Sudomotor function refers to the autonomic nervous system control of sweat gland activity in response to various environmental and individual factors.
[3] They are located within the reticular dermal layer of the skin and distributed across nearly the entire surface of the body with the largest numbers occurring in the palms and soles.
Eccrine glands are primarily innervated by small-diameter, unmyelinated class C-fibers from postganglionic sympathetic cholinergic neurons.
[6] Increases in body and skin temperature are detected by visceral and peripheral thermoreceptors, which send signals via class C and Aδ-fiber afferent somatic neurons through the lateral spinothalamic tract to the preoptic nucleus of the hypothalamus for processing.
[7] Efferent pathways then descend ipsilaterally from the hypothalamus through the pons and medulla to preganglionic sympathetic cholinergic neurons in the intermediolateral column of the spinal cord.
[6] When the action potential reaches the axon terminal of the postganglionic neuron, acetylcholine is released which binds and activates muscarinic M3 receptors on the basolateral membrane of the clear cells in the secretory coil of the eccrine gland.
Depending on the severity of dyshidrosis, it may result in hyperkeratosis, rhagades, ulcerations, and poor wound healing due to altered epidermal moisturization.
Newer methods may offer simpler, potentially more sensitive, and more widely available alternatives for screening and monitoring in the clinic of autonomic and small fiber neuropathies, particularly those associated with diabetes.
The thermoregulatory sweat test (TST) was developed in the 1940s by Ludwig Guttmann to measure both preganglionic and postganglionic sudomotor function objectively.
An indicator dye is evenly applied to the ventral surface of the patient’s skin excluding the eyes, ears, and perioral region.
The dye changes color in response to a decrease in skin pH which occurs upon the onset of sweating as the room temperature is gradually raised.
The temporal resolution, magnitude, and onset latency of the sweat response are digitally recorded and analyzed using specialized software.
[6][4][15] QSART requires highly specialized equipment needing regular calibration, a humidity- and temperature-controlled room, and trained personnel.
Electrochemical skin conductance is an objective, quantitative, non-invasive method for the assessment of sudomotor function that utilizes chronoamperometry (the application of rectangular direct current (DC) pulses of varying voltage amplitudes) to electrically stimulate eccrine sweat glands, and reverse iontophoresis (the migration of electrolytes from the human sweat to the electrodes) for quantitative measurement of the resulting flow of Cl- ions.
In vitro electrochemical studies were then carried out in conventional three-electrode cells to identify the origin of currents measured upon the application of low voltage potentials with variable amplitudes to stainless steel electrodes applied to the skin during clinical tests.
In general, decreased ESC values indicate a higher risk of sudomotor dysfunction, and thus a greater likelihood of small fiber neuropathy.
It is highly sensitive, rapid, more accessible and less technically complex than current gold standard sudomotor function tests, and causes minimal-to-no patient discomfort, so very suitable for routine use.
Following iontophoresis of a cholinergic agonist, a thin layer of silicone is applied to the tested skin area until polymerization is complete (about 5 minutes).
The silicone imprints are then analyzed, either by microscope or computer-assisted analysis, for sweat droplet size, number, and distribution, and compared to lower limits of normal.
[4][15][39] The silicone imprint method is relatively inexpensive and can be performed in non-specialized testing centers; however, the method is prone to artifacts caused by residual hair and dirt, as well as skin surface texture and air bubble formation; the accuracy of the results depends on the silicone material used; the processing of the sweat impressions is time consuming; and the technique requires standardization.
[4][16][39] The QDIRT was developed in 2008 by Christopher Gibbons and colleagues as a means for the evaluation of postganglionic sudomotor function outside of specialized autonomic testing centers.
Similar to QSART, it involves the iontophoresis of 10% acetylcholine solution to induce axon-reflex sweating; however, it utilizes an automated imaging analysis software that is less technically complex.
[4][41] Prior to iontophoresis, the skin is dried and covered with an indicator dye consisting of povidone-iodine mixed with corn starch and mineral oil.
The procedure is initiated by the iontophoresis of 0.5% pilocarpine solution over a 2.25 cm2 skin area, which stimulates the underlying sweat glands directly through the activation of muscarinic M3 receptors.
A customized miniature camera can follow the secretions of up to 400 sweat glands at a time for up to 60 seconds, analyzing the enlargement rate and area of each spot.
[46] Nerve fibers innervating sweat glands are stained with Protein Gene Product 9.5 and quantified using manual morphometry with light microscopy.
Inspection of the patient’s skin, particularly on the lower extremities, in conjunction with a thorough medical history, can provide valuable information regarding the possible presence of sudomotor dysfunction.