Baoqi Yang

Furen Zhang

Guizhi Zhou

Yaru Wang

English

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273Acta Dermatovenerol Croat                              2018;26(3):273-275                               LETTER TO THE EDITORACTA DERMATOVENEROLOGICA CROATICATwo Cases of Dermatitis Herpetiformis Successfully Treated with Tetracycline and NiacinamideDear Editor,Dermatitis herpetiformis (DH) is a chronic, poly-morphic, pruritic autoimmune blistering skin disease characterized by subepidermal blisters, neutrophilic microabscesses, and granular IgA deposition within the dermal papillae. DH is classified as a cutaneous manifestation of coeliac disease, a type of gluten-sen-sitive enteropathy (1). The treatment of DH includes dapsone and a gluten-free diet (GFD). Other thera-pies should be considered in patients who are un-able to tolerate dapsone, including sulfapyridine and glucocorticoids. Herein we present two cases of DH with good responses to tetracycline and niacinamide combination therapy. Case 1 was a 42-year-old man who was admit-ted to our hospital with a 3-year history of recurrent pruritic papules and bullous lesions involving the trunk and upper limbs. On examination, the patient showed disseminated erythematous papules on the upper limbs and back as well as vesicles. Nikolsky’s sign for vesicles was negative (Figure 1, a-c). The results of routine blood examinations were within normal ranges. He did not have a history of chronic Figure 1. Clinical appearance before treatment (a, b, c) and after 2 weeks of treatment (d, e, f ) in case 1. Subepidermal blisters and accumulation of neutrophils at the papillary dermis of the involved skin. (g) (hematoxylin and eosin, ×400). Direct im-munofluorescence revealed fibrillar deposition of IgA on the dermal papillae (h).274 ACTA DERMATOVENEROLOGICA CROATICAdiarrhea. The histologic examination showed subepi-dermal blisters and accumulation of neutrophils at the papillary dermis of the involved ski. Direct immu-nofluorescence revealed fibrillar deposition of IgA on the dermal papillae (Figure 1. g, h). Case 2 was a 34-year-old woman who had a his-tory of skin rash and pruritic lesions predominantly involving the arms and legs, which had been present for 10 months. She had been treated with prednisone (30 mg daily) with improvement; however, the lesions reappeared when the prednisone was discontinued. She had a history of constipation. On physical exami-nation, the skin lesions manifested as erythematous papules, vesicles, and scabs on the limbs (Figure 2. a-c). She felt apparently pruritic. The histologic exami-nation of the biopsy identified subepidermal blisters with a neutrophil infiltrate in the upper dermis. Direct immunofluorescence revealed granular deposition of IgA on the dermal papillae (Figure 2. e, f ). The results of routine blood examinations were within normal ranges, with the exception of elevated IgE concentra-tion (222.5 ku/L (normal range, 0-100 ku/L)). The clinical manifestations and histologic and immunofluorescence examinations of the two cases confirmed the diagnosis of DH. The two patients were subsequently started on a strict GFD. At that time, dapsone was not available in the hospital. The pa-tients were treated with oral tetracycline (500 mg four times daily) and nicotinamide (500 mg three times daily). The rash affecting case 1 resolved entirely in 2 weeks. The patient discontinued the medications af-ter 6 months, and occasionally presented with a few Figure 2. Clinical appearance before treatment (a, b) and after 1 month of treatment (c, d) in case 2. Subepidermal blis-ters and neutrophil infiltration at the upper dermis (e) (hematoxylin and eosin, ×400). Direct immunofluorescence revealed granular deposition of IgA on the dermal papillae (f ). Letter to the editor Acta Dermatovenerol Croat2018;26(3):273-275275ACTA DERMATOVENEROLOGICA CROATICApruritic papules and vesicles, but the lesions