amount of fluid in the contralateral joint. Abnormal bone marrow is also mostly unilateral. Many patients have unilateral pain or more pain on one side. In a regression analysis the self-reported in-patient TMJ pain side difference was positively dependent on TMJ effusion and condyle marrow abnormalities, but negatively dependent on cortical bone abnormalities. Of the joints with effusion only one fourth showed osteoarthritis. Thus, there seems to be a subgroup of TMD patients showing more severe intra-articular pathology than disc displacement alone, and mostly without osteoarthritis. It should, however, be emphasized that patients with TMJ effusion and/or abnormal bone marrow in the mandibular condyle seem to constitute only a minor portion (less than one fourth) of consecutive TMD patients referred for diagnostic TMJ imaging. The majority of patients have internal derangement related to disc displacement, but without accompanying joint abnormalities. In patients with rheumatoid arthritis and other arthritides TMJ involvement may mimick the more common TMDs. Using MRI it is possible, in most cases, to distinguish these patients from those without synovial proliferation.     

Cytokine-Based Therapy in Psoriasis

Psoriasis and psoriatic arthritis are chronic inflammatory diseases of unknown etiology, affecting 2–3% of the world population. Initially, psoriasis was thought to be a hyper-proliferation disorder of keratinocytes only, but as time passed, the role of immune system became more evident and now both diseases are considered autoimmune disorders. In last few years, the discovery of interleukin (IL)-23/Th17 axis in pathophysiology of psoriatic diseases shifts the cytokine paradigm from Th1 to Th17 cytokines, focused mainly on IL-17 and IL-22. Therapeutic experiences strongly support the use of cytokine antagonists as an important modality in the treatment of psoriatic arthritis and plaque psoriasis. Studies examining these therapeutic agents which target different steps of the psoriatic inflammatory cascade have also shown significant efficacy. The relatively new IL-23/Th17 axis in psoriatic diseases got more importance with the success of ustekinumab, a new monoclonal antibody against IL-12 and IL-23. In IL-17 and IL-22 knock-out and transgenic mouse models, it has been found that recombinant IL-23 fails to produce epidermal hyperplasia which resembles psoriasis. Also, some success in animal models of psoriasis was found with anti IL-17A and anti IL-22. More studies are needed to validate the efficacy and safety of these cytokine antagonists in psoriatic diseases. Using a historical perspective and a chess game as an analogy, the main objective of this review is to summarize the central role of some of these cytokines in psoriasis pathophysiology and to develop a strategic approach to new therapeutic weapons within the armamentarium of psoriasis treatment.     

Differential major histocompatibility complex class I chain-related A allele associations with skin and joint manifestations of psoriatic disease

About 30% of patients with psoriasis have psoriatic arthritis (PsA), an inflammatory arthritis that can affect both axial and peripheral joints. Major histocompatibility complex class I chain-related A (MICA) alleles have previously been shown to be associated with PsA; however it is unclear whether there is a differential association of MICA alleles with skin and joint manifestations of PsA. Here, we describe a case-control study that aims to validate previously reported MICA allele associations with PsA and determine whether MICA alleles differentiate patients with PsA from those with psoriasis without PsA. Two hundred forty-nine unrelated Caucasian PsA patients, 243 psoriasis patients without arthritis, and 248 healthy controls were genotyped for 55 MICA alleles using PCR-SSP, and for human leucocyte antigen (HLA)-B and HLA-C alleles by PCR-SSO reverse line blot. Allele frequencies were calculated and logistic regressions were performed, adjusting for HLA-B and HLA-C alleles previously shown to be associated with psoriasis and/or PsA. Several MICA alleles were associated with psoriatic disease, PsA, and psoriasis compared with controls, and PsA compared with psoriasis in univariate analyses. Haplotype analysis showed evidence of strong linkage disequilibrium (LD) between PsA and psoriasis risk alleles of HLA-C, HLA-B, and MICA. After adjusting for significant HLA-B and HLA-C alleles in multivariate analyses, MICA*016 remained significantly associated with psoriasis [odds ratio (OR) = 5.5, P = 0.008]. MICA*00801 homozygosity was associated with susceptibility to PsA when compared with patients with psoriasis alone (OR = 2.26, P = 0.009). We conclude that most MICA allele associations with psoriasis and PsA are dependent on LD with HLA-B and HLA-C risk alleles. Independent of HLA, only MICA*016 influences the risk of developing psoriasis without arthritis, and homozygosity for MICA*00801 increases the risk of developing PsA in patients with psoriasis.     

