Management of long‐term therapy with biological drugs in psoriatic patients with latent tuberculosis infection in real life setting

Psoriatic patients with latent tuberculosis infection (LTBI) need a prophylaxis before starting a treatment with biological drugs. The aim of this study is to investigate the safety and efficacy of prophylaxis of LTBI in psoriatic patients receiving long‐term biological drugs. The study included 56 patients (42 male and 14 female) affected by moderate‐to‐severe psoriasis (mean PASI: 12.8 ± 6.9 SD) treated with anti‐TNF‐α and/or anti IL 12, 23 and/or anti‐CD11 drugs with a diagnosis of LTBI. LTBI diagnosis was based on tuberculin skin test and/or QuantiFERON TB Gold test positivity and chest X‐ray suggestive, without clinical, or microbiological evidence of active disease. All patients received prophylactic therapy for 9 months with isoniazid (INH) 300 mg/day, starting 3 weeks before the beginning of biological treatment. Fifty‐four patients completed prophylaxis with INH without any adverse events or intolerance; they continue the biological treatment without appearance of active tuberculosis. One patient developed tuberculosis pleurisy in course of treatment with etanercept. The infection has been treated and after a stable remission, treatment was restarted without tuberculosis reactivation. In this retrospective analysis, the prophylaxis of LTBI whit INH was effective and safe in longer follow‐up period.     

Tuberculosis screening in patients with psoriasis before antitumour necrosis factor therapy: comparison of an interferon-γ release assay vs. tuberculin skin test

Background Antitumour necrosis factor (anti‐TNF) treatments may reactivate latent tuberculosis infection (LTBI). For detecting LTBI, the tuberculin skin test (TST) has low sensitivity and specificity. Interferon‐γ release assays (IGRA) have been shown to be more sensitive and specific than TST. Objective To compare the TST and the T‐SPOT.TB IGRA for identifying LTBI in patients with psoriasis before anti‐TNF treatment. Methods A retrospective study was carried out over a 4‐year period on patients with psoriasis requiring anti‐TNF treatment. All were subjected to the TST, T‐SPOT.TB and chest X‐ray. Risk factors for LTBI and history of bacillus Calmette–Guérin (BCG) vaccination were recorded. The association of T‐SPOT.TB and TST results with risk factors for LTBI was tested through univariate logistic regression models. Agreement between tests was quantified using kappa statistics. Treatment for LTBI was started 1 month before anti‐TNF therapy when indicated. Results Fifty patients were included; 90% had prior BCG vaccination. A positive T‐SPOT.TB was strongly associated with a presumptive diagnosis of LTBI (odds ratio 7·43; 95% confidence interval 1·38–39·9), which was not the case for the TST. Agreement between the T‐SPOT.TB and TST was poor, κ = 0·33 (SD 0·13). LTBI was detected and treated in 20% of the patients. In 20% of the cases, LTBI was not retained in spite of a positive TST but a negative T‐SPOT.TB. All patients received an anti‐TNF agent for a median of 56 weeks (range 20–188); among patients with a positive TST/negative T‐SPOT.TB, no tuberculosis was detected with a median follow‐up of 64 weeks (44–188). One case of disseminated tuberculosis occurred after 28 weeks of adalimumab treatment in a patient with LTBI in spite of treatment with rifampicin. Conclusion This study is the first to underline the frequency of LTBI in patients with psoriasis (20%), and to support the use of IGRA instead of the TST for its detection. Nevertheless, there is still a risk of tuberculosis under anti‐TNF therapy, even if LTBI is correctly diagnosed and treated.     

