granuloma faciale ( gf ) is an uncommon , benign , inflammatory skin disorder of unknown etiology .
it is characterized by single or multiple , grey - brown or violaceous nodules or plaques primarily occurring on the face and occasionally at extra - facial sites .
the disease is notoriously resistant to therapies and often tends to relapse when treatment is discontinued .
we present a patient with multiple lesions of gf and its response to topical tacrolimus .
a 35-year - old female presented to our department with a 5 year history of single , asymptomatic , grey - brown pigmented , nodule over the left cheek [ figure 1 ] .
it started as a pin head sized papