Do training-dependent differences in perspiration exist between healthy and atopic subjects?

Sweating (perspiratio sensibilis) serves predominantly for thermoregulation and is triggered, among other stimuli, by physical stress. Although consensus on sex-dependent differences in sweating has not been reached so far and recent studies revealing abnormal diminution of the sweating capacity in atopic subjects are mainly based on heat exposure experiments, the influence of endurance training on perspiration in atopics has not yet been evaluated. Using a special sweat collector device reliable even during intensive body movement, we compared the sweat production of age-matched male and female healthy controls (14 m, 10 f) to that of in-patients with atopic eczema (AE: 14 m, 10 f) during and 5 min after physical exercise (30 min) with a bicycle ergometer under standardized experimental conditions. The individual stress limit was determined by a previous endurance test including repeated lactate blood level measurements and continuous heart rate control. Informed consent was obtained from every participant in the study. One half of both the patients and the controls underwent three week endurance training, and the preceding sweat measurements were repeated in all patients and controls after the training period under identical conditions. On average, the healthy males perspired nearly twice as much as the corresponding females (p < 0.0016). Highly significant mean differences of maximum sweat secretion rates were also found between the atopics and the controls. Healthy individuals of both sexes perspired nearly three times as much as did the patients with AE (males: p < 0.0004; females: p < 0.00009). Among the atopics there were remarkable, yet statistically insignificant, sexual differences in sweat production. After three weeks, sweating rates were similar to the initial ones in the training group as well as in the non-trained control group. Gender differences in perspiration do not only exist between healthy males and females but also in patients with atopic skin disorder, yet the latter ones at significantly lower levels as compared to healthy control subjects. No influence of a three-week-exercise phase on sweat secretion in atopics and controls could be proven. For designing further studies on intra- or intersexual differences of drug-independent perspiration, standardized physical stress can be recommended as an experimental prerequisite for sweat measurements.

Recent studies of cutaneous nociception in atopic and non-atopic subjects.

Itching reflects a distinct quality of cutaneous nociception elicited by chemical or other stimuli to neuronal receptors at the superficial layers of the skin and muco-cutaneous orifices. Although recent experimental studies of the conduction and perception of itch have yielded deeper insight into the physiology of this sensory quality, little is known about the neuromechanisms involved in pruritus accompanying many inflammatory skin diseases, in particular, in atopic eczema. Previous case-control studies of our research group with patients suffering from atopic eczema (AE) revealed significantly diminished itch perception after iontophoretic application of different doses of histamine as well as substance P (i.c. injected). Further experiments using acetylcholine (ACh, i.c.) clearly demonstrated that ACh elicits pruritus instead of pain in patients with AE. The first part of the present review deals with the results of our most recent case-control studies on histamine-induced itch perception in atopics devoid of eczema as well as in patients with urticaria or psoriasis compared to atopics with or without manifest eczema. We demonstrated that both focal itch and perifocal alloknesis (i.e., itch elicited by a slight mechanical, otherwise non-itching stimulus) were significantly reduced in eczema-free atopics yet were normal in non-atopics suffering from urticaria or psoriasis. In further studies using ACh i.c. injected into the uninvolved skin of patients with AE, lichen ruber, psoriasis, type IV contact eczema, or non-specific nummular eczema (n = 10/each group), all the atopics and 6/10 psoriatics felt itch instead of burning pain, but none of the others did. Different doses of vasoactive intestinal peptide (VIP) i.c. applied to the controls and the atopics with or without eczema did not markedly increase the intensity of nociceptive sensations. However, ACh induced pain in the controls, pure pruritus in the atopics with acute eczema, and a 'mixture' of pain and itch in the atopics just free from eczema. Obviously, the quality of sensations evoked by ACh and VIP depends on the inflammatory or non-inflammatory state of the atopic skin. In a placebo-controlled, double blind study on histamine-induced focal itch and alloknesis with healthy subjects (n = 15) using naltrexone (opioid receptor antagonist) and cetirizine (H1-blocking agent), naltrexone was found to significantly reduce both itching and alloknesis. Cetirizine reduced focal itch but failed to influence the alloknesis phenomenon. The wheal and flare reaction was suppressed only by cetirizine. These different effects point to a mainly CNS-based activity of naltrexone but a peripheral level effect of cetirizine. Due to long-lasting experience with group sport as a supporting adjuvant for inpatients with AE, we evaluated, by clinical, psychometric, and physiological studies, the therapeutic efficacy of controlled physical exercise in addition to otherwise equal anti-eczematous therapy for both voluntary participants and non-participants in sports by performing several case-control studies, one followed-up to 6 months after the patients' discharge from the hospital. Regular moderate exercises neither deteriorated nor impeded the recovery from AE, ameliorated the participants' scratch controlling ability and significantly their depressed emotional mood. The non-participants failed to achieve these aims. Sweating-induced itch was inhibited in almost all participants if simple skin care (clearing by warm shower, ointment) and short-term rest were used by informed patients. In conclusion, there are several indications that itching is elicited in individuals inclined to cutaneous atopy, regardless of their eczematous or just eczema-free state, by a different physiological pathway from that in non-atopic individuals. Therefore, antipruritic agents influencing the centrally altered nociception of atopics are needed and may be expected in near future. (ABSTRACT TRUNCATED)

