Thermogenic and psychogenic sweating in humans: Identifying eccrine glandular recruitment patterns from glabrous and non-glabrous skin surfaces.

In this experiment, psychogenic (mental arithmetic), thermogenic (mean body temperature elevation of 0.6 °C) and combined thermo-psychogenic treatments were used to explore eccrine sweat-gland recruitment from glabrous (volar hand and forehead) and non-glabrous skin surfaces (chest). It was hypothesised that each treatment would activate the same glands, and that glandular activity would be intermittent. Nine individuals participated in a single trial with normothermic and mildly hyperthermic phases. When normothermic, a 10-min arithmetical challenge was administered, during which sudomotor activity was recorded. Following passive heating and thermal clamping, sweating responses were again evaluated (10 min). A second arithmetical challenge (10 min) was administered during clamped hyperthermia, with its sudorific impact recorded. The activity of individual sweat glands was recorded at 60-s intervals, using precisely positioned, and uniformly applied, starch-iodide papers. Those imprints were digitised and analysed. Peak activity typically occurred during the thermo-psychogenic treatment, revealing physiologically active densities of 128 (volar hand), 165 (forehead) and 77 glands.cm-2 (chest). Except for the hand (46%), glands uniquely activated by one treatment were consistently <10% of the total glands identified. Glandular activations were most commonly of an intermittent nature, particularly during the thermogenic treatment. Accordingly, we accepted the hypothesis that psychogenic, thermogenic and thermo-psychogenic stimuli activate the same sweat glands in both the glabrous and non-glabrous regions. In addition, this investigation has provided detailed descriptions of the intermittent nature of sweat-gland activity, revealing that a consistent proportion of the physiologically active glands are recruited during these thermal and non-thermal stimuli.

Generalized hyperhidrosis secondary to presumed eccrine gland dysfunction with possible apocrine metaplasia.

We present a 57 year-old man presented with generalized hyperhidrosis and widespread, smooth, flesh colored papules on the torso and extremities.Histological examination from multiple biopsies demonstrated morphologic alteration of the eccrine glands with an apocrine phenotype, suggesting eitherapocrine metaplasia or the presence of "apoeccrine glands." The morphologic similarities between eccrine, apocrine, and apoeccrine as they relate to ourpatient's histologic findings are discussed. We consider secondary causes of generalized hyperhidrosis, which may also play a role in this patient's presentation. Treatment and further workup are discussed, whilemanagement of this patient remains in progress.

Hyperhidrosis, bromhidrosis, and chromhidrosis: Fold (intertriginous) dermatoses.

Human sweat glands disorders are common and can have a significant impact on the quality of life and on professional, social, and emotional burdens. It is of paramount importance to diagnose and treat them properly to ensure optimal patient care. Hyperhidrosis is characterized by increased sweat secretion, which can be idiopathic or secondary to other systemic conditions. Numerous therapeutic options have been introduced with variable success. Novel methods with microwave-based and ultrasound devices have been developed and are currently tested in comparison to the conventional approaches. All treatment options for hyperhidrosis require frequent monitoring by a dermatologist for evaluation of the therapeutic progress. Bromhidrosis and chromhidrosis are rare disorders but are still equally disabling as hyperhidrosis. Bromhidrosis occurs secondary to excessive secretion from either apocrine or eccrine glands that become malodorous on bacterial breakdown. The condition is further aggravated by poor hygiene or underlying disorders promoting bacterial overgrowth, including diabetes, intertrigo, erythrasma, and obesity. Chromhidrosis is a rare dermatologic disorder characterized by secretion of colored sweat with a predilection for the axillary area and the face. Treatment is challenging in that the condition usually recurs after discontinuation of therapy and persists until the age-related regression of the sweat glands.

Quantification of eccrine sweat glands with acetylcholine sweat-spot test and anatomical redistribution of sweating after T2-T3 thoracoscopic sympathicolysis.

