Prevalence of physical symptoms of itch, pain and fatigue in patients with skin diseases in general practice

BACKGROUND: Physical symptoms of skin diseases have been shown to negatively affect patients' wellbeing. Although insight into physical symptoms accompanying skin diseases is relevant for the management and treatment of skin diseases, the prevalence of physical symptoms among patients with skin diseases is a rather unexplored territory. OBJECTIVES: The goal of the present study was to examine the prevalence of physical symptoms of itch, pain and fatigue in patients with skin diseases. METHODS: On the basis of a systematic morbidity registration system in primary care, questionnaires were sent to 826 patients with skin diseases. Eventually, questionnaires from 492 patients were suitable for our analyses. RESULTS: Results indicated that patients with skin diseases particularly experience symptoms of itch and fatigue. Approximately 50% of all patients report experiencing these symptoms and about 25% experience these symptoms as relatively severe. Pain was relatively less frequently reported by 23% of all patients, and was on average somewhat less intense. The physical symptoms showed relatively strong correlations with disease-related quality of life and self-reported disease severity. In contrast, only moderate correlations were found with comorbidity and demographic variables, which suggests that the physical symptoms of itch, pain and fatigue are consequences of the skin diseases. CONCLUSIONS: Itch and fatigue and, to a somewhat lesser extent, pain have a high prevalence among patients with skin diseases. Clinicians should be encouraged to carefully assess itch, pain and fatigue in patients with skin diseases, and where appropriate focus treatment to these symptoms.     

Psyche, opioids, and itch: therapeutic consequences

ABSTRACT:  A patient's psychological condition can substantially affect the presence and severity of pruritus, a phenomenon thought to be mediated by the central nervous system's (CNS) opioid neurotransmitter system. Specific psychodermatologic disorders associated with psychogenic pruritus, including depression, anxiety, chronic tactile hallucinations, delusions of parasitosis, neurotic excoriations, and other cutaneous compulsions are likely controlled by this pathway. Therefore, in treating these conditions, medications specifically directed at the CNS can be the most effective therapies, whereas topical and supportive therapy may be important adjuncts in targeting the associated pruritus. Furthermore, the impact of an understanding clinician and a good physician–patient relationship cannot be underestimated in determining ultimate prognosis. This review will begin by discussing the relationship between the psyche and pruritus as well as the opioid neurotransmitter system. Following this, several disorders characterized by psychogenic pruritus will be described, and CNS-specific and adjunctive topical and supportive therapies for these conditions will be detailed.     

Preclinical and human surrogate models of itch

Pruritus, or simply itch, is a debilitating symptom that significantly decreases the quality of life in a wide range of clinical conditions. While histamine remains the most studied mediator of itch in humans, treatment options for chronic itch, in particular antihistamine‐resistant itch, are limited. Relevant preclinical and human surrogate models of non‐histaminergic itch are needed to accelerate the development of novel antipruritics and diagnostic tools. Advances in basic itch research have facilitated the development of diverse models of itch and associated dysaesthesiae. While experimental itch in humans is induced over a short period of time and usually assessed psychophysically, the study of itch reactions in animals allows for both short‐term and long‐term studies but relies heavily on behavioural assessments. This review provides a background and a presentation of the established models of itch currently applied in animals and humans with emphasis on translatability.     

A novel player in the field: Merkel disc in touch,itch and pain

The mechanosensitive Merkel cell‐neurite complex comprising two distinct cell types in both hairy and glabrous skin has been widely recognized as touch receptor for more than 100 years. In 2014, three elegant studies further demonstrated that the Merkel cell‐neurite complex mediates touch transduction via the mechanosensitive Piezo2 channel. However, whether it is involved in genesis of itch and pain sensations, has been unclear. Recently, we reported that Merkel cells modulate the development of mechanical itch under the conditions of dry skin and aging, whereas two other studies demonstrated that Piezo2 channel mediates mechanical pain. In this assay, we summarized the current knowledge of Merkel disk under both normal and pathological conditions, with a focus on its role in touch, itch, and pain.     

Generalized and symptom-specific sensitization of chronic itch and pain

Background Physicians are frequently confronted with patients reporting severe itch and pain. Particularly in patients suffering from persistent itch and pain, central and peripheral sensitization processes are assumed to be involved in the long‐term maintenance and aggravation of the symptoms. The present study explores generalized and symptom‐specific sensitization processes in patients suffering from persistent itch and pain. Specifically, it examines whether patients with chronic itch and pain are more sensitive to somatosensory stimuli (generalized sensitization) and simultaneously perceive somatosensory stimuli as a symptom of their main physical complaint, e.g. pain in chronic pain patients (symptom‐specific sensitization). Methods Thresholds for different mechanical and electrical sensory stimuli of Quantitative Sensory Testing were determined in 15 female patients suffering from chronic itch associated with atopic dermatitis, 15 female chronic pain patients diagnosed with fibromyalgia, and 19 female healthy controls. Intensities of itch and pain sensations were rated on a visual analogue scale. Results As expected, the patient groups had significantly lower tolerance thresholds for the somatosensory stimuli applied than the healthy controls, supporting generalized sensitization. Moreover, patients with chronic itch consistently reported more itch, while patients with chronic pain partly reported more pain in response to analogous somatosensory stimuli than the healthy controls and the other patient group, indicating symptom‐specific sensitization. Conclusion The present study provides preliminary support that both generalized and symptom‐specific sensitization processes play a role in the regulation and processing of somatosensory stimulation of patients with chronic itch and pain.     

