Position Statement: Linear prurigo is a subtype of chronic prurigo.

BACKGROUND: Chronic prurigo (CPG) is a distinct disease characterized by chronic pruritus, history and/or signs of prolonged scratching and multiple pruriginous lesions. It may present with various clinical manifestations, including papules, nodules, plaques or umbilicated lesions. Some patients with chronic pruritus show pruriginous linear and scaring scratch lesions (LSSL) and it is unclear whether these lesions belong to the spectrum of CPG. OBJECTIVE: To achieve a consensus on the classification of pruriginous LSSL and establish criteria to differentiate them from similar appearing conditions of different nature. METHODS: Members of the Task Force Pruritus (TFP) of the European Academy of Dermatology and Venereology participated in the consensus conference, discussing representative clinical cases. Using the Delphi method, consensus was reached when ≥75% of members agreed on a statement. RESULTS: Twenty-one members of the TFP with voting rights participated in the meeting. It was consented that LSSL occurs due to chronic pruritus and prolonged scratching, and share common pathophysiological mechanisms with CPG. LSSL were thus considered as belonging to the spectrum of CPG and the term 'linear prurigo' was chosen to describe this manifestation. CONCLUSION: Considering linear prurigo as belonging to the spectrum of CPG has important clinical implications, since both the diagnostic and therapeutic approach of these patients should be performed as recommended for CPG. Importantly, linear prurigo should be differentiated from self-inflicted skin lesions as factitious disorders or skin picking syndromes. In the latter, artificial manipulation rather than pruritus itself leads to the development of cutaneous lesions, which can show clinical similarities to linear prurigo.

Intellectual disability and cognitive ability in Darier disease: Swedish nation-wide study.

BACKGROUND: Darier disease is an autosomal dominant skin disorder caused by mutations in the ATP2A2 gene. Anecdotal reports suggest a relationship between Darier disease and intellectual disabilities, but these reports are based on small clinical samples and limited by absence of control populations. OBJECTIVES: To examine the risk of intellectual disability and subclinical impairments in cognitive ability in Darier disease. METHODS: We conducted a matched cohort study based on Swedish Population-, Patient- and Conscript Registers. The risk of being diagnosed with intellectual disability was estimated in 770 individuals with Darier disease, compared with matched comparison individuals without Darier disease. Associations were examined with risk ratios from conditional logistic regressions. In addition, we analysed test-based cognitive ability data (i.e. IQ data) from the Swedish conscript examination, for a subset of patients without diagnosed intellectual disability. RESULTS: Individuals with Darier disease had a sixfold increased risk of being diagnosed with intellectual disability (risk ratio 6.2, 95% confidence interval 3.1-12.4). For conscripted individuals with Darier disease but no diagnosed intellectual disability, mean cognitive ability scores were about half a standard deviation lower than for comparison subjects. CONCLUSIONS: Darier disease is associated with intellectual disability and subclinical impairments in cognitive ability. The Darier-causing mutations merit further attention in molecular genetic research on intellectual disability and cognitive ability.

Use of serotonin reuptake inhibitors in patients with psoriasis is associated with a decreased need for systemic psoriasis treatment: a population-based cohort study.

OBJECTIVE: To investigate whether psoriasis is affected by the use of serotonin reuptake inhibitors (SSRIs). DESIGN: A population-based cohort study. SETTING: The general adult population with plaque psoriasis in Sweden between 1997 and 2006. SUBJECTS: A total of 69 830 patients with plaque psoriasis were identified in the National Patient Register. Whether study subjects were exposed to SSRIs was identified through the Swedish Prescribed Drug Register. The SSRI-exposed subjects (n = 1282) had a prescription for SSRIs dispensed twice during 6 months at a Swedish pharmacy between 1 July 2006 and 1 April 2008, with a wash-out period of 1 year or longer. The reference subjects (n = 1282), who were not exposed to SSRIs, were matched for age, county of residence, sex, psoriasis severity and seasonal variation. MAIN OUTCOME MEASURE: Change in psoriasis severity defined by switching between nonsystemic and systemic psoriasis treatments 6 months after exposure to SSRIs. RESULTS: The risk of switching from nonsystemic to systemic psoriasis treatments was significantly decreased in the SSRI-exposed group (odds ratio 0.44, 95% confidence interval 0.28-0.68). CONCLUSION: SSRI use in patients with psoriasis is associated with a decreased need for systemic psoriasis treatment.