BACKGROUND: In this study, patients treated by thoracoscopic sympathicolysis for palmar hyperhidrosis were evaluated to determine the number and response of sweat glands to intradermal acetylcholine stimulus. METHODS: A total of 30 patients were included in the study. Group A consisted of 10 patients with palmar hyperhidrosis who underwent thoracoscopic sympathicolysis in October 2005, and group B consisted of 20 patients who underwent surgery during the years 1999, 2000, and 2001. The study procedure involved applying iodine alcohol to the palm and then intradermally injecting 0.1 ml 1% acetylcholine. This activated the sweat glands, which were then photographed and counted. The study procedure was performed prospectively over different periods in group A and retrospectively in group B. RESULTS: In group A, the mean number of glands activated 1, 3, 6, and 12 months after surgery were 41, 174.20, 522.8, and 747.2, respectively; this gradual increase was statistically significant over the first 6 months (p = 0.004) but not between months 6 and 12 (p = 0.255). The trend towards an increasing number of active glands occurred in both groups, with a mean of 1369.8 active glands in group B compared to 747.2 (p = 0.095) in group A after 12 months. CONCLUSION: It is well-known that Cannon's law of denervation (1939) is not applicable to the sweat glands, that is, there is no hyperactivation following intradermal acetylcholine stimulation. However, some response, which increased over the first 6 months following surgery, was observed in our study. Nevertheless, this activation is subsequently self-limiting, resulting in no gland atrophy, and reinnervation occurs without patient awareness.

Impaired left ventricular filling in patients with essential hyperhidrosis: an echo-Doppler study.

Essential hyperhidrosis is a well recognized dermatologic and neurologic disorder, characterized by excessive sweating of the eccrine sweat glands. It is also associated with cardiac autonomic dysfunction because sympathetic fibers to eccrine glands of palms of the hand arise from stellate and upper thoracic ganglia, which also innervate the heart. In this study, we investigated cardiac function in patients with essential hyperhidrosis by conventional and tissue Doppler imaging methods. Eighteen subjects with essential hyperhidrosis and eighteen control subjects were included in this study. Pulsed-wave Doppler parameters of the left and right ventricles, which represent diastolic filling abnormalities, were obtained by conventional Doppler and tissue Doppler imaging. Isovolumetric relaxation time, isovolumetric contraction time, ejection time and myocardial performance index were also calculated. Mitral inflow peak early (E(M)) and late (A(M)) velocities and E(M)/A(M) ratio, which represent diastolic filling of left ventricle, were significantly lower in hyperhidrotic subjects than in controls. Also, mitral lateral annulus early and late velocities and early/late velocity ratio, reflecting diastolic filling of left ventricle, were significantly lower in hyperhidrotic subjects than those of controls. However, there were no differences between hyperhidrotic subjects and control subjects with regard to the other echocardiographic indices of left and right ventricle diastolic functions. In conclusion, decreased mitral inflow suggests left ventricle diastolic dysfunction in patients with essential hyperhidrosis. This indicates that hyperactivity of sympathetic nervous system in patient with hyperhidrosis may alter cardiac function in long term.

Axillary hyperhidrosis: eccrine or apocrine?

We review the literature regarding axillary hyperhidrosis, discuss normal sweat gland function and postulate on the respective roles of the eccrine, apocrine and apo-eccrine glands in the pathophysiology of excessive axillary sweating.

Vulvar hidradenitis suppurativa. Immunohistochemical evaluation of apocrine and eccrine involvement.