Severe psoriasis entering remission after treatment for latent tuberculosis with isoniazid: Report of two cases

Psoriasis is a multifactorial systemic disease with predominantly cutaneous manifestations. The role of tuberculosis infection in the pathogenesis of psoriasis has not been consistently proven. Current guidelines recommend screening for tuberculosis infection in any patient with psoriasis when the initiation of biologic therapy is being considered. Isoniazid is an antibiotic with high bactericidal effect on replicating mycobacteria and constitutes the most commonly prescribed treatment for latent tuberculosis infection. Here, we report two cases of patients with psoriasis who presented at our clinic with extensive cutaneous involvement despite previous treatments with topical and systemic therapies. Both were considered as candidates for biologic therapy. As part of the screening protocol, a tuberculin test was performed with a positive result. In the absence of symptoms and chest radiography findings, isoniazid 300 mg/day for 6 months was prescribed to treat latent tuberculosis infection. This resulted in significant clearing of their skin lesions in the absence of any other concurrent treatment, apart from emollients. Both patients remained clinically stable and with no need of further systemic treatment. This situation has only been described twice before in the English‐language published work. These cases highlight the possible role of tuberculosis infection in the pathogenesis of psoriasis, suggesting the possible existence of a link between untreated infection and skin lesions. This can lead to consideration of novel therapeutic strategies and new lines of investigation.     

Dermatologic comorbidities of the patients with severe COVID‐19: A case‐control study

The current studies focus on the association between COVID‐19 and certain comorbidities. To the best of our knowledge, the association between severe COVID‐19 and dermatologic comorbidities has not been reported yet. In this study, we aimed to describe the dermatologic comorbidities of patients with severe COVID‐19 and compare it with the control group. Patients who have died at U?ak Training and Research Hospital due to COVID‐19 and other diseases in the COVID‐19 Intensive Care Units and Internal Medicine Intensive Care Units were recruited into the study. Two groups were compared with each other regarding the most common dermatologic comorbidities. A total of 198 patients including 111 patients with COVID‐19 and 87 age and sex‐matched patients with other diseases were enrolled in the study. The most common dermatologic comorbidities were pruritus (8.1%), eczema (6.3%), skin infections (3.6%), leukocytoclastic vasculitis (1.8%), and urticaria (0.9%) in the COVID‐19 group while they were skin infections (9.2%), eczema (3.4%), pruritus (2.3%), and urticaria (1.1%) in the control group. None of patients in the control group had leukocytoclastic vasculitis. There were no significant differences between COVID‐19 and control groups in terms of pruritus, eczema, skin infections, and urticaria (P values were .117, .517, .181, .505, and 1.000, respectively). In conclusion, although it is not statistically significant, it appears that pruritus and leukocytoclastic vasculitis are more common in severe COVID‐19 patients. These cytokines‐related diseases in the immuno‐cutaneous systems may give some clues on the COVID‐19 severity. Further studies are required to elucidate the relationship between the immuno‐cutaneous system and COVID‐19 severity.     

Serial Quantiferon‐TB Gold test results in 279 patients with psoriasis receiving biologic therapy

The risk of active tuberculosis is still a concern in patients receiving biologics. To determine the risk of latent tuberculosis infection (LTBI) reactivation by Quantiferon‐TB Gold (QFT) assay in psoriatic patients treated with biologics in 11 years' follow‐up, along with chest radiography alterations. This retrospective study included 279 patients with plaque‐type and/or pustular, or nail psoriasis who were treated with biologics, and had results for ≥2 LTBI tests. The QFT outcomes were defined according to the baseline and the follow‐up QFT results; seroconversion as from negative to positive, seroreversion as from positive to negative, persistently seronegative as invariantly negative, persistently seropositive as invariantly positive, and other any result was accepted as indeterminate. Demographic features, the presence and the type of any chest X‐ray abnormality was noted during the follow‐up. Of 279 baseline QFT tests, the vast majority were negative (n = 193; 69%), with a less of positive (n = 86; 31%). Ten (5.2%) of 193 patients converted from negative to positive QFT status after starting biologic therapy (P < 0.001) during 11 years' follow‐up. Although these 10 patients exhibited seroconversion of QFT from negative to positive, only one patient was diagnosed with active TB. There was no statistically significant difference among biologics as regards with QFT seroconversion risk (P = .09). This study showed that 5.2% of patients showed seroconversion. Annual QFT testing remains a necessary and mandatory tool to prevent further TB reactivation in psoriasis patients taking biologic therapy although only one patient was diagnosed with active TB in this cohort.     

