ORIGINAL ARTICLE Head and neck sarcoidosis, from wait and see to tumor necrosis factor alpha therapy: A pilot study Andreas Knopf, MD, 1 * Tobias Lahmer, MD, 2 Adam Chaker, MD, 1 Thomas Stark, MD, 1 Benedikt Hofauer, 1 Anja Pickhard, MD, 1 Klaus Th€ urmel, MD, 2 Murat Bas, MD 1 1 Hals-Nasen-Ohrenklinik und Poliklinik, Technische Universit € at M€ unchen, Munich, Germany, 2 Abteilung f€ ur Nephrologie der II Medizinischen Klinik und Poliklinik, Technische Universit € at M€ unchen, Munich, Germany. Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.23022 ABSTRACT: Background. To suggest treatment modalities with respect to the specific requirements of head and neck sarcoidosis. Methods. Head and neck sarcoidosis was diagnosed in 31 patients. Treatment regimes comprised wait and see, corticosteroid-pulse, stable- dose corticosteroids, or adalimumab. Results. In all, 21 patients had isolated head and neck sarcoidosis and a further 8 patients showed concomitant pulmonary sarcoidosis. Two patients with pulmonary sarcoidosis developed subsequent head and neck manifestation. Most patients with isolated head and neck sarcoidosis did not receive systemic therapy. None exhibited relapsing disease. Three patients with head and neck manifestation underwent corticosteroid pulse. Complete remission (CR) was detected for all after 5 months. Six patients were treated with stable-dose corticosteroids. Five of 6 showed CR after 12 months and 1 of 6 patients partial remission (PR) after 24 months. Five of 6 patients exhibited relapses. Two patients underwent adalimumab therapy and showed PR after 65 or CR after 26 months, respectively. Conclusions. Most patients with head and neck sarcoidosis did not require systemic therapy. We suggest corticosteroid-pulse therapy for patients with severe head and neck manifestation. Adalimumab might be potent for nonresponder. V C 2012 Wiley Periodicals, Inc. Head Neck 00: 000–000, 2012 KEY WORDS: sarcoidosis, head and neck, therapy, corticosteroid, tumor necrosis factor inhibitor INTRODUCTION Sarcoidosis (syn. M. Boeck, M. Besnier-Boeck-Schau- mann) is an inflammatory systemic disease characterized by noncaseating granulomas composed of epitheloid giant cells, macrophages, and lymphocytes. 1,2 Although the eti- ology of sarcoidosis remains unclear, several studies sug- gest an interaction of genetic predisposition and triggering substances. Herpes simplex virus (HSV), Epstein–Barr vi- rus (EBV), retrovirus, Coxsackie B virus, Borrelia burg- dorferi, typical and atypical mycobacteria, rickettsia, pro- pioni-bacterium acnes, aluminum, zirconium, or pine pollen are discussed as trigger factors. 3,4 Pathophysiologic mechanisms focus on a dysregulation of the T-cell system with enhanced Th-1 immune response. The inflammatory condition usually affects the lungs, although extrapulmo- nary manifestation in liver, eyes, lymph nodes, skin, heart, and parotid gland occurs infrequently. Some impor- tant mediators (interleukin 2 [IL-2], IL-2 receptor, 1,25- dihydroxycholecalciferol, immunoglobulin G [IgG], and angiotensin-converting enzyme [ACE]) have been identi- fied in the development of this granulomatous disease, but the molecular mechanisms underlying different dis- ease manifestation remain unclear. In fact, there are nota- ble differences in the clinical course of patients with pul- monary sarcoidosis compared with their extrathoracic counterparts. Although pulmonary sarcoidosis is often incidentally diagnosed via chest x-ray, patients with iso- lated extrathoracic impairment usually present distinct clinical symptoms. Treatment regimes vary broadly due to disease burden and/or disease duration. Most authors agree that patients with "limited’’ disease do not require any systemic therapy. Corticosteroids (0.5 mg/kg/day), slowly reduced for at least 6 months, still represent the treatment of choice when systemic therapy is appro- priate. 5–7 Corticosteroid-sparing methotrexate replaces or supplements corticosteroids in long-term therapy regimes. Recent studies suggest the application of tumor necrosis factor alpha (TNF-a) antagonists for patients with severe extrapulmonary systemic sarcoidosis. 5 The literature lacks detailed analysis about treatment modalities in head and neck sarcoidosis. Sufficiently powered double-blind, pla- cebo-controlled studies do not exist. PATIENTS AND METHODS From November 2007 to July 2011, 31 patients with head and neck sarcoidosis were treated in the outpatient clinic of the Department of Otorhinolaryngology and Head and Neck Surgery at Technical University Munich. *Corresponding author: A. Knopf, Department of Otorhinolaryngology/Head and Neck Surgery, Technische Universit€ at M€ unchen, Ismaningerstrasse 22, D-81675 M€ unchen, Germany. E-mail: a.knopf@lrz.tum.de HEAD & NECK—DOI 10.1002/HED MONTH 2012 1