OBJECTIVE: To evaluate the pathology of vulvar hidradenitis suppurativa (HS). STUDY DESIGN: A retrospective review of the histology of resections for vulvar HS was performed, and a battery of immunohistochemical stains was performed. They included markers of apocrine differentiation (GCDFP-15, CD15, lysozyme) and eccrine differentiation (GCDFP-15, S-100, CA-19.9, HMB45). RESULTS: Thirteen cases were available for review. Eccrine glands accounted for the majority of glands in all cases. Apocrine glands were not seen or were present only away from the area of active inflammation in 10 cases. In two cases, glands were totally destroyed in the areas of inflammation. Evidence of follicular obstruction was present in 11 of 13 cases. Severity of inflammation was variable, ranging from minimal, with burned-out disease, to severe. Fibrosis was variable but was greater with less inflammation, suggesting a later stage in disease evolution. Inflammation of the glands was often absent or minimal and seen only with associated poral occlusion. GCDFP-15 stained both apocrine and eccrine glands (only the dark cells). S-100 stained only the secretory (clear) cells of the eccrine glands. CD15 stained apocrine glands. Lysozyme stained apocrine glands, but this was not a consistent finding. CA19-9 gave inconsistent results in eccrine glands. HMB-45 was negative in all cases. CONCLUSION: Cases of vulvar HS showed a majority of eccrine glands in active areas. Apocrine glands, when present, were away from active inflammation. Inflammation and eventual destruction of glands appear to be a secondary part of the disease process. GCDFP-15 is a reliable marker for both apocrine differentiation and the dark cells of eccrine glands. S-100 is a reliable marker for the clear cells of eccrine glands. CD15 also was reliable for apocrine differentiation. Lysozyme showed weak apocrine staining. CA19-9 and HMB-45 were not reliable markers for apocrine or eccrine gland differentiation.

Skin morphological changes in growth hormone deficiency and acromegaly.

OBJECTIVE: To evaluate the histomorphology of skin and its appendages, especially eccrine sweat glands, in patients with GH disorders, because reduced sweating ability in patients with growth hormone deficiency (GHD) is associated with increased risk of hyperthermia under stressed conditions. DESIGN AND METHODS: A skin biopsy was obtained from 17 patients with GHD treated with GH, five patients with untreated GHD, 10 patients with active acromegaly and 13 healthy controls. RESULTS: The sweat secretion rate (SSR) was significantly decreased in both the untreated (median 41 mg/30 min, range 9-79 mg/30 min) and the GH-treated (median 98 mg/30 min, range 28-147 mg/30 min) patients with GHD compared with that in controls (median 119 mg/30 min, range 90-189 mg/30 min; P=0.001 and 0.01 respectively). Epidermal thickness was significantly decreased in both untreated (median 39 microm, range 28-55 microm) and GH-treated patients with GHD (median 53 microm, range 37-100 microm), compared with that in controls (median 66 microm, range 40-111 microm; P<0.02). A statistically non-significant tendency towards thinner epidermis (median 59 microm, range 33-83 microm) was recorded in acromegalic patients (P=0.08) compared with controls. There was no significant difference in the area of the sebaceous glands in the biopsies between the three groups and the controls. The area of eccrine sweat gland glomeruli was significantly decreased in the untreated patients with GHD (median 16407 microm2, range 12758-43976 microm2) compared with that in controls (median 29446 microm2, range 13511-128661 microm2; P=0.03), but there was no significant difference between the GH-treated patients with GHD and controls. CONCLUSIONS: We conclude that GH, either directly or via IGF-I, may have both a structural and a functional effect on human skin and its appendages, and that patients with GHD have histomorphological changes in skin compared with controls. Importantly, these changes are not fully reversed despite long-term and adequate GH treatment in patients with childhood onset GHD.

[Toxin treatment of sweat pearls. A review of the treatment of hyperhidrosis with a special view of a new therapy option using botulinum toxin A]. / Die Giftbehandlung von Schweissperlen. Eine Ubersicht der Hyperhidrose-Behandlung unter speziellem Blickwinkel der neuen Therapieoption mit Botulinumtoxin A.

