Granuloma faciale: clinical, morphological and immunohistochemical aspects in a series of 10 patients*

Granuloma faciale is a chronic, benign, cutaneous vasculitis with well-established clinical and morphological patterns, but with an unknown etiology. This study describes clinical and pathologic aspects of patients diagnosed with granuloma faciale. The authors analyzed demographic, clinical, morphological and immunohistochemical data from patients with a final diagnosis of granuloma faciale, confirmed between 1998 and 2012. There was a proportional and mixed inflammatory infiltrate, Grenz zones were present in almost all the samples. Immunophenotyping confirmed a higher intensity of T lymphocytes than B lymphocytes in thirteen samples, with a predominance of T CD8 lymphocytes in 64% of cases, in contrast to the literature, which indicates that the major component is T CD4 lymphocytes. All cases were positive for IgG4 but the majority (12/14) had less than 25% of stained cells. The pathogenesis of granuloma faciale remains poorly understood, making studies of morphological and immunohistochemical characterization important to better understand it.


INTRODUCTION
Granuloma faciale is a chronic, benign, cutaneous vasculitis with well-established clinical and morphological patterns, but with an unknown etiology. 1 Studying clinical and histopathological manifestations may be a way to clarify the variables that influence the disease's onset and course. This study discusses cases of Brazilian patients diagnosed with granuloma faciale at a health referral service, characterizing the clinical, epidemiological, histopathological and immunohistochemical features of the lesions. and an IgG4/IgG ratio higher than 40%.

METHODS
Demographic data and medical history were collected from medical records, tabulated and submitted for descriptive analysis.

RESULTS
Between 1998 and 2012, the authors identified 10 patients with granuloma faciale, four of which had had two manifestations in two different years. Most patients (60%) were female and age ranged between 36 and 59 years. Regarding comorbidities, four patients were smokers, and some had hypertension (n = 1), diabetes mellitus (n = 1), dyslipidemia (n = 1), systemic lupus erythematosus (n = 1) and cutaneous malignant epithelial tumors (n = 2). No relationship was found between the lesions and local trauma, though one patient's lesion was near a surgical scar ( Table 1). Seven patients underwent clinical treatment with topical corticoids but only in one case long-teerm resolution was observed.
( Table 2). One patient treated with photodynamic therapy (PDT) relapsed after three years and one patient experienced spontaneous resolution.

DISCUSSION
Although the literature reports that granuloma faciale is more common in males, appearing between the second and seventh decades of life, 1,6,7,8 our series of 10 patients revealed a predominance of women, while the age range included the interval between the fourth and sixth decades of life. Lesions are described primarily in the regions exposed to light, as plaques or papules, single or multiple, usually with an erythematous appearance. 1,2,7,8,9,10 The face is predominantly affected, as observed in this study. 11 Extra-facial lesions are reported in the literature, some of them concurrent to the facial lesions. 5,7,11 In a study by Thiyanaratnam et al. (2009), the authors reported that 90% of the lesions began on the face. 8 The disease has a  Granuloma faciale manifests in isolation, predominantly on the face. As regards morphology, there is an overlap of histopathological findings. Some authors highlight that EED has a major fibrosis component and that granuloma faciale has more inflammatory infiltrate with the Grenz zone. However, it is known that these changes present in a very similar pattern in two entities, not being sufficient for differentiation. 4 All the patients in this study had facial lesions.
Most samples entailed a typical, perivascular, inflammatory pattern.  had a history of local trauma due to surgery to remove skin cancer.
Histopathological examination is an essential feature for diagnosing this entity and it is characterized by a dense, perivas- Recently, the literature has emphasized topical tacrolimus in treating these lesions 8,9,13 , though no patient in the study was subjected to this treatment. Tacrolimus is a macrolide antibiotic used in transplant patients by inhibiting lymphocyte activation through interleukins, with consequent reduction in interferon gamma levels. 13 Gupta et al.