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.     

Immunohistochemical studies of normal sweat glands, sweat gland tumors and extramammary Paget's disease. I. Immunohistochemical studies of normal sweat glands

Localizations of 18 antigens in normal sweat glands were analyzed. The antigens were roughly classified into 8 antigens: 1) distributed throughout the epithelial cells; 2) localized in whole sweat glands; 3) localized only in the secretory portion of sweat glands; 4) localized only in the inner cells of ductal portion of sweat glands; 5) localized in the myoepithelial cells; 6) localized only in the outer cells of dermal ducts of eccrine glands; 7) localized only seen in some of apocrine glands; 8) seen in the inflamed sweat glands. Based on these findings, I discussed about the forms and meanings of localization of those antigens.     

Immunohistochemical study of angiotensin receptors in normal human sweat glands and eccrine poroma

BACKGROUND: Angiotensin II exerts its actions through its specific receptors. However, expression of these receptors has not been determined in sweat glands. OBJECTIVES: To clarify the expression and localization of the angiotensin receptors in normal human sweat glands and eccrine poroma. METHODS: Expression of angiotensin type 1 (AT1) and type 2 (AT2) receptors in normal human eccrine and apocrine sweat glands and 12 cases of eccrine poroma was studied using immunohistochemistry. RESULTS: In eccrine sweat glands, the acrosyringium and the inner surfaces and luminal cells of the intradermal duct showed positive staining with AT1. In apocrine sweat glands, the intraepithelial duct and luminal cells of the intradermal duct showed positive staining with AT1. In 12 cases of eccrine poroma, some of the tumour cells in the tumour strands and cells surrounding the luminal structures stained positively. There were no positive findings with AT2. CONCLUSIONS: Studying AT1 distribution may be useful in understanding the pathophysiology of sweat glands and sweat gland tumours.     

Glycoconjugates in sweat glands and other structures of skin from normal and cystic fibrosis subjects

In this study, glycoconjugates of human skin varied in structure between cell types in an individual and often between individuals for a given cell type. Stored secretory material in dark cells of the sweat gland coil contained complex carbohydrate with terminal alpha-galactose, N-acetylgalactosamine, fucose, or sialic acid. The plasmalemma of clear cells in the secretory coil stained conspicuously for terminal alpha-N-acetylgalactosamine, and the cytosol of clear cells contained lectin-reactive glycogen in the majority of specimens. Superficial and deep cells of the sweat duct evidenced plasmalemmal glycoconjugate with terminal N-acetylgalactosamine. However, only the superficial cell plasmalemma in the duct stained for terminal alpha-N-acetylgalactosamine, fucose, and sialic acid. In several specimens, only the deep cells in the sweat duct revealed plasmalemmal glycoconjugate with terminal beta-galactose. Sebaceous glands alone displayed lectin affinity demonstrative of terminal alpha-galactose and like other sites stained for terminal beta-galactose and alpha-N-acetylgalactosamine. The epithelium in epidermis and hair follicles appeared similar, except for epidermis failing to evidence fucose and alpha-N-acetylgalactosamine with certain lectins. Both underwent changes in glycoconjugate composition with cell maturation. Skin from control subjects and patients with cystic fibrosis did not differ in lectin-binding properties. Abnormalities observed in cystic fibrosis specimens included decreased volume of sebaceous glands and, in two cases, increased infiltration of macrophages staining for terminal N-acetylgalactosamine.     

Immunohistochemical studies of normal sweat glands, sweat gland tumors and extramammary Paget's diseases. II. Immunohistochemical studies of sweat gland tumors and extramammary Paget's diseases

Localizations of 18 antigens were analyzed in 41 cases with benign sweat gland tumors (13 with eccrine acrospiroma, 4 with eccrine spiradenoma, 2 with hidroacanthoma simplex, 9 with chondroid syringoma, 4 with syringocystadenoma papilliferum, 1 with tubular apocrine adenoma, 1 with papillary eccrine adenoma, 1 with apocrine cystadenoma, 1 with cylindroma, 5 with syringoma), 14 with malignant sweat gland tumors (7 with eccrine porocarcinoma, 3 with eccrine duct carcinoma, 3 with apocrine gland carcinoma, 1 with mucinous carcinoma) and 13 with extramammary Paget's disease. The results I obtained were compared with those in the normal sweat glands for determination of a differentiation of each tumor.     