Hyperhidrosis is defined as an excess of sweating beyond the amount needed to cool down elevated body temperature. We distinguish a primary and a secondary form, where an underlying endocrinological or neurological disease is found. The innervation of eccrine sweat glands is sympathetic but the transmitter is cholinergic (ACh). There are variable modalities in the treatment of focal hyperhidrosis, such as topical aluminium chloride application, tapwater iontophoresis, anticholinergic drugs or surgery (axillary sweat gland extraction, liposuction or thoracoscopic sympathectomy). Only recently botulinum toxin (BTX) has been introduced as a therapeutic tool for hyperhidrosis. As BTX inhibits the release of ACh at the cholinergic synapse, perspiration is arrested completely after intradermal injection. BTX is a very potent alternative to the surgical approach in the treatment of hyperhidrosis, though the treatment must be repeated regularly to maintain the effect.

Abnormal sudomotor function in the hypomelanotic macules of tuberous sclerosis complex.

To investigate the integrity of sympathetic innervation in the hypomelanotic macules of tuberous sclerosis complex, we studied sudomotor function in nine patients with tuberous sclerosis complex. Postganglionic sudomotor function was assessed using the Silastic imprint test in nine patients with tuberous sclerosis complex who have at least one hypomelanotic macule greater than 2 cm in diameter. Sweating was induced by iontophoresis with 0.5% pilocarpine nitrate and sweat droplets were counted under a microscope using a 1 x 1 cm grid. Silastic imprint testing of an analogous skin area contralateral to the hypomelanotic macule was measured as a control. Sweat volume quantitation using sweat collectors was performed in five of the subjects. The sweat volume collected from the hypomelanotic macule was reduced compared to the control skin in four of the five subjects. Sweat droplet counts from the hypomelanotic macule were significantly reduced in only one of nine subjects. These data suggest that, although there is no difference in the number of functioning sweat glands in most hypomelanotic macules, the sweat glands produce less sweat (ie, decreased sweat volume) than in normal skin. We hypothesize that focal abnormalities of sympathetic innervation might be responsible for the hypomelanotic macules of tuberous sclerosis complex.

Nonneoplastic disorders of the eccrine glands.

Eccrine glands are uniquely susceptible to a variety of pathologic processes. Alteration in the rate of sweat secretion manifests as hypohidrosis and hyperhidrosis. Obstruction of the eccrine duct leads to miliaria. The excretion of drugs into eccrine sweat may be a contributory factor in neutrophilic eccrine hidradenitis (NEH), syringosquamous metaplasia (SSM), coma bulla, and erythema multiforme (EM). Alterations in the electrolyte composition of eccrine sweat can be observed in several systemic diseases, most notably cystic fibrosis. This article summarizes current knowledge of eccrine gland pathophysiology.

Nonneoplastic disorders of the eccrine glands

Eccrine glands are uniquely susceptible to a variety of pathologic processes. Alteration in the rate of sweat secretion manifests as hypohidrosis and hyperhidrosis. Obstruction of the eccrine duct leads to miliaria. The excretion of drugs into eccrine sweat may be a contributory factor in neutrophilic eccrine hidradenitis (NEH), syringosquamous metaplasia (SSM), coma bulla, and erythema multiforme (EM). Alterations in the electrolyte composition of eccrine sweat can be observed in several systemic diseases, most notably cystic fibrosis. This article summarizes current knowledge of eccrine gland pathophysiology.

Dry skin (xerosis) in patients undergoing maintenance haemodialysis: the role of decreased sweating of the eccrine sweat gland.

The aetiology and the pathophysiological mechanisms underlying the development of dry skin in uraemia are still unclear, but the hydration status of stratum corneum clearly influences the appearance of skin. The xerotic skin texture is often referred to as 'dry skin' and has been suggested as a cause of uraemic pruritus. To understand the aetiology of dry skin in uraemia we measured the status of skin surface hydration of uraemic patients with the corneometer and skin surface hydrometer, the functional capacity and the urea concentration of stratum corneum and the response of eccrine sweat gland to sudorific agent (0.05% pilocarpine HCL) in 18 age-matched haemodialysis patients and 10 healthy volunteers. We also performed the water sorption-desorption test to uraemic and control subjects after application of urea in various concentrations. Uraemic patient's skin showed decreased water content compared to control subjects. However, we found no correlation between dry skin and pruritus. Although the urea concentration of the horny layer in uraemic patients was elevated compared to control subjects (28.2 microgram/cm2 vs 5.04 micrograms/cm2, P < 0.05), its moisturizing effect to relieve pruritus is questionable because its artificial application revealed no improvement of the functional capacity of horny layer in concentration 5 times higher than the physiological concentration. Uraemic patients showed decreased sweating response to sudorific agent. In conclusion, the functional abnormalities of eccrine sweat glands may be account for dry skin in uraemic patients at least in part, but there is no correlation between xerosis and pruritus.

