Abstract
Background:
Survey studies have found an increased prevalence of migraine in patients with inflammatory bowel disease (IBD). However, the clinical characteristics of migraines in this population are unknown. We conducted a retrospective medical record review study to characterize migraines in the IBD population.
Methods:
Six hundred seventy-five migraine patients (280 with IBD, 395 without IBD) who were evaluated at Mayo Clinic Rochester, Mayo Clinic Arizona, or Mayo Clinic Florida between July 2009 and March 2021 were included. Patients with ICD codes for migraine and either Crohn’s disease (CD) or ulcerative colitis (UC) were selected. Electronic health care records were reviewed. Patients confirmed to have IBD and migraine were included. Demographic, IBD, and migraine characteristics were collected. Statistical analysis was completed using SAS.
Results:
Patients with IBD were less often male (8.6% vs 21.3%, P < .001) and had a higher Charlson Comorbidity Index (>2: 24.6% vs 15.7%, P = .003); 54.6% had CD and 39.3% had UC. Patients with IBD had migraine with aura and without aura more frequently ( OR 2.20, P < .001 and OR 2.79, P < .001, respectively) than non-IBD patients. Additionally, those with IBD less commonly had chronic migraine (OR 0.23, P < .001) and less commonly had chronic migraine or treatment for migraine (ORs 0.23-0.55, P ≤ .002).
Conclusions:
Migraine with and without aura have increased prevalence in IBD patients. Further study of this topic will be helpful to clarify the prevalence of migraine, establish this population’s response to treatment, and better understand the reason(s) for a low rate of treatment.
Keywords: IBD, migraine, headache, Crohn’s, ulcerative colitis
Introduction
Survey studies have found an increased prevalence of migraine in patients with inflammatory bowel disease (IBD).1-3 However, the clinical characteristics of migraines in this patient population are unknown.4 We conducted a medical record review study to characterize migraines in patients with IBD.
Migraines occur more frequently in younger females.5,6 Similarly, autoimmune conditions such as systemic lupus erythematosus (SLE), Sjögren’s disease, rheumatoid arthritis, and Crohn’s disease (CD) share an increased prevalence in younger females.2 Similarly to those with IBD, migraineurs have been found to have abnormalities in TNF- α, IL-1β, IL-6, and IL-8, along with dysfunction in NK cells, aberrant ratios of CD4 to CD8 T cells, and endothelial dysfunction.2,4 Patients with IBD have been found to have dysregulation of natural killer (NK) cells and aberrant cytokine responses.7 Additionally, patients with migraine have an increased risk of developing autoimmune conditions later in life.
The overlap of inflammatory cytokines found in patients with primary migraine and autoimmune disorders suggests an association between the two.8 Immunodysregulation is likely to be the major cause of disease in IBD as well as a contributor in migraine.
The concept of gut-brain axis refers to the relationship between the gastrointestinal tract and the central nervous system (CNS). The brain sends both nervous inputs and hormones to the gut while the gut can return sensory inputs and hormones back to the brain.9 Disruption of the brain-gut access by celiac disease, Helicobacter pylori, and irritable bowel syndrome have been implicated in CNS disorders such as migraine, multiple sclerosis (MS), anxiety, and Alzheimer’s disease.9 Celiac disease has been shown to have a strong relationship with migraine, and the removal of gluten from the diet may lead to migraine improvement or resolution.10
The characteristics of migraines in autoimmune conditions other than IBD have previously been described.2,4 SLE patients have migraine prevalence that is similar to non-SLE controls. Migraineurs with SLE are more likely to have migraine with aura. Patients with MS have increased rates of migraine with aura.11 Patients with Sjögren’s syndrome and rheumatoid arthritis have been found to have migraine without aura at rates higher than healthy controls.2,4,11
Our research hypothesis was that patients with IBD have a higher prevalence of migraines with and without aura compared to non-IBD patients. Therefore, we conducted a retrospective multicenter study of the prevalence and clinical characteristics of migraines in patients with and without IBD.