Gender Difference in Prevalence of Signs and Symptoms of Temporomandibular Joint Disorders: A Retrospective Study on 243 Consecutive Patients

Background: This study evaluated the prevalence of the signs and symptoms of temporomandibular joint disorder (TMD) among patients with TMD symptoms. Methods: Between September 2011 and December 2011, 243 consecutive patients (171 females, 72 males, mean age 41 years) who were referred to the Department of Prosthodontics, Faculty of Dentistry, Karadeniz Technical University, Trabzon were examined physically and completed a questionnaire regarding age, gender, social status, general health, antidepressant drug usage, dental status, limited mouth opening, temporomandibular joint (TMJ) sounds, and parafunctions (bruxism, clenching). The data were analyzed using the chi-square test and binary logistic regression model (alpha = 0.05). Results: With a frequency of 92%, pain in the temporal muscle was the most common symptom, followed by pain during mouth opening (89%) in both genders. TMJ pain at rest, pain in the masseter muscle, clicking, grinding, and anti-depressant use were significantly more frequent in females than males. Age (p=0.006; odds ratio 0.954; 95% CI 0.922-0.987) and missing teeth (p=0.003; odds ratio 3.753; 95% CI 1.589-8.863) had significant effects on the prevalence of TMD. Conclusion: Females had TMD signs and symptoms more frequently than males in the study population. The most common problem in both genders was pain.     

TNFα Inhibitors in the Treatment of Psoriasis and Psoriatic Arthritis

Psoriasis is a chronic inflammatory skin disease that can lead to significant physical and psychologic distress for patients. Psoriatic arthritis (PsA), originally thought to be quite a mild disorder, is now recognized as a progressive and destructive arthritis. To date, therapies for both these conditions have been non-specific and unable to maintain long-lasting remission. In addition, many of the current therapies have significant adverse effects, limiting their usefulness. However, elucidation of the pathogenesis of psoriasis and PsA at a molecular level and the development of selective biologic agents have led to an enormous expansion of the armamentarium available to psoriasis patients. Two agents (infliximab and etanercept) selectively block the role of the cytokine tumor necrosis factor (TNF)-alpha and have proved effective in clinical trials in the treatment of both the skin and the joint manifestations of psoriasis. A third anti-TNF alpha agent (adalimumab Humira) is licensed for the treatment of rheumatoid arthritis; however, no studies have been published to date on its use in PsA or psoriasis. It is known that TNF alpha is elevated in both the skin and synovium of psoriatic patients and the effectiveness of its blockade by these two agents in psoriasis and PsA confirms its role in their pathogenesis. Randomized, double-blind, placebo-controlled trials have been performed with both agents in the treatment of psoriasis and PsA; in the case of etanercept these have been to support US FDA approval for use in psoriatic arthropathy. These studies are supported by smaller cohorts in open-label studies and anecdotal reports in the literature. Anti-TNF alpha therapy has proved to have disease-reducing activity in PsA and psoriasis and appears to be well tolerated. These studies have generally featured small numbers of patients and, until a larger cohort of treated patients is available, vigilance must be exercised. A considerable body of post-marketing safety data exists on the use of infliximab in rheumatoid arthritis and Crohn disease and for etanercept in rheumatoid arthritis and PsA. Certain issues, particularly the risk of infection, have emerged as features of the use of these agents. It remains to be seen whether effects seen in other disease entities may be extrapolated to psoriatic patients. More long-term data and experience are needed to define the role of anti-TNF alpha agents in the management of psoriasis and PsA. In particular, more studies are required to elucidate the finer points of co-medication; in some studies both agents have been used with other medications but there have been no formal trials of various possible combinations.     

A Cutting Edge Overview: Psoriatic Disease

Psoriasis is a lifelong skin disease, affecting about 2% of the global population. Generalized involvement of the body (erythroderma), extensive pustular lesions, and an associated arthritis known as psoriatic arthritis (PsA) are severe complications of psoriasis. Genetic, immunologic, and environmental factors contribute to its pathogenesis. A complete understanding of the pathogenesis of psoriasis and psoriatic arthritis is lacking. Cytokines, chemokines, adhesion molecules, growth factors like NGF, neuropeptides, and T cell receptors all act in an integrated way to evolve into unique inflammatory and proliferative processes typical of psoriasis and PsA. Management of psoriasis requires exemplary skin care along with careful monitoring of arrays of comorbidities which includes arthritis and coronary artery disease. In many ways, psoriasis can be considered a model autoimmune disease. This statement itself is ironic considering that it was not recognized as immune mediated until relatively recently. Fortunately, the immunobiology has made enormous strides and there are now excellent therapeutic options for patients. In this thematic review, we have attempted to provide summaries of not only basic science and clinical research, but also an overview of future research directions.     