Proinflammatory cytokines and their corresponding receptor proteins in eccrine sweat glands in normal and cutaneous leishmaniasis human skin

Abstract Paraformaldehyde-fixed biopsy specimens of normal and chronic cutaneous leishmaniasis human skin were investigated for the presence and cellular distribution of interleukin-1α, interleukin-1β, interleukin-6 and tumour necrosis factor-α and the corresponding receptors in eccrine sweat glands, using an indirect immunoperoxidase technique. There was cytoplasmic staining for all 4 cytokines as well as their receptor proteins in the clear cells of the eccrine sweat glands of both normal and inflamed skin specimens. No staining could be seen in the dark cells or the myoepithelial cells, neither in normal nor in inflamed skin. However, a difference between normal and inflamed skin was observed in the ductal syslem. Thus, cell layers of the dermal ducts in leishmaniasis skin were stained for all 4 cytokines, with more intense labelling in the basal cell layer of the coiled ducts, while in the normal skin, an intense staining was more evident in the inner luminal layer, with variable and less intense labelling of the basal layer. The immunolabelling for the cytokine receptors within the dermal ducts exhibited similar staining intensity in both luminal and basal cell layers, except in the case of the IL-6 receptor, which showed a moderate to intense signal in the basal cell layer but a weak staining of the luminal cell layer. Infiltrating inflammatory cells around the sweat gland apparatus in leishmaniasis skin exhibited immunoreactivilies for all cylokines and their corresponding receptors.     

Tissue kallikrein and kininogen in human sweat glands and psoriatic skin

The cellular localization of immunoreactive tissue kallikrein and kininogen was studied in normal and psoriatic human skin. Immunoreactivity to both enzyme and substrate was observed in secretory granules of the dark cells in the secretory fundus (acinus) of the sweat glands. Double immunostaining revealed a segmental distribution of the two antigens. Each acinar section contained either tissue kallikrein or kininogen. However, there appeared to be a junctional zone in which both were present, but in separate dark cells. Immunoreactivity for both antigens was also observed in close apposition to the luminal microvilli of the duct cells. No specific immunostaining was seen in sebaceous glands, hair follicles, keratinocytes and other cells of the secretory unit such as myoepithelial or clear cells. In psoriatic skin there were in addition many neutrophils immunoreactive for tissue kallikrein in the epidermis and psoriatic scales. Mitogenic action of kinins may account to some extent for the characteristic accelerated turnover of epidermal cells in psoriasis and locally applied kinin antagonists may prove of value in the treatment of this disease.     

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.     

Pathogenic role of palatine tonsils in palmoplantar pustulosis: A review

Palmoplantar pustulosis (PPP) is characterized by symmetrical, erythematous, scaly plaques, with numerous, sterile, non‐bacterial, pinpoint pustules, which are restricted to the palms and soles. Because several reports have described the efficacy of tonsillectomy for improvement in PPP skin lesions, we consider that PPP is tonsil‐induced autoimmune/inflammatory syndrome (TIAS) while other factors are also involved in the pathogenesis of PPP. Here, the association between PPP pathogenesis and TIAS was examined, with a focus on results of previous studies. PPP patients show a hyperimmune response to indigenous bacteria such as α‐streptococci, due to impaired immunological tolerance towards such organisms. Such a novel immune response leads to T‐cell activation through the abnormal expression of secondary stimulation molecules, including cytotoxic T‐lymphocyte‐associated antigen 4, inducible T‐cell co‐stimulator and Smad7, in the tonsils of PPP patients. Activated tonsillar T cells express cutaneous lymphocyte antigen (CLA), CCR6 and β1‐integrin, enter the blood circulation and are recruited to PPP skin lesions. Within lesions, T cells roll onto endothelial cells through the interaction between CLA and E‐selectin, migrate into the extravascular area through β1‐integrin–vascular cell adhesion molecule 1 binding, and assemble in the skin through CCL20–CCR6 binding. Hyperimmune responses to autoantigens such as keratin and heat shock proteins could also be involved in PPP pathogenesis, through the stimulation of the T‐helper 17 reaction.     