Materials and Methods
A total of 675 migraine patients (280 with IBD, 395 without IBD) seen at the Mayo Clinic Rochester, Mayo Clinic Arizona, or Mayo Clinic Florida between July 2009 and March 2021 were included in this retrospective study. Patients who had ICD codes for both migraine and either CD or UC were selected. Electronic health care records were then reviewed and patients confirmed to have both IBD and migraine by Mayo Clinic gastroenterology and neurology providers respectively, were included. Information was collected regarding patient characteristics (age, sex, BMI, Charlson Comorbidity Index, smoking), IBD characteristics (type of IBD, IBD treatment history, extraintestinal manifestations of IBD), and migraine characteristics (migraine type, headache type, age at migraine diagnosis, migraine-associated symptoms, migraine treatments).
The study was approved by the Mayo Clinic Institutional Review Board.
Statistical Analysis
Continuous variables were summarized with the sample median and range. Categorical variables were summarized with number and percentage of patients. Comparisons of patient characteristics between those with and without IBD were made using a Wilcoxon rank sum test (continuous and ordinal variables) or Fisher’s exact test (categorical variables).
Comparisons of migraine characteristics between the IBD and non-IBD groups were made using unadjusted and multivariable linear (continuous variables) and logistic (categorical variables) regression models. Multivariable models were adjusted for all patient characteristics that differed between the IBD and non-IBD patients with a P-value < .05. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from logistic regression models, while regression coefficients (denoted as β) and 95% CIs were estimated from linear regression models. Note that adjusting for all of the desired patient characteristics was not possible for rarer binary categorical migraine characteristics, as recommended guidelines suggest that there are at least 10 patients with the given characteristic for each one variable included in the given logistic regression model.12 Therefore, in these cases we adjusted for the patient characteristics that differed most strongly between the IBD and non-IBD groups while adhering to these guidelines, unless it was not appropriate to adjust for any variables, in which case multivariable analysis was not performed. Comparisons of migraine characteristics between migraine patients with CD and migraine patients with UC were made using Fisher’s exact test. P-values < .05 were considered statistically significant. All statistical tests were 2-sided. Statistical analyses were performed using SAS (version 9.4; SAS Institute, Inc., Cary, North Carolina).
Results
Comparisons of migraine characteristics between the IBD and non-IBD groups were made using unadjusted and multivariable linear (continuous variables) and logistic (categorical variables) regression models. Multivariable models were adjusted for all patient characteristics that differed between the IBD and non-IBD patients with a P-value < .05. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from logistic regression models, while regression coefficients (denoted as β) and 95% CIs were estimated from linear regression models. Note that adjusting for all of the desired patient characteristics was not possible for rarer binary categorical migraine characteristics, as recommended guidelines suggest that there are at least 10 patients with the given characteristic for each one variable included in the given logistic regression model.12 Therefore, in these cases, we adjusted for the patient characteristics that differed most strongly between the IBD and non-IBD groups while adhering to these guidelines, unless it was not appropriate to adjust for any variables, in which case multivariable analysis was not performed. Comparisons of migraine characteristics between migraine patients with CD and migraine patients with UC were made using Fisher’s exact test.
A comparison of patient characteristics between the 280 IBD patients and the 395 non-IBD patients is shown in Table 1. Compared to patients without IBD, patients with IBD were less often male (8.6% vs 21.3%, P < .001), had a higher Charlson comorbidity index (>2: 24.6% vs 15.7%, P = .003), and were less often current smokers (8.0% vs 14.3%, P = .024). For IBD patients, the most common type was CD (54.6%) followed by UC (39.3%) and both CD and UC (6.1%). The most common IBD treatments were mesalamine (47.1%), biologics (43.6%), and prednisone (41.4%) and the most frequent extraintestinal manifestations of IBD were arthritis (10.0%) and primary sclerosing cholangitis (6.4%). Comparisons of migraine characteristics between IBD and non-IBD patients are displayed in Table 2.
Table 1.
