RESUMO
BACKGROUND: Antimalarials are first-line systemic therapy for cutaneous lupus erythematosus (CLE). While some patients unresponsive to hydroxychloroquine (HCQ) alone benefit from the addition of quinacrine (QC), a subset of patients is refractory to both antimalarials. METHODS: We classified CLE patients as HCQ-responders, HCQ+QC-responders, or HCQ+QC-nonresponders to compare immune profiles. Immunohistochemistry, immunofluorescence, and qRT-PCR were used to characterize inflammatory cells and cytokines in lesional skin. RESULTS: Immunohistochemistry showed that CD69+ T cells were higher in HCQ+QC-nonresponders compared to HCQ- and HCQ+QC-responders (p < 0.05). Immunofluorescence further identified these cells as CD69+CCR7+ circulating activated T cells. Myeloid dendritic cells were significantly higher in HCQ+QC-responders compared to both HCQ-responders and HCQ+QC-nonresponders. Plasmacytoid dendritic cells were significantly increased in HCQ-responders compared to HCQ- and HCQ+QC-nonresponders. No differences were found in the number of autoreactive T cells, MAC387+ cells, and neutrophils among the groups. CLASI scores of the HCQ+QC-nonresponder group positively correlated with CD69+CCR7+ circulating activated T cells (r = 0.6335, p < 0.05) and MAC387+ cells (r = 0.5726, p < 0.05). IL-17 protein expression was higher in HCQ+QC-responders compared to HCQ-responders or HCQ+QC-nonresponders, while IL-22 protein expression did not differ. mRNA expression demonstrated increased STAT3 expression in a subset of HCQ+QC-nonresponders. CONCLUSION: An increased number of CD69+CCR7+ circulating activated T cells and a strong correlation with CLASI scores in the HCQ+QC-nonresponders suggest these cells are involved in antimalarial-refractory skin disease. STAT3 is also increased in HCQ+QC-nonresponders and may also be a potential target for antimalarial-refractory skin disease.
Assuntos
Lúpus Eritematoso Cutâneo/tratamento farmacológico , Receptores CCR7 , Fator de Transcrição STAT3 , Antígenos CD , Antígenos de Diferenciação de Linfócitos T , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Feminino , Imunofluorescência , Humanos , Hidroxicloroquina/uso terapêutico , Imuno-Histoquímica , Lectinas Tipo C , Lúpus Eritematoso Cutâneo/imunologia , Masculino , Pessoa de Meia-Idade , Quinacrina/uso terapêutico , Receptores CCR7/uso terapêutico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Linfócitos T , Resultado do TratamentoRESUMO
Systemic polyarteritis nodosa is a necrotizing vasculitis that involves small and medium-sized muscular arteries in the multiple organ systems, whereas cutaneous polyarteritis nodosa (CPAN) is a localized disease characterized by necrotizing vasculitis of small and medium-sized arteries in the skin without life-threatening organ involvement. CPAN is usually limited to skin, muscle, and joints. It is chronic but takes a benign course. The most common cutaneous manifestations include nodules, ulcers and a livedo reticularis pattern on the extremities. We describe three cases with CPAN showing necrotizing vasculitis on the skin without systemic symptoms or visceral involvement. In Korea, most previously published cases with CPAN have shown a good response to a short term of corticosteroids or colchicine administration. However, two of our three patients required another immunosuppressive agent in addition to corticosteroids to manage their intractable skin lesions, and the remaining one showed a good response to a short course of prednisolone. In addition, there was one patient with CPAN having hepatitis B surface antigen, which might be associated with his refractory skin disease.
