Efrain Olszewer, MD

Skin changes associated with pruritus without defining a known cause or after testing to decharacterize other types of dermatitis are known as neurodermatitis and are associated with disorders of the sympathetic/parasympathetic system and should be considered for the introduction of treatments that modulate neurotransmitters in controlling the disease.

As the incidence of stress in its chronic phase and in the post-traumatic stress phase increases, the presence of isolated or conjugated cases of dermatitis associated with intense pruritus are increasingly seen, most of the time without expression of papules present and only determined by migratory itching, which can take days, weeks, or months to eventually be controlled.

This type of patient is treated by dermatologists and allergist ordering every type of test known, including biopsies, treating via desensitization, anti-allergic drugs, corticosteroids, immunotherapy without obtaining a satisfactory therapeutic result.

After eliminating all known possibilities, it is important to include in the differential diagnosis secondary neurodermatitis to pure dysautonomy or dysautonomy within the EOK12 syndrome (dysautonomy secondary to prolapse escape of the mitral valve) that is associated with behavioral disorders that can range from depression, dysthymia, anxiety, generalized anxiety disorder and others.

In general, the symptomatology of patients include:

• Itch
• With or without papules
• Migratory character
• Changes location frequently
• Interferes with quality of life and sleep
• Does obtain relief with classic medicine.

It gets worse when the patient scratches the region.

In its pathophysiology, patients with dysautonomy, with behavioral disorders such as stress, trigger the release of catecholamines with a predominance of adrenaline that produces a peripheral vasoconstriction associated with a central vasodilation, which provides the conditions to release vasoactive substances that induce pruritus, including:

• Histamine
• Bradykinin
• Slow substance of anaphylaxis
• Serotonin
• Cytokines

Several pruritogenic substances involved in the activation of peripheral nerve fiber receptors have already been identified. This group includes several mediators such as histamine, several interleukins (IL6, IL8, IL31), leukotrienes, tumor necrosis factor alpha (TNFα), and neuronal growth factor, among others. These substances are released after tissue damage by keratinocytes, fibroblasts, mast cells and macrophages, among others, activating peripheral nerve fibers.

In the transmission of pruritus at the peripheral level, unmyelinated nerve fibers of type C play an essential role. These are divided into two groups. Fibers insensitive to mechanical stimuli (IMC) are activated by histamine and express H1 and H4 receptors, as well as TRPV1.

Recently, type C nerve fibers sensitive to mechanical stimuli and elevated temperatures (HCM) have been discovered, which also play an important role in the transmission of pruritus. These are insensitive to histamine, are activated by cowage, a substance found in the tropical plant Mucuna pruriens, and express several receptors such as TRPV1 and PAR-2.8

Also, the nerve fibers of type Aδ are involved in the peripheral transmission of pruritus.

At the central level, different groups of neurons have been linked to the transmission of pruritus. Neurons expressing neurokine 1 receptors are linked to the transmission of pain and itching, while neurons expressing receptors of the gastrin-releasing peptide (GRPR) are specifically involved in the transmission of pruritus.

Inhibitory interneurons also can suppress pruritus at the spinal level. Through the spinothalamic tract, nerve impulses are transported to the thalamus, and from this structure they are distributed to various brain centers.

Both cortical and subcortical centers participate in the central processing of pruritus, including sensory information processing centers, affective and motor activity. In part, these centers correspond to the centers activated in states of pain. There is, however, no specific brain activation matrix of pruritus.

Therapeutic Possibilities

The pathway that in practical terms controls neurodermatitis by dysautonomy and the modulation of the deficit or excess of neurotransmitters is what generally determines the therapeutic success.

Most patients with neurodermatitis in general have levels of catecholamines (dopamine, noradrenaline, adrenaline normally high) and Gaba at normal or high levels that and a compensated picture, or very low levels in the phase of decompensation, the vast majority of patients respond to the use of gabaminergic that include:

• Benzodiazepines (alprazolam,bromazepam,clonazepam etc.)
• Anticonvulsants (sodium valproate, topiramate, lamotrigine, carbamazepine, oxycarbamazepine, valproic acid etc.)
• Herbal medicines (Theanine, phenibut, passionflower etc.)

It is important to associate treatment to modulate inflammation, and when necessary, initially low doses of antihistamines with sedative effects.

Conclusions

Dysautonomy neurodermatitis is a pathological but frequent situation that is very often confused with and diagnosed as different types of dermatitis and treated as such, without any therapeutic success. It is closely associated with behavioral disorders, which trigger a catecholaminergic sympathetic reaction with release of vasoactive substances, which respond to treatments that modulate the levels of neurotransmitters within the body,

Obviously, we must be more attentive to these conditions through an adequate anamnesis that allows us to make a differential diagnosis to define the therapeutic course of action.

References

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Published June 15, 2024

About the Author

Efrain Olszewer, MD, who specializes in internal medicine and cardiology, is clinical director of the International Center of Prevention Medicine (CMP) in Brazil. He is the president of the Brazilian Orthomolecular Society and editorial director of the Journal of Orthomolecular Practice. He has written 93 books on health and medicine.