Rhythmical changes of the cutaneous blood flow in the forehead region under the condition of hypnoid relaxation.

BACKGROUND: A characteristic and stable blood flow rhythm can be detected for the skin of the forehead and ear lobes with frequencies of approx. 0.15 Hz (9/min), which were primarily not related to the respiratory rhythm. PATIENTS AND METHODS: The perfusion of the skin in the forehead region was investigated non-invasively with laser Doppler fluxmetry in ten healthy subjects before and during Hypnoid Relaxation (HyR). The HyR-state was induced by suggesting formulas regarding to the well known Autgeneous Training. RESULTS: In all test subjects rhythmical fluctuations of bloodflow with a frequency of approx. 0.15 Hz could be observed both, before and during HyR. We found that the amplitude of these fluctuations clearly (> 20% from individual baseline) increased in five of ten test subjects under the condition of HyR. Furthermore, in three of ten cases the spontaneous respiration under HyR adjusted to the frequency of the described bloodflow rhythm, which exists both, before and during HyR. CONCLUSIONS: These phenomena suggest an individually stabil and autonomous rhythm which is effected by alterations in the level of conciousness and which may be caused by the close linkage between the nerval structures for control of respiratory and circulatory systems. May be, this autonomic rhythm could be used as a trigger for breathing therapies or as a parameter for the impact of relaxation techniques on hemodynamics, e.g. in complementary therapy of vascular diseases like systemic sclerosis.

Graft-versus-host-like mucocutaneous eruptions with serological features of paraneoplastic pemphigus and systemic lupus erythematosus in a patient with non-Hodgkin's lymphoma.

A 63-year-old male patient spontaneously developed severe erosive orogenital mucositis, palmoplantar and gluteal inflammatory lesions resistant to therapy. The skin lesions clinically and histologically resembled lichen-planus-like graft-versus-host disease. Investigation for an underlying autoimmune or malignant disorder revealed a centrocytic-centroblastic low-grade non-Hodgkin's lymphoma (according to the Kiel classification) in the bone marrow, mesenterial and iliacal lymphoma. Serological titers were intermittently positive for ANA, anti-Sm/U1RNP, anti-Ro and anti-dsDNA. Immunoprecipitation of lysates from radiolabeled human keratinocytes with the patient's serum revealed circulating antibodies against 210-kD (desmoplakin II), 190- and 170-kD antigens but none against the 230-kD antigen or 250-kD desmoplakin I. Under cytostatic chemotherapy the lymphomas showed complete and long-lasting remission, whereas the mucocutaneous lesions persisted. Six years after diagnosis, the mucocutaneous lesions are sufficiently controlled by immunosuppressive therapy. In the presented case, several features of lymphoma-associated dysimmunoreactivity are assumed that bring about the intrinsic production of various autoantibodies typical of paraneoplastic pemphigus and systemic lupus erythematosus.