Screening for latent tuberculosis infection in psoriasis and psoriatic arthritis patients in a tuberculosis‐endemic country: a comparison of the QuantiFERON®‐TB Gold In‐Tube test and tuberculin skin test

Since the introduction of biologic therapies for tuberculosis (TB), screening for latent TB infection has increased in importance, especially in countries in which TB is endemic. The aim of this study was to evaluate the effect of psoriasis on tuberculin skin test (TST) results and to compare two TB screening tests, the TST and QuantiFERON^®‐TB Gold In‐Tube (QFT–GIT) test, in psoriasis and psoriatic arthritis (PA) patients living in a TB‐endemic country (Turkey). This prospective study included 61 psoriasis and 40 PA patients, and 58 healthy controls. Demographic data, medical history, human immunodeficiency virus (HIV) status, level of education, smoking status, exposure to TB, personal and family histories of TB, and bacillus Calmette–Guérin (BCG) vaccination status were recorded for all participants. The TST and QFT–GIT were performed in all participants. The mean ± standard deviation TST indurations in the patient and control groups were 12.6 ± 6.4 mm and 10.2 ± 6.5 mm, respectively (P = 0.051). The TST positivity rate was higher in patients than in controls (86.1% vs. 37.9%; P < 0.001), whereas QFT–GIT positivity did not differ significantly (patients: 20.8%; controls: 17.2%; P = 0.737). False positive results can lead to unnecessary prophylactic TB treatment; therefore, the cut‐off point for TST positivity in psoriasis and PA patients should be re‐evaluated, or other tests, such as the QFT–GIT, should be used.     

The impact of COVID‐19 in patients with psoriasis: A multicenter study in Istanbul

There is widespread concern about treatment of psoriasis in COVID‐19 pandemic. We aimed to evaluate the epidemiological data, clinical characteristics, treatment features of the psoriasis patients during the pandemic period. We conducted a study in dermatology clinics of seven different tertiary centers. All adult psoriasis patients who were followed up between 11 March 2020 and 28 June 2020, were phone called or questioned in their visit to their follow‐up clinics. A semistructured questionnaire was applied and patients' demographics and disease characteristics were recorded. Of 1322 patients, 52.4% were male, and 47.6% were female. According to the questionnaire responses, 964 (72.9%) of these patients could not communicate with their physician during this period, remained 358 (27.1%) patients contacted the physician by phone, email, or hospital visit. From the patients diagnosed as probable/confirmed COVID‐19, 14 were female, and 9 were male. Nine of 23 (39.1%) patients were using biologic treatment. There was no statistically significant difference in terms of hospitalization from COVID‐19 between the patients using biologics (n = 9) and those who did not (n = 14) (P = 1.00). No mortality was observed among them. Obesity, smoking, age, and accompanying psoriatic arthritis were not among the risk factors affecting the frequency of COVID‐19. We only encountered an increased risk in diabetic patients. Also, an exacerbation of psoriasis was observed with the infection. No difference was found in patients with psoriasis in terms of COVID‐19 infection in patients who use biologics and those who don't.     

A prospective case‐controlled cohort study of endothelial function in patients with moderate to severe psoriasis

Background There is well‐documented evidence that patients with moderate and severe psoriasis have a significantly increased risk of cardiovascular disease (CVD). While this risk can, at least in part, be attributed to the high prevalence of traditional risk factors in the population with psoriasis, some epidemiological evidence suggests it may be independent of these. Objectives This prospective, case‐controlled study investigates whether psoriasis is a risk factor for CVD using two, validated, sensitive markers of CVD, endothelial dysfunction and high‐sensitivity C‐reactive protein (hsCRP). Methods Patients were recruited from a tertiary referral psoriasis clinic and exclusion criteria included established CVD and/or conventional risks for CVD. Preclinical CVD was assessed using flow‐mediated brachial artery dilatation, which measures endothelial dysfunction, and hsCRP, a serological marker of atherosclerosis. Results Sixty‐four patients (22%) out of a total of 285 consecutive patients attending the severe psoriasis clinic were entered into the study. One hundred and sixty‐one (56%) were excluded following identification of cardiovascular risk; 39 of the 161 (24%) had at least two cardiovascular risk factors. A further 16 (6%) patients were excluded because of established CVD. No statistically significant difference in endothelial dysfunction was observed between patients with psoriasis (n = 60) and healthy controls (n = 117) (P = 0·508). The hsCRP level was, however, significantly elevated in the psoriasis group (2·828 mg L^?1, SEM 0·219; controls 0·728 mg L^?1, SEM 0·142; P < 0·05). Conclusion This large, investigative study is the first to assess endothelial function in patients with psoriasis after exclusion of traditional risk factors for CVD. These data suggest that psoriasis per se is not a risk factor for CVD and that elevated hsCRP is possibly independent of atheroma risk. There was a high prevalence of traditional risk factors in our population with severe psoriasis.     