Interleukin-8 immunoreactivity in the skin of healthy subjects and patients with palmoplantar pustulosis and psoriasis.

Previous studies have shown that neutrophil-activating peptide 1/interleukin-8 (IL-8) is present in psoriatic scales and to a lesser extent in normal human epidermis. A panel of monoclonal antibodies and polyclonal antisera raised against IL-8 was used to localize IL-8 with immunoperoxidase techniques in non-lesional and lesional skin of patients with psoriasis and palmo-plantar pustulosis (PPP), and in corresponding sites from healthy subjects. Intracellular IL-8 immunoreactivity was found in all epidermal cell layers in biopsies of healthy subjects and in non-lesional and lesional skin in both PPP and psoriasis. The most intense immunolabeling was regularly found in the basal cell layer. Intercellular epidermal IL-8 immunolabeling was regularly detected in lesional biopsies in PPP and psoriasis, but not in healthy subjects or non-lesional skin in PPP and psoriasis. No intercellular immunolabeling was detected after successful treatment of lesional skin. The majority of cells along the eccrine sweat glands, dermal mononuclear cell infiltrates, and endothelial cells were IL-8 immunoreactive in all biopsies studied. The present study suggests that IL-8, its precursor form, or, alternatively, a degradation product is present in normal human epidermis.     

HNK-I antibody reacts with peripheral nerves and sweat glands in the skin

The distribution of Leu-7 antigen was investigated using immunoperoxidase staining technique. It was found that HNK-I monoclonal antibody reacted with peripheral nerves and sweat glands (both apocrine and eccrine) of the skin. HNK-I antibody is a new marker for them, and may help to elucidate the nature of some skin tumours.     

Clinical characteristics and associations of palmoplantar pustulosis: an observational study

BackgroundPalmoplantar pustulosis is a chronic and relapsing disease of the palms and soles, which is characterized by scattered clusters of pinhead-sized, sterile pustules.ObjectiveThe aim of the present study was to determine demographic features, co-morbidities, and relation of palmoplantar pustulosis with psoriasis.MethodsA total of 48 patients (M/F: 15/33) were enrolled in the present study. A detailed history regarding age of onset, palmoplantar pustulosis duration, number of recurrences, personal and family history of psoriasis, accompanying arthritis, sternoclavicular tenderness, dental fillings, smoking status, and autoimmune disease was obtained; thorough dermatological examination was carried out. Patch testing results and laboratory investigations for thyroid autoimmunity were recorded.ResultsThirty-five of 48 patients (72.9%) were current smokers. Twenty of the 48 patients (41.7%) had dental fillings. There was not any significant correlation between palmoplantar pustulosis duration and dental filling duration (p = 0.170). Psoriasis was not detected in any patients either in history or in dermatological examination. Nail involvement and joint complaints were observed in seven of 48 patients (14%) and in nine of 48 patients (18%), respectively. Autoimmune thyroiditis was observed in four of 48 patients (12%). Patients with patch testing positivity (12.5% of patients, M/F: 1/5) had no considerable association for history of external contact with these materials.Study limitationsRetrospective analysis.ConclusionPalmoplantar pustulosis appears to be a distinct entity from psoriasis. Routine thyroid functions test could be analyzed, but patch testing is not required in patients with palmoplantar pustulosis. Also, patients with palmoplantar pustulosis must be evaluated for musculoskeletal symptoms and signs.     

