Granuloma Annulare: a Review of the Literature

Autores

DOI:

https://doi.org/10.17921/1415-6938.2020v24n4p410-415

Resumo

Granuloma annulare (GA) is a form of noninfectious skin granuloma, first described in 1895 as a rash in the form of a ring (annular), with regular, rounded edges. Around 50% of the cases are cured spontaneously within 2 years, however, a percentage of patients suffer from recurrent lesions or persistence for years. The pathogenesis of GA lesions is not well understood, with studies linking its expression to the presence of histocompatibility genes (HLA)-Bw35 or AH8.1 allele. These genes are related to the production of TNF-α (Tumor Necrosis Factor-α) by mononuclear cells. The pathogenesis includes the migration of macrophages to the dermis, the presence of cytokines, late hypersensitivity reaction, defects in regulating the neutrophil chemotaxis and degradation of the connective tissue. Its outbreak may be linked to predisposing factors, such as diabetes mellitus, thyroid changes and viral infectious diseases. The macrophages present in GA lesions may receive stimuli that result in its modulation to M1 or M2 activation patterns. The study of the M1 and M2 modulation mechanism in the lesion is important for an understanding of GA development.

 

Keywords: Granuloma Annulare. Macrophage. Immunology. Pathogenesis and Modulation.    

Resumo

O Granuloma Anular (GA) é um tipo de granuloma cutâneo não infeccioso, que foi descrito em 1895, como uma exantema em formato de anel (anular), de bordas regulares e arredondadas. Cerca de 50% dos casos têm cura espontânea em 2 anos, mas parte dos pacientes apresentam recidivas das lesões ou persistência por anos. A patogênese das lesões do GA é pouco conhecida. Estudos relacionam sua expressão à presença de genes de histocompatibilidade (HLA)-Bw35 ou AH8.1, que são relacionados à produção de TNF-α (Tumor necrosis factor - α), pelas células mononucleares. A patogênese também inclui migração de macrófagos para derme, presença de citocinas, reação de hipersensibilidade tardia, defeito na quimiotaxia de neutrófilos e degradação do tecido conectivo. O surgimento das lesões pode estar associado a fatores predisponentes, como diabetes mellitus, alterações tireoidianas e doenças infecciosas virais. Os macrófagos presentes nas lesões de GA podem sofrer estímulos que acarretem sua modulação para os padrões de ativação M1 ou M2. O estudo de tais mecanismo de modulação é importante para a compreensão da instalação e desenvolvimento do GA nos pacientes afetados.

 

Palavras-chave: Granuloma Anular. Macrófagos. Modulação. Imunologia e Patogênese.

Biografia do Autor

Tânia Aguiar Passeti, Universidade Anhanguera de São Paulo, Programa de Pós-Graduação Stricto Sensu em Farmácia. SP, Brasil.

Farmacêutica com mestrado e doutorado na USP em ciências, área de concentração Imunologia. Docente no ensino superior a cerca de 20 anos, atualmente fazendo pós doutorado no stricto sensu em Farmácia.

Wesley Pascoal Lisboa, Faculdade de Medicina do ABC. SP, Brasil.

Estudante do curso de Medicina

Gabrielle Ellen Rodrigues Grinblat, Faculdade de Medicina do ABC. SP, Brasil.

Estudante do curso de Terapia Ocupacional

Fernando Luiz Affonso Fonseca, Faculdade de Medicina do ABC. SP, Brasil

PhD em Análises Clínicas e vice diretor da Faculdade de Medicina do ABC – FMABC

Paulo Ricardo Criado, Faculdade de Medicina do ABC. SP, Brasil.

PhD em Dermatologia e médico do Departamento de Dermatologia da  Faculdade de Medicina do ABC – FMABC

Referências

ASAI, J. What is new in the histogenesis of granulomatous skin diseases? J Dermatol., v. 44, n. 3, p. 297–303, 2017.

