this report describes a case of granulomatosis with polyangiitis ( gpa ) in which the gingival manifestation was crucial in both making an early diagnosis and possibly in deciding the approach to treatment . a 57-year - old sailor presented to the department of dentistry at ulsan university hospital complaining of gingival swelling since approximately 2 months . the diagnosis of gpa was made on the basis of clinical symptoms and signs , and confirmed by the presence of the anti - neutrophil cytoplasmic antibody and a positive biopsy . the patient was admitted to the hospital and subsequently placed on a disease - modifying therapy regimen that included methotrexate and prednisone . identification of the gingival manifestation of the disease permitted an early diagnosis and prompt therapy in a disease in which time is a crucial factor . because of its rapid progression and potentially fatal outcome , an early diagnosis of gpa is important . therefore , dentists should be aware of the oral signs and symptoms of such systemic diseases . several systemic diseases exhibit oral and gingival manifestations , and thus dentists can play an important role in the early diagnosis of these diseases . granulomatosis with polyangiitis ( gpa ) , formerly known as wegener 's granulomatosis , is one such disease that may have gingival manifestations . gpa is a potentially life - threatening disease characterized by necrotizing granulomatous inflammation and small vessel vasculitis . it chiefly affects the upper and lower respiratory tract and kidneys , but can affect any part of the body or any of its organs . treatment gpa usually runs a rapid and fatal course with most patients not surviving more than a year after diagnosis . oral involvement of gpa has been observed in approximately 6%13% of patients   and its manifestation includes oral mucosal ulcerations and nodules . however the most characteristic oral lesion is hyperplastic gingivitis presenting with a  strawberry like  appearance . occasionally oral lesions the diagnosis of gpa is made based on clinical symptoms and signs , the presence of the anti - neutrophil cytoplasmic antibody ( anca ) , and a positive biopsy . . therefore , knowledge and information about lesions that are considered strongly indicative of gpa would be valuable for facilitating diagnosis . the observation of the gingival manifestation led us to suspect and make an early diagnosis of gpa , allowing rapid treatment to be initiated . in this report we also describe a review of the current literature with a focus on current knowledge of the disease characteristics , the criteria for diagnosis , and the treatment options . a 57year - old sailor presented to the department of dentistry at ulsan university hospital complaining of gingival swelling since approximately 2 months that had worsened over the preceding 2 weeks . he had also observed multiple skin ulcers on his face ; these symptoms had prompted him to visit the department of dermatology at our hospital immediately prior to his visit to our department . because he was a sailor , he had not been able to seek proper treatment before leaving his ship . , he had swollen erythematous gingivae with petechiae that had the appearance of the surface of a strawberry . besides the facial skin ulceration and gingival lesions the examination revealed nothing remarkable ( figure 1 ) . panoramic radiographs revealed no evidence of any underlying bone involvement although multiple teeth mobility was observed . laboratory results revealed a c - reactive protein concentration of 0.72 mg / dl and an erythrocyte sedimentation rate of 28 mm / hr but no leucocytosis ( 7,390/l ) . a human immunodeficiency virus test was negative , renal function and urinary sediment tests were normal , and all other results were unremarkable . an image showing the granulomatous ulcerations on the patients face and the  strawberry - likeappearance of the upper / lower gingivae . the initial differential diagnosis included pyogenic granuloma ( pg ) and gpa . because a  strawberry - like gingivitis has been suggested to be a characteristic sign of gpa , the patient was advised to undergo an incisional biopsy of the affected gingiva . the patient was immediately started on a course of antibiotics whilst the histopathology results were awaited . the patient failed to show any signs of recovery as a result of the antibiotic treatment . on a return visit to the hospital one week later , the patients signs and symptoms had worsened with partial bony exposure of the maxillary anterior alveolar portion evident ( figure 2 ) . the histopathologic examination of the biopsied tissue showed chronic active inflammation with abscess , fibrinoid vasculitis and granulation of the tissue ( figure 3 ) . based on these findings , and the clinical presentation of strawberry gingivitis