[Lupus erythematosus/lichen ruber planus overlap syndrome. 5 cases in a patient sample of the Erlangen University Dermatology Clinic (1894-1995)]. / Lupus-erythematodes-/Lichen-ruber-planus-Overlap-Syndrom. 5 Fälle im Patientengut der Dermatologischen Universitätsklinik Erlangen (1984-1995).

The simultaneous occurrence of lupus erythematosus (LE)- and lichen ruber (LP)-like symptoms is called LE/LP-overlap syndrome (LE/LP-OS). It is defined by concomitant clinical, histologic and immunhistologic features of both diseases. To date, 47 cases of this rare dermatosis have been reported with marked differences in the skin lesions: They are either of intermediate appearance between LE and LP (type I = intermediate type), or show a coexistence of LE- and LP-specific lesions (type II = polar type). To determine the frequency and characteristics of the LE/LP-OS we reviewed our LE-patients from 1984-1995. 5 cases were diagnosed. The frequency of LE/LP-OS in our patients is higher than generally assumed. Due to its variable clinical, histological and immunhistological appearance and the lack of unequivocal pathognomonic signs, this overlap-dermatosis may be underdiagnosed. Since therapeutic consequences result from the diagnosis, criteria are suggested to facilitate the recognition of the LE/LP-OS.

[Sex-dependent differences in sweating of normal probands and atopic patients in cardiovascular stress]. / Geschlechtsabhaängige Unterschiede im Schwitzverhalten von Normalpersonen und Atopikern unter Kreislaufbelastung.

Sweating (perspiratio sensibillis) due to cholinergic sweat gland activity serves predominantly for thermoregulation and is triggered among others by physical stress. Individuals suffering from atopic eczema usually respond to sweating with generalized itching. Different sweat regulation in atopic patients and healthy controls under cholinergic stimulation and heat chamber provocation tests has already been examined in several studies. However, no clinical trial has yet been done on atopic sweat regulation during physical stress. Sex-specific sweat secretion rates have not been evaluated. In our trial we compared sweat amounts of male and female atopics (14 m, 10 f) and healthy controls (14 m, 10 f) during and after physical activity on a bicycle ergometer. We used a special sweat collector system reliable even at intensive body movement. The individual stress limit had been determined by previous endurance training with lactate level and heart rate measurement. We found a highly significant difference in maximum sweat amounts between atopics and controls. On average, healthy individuals (of both sexes) perspired nearly three times as much as atopic patients. Male controls perspired nearly twice as much as corresponding females. Among the atopics, sex-specific differences were found to be not statistically relevant.

[Aphthae and aphthous lesions of the mouth mucosa]. / Aphten und aphthoide Läsionen der Mundschleimhaut.

Recurrent aphthae (or aphthoses) are the most frequent inflammatory lesions of the oral mucosa. Aphthae can clearly be defined, but may also be barely discernible from aphthoid erosions and ulcers of heterogeneous origin. Although a subject of molecular research, the etiopathogenesis of oral aphthoses is still unknown. However, the clinical differentiation of a "benign" type of aphthosis from a "pernicious" one, such as Behçet's disease (BD), is a diagnostic matter of great significance. BD has been found clinically in increasing numbers in central Europe and represents an (auto-)hyperimmune multisystem life-threatening vasculitis. In this disorder possible damage can occur to many visceral organs and/or the cerebrospinal system. The prognosis of BD may depend on the changing involvement of very different organs, as well as the early recognition of the disease per se. The most prominent feature is a multilesional aphthous stomatitis that is almost never absent during acute episodes of BD. Hence, the occurrence of this peculiar type of aphthosis strongly indicates an active BD. The plethora of other aphthoid lesions can be challenging to the diagnostic competence of all physicians and may confuse the correct recognition of the severity of the disease present. This review particularly details the wide range of diagnostic, therapeutic and prognostic aspects of the various oral aphthoses.

[Glossitis granulomatosa--an unusual subtype of Melkersson-Rosenthal syndrome]. / Glossitis granulomatosa--ein ungewöhnlicher Subtyp des Melkersson-Rosenthal-Syndroms.