Comparison of Patient Characteristics Between Migraine Patients With and Without IBD.
| Variable | Migraine patients with IBD (N = 280) | Migraine patients without IBD (N = 395) | |||
|---|---|---|---|---|---|
| N | Median (minimum, maximum) or No. (%) | N | Median (minimum, maximum) or No. (%) | P-value | |
| Age at visit (years) | 280 | 42 (16, 87) | 395 | 41 (17, 81) | .11 |
| Age at IBD diagnosis | 262 | 27 (5, 91) | N/A | N/A | N/A |
| Sex (Male) | 280 | 24 (8.6%) | 395 | 84 (21.3%) | <.001 |
| BMI | 278 | 27.1 (13.5, 57.4) | 367 | 27.4 (17.3, 99.0) | .14 |
| Charlson comorbidity index | 280 | 395 | .003 | ||
| 0 | 103 (36.8%) | 169 (42.8%) | |||
| 1 | 65 (23.2%) | 121 (30.6%) | |||
| 2 | 43 (15.4%) | 43 (10.9%) | |||
| 3 | 26 (9.3%) | 25 (6.3%) | |||
| 4 | 16 (5.7%) | 13 (3.3%) | |||
| ≥5 | 27 (9.6%) | 24 (6.1%) | |||
| Smoking | 275 | 370 | .024 | ||
| Never | 191 (69.5%) | 252 (68.1%) | |||
| Former | 62 (22.5%) | 65 (17.6%) | |||
| Current | 22 (8.0%) | 53 (14.3%) | |||
| Type of IBD | 280 | N/A | |||
| Crohn’s disease | 153 (54.6%) | N/A | N/A | ||
| Ulcerative colitis | 110 (39.3%) | N/A | N/A | ||
| Both Crohn’s disease and ulcerative colitis | 17 (6.1%) | N/A | N/A | ||
| IBD treatment history | 280 | N/A | |||
| Budesonide | 50 (17.9%) | N/A | N/A | ||
| Prednisone | 116 (41.4%) | N/A | N/A | ||
| Mesalamine | 132 (47.1%) | N/A | N/A | ||
| MTX | 20 (7.1%) | N/A | N/A | ||
| Azathioprine | 59 (21.1%) | N/A | N/A | ||
| Biologic | 122 (43.6%) | N/A | N/A | ||
| Extra intestinal manifestations of IBD | 280 | ||||
| Colic type arthritis | 28 (10.0%) | N/A | N/A | N/A | |
| Ankylosing spondylitis | 12 (4.3%) | N/A | N/A | N/A | |
| Hypertrophic osteoarthropathy: clubbing | 1 (0.4%) | N/A | N/A | N/A | |
| Hypertrophic osteoarthropathy: periostitis | 0 (0.0%) | N/A | N/A | N/A | |
| Osteoporosis | 13 (4.6%) | N/A | N/A | N/A | |
| Aseptic necrosis | 1 (0.4%) | N/A | N/A | N/A | |
| Polymyositis | 0 (0.0%) | N/A | N/A | N/A | |
| Erythema nodosum | 0 (0.0%) | N/A | N/A | N/A | |
| Pyoderma gangrenosum | 2 (0.7%) | N/A | N/A | N/A | |
| Aphthous ulcers | 6 (2.1%) | N/A | N/A | N/A | |
| Necrotizing vasculitis | 4 (1.4%) | N/A | N/A | N/A | |
| Oral Crohn’s disease | 6 (2.1%) | N/A | N/A | N/A | |
| Primary sclerosing cholangitis | 18 (6.4%) | N/A | N/A | N/A | |
| Bile-duct carcinoma | 1 (0.4%) | N/A | N/A | N/A | |
| Uveitis/iritis | 6 (2.1%) | N/A | N/A | N/A | |
| Episcleritis | 0 (0.0%) | N/A | N/A | N/A | |
| Scleromalacia | 0 (0.0%) | N/A | N/A | N/A | |
| Corneal ulcers | 0 (0.0%) | N/A | N/A | N/A | |
| Retinal vascular disease | 0 (0.0%) | N/A | N/A | N/A | |
| Calcium oxylate stones | 6 (2.1%) | N/A | N/A | N/A | |
| None | 178 (63.6%) | N/A | N/A | N/A | |
P-values result from a Wilcoxon rank sum test (continuous variables) or Fisher’s exact test (categorical variables).
Table 2.