Certolizumab pegol for the treatment of psoriatic arthritis and plaque psoriasis

ABSTRACT

Introduction: Certolizumab pegol (CZP) is an Fc-free PEGylated TNF-α inhibitor approved for the treatment of psoriatic arthritis (PsA) and plaque psoriasis in many countries. It demonstrated favorable results in PsA in terms of improvement in peripheral arthritis, dactylitis, and enthesitis in a phase III trial (RAPID-PSA) and in real-life experiences. Recently, three phase III randomized clinical trials (CIMPASI-1, CIMPASI-2, CIMPACT) showed significant and sustained improvements in signs and symptoms of moderate-to-severe plaque psoriasis as well as in quality of life parameters as compared to placebo and etanercept.

Areas covered: We reviewed the structure and the mechanism of action of CZP, and critically analyzed data from clinical trials and real-life, concerning its efficacy and safety in all aspects of the psoriatic disease. We designed a comprehensive literature search on this topic, by a review of published articles in indexed international journals up until 31 July 2019.

Expert opinion: CZP demonstrated positive results in several domains of psoriatic disease, also in patients previously exposed to other TNF-α inhibitors and in patients receiving re-treatment after treatment interruption. The peculiar chemical structure, along with its well-established efficacy and safety, support CZP as the drug of choice in specific subgroups of patients with psoriatic disease, in particular patients with comorbidities and pregnant or breastfeeding female patients.     

On the involvement of the temporomandibular joint in rheumatoid arthritis

64 patients with rheumatoid arthritis (RA) were examined for temporomandibular joint (TMJ) symptoms as well as for the severity and incidence of their symptoms. In detailed interviews, a total of 34 patients (53.1%) reported TMJ symptoms, the main complaints being problems during opening and closing of the mouth (45.2%). RA patients with TMJ symptoms differed significantly from those without TMJ symptoms (p < 0.01) in the duration (121.7 +/- 100.5 months vs. 37.1 +/- 27.6 months) and the state of activity of the basic disease. The patients subjectively evaluated the severity of the TMJ symptoms as mild to moderate (grade: 2-3; severity: 241 +/- 1.01). Almost 70% reported occasional symptoms, 22.5% frequent symptoms and 10.6% permanent symptoms (p < 0.01). 61.8% (21/34) of the patients showed no radiographic change in the shape of the TMJ condyle, whereas 11.8% (4/34) demonstrated a change on one side an 26.4% (9/34) a change on both sides. There was no difference in the severity of the TMJ symptoms between patients with an unchanged condyle (n = 21; severity: 2.33 +/- 0.96) and patients with changes in condylar shape (n = 13; severity: 2.5 +/- 1.12). A frequent involvement of the temporomandibular joint in RA can be considered certain. The symptoms, which were generally moderate, can cause a marked impairment of daily used functions, such as chewing and speaking.     

CD3+CD56+ NK T cells are significantly decreased in the peripheral blood of patients with psoriasis

Psoriasis is a chronic, inflammatory, hyperproliferative skin disease, in which autoimmunity plays a great role. Natural killer T cells (NK T cells), are suggested to be involved in the pathogenesis of different autoimmune diseases. To examine the involvement of CD3+CD56+ NK T cells in the pathogenesis of psoriasis, we investigated the lymphocyte subpopulations obtained from blood samples of psoriatic patients before and after treatment, and of healthy controls, using two-colour flow cytometry. We found no significant differences between total T cells, total B cells, T helper cells, T cytotoxic cells and NK cells in patients with psoriasis before and after treatment and in controls. Increased percentage of memory T cells and decreased percentage of naive T cells was detected in psoriatic patients compared to controls, but these changes were not statistically significant. The CD3+CD56+ cells of psoriatic patients were significantly decreased relative to controls. The percentage of CD3+CD56+ cells increased after different antipsoriatic therapies, but remained significantly lower than those found in controls. CD3+CD56+ cells of healthy controls were capable of rapid activation, while in psoriatic patients activated NK T cells were almost absent. The decrease in the number of CD3+CD56+ cells may represent an intrinsic characteristic feature of patients with psoriasis, which is supported by the fact that after treatment NK T cells do not reach the values found in controls. In conclusion our results suggest that CD3+CD56+ NK T cells could be actively involved in the development of Th1 mediated autoimmune diseases.     

Ixekizumab for the treatment of psoriasis: an update on new data since first approval

Introduction: Psoriasis is a chronic immune-mediated skin disease with a multifactorial etiology. Studies have shown that the inflammatory cytokine interleukin-17A (IL-17A) is a key mediator in the pathogenesis. Targeted biologics have changed the outcome for patients in a variety of diseases including psoriasis. Ixekizumab is a humanized monoclonal antibody directed against IL-17A and it has been approved for the treatment of moderate-to-severe plaque psoriasis, and recently also psoriatic arthritis.