So-called "glossitis granulomatosa", described in 1952 by H. Schuermann as a peculiar manifestation of Melkersson-Rosenthal syndrome (MRS), is little known in oral medicine due to the paucity of cases published so far. During the past 25 years the author has observed eight definite cases of glossitis granulomatosa and confirmed its close connections with MRS. The recurrent inflammation tends to change into persisting macroglossia with considerable functional and sensory oral disturbances. The clinical diagnosis, histologically supported by biopsy, can definitely be established, yet the outcome of the mostly chronic macroglossitis (with danger of later tongue carcinoma) may be very doubtful. Knowledge of Schuermann's glossitis, a member of the group of etiologically unclarified lingual inflammations, is important for physicians involved in oral medicine because of its therapeutic and prognostic implications.

Acetylcholine is an inducer of itching in patients with atopic eczema.

As previous experimental studies disproved histamine as the main mediator of eliciting pruritus in atopic eczema (AE), we examined the neurocutaneous sensations in 15 patients with AE and in 15 age- and sex-matched non-atopic controls after i.c. injection of acetylcholine (Ach, 0.5 M, 20 microliters) or buffered saline. The sensory perceptions were rated by the participants of the study with regard to their quality and intensity using a visual analogue scale. Simultaneously, the vascular reactions to Ach were recorded by the examinators via laser Doppler fluxmetry as well as flare and wheal planimetry. In contrast to the approximately equal flare and wheal extensions in either group, the cutaneous sensations differed significantly. The patients complained of 'pure' itching that developed shortly after Ach injection, whereas the control subjects reported only burning pain. Moreover, the patients perceived their sensations significantly earlier and significantly longer than did the controls. The study provides evidence that Ach plays an important role in the pathogeny of pruritus in patients with AE. Further investigations of the neuronal mechanisms involved in this atopy-related effect of Ach have to be performed.

CD36 (OKM5) antigen expression on human mucosal epithelia is associated with keratinization type.

The glycoprotein CD36 functions as a thrombospondin receptor and is expressed on a variety of cell types, including platelets, monocyte/macrophages, and endothelial cells. In human skin, the presence of CD36 on keratinocytes was initially found in lesional areas of T-cell mediated inflammatory dermatoses. Controversy still exists on the interpretation of this expression as an inflammatory or differentiation-associated marker. So far, only limited data are available on CD36 expression in oral epithelia. The present immunohistochemical study was therefore performed to determine the presence of CD36 on keratinocytes of healthy and disease-affected epithelia of the oral cavity in 80 biopsy specimens. As results, we found an inflammation-independent strong expression of CD36 in oral epithelia with ortho- and parakeratinization, such as the oral side of the gingiva, the hard palate, and the back of the tongue. Non-keratinized epithelia such as the gingival pocket epithelium, the soft palate, the lip, the buccal mucosa, and the side of the tongue were CD36 negative. We therefore suggest that CD36 expression in keratinocytes from oral epithelia is an epithelial differentiation marker.

Melkersson-Rosenthal syndrome--a challenge for dermatologists to participate in the field of oral medicine.

Melkersson-Rosenthal syndrome (MRS) is a neuro-muco-cutaneous disorder involving remittently both the oro-facial innervation and muco-cutaneous tissues in a pathosis of complex origin characterized by recurrent edema, facial or other palsies, and nerval dysfunctions frequently associated with plicated tongue. Biopsies taken from the edematous tissues often reveal a temporary pattern of moderate epitheloid granulomatous inflammation scattered scarcely within remarkable tissue edema. However, this histological pattern is not a prerequisite for the diagnosis of MRS. The disease usually runs an intermittent and unpredictable course over years or decades and may have, if the edemas involve the tongue or the central nervous system, an ambiguous outcome. Greatly disfiguring oro-facial swellings often result from secondary persistence of the primarily recurrent edemas. A classification on grounds of different 'major' and 'minor signs' of MRS is proposed in the present paper. In recent years, novel therapeutic approaches involving either oral clofazimine or laser beam acupuncture (according to the principles of traditional Chinese medicine) have proven to be successful in some cases of MRS. Dermatology could play a larger role in oral medicine by taking diseases such as MRS into account in studies among specialties dealing with oro-facial pathoses.