resolved within 1 week. The lesions affecting case 2 completely healed within 1 month. The patient continued taking those medications and no recurrence of the skin le-sions occurred during 2 years of follow-up.Dapsone is considered first-line therapy for pa-tients with DH (2). Recent findings have shown dap-sone and lower dosages of sulfasalazine combination therapy in DH are effective and well-tolerated (3). Alternative monotherapeutic agents in mild autoim-mune bullous diseases such as DH include a tetra-cycline group of antibiotics with niacinamide or its derivatives as well as sulfasalazine. Because dapsone is difficult to obtain in China except for patients with leprosy, we treated the patients with tetracycline and nicotinamide. To our knowledge, only a few cases of DH have been successfully treated with oral tetracy-cline and niacinamide (2,4). One of the patients was also prescribed heparin (4). Tetracycline has anti-in-flammatory properties due to the inhibition of me-talloproteinase activity and mast cell activation (5). Nicotinamide is a potent modulator of several pro-inflammatory cytokines. Nicotinamide can inhibit cytokine release (IL-1, IL-6, IL-8, and TNF-α) from im-mune cells, inhibit chemotaxis and degranulation of immune cells, inhibit lymphocyte blast transforma-tion, and suppress T-cell activity (6). The non-antibi-otic properties of tetracycline in combination with nicotinamide may participate in inhibition of anti-body formation, modulation of pro-inflammatory cy-tokines, inflammatory cell accumulation, lymphocyte transformation, and T-cell activation.In summary, we reported two typical cases of DH that were successfully treated with oral tetracycline and niacinamide, which completely healed the rash and relieved the symptoms within 1 month. The combination of tetracycline and nicotinamide can be recommended as a useful therapy for patients where dapsone is not available or for patients who do not tolerate dapsone.Acknowledgments:This study was supported by a grant from the Key Research and Development Program of Shandong (2015GSF118126) and The Innovation Project of Shandong Academy of Medical Sciences.References:1.  Kárpáti S. Dermatitis herpetiformis. Clin Dermatol. 2012;30:56-9. 2.  Zemtsov A, Neldner KH. Successful treatment of dermatitis herpetiformis with tetracycline and nicotinamide in a patient unable to tolerate dap-sone. J Am Acad Dermatol. 1993;28:505-6.3.  Bevans SL, Sami N. Dapsone and sulfasalazine combination therapy in dermatitis herpetiformis. Int J Dermatol. 2017;56:e90-e92.4.  Shah SA, Ormerod AD. Dermatitis herpetiformis effectively treated with heparin, tetracycline and nicotinamide. Clin Exp Dermatol. 2000;25:204-5.5.  Perret LJ, Tait CP. Non-antibiotic properties of te-tracyclines and their clinical application in derma-tology. Australas J Dermatol. 2014;55:111-8.6.  Abdelmaksoud A. Tetracyclines and/or nicotina-mide in blistering dermatosis. J Eur Acad Der-matol Venereol. 2017;31:e291.Yaru Wang1,2,3,4, Baoqi Yang2,3,4, Guizhi Zhou2,3,4, Furen Zhang2,3,41Department of Dermatology, School of Medicine and Life Sciences, University of Jinan-Shandong Acad-emy of Medical Sciences, Jinan, Shandong, China2Department of Dermatology, Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, Shandong, China3Department of Dermatology, Shandong Provincial Hospital for Skin Diseases, Jinan, Shandong, China4Shandong Provincial Key Lab for Dermatovenere-ology, Jinan, Shandong, ChinaCorresponding author:Baoqi Yang, MDDepartment of DermatologyShandong Provincial Institute of Dermatology and VenereologyShandong Academy of Medical Sciences27397 Jingshi Road, Jinan, Shandong250022, Chinabaoqiyang@126.comReceived: August 1, 2017Accepted: July 11, 2018Letter to the editor Acta Dermatovenerol Croat2018;26(3):273-275

Two Cases of Dermatitis Herpetiformis Successfully Treated with Tetracycline and Niacinamide

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