The topography of eccrine sweating in humans during exercise.

The purpose of this study was to investigate the distribution of steady-state sweating rates (msw), during stressful exercise and heat exposures. Six men completed 42-min trials: 2-min rest and 40-min cycling at 40% peak power in 36.6 degrees C (relative humidity 46.0%). The msw was monitored using ventilated capsules at the forehead, and at three additional sites. Repeat trials allowed monitoring from eleven skin surfaces. Auditory canal temperature (Tac) and 11 skin temperatures were measured. After normalising msw to the forehead response within subjects, differences in Tac and onset time thresholds, and transient and steady-state msw were examined. The pooled, lower torso msw onset [mean 45.5 (SEM 42.0) s] preceded that of the head [mean 126.5 (SEM 34.8) s, P < 0.05], but was not significantly different from the legs [mean 66.6 (SEM 25.7) s], upper torso [mean 80.2 (SEM 36.8) s] or arms [mean 108.6 (SEM 31.2) s]. Transient msw did not differ among regions (P = 0.16). Mean, steady-state forehead msw [3.20 (SEM 0.51) mg.cm-2.min-1] was not significantly greater than the scapula, forearm, hand, stomach and lower back msw (in descending order), but was greater than the chest [1.6 (SEM 0.2)], upperarm [1.6 (SEM 0.2)], calf [1.5 (SEM 0.3)] and thigh msw [1.0 (SEM 0.2), P < 0.05 for all comparisons]. The results did not support the caudal-to-rostral sweat onset evident during supine, resting heat stress. Equivalent Tac sweat thresholds existed between sites, while steady-state state msw topography varied among subjects and was not dominated by central regions.

Changes in cholinergic sweat gland activation in diabetic neuropathy identified by computerised sweatspot analysis.

Peripheral small-fibre denervation has been reported to result in decreased activation of eccrine sweat glands to muscarinic cholinergic agents. Using computerised image-analysis of pilocarpine-activated sweatspot prints of a 4 cm2 area of the dorsum of the foot in 79 randomly selected diabetic patients we have identified a group of neuropathic patients (18%) with decreased sweatspot activation (less than 20/cm2), and a smaller group (6%) of younger patients with less marked neuropathy who had increased activation (greater than 132/cm2), probably resulting from denervation supersensitivity. The associations between sweatspot density and other conventional tests of peripheral nerve function were weak. The prevalence of abnormal sweatspot density, 24%, was similar to that of other tests, except thermal thresholds at the feet (35-37%), which were not correlated with sweatspot activation, suggesting that diabetic neuropathy has differing effects on afferent and efferent small fibres. The method is rapid and reproducible (median coefficient of variation 14%) and its ability to identify patients with increased, as well as decreased, peripheral nerve function may be of value in the characterisation and longitudinal follow-up of small-fibre abnormalities in diabetes.

Localized hyperhidrosis in pretibial myxedema.

Two cases of spontaneous hyperhidrosis limited to pretibial myxedema lesions were studied. Quantitative measurements of stimulated eccrine sweat were made after the intradermal injection of methacholine. The sweat rate was two to four times greater in the lesional skin than in perilesional skin. Eccrine secretory glands in excisional biopsy specimens from the pretibial lesions were significantly larger than those in perilesional skin. To our knowledge, hyperhidrosis localized to areas of pretibial myxedema has not been reported.