Acetylcholine-induced whealing in cholinergic urticaria - What does it tell us?

BACKGROUND: Cholinergic urticaria (CholU) is characterized by the occurrence of itchy wheals induced by sweating. Intradermal injections of acetylcholine (ACh) have been proposed to help with diagnosing CholU and subgrouping of patients, but controlled studies are largely missing. OBJECTIVE: To compare the rates of positive ACh test results in well characterized CholU patients and controls and to identify clinical features of CholU linked to ACh reactivity. METHODS: Acetylcholine was injected intradermally into 38 CholU patients and 73 matched healthy controls. Wheal and flare skin responses were assessed after 15 and 30 min and correlated with clinical features of CholU. RESULTS: At 15 min after intradermal injections of ACh, wheal and flare responses were significantly more frequent in CholU patients than healthy controls, wheals: 34 % vs.15% (P = 0.028); flares: 50 % vs.18 % (P <0.001). Also, wheals were 37 % and flares 172 % larger and of longer duration in CholU patients than in healthy controls (both P < 0.01). CholU patients with ACh-induced wheals (ACh+) had larger flare but not wheal responses in response to histamine than those without (ACh-; P = 0.011). Also, ACh-induced wheal responses were significantly correlated with sweating (r = 0.54, P = 0.046) in CholU patients. Finally, wheal responses lasted longer in ACh+ than in ACh- patients (P = 0.03). CONCLUSION: Intradermal ACh testing does not allow for the identification of CholU patients due to its low sensitivity. ACh-induced wheals, in patients with CholU, is linked to sweating and longer lasting symptoms. Intradermal ACh testing is an interesting tool for mechanistic studies in CholU.

Quantity and quality of sweating in atopic dermatitis.

Sweat may be an important factor in triggering an exacerbation of atopic dermatitis. It was the aim of this study to evaluate a possible correlation between atopic patients and hyperhidrosis-measured by a questionnaire-and to find out whether there are qualitative differences in sweat response-measured by sudomotor activity (sympathetic skin response test, SSR). Included were 100 study participants, of whom 50 were patients with atopic dermatitis and 50 were serving as control group. The frequency of hyperhidrosis is higher in atopic patients than in the control group (30 vs. 16%), but has no statistical significance. In addition, patients with hyperhidrosis and atopic dermatitis have a significantly higher exacerbation rate of atopic dermatitis in summertime. The group of atopic patients shows a statistically significant prolonged SSR latency period, which indicates an insufficient sympathetic innervation. In our tests, type IV allergic patients showed clear differences in terms of SSR latency and amplitude. Atopic patients have a higher incidence of hyperhidrosis. The study clearly shows that there is a dysfunction of sudomotor activity in the sympathetic nervous system of atopic patients. Our findings suggest that a deficient innervation of sweat glands in atopic patients may lead to an increase in the development of type IV allergies.

Decreased sudomotor function is involved in the formation of atopic eczema in the cubital fossa.

BACKGROUND: Eczema in the cubital fossa, which is susceptible to sweat, is frequently observed in atopic dermatitis (AD). However, there has been no direct evidence that sweating causes eczema in the cubital fossa. METHODS: To investigate this issue, axon reflex-mediated sweating volume (AXR) and skin barrier function in the cubital fossa were measured in subjects with AD and in healthy volunteers, and were applied to clinical feature of the cubital fossa. RESULTS: AXR in the cubital fossa decreased in AD subjects; it positively correlated only with water-holding capacity in healthy subjects but not in patients with in AD. Furthermore, AD subjects with lichenoid eczema and either prurigo or papules over the cubital fossa showed extremely decreased AXR. CONCLUSIONS: These results suggest that decreased sweating is a major source of water in the stratum corneum, and decreased sudomotor function may be involved in both the cause and aggravation of representative atopic eczema in the cubital fossa.

Sudomotor dysfunction in autoimmune autonomic ganglionopathy.