Increased expression of glucagon‐like peptide‐1 receptors in psoriasis plaques

Recent case reports suggest that treatment with glucagon‐like peptide‐1 (GLP‐1) agonists results in clinical improvement of psoriasis. The purpose of this study was to determine whether GLP‐1 receptors (GLP‐1Rs) are found in the skin of healthy volunteers and psoriasis patients and if so, whether GLP‐1Rs are located on keratinocytes or immune cells. Three mm‐punch skin biopsies were taken for gene expression analysis from six healthy volunteers and from affected and unaffected skin of six psoriasis patients. In addition, a blood sample was obtained from all participants. Cultured human keratinocytes were either untreated or incubated with tumor necrosis factor‐ α (TNF‐α), interferon‐γ (IFN‐γ) or a combination of TNF‐α and IFN‐γ for 48 h. Total RNA was extracted from all the samples, reversely transcribed and analysed for the expression of GLP‐1R using real‐time PCR. Gene expression analysis showed expression of GLP‐1Rs in five of six skin biopsies from psoriasis plaques, in one of six biopsies from unaffected psoriatic skin and in one of six biopsies from healthy skin. GLP‐1R expression was found in the blood of both healthy volunteers and psoriasis patients. No GLP‐1R expression was found in either stimulated or unstimulated cultured human keratinocytes. Our results show increased presence of GLP‐1Rs in psoriasis plaques and that this most likely is due to infiltration with immune cells. This offers a possible explanation for the positive effect of treatment with GLP‐1R agonists in patients with psoriasis.     

SF‐36 healty survey on psoriasis quality‐of‐life: A study of 414 Taiwanese patients

Psoriasis is a chronic debilitating disease that impairs patients' physical and social functioning. The assessment of health‐related quality of life (HRQoL) provides a comprehensive insight into the actual disease burden that are not captured by the traditional clinical parameters. The objective of this study is to identify factors that may impact patients' HRQoL. We conducted a cross‐sectional study, recruiting a total of 414 psoriasis vulgaris patients between January 2008 and December 2011. Our study found no significant correlation between disease severity or duration of psoriasis with HRQoL. Female patients have poorer HRQoL. Psoriatic arthritis, nail involvement, burning and itching sensation have a detrimental effect on HRQoL. This study highlighted that specific disease‐associated symptoms such as itching and burning sensation, nail involvement and/or concomitant arthritis were important factors that may impact patients' HRQoL devoid of clinical severity. Physicians should carefully consider these factors when treating psoriasis patients.     

Prevalence and characteristics of metabolic syndrome in South‐East Asian psoriatic patients: A case–control study

The prevalence of metabolic syndrome in Asian psoriatic patients compared with that of the general population shows variable results. This study aimed to examine the association between psoriasis and metabolic syndrome in a Thai population. This case–control study included 199 psoriatic patients and 199 controls matched for sex and age from the general Thai population. There were 111 men (55.8%) and 88 women (44.2%) in both the psoriatic and control groups. The mean age (± standard deviation) of both groups was 50.04 ± 13.81 and 49.96 ± 14.39 years (P = 0.91), respectively. The majority of psoriatic cases (82.9%) were of plaque type. The prevalence of metabolic syndrome was significantly higher in psoriatic patients than in the general population at 49.25% versus 30.65%. After controlling for age, sex, smoking and alcohol drinking the odds ratio was 2.25 (P < 0.0001). The metabolic components which were significantly higher in the cases than controls included hyperglycemia, high blood pressure (HBP) and abdominal obesity. No statistically significant difference was found between the cases and controls regarding prevalence of obesity, hypertriglyceridemia and low high‐density lipoprotein cholesterol. Thai psoriatic patients had a higher prevalence of metabolic syndrome than the general population. In conclusion, the prevalence of HBP, hyperglycemia and abdominal obesity was significantly higher in cases than in controls.     