Comparison of Migraine Characteristics Between Migraine Patients With and Without IBD.
| Variable | Migraine patients with IBD (N = 280) | Migraine patients without IBD (N = 395) | Unadjusted analysis | Adjusting for sex, Charlson comorbidity index, and smoking | |||||
|---|---|---|---|---|---|---|---|---|---|
| N | Median (minimum, maximum) or No. (%) | N | Median (minimum, maximum) or No. (%) | Association measure | Estimate (95% CI) | P-value | Estimate (95% CI) | P-value | |
| Migraine type | 280 | 395 | |||||||
| Migraine without aura | 93 (33.2%) | 75 (19.0%) | OR | 2.12 (1.49, 3.02) | <.001 | 2.20 (1.51, 3.22) | <.001 | ||
| Migraine with aura | 108 (38.6%) | 73 (18.5%) | OR | 2.77 (1.95, 3.93) | <.001 | 2.79 (1.93, 4.04) | <.001 | ||
| Chronic migraine | 79 (28.2%) | 247 (62.5%) | OR | 0.24 (0.17, 0.33) | <.001 | 0.23 (0.16, 0.32) | <.001 | ||
| Headache type | |||||||||
| Migraine | 280 | 280 (100.0%) | 395 | 395 (100.0%) | N/Aa | N/Aa | 1.00 | N/A | N/A |
| Tension type headache (TTH) | 280 | 4 (1.4%) | 395 | 13 (3.3%) | OR | 0.43 (0.14, 1.32) | .14 | N/A | N/A |
| Trigeminal autonomic cephalgias (TACs) | 280 | 0 (0.0%) | 395 | 3 (0.8%) | N/Aa | N/Aa | .27 | N/A | N/A |
| Daily persistent headache | 280 | 7 (2.5%) | 395 | 24 (6.1%) | OR | 0.40 (0.17, 0.93) | .034 | 0.44 (0.18, 1.08) | .072 |
| Age at migraine diagnosis (years) | 190 | 25.5 (4.0, 82.0) | 381 | 39.0 (6.0, 79.0) | β | -10.49 (-13.00, −7.98) | <.001 | -11.54 (-13.93, −9.16) | <.001 |
| Migrainous associated symptoms | |||||||||
| Nausea | 280 | 175 (62.5%) | 395 | 299 (75.7%) | OR | 0.54 (0.38, 0.75) | <.001 | 0.54 (0.38, 0.78) | .001 |
| Vomiting | 280 | 79 (28.2%) | 395 | 144 (36.5%) | OR | 0.69 (0.49, 0.95) | .025 | 0.65 (0.46, 0.92) | .016 |
| Photophobia | 280 | 196 (70.0%) | 395 | 321 (81.3%) | OR | 0.54 (0.38, 0.77) | .001 | 0.57 (0.39, 0.84) | .004 |
| Phonophobia | 280 | 140 (50.0%) | 395 | 299 (75.7%) | OR | 0.32 (0.23, 0.45) | <.001 | 0.34 (0.24, 0.48) | <.001 |
| Vertigo | 280 | 4 (1.4%) | 395 | 40 (10.1%) | OR | 0.13 (0.05, 0.36) | <.001 | 0.12 (0.04, 0.34) | <.001 |
| Ptosis | 280 | 1 (0.4%) | 395 | 27 (6.8%) | OR | 0.05 (0.01, 0.36) | .003 | 0.05 (0.01, 0.36) | .003 |
| Lacrimation | 280 | 7 (2.5%) | 395 | 31 (7.8%) | OR | 0.30 (0.13, 0.69) | .005 | 0.32 (0.14, 0.76) | .010 |
| Conjunctival injection | 280 | 3 (1.1%) | 395 | 23 (5.8%) | OR | 0.18 (0.05, 0.59) | .005 | 0.19 (0.06, 0.65) | .008 |
| Rhinorrhea | 280 | 6 (2.1%) | 395 | 30 (7.6%) | OR | 0.27 (0.11, 0.65) | .004 | 0.28 (0.11, 0.70) | .006 |
| Migraine treatments | |||||||||
| Botox | 280 | 46 (16.4%) | 395 | 105 (26.6%) | OR | 0.54 (0.37, 0.80) | .002 | 0.55 (0.37, 0.81) | .003 |
| Topiramate | 280 | 67 (23.9%) | 395 | 214 (54.2%) | OR | 0.27 (0.19, 0.37) | <.001 | 0.25 (0.17, 0.36) | <.001 |
| Lamotrigine | 280 | 5 (1.8%) | 395 | 18 (4.6%) | OR | 0.38 (0.14, 1.04) | .059 | 0.34 (0.12, 0.94) | .037 |
| TCAs | 280 | 51 (18.2%) | 395 | 195 (49.4%) | OR | 0.23 (0.16, 0.33) | <.001 | 0.23 (0.16, 0.34) | <.001 |
| Beta blocker | 280 | 46 (16.4%) | 395 | 152 (38.5%) | OR | 0.31 (0.22, 0.46) | <.001 | 0.31 (0.21, 0.45) | <.001 |
| Triptans | 280 | 150 (53.6%) | 395 | 271 (68.6%) | OR | 0.53 (0.39, 0.73) | <.001 | 0.52 (0.37, 0.74) | <.001 |
| NSAIDS | 280 | 83 (29.6%) | 395 | 235 (59.5%) | OR | 0.29 (0.21, 0.40) | <.001 | 0.31 (0.22, 0.43) | <.001 |
Abbreviations: OR = odds ratio; β = regression coefficient.
