Neuropeptides and their receptors in psoriatic skin in relation to pruritus

BACKGROUND: Pruritus in patients with psoriasis has been reported to be more common than previously thought. OBJECTIVES: To determine the actual prevalence of pruritus in psoriasis according to severity of psoriasis and to verify the hypothesis of involvement of neuropeptides and their receptors in psoriatic pruritus. METHODS: We analysed questionnaire replies from 152 patients with chronic plaque-type psoriasis and we assayed the expression of neuropeptides and their receptors in lesional skin biopsies obtained from psoriatic patients with pruritus compared with those from psoriatic patients without pruritus, nonlesional skin of patients with pruritic psoriasis and normal controls by confocal laser scanning microscopy. RESULTS: Of the 152 patients with psoriasis, 112 (73.7%) had pruritus, and these patients had a higher mean Psoriasis Area and Severity Index (PASI) score than psoriatic patients without pruritus. There was positive correlation between the PASI score and the intensity of pruritus. Keratinocytes in the psoriatic plaques of patients with pruritus showed consistently increased expression of substance P receptor (SPR), high-affinity nerve growth factor receptor (TrkA) and calcitonin gene-related peptide receptor (CGRPR). CONCLUSIONS: Pruritus is a common feature in psoriasis. Considering the well-known roles of neuropeptides in pathogenesis of both psoriasis and pruritus, increased SPR, TrkA and CGRPR may be involved in the pathogenesis of pruritus in psoriasis and in the severity of psoriasis.     

Patients' perspective of pruritus in chronic plaque psoriasis: a questionnaire-based study

Background  Pruritus in psoriasis patients has not been regarded as a major symptom.
Objective  To study the pattern of pruritus in chronic plaque psoriasis.
Methods  A questionnaire was sent out to 109 patients with a diagnosis of chronic plaque psoriasis, who attended our outpatient departments during the period of January 2006 to January 2007.
Results  Out of 109 patients, 80 patients (74%) answered the questionnaire. Pruritus was found in 80% of the patients, with an intensity of 5.2 ± 2.6 (±SD) using a visual analogue scale (0–10). The frequency and intensity of pruritus were higher in women. Lower leg and scalp were reported to be the most commonly affected sites. Major aggravating factors for pruritus were stress and dryness of skin. Sun, sleep and vacation could relieve pruritus. The most common antipruritic treatments used by the patients were topical steroids, topical vitamin D, emollients and ultraviolet light therapy, whereas antihistamines were used by a small number of patients. Mood, concentration and sleep were negatively affected by pruritus.
Conclusion  Pruritus is a common symptom in patients with chronic plaque psoriasis.     

Relationship between anger and pruritus perception in patients with chronic idiopathic urticaria and psoriasis

Background  There is evidence that chronic idiopathic urticaria (CIU) and psoriasis are associated with personality based difficulties in emotional regulation particularly with regard to the feeling of anger. This deficit in emotional awareness could lead to the phenomenon that emotions are rather experienced in bodily symptoms such as pruritus.
Aim  We investigated whether there is a relationship between pruritus as major symptoms in CIU and psoriasis and the experience of negative emotions.
Setting  Forty-one CIU patients and 44 psoriasis patients treated at Bonn University Hospital and 49 healthy controls were included.
Method  Patients and controls were compared on questionnaires measuring alexithymia (TAS-20), emotional distress (SCL-90-R) and anger (STAXI). In skin-disordered patients, separate stepwise regressions with pruritus severity as dependent variable and questionnaires, skin status, duration, sex and age as independent variables were calculated.
Results  CIU and psoriasis patients showed higher alexithymia, emotional distress, depression, anxiety and state anger compared with controls. State anger was the only significant predictor of pruritus severity in CIU explaining 19% of variance. Depression was the only significant predictor of pruritus severity in psoriasis explaining 12% of variance.
Conclusions  Our findings suggest a relationship between pruritus severity and anger in CIU. Furthermore, our results indicate a relationship between pruritus severity and depression in psoriasis.     

Brachioradial pruritus successfully treated with gabapentin

Brachioradial pruritus (BRP) is a mysterious entity characterized by localized pruritus of the dorsolateral aspect of the arm. The precise etiology of BRP remains unknown, but sun exposure and/or cervical spine lesions seem to be triggering or at least aggravating factors. Many treatment alternatives including non‐steroidal anti‐inflammatory drugs, topical capsaicin, topical corticosteroids, photoprotection, carbamazepine and acupuncture have been used with different success rates. Recently, gabapentin, an antiepileptic agent, has been reported to be an effective therapeutic agent in BRP. Herein, we report a 64‐year‐old man with BRP who showed good response to gabapentin therapy.     

Drug survival of biologic agents for psoriatic patients in a real-world setting in Japan

This is a Japanese retrospective single-center study carried out between 1 January 2010 and 21 November 2018 at the Department of Dermatology in Jichi Medical University Hospital. The drug survival rate for six biologic agents used for the treatment of psoriasis was investigated. We reviewed the clinical records of 315 treatment series of 205 patients with moderate to severe psoriasis treated with adalimumab (103 cases), infliximab (70 cases), ustekinumab (66 cases), secukinumab (38 cases), brodalumab (12 cases) and ixekizumab (26 cases). In our study, ustekinumab revealed a trend towards higher drug survival among the six biologic agents. Ustekinumab had a higher drug survival rate than infliximab and secukinumab with significant differences by log–rank test among all patients and among biologic-naive (bio-naive) patients. There was no significant difference in drug survival between bio-naive and biologic-experienced (non-naive) patients in the treatment courses with adalimumab, infliximab, ustekinumab, secukinumab and ixekizumab. The dose augmentation therapy in infliximab-treated patients was associated with longer drug survival. Of all patients, 25 cases with generalized pustular psoriasis (GPP) were included, who functioned as the negative predictor for drug persistence with a hazard ratio of 1.87 (95% confidence interval, 1.12–3.11; P = 0.016). Our results reveal that ustekinumab had a superior drug survival, which is supported by the previous studies. Further studies are needed to clarify the efficacy of biologic agents on patients with GPP.     

银屑病患者自身免疫性甲状腺炎调查分析

目的:调查我院银屑病患者中自身免疫性甲状腺炎的发生率。方法:纳入157例银屑病患者和年龄、性别及BMI相匹配的100例对照病例(非炎症性皮肤病患者)进行回顾性分析,测定三碘甲状腺原氨酸(T3)、甲状腺素(T4)、促甲状腺激素(TSH)、甲状腺球蛋白(TG)、甲状腺球蛋白抗体(TGAb)、抗甲状腺过氧化物酶抗体(TPOAb)水平。其中,TGAb和(或)TPOAb阳性界定为自身免疫性甲状腺炎。比较两组中自身免疫性甲状腺炎的发生率、甲状腺激素水平,并进行危险因素分析。结果:银屑病组中自身免疫性甲状腺炎发生率高于对照组(11.5%vs 9%),但两组间无明显差异(x~2=0.40,P>0.05)。银屑病中自身免疫性甲状腺炎的发生与发病年龄、病程、PASI评分和肥胖无关(P值均>0.05)。银屑病中血清TT3、FT3和TSH水平显著高于对照组(P<0.05),差异有统计学意义。结论:银屑病患者与正常人群相比,发生自身免疫性甲状腺炎的风险无增加;但血清T3可能在银屑病发病中发挥作用。     

An epidemiology study of patients with uremic pruritus

BACKGROUND: Pruritus is a common problem in continuous ambulatory peritoneal dialysis (CAPD) and haemodialysis patients. There are few studies on the clinical characteristics of uremic itch, the cause of which is still unknown. OBJECTIVES: The aim of this study was to define the prevalence and clinical characteristics of pruritus in CAPD and haemodialysis patients. METHODS: A questionnaire was used to evaluate pruritus in 52 CAPD and 289 haemodialysis patients in two dialysis units. The relationship of various factors and medical parameters to itch was examined. RESULTS: Of the 341 patients, 177 (51.9%) had pruritus at the time of examination, 97 (28.4%) had pruritus in the past. Pruritus was present in 145 (50.2%) of the haemodialysis patients and 32 (61.5%) of the CAPD patients. Men, patients with liver disease, and patients with pruritus before starting dialysis treatment were more likely to have uremic pruritus. CONCLUSIONS: This study showed us that uremic pruritus was observed more in men than women. The high prevalence of uremic pruritus in our study does not support the decrease of pruritus due to an improvement in the management of dialysis patients.     

Body mass index in psoriatic patients with or without familial psoriasis

Psoriasis is a chronic inflammatory disease caused by both genetic and environmental factors. The occurrence of psoriasis in family members indicates a genetic predisposition, while obesity is also a major contributor to psoriasis. We examined whether patients with versus without familial psoriasis were obese at the onset of psoriasis. Clinical information, including age at onset, age at first visit and body mass index (BMI) at first visit, was extracted from the Fukuoka University Psoriasis Registry. To compare BMI, patients aged 10 years or older who visited the clinic within 3 years of onset were selected. Familial psoriasis was observed in 27 patients (15 male, 12 female) out of 428 individuals (264 male, 164 female) with psoriasis, accounting for 6.3% of cases. Age at onset was younger for both men and women with familial psoriasis (34 ± 17 and 40 ± 15 years, respectively) relative to those with non-familial psoriasis (48 ± 19 and 53 ± 19 years, respectively). We examined age- and sex-adjusted average values of BMI at initial presentation after onset of psoriasis, finding that patients with familial psoriasis had lower BMI (22.0 kg/m² [95% confidence interval, 21.8–22.4]) than those with non-familial psoriasis (23.2 [23.1–23.3], P < 0.001). Individuals with a family history of psoriasis should be considered to be at risk for developing the disease even if obesity is not present.     

伴发代谢综合征的银屑病患者临床特征分析

1998年WHO将一组具有共同病理生理基础的代谢异常的病症正式命名为代谢综合征(metabolic syndrome)[1],主要包括糖耐量受损、脂代谢紊乱、高血压、肥胖、微量白蛋白尿等.银屑病除累及皮肤外,常伴发糖尿病、高脂血症、高血压等.     

Efficacy and safety of secukinumab in a psoriatic patient affected by comorbid metabolic disorders

Psoriasis is a common, chronic, immune‐mediated disease occurring more frequently in association with comorbid metabolic disorders. The management of patients with multiple organ dysfunction is challenging since the use of all conventional systemic agents is limited or contraindicated. In the last two decades, the introduction of biological drugs has revolutionized treatment paradigms of psoriasis and enabled numerous patients to achieve disease control with an acceptable safety profile. We reported for the first time the case of a 66‐year‐old female psoriatic patient affected by myocardial infarction, hypertension, chronic renal failure, hyperthyroidsm and morbid obesity, who experienced remarkable improvement in skin and joint synthoms and metabolic parameters after 48 weeks of secukinumab monotherapy. In our patient, secukinumab was well tolerated and no side effects have been observed. Our observation suggests that secukinumab could be a safe therapeutic option in patients with organ impairment or failure in which the majority of conventional systemic agents are contraindicated.     

Enhancement of monocyte chemotactic activity in the sera of psoriatic patients after heat treatment

The chemotactic activity for neutrophils and monocytes was examined in the sera of psoriatic patients and healthy controls using a Boyden chamber method. There were no significant differences in neutrophil chemotactic activity between the sera of psoriatic patients and healthy controls. However, the monocyte chemotactic activity of psoriatic serum was lower than that of control serum. Furthermore, there was a significant increase in the monocyte chemotactic activity of psoriatic sera after heat treatment (42°C, 1 hr). These results suggest that psoriatic serum has a defect of monocyte chemotaxis which can be corrected, in part, by heat treatment.     

Risk factors associated with having psoriatic arthritis in patients with cutaneous psoriasis

The aim of this study was to determine if the following characteristics were associated with the presence of psoriatic arthritis in a sample of psoriasis patients: race, family history of psoriasis and psoriatic arthritis, age of onset of psoriasis, smoking, alcohol consumption and the maximum body surface area (BSA) affected by psoriasis. This was a case–control study involving 400 psoriasis patients who attended the Psoriasis and Photo‐medicine clinic in the National Skin Center of Singapore over a 1‐year period. Cases were psoriasis patients with psoriatic arthritis while controls were psoriasis patients without psoriatic arthritis. The diagnosis of psoriatic arthritis was made by rheumatologists and participants completed a self‐administered standardized questionnaire. The maximum BSA involved was determined from the case notes. Psoriatic arthritis was not significantly associated with sex, race, age of onset of psoriasis, a family history of psoriasis, smoking and alcohol consumption but was significantly associated with a family history of psoriatic arthritis (P < 0.001) and the maximum body surface involved (P = 0.05). Using multivariate analysis to control for variables, the presence of psoriatic arthritis was significantly associated with a family history of psoriatic arthritis (odds ratio [OR] = 20.5; 95% confidence interval [CI] = 2.49–169.10) and the maximum BSA involved (OR = 2.52; 95% CI = 1.33–4.75). Indian psoriatic patients were more likely to have psoriatic arthritis compared to the other races. A family history of psoriatic arthritis and a greater maximum body surface involved may be associated with having psoriatic arthritis in this study population of psoriasis patients.     

Hyperuricemia is an independent risk factor for psoriatic arthritis in psoriatic patients

Psoriatic arthritis (PsA) is a spondyloarthritic condition mainly seen in patients with psoriasis. Psoriatic patients with plaques on the scalp, gluteal fold or nail lesions are known to develop PsA more frequently, but other markers for PsA have not yet been identified. To determine which psoriatic patients are at greatest risk of developing PsA, psoriasis vulgaris (PsV) patients who visited the Department of Dermatology, Fukuoka University Hospital in 2015 were enrolled. Patients with and without PsA were statistically compared with respect to age, sex, age at onset, body mass index (BMI), smoking and drinking habits, familial history of psoriasis and comorbidities. Of 331 patients (237 men, 94 women), 55 had PsA (17%; 39 men, 16 women). PsA patients had significantly higher frequencies of nail lesions (PsA vs PsV‐only, 62% vs 29%; P < 0.0001) and hyperuricemia (PsA vs PsV‐only, 22% vs 9%; P = 0.01). These were confirmed as independent risk factors for PsA by logistic regression analysis, with odds ratios of 5.05 for nail lesions (P < 0.0001) and 4.18 for hyperuricemia (P < 0.01). There was no difference in age at onset, sex, BMI and incidence of diabetes mellitus, hypertension or dyslipidemia. Hyperuricemia is also known to be more frequent in psoriatic subjects than the normal population. Uric acid crystals are a strong stimulator of innate immunity. Considering that none of our cohort had gouty arthritis, hyperuricemia may increase uric acid crystallization in and around joints, thereby inducing PsA in psoriatic subjects. Hyperuricemia appears to be an independent risk factor for PsA.