ATKINSON, M.A.; EISENBARTH, G.S.; MICHELS, A.W. Type 1 diabetes. Lancet., v. 383, p. 69–82, 2014.

BARBOSA, N.G. et al. Immunohistochemical study of macrophages subpopulations associated with squamous cell carcinoma of the tongue, with and without metastasis. J. Bras. Patol. Med. Lab., v. 51, n. 6, p. 415-21, 2015.

BASTARD, J.P. et al. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur. Cytokine Netw., v. 17, n. 1, p. 4–12, 2006.

BERETTA-PICCOLI, B. et al. Cutaneous Granulomatosis: a Comprehensive Review. Clin Rev Allergy Immunol., v.54, n.1, p.131-146, 2018.

BLAKYTNY, R.; JUDE, E.B. Altered molecular mechanisms of diabetic foot ulcers. Int. J. Low. Extremity. Wounds., v. 8, n. 2, p. 95–104, 2009.

BONOMO, L.; GHONEIM, S.; LEVITT, J. Case Report A Case of Granuloma Annulare Associated with Secukinumab Use. Case Reports in Dermatol. Med., ID 5918708, 2017.

BUECHNER, S.A.; WINKELMANN, R.K.; BANKS, P.M. Identification of T-cell subpopulations in granuloma annulare. Arch. Dermatol., v. 119, n. 2, p.125–8, 1983.

COHEN, P.R.; CARLOS, C.A. Granuloma annulare mimicking sarcoidosis: report of patient with localized granuloma annulare whose skin lesions show 3 clinical morphologies and 2 histology patterns. Am. J. Dermatopathol., v. 37, n. 7, p. 547–50, 2015.

EISENBARTH, G.S. Update in type 1 diabetes. J. Clin. Endocrinol. Metab., v. 92, n. 7, p. 2403–7, 2007.

ERRICHETTI, E. et al. A Clinical and Histological Correlation Study. Dermatology., v. 233, n. 1, p. 74-79, 2017.

FAYYAZI, A. et al. Expression of IFN gamma, coexpression of TNF alpha and matrix metalloproteinases and apoptosis of T lymphocytes and macrophages in granuloma annulare. Arch. Dermatol. Res., v. 292, n. 8, p.384–90, 2000.

GANNON, T.F.; LYNCH, P.J. Absence of carbohydrate intolerance in granuloma annulare. J. Am. Acad. Dermatol., v. 30, n. 4, p. 662–3, 1994.

GAVIOLI, C.F.B. et al. Actinic Granuloma Annulare With Scarring and Open Comedones. Am. J. Dermatopathol., v. 39, n. 8, p. 625-627, 2017.

GORDON, S.; MARTINEZ, F.O. Alternative activation of macrophage: mechanism and function. Immunity., v. 32, n. 5, p. 593-04, 2010.

GROGG. K.L.; NASCIMENTO. A.G. Subcutaneous granuloma annulare in childhood: clinicopathologic features in 34 cases. Pediatrics., v. 107, n. 3, p. E42, 2001.

GROISMAN, G.M. et al . Expression of the histiocytic marker PG-M1 in granuloma annulare and rheumatoid nodules of the skin. J. Cutan. Pathol., v. 29, n. 10, p. 590-5, 2002.

GÜNEŞ, P. et al. Collagen elastic tissue changes and vascular involvement in granuloma annulare: a review of 35 cases. J. Cutan. Pathol., v. 36, p. 838-44, 2009.

HAIM, S.; FRIEDMAN-BIRNBAUM, R.; SHAFRIR, A. Generalized granuloma annulare: relationship to diabetes mellitus as revealed in 8 cases. Br. J. Dermatol., v. 83, n. 2, p. 302–5, 1970.

HAIM, S. et al. Carbohydrate tolerance in patients with granuloma annulare. Study of fifty-two cases. Br. J. Dermatol., v. 88, n. 5, p.447–51, 1973.