Itching for an answer: A review of potential mechanisms of scalp itch in psoriasis

Scalp psoriatic itch is a common complaint and often poses a therapeutic challenge. The pathophysiology of this phenomenon is unclear. The unique anatomy of the scalp contains richly innervated hair follicles, abundant vasculature and perifollicular inflammatory cytokines which may all contribute to this common sensory complaint. The mast cell, in particular, is portrayed as one of the main itch conductors for its ability to trigger neurogenic inflammation, activate the peripheral hypothalamic‐pituitary‐adrenal‐axis, process and integrate itch signalling through its interactions with the scalp hair follicles. Herein, we explain and speculate upon potential mechanisms underlying itchy scalp psoriasis, involving interconnections between the neuroimmune, neurovascular and neuroendocrine systems. Many factors may play roles in itchy scalp psoriasis including the scalp hair structure, immune system, endocrine system, nervous system and vascular system. These may warrant further exploration as therapeutic targets that go beyond the application of mere anti‐inflammatory agents.     

Are itch and scratching the nausea and vomiting of skin?

The physiologic similarities between itch and nausea may not be evident initially, but they share the role of repelling irritants and toxins from the body by inducting scratching and vomiting, respectively. In addition, itch and nausea frequently occur together in certain conditions such as uraemia. Here we show that the mechanisms underlying itch and nausea overlap and that advances in either field may influence the identification of novel drug targets, particularly for itch.     

Effects of family constellation seminars on itch in patients with atopic dermatitis and psoriasis: A patient preference controlled trial

Family dynamics play a major role in itch related dermatoses. The aim of the study was to evaluate the effectiveness of family constellation seminars (FCS) in the decrease of itch in atopic dermatitis (AD) and psoriasis. Thirty‐one adult patients with chronic itch (16 with AD and 15 with psoriasis) were allocated to intervention group (FCS + G) and control group (CG). Patients from FCS + G have participated in a series of four FCS for 3 months. During the study period, all patients used only emollients. Itch was evaluated by 27‐item questionnaire and skin condition was evaluated by SCORAD and PASI. The severity of itch in FCS + G decreased (Median; (25%;75%)) from 8.42 (6.57;11.92) initially to 4.78 (1.36;9.14); p < .01 after 1 month and (0.61 (0;6.66); p < .001) after 9 months after the psychological intervention with no significant changes in the CG. In the patients with AD in the FCS + G, SCORAD decreased (21.5 (14.4;40); 14.1 (7.3;15.5) p < .05; 7.2 (3.6;11); p < .05). In the FCS + G, itch decreased both in patients with AD and psoriasis, with less significant visible changes of skin in patients with psoriasis. Participation in FCS in a series of four seminars has high effect (r = .53) on reduction of itch and high effect (r = .74) on improvement of AD signs with lower effect on skin condition in patients with psoriasis for 4 months. Positive effect of FCS gradually increases during at least 9 months. Further studies for understanding FCS influence on the patients with itch are needed.     

温针灸治疗功能性早泄的疗效观察

目的:观察温针灸治疗功能性早泄的疗效。方法:采用温针灸治疗功能性早泄42例,辨证分为肝气郁结型与肾精亏虚型,并进行分型治疗。结果:42例患者总有效率为83.3%。观察表明患病年纪越轻,早泄治疗效果越好;年纪越大,治疗效果越差。患病时间越短,早泄治疗效果越好;时间越长,治疗效果越差。结论:温针灸治疗功能性早泄疗效可靠。     

Cutaneous manifestations of COVID‐19: A review of the published literature

COVID‐19 is a highly contagious respiratory tract infection caused by severe acute respiratory syndrome coronavirus 2. COVID‐19 outbreak, which caused thousands of deaths, has been declared a pandemic by the World Health Organization in March 2020. The infection has been reported to demonstrate different types of cutaneous manifestations including urticarial, maculopapular, papulovesicular, purpuric, livedoid, and thrombotic‐ischemic lesions. Given the high mortality rate of the infection, timely and accurate identification of relevant cutaneous manifestations may play a key role in the early diagnosis and management. In this study, we provide a review with a focus on the reported cutaneous manifestations of COVID‐19.     