ORs, 95% CIs, and P-values result from logistic regression models. β values, 95% CIs, and P-values result from linear regression models. All multivariable models were adjusted for sex, Charlson comorbidity index, and smoking, with the exception of TTH (no adjustment), TACs (no adjustment), daily persistent headache (no adjustment for smoking), ptosis (no adjustment for Charlson or smoking), lacrimation (no adjustment for smoking), conjunctival injection (no adjustment for Charlson or smoking), rhinorrhea (no adjustment for smoking), and Lamotrigine (no adjustment for Charlson or smoking), where a full multivariable analysis was not possible owing to the fewer number of patients who experienced these outcomes. aLogistic regression was not possible due to a zero cell count; the P-value results from Fisher’s exact test.
In multivariable analysis adjusting for sex, Charlson comorbidity index, and smoking, when compared to non-IBD patients, patients with IBD had migraine with aura and without aura more frequently (OR = 2.20, P < .001 and OR = 2.79, P < .001, respectively). Additionally, those with IBD less commonly had chronic migraine (OR = 0.23, P < .001), had a younger age at migraine diagnosis (β: −11.54, P < .001), less commonly had each migraine-associated symptom (ORs 0.05-0.65, all P ≤ .016), and less commonly had treatment for migraine (ORs 0.23-0.55, all P ≤ .037). Comparisons of migraine characteristics and treatment between those with CD and UC are displayed in Table 3.
Table 3.
Comparison of Migraine Characteristics Between Migraine Patients With Crohn’s Disease Versus Ulcerative Colitis.
| Variable | Migraine patients with Crohn’s disease (N = 153) | Migraine patients with Ulcerative colitis (N = 110) | P-value | ||
|---|---|---|---|---|---|
| N | No. (%) | N | No. (%) | ||
| Migraine type | 153 | 110 | .38 | ||
| Migraine without aura | 47 (30.7%) | 43 (39.1%) | |||
| Migraine with aura | 62 (40.5%) | 40 (36.4%) | |||
| Chronic migraine | 44 (28.8%) | 27 (24.5%) | |||
| Headache type | |||||
| Migraine | 153 | 153 (100.0%) | 110 | 110 (100.0%) | 1.00 |
| Tension type headache (TTH) | 153 | 1 (0.7%) | 110 | 2 (1.8%) | .57 |
| Trigeminal autonomic cephalgias (TACs) | 153 | 0 (0.0%) | 110 | 0 (0.0%) | 1.00 |
| Daily persistent headache | 153 | 2 (1.3%) | 110 | 5 (4.5%) | .13 |
| Migraine treatments | |||||
| Botox | 153 | 23 (15.0%) | 110 | 21 (19.1%) | .41 |
| Topiramate | 153 | 33 (21.6%) | 110 | 30 (27.3%) | .31 |
| Lamotrigine | 153 | 3 (2.0%) | 110 | 1 (0.9%) | .64 |
| TCAs | 153 | 28 (18.3%) | 110 | 21 (19.1%) | .87 |
| Beta blocker | 153 | 26 (17.0%) | 110 | 18 (16.4%) | 1.00 |
| Triptans | 153 | 79 (51.6%) | 110 | 62 (56.4%) | .46 |
| NSAIDS | 153 | 42 (27.5%) | 110 | 40 (36.4%) | .14 |
P-values result from Fisher’s exact test.