HITCHON, C.A. et al. Gelatinase expression and activity in the synovium and skin of patients with erosive psoriatic arthritis. J. Rheumatol., v. 29, n. 1, p. 107–117, 2002.

HORENSTEIN, R.B.; SHULDINER, A.R. Genetics of diabetes. Rev. Endocr. Metab. Disord., v. 5, n. 1, p. 25–36, 2004.

JAACKS, L.M. et al. Type 2 diabetes: a 21st century epidemic. Best Pract Res Clin Endocrinol. Metab., v. 30, n. 3, p. 331–43, 2016.

KAPPELER, D.; TROENDLE, A.; MUELLER, B. Localized granuloma annulare associated with autoimmune thyroid disease in a patient with a positive family history for autoimmune polyglandular syndrome type II. Eur. J. Endocrinol., v. 145, n. 1, p. 101–2, 2001.

KEIMIG, E.L. Granuloma Annulare. Dermatol. Clin., v. 33, p. 315–329, 2015.

KNOELL, K.A. Efficacy of adalimumab in the treatment of generalized granuloma annulare in monozygotic twins carrying the 8.1 ancestral haplotype. Arch. Dermatol., v. 145, n. 5, p. 610–611, 2009.

LIMA, A.L. et al. Cutaneous Manifestations of Diabetes Mellitus: A Review. Am. J. Clin. Dermatol., v. 18, n. 4, p. 541-553, 2017.

LO SCHIAVO, A. et al. Granulomatous dysimmune reactions (sarcoidosis, granuloma annulare, and others) on differently injured skin areas. Clin Dermatol., v. 32, n. 5, p. 646–653, 2014.

MAGALHÃES, G.M.; GUIMARÃES, C.F.; PAULA, M.C. Case for diagnosis. Patch granuloma annulare. An. Bras. Dermatol., v. 92, n. 3, p. 419-20, 2017.

MARTINEZ. F.O.; HELMING, L.; GORDON, S. Alternative activation of macrophage: an immunologic functional perspective. Annu. Ver. Immunol., v. 27, p. 451-83, 2009.

MASCHIO, M. et al. A rare case of granuloma annulare in a 5-year-old child with type 1 diabetes and autoimmune thyroiditis. Am. J. Dermatopathol., v. 35, n. 3, p. 385–7, 2013.

MASSON, E. Granulomes cutanés non infectieux. 2017, In: EM-Consulte. http://www.em-onsulte.com/article/195548/granulomes-cutanesnon-infectieux. Accessed 16 Nov 2018.

MEMPEL, M. et al. T-cell receptor repertoire and cytokine pattern in granuloma annulare: defining a particular type of cutaneous granulomatous inflammation. J. Invest. Dermatol., v. 118, p. 957-66, 2002.

MUHLEMANN, M.F.; WILLIAMS, D.R. Localized granuloma annulare is associated with insulin-dependent diabetes mellitus. Br. J. Dermatol., v. 111, n. 3, p. 325–9, 1984.

MUYLAERT, B.P.B.; ALMADA, R.; VASCONCELOS, R.C.F. Granuloma annulare treated with narrowband UVB phototherapy. An. Bras. Dermatol., v. 92, p. 1-10, 2017.

NEBESIO CL, LEWIS C, CHUANG TY. Lack of an association between granuloma annulare and type 2 diabetes mellitus. Br. J. Dermatol., v. 146, n. 1, p. 122–4, 2002.

PESCE, J.T. et al. Arginase 1 expressing macrophage suppress TH2 cytokines-driven inflammation and fibrosis. PLoS Pathog., v. 5, n. 4, e100037, 2009.

PICCOLI, B.T. et al. Cutaneous Granulomatosis: A Comprehensive Review. Clin. Rev. Allergy Immunol., v. 54, n. 1, p. 131-146, 2018.

