RESUMO
La enfermedad relacionada con inmunoglobulina (Ig) G4 es una enfermedad de reciente conocimiento que puede comprometer cualquier órgano teniendo preferencias por ciertas regiones del cuerpo, donde la región de cabeza y cuello es uno de sus principales puntos afectados, pudiendo comprometer tanto la órbita, glándulas salivales, glándulas lagrimales, glándula tiroides, cavidades paranasales, hueso temporal, faringe y laringe. Este último órgano es infrecuentemente comprometido, solo existiendo 12 casos registrados en la literatura antes de la publicación de este escrito. Presentamos un caso de una mujer de 49 años con historia de disnea frente a esfuerzo, diagnosticándose una estenosis subglótica la cual fue manejada quirúrgicamente con una reconstrucción laringotraqueal. En el estudio histopatológico se evidenció histología compatible con enfermedad relacionada con IgG4, por lo que se inició tratamiento médico con corticotera- pia oral por un lapso de 2 meses en conjunto con inmunología. Paciente luego de 4 años de seguimiento, no ha presentado recaídas, manteniendo un lumen subglótico adecuado.
Immunoglobulin (Ig) G4-related disease is a medical condition of recent knowledge that can compromise any organ, having preferences for certain regions of the body, where the head and neck region is one of the main affected points, being able to affect orbit, salivary glands, lacrimal glands, thyroid gland, paranasal cavities, temporal bone, pharynx and larynx. The latter is infrequently compromised, with only 12 cases registered in the literature before the publication of this writing. We present a case of a 49-year-old woman with a history of exertional dyspnea, diagnosed with a sub- glottic stenosis which was managed surgically with laryngotracheal reconstruction. The histopathological study revealed histology compatible with IgG4-related disease, so medical treatment with oral corticosteroid therapy was started for a period of 2 months in conjunction with immunology. After 4 years of follow-up, the patient has not presented relapses, maintaining an adequate subglottic lumen.
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/diagnóstico por imagem , Anti-Inflamatórios/uso terapêutico , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Doença Relacionada a Imunoglobulina G4/imunologia , Pescoço/patologia , Pescoço/diagnóstico por imagemRESUMO
OBJECTIVES: To evaluate the prevalence and meaning of antineutrophil cytoplasmic antibodies (ANCA) positivity in a cohort of IgG4-related disease (IgG4-RD). METHODS: We identified patients with ANCA determination from a retrospective cohort of 69 patients with IgG4-RD. ANCA were measured by indirect immunofluorescence microscopy (IIF) and/or proteinase 3 (PR3)-ANCA and MPO-ANCA by ELISA. IIF patterns were classified as perinuclear (P-ANCA), cytoplasmic (C-ANCA) and atypical (X-ANCA). We compared the ANCA-positive vs the ANCA-negative IgG4-RD group. RESULTS: Out of 69 patients, 31 IgG4-RD patients had an ANCA determination. Four patients with concomitant systemic autoimmune diseases were excluded. We found positive ANCA by IIF in 14 (56%) of 25 patients tested. The most common IIF pattern was C-ANCA in eight (57.1%), followed by dual C-ANCA/X-ANCA in four (28.6%) and P-ANCA and dual C-ANCA/P-ANCA in one each (7.1%). Of the 20 patients with ANCA determination by both IIF and ELISA, four have positive ANCA by ELISA (three for MPO-ANCA and one for PR3-ANCA). Of the two patients with only ELISA determination, one was positive for MPO-ANCA. The prevalence of ANCA positivity by ELISA was 22.7% (5 out of 22 patients). ANCA was more frequent in the Mikulizc/systemic phenotype (42.9%) compared with other phenotypes (P = 0.04). ANCA-positive IgG4-RD patients had more frequently lymph node and kidney involvement, high IgG1 levels and erythrocyte sedimentation rate, and positive antinuclear antibodies. CONCLUSION: ANCA are found in a significant number of patients with IgG4-RD and differed from the ANCA-negative group in terms of clinical and serological features.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos/imunologia , Doença Relacionada a Imunoglobulina G4/imunologia , Nefropatias/imunologia , Linfonodos/imunologia , Mieloblastina/imunologia , Peroxidase/imunologia , Adulto , Idoso , Doenças da Aorta/imunologia , Doenças Biliares/imunologia , Estudos de Casos e Controles , Feminino , Humanos , Doenças do Aparelho Lacrimal/imunologia , Hepatopatias/imunologia , Masculino , Microscopia de Fluorescência , Pessoa de Meia-Idade , Mieloblastina/metabolismo , Pancreatopatias/imunologia , Peroxidase/metabolismo , Espaço Retroperitoneal , Estudos Retrospectivos , Doenças das Glândulas Salivares/imunologiaRESUMO
The clinical utility of serum immunoglobulin free light chains (sFLC) in IgG4-related disease (IgG4-RD) is unknown. Herein we evaluated their association with clinical phenotypes, serology and activity in patients with IgG4-RD. Cross-sectional study that included 45 patients with IgG4-RD, and as controls 25 with Sjögren's syndrome (SS) and 15 with sarcoidosis. IgG4-RD patients were classified in clinical phenotypes: pancreato-hepato-biliary, retroperitoneum/aorta, head/neck-limited and Mikulicz/systemic; as well as proliferative vs. fibrotic phenotypes. We assessed the IgG4-RD Responder Index (IgG4-RD RI) at recruitment and measured IgG1, IgG4, κ and λ sFLC serum levels by turbidometry. sFLC levels were similar among IgG4-RD, SS and sarcoidosis groups. Regarding the IgG4-RD patients, the mean age was 49 years, 24 (53.3%) were men and 55.5% had activity. Eight (17.7%) belonged to pancreato-hepato-biliary, 6 (13.3%) to retroperitoneum/aorta, 14 (31.1%) to head/neck-limited, 16 (35.5%) to Mikulicz/systemic phenotypes, whereas 36 (80%) to proliferative and 9 (20%) to fibrotic phenotypes. High κ sFLC, λ sFLC and κ/λ ratio were present in 29 (64.4%), 13 (28.9%) and 13 (28.9%) of IgG4-RD patients, respectively. There were no differences in sFLC among IgG4-RD phenotypes. κ sFLC and κ/λ ratio correlated positively with the number of involved organs and IgG4-RD RI. Patients with renal involvement had higher κ sFLC and λ sFLC. The AUC for κ sFLC and λ sFLC, for renal involvement was 0.78 and 0.72, respectively. Active IgG4-RD had higher levels of κ sFLC and more frequently a high κ/λ ratio. The AUC for κ sFLC and κ/λ ratio for predicting active IgG4-RD was 0.67 and 0.70, respectively. sFLC correlated positively with IgG1 and IgG4 levels. sFLC may be useful as a biomarker of disease activity as well as multiorgan and renal involvement. In particular, a high κ/λ ratio may identify patients with active disease.