There was no significant difference between CD and UC for any variable analyzed in the study, including rate of migraine with aura (62% vs 40%, P = .38), migraine (47% vs 43%, P = .88) without aura, and chronic migraine (44% vs 27%, P = .38) for CD versus UC respectively.
Discussion
To our knowledge, this is the first study to characterize migraines in IBD patients. Of the 280 patients diagnosed with migraines and IBD, 33.2% had migraine without aura, 38.6% migraine with aura, and 28.2% chronic migraine. In our internal control, which consisted of patients seen by neurology providers at Mayo Clinic, 19% of subjects had migraine without aura, 18.5% migraine with aura, and 62.5% chronic migraine. Review of the literature shows prevalence of migraine without aura, with aura, and chronic migraine to be approximately 70%, 25%, and 3% respectively among migraineurs.5,13 In our study, IBD patients had higher rates of migraine with aura and chronic migraine compared to historical non-IBD migraineur controls and higher rates of migraine with aura and migraine without aura when compared to our internal control. The lack of correlation between the rates of migraine with aura, without aura, and chronic migraine in our control group and in the literature is likely due to several factors. Mayo Clinic is a tertiary care center which may lead to referral bias of patients with more severe migraines, particularly chronic migraines that have failed multiple treatments. To avoid self-diagnosis of migraine, we included patients who had an ICD code of migraine and had been seen in a neurology headache clinic. This may have led to a referral bias that favored patients with more severe migraines, as a certain percentage of migraineurs do not see a specialist or get treatment at all. Overall, both the IBD cohort and internal control cohort likely had difficult to control migraines given that they were treated at a tertiary care center.
Migraine characteristics were compared among patients with CD and UC. In CD patients, 30.4% had migraine without aura, 35.1% migraine with aura, and 34.6% chronic migraine. In the UC group, 34.8%, 31.1%, and 34.1% had migraine without aura, migraine with aura, and chronic migraine respectively; there was no significant difference in migraine subtype between the CD and UC cohorts. When compared to other autoimmune conditions, the increased rate of migraine with aura is similar to SLE, Bechet’s syndrome, and MS; however, patients with rheumatoid arthritis and Sjögren’s syndrome do not have increased rates of migraine with aura.2 While SLE and some vasculitides may cause direct CNS disease, studies looking at direct CNS damage have failed to show that primary brain involvement is needed to have migraine; this leads to the suggestion that migraine may be secondary to generalized inflammation or the stress of having a severe chronic condition.
While data was collected regarding treatment and treatment response, we were not able to assess response to migraine treatment due to limitations in the reporting of patient response in the medical record. However, it was noted that patients with migraine and IBD were less likely to be taking an abortive or prophylactic medication for migraine. It has been noted in the literature that other comorbidities of IBD are unrecognized likely due to a focus on gastrointestinal symptoms.14 Similarly, migraine is likely underdiagnosed in this population and even when it is correctly diagnosed, patients appear to be treated less frequently. Recent studies and recommendations focused on comorbidities and health maintenance in the IBD population should be helpful in increasing awareness of migraines and other comorbid conditions commonly encountered in the patient population.15
Limitations of our study include its retrospective design, which may have introduced data collection biases. Additionally, our study was not designed to evaluate IBD disease activity and its possible correlation with migraines.
In conclusion, patients with IBD appear to have migraines with higher prevalence than the general population. IBD patients with migraine have higher rates of migraine with aura and chronic migraine. Patients with IBD and migraine are less likely to be treated for migraine, but it remains to be seen if this is due to patient and/or provider factors. Further study of this topic including patients from both community and tertiary referral centers will be helpful to clarify the prevalence of migraine with and without aura and chronic migraine.
Further studies will be helpful to establish this patient population’s response to treatment and better understand resistance to treatment.
Conclusions
Patients with IBD have increased rates of migraine with and without aura compared to migraineurs without IBD and are less likely to be treated for migraine compared to migraineurs without IBD. There was no difference in the character or incidence of migraine when comparing ulcerative colitis and Crohn’s disease.
Footnotes
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.
ORCID iDs: Jose R. Valery 
https://orcid.org/0000-0003-2671-7854
Dana M. Harris
https://orcid.org/0000-0003-0820-9215
Fernando F. Stancampiano
https://orcid.org/0000-0002-9162-1632
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