Prurigo Simplex or "Itchy Red Bump" Disease: Review and Case Series.

Prurigo simplex or "itchy red bump" disease is a controversial pruritic papular eruption. The objective of this study was to delineate the diagnostic criteria for this disease. A PubMed search was performed for: "prurigo simplex", "prurigo simplex subacuta", "subacute prurigo", "chronic papular dermatitis in adults" and "itchy red bump disease". Medical charts of patients with prurigo diagnoses in a university setting were analysed. The literature search revealed 32 relevant studies (431 patients) on different aspects of the disease. Out of 50 patients with prurigo diagnoses, 5 patients (4 women, mean age at onset 54 years) matched the description in literature. Small, severely itchy papules without secondary skin lesions continued to appear for years (mean 5.6 years). Skin biopsies revealed lymphocytic perivascular infiltrates, few eosinophils and occasionally spongiosis. Treatment with long-term metho-trexate or cyclosporine cleared the symptoms. Some major and minor diagnostic criteria for prurigo simplex are proposed and compared with chronic prurigo.

Lung Mast Cells Have a High Constitutive Expression of Carboxypeptidase A3 mRNA That Is Independent from Granule-Stored CPA3.

The mast cell granule metalloprotease CPA3 is proposed to have important tissue homeostatic functions. However, the basal CPA3 mRNA and protein expression among mast cell populations has remained poorly investigated. Using a novel histology-based methodology that yields quantitative data on mRNA and protein expression at a single-cell level, the present study maps CPA3 mRNA and protein throughout the MCT and MCTC populations in healthy skin, gut and lung tissues. MCTC cells had both a higher frequency of CPA3 protein-containing cells and a higher protein-staining intensity than the MCT population. Among the tissues, skin MCs had highest CPA3 protein intensity. The expression pattern at the mRNA level was reversed. Lung mast cells had the highest mean CPA3 mRNA staining. Intriguingly, the large alveolar MCT population, that lack CPA3 protein, had uniquely high CPA3 mRNA intensity. A broader multi-tissue RNA analysis confirmed the uniquely high CPA3 mRNA quantities in the lung and corroborated the dissociation between chymase and CPA3 at the mRNA level. Taken together, our novel data suggest a hitherto underestimated contribution of mucosal-like MCT to baseline CPA3 mRNA production. The functional consequence of this high constitutive expression now reveals an important area for further research.

Chronic Nodular Prurigo: A European Cross-sectional Study of Patient Perspectives on Therapeutic Goals and Satisfaction.

Chronic nodular prurigo is characterized by recalcitrant itch. Patient perspectives on therapeutic goals, satisfaction with therapy and efficacy of therapeutic regimens for this condition are unknown. This questionnaire study examined these issues in 406 patients with chronic nodular prurigo from 15 European dermatological centres. Improvements in itch, skin lesions and sleep were the most important goals. Emollients, topical corticosteroids and antihistamines were the most frequently used treatments, while a minority of patients were prescribed potent medications, such as systemic immunosuppressants and gabapentinoids. Most patients were not satisfied with their previous therapy (56.8%), while 9.8% did not receive any therapy despite having active disease. A substantial number of respondents (28.7%) considered none of the therapeutic options effective. Although chronic nodular prurigo is a severe disease, most patients were not treated with potent systemic drugs, which may contribute to the high levels of dissatisfaction and disbelief in available therapies. Specific guidelines for chronic nodular prurigo and the development of novel therapies are necessary to improve care.

European S2k Guideline on Chronic Pruritus.

Pruritus is a frequent symptom in medicine. Population-based studies show that every 5th person in the general population has suffered from chronic pruritus at least once in the lifetime with a 12-month incidence of 7%. In patient populations its frequency is much higher depending on the underlying cause, ranging from around 25% in haemodialysis patients to 100% in skin diseases such as urticaria and atopic dermatitis (AD). Pruritus may be the result of a dermatological or non-dermatological disease. Especially in non-diseased skin it may be caused by systemic, neurological or psychiatric diseases, as well as being a side effect of medications. In a number of cases chronic pruritus may be of multifactorial origin. Pruritus needs a precise diagnostic work-up. Management of chronic pruritus comprises treatment of the underlying disease and topical treatment modalities, including symptomatic antipruritic treatment, ultraviolet phototherapy and systemic treatment. Treating chronic pruritus needs to be targeted, multimodal and performed in a step-wise procedure requiring an interdisciplinary approach. We present the updated and consensus based (S2k) European guideline on chronic pruritus by a team of European pruritus experts from different disciplines. This version is an updated version of the guideline that was published in 2012 and updated in 2014 (www.euroderm.org).

Definition of Sensitive Skin: An Expert Position Paper from the Special Interest Group on Sensitive Skin of the International Forum for the Study of Itch.

Sensitive skin is a frequent complaint in the general population, in patients, and among subjects suffering from itch. The International Forum for the Study of Itch (IFSI) decided to initiate a special interest group (SIG) on sensitive skin. Using the Delphi method, sensitive skin was defined as "A syndrome defined by the occurrence of unpleasant sensations (stinging, burning, pain, pruritus, and tingling sensations) in response to stimuli that normally should not provoke such sensations. These unpleasant sensations cannot be explained by lesions attributable to any skin disease. The skin can appear normal or be accompanied by erythema. Sensitive skin can affect all body locations, especially the face". This paper summarizes the background, unresolved aspects of sensitive skin and the process of developing this definition.