Physical stress-induced secretion of adrenal and pituitary hormones in patients with atopic eczema compared with normal controls.

Atopic eczema is a chronic inflammatory skin disease which shares some psychological and neuroendocrine disturbances with patients suffering from depression. In view of recent findings of an attenuated response of the hypothalamic-pituitary-adrenal (HPA) system in patients with atopic eczema during a human corticotropin-releasing hormone (hCRH) challenge paradigm fourteen consecutive non-specifically trained in-patients with atopic eczema (8 men, 6 women) and an age-matched control group (8 men, 6 women) performed exhausting incremental graded bicycle exercise to evaluate cortisol, adrenocorticotropin (ACTH), beta-endorphin, epinephrine and norepinephrine releases induced by physical stress. The exercise yielded significant increases in cortisol, ACTH, beta-endorphin, epinephrine and norepinephrine concentrations in both groups. Patients with severe eczema displayed a significantly lower increase in norepinephrine levels when compared with the less affected patient group. In contrast to the challenge with exogenous hCRH no substantial difference in the net responses of ACTH and cortisol could be detected between patients with atopic eczema and controls using the physical stress paradigm. These substantial differences in the net outcome between both challenges may be related to the potential synergizing effects of various neuropeptides, e.g. CRH and vasopressin, when activating the HPA system by challenges at a suprapituitary site which may override subtle disturbances in the responsivity of the HPA system as revealed by CRH challenge alone in patients with atopic eczema.

Respiratory-dependent laser-Doppler flux motion in different skin areas and its meaning to autonomic nervous control of the vessels of the skin.

The aim of this study is to evaluate and quantify the respiratory dependency of cutaneous laser-Doppler flux motion in two variable innervated sites of the upper extremity (the proximal volar forearm and the fingertip) by using a computer-supported system. Various spontaneous (6-17/ min) and externally triggered (12 or 6/min) respiratory frequencies were used for comparative frequency analysis of the laser-Doppler flux signal. Further, an index (MIRSF) was determined as an indicator of the correlation between flux motion and respiration. The MIRSF is defined as the ratio of the power spectrum of the LDF signal at the specific respiratory frequency divided by the time-averaged LDF for that time period. The MIRSF enables a comparison of different intra- and interindividual flux values. A very high correlation was seen between the respiratory frequency and the MIRSF during spontaneous respiration in the skin of the proximal volar forearm; the lower the spontaneous respiratory frequency, the higher the MIRSF. However, this correlation could not be found in the results of the fingertip. The presence of a constant and therefore externally triggered respiratory frequency increased the modulations of the LDF at both measurement locations. While triggered respiration produced a decline in the taLDF of the fingertip, the taLDF of the forearm was unaffected. Considering the different innervation and hydrostatic effects the results lead to the following conclusion: the finger vessels are richly innervated with adrenoceptors which causes alpha 1-mediated vasoconstriction. In contrast to the vessels of the fingers those of the forearm seem to be under andrenergic as well as cholinergic control. Hydrostatic components appear to be more prevalent in the volar forearm site.

[Antipruritic effect of antihistaminic and local anesthetic topical agents after iontophoretic histamine stimulation]. / Antipruritugener Effekt antihistaminerger und lokalanästhetischer Externa nach iontophoretischem Histaminreiz.

