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Diet and Headache: Part 1


Headache: The Journal of Head and Face Pain, 56: 1543–1552. (2016) doi:10.1111/head.12953

Martin, V. T. and Vij, B.



The role of diet in the management of the headache patient is a controversial topic in the headache field.


To review the evidence supporting the hypothesis that specific foods or ingredients within foods and beverages trigger attacks of headache and/or migraine and to discuss the use of elimination diets in the prevention of headache disorders


This represents part 1 of a narrative review of the role of diet in the prevention of migraine and other headache disorders. A PubMed search was performed with the following search terms: “monosodium glutamate,” “caffeine,” “aspartame,” “sucralose,” “histamine intolerance syndrome,” “tyramine,” “alcohol,” “chocolate,” “nitrites,” “IgG elimination diets,” and “gluten.” Each of these search terms was then cross-referenced with “headache” and “migraine” to identify relevant studies. Only studies that were written in English were included in this review.


Caffeine withdrawal and administration of MSG (dissolved in liquid) has the strongest evidence for triggering attacks of headache as evidenced by multiple positive provocation studies. Aspartame has conflicting evidence with two positive and two negative provocation studies. Observational studies provide modest evidence that gluten- and histamine-containing foods as well as alcohol may precipitate headaches in subgroups of patients. Two of three randomized controlled trials reported that an elimination diet of IgG positive foods significantly decreased frequency of headache/migraine during the treatment as compared to baseline time period.


Certain foods, beverages, and ingredients within foods may trigger attacks of headache and/or migraine in susceptible individuals. Elimination diets can prevent headaches in subgroups of persons with headache disorders.

Also of interest:

Diet and Headache: Part 2


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Psoriasis: a mixed autoimmune and autoinflammatory disease


Current Opinion in ImmunologyVolume 49, December 2017, Pages 1-8 – https://doi.org/10.1016/j.coi.2017.07.007Get rights and content

Yun Liang, Mrinal K Sarkar, Lam C Tsoi,Johann E Gudjonsson (Department of Dermatology, University of Michigan, 1910 Taubman Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA; Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA)


• Plaque psoriasis exhibits both autoimmune and autoinflammatory immune responses.

• The autoinflammatory loop in psoriasis is driven by IL-36 cytokine responses.

• Neutrophils and keratinocytes promote autoinflammatory responses in psoriasis.

• Psoriasis subtypes have variable balance of autoimmune and autoinflammatory responses.

In recent years marked progress has been made in our understanding of the critical biologic and immunologic pathways involved in psoriasis. Genetic studies have demonstrated that susceptibility to psoriasis involves components of both the adaptive and innate immune system and not surprisingly activation of both of these arms of the immune system is found in psoriatic skin. While adaptive immune responses predominate in chronic plaque psoriasis, innate and autoinflammatory responses dominate in pustular forms of psoriasis, with other clinical subtypes extending on a spectrum between plaque and pustular psoriasis. This makes psoriasis a unique disease where both autoimmune and autoinflammatory responses co-exist, with the balance between the two being critical in shaping its clinical presentation.

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Histopathology of Urticaria


Current Treatment Options in Allergy, pp 1–8 – First Online: 08 September 2017

Eriko Itoh, Minao Furumura, Masutaka Furue (Department of Dermatology, Fukuoka Dental College, Fukuoka, Japan; Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan)

Urticaria and Atopic Dermatitis (M Hide, Section Editor)

Part of the following topical collections: Topical Collection on Urticaria and Atopic Dermatitis

Opinion statement

Purpose of review

Urticaria is a common skin manifestation with many different causes. It is characterized by local or generalized edematous erythema with itching and increased blood flow and vascular permeability. Individual urticaria lesions typically last less than 24 h (usually less than 12 h), but new lesions may appear and resolve sporadically. Since the diagnosis is usually made based on the history and clinical appearance of the lesions, skin biopsy is not necessarily performed, but it is recommended for evaluating patients with refractory eruptions or suspicion of other diseases exhibiting urticaria-like lesions. The histopathological features of urticaria are dermal edema and perivascular and interstitial inflammatory cell infiltration, and there is only minimal change in the epidermis. Cellular infiltrates are composed of lymphocytes, neutrophils, and eosinophils.