Substance P alterations in skin and brain of chronically stressed atopic-like mice.

BACKGROUND: Stress is known to worsen the symptoms of atopic eczema (AE). Substance P is likely to play an important role in the development and pathogenesis of AE. OBJECTIVE: To examine a possible connection between chronic mild stress and changes in the expression of substance P and its receptor (R) neurokinin (NK) 1 in the skin and stress-related brain regions in NC/Nga atopic-like mice. METHODS: The mice were divided into three groups (eight animals per group): SE (stressed eczematous), NSE (non-stressed eczematous) and SC (stressed control). Ears and brains of the mice were investigated using immunohistochemistry and RT-PCR. RESULTS: In the skin, there was a decrease in the number of substance P immunoreactive nerve fibres in SE compared with SC group. RT-PCR showed a strong tendency to an increase in mRNA for NK1R in the skin of SE compared with NSE mice. There was an increase in the number of mast cells and the degree of their degranulation in the SE compared with both other groups. A decrease in substance P immunoreactivity in medial hippocampus was found in SE compared with NSE animals. In prefrontal cortex and central amygdala, there were no significant differences in substance P immunoreactivity between the three groups. CONCLUSION: Exposure to chronic mild stress in NC/Nga atopic-like mice may result in altered expression patterns of substance P in the skin and hippocampus.

Expression of tachykinins and their receptors in plaque psoriasis with pruritus.

UNLABELLED: BACKGROUND Various mediators of pruritus have been suggested that might be responsible for the mechanism of pruritus in psoriasis. OBJECTIVES: To study the expression levels of members of the tachykinin family, substance P and neurokinin (NK) A and their receptors, NK-1 and NK-2, in psoriasis and to correlate their expression with the intensity of pruritus. A possible correlation with chronic stress and depression was also evaluated. METHODS: Biopsies were obtained from 28 patients with chronic plaque psoriasis; the majority had pruritus. The samples were taken from lesional and nonlesional areas on the back and also from 10 healthy controls, for immunohistochemistry staining, and from lesional skin for radioimmunoassay. Prior to biopsy, the clinical severity of the psoriasis of each patient was assessed by the Psoriasis Area and Severity Index (PASI) and the intensity of pruritus was measured by using a visual analogue scale (VAS). Levels of depression and stress were measured using Beck's Depression Inventory (BDI) and the salivary cortisol test, respectively. RESULTS: Substance P-, NKA- and NK-2 receptor-immunoreactive nerves, and non-neuronal inflammatory cells positive for substance P and NKA and their respective receptors, NK-1 and NK-2, were numerous in psoriasis compared with healthy controls. The numbers of substance P-positive nerves and NK-2 receptor-positive cells in lesional skin were significantly correlated to pruritus intensity. The cortisol ratio was inversely correlated with the number of NK-1 receptor-immunoreactive inflammatory cells in lesional and nonlesional psoriasis skin. There was also a positive correlation between the BDI score and the number of substance P-positive cells in nonlesional skin and with NK-1 receptor-positive cells in lesional and nonlesional skin. CONCLUSIONS: Tachykinins may play a role in psoriasis per se, in addition to pruritus in this disease. Targeting the combined NK-1 and NK-2 receptors might be a possible treatment.

Responses to intradermal injections of substance P in psoriasis patients with pruritus.

BACKGROUND: Various mediators have been suggested for the pathogenesis of pruritus in psoriasis. METHODS: To investigate cutaneous responses of substance P in pruritic lesional and nonlesional areas of psoriasis patients and in healthy controls, substance P, saline and histamine were injected intradermally. After each injection, pruritus, flare and wheal were recorded. RESULTS: There was no statistical difference in the latency period, duration, area under the curve and maximum intensity of pruritus evoked by substance P (10(-5) and 10(-6) mol/l) between psoriasis and healthy control skin. Substance P (10(-5) mol/l) induced a tendency to a greater intensity of pruritus in lesional compared to nonlesional psoriatic skin (p = 0.08). Histamine produced a shorter itch latency period (p < 0.05) and a lower maximum intensity of pruritus (p = 0.05) in lesional psoriasis skin than in healthy control skin. No significant difference in flare area was observed between the psoriasis patients and healthy controls. The histamine-induced wheal was smaller in psoriasis patients than in healthy individuals (p < 0.05). CONCLUSION: Intradermally injected substance P induced pruritus, flare and wheal in psoriasis patients. However, these responses did not differ significantly from those of the healthy controls.