Costs and quality of life in patients with moderate to severe plaque‐type psoriasis in Germany: A multi‐center study

Background: This study evaluated costs, disease severity and health‐related quality of life (QoL) in patients with moderate to severe plaque‐type psoriasis. Patients and Methods: Patients with a ‘psoriasis area and severity index’ (PASI) > 12 and/or a body surface area (BSA) > 10 were enrolled in dermatological practices and hospital outpatient departments (n = 184) and the total costs of illness generated during the last 12 months were retrospectively calculated. QoL was assessed using the SF‐36 and the DLQI. Participants were stratified into three subgroups according to the treatment received during the 1 year documentation period; a) patients without and b) patients with phototherapy or standard systemic therapy, and c) patients who had failed, were intolerant or had contraindications to at least two standard systemic therapies. The study was performed before biologics became available for the treatment of psoriasis in Germany. Results: Included patients had severe skin symptoms (mean PASI 18.2) and a highly impaired QoL (mean DLQI 10.6). Total annual costs amounted to € 6,709. Patients belonging to subgroup C had the most severe skin symptoms (mean PASI 22.2), the lowest QoL (mean DLQI 12.6), the highest hospitalization rate and largest loss of productivity.These patients produced the highest total costs of 8.831 €/y. Conclusions: Patients who cannot (or can no longer) be adequately managed with standard treatments are characterized by high disease activity, high costs and reduced QoL. Improved treatment options particularly for these patients are medically necessary and appear economically sensible.     

Distinguishing features of body mass index and psoriasis in men and women in Japan: A hospital‐based case–control study

Psoriasis is a chronic inflammatory disease and recent studies reported an association between obesity and psoriasis. To further investigate the association between body mass index (BMI) and psoriasis, a hospital‐based retrospective case–control study was conducted in patients at the Department of Dermatology, Fukuoka University Hospital in 1998–2012. BMI values of psoriatic patients were compared with those of controls, who had skin diseases other than psoriasis. A total of 429 psoriatic patients (295 male, 134 female) and 16 028 controls were enrolled. The number of male patients with psoriasis sharply increased in their 30s, peaked in their 50s and remained relatively high through the 60s. The number of female patients showed a gradual increase to their 60s. Mean BMI was higher in psoriatic patients (23.96 ± 4.46) than in controls (22.22 ± 3.98, P < 0.0001). Age‐stratified mean BMI in psoriatic patients was significantly higher at different ages in each sex. The odds ratio for psoriasis was significantly higher in obese patients. Stratified by age, there was a high odds ratio for psoriasis in men in their 40s, 70s and 80s, and in women in their 20s, 30s and 70s. The study suggests that, apart from those with a genetic predisposition, young women are less likely to develop psoriasis unless they have a high BMI, while men are more likely to acquire psoriasis if they have mild obesity in middle or older age. Our data may partially explain the higher male : female ratio (usually 2:1) in Japanese psoriatic patients.     

Incidence of tuberculosis infection in psoriatic patients on anti‐TNF therapy: report of a case series with 144 patients