Clinical and epidemiological comparison of patients affected by palmoplantar plaque psoriasis and palmoplantar pustulosis: a case series study

Summary Background In 2007 the International Psoriasis Council proposed that palmoplantar pustulosis (PPP) should be considered a separate condition from psoriasis, despite the presence of certain phenotypes common in both diseases. Objectives To describe and compare demographic and clinical characteristics among patients with PPP and palmoplantar plaque psoriasis. Methods This was a retrospective case series study from 2005 to 2010. The following data were obtained: age, sex, family history, smoking habits, nail involvement, joint involvement, disease duration, lesion morphology (plaque or pustular), histological diagnosis, comorbidities, and Physician’s Global Assessment (PGA) score for extrapalmoplantar lesions. The sample size calculation indicated that 80 patients, 40 patients for each group (palmoplantar plaque psoriasis and PPP) were needed to see clinically relevant differences between groups. Results Ninety patients were selected, 51 with palmoplantar plaque psoriasis and 39 with PPP. No statistically significant differences were registered between patients affected by PPP and palmoplantar plaque psoriasis as regards age at onset of the disease (48 vs. 44 years; P = 0·4), disease duration (6 vs. 10 years; P = 0·1), family history of psoriasis (28% vs. 33%; P = 0·7), concomitant arthritis (26% vs. 25%; P = 1·0), or smoking habits (54% vs. 41%; P = 0·2). We observed a female predominance (P = 0·01) and a lesser frequency of nail involvement (P = 0·03) in patients affected by PPP. Conclusions Our data suggest a close relationship between PPP and psoriasis. The existing data concerning epidemiology, clinical presentation, genetics, histopathology and pathogenesis do not permit a clear distinction between these two entities, which seem to coincide in many aspects. PPP appears to have a marked predilection among female smokers.     

Nature of the sweat glands in the hairy skin of the beagle.

The local pharmacology, the thermal response and the response to hypothalamic stimulation of sweat glands of the hairy surface of the beagle are described. The results, together with those of electron-microscopic examinations, support the idea that these sweat glands are apocrine and are not directly innervated. No clear relationship with thermoregulation could be found and a pheromonal function is tentatively suggested.     

Acitretin and etretinate in the treatment of palmoplantar pustulosis: a double-blind comparative trial

Sixty patients with palmoplantar pustulosis were treated in a double-blind trial with either acitretin (etretin, Ro 10–1670) or with etretinate. The study consisted of 4 weeks of therapy with three 10 mg capsules/day followed by 8 weeks of therapy with a varying number of capsules given daily according to therapeutic response. At the end of the 12-week treatment period, the mean number of pustules (± SEM) had decreased from 57.8 (± 8.6) to 3.9 (± 1.6) in the acitretin group and from 57.1 (± 14.1) to 5.7 (± 2.7) in the etretinate group. With regard to influence on erythema, infiltration, scaling, and area involved, similar improvements were obtained in both treatment groups. Adverse reactions of the hypervitaminosis A type were observed with almost the same frequency and severity in both treatment groups. The mean number of 10 mg capsules used daily was comparable in the two groups: 2.82 (range 1.23–4.67) for acitretin and 2.77 (range 1.60–4.82) for etretinate. It can be concluded that acitretin and etretinate do not significantly differ with regard to efficacy and overall safety in the treatment of patients with palmoplantar pustulosis.     

Identification of secretory immunoglobulin A in human sweat and sweat glands

Secretory immunoglobulin A (sIgA) plays an important role in local immune defense mechanisms. Although skin is always exposed to external antigens, the role of local immune defenses involving sIgA in the skin has not been adequately studied. In order to evaluate the presence of sIgA in sweat, we have measured the concentration of sIgA in human sweat by enzyme immunoassay and have localized the components of sIgA in the sweat glands of human axillary skin. The concentration of sIgA in sweat was found to be 10 times higher in men than in women (13.0 +/- 0.9 micrograms/ml versus 1.6 +/- 0.9 micrograms/ml). Secretory component (SC) was localized immunohistochemically in protein synthetic organelles, such as the perinuclear spaces and Golgi complex, in cytoplasmic vesicles, and along the external surface membranes of mucous cells on the terminal segment of eccrine sweat glands. IgA and J chain were present in plasma cells in the protein synthetic organelles. The luminal aspects of eccrine sweat ducts also strongly express SC, as well as IgA and J chain. Neither SC, IgA, or J chain were identified in epithelial cells of apocrine sweat glands. These findings are consistent with the theory that J chain complexed with dimeric IgA is synthesized in plasma cells and is transported by SC-mediated endocytosis transfer across mucous cells of eccrine sweat glands and thus into sweat.