Neuronal changes in psoriasis exacerbation.

BACKGROUND: The nervous system contributes to inflammatory skin diseases. Objective The aim of this investigation was to study the neuronal contribution to psoriasis at the remission and exacerbation phases. METHODS: We examined the expression of the neuronal markers protein gene product 9.5 (PGP 9.5), growth-associated protein-43 (GAP-43) and substance P, in addition to its receptor (R), neurokinin-1R (NK-1R) in psoriatic skin from seven female patients at remission and exacerbation, using immunohistochemistry. RESULTS: The number of epidermal PGP 9.5 immunoreactive nerve fibres in the involved skin during exacerbation was decreased (P < 0.01) compared to involved skin at remission and non-involved skin at the exacerbation phase. GAP-43-positive nerve fibres were decreased (P < 0.05) in the involved skin in contrast to non-involved skin, during exacerbation. Substance P expression was seen on both immunoreactive nerve fibres and cells with a down-regulation (P < 0.01) in the number of positive nerve fibres in the involved skin compared to non-involved skin, at the exacerbation phase. The number of substance P-positive cells was slightly lower in the involved skin at exacerbation than at remission. The number of NK-1R immunoreactive cells was increased (P < 0.01) in the involved skin in contrast to non-involved skin, at the exacerbation phase. CONCLUSION: Our findings suggest a crosstalk between the nervous system and inflammation during psoriasis exacerbation in the form of an altered expression of nerve fibres, substance P and its NK-1R.

Expression of serotonin and its 5-HT1A receptor in canine cutaneous mast cell tumours.

Mast cells of a number of different animal species have been reported to contain serotonin (5-hydroxytryptamine; 5-HT), a monoamine capable of numerous and complex actions, which may include an impact on tumour growth. Limited previous studies have suggested that normal or neoplastic canine mast cells do not express 5-HT. In the present study, canine cutaneous mast cell tumours (MCTs) of Patnaik histological grades I-III were investigated immunohistochemically for expression of 5-HT and its receptor (R) 5-HT1A. The proportion of positively labelled cells and the intensity of labelling of individual cells were determined. Both 5-HT and the 5-HT1A receptor were expressed by non-neoplastic dermal mast cells and neoplastic mast cells. More neoplastic mast cells expressed 5-HT than the 5-HT1AR. Poorly differentiated tumours expressed fewer of both molecules, but the better differentiated mast cells at the periphery of such lesions had more consistent 5-HT expression. 5-HT and the 5-HT1A receptor may be involved in the differentiation of canine MCTs and in the microvascular complications associated with these neoplasms.

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.

Psoriasis and stress: a prospective study.

BACKGROUND: Psoriasis is generally thought to be worsened by stress. This presumption has been supported primarily by retrospective studies using questionnaires. No controlled prospective study on this issue has been performed. METHODS: Nine women with moderate plaque psoriasis were enrolled in the study. They all believed that their psoriasis was worsened by stress. They filled in a daily diary with estimations of actual stress levels and grades of psoriasis. The study of each patient started when her skin disease was in a stable phase and was concluded when her psoriasis was worsened by at least 25% from the starting level. Psoriasis area severity index scores were recorded at the start, as soon as possible after exacerbation and 2 weeks later. Stress-related blood samples were taken at the same visits. The study was analysed as a nine-case study. RESULTS: No clear pattern was found between stress levels and worsening of psoriasis in our nine patients. One patient had elevated stress levels 13 days before exacerbation of psoriasis, but for at least seven patients, there were no identifiable time relationships between stress and psoriasis appearance. For two patients, there were clear elevations of stress levels after psoriasis outbreak. CONCLUSION: This limited study does not support the assumption that stress is a worsening factor in psoriasis.

Neuroimmune mechanisms in patients with atopic dermatitis during chronic stress.