PIETTE, E.W.; ROSENBACH, M. Granuloma annulare: clinical and histologic variants, epidemiology, and genetics. J. Am. Acad. Dermatol., v. 75, n. 3, p. 457–465, 2016.

PORQUERAY, F. et al. Macrophage activation switching: an asset for the resolution of inflammation. Clin. Exp. Immunol., v. 142, n. 3, p. 481-9, 2005.

RAJARAM, M.V., et al. Mycobactetium tuberculosis activates human macrophage peroxisome proliferator-activated receptor gamma linking mannose receptor recognition to regulation of immune responses. J. Immunol., v. 185, n. 2, p. 929-42, 2010.

SANTAMARIA, J.R.; DEONIZIO, J.D. Fototerapia. http://antoniorondonlugo.com/blog/wp-content/uploads/2010/05/77-Fototerapiaindicaciones-no-usuales.1.pdf (Accessed 16 Nov 2018).

SUMIKAWA, Y. et al. Interstitial type granuloma annulare associated with Sjögren’s syndrome. J. Dermatol., v. 37, n. 5, p. 493–495, 2010.

TÖRÖCSIK, D.T. et al. Detection of factor XIII-A is a valuable tool for distinguishing dendritic cells and tissue macrophages in granuloma annulare and necrobiosis lipoidica. JEADV., v. 28, p. 1087–1096, 2014.

WANDERLEY SOUB, C.R.; CARRIJO, M.; CUZZI, R.T. Granuloma Annulare: tissue distribution of factor XIIIa dermal dendrocytes, thrombomodulin dermal cells and CD68 macrophages. An. Brás. Dermatol., v. 78, n. 3, p. 289-298, 2013.

WANG, J.; KHACHEMOUNE, A. Granuloma Annulare: A Focused Review of Therapeutic Options. Am. J. Clin. Dermatol., v. 19, n. 3, p. 333-344, 2018.

WILLEMSEN, M.J. et al. Autoimmune thyroiditis and generalized granuloma annulare: remission of the skin lesions after thyroxine therapy. Dermatology., v. 175, n. 5, p. 239–243, 1987.

VAL, D.; COLLARD, A.; VAL-BERNAL, J.F. Lichen sclerosus and granuloma annulare of the foreskin: a significant association. Rom. J. Morphol. Embryol., v. 56, n. 3, p. 1179–1183, 2015.

VÁZQUEZ-LÓPEZ, M.A. et al. Localized granuloma annulare and autoimmune thyroiditis: a new case report. J. Am. Acad. Dermatol., v. 43, n. 5, p. 943–945, 2003.

VÉNÉREAU, E.; CERIOTTI, C.; BIANCHI, M.E. DAMPs from Cell Death to New Life. Front. Immunol., v. 18, n. 6, p. 422-8, 2015.

VERALDI, S. et al. Laboratory abnormalities in granuloma annulare: a case-control study. Br. J. Dermatol. v. 136, n. 4, p. 652–3, 1997.

ZHU, J. et al. Parasitic antigens alter macrophage polarization during Schistosoma japonicum infection in mice. Parasit. Vectors.,v. 7, p. 122-5, 2014.

Downloads

Publicado

2020-12-02

Como Citar

PASSETI, Tânia Aguiar; LISBOA, Wesley Pascoal; GRINBLAT, Gabrielle Ellen Rodrigues; FONSECA, Fernando Luiz Affonso; CRIADO, Paulo Ricardo; NOGUEIRA DINIZ, Susana. Granuloma Annulare: a Review of the Literature. Ensaios e Ciência C Biológicas Agrárias e da Saúde, [S. l.], v. 24, n. 4, p. 410–415, 2020. DOI: 10.17921/1415-6938.2020v24n4p410-415. Disponível em: https://ensaioseciencia.pgsscogna.com.br/ensaioeciencia/article/view/7672. Acesso em: 26 abr. 2024.

Edição

Seção

Artigos