Objective: To describe a series of 41 patients with fresh lesions of Sweet syndrome in which the histopathologic study demonstrated an inflammatory infiltrate mostly composed of histiocytoid mononuclear cells. Design: Histopathologic, immunohistochemical, and cytogenetic studies of the inflammatory infiltrate in a case series of histiocytoid Sweet syndrome. Setting: University departments of dermatology and a private laboratory of dermatopathology. Methods: Conventional histopathologic study as well as immunohistochemical investigations were performed using the alkaline phosphatase antialkaline phosphatase technique with a large panel of antibodies. In some cases, fluorescent in situ hybridization studies were performed to investigate the presence of the bcr/abl gene fusion. Results: Immunohistochemical studies demonstrated that most cells of the infiltrate showed immunoreactivity for CD15, CD43, CD45, CD68, MAC-386, HAM56, and ly-sozyme, which is consistent with a monocytichistiocytic immunoprofile. However, intense myeloperoxidase reactivity was detected in most of the cells with histiocytic appearance, which raised the possibility of specific cutaneous involvement by myelogenous leukemia. Nevertheless, cytologic peripheral blood examinations, fluorescent in situ hybridization studies to investigate the bcr/abl gene fusion, and follow-up of the patients, taken all together, ruled out this possibility. Conclusions: This case series demonstrates that some fresh cutaneous lesions of Sweet syndrome are histopathologically characterized by an infiltrate mostly composed of cells that may be misinterpreted as histiocytes, when in fact they are immature myeloid cells. We named this histopathologic variant histiocytoid Sweet syndrome, which should not be mistaken with leukemia cutis or other inflammatory dermatoses that are histopathologically characterized by histiocytes interstitially arranged between collagen bundles of the dermis.

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like TNF-α 6. In IMIDs, there is a TH1 main reaction and also a reduction of the differentiation to TH2 response on the part of T lymphocytes 7. Once an antigen in IMIDs initiates the inflammatory response, a higher production of pro-inflammatory cytokines is observed as TNF-α, IL-1, IL-6 and the reduction of other cytokines such as IL-10 and IL-4 8,9. Regarding the group of IMIDs, all the diseases with autoimmune origin and essentially TH1 response are included. Among these diseases, different specialities as Endocrinology, Gastroenterology, Hepatology, Rheumatology and Dermatology are involved provided that the complexity of these pathologies usually demanding a multidisciplinar team for the evaluation and monitoring of these diseases. Inflammatory bowel diseases including Crohn's disease, ulcerative colitis and IBD-unclassified, are some of the immune-mediated diseases which affect up to 2.2 million patients in Europe with an annual incidence ranging between 9 and 15% depending on the geographical area 10-12. Recently, an annual incidence of 9%-20% of IMIDs associated to IBD was described as well as its association with extraintestinal manifestations and family history of IBD 13. However, there is a lack of knowledge related to the association between IMIDs and IBD and their influence in the evolutive course of these diseases and also the therapeutic requirements of immumomodulators or biological therapy 14. Most of the studies described the association between IBD and thyroid disorders 15-17 , skin psoriasis among others diseases and different conclusions are discussed about prognostic implications of these diseases in IBD 18,19. Furthermore, recent data showed the need of more surgical procedures in patients with IMIDs even other studies showed disparities with the results 20. For this reason, we designed a study with two essential aims: on the one hand, to describe IMIDs associated to IBD in a cohort of patients and on the other hand, the clinical differences and therapeutic requirements in relation to the presence or lack of IMIDs in said patients.

Objective: The objective of this study was to analyze the evolution of alpha and beta-CGRP circulating levels throughout CGRP monoclonal antibodies (mAbs) treatment in patients with chronic migraine (CM). Methods: We recruited patients with CM beginning mAbs along with sex and age paired healthy controls (HCs). Blood was extracted before, 2 weeks (M0.5) and 3 months (M3) after the first dose of mAbs, always in free-migraine periods, and once for HCs. Alpha and beta-CGRP serum levels were measured using enzyme-linked immunosorbent assays (ELISAs) specific for each isoform. Results: Baseline alpha-CGRP levels were significantly elevated in 103 patients with CM (median = 50.3, 95% confidence interval [CI] = 40.5-57.0 pg/ml) compared to 78 HCs (median = 37.5, 95% CI = 33.9-45.0 pg/ml; 95% CI of differences = 2.85-17.08 pg/ml) and significantly decreased (n = 96) over the course of mAb treatment (M0.5: median = 40.4, 95% CI = 35.6-48.2 pg/ml; and M3: median = 40.9, 95% CI = 36.3-45.9 pg/ml). Absolute decrease of alpha-CGRP throughout the treatment positively correlated with the decrease in MMDs. Negative modulation of alpha-CGRP significantly associated with positive scores at the Patient Global Impression of Change scale and with analgesic overuse reversal. Beta-CGRP did not differ at baseline between patients with CM (median = 4.2, 95% CI = 3.0-4.8 pg/ml) and HCs (median = 4.4, 95% CI = 3.4-5.6 pg/ml; À1.09 to 0.60) nor was modulated by mAb treatment (n = 96; M0.5: median = 4.5, 95% CI = 3.5-5.2 pg/ml; and M3: median = 4.6, 95% CI = 3.7-5.2 pg/ml). Interpretation: Treatment with mAbs, regardless of its target, is able to progressively normalize basally increased alpha-CGRP levels in CM and this effect correlates with efficacy measures, which supports a role of this neuropeptide as the first CM biomarker.