Background Worldwide clinical trials and post‐marketing surveillance data have demonstrated an increased incidence of tuberculosis (TB) disease associated with antitumour necrosis factor (anti‐TNF) agents. The majority of these cases are presumed to result from a reactivation of latent disease, while the rate of new infections is unknown. A study was performed to evaluate the incidence of latent tuberculosis infection (LTBI) in psoriatic patients screened for biological therapy in a high‐incidence area, such as Madrid, Spain. Patients and methods One hundred and forty‐four patients with moderate‐to‐severe psoriasis treated with anti‐TNF agents were recruited. All of them were screened for active TB or LTBI before therapy. The screening included a detailed medical study, physical examination, chest X‐ray, tuberculin skin test (TST) with purified protein derivative and re‐TST. Results A total of 42 (29%) patients were diagnosed with LTBI based on a positive TST or re‐TST, and/or signs of past TB in the chest X‐ray. All of them received chemoprophylaxis with isoniazide. One patient developed a primary active lymphnode TB. Conclusion This is the first study to underscore the incidence of LTBI in patients with psoriasis treated with anti‐TNF therapy in the Spanish population. We support that the use of TST is still reliable and an effective diagnostic method for the detection of LTBI in anti‐TNF therapy.     

Expression of human leucocyte antigen‐G primarily targets affected skin of patients with psoriasis

Background The nonclassical human leucocyte antigen (HLA)‐G molecule has been well recognized as a tolerogenic molecule and few studies have evaluated the role of the molecule in inflammatory cutaneous autoimmune diseases. Objectives To evaluate the expression of HLA‐G in skin specimens of patients with psoriasis and to analyse its correlation with epidemiological and clinical variables. Methods Thirty untreated patients with psoriasis and 32 healthy individuals were enrolled. Immunohistochemistry was applied to identify HLA‐G expression in formalin‐fixed paraffin‐embedded cutaneous skin biopsies. Results Soluble and membrane‐bound HLA‐G expression was detected in 30 (90%) of the skin specimens from patients presenting clinical and histopathological features of psoriasis. Although infiltrating lymphomononuclear cells of the dermis exhibited HLA‐G expression, the epidermis was primarily targeted. HLA‐G expression was also observed in 27% (three of 11) of the specimens that exhibited no clinical and histopathological features of psoriasis (nonaffected areas). In contrast, skin specimens obtained from healthy individuals exhibited no HLA‐G expression (P < 0·0001). The intensity of HLA‐G expression was not associated with type I/II psoriasis, Psoriasis Area and Severity Index score or clinical forms. Conclusions As the HLA‐G molecule was consistently expressed in affected and, to a lesser extent, in nonaffected areas of untreated patients with psoriasis, irrespective of the severity of the clinical variants, one may hypothesize that the presence of HLA‐G may be responsible, at least in part, for the regulation of autoimmune effector cells.     

Possible association of hepatitis C virus infection with late‐onset psoriasis: A hospital‐based observational study

Psoriasis is a chronic inflammatory disease mainly involving the skin and joints, mediated by pro‐inflammatory cytokine tumor necrosis factor (TNF)‐α. In hepatitis C, continuous inflammation mediated by TNF‐α leads to liver cirrhosis and diabetes mellitus. Hence, psoriasis and hepatitis C have pathophysiological factors in common. An epidemiological association between the two conditions has been reported, but no detailed research has yet been performed. Frequency of hepatitis C virus (HCV) infection was assessed in 717 patients with psoriasis and 38 057 with all other dermatological diseases who visited Fukuoka University Hospital in 1998–2011. HCV⁺ and HCV^? psoriatic patients were further compared. Frequency of HCV infection was significantly higher in psoriasis (7.5%) than in controls (3.3%) in overall ages. When stratified by age at the first visit, the frequency was significantly higher in patients with psoriasis than in controls aged in their 60s (11.8% vs 6.6%, respectively, P = 0.0215) and 70s (19.5% vs 7.3%, P < 0.0001). HCV⁺ psoriatic patients were significantly older at onset than HCV^? ones (median, 54 vs 39 years), stronger male predominance (male/female ratio, 4.4:1), similar family history of psoriasis, higher association of diabetes mellitus and hypertension, and significantly lower body mass index (22.4 ± 2.73 vs 24.2 ± 4.61), in age‐stratified (≥40 years) analysis. HCV⁺ psoriatic patients were less obese, but still had a higher frequency of diabetes mellitus and hypertension, possibly due to chronic inflammation in the liver and other organs. HCV infection may trigger psoriasis, especially late‐onset psoriasis, possibly via overproduction of TNF‐α, a common mediator of the two conditions.