and facial lesions , a diagnosis of gpa was strongly suspected and it was decided to analyze blood levels of anca . laboratory testing demonstrated a positive cytoplasmic anti - neutrophil cytoplasmic antibody ( c - anca ) result and an associated increase in proteinase 3 anca ( pr3-anca ) levels suggesting a diagnosis of gpa . ( a ) a diffuse mixed inflammatory cell infiltrate comprising mostly neutrophils that formed micro - abscesses . ( a , b : h&e staining ) we referred the patient to the department of internal medicine , for further evaluation and a systemic work - up , where the diagnosis of gpa was confirmed . the patient was admitted and started on a disease - modifying therapy regimen , which included 12.5 mg of methotrexate a day , once every 7 days , and 40 mg of prednisone daily . after 10 days of treatment , improvement in the patient was observed ( figure 4 ) , and he was discharged from the hospital on day 14 . as the oral hygiene and periodontal status of the patient had worsened due to the gingival swelling , we advised him on good oral hygiene and performed scaling on the day of discharge . two months after initiation of the treatment , prednisone was progressively tapered to 2.5 mg for maintenance ; the facial and gingival lesions did not show signs of relapse . an image showing the dramatic improvement in the patients ulcerative facial lesions and gingivae following treatment . some of these systemic conditions , including sarcoidosis , inflammatory bowel disease ( ibd ) , melkersson  rosenthal syndrome ( mrs ) , and gpa , can show oral granulomatous lesions . gpa was first described as a separate entity from peri - arteritis nodosa by friedrich wegener in 1937 and was formerly known as wegener 's granulomatosis . it is a form of primary systemic vasculitis characterized by granulomatous inflammation of the soft tissue as well as fibrinoid vasculitis of the small to medium sized vessels of the body . the precise etiology remains unknown , although microbes such as bacteria and viruses as well as genetic factors have been implicated in its pathogenesis . the reported annual incidence of gpa varies from 212 per million and its prevalence is estimated to be 24157 per million . although the age of the patient at diagnosis is generally 4560 years , it can present at any age . the incidence of gpa is equal in men and women , and it is more common in caucasians than in other ethnic groups . localized forms of gpa predominantly affect the upper respiratory tract , whereas generalized forms can show various combinations of renal manifestations , alveolar hemorrhage , and vital organ involvement with altered general condition . the incidence of oral manifestations in gpa range from 6%13% of patients , and the mouth is the initial site of clinical presentation in 5%6% of cases . oral manifestations of gpa include mucosal ulceration that can affect the buccal or lingual mucosa , mouth floor , posterior pharynx and tonsils , and labial mucosal nodules . upper anterior gingivae are usual oral site of involvement of gpa ; the affected gingivae may be red to purple in color and have petechiae that resemble an  over - ripe strawberry  . the  strawberry - like  appearance of the gingivitis has been suggested to be a particularly characteristic sign of gpa . osteomyelitis or necrosis of the underlying bone can develop with subsequent mobility and loss of teeth . oral lesions can remain localized for unusually long periods of time before multi - organ involvement occurs . the american college of rheumatology criteria for the classification of gpa are as follows : abnormal urinary sediment ( the presence of red cell casts or greater than five red blood cells per high power field ) , abnormal findings on chest radiograph ( nodules , cavities , or fixed infiltrates ) , oral ulcers or nasal discharge , and granulomatous inflammation on biopsy . for the diagnosis of gpa , a patient must have at least two of these four criteria . the presence of any two or more criteria gives a sensitivity of 88.2% and a specificity of 92.0% . these tests in combination with biopsies were used before the discovery of anca and have greatly facilitated the diagnosis of gpa . the presence of anca is the most important serological test in the diagnosis of vasculitis . in patients with gpa , a positive anca result with a cytoplasmic distribution that binds to pr3-anca using an enzyme - linked immunosorbent assay is a typical finding . anca serology has a sensitivity of 90% and a specificity of 96% in detecting gpa . therefore , a combination of clinical presentation , biopsy , and a positive c - anca result provides the most effective approach for diagnosis . delay in the diagnosis of gpa is unfortunately common and this often leads to serious morbidity or even fatal outcomes . left untreated , only 18% of gpa patients