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

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.