Assuntos
Doença Relacionada a Imunoglobulina G4/sangue , Cadeias Leves de Imunoglobulina/sangue , Adulto , Biomarcadores/sangue , Feminino , Humanos , Imunoglobulina G/sangue , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/imunologia , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , FenótipoRESUMO
IgG4-related disease is a recently-described fibro-inflammatory condition with characteristic histopathological findings in the organs involved. The most commonly affected organs are pancreas, lymph nodes, and retroperitoneum. Liver disease usually involves bile structures and therefore IgG4-related disease is considered a cause of secondary sclerosing cholangitis. One out of three patients with IgG4 sclerosing cholangitis also presents autoimmune pancreatitis, although it can be associated with manifestations in other organs. One of the main features of IgG4-related disease is its good prognosis due to the great response to glucocorticoid therapy. However, relapse of the disease is not uncommon, especially when steroid therapy is decreased or stopped. Rituximab seems to be an effective treatment to achieve remission of the disease. We report the case of a 74 year-old man diagnosed with IgG4-related disease based on increase of serum IgG4 levels, imaging and histopathological findings, with systemic involvement including sclerosing cholangitis. Despite the absence of liver fibrosis at onset, the early use of glucocorticoids and rituximab therapy, the patient presented clinical and analytical deterioration, leading to secondary biliary cirrhosis. In conclusion, this clinical case highlights the importance of prompt diagnosis and therapeutics for sclerosing cholangitis secondary to IgG4-related disease in order to avoid progression of the disease and development of liver cirrhosis, as well as the refractory, aggressive nature of the disease in some cases as this one.
Assuntos
Colangite Esclerosante/diagnóstico , Doença Relacionada a Imunoglobulina G4/diagnóstico , Imunoglobulina G/sangue , Fígado/diagnóstico por imagem , Rituximab/uso terapêutico , Idoso , Biópsia , Colangiopancreatografia por Ressonância Magnética , Colangite Esclerosante/tratamento farmacológico , Colangite Esclerosante/imunologia , Diagnóstico Diferencial , Humanos , Imunoglobulina G/imunologia , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/imunologia , Fatores Imunológicos/uso terapêutico , Masculino , Tomografia por Emissão de PósitronsRESUMO
Retroperitoneal fibrosis (RF) is part of a rare fibrosclerotic disorder. Oral steroids are the initial treatment. Steroid combination with other immunosupressants is used in refractory cases. Steroids refractoriness has been observed in chronic cases. Some cases of RF represent a manifestation of the IgG4 related disease (IgG4-RD) that is associated to a dramatic response to steroid therapy. It is uncertain if RFÌs treatment response differs according to its association with IgG4-RD. We hypothesize that RFÌs treatment response to steroids depends on the association with IgG4-RD, thus, we collected and compared clinical data from 10 RF cases; 6 male, mean age 50.6 (±16.15 SD) years. Mean FU was 28 (±25.7 SD) months. According to IgG4 levels, patients were categorized as idiopathic RF (IRF nâ¯=â¯5) or RF-IgG4-RD (nâ¯=â¯5). Therapy response was categorized as complete, partial, stable disease, recurrence or non-response. Nine cases received initial therapy with prednisone; complete response was achieved in 4 RF-IgG4 RD. The remaining 5 cases (1 RF-IgG4RD and 4 IRF) underwent a 2nd line therapy; 4 prednisoneâ¯+â¯tamoxifen and 1 prednisoneâ¯+â¯azathioprine. Prednisoneâ¯+â¯tamoxifen combination achieved complete response in 1 case (RF-IgG4RD), partial response in 1 IRF; in 1 IRF case, disease remained stable and 1 did not respond. The prednisoneâ¯+â¯azathioprine treatment achieved complete response. At follow-up all patients remained stable and no recurrence was registered. These observations suggest and support the hypothesis that response to steroid monotherapy depends on the association of RF with IgG4, suggesting that IRF cases might benefit from initial combination therapies instead of steroid monotherapy.