Recent findings

In our 64 patients with urticaria, severe edema was found in 48 cases (75%) with mixed cellular infiltration in 45 (70%), lymphocytic infiltration in 17 (27%), and neutrophilic infiltration in 2 cases (3%). Perivascular infiltration was found in 35 cases (55%), and the others were classified into the perivascular and interstitial infiltration type. Subcutaneous cellular infiltration has been shown to be associated with poor treatment response.


In this review, we summarize the histopathological findings of urticaria and its differential diagnosis. Evaluation of the histopathological features may provide further insight into the mechanism of urticaria and potentially provide valuable information to develop more effective treatments.


Urticaria Histopathology Chronic spontaneous urticaria Urticarial vasculitis

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Cirsium maritimum Makino Inhibits the Antigen/IgE-mediated Allergic Response In Vitro and In Vivo


J. Agric. Food Chem., Publication Date (Web): September 6, 2017 – DOI: 10.1021/acs.jafc.7b03322

Mamoru Tanaka, Masanobu Suzuku, Yuichiro Takei, Takeaki Okamoto, and Hiroyuki Watanabe


We investigated whether Cirsium maritimum Makino (CMM) can inhibit IgE-mediated allergic response in rat basophilic leukemia (RBL-2H3) cells, and passive cutaneous anaphylaxis (PCA) in BALB/c mice. In vitro, the ethyl acetate extract of CMM (ECMM) significantly inhibited β-hexosaminidase release and decreased intracellular Ca2+ levels in RBL-2H3 cells. Moreover, ECMM leaves more strongly suppressed the release of β-hexosaminidase than ECMM flowers. ECMM leaves also significantly suppressed the PCA reaction in the murine model. HPLC, and 1H and 13C NMR indicated that cirsimaritin, a flavonoid, was concentrated in active fractions of the extract. Our findings suggest that ECMM leaves have a potential regulatory effect on allergic reactions that may be mediated by mast cells. Furthermore, cirsimaritin may be the active anti-allergic component in CMM.

Copyright © 2017 American Chemical Society

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Quercetin and its analogues: Optical and acido-basic properties


Citation: Phys. Chem. Chem. Phys., 2017, Accepted Manuscript – first published on 07 Sep 2017 – DOI: 10.1039/C7CP03845C

Michal Biler, David Biedermann, K. Valentova, Vladimir Kren and Martin Kubala


This study is focused on eight structurally analogous natural flavonoids that exhibit wide range of biological activities, which are of interest in pharmacy, cosmetics or food industry. Using both experimental and theoretical approaches, we relate their fundamental physico-chemical properties to the structural motifs, with particular focus on UV/Vis absorption properties and pH dependence. We highlight the role of the C2-C3 double bond, whose presence or absence is responsible for the switch between absorption bands in the UVB and UVA region, which is rationalized by strong modification of involved molecular orbitals. After deprotonation in alkaline environment, typical switch in intensities at maximum absorption wavelength (λmax) is observed enabling to calculate pKa values for compounds with the single C2-C3 bond, whereas a bathochromic shift of λmax vs. pH is observed for the C2-C3 double bond containing compounds. These behaviors are also rationalized and understood by MO analysis. Interestingly, high pH (above 11 for ampelopsin and above 9 for myricetin) induces formation of a long-wavelength peak arising from double and/or triple deprotonation. Substitution at position C3 by OH group has almost no effect on λmax for taxifolin and eriodictyol, whereas the effect is larger for quercetin and luteolin. Additional sugar moiety at C3 has a stabilizing effect and induces only minor changes in spectral behavior.

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Intern Med J, 47: 8. (2017)

Bakhtiar, M., Too, C., Tan, L., Sulaiman, S., Tang, M., Fauzi, N.-A., Nagum, A., Joseph, C., Kwok, F. and Rayappa, G.