OBJECTIVE: To identify pathoaetiological neuroimmune mechanisms in patients with atopic dermatitis (AD) and chronic stress, focusing at nerve density, sensory neuropeptides, and the serotonergic system. METHODS: Eleven patients with AD with histories of stress worsening were included. Biopsies from involved and non-involved skin were processed for immunohistochemistry. Salivary cortisol test was done as a marker for chronic stress. RESULTS: There were more acanthosis and fewer nerve fibres in epidermis and papillary dermis of involved compared with non-involved skin. Whereas there was no significant change in the number of substance P and calcitonin gene-related peptide-positive nerve fibres between the involved and non-involved skin, there was an increase in the epidermal fraction of 5-hydroxtrytamine 1A (5-HT1A) receptor and serotonin transporter protein (SERT) immunoreactivity in the involved skin. The number of 5-HT2AR, CD3-positive cells, and SERT-positive cells, most of them being CD3 positive, was increased in involved skin. There was an increase in mast cells in the involved skin, and these cells were often located close to the basement membrane. There was a strong tendency to a correlation between 5-HT2AR positive cells in the papillary dermis of involved skin and low cortisol ratios, being an indicator of chronic stress. CONCLUSION: A changed innervation and modulation of the serotonergic system are indicated in chronic atopic eczema also during chronic stress.

Upregulation of the axonal growth and the expression of substance P and its NK1 receptor in human allergic contact dermatitis.

Nerve fibers and sensory neuropeptides substance P and calcitonin gene-related peptide (CGRP) have been reported to be involved in allergic contact dermatitis (ACD). In the present study, we investigated the general innervation (using antibody against protein gene product 9.5, PGP 9.5), axonal growth (using antibody against growth associated protein, GAP-43), CGRP, and substance P with its receptor neurokinin 1 (NK1), in positive epicutaneous reactions to nickel sulphate from nickel-allergic patients, at the peak of inflammation, 72 hr after challenge with the antigen. There was an increased (p < 0.01) number of GAP-43 positive fibers in the eczematous compared with control skin, indicating an increased axonal growth already at 72 hr postchallenge. Double staining revealed a coexpression of CGRP and GAP-43 on dermal nerve fibers. There was no difference in the number of substance P and CGRP positive nerve fibers between eczematous and control skin. However, semiquantification analyses showed an increased expression of substance P positive inflammatory cells, being CD3, CD4, or CD8 positive, and NK1R positive inflammatory cells, being tryptase or CD3 positive. These results indicate a contribution of regenerating nerve fibers and substance P to the contact allergic reaction.

Study of innervation, sensory neuropeptides, and serotonin in murine contact allergic skin.

Density of nerve fibers, axonal growth, calcitonin gene-related peptide (CGRP), and substance P, and serotonin immunoreactivity as well as concentration were all determined in a murine model of contact allergy. Female Balb/c mice were sensitized on the back with oxazolone and 6 days later challenged with the same antigen on the dorsal surface of the ears, while control mice received the vehicle only. Then, 24 hr postchallenge, one ear was processed for immunohistochemical staining, while the other was frozen and processed for gas chromatography-mass spectrometry or radioimmunoassay (RIA). Protein gene product 9.5 (PGP 9.5) positive nerve fibers showed a tendency to increase in inflamed ears versus control ears in epidermis as well as the dermis. Growth-associated protein-43 (GAP-43) positive fibers in the epidermis were increased (p < .01) in inflamed ears, compared with control ears, as was the case for the dermal fibers, indicating increased axonal growth. Total (epidermis and dermis) numbers of CGRP and substance P positive nerve fibers tended to increase in the inflamed skin in contrast to control skin. In contrast, RIA demonstrated a lower (p < .05) concentration of CGRP in the inflamed ears compared with controls and a tendency for substance P to decrease in concentration in eczematous ears versus controls. There was no difference in serotonin concentration, or in the number of serotonin positive mast cells, between the inflamed and control skin, whereas semiquantification of serotonin positive platelets showed an increase in the inflamed (+/+) compared with control ears (+). Our results indicate that 24 hr after being challenged with the antigen, at the peak of murine skin inflammation, axonal growth, sensory neuropeptides, as well as serotonin may be involved.

Expression of heat shock proteins in heavy metal-provoked inflamed human skin.

The expression of heat shock protein (hsp) 65, 72 and 90 was studied in human inflamed skin after heavy metal salt treatment, by using epicutaneous patch-testing procedure and immunohistochemistry. There was a slight immunoreactivity to hsp 65 and hsp 72, but not to hsp 90 in keratinocytes in normal skin. An increased immunoreactivity to hsp 72 was obtained in apically located keratinocytes in a statistically significant (p<0.01) increased number of reactions to cobalt chloride and gold chloride compared to control skin. These metal salts also induced the highest degree of expression of keratinocyte intercellular adhesion molecule (ICAM)-1. There were epidermal dendritic cells as well as macrophage-like cells in the dermis, which expressed hsp 65 and hsp 90, in biopsies from metal salt-treated and control skin, while expression of hsp 72 in macrophage-like cells was found only in the dermis.

