Rheumatology key message IgG4-related disease is a protean disease, with various and still not well known manifestations. Sir, We report a case of a woman with a biopsy-proven IgG4-related ulcerative lesion of the superior lip, extended to the nasal cavities, and serum positivity for pANCA assay. A 54-year-old Caucasian women was referred to the ENT unit of our hospital with a 6-month history of a progressive enlarging, ulcerated lesion of the right nasal vestibule. Her medical history was unremarkable, except for a multiple drug allergy. The patient was a non-smoker and denied any use of illicit drugs. On clinical examination, the lesion, measuring 4 cm, extended from the superior lip deep into the nasal vestibule (Fig. 1A). It showed reddish, crusted and infiltrated borders overhanging the ulcer bed. On rigid nasal endoscopy, an almost complete erosion of the anterior two-thirds of the nasal septum and of the middle and inferior turbinates was appreciated. The nasal cavities were occupied by a crusty, hypertrophic material, which was firmly attached to the underlying mucosa. A chest and neck CT scan revealed irregular thickening of the nasal vestibulum, with contrast enhancement. Several laterocervical and submandibular lymphadenopathies and a diffuse ground-glass appearance of the lower lung lobes were also observed (supplementary Fig. S1, available at Rheumatology online). Laboratory tests showed a positivity for pANCA on indirect immunofluorescence, but the specificity of the ANCA was not against MPO or PR3 by ELISA. A biopsy was performed at the border of the lesion in the nasal vestibule. It showed a severe mixed inflammatory infiltrate, rich in eosinophils, involving the dermis, with ulceration of the overlying epidermis with no signs of vasculitis or granulomatous inflammation. There was no evidence of neoplasia, infection or polychondritis. Fig. 1 View largeDownload slide Macroscopic aspect of the lesion before and after treatment and histologic appearance Vestibular lesion of the patient before (A) and after (B) prednisone treatment, and histological aspect of the lesion, showing a mixed inflammatory infiltrate, rich in eosinophils and plasma cells (yellow arrow), involving the dermis, with ulceration of the overlying epidermis (red arrow), with no signs of vasculitis, granulomatous flogosis, neoplasia, infections or polychondritis (C). Immunohistochemical characterization of the dermal infiltrate showed an abundant presence of IgG4-positive plasma cells (IgG4/IgG plasma cells ratio >40%) (D). Fig. 1 View largeDownload slide Macroscopic aspect of the lesion before and after treatment and histologic appearance Vestibular lesion of the patient before (A) and after (B) prednisone treatment, and histological aspect of the lesion, showing a mixed inflammatory infiltrate, rich in eosinophils and plasma cells (yellow arrow), involving the dermis, with ulceration of the overlying epidermis (red arrow), with no signs of vasculitis, granulomatous flogosis, neoplasia, infections or polychondritis (C). Immunohistochemical characterization of the dermal infiltrate showed an abundant presence of IgG4-positive plasma cells (IgG4/IgG plasma cells ratio >40%) (D). Due to the suspicion of an ANCA-associated vasculitis, the patient was referred to the Rheumatology Unit of our Hospital. Blood test showed eosinophilia (702/μl), CRP 17 900 µg/l, ESR 79 mm/h and a marked increase in IgE (7344 U/ml). Urine analysis was unremarkable. On further investigation, no clinical features of a systemic vasculitis were present. An increase in IgG4 serum levels was demonstrated (362 mg/dl; normal range 4–86 ml/dl), raising the question of a possible IgG4-related disease (IgG4RD) and prompting the review of the patient’s biopsy sample . Immunohistochemical characterization of the dermal inflammatory infiltrate showed a prevalence of CD138+ plasma cells (>200×/high-power field) with an IgG4/IgG plasma cells ratio of >40%. Neither obliterative venulitis nor plexiform fibrosis were observed. Altogether, these findings fulfilled the criteria for the diagnosis of definite IgG4RD . Oral administration of 50 mg/daily prednisone was started. After a month of treatment, an almost complete resolution of the lesion was observed (Fig. 1B). On repeated endoscopic examination the nasal cavities mucosa looked normal. The prednisone treatment was slowly tapered until suspension during the following 6 months, without relapses and with an almost complete normalization of serum IgG4 levels (89 mg/dl; normal range 4–86 ml/dl). After 1.5 years of follow-up, the patient showed a persistent, treatment-free remission. IgG4RD is an immune-mediated, systemic condition, characterized by infiltration of IgG4 plasma cells into the tissues