BACKGROUND: Autoimmune autonomic ganglionopathy is characterized by impairment of multiple autonomic domains of which sudomotor function is among the most common. Many patients with this disorder have difficulties with thermoregulation and anhidrosis. Our objective was to characterize the distribution and severity of sudomotor dysfunction in this disorder. METHODS: Sudomotor function was analyzed in a cohort of 21 patients with ganglionic alpha3 nicotinic acetylcholine receptor (nAChR) antibody positive autoimmune autonomic ganglionopathy. Standard measurements of sudomotor function were used including the Thermoregulatory Sweat Test and Quantitative Sudomotor Axon Reflex Test. RESULTS: The clinical presentation in all patients was characterized by widespread sudomotor dysfunction. Sudomotor impairment was predominantly postganglionic in 17 of the 21 patients studied. Higher ganglionic alpha3 nAChR antibody levels resulted in progressive postganglionic predominant dysfunction (postganglionic, r = 0.637, p = 0.002; mixed ganglionic, r = 0.709, p < 0.001). The pattern of anhidrosis on Thermoregulatory Sweat Testing was consistent with a ganglionopathy in the majority of patients (14 of 21) and a distal pattern in a minority of patients (8 of 21). These patterns of anhidrosis coupled with increasing postganglionic dysfunction in a proximal to distal pattern (foot > distal leg > proximal leg > forearm) indicate lesions at both the ganglia and distal axon of the postganglionic sudomotor sympathetic neuron. CONCLUSIONS: Our data characterize the unique sudomotor dysfunction in autoimmune autonomic ganglionopathy as widespread, predominantly postganglionic, and a result of lesions at both the ganglia and distal axon. This study provides important support to the hypothesis that this disorder represents a ganglionic neuropathy.

Sudomotor testing predicts the presence of neutralizing botulinum A toxin antibodies.

The increasing number of patients being treated with botulinum toxin A complex (BoNT/A) has led to a higher incidence of neutralizing anti-BoNT/A antibodies (ABAs). Because BoNT/A is known to inhibit sweating, here we report sudometry as a possibility for predicting the presence of ABA. Sixteen patients suffering from spasmodic torticollis were selected: in 2 patients, BoNT/A treatment continued to be effective, in 9 patients, the treatment effect was impaired, and in 5 patients, secondary treatment failure developed. BoNT/A (100 mouse units, Dysport; Ipsen Pharma, Berkshire, United Kingdom) was injected subcutaneously into the lateral calves. Sweating was visualized with iodine starch staining. In addition, quantitative sudomotor axon reflex testing was performed at the injection site. Individual ABA titers were determined with a mouse bioassay. Results of sudometry significantly correlated with the BoNT/A treatment success. The quantitative sudomotor axon reflex testing was 0.58 +/- 0.63 fraction of the normal mean in patients with treatment failure, 0.18 +/- 0.13 fraction of the normal mean in those who responded partially, and 0 in responders (p < 0.01). Accordingly, the areas of the anhidrotic skin after subcutaneous injections were 4.5 +/- 10.3 cm(2), 32.7 +/- 16.5 cm(2), and 62 cm(2) (p < 0.01). Discrimination analysis indicated that the presence of ABA (6 ABA-positive and 10 ABA-negative) could be predicted correctly in all patients from the results of sudometry. Therefore, sudometry is a useful tool for identifying patients with neutralizing ABAs and might be helpful for identifying reasons for BoNT/A treatment failure.

Miliaria rubra / Miliaria rubra

La miliaria es una erupción que afecta predominantemente a los neonatos y a la primera infancia, se produce por obstrucción del poro sudoríparo y, en su aparición, intervienen factores como exceso de sudación infecciones superficiales y aplicación de cremas. Dependiendo de la profundidad de la obstrucción, la miliaria puede ser cristalina, que es la más superficial, rubra que es la intermedia, y profunda. Las lesiones varían de vésiculas transparentes a papulovesículas o a pápulas edematosas. No se acompaña casi de síntomas y evoluciona favorablemente; desaparece en pocos días cuando cesa, el estímulo causal (AU)

Sudoriferous acrosyringeal acantholytic disease. A subset of Grover's disease.

Three selected cases of transient acantholytic dermatosis were studied because of their definitive correlation with sweating due to fever and/ or bed-ridden situations. Biopsy specimens were serially sectioned and acantholysis was found in the acrosyringium or traced to connect to the acrosyringium in all biopsy specimens. Carcinoembryonic antigen (CEA) and eccrine gland-specific monoclonal antibody, IKH-4, were positive in acantholytic cells. Electron microscopy revealed electron dense material filling the lumen of intraepidermal eccrine ducts. This material leaked into lateral intercellular spaces of the luminal cells, passing tight junctions. Marked edema and numerous lysosomes were reminiscent of those found when eccrine acrosyringium is formed in the embryo; this suggested that an occluded and damaged eccrine intraepidermal duct was being rebuilt via lysosomal digestion.