Non-steroidal anti-inflammatory drugs (NSAIDs) hypersensitivity is one of the leading cause of adverse reactions and a matter of concern in susceptible patients, with NSAIDs induced urticaria/angioedema (NIUA) being the commonest phenotype. Positive associations between the human leukocyte antigen (HLA) and NSAIDs hypersensitivity have been observed in different populations.


The aims of this study were to determine the frequency of HLA genes in NIUA patients and NSAID-tolerant controls and, demonstrate the HLA associations of NIUA in a Malay population.


35 Malay patients with at least two chemically different NSAIDs hypersensitivity of the NIUA phenotype and 35 NSAIDs-tolerant controls following the 2013 European Network for Drug Allergy (ENDA) guideline for NSAIDs hypersensitivity were recruited. These subjects were genotyped for HLA-A, -B, -DRB1 and -DQB1 using polymerase chain reaction sequence-specific oligonucleotide probe hybridisation (PCR-SSO) method. A haplotype analysis was performed comparing the NIUA cases with 951 normal healthy controls.


The frequency of HLA-A*11:01 alleles was 27.1% in the NIUA group, compared with 8.6% in the NSAIDs tolerant group (odds ratio [OR] = 3.35, 95% confidence interval [CI] = 1.31–8.60, P < 0.05). The haplotype analysis revealed that HLA-A*11:01-B*15:02-DRB1*12:02-DQB1*03:01 and HLA-A*11:01-B*15:13-DRB1*12:02-DQB1*03:01 were significantly higher in NIUA (11.4% and 5.71% respectively) than in normal healthy controls (1.1%, OR = 11.76, 95% CI = 3.50–39.52, P = 0.001 and 0.21%, OR = 28.76, 95% CI = 3.93–210.48, P = 0.007 respectively).


These findings showed that HLA-A*11:01 was positively associated with NIUA in a Malay population. The haplotype findings also suggest that the HLA-A*11:01-B*15:02-DRB1*12:02-DQB1*03:01 and HLA-A*11:01-B*15:13-DRB1*12:02-DQB1*03:01 may be used as genetic markers to determine the NIUA phenotype in this population.

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Recurrence of Chronic Urticaria: Incidence and Associated Factors


The Journal of Allergy and Clinical Immunology: In Practice – Available online 6 September 2017

Julie K. Kim, MD, Daniel Har, MD, L. Steven Brown, MS, David A. Khan, MD (Department of Internal Medicine, Division of Allergy & Immunology, University of Texas Southwestern Medical Center, Dallas, Tex; Health System Research, Parkland Health and Hospital System, Dallas, Tex)


Chronic urticaria (CU) is urticaria that has been present continuously or intermittently for at least 6 weeks. Although the prevalence and characteristics of CU are well established, little is known about recurrent CU (RCU).


We sought to establish a definition, determine the frequency, and evaluate risk factors for RCU.


A retrospective chart review of adult patients with CU evaluated at the University of Texas Southwestern allergy and immunology clinic was performed. RCU was defined as CU recurring at least 6 months after cessation of controller therapy and resolution of prior CU symptoms. Charts were reviewed for symptom resolution and recurrence, subtypes of CU (idiopathic, physical, and urticarial vasculitis), and medication usage (first-line agents, alternative agents, and steroid dependence).


Forty-five of 341 patients (13%) had RCU. The recurrence group had a higher frequency of alternative agent use at 57.8% (n = 26) compared with the nonrecurrence group at 34.8% (n = 103), which was statistically significant (P < .01). The rate of steroid dependence was similar in both groups (13.3% in the recurrence group vs 14.5%) and not statistically significant. Individuals exposed to anti-inflammatory agents, immunosuppressants, and omalizumab had a significantly higher relative risk of recurrence compared with those who only used first-line agents (relative risk [RR] 2.32, P < .01; RR 2.69, P < .01; and RR 2.18, P = .05, respectively).


RCU occurs in approximately 13% of patients with CU in our clinic population. Alternative agent use and antihistamine refractoriness appear to place patients at increased risk for recurrence compared with first-line agent use alone.

Key words

Chronic urticaria; Chronic idiopathic urticaria; Physical urticaria; Urticarial vasculitis; Recurrent chronic urticaria

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