Topical non-peptide antagonists of sensory neurotransmitters substance P and CGRP do not modify patch test and prick test reactions: a vehicle-controlled, double-blind pilot study.

Immunologic responses in the skin can be modulated by such neurotransmitters of sensory nerve fibers as substance P (SP) and calcitonin gene-related peptide (CGRP). The first-generation receptor antagonists were peptides with large molecules and had to be injected intracutaneously. The aim of this study was to examine the topical effects of non-peptide antagonists to substance P (aprepitant) and CGRP (telcagepant), respectively, on delayed and immediate reactions in the skin and on associated pruritus. A lipophilic formulation of aprepitant 5% and a hydrophilic formulation of telcagepant 1% were developed. Their effect on the skin barrier was measured in terms of transepidermal water loss (TEWL) while permeation was calculated using permeation coefficients. Patch tests in patients allergic to nickel and prick test reactions to histamine were used as models. None of the treatments increased TEWL, suggesting there to be no impairment of the skin barrier. Permeation coefficients indicated moderate permeation. Histamine prick tests induced a flare with a mean area of 662 + 275 mm(2) and a weal with a mean volume of 49 + 11 mm(3). These reactions as well as histamine-induced pruritus were not affected significantly by any of the treatments. Treatment with aprepitant and its vehicle alone resulted in a potentiating of the infiltration of nickel reactions compared with test reactions obtained after no treatment (1147 + 423 mm(3) and 1427 + 566 mm(3) vs 683 +202 mm(3)) (p = 0.03). Telcagepant induced vasoconstriction in the skin but did not change the infiltration of nickel reactions. None of the treatments influenced the nickel patch test induced pruritus. The data suggest that the topical application of non-peptide antagonists penetrates the skin but does not inhibit contact dermatitis or pruritus.

Psychosomatic factors in pruritus.

Pruritus and psyche are intricately and reciprocally related, with psychophysiological evidence and psychopathological explanations helping us to understand their complex association. Their interaction may be conceptualized and classified into 3 groups: pruritic diseases with psychiatric sequelae, pruritic diseases aggravated by psychosocial factors, and psychiatric disorders causing pruritus. Management of chronic pruritus is directed at treating the underlying causes and adopting a multidisciplinary approach to address the dermatologic, somatosensory, cognitive, and emotional aspects. Pharmcotherapeutic agents that are useful for chronic pruritus with comorbid depression and/or anxiety comprise selective serotonin reuptake inhibitors, mirtazapine, tricyclic antidepressants (amitriptyline and doxepin), and anticonvulsants (gabapentin, pregabalin); the role of neurokinin receptor-1 antagonists awaits verification. Antipsychotics are required for treating itch and formication associated with schizophrenia and delusion of parasitosis (including Morgellons disease).

Identification of core competencies for primary care of allergy patients using a modified Delphi technique.

BACKGROUND: The majority of allergy patients who seek medical advice are seen in primary care. In-service training of professionals in general practice is needed in order to increase knowledge among primary care clinicians about allergy. Therefore it is important to establish a consensus about what primary care professionals should be able to do, and what the public can expect. We sought to identify core competencies for good practice amongst primary care providers with respect to diagnosis and therapy of allergic diseases and to outline learning objectives for a postgraduate training programme in this field. METHODS: The study involved three rounds, involving a total of 43 expert panelists. In the first round, a panel was asked to indicate competencies (knowledge, diagnostics, therapy and communication) necessary for primary care providers. The second and third rounds were answered by primary care physicians (26) and nurses (10). A Likert scale 1-4 was applied in the second round and two choices ("agree"/"disagree") in the third round, with a criterion of 75% being adopted. RESULTS: The second round included 80 competencies and the third 50. The third round selected a consensus of 46 competencies defining nine learning outcomes for in-service medical training. CONCLUSIONS: The competencies in the field of allergy recommended in this study may serve as a reference of what can be expected from primary care providers.

Tea tree oil attenuates experimental contact dermatitis.

Herbs and minerals have been used in clinical dermatology for hundreds of years and herbal ingredients are becoming increasingly popular with the public in treatment of various dermatological conditions characterised by inflammation and pruritus. The aim of this study was to compare the efficacy of traditional topical therapeutic agents with a moderate potency topical glucocorticoid on experimental contact dermatitis and contact urticaria. The effects of ichthammol 10% pet, zinc oxide 20% pet, camphor 20% pet, levomenthol 10% pet, tea tree oil 20 or 50% and clobetason butyrate 0.05% ointment were studied in the following experimental models: elicitation of allergic contact dermatitis to nickel, irritant contact dermatitis to benzalkonium chloride, and in immediate reactions to histamine and benzoic acid (non-immunological contact utricaria) respectively. Delayed reactions were evaluated using a clinical scoring system and immediate reactions were estimated by planimetry. Histamine-induced pruritus was evaluated using VAS. Tea tree oil reduced allergic contact dermatitis by 40.5% (p = 0.003), zinc oxide by 17.4% (p = 0.04) and clobetason butyrate by 23.5% (p = 0.01). Zinc oxide reduced histamine induced flare by 18.5% (p = 0.01), ichthammol by 19.2% (p = 0.02) and clobetason butyrate by 44.1% (p = 0.02). Irritant contact dermatitis and non-immunological contact urticaria were not influenced by the pre-treatments. Pruritus induced by histamine also remained unchanged. In conclusion, tea tree oil seems to be a more effective anti-eczematic agent than zinc oxide and clobetasone butyrate, while clobetasone butyrate is superior to both ichthammol and zinc oxide in topical treatment of urticarial reactions.