Expression of nicotinic receptors in the skin of patients with palmoplantar pustulosis.

BACKGROUND: A suggested role for nicotine in the pathogenesis of palmoplantar pustulosis (PPP) has been discussed. The target for the inflammation in PPP is the acrosyringium. Nicotine acts as an agonist on nicotinic acetylcholine receptors (nAChRs) and can influence a variety of cellular functions. OBJECTIVES: To study the alpha 3- and alpha 7-nAChR expression in palmar skin of patients with PPP in comparison with that in healthy smoking and non-smoking controls. METHODS: Biopsies from 20 patients with PPP, seven healthy smokers and eight healthy non-smokers were studied by immunohistochemistry with a monoclonal anti-alpha 3 and a polyclonal anti-alpha 7 antibody. RESULTS: In healthy controls both nAChR subtypes showed stronger immunoreactivity in the eccrine glands and ducts than in the epidermis. The papillary endothelium was positive for both subtypes. Epidermal alpha 3 staining was stronger and that of the coil and dermal ducts weaker in healthy smokers than in healthy non-smokers. In involved PPP skin, granulocytes displayed strong alpha 3 immunoreactivity. The normal epidermal alpha 7 staining pattern was abolished in PPP skin and was replaced by strong mesh-like surface staining, most markedly adjacent to the acrosyringium, which in controls was intensely alpha 7 positive at this level. Endothelial alpha 7 staining was stronger in PPP skin than in the controls. CONCLUSIONS: Smoking can influence nAChR expression. The altered nAChR staining pattern in PPP skin may indicate a possible role for nicotine in the pathogenesis of PPP. We hypothesize that there is an abnormal response to nicotine in patients with PPP, resulting in inflammation.

Early DNA synthesis and cytokine expression in the nickel activation of peripheral blood mononuclear cells in nickel-allergic subjects.

BACKGROUND AND OBJECTIVE: Nickel sulphate stimulates the proliferation of lymphocytes in nickel-allergic subjects. However, nickel-induced stimulation of lymphocytes from control persons without clinical symptoms of nickel allergy has also been reported. The aim of the present study was to correlate T cell activity, measured by DNA synthesis and the expression of Th1 [interleukin (IL)-2, tumour necrosis factor (TNF)-beta and interferon (IFN)-gamma] and Th2 (IL-4) cytokines, in short-term (up to 72 h) culture of nickel-stimulated peripheral blood mononuclear cells (PBMC) from nickel-allergic patients compared to control subjects. METHODS: DNA synthesis was measured by the incorporation of [methyl-(3)H]thymidine. The production of IL-2, TNF-beta, IFN-gamma and IL-4 was measured in the supernatants of the cultures by ELISA. In situ hybridization for mRNA was performed using oligonucleotide probes for IL-4, IFN-gamma and TNF-beta in cell smears. RESULTS: Already after 24 h and proceeding through the remaining culture period, there was a statistically significant (p<0.001) difference in the concentrations of IL-2 between patients and controls. There was a significant (p<0.01) difference in DNA synthesis (stimulation index) between the patients and control subjects at 72 h, and also at the same time a difference in the concentrations of TNF-beta (p<0.05) and IL-4 (p<0.01). In the in situ hybridization study, TNF-beta was found to be the only one of the studied cytokines that differed between the nickel-allergic and control subjects, this difference being most evident at 72 h (p<0.01). CONCLUSIONS: Our results indicate a difference between nickel-allergic and non-allergic subjects in the synthesis of DNA and production of cytokines when PBMC are stimulated by nickel sulphate, and IL-2 may be regarded as a critical and early-occurring cytokine.

Skin nerve fibres and their contacts with mast cells in patients with palmoplantar pustulosis.

