Headache and immunological/autoimmune disorders: a comprehensive review of available epidemiological evidence with insights on potential underlying mechanisms

Abstract

Several lines of evidence support a role of the immune system in headache pathogenesis, with particular regard to migraine. Firstly, alterations in cytokine profile and in lymphocyte subsets have been reported in headache patients. Secondly, several genetic and environmental pathogenic factors seem to be frequently shared by headache and immunological/autoimmune diseases. Accordingly, immunological alterations in primary headaches, in particular in migraine, have been suggested to predispose some patients to the development of immunological and autoimmune diseases. On the other hand, pathogenic mechanisms underlying autoimmune disorders, in some cases, seem to favour the onset of headache. Therefore, an association between headache and immunological/autoimmune disorders has been thoroughly investigated in the last years. The knowledge of this possible association may have relevant implications in the clinical practice when deciding diagnostic and therapeutic approaches. The present review summarizes findings to date regarding the plausible relationship between headache and immunological/autoimmune disorders, starting from a description of immunological alteration of primary headaches, and moving onward to the evidence supporting a potential link between headache and each specific autoimmune/immunological disease.

The Problem of Pain in Rheumatology: Clinical Profiles Associated With Concomitant Diagnoses With Chronic Overlapping Pain Conditions

“…In addition, Schrepf et al found that the true positive rate for using ICD‐10 code for FM was 95%, giving us confidence in the use of this code ( 8 ). In addition, we found that the prevalence of migraines, CTTH, and CLBP in our study were comparable to those found in other studies ( 24 , 25 ).…”

Dural Immune Cells, CGRP, and Migraine

“…Other evidence that doesn't rely on peripheral markers are comorbidities with immune disorders and migraine. Meta-analysis noted that headache had overlap with several autoimmune diseases like multiple sclerosis, rheumatoid arthritis, vasculitis, and allergic diseases ( 45 ). The authors hypothesize that headache or migraine phenotypes may be a “consequence of general inflammatory mechanisms involving meningeal vessels and activating trigeminal terminals, especially in individuals with a previous history of headache…” ( 45 ).…”

“…Meta-analysis noted that headache had overlap with several autoimmune diseases like multiple sclerosis, rheumatoid arthritis, vasculitis, and allergic diseases ( 45 ). The authors hypothesize that headache or migraine phenotypes may be a “consequence of general inflammatory mechanisms involving meningeal vessels and activating trigeminal terminals, especially in individuals with a previous history of headache…” ( 45 ). A study investigating irritable bowel disorder (IBS) gave some evidence of a causal relationship between IBS and migraine ( 46 ).…”

Refractory Headaches

“…91 125 However, more evidence is needed to determine whether meningeal neurogenic inflammation can actually trigger meningeal nociception. 125 Other hypotheses regarding the pathophysiology of persistent post-COVID19 headache include autoimmunity, 126 persistent local inflammation, 127 128 and NDPH. 90…”