This systematic review and meta-analysis demonstrated that there is a significant correlation between migraine and psoriasis with overall OR 1.64 (95% CI 1.28; 2.11). Besides, in our results presented that the rate of migraine occurred in psoriasis patient (pooled rate 0.21; 95% CI 0.13; 0.35), is higher than the prevalence rate 14.4% of the general adult population[9, 24]. The included two large cohort studies[31, 32] also strengthened the evidence for the causal association. The studies’ heterogeneity was presented in this meta-analysis, which might originate from the difference in selection criteria, population demography and population sizes.
Although the underlying fundamental causes for this observed association remained unclear, the aspects of pathophysiology, molecule, and therapy need to be taken into consideration as explanatory factors.
The Clinic Characteristic Phenotype
In precisely, according to an analysis from the 2016 Global Burden of disease study, the prevalence of migraine worldwide is around 14.4% overall, 18.9% in women, and 9.8% in men[33]. In our results showed that the pooled rate 21% is higher than 14.4%. Meanwhile, after integration of the differences in sex and age stratification of included studies, studies showed large discrepancies. One cohort study[31] reported psoriasis was related with increased risk of migraine in both sex; While, another study demonstrate it was higher in male patients and in the age 45 to 49 group[32]. It might attribute to the lack of relevant evaluations to confirm the results, and different methods to adjust the socioeconomic and lifestyle factors. Thus, additional larger randomized control studies are necessary to evaluate whether the sex or age could be a single increased risk of migraine in psoriasis.
The correlation between the clinic classification or the severity of migraine and psoriasis was also involved in some studies. Capo, A 2018[24] demonstrated that the classification of migraine with aura (MA) was more prevalent in psoriasis compared with non-psoriatic migraine population (62.5% vs 16%-20%)[24], Furthermore the mean number of crises is much higher than general data found in MA patients without psoriasis[24]. MA has been an established independent risk factor for CV less than 45 years old[33, 34] and the number of MA crises is a sign of CV disease severity[24, 35]. CV also is the highest caused death rate among the commodity with psoriasis, which indicating that MA might be an adjunctive risk factor in psoriasis for CV event. While, it might suggest that there would be a shared pathophysiologic pathway located further upstream or downstream in migraine and psoriasis, further detailed studies are necessary to confirm the new assessment sides of migraine as an essential comorbidity of psoriasis disorder and their possibilities in development of CV events.
The Pathophysiologic Mechanism
More and more studies suggest that migraine is not only a neurologic disorder[36], and psoriasis have already been redefined as from a skin disease to a chronic, immune-mediated systemic disorder[1]. In clinical aspects, psoriatic lesions could occur on the skin with bilateral symmetrical distribution, which indicate that the nervous system involvement in this pathological development, and the psychosocial stress exacerbate symptoms and correlated commodity in psoriasis patients[37–40], furthermore, psoriatic lesions don’t occur on the sites where there is injury to the nervous system in a that region, the reason might be the fewer neural related molecule to adjust the immune cells and to maintain the hyper-proliferation of keratinocyte[40, 41].
In molecular aspect, there is evidence to support the participant of neurotransmitter, the interaction between neuropeptides and immune response in psoriatic skin[42], and the nervous system take significant part in the development of the inflammatory reaction via the synthesis of neuropeptides and neurotransmitter, and these molecules’ correspondent receptors are also presented in the innate and adaptive immune cells, which build up the correlation between the neurological and immunological systems[43]. While, the inflammatory etiology of migraine pain involves many aspects[44], and increasing evidence suggest a type of sterile inflammatory in the intracranial meninges trigger the trigeminal meningeal nociceptors being activated[45]. The sterile inflammatory is defined as the interaction of neuropeptides (such as substance p (SP), calcitonin gene related peptide (CGRP)) from the trigeminal innervation[42, 45]. Indeed, the correlation between pain and inflammation and increased dysfunction of the neuroimmune system which appear to be shared in the pathophysiologic mechanism of psoriasis and migraine.
Significant correlation and overlap of the proinflammatory of mediators in neurovascular mechanism and neuroinflammatory mechanism plays a vital role in psoriasis and migraine[42, 43, 45]. Further specific studies are warranted and needed to determine a clear correlation between these two diseases.
Treatment Or Sides-effect
Along with sharing the potential similar pathophysiologic pathway or inflammatory mediator, the treatment targets might have similarities or overlapping parts between psoriasis and migraine.
Biologic medication has represented a great advancement in psoriasis and migraine[1, 15, 44]. Firstly, as for various chronic pain therapy, biologic therapies-monoclonal antibodies (mAbs) increasingly applied in it[46], anti-CGRP mAbs are an innovative therapeutic class for migraine[47]. In the skin, the ability of neuropeptides (SP, CGRP, vasoactive intestinal peptide (VIP), protein gene product 9.5 (PGP9.5), nerve growth factor (NGF)) to initiate and maintain inflammation in psoriasis[39, 47]. Meanwhile, some biologics or drugs that regulate neuropeptides improve the skin symptom of psoriasis, such as capsaicin (analgesic), and Peptide T (VIP analogue)[38, 48, 49]. It suggests the possibility of innovative migraine therapies to relieve the symptoms of psoriasis or psoriatic arthritis (painful knee).
Secondly, Tumor necrosis factor alpha (TNF-α) inhibitors are widely and safely applied in psoriasis and psoriatic arthritis which have gotten great advancement. While, the expression of TNF-α and TNF-α-Induced inflammatory molecules, has been detected at a various levels in peripheral and central mechanism during the transmission of pain in both human and mice studies[44, 46]. Currently some available biologic drug that target TNF-α could inhibit pain related signaling pathway in arthritis and improve the symptoms in psoriatic arthritis[50], which suggesting the possible target for anti-inflammatory biologic therapy in migraine headache. But the specific efficiency of TNF-α inhibitors that could alleviate pain would be complicated, it also included the aspect caused by specific pain/stimulus pathways[46]. As refer to the specific aspect of pain, TNF-α inhibitors should be re-evaluated in certain condition; and it would help us complement the recommendations in the future.
In addition, headache is commonly reported as a side-effect symptom of certain systemic anti-psoriatic therapies including the biologic medicine[17, 51]. Multiple neurological side-effects [17] (e.g. Headache, Demyelinating disorder, Leukoencephalopathy) have been a constant concern. The evaluation of neurologic complications of biologic agents could be needed before or after the treatment of psoriasis.