Acta Dermato-Venereologica Issue No. 97-5 97-5CompleteContent | Page 21

SHORT COMMUNICATION Increased Serum Levels of Th2-type Cytokines and Eotaxin in Fibrillar-type Dermatitis Herpetiformis Teruhiko MAKINO 1 , Yoko YOSHIHISA 1 , Megumi MIZAWA 1 , Kiyohiro TSUTSUI 2 , Chihiro NISHIJIMA 3 , Makoto INAOKI 3 and Tadamichi SHIMIZU 1 1 Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama 930- 0194, 2 Department of Dermatology, Ishikawa Prefectural Central Hospital, Ishikawa, and 3 Department of Dermatology, National Hospital Organization Kanazawa Medical Center, Kanazawa, Japan. E-mail: [email protected] Accepted Dec 15, 2016; Epub ahead of print Dec 16, 2016 Dermatitis herpetiformis (DH) is a pruritic papulovesi- cular disease that is symmetrically distributed over the shoulders, elbows, back and knees. Immunofluorescence has revealed granular IgA deposition in the papillary der- mis. IgA antibodies to both epidermal transglutaminase (eTG) and tissue transglutaminase (tTG) are usually detected in patients with DH. DH is commonly thought to be a cutaneous manifestation of gluten-sensitive enteropathy (GSE) (1, 2). We refer to this condition as “granular-type DH”. Although DH is a relatively com- mon disease in Caucasian populations, it is rare in Japan. Most Japanese patients with DH show unique features, including a high frequency of fibrillar IgA deposition in the papillary dermis, rare occurrence of GSE, absence of the HLA-DQ2/DQ8 haplotype and rare associations with autoimmune disease and lymphoma, although the histo- logical findings appear to be similar to those of granular- type DH (3, 4). Furthermore, as reported previously, these patients appear to have IgA antibodies to eTG, but not tTG (5). We refer to this condition as “fibrillar-type DH”. The clinical and histological findings of typical fibrillar-type DH are shown in Fig. S1 1 . Fibrillar-type DH appears to be rare in Caucasian populations (6). While the pathogenesis of DH is unclear, previous studies have suggested that the expression of interleukin (IL)-8, granulocyte-macrophage colony-stimulating factor (GM- CSF) and Th2-type cytokines could be important in the tissue infiltration process of eosinophils and neutrophils in granular-type DH (7, 8). The present study investigated the levels of serum cytokines and chemokines in order to clarify their presence and activity in the pathogenesis of fibrillar-type DH. Table I. Characteristics of study patients with fibrillar-type dermatitis herpetiformis Age, years/ Sex DIF (IgA deposition) 73/M 41/M 81/M 65/M 78/M Fibrillar Fibrillar Fibrillar Fibrillar Fibrillar GSE HLA-DQ2 or DQ8 IgA antibodies to eTG (cut-off <18 AU/ml) IgA antibodies to tTG (cut-off <18 AU/ml) – – – – – n.d. n.d. – – – 114.5 47.5 58.6 95.8 70.9 3.6 8.1 1.5 0.16 0.59 DIF: direct immunofluorescence; GSE: gluten-sensitive enteropathy; n.d.: not done; eTG: epidermal transglutaminase; tTG: tissue transglutaminase. MATERIALS AND METHODS ( see Appendix S1 1 ) RESULTS The study population included 5 patients with fibrillar- type DH (mean age 67.4 years; age range 41–81 years) in the active stage of the disease, who had not received any treatment and in whom the development of new lesions had been observed (Table I). The levels of IgA antibodies against eTG were markedly increased in all patients. However, no IgA antibodies against tTG were detected in any of the patients. None of the patient’s intestinal tissue specimens showed villous atrophy or lymphocytic cell infiltration. The serum level of interferon (IFN)-γ, a Th1-like cytokine, was increased slightly in the patients with DH (mean 0.414  ±  0.23; range 0.21–0.80 pg/ml) in compa- rison with the control subjects; however, the difference was not statistically significant. IL-12, another Th1-like cytokine, was not detected in either the patients with DH or the control subjects (Fig. S2a 1 ). The patients’ serum levels of Th2-like cytokines IL-4 (mean14.55  ±  5.3 pg/ml; range 6.84-21.71 pg/ml, https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-2604 p < 0.005), IL-5 (mean 6.09  ±  0.99 pg/ml; range 4.84–7.49 pg/ml, p < 0.001) and IL-13 (mean 1.14  ±  0.20 30 10 pg/ml; range 0.85–1.36 pg/ml, p < 0.005) were ** IL-5 IL-4 * significantly increased in comparison with 25 8 the normal subjects: IL-4: mean 0.04  ±  0.09 20 6 pg/ml; range 0-0.21 pg/ml, IL-5: mean 15 4 0.55  ±  0.14 pg/ml; range 0.37–0.72 pg/ml, IL- 10 13: mean 0.21  ±  0.09 pg/ml; range 0.08–0.29 2 5 pg/ml, respectively (Fig. 1 and Fig. S2b 1 ). 0 0 Patient Healthy Patient Healthy The serum IL-8 level in the patients with (n=5) control (n=5) control DH (mean 39.4  ±  43.5; range 1.1–93.81 pg/ (n=5) (n=5) ml) tended to be increased in comparison Fig. 1. Increased serum levels of cytokines IL-4 and IL-5 in patients with fibrillar- with the control subjects (mean, 0.26  ±  0.59 type DH. Values are shown as mean  ±  standard deviation. *p  < 0.005; **p  < 0.001. doi: 10.2340/00015555-2604 Acta Derm Venereol 2017; 97: 642–643 1 642 This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2017 Acta Dermato-Venereologica.