Areas covered: In this review, we summarize the latest clinical study results on ixekizumab. Long-term Phase III study data on efficacy and safety are now available for both plaque psoriasis and psoriatic arthritis. Additionally, new indications for ixekizumab are under investigation.

Expert commentary: Overall, the efficacy and safety of ixekizumab are promising. In plaque psoriasis, the efficacy of ixekizumab was superior to etanercept and ustekinumab, while the efficacy was comparable to adalimumab in psoriatic arthritis. The safety profile has also been found very tolerable and similar to other biologics; however, vigilance regarding non-invasive Candida infections is necessary. Also, caution is advised when treating patients with concomitant inflammatory bowel disease, since ixekizumab could cause exacerbations. Long-term studies in real-life treatment settings are needed to decide the actual potential and safety of ixekizumab.     

Current knowledge on autoantigens and autoantibodies in psoriasis

In the past decades, clinical and experimental evidence has demonstrated that psoriasis is an immune-mediated inflammatory disease of the skin that occurs in genetically susceptible individuals. Psoriasis also shows clear autoimmune pathomechanisms, but specific cellular targets for the onset and maintenance of psoriatic lesions were not established until 2014. Since then, four psoriasis autoantigens were discovered, namely cathelicidin LL-37, melanocytic ADAMTSL5, lipid antigen PLA2G4D and keratin 17. Autoreactive T cells against these autoantigens were found in a number of patients with moderate-to-severe plaque psoriasis. Moreover, the discovery of autoantibodies against LL-37 and ADAMTSL5 and their strong association with psoriatic arthritis (PsA) suggest a potential role of these autoantibodies in the pathogenesis of PsA. This review discusses the current studies on psoriatic autoantigens and the associated circulating autoantibodies and their mechanisms involved in the development and maintenance of psoriatic plaques. Recent autoimmune evidence fuelled the discussion on psoriasis as an autoimmune skin disorder and has the potential to develop new treatment strategies with protective and therapeutic antigen-targeted methods.     

Psoriatic Arthritis: a Critical Review

Psoriatic arthritis is a chronic inflammatory arthritis that affects about 5–25% of patients with psoriasis. The prevalence varies from 20–420 per 100,000 population across the world except in Japan where it is 1 per 100,000. Psoriatic arthritis affects both genders equally and in more than half it follows long-standing psoriasis. Psoriatic arthritis has been grouped into five subtypes: distal interphalangeal (DIP) predominant, symmetrical polyarthritis, asymmetrical oligoarthritis and monoarthritis, predominant spondylitis, and arthritis mutilans. Oligoarthritis occurs in nearly 60% during early disease but later polyarticular disease predominates mainly due to evolution of oligoarthritis to polyarthritis. In 50–60% polyarthritis is symmetrical. Dactylitis and enthesopathy are other major features seen in nearly one third of patients. The diagnosis of psoriatic arthritis is easy in the presence of typical skin lesions, however it can also be made in absence of skin lesions using Classification of Psoriatic Arthritis criteria. Though 30–40% of patients develop joint deformities at a follow-up of 5–10 years but most retain good functional status. Clinical damage has a strong relationship with number of swollen joints, erythrocyte sedimentation rate, and duration of arthritis. Radiological damage occurs early and erosions are present in nearly 50% at 10 years of disease. Spinal disease also has good outcome with maintained spinal mobility in majority of the patients. Screening of patients with psoriasis using questionnaire can help in early diagnosis. Nail dystrophy, scalp lesions, and intergluteal/perianal psoriasis are associated with higher chance of development of psoriatic arthritis. Early diagnosis will lead to early treatment and better outcome especially with advent of new drugs.     

Biologic therapies in psoriasis: a new therapeutic approach

Chronic plaque psoriasis is an immune-mediated, inflammatory skin disease with a heavy burden on quality of life of patients. The disease has a chronic relapsing course and may be life long. Comorbid disorders include psoriatic arthritis, obesity, dyslipidemia, hypertension and an increased rate of cardiovascular disease. Conventional systemic treatments include methotrexate, cyclosporine and acitretin, which are associated with end organ toxicity that precludes long term therapy. Biological drugs are designed to selectively interfere with the immune mechanisms that induce psoriasis. Efalizumab is effective for skin psoriasis but not psoriatic arthritis. Anti-TNF-alpha agents (etanercept, infliximab and adalimumab) are active on both psoriasis and psoriatic arthritis. Infliximab is the most effective and rapid agent, but its safety profile may be less favourable. Moreover, efficacy can reduce over time. Etanercept is moderately active but has a better safety profile, and can be discontinued and re-used without loss of efficacy. The long term safety of all these agents has not been established.