survive beyond one year , with renal failure being the most common cause of death . the aim of treatment is twofold : to target the outward signs of the disease in order to improve the patient 's symptoms , and to prevent the onset of severe renal disease . it has been suggested that the choice of therapeutic agents for the treatment of gpa should depend on the severity of the disease and whether the signs are localized or generalized . in recent times mortality due to gpa has been significantly reduced by the use of cytotoxic therapy with cyclophosphamide and glucocorticoids . after the introduction of cytotoxic drugs in combination with steroids , although the recommended treatment consists initially of high doses of steroids in combination with immunosuppressive therapy using cyclophosphamide , long - term treatment with cyclophosphamide has been associated with an increased incidence of severe side effects such as hemorrhagic cystitis , bladder cancer , lymphoma , and bone marrow suppression . therefore , methotrexate or azathioprine have been suggested as a substituted for cyclophosphamide . in the present case methotrexate although some lesions respond well to treatment , relapse and acute renal failure can occur within months . thus , frequent follow - up examinations are required to ensure adequate control of the disease . facial granulomatosis is an important element in the differential diagnosis of other granulomatous diseases , such as tuberculosis , systemic fungal infections , leprosy , and foreign body reactions . hence , these pathologies can also be suspected when patients present with only the facial lesions . in fact , our patient s dermatologist suspected tuberculosis or other infection based purely on the physical examination of the face . however , they were later ruled out based on the patient s medical history , general and systemic examination , and the laboratory results . patients with sarcoidosis , ibd , and mrs can also present with similar orofacial granulomatous lesions , and these diseases should be ruled out . the skin lesions of sarcoidosis usually resolve spontaneously in 24 weeks , but our patient s lesions had worsened over 2 months . moreover , he did not have abdominal pain , diarrhea , and rectal bleeding commonly associated with ibd , and recurring facial paralysis and swelling associated with mrs . although pg commonly manifests as lesions on the skin or in the oral cavity and the gingiva , they rarely exceed 2.5 cm in size . moreover , because a strawberry - like  gingivitis is a characteristic sign of gpa , we suspected gpa based on his clinical presentation and histology . hence , we decided to perform the anca test that revealed a positive c - anca titer and associated pr3-anca levels coinciding with the diagnosis of gpa . in conclusion , this patient presented with orofacial granulomatous lesions . because of the presentation , we believe we were better able to identify gpa as a potential diagnosis than a dermatologist who , based purely on an examination of the patient 's face , would be more likely to have suspected tuberculosis or another infection . the specific gingival manifestation of strawberry gingivitis permitted an early diagnosis and prompt therapy in a disease where time is a crucial factor . the present case report highlights the critical role dentists can play in the diagnosis and even management of gpa . because failure to recognize the diagnostic clinical picture may result in a potentially lethal delay in deciding on an appropriate treatment strategy for this disease , dentists should be aware of the oral signs and symptoms of systemic diseases such as gpa .
purposethis report describes a case of granulomatosis with polyangiitis ( gpa ) in which the gingival manifestation was crucial in both making an early diagnosis and possibly in deciding the approach to treatment.methodsa 57-year - old sailor presented to the department of dentistry at ulsan university hospital complaining of gingival swelling since approximately 2 months . 
 he had orofacial granulomatous lesions and the specific gingival manifestation of strawberry gingivitis.resultsthe diagnosis of gpa was made on the basis of clinical symptoms and signs , and confirmed by the presence of the anti - neutrophil cytoplasmic antibody and a positive biopsy . 
 the patient was admitted to the hospital and subsequently placed on a disease - modifying therapy regimen that included methotrexate and prednisone.conclusionsidentification of the gingival manifestation of the disease permitted an early diagnosis and prompt therapy in a disease in which time is a crucial factor . because of its rapid progression and potentially fatal outcome , an early diagnosis of gpa is important . 
 therefore , dentists should be aware of the oral signs and symptoms of such systemic diseases .