Somatic and psychiatric comorbidity in patients with chronic pruritus.

It has been reported that 10-50% of patients with pruritus but no skin rash have an underlying systemic disease and up to 70% a psychiatric one. The aim of this retrospective study was to review the records of a large number of patients with chronic pruritus for concomitant diseases and treatment options. Medical records of 139 patients (52 males, 87 females) with chronic pruritus who visited the outpatient dermatological clinic during a 17-month period were reviewed. Itch was the presenting symptom in 6 of 47 patients with systemic disease and in 17 of 31 patients with psychiatric disease. Twenty-four patients had neuropathic itch and 37 patients had pruritus of unknown origin. The most severe and long-lasting itch was found in patients with multiple systemic diseases and in those with pruritus of unknown origin. Pruritus of the scalp and face was most common in psychogenic pruritus. Phototherapy was found to be a useful therapeutic option. In conclusion, systemic diseases are unlikely to cause chronic pruritus in patients consulting a dermatology department.

Self-healing photo-neuropathy and cervical spinal arthrosis in four sisters with brachioradial pruritus.

The cause of brachioradial pruritus (a localized itching on the arms or shoulders) is controversial. The role of sun and cervical spine disease has been discussed. This is a report on four sisters suffering from brachioradial pruritus recurring every summer. The sisters spent much time outdoors and exposed themselves extensively to the sun. They also had occupations requiring heavy lifting. Cervical radiographs indicated arthrosis. The density of sensory nerve fibers in the skin biopsies from the itchy skin of the arms, visualized by antibodies against a pan-neuronal marker, protein gene product 9.5, was reduced compared with biopsies from the same skin region during the symptom-free period in the winter. This data exemplifies that brachioradial pruritus is a self healing photoneuropathy occurring in middle aged adults predisposed by cervical arthrosis.

Urticarial dermographism: clinical features and response to psychosocial stress.

Studies report that urticarial dermographism is exacerbated by "life events" and emotions. The aim of this study was to determine what aspects of life quality are affected by symptomatic dermographism and whether acute stress is a potential triggering factor. A total of 21 adult patients with urticarial dermographism completed a questionnaire on symptoms and quality of life. Twelve patients agreed to enrol in the study, which involved provocation by prick test and dermographism before and after a standardized psychosocial stress test (Trier Social Stress Test). Seventeen age-matched controls underwent corresponding tests. Of the patients answering the questionnaire, 43% reported that their disease had an impact on their quality of life and 33% that psychosocial stress precipitated the symptoms. However, the dermographic reaction in patients with urticaria factitia was not significantly intensified after the stress test. We conclude that the acute psychosocial stress test does not alter the magnitude of the dermographic reactions.

Clinical classification of itch: a position paper of the International Forum for the Study of Itch.

Chronic itch is a common and distressing symptom that arises from a variety of skin conditions and systemic diseases. Despite this, there is no clinically based classification of pruritic diseases to assist in the diagnosis and cost-effective medical care of patients with pruritus. The proposed classification focuses on clinical signs and distinguishes between diseases with and without primary or secondary skin lesions. Three groups of conditions are proposed: pruritus on diseased (inflamed) skin (group I), pruritus on non-diseased (non-inflamed) skin (group II), and pruritus presenting with severe chronic secondary scratch lesions, such as prurigo nodularis (group III). The next part classifies the underlying diseases according to different categories: dermatological diseases, systemic diseases including diseases of pregnancy and drug-induced pruritus, neurological and psychiatric diseases. In some patients more than one cause may account for pruritus (category "mixed") while in others no underlying disease can be identified (category "others"). This is the first version of a clinical classification worked out by the members of the International Forum for the Study of Itch. It is intended to serve as a diagnostic route for better evaluation of patients with chronic pruritus and aims to improve patients' care.

Neuroanatomy and neurophysiology of itch.

The specific pathway of "pure," histaminergic itch is traced from the mechano-insensitive nerve fibers in the skin to their central cortical projections. Neuropathic itch created at different levels of this anatomical pathway is reviewed. In this review the present author discusses damage to pruritoceptors in the skin, entrapment syndromes, damage to spinal ganglia, nerve root impingement, injury of the spinal cord, and cerebral damage in the distribution of the middle cerebral artery, capsula interna, or thalamus. Itch in inflamed skin resulting from interactions between nerve transmitters and other mediators of inflammation is described.