No adequate topical therapy is available for pruritus. As little is known about the local influence of antihistamines and topical anaesthetics on the pruritic effect of histamine, we studied these agents in 12 volunteers. The antipruritic effect of 15-min topical application of dimethindene maleate (Fenistil gel) and different agents (Optiderm, EMLA, Xylocaine-Salbe 5%) on subsequent focal histamine stimulus (20 mC) given by iontophoresis was evaluated. The results were compared with those of pretreatment with the corresponding placebo creams and observations on skin. Wheal and flare areas were evaluated planimetrically. Itch or pain ratings were entered on a scale every minute over a 24-min period. The examination also comprised alloknesis, i.e. elicitation of perifocal itch sensation by usually non-itch-inducing (e.g. mechanical) stimuli. Remarkably, all topically applied substances, regardless of antihistaminic or anaesthetic potential, reduced the area of alloknesis significantly. This is likely to be a result of diminished excitability of the cutaneous mechanoreceptors. Itching was significantly reduced by all active substances, including the placebo cream corresponding to Optiderm, which might be due to the presence of urea.

Immunohistochemical localization of very late activation integrins in healthy and diseased human gingiva.

The beta 1-integrins (VLA family) are cellular adhesion molecules (CAM) that play a major role in cell-cell and cell-matrix interactions. The expression pattern of CAM was studied in 5 clinically normal volunteers with healthy gingiva and in 18 patients with clinically different stages of periodontitis. In healthy human gingiva alpha 2, alpha 3 and alpha 6 integrin chains were found in a characteristic distribution, showing a broad continuous expression on the junctional and sulcular epithelium sites. The expression of these integrins was demonstrated primarily on the basal cell layers and in some cells of the stratum spinosum. Inflammatory stages of periodontitis revealed further upregulation of alpha 2, alpha 3 and alpha 6 integrins into the junctional and sulcular epithelial cells, which correlated with the stage of the periodontitis and the extent of the cellular infiltration. alpha 4 and alpha 6 were found to be the predominant beta 1 integrin chains on inflammatory cells. The amount of alpha 4 and alpha 6 positive infiltrative cells increased with the number of inflammatory cells. VCAM-1, the corresponding cell-cell ligand of VLA-4 (alpha 4) was present on the majority of subepithelial vessels in all stages of gingivitis and periodontitis. The alpha 5 subunit was expressed on both endothelium and gingival connective tissue cells. Samples from advanced periodontitis cases showed a higher number of alpha 5 positive mononuclear cells. In comparison to normal epidermis, human gingival epithelial cells express higher levels of integrins. This expression is further upregulated in advanced stages of periodontitis, indicating changes of the beta 1 integrin organization.

Acetylcholine induces different cutaneous sensations in atopic and non-atopic subjects.

The mediators eliciting pruritus in atopic eczema are a matter of discussion, since several substances may be involved and histamine is unlikely to be the main agent. Hence, in this study we examined the cutaneous sensations and vascular reactions in 15 patients with atopic eczema and in 15 non-atopic subjects after i.c. injection of acetylcholine (Ach, 0,5 M, 20 microliter) or buffered saline, respectively. The sensory perceptions were rated by a visual analogue scale (VAS) as to quality and intensity, and the vascular reactions were monitored by laser Doppler flowmetry and evaluated planimetrically as to flare and wheal extension. The flares and wheals in both groups were similar; yet the cutaneous sensations significantly differed, since all patients with atopic eczema complained of "pure" itching after Ach-injection, whereas the controls reported a burning pain. The patients with atopic eczema started their ratings significantly earlier and rated significantly longer than the controls. Our results provide evidence that Ach may play an important role in the etiology of pruritus in atopic eczema patients.

Systemic corticosteroids are important in the treatment of Fournier's gangrene: a case report.

Fournier's gangrene represents an acute severe necrotizing inflammatory process affecting the scrotum and penis. It has an associated mortality of 30-50%. In most cases, aetiological factors can be identified, such as diabetes mellitus, chronic alcoholism and perianal, perirectal or periurethral infection. The disease is characterized by a polybacterial infection, and the classic treatment includes surgical removal of the necrotic tissue and the use of broad-spectrum antibiotics. We report a case of Fournier's gangrene, histologically characterized by a necrotizing vasculitis, in which surgical resection of the necrotic tissue and antibiotic treatment failed to halt progression of the disease, whereas complete remission was achieved by high-dose corticosteroid therapy. This suggests that Fournier's gangrene is related to some form of localized vasculitis, and represents a local Shwartzman phenomenon.