Patients with palmoplantar pustulosis (PPP) frequently report that stress worsens their condition. A study was therefore made of the distribution and number of nerve fibres positive for protein gene product (PGP) 9.5 (a general nerve marker) and nerve fibres with substance P- and calcitonin gene-related peptide-like immunoreactivity in involved skin from patients with PPP and in skin from healthy controls. The number of mast cells in the papillary dermis was larger (P = 0.0003) in lesional palmar PPP skin than in control skin, and the number of contacts between mast cells and nerve fibres was significantly larger (P = 0.02) in PPP skin than in control skin. Image analysis of the nerve fibres around the sweat glands showed that the positively stained area as a percentage of the total area of the sweat gland (coil + surrounding nerves) was significantly lower in PPP skin (P = 0.0006). Furthermore, the nerves seemed to be fragmented. Neutrophils within and below the pustules and in the papillary dermis showed positive substance P staining. The increased number of contacts between nerves and mast cells in PPP skin and the intense substance P-like immunoreactivity of the neutrophils indicate that neuromediation may influence the inflammation in PPP, whereas the destruction of the nerve fibres around the sweat glands might be a result of the inflammation.

Expression of heat shock proteins 65, 72 and 90 in mercuric chloride-treated human peripheral blood mononuclear cells.

Peripheral blood mononuclear cells (PBMC) were challenged with different concentrations of mercuric chloride and the expression of heat shock protein (hsp) 65, 72 and 90, were investigated by an indirect peroxidase method as well as the proliferation was measured by uptake of tritiated thymidine into DNA. Hsp 65 immunoreactivity was peripherally located in the cells at a mercuric chloride concentration of 5.5-2.8x10(-5) mol/L, which also gave a decreased DNA synthesis. Hsp 72 positive cells, with a nuclear and cytoplasmic immunoreactivity, were found at a concentration of 5.5-2.2x10(-5) mol/L. Hsp 90 positive cells also with an immunoreactivity at a nuclear and cytoplasmic level, were found at 1.1x10(-5)-5.5x10(-6) mol/L. A stimulated DNA synthesis was obtained already at 2.2x10(-5) mol/L and was found down to 5.5x10(-6) mol/L. High concentrations of mercuric chloride might induce expression of hsp 65 and 72 as a protective mechanism. Hsp 90 as well as hsp 72 might be involved in the proliferation of human PBMC to mercuric chloride. Thus, this expression of hsp 72 may have a dual role.

The distribution of choline acetyltransferase- and acetylcholinesterase-like immunoreactivity in the palmar skin of patients with palmoplantar pustulosis.

The distribution of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in involved skin in patients with palmoplantar pustulosis (PPP) and in normal palmar skin in healthy non-smokers and smokers has been studied by immunohistochemistry, especially in relation to the sweat gland apparatus. The sweat gland and its duct showed ChAT- and AChE-like immunoreactivity (LI) of varying intensity in all three groups and with stronger reactivity than in the epidermis. ChAT-LI was present in the coil and in the duct except in the corneal layer. Smokers and patients with PPP displayed significantly fewer ChAT+ acrosyringia than non-smokers. In the patients with PPP, the granulocytes in the pustules and in the papillary dermis displayed ChAT-LI. Western blot analysis of granulocytes from peripheral blood from healthy donors confirmed the presence of ChAT-like proteins in large amounts in neutrophils and small amounts in eosinophils. AChE-LI of varying intensity was found in all parts of the sweat gland apparatus in all three groups. The strongest AChE-LI in the acrosyringia was seen in the lowest part of the stratum corneum, where the PPP pustules are located. No significant differences in staining pattern or intensity were found between the coils, nerve fibres surrounding the coils or ducts. The number of mast cells in the papillary dermis was about four times larger in the patients with PPP than in the control subjects. AChE-LI was observed in about 25% of the mast cells in non-smoking control subjects and in patients with PPP, but only in 10% of those in the smoking control subjects. Our findings indicate that the (non-neuronal) cholinergic system may be involved in cutaneous inflammatory processes.

Expression of interleukin-6 in human dorsal root ganglion cells.

The expression of Interleukin-6 (IL-6) was studied in normal dorsal root ganglia (DRG) of juvenile and foetal humans, using immunohistochemistry and in situ hybridization techniques. There was an expression of IL-6-like immunoreactivity in more than 75% out of neuronal cells in the juvenile ganglia with a peripheral localization, and also an expression in the foetal ganglion cells. There was a co-localization of IL-6 with substance P (SP) and calcitonin gene-related peptide (CGRP) in more than 60% of the DRG cells, respectively. By in situ hybridization 0.9% of the cells in the juvenile ganglia and 1.1% of the cells in the foetal ganglia showed a positive signal for IL-6. In addition, expression of IL-6 was found in juvenile medulla spinalis, preferentially in the white matter.