Introduction: Vitiligo is a relatively common autoimmune depigmenting disorder of skin. There has been a great advance in understanding the pathological basis, which has led to development and utilisation of various new molecules in treating vitiligo.This review aims at a comprehensively describing the treatments available and the emerging treatment aspects and the scope for future developments.Areas covered: This study comprehensively summarises the current concepts in the pathogenesis of vitiligo with special focus on the cytokine and signalling pathways, which are the targets for newer drugs. JAK kinase signalling pathways and the cytokines involved are the focus of vitiligo treatment in current research, followed by antioxidant mechanisms and repigmenting mechanisms. Topical immunosuppressants may be an alternative to steroids in localised vitiligo. Newer repigmenting agents like basic fibroblast growth factors, afamelanotide have been included and a special emphasis is laid on the upcoming targeted immunotherapy. Expert opinion:The treatment of vitiligo needs to be multimodal with emphasis on targeting different limbs of the pathogenesis. Topical and oral JAK inhibitors are the most promising new class of drugs currently available for treating vitiligo and acts best in conjunction with NB-UVB.

Botulinum toxin (BTX) is a neurotoxin derived from the Clostridium botulinum bacterium that inhibits the release of acetylcholine at the neuromuscular junction level whose effects has been used for many years to treat a variety of muscular/neuromuscular conditions and more recently also for cosmetic use. BTX has experimented in some dermatological conditions, which include Rosacea and facial flushing treatment with good results. The complex mechanism underlying those results is not completely understood but was proposed a release inhibition of acetylcholine from peripheral autonomic nerves of the cutaneous vasodilatory system combined with the blockade substance P and calcitonin gene-related peptide (CGRP) thus modulating blood vessel dilatation. We analysed the published data on BTX off label applications rosacea and flushing retrieved from PubMed.

Isotretinoin (ISO) is a first‐generation retinoid discovered in 1952 and approved by the FDA for the treatment of nodulocystic acne in 1982. The anti‐inflammatory properties of ISO have found its use in disorders other than acne. ISO can create psychiatric problems, including depression and suicidal ideation. These neuropsychiatric problems are very similar to disorders secondary to hyperhomocysteinemia (HHcy), vitamin B12, and folic acid (vitamin B9) deficiencies. Given that previous literature suggested folate supplementation improved the efficacy of traditional antidepressant medications, clinicians may wish to consider folate supplementation for patients with depression or possible depressive symptoms, such as acne patients with genetic susceptibility. Brain‐derived neurotrophic factor may be a cytokine‐specific screening biomarker in immune‐based antidepressive therapy.

Insomnia means difficulty in falling asleep and/or stays asleep. Insomnia commonly leads to daytime sleepiness, lethargy, and a general feeling of being unwell. The most common treatment of insomnia includes GABAA receptor positive allosteric modulators or Melatonin agonists. Our study aimed to evaluate the efficacy of Magnesium- melatonin-vitamin B complex supplement in the treatment of insomnia. The study included 60 patients diagnosed with insomnia. The patients were randomly divided into study group (N = 30), and control group (N = 30), and study group was treated with Magnesium-melatonin-vitamin B complex (one dose contains 175 mg liposomal magnesium oxide, 10 mg Vit B6, 16 μg vit B12, melatonin 1 mg, Extrafolate-S 600 μg) once a day 1 hour before sleep, during the 3 months. The severity of insomnia symptoms was measured by self-reported Athens insomnia scale (AIS), with a cut-off score by Soldatos (AIS score ≥ 6). Mean AIS score at zero points was 14.93 ± 3.778 in the study group and 14.37 ± 4.081 in the control group (p = 0.476), indicating the compatibility of the groups, and both scores correspond to mild to moderate insomnia. Mean AIS score after 3 months of the Magnesium- melatonin- vitamin B complex supplementation was 10.50 ± 4.21 corresponding to mild insomnia, while median AIS score in the control group was 15.13 ± 3.76 which is referred to moderate insomnia, and difference among groups was significant (p = 0.000). Our founding’s indicating that 3 months of the Magnesium- melatonin-vitamin B complex supplementation has a beneficial effect in the treatment of insomnia regardless of cause.

Botulinum toxin (BTX) is a neurotoxin protein derived from the Clostridium botulinum bacterium that inhibits the release of acetylcholine at the neuromuscular junction level whose effects has been used for many years to treat a variety of muscular/neuromuscular conditions and more recently also for cosmetic use. BTX has experimented in some dermatological conditions which include scar prevention and treatment with good results. The complex mechanism underlying those results is not completely understood but several mechanisms were proposed: release inhibition of different substances like (TGF)-β, substance P, calcitonin gene-related peptide (CGRP) and glutamate thus modulating cutaneous inflammation and wound healing. We analysed the published data on BTX off label applications on scars and keloids retrieved from PubMed.