resulting in fibrosis and organ dysfunction. The protean manifestations of IgG4RD mimic many neoplastic, inflammatory and infectious pathologies, with a broad spectrum of diseases in the differential diagnosis. Moreover, history of allergy, peripheral eosinophilia and high serum level of IgE are common findings in IgG4RD patients. First-line treatments for IgG4RD are glucocorticoids, usually prednisolone at the dose of 0.6–1 mg/kg daily followed by a slow tapering. In case of relapses during tapering or intolerance to high-dose glucocorticoid treatment, a steroid-sparing agent (AZA, MMF or MTX) can also be introduced. Recently, a growing number of reports also support the efficacy of B-cell depletion in this condition . The diagnosis of a definite IgG4RD requires the fulfillment of three diagnostic criteria, including: (i) organ enlargement or nodular/hyperplastic lesions in various organs; (ii) a serum IgG4 concentration >135 mg/dl; and (iii) histopathological findings of >10 IgG4+ plasma cells/high-power field and an IgG4+/IgG+ plasma cell ratio >40% . We describe a case of IgG4RD with an unusual clinical presentation, consisting of an isolated, non-healing, ulcerative, cutaneous vestibulo-nasal lesion, raising the differential diagnosis between an infectious and a vasculitic process. The differential diagnosis of this case includes also the cocaine-induced midline destructive lesions, characterized by ANCA positivity and histologic features like fibrinoid necrosis, leucocytoclastic vasculitis, microabscesses and mononuclear cell infiltration . The review of a bioptic specimen allowed exclusion of other aetiology and establishmeant of a correct diagnosis, underlying the importance of awareness of IgG4RD for both the clinician and pathologist. Sinonasal involvement by IgG4RD is not frequent, and includes chronic rhinitis, nasal polyps and nasal soft tissue lesions with or without bone destruction. To our knowledge, this is the first description of an extension of the pathologic process from the nasal cavity to the facial skin, resulting in an ulcerative lesion . Although ANCA have been traditionally considered as highly specific for ANCA-associated vasculitis, several reports have shown that patients with a histologically proven IgG4RD can also present increased serum ANCA, especially in case of head or neck involvement . In this patient, the cutaneous lesion seemed isolated; however, on CT scan the patient showed features of lung interstitial involvement. This is in keeping with previous reports, describing several patterns of lung manifestations in IgG4RD . In conclusion, IgG4RD can mimic several other disorders and it is yet an underrecognized protean disease. Particularly in the presence of atypical manifestations, such as those of the present case, histopathology remains the main tool for an accurate diagnosis of IgG4RD. Acknowledgements Authors’ contributions: R.P., B.L., B.C., C.A., G.D’A. and M.F. cared for the patient and contributed equally to writing of the report. The other authors cared for the patient. Written consent to publication was obtained. Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this manuscript. Disclosure statement: The authors have declared no conflicts of interest. Supplementary data Supplementary data are available at Rheumatology online. References 1 Tokura Y, , Yagi H, , Yanaguchi H et al. IgG4‐related skin disease . Br J Dermatol 2014 ; 171 : 959 – 67 . Google Scholar CrossRef Search ADS PubMed 2 Umehara H, , Okazaki K, , Masaki Y et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011 . Mod Rheumatol 2012 ; 22 : 21 – 30 . Google Scholar CrossRef Search ADS PubMed 3 Kamisawa T, , Zen Y, , Pillai S, , Stone JH. IgG4-related disease . Lancet 2015 ; 385 : 1460 – 71 . Google Scholar CrossRef Search ADS PubMed 4 Trimarchi M , Gregorini G , Facchetti F et al. Cocaine-induced midline destructive lesions: clinical, radiographic, histopathologic, and serologic features and their differentiation from Wegener granulomatosis . Medicine (Baltimore) 2001 ; 80 : 391 – 404 . Google Scholar CrossRef Search ADS PubMed 5 Prabhu SM, , Yadav V , Irodi A , Mani S , Varghese AM. IgG4-related disease with sinonasal involvement: a case series . Indian J Radiol Imaging 2014 ; 24 : 117 – 120 . Google Scholar CrossRef Search ADS PubMed 6 Della-Torre E , Lanzillotta M , Campochiaro C et al. Antineutrophil cytoplasmic antibody positivity in IgG4-related disease: a case report and review of the literature . Medicine (Baltimore) 2016 ; 95 : e4633 . Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: email@example.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)
Rheumatology – Oxford University Press
Published: Mar 19, 2018
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