Ethnic differences in pain,itch and thermal detection in response to topical capsaicin: African Americans display a notably limited hyperalgesia and neurogenic inflammation

Background Topical application of capsaicin commonly produces burning, stinging and itching as well as hyperalgesia to heat stimuli via activation of transient receptor potential vanilloid subtype 1. Objectives To investigate whether there are differences in sensory response and neurogenic inflammation to topical capsaicin in four different ethnic populations with different skin types. Methods The study was performed in 40 healthy subjects consisting of 10 African Americans, 10 East Asians, 10 Hispanics and 10 Caucasians. Warmth sensation and heat pain detection thresholds, as well as pain intensity, were measured before and after application of capsaicin or placebo on forearms along with skin blood flow and the extent of the flare reaction. Results In African Americans the heat pain detection threshold, pain intensity and skin blood flow did not change significantly after capsaicin application, while in the other three ethnic groups a significant change occurred characterized by hyperalgesia and vasodilatation. The postcapsaicin warmth sensation threshold increased in African Americans and decreased in Hispanics, the latter also uniquely experiencing postcapsaicin itch. Conclusions Our observations indicate that African Americans display a limited hypersensitivity following topical capsaicin, compared with the three other ethnic groups.     

Itchy body: Topographical difference of itch and scratching and C Nerve fibres

Itch, also known as pruritus, is an unpleasant sensation that results in an urge to scratch. We can feel itch at any location where itch occurs from the top of the head to the toes. However, there are topographical differences in itch intensity. Itch is mainly conducted by C nerve fibres from the skin where itch emanates to the central nervous system. However, the abundancy of C fibres does not necessarily lead to higher itch intensity. Interestingly, reduction and/or structural changes in C fibres seem to play a role in itch sensation. In addition, C tactile fibres (CT afferents), which are activated by gentle “affective” touch and seem to be associated with scratching pleasurability and the reward system in the brain, can be involved in itch sensation and topographical differences of itch.     

Coping as mediator of the relationship between stress and itch in patients with atopic dermatitis: a regression and mediation analysis

Even though it has been shown that stress and itch are associated in patients with atopic dermatitis (AD), it remains unclear whether this relationship occurs due to certain coping strategies being activated under stress. Therefore, this study investigates the role of coping as possible mediating factor between stress and itch in 31 patients with AD. Coping and itch were assessed by self‐reported measures, while stress was measured both by a validated questionnaire and by a physiological stress marker, the postawakening cortisol. Using a regression and a mediation analysis, this study showed a relationship between perceived stress and itch (corrected R² = 0.21), which was fully mediated by negative itch‐related cognitions. 62.3% of the variance of itch intensity could be explained by negative itch‐related cognitions. This finding helps to explain the positive effects of cognitive restructuring in the treatment of chronic itch.     

Production of acute and chronic itch with histamine and contact sensitizers in the mouse and guinea pig

Itch is a major symptom of skin disease and is poorly understood, in part due to the lack of adequate small animal models. We show, using iontophoresis of histamine and capsaicin, that it is possible to induce scratching behaviour in both guinea pig and mouse. Use of iontophoresis may obviate the problems of induction of pain as well as itch when injection is used. The behavioural response to capsaicin, however, differs from that seen with histamine, raising the possibility that the use of scratch counts as a method of measuring itch severity needs to be set in the context of other responses. Naloxone partly inhibits scratching in mouse and guinea pig due to histamine. We also show that contact sensitization with 2-4 dinitrochlorobenzene (DNCB) can be used as a simple assay for chronic itch allowing study of scratching over at least a 15-h period. The characteristics of scratching (but not the time course) induced with DNCB are similar to those seen with histamine.     

Adult‐onset inflammatory linear verrucous epidermal nevus: Immunohistochemical studies and review of the literature

Adult‐onset inflammatory linear verrucous epidermal nevus (ILVEN) is an uncommon cutaneous disease compared to childhood‐onset ILVEN. The typical histopathologic features are alternating parakeratosis and orthokeratosis with an absent granular layer underneath parakeratosis, in contrast to a thickened granular layer below the foci of orthokeratosis in psoriasiform epidermal hyperplasia. Herein, we present a 49‐year‐old woman with typical clinical and histopathologic characteristics of adult‐onset ILVEN, including linear arrangement of thick scaly papules and plaques localized on the medial side of her right leg, ankle, and foot. Immunohistochemical studies included involucrin, Ki‐67, and keratin‐10. Compared to the staining pattern in psoriasis, the expression of involucrin in this case was of lower intensity and localized to upper epidermal layers with relatively less extensive staining beneath regions of parakeratosis as compared to orthokeratosis; Ki‐67 showed lower basal layer proliferative activity; and keratin‐10 showed a greater intensity of staining within suprabasal epidermis.