It is determined that 30% of patients with depression are resistant to antidepressant medication. The increased concentration of inflammation factors, such as C-reactive protein, and pro-inflammatory cytokines, have been detected in serum in these patients. It is necessary to establish new therapeutic possibilities and protocols that are created to overcome the difficulties caused by increased concentration of inflammatory biomarkers in depressive patients. The Selective Serotonin Reuptake Inhibitors (SSRIs) are considered to be the most powerful antidepressants, increasing the level of serotonin in endogenous depression, as well as in that caused by immunological mechanisms. It is believed that agents that influence cytokines, immunological signal pathways and cytokine syntheses, like the inhibitors of cyclooxygenase enzyme and other non-steroidal anti-inflammatory drugs (NSAIDs), are very important in the potential treatment of residual symptoms of depression. Treatment with cytokine antagonists is one of the potential adjuvant therapies, along with antidepressants. Signal pathways blockers, such as the inhibitors of cyclooxygenase and other NSAIDs, are in the phase of research, in terms of their antidepressant effects. Also, it has been shown that the inhibition of indolamin-2,3 deoxygenase (IDO) and kynurenine (KYN) signal pathways in the synthesis of neurotransmitters, by application of IDO antagonists, are leading to suppression of pro-inflammatory cytokine effects. Antidepressants may have anti-inflammatory effects, depending on dose and type, and they achieve this effect through the decrease of pro-inflammatory cytokine production and increase of anti-inflammatory cytokines. Also, antidepressants modulate the humoral and cellular immune system. This work aims to summarise certain neurobiological and neuroimmunological specificities that have been observed in patients with depression, antidepressants and immunomodulation agents. The understanding of complex and heterogenic pathophysiology of depression through the prism of the altered immune system, is of major importance, in terms of better optimisation of pharmacotherapy, and options for a personalised approach in depressive disorder treatment.

Understanding the mechanisms of cancer immune-tolerance is one of the most important challenges. Several studies have demonstrated the potential anticarcinogenic effects of beta-blockers, in patients with prostate cancer, breast cancer, and melanoma. At the other side variety of dermatoses may be caused or aggravated by β-blockers-psoriasis, lichen planus-like drug eruptions (LDE), acrocyanosis, alopecia etc.   Beta-blockers have been shown to improve the prognosis of melanoma patients significantly. Propranolol inhibits melanoma by downregulating the tumour angiogenesis but also tumour cell proliferation, invasiveness and local immune suppression. Studies showed that only β3-but, not β2-adrenoceptors, were up-regulated under hypoxia in peripheral blood mononuclear cells and selectively expressed in immune cell sub-populations including Treg, MDSC, and NK. They increased NK and CD8 number and cytotoxicity. Catecholamines may retard melanoma progression and that β-blockers may have unrecognised potential as a therapeutic intervention for melanoma, in the prevention of the growth of melanoma in all stages and as adjuvant therapy with other targeted and immune therapies for melanoma.

T The P.N.E.I. (Psycho-Neuro-Endocrine-Immunology) approach is represented by the interdisciplinary concept of bidirectional cross-talk between the psycho-neuro-endocrine and immune systems, which can influence the immune response. The well-known Gut-Brain Axis and the Gut-Skin Axis can be merged in a bigger network- the Gut-Brain-Skin Axis, with complex regulation by cytokines, neuro-peptides, neuro-hormones and another messenger (signalling) molecules and maybe the most important modulator of the Gut-Brain-Skin Axis/ the gut microbiota. The role of gut bacterial homeostasis is very important, and the homeostatic imbalance of the immune response may be a relevant etiologic/pathophysiologic factor for extra-intestinal and intestinal inflammatory, allergic and autoimmune diseases. The Low Dose Cytokines Medicine (LDM) is an innovative therapeutic approach. It is based on the most advanced knowledge in molecular biology and low dose pharmacology with the primary outcome. The SKA (Sequential Kinetic Activation) technology, codified and standardised by GUNA S.p.a. -Italy- makes the low doses of signalling molecules able to be active even below the minimum dose classically considered as effective and the significative efficacy of orally administered low-dose signalling molecules is the most representative aspect of LDM. The Physiologic Nutraceuticals and the Low Dose Medicine are two of the most promising approaches for the treatment of skin diseases based on the rebalance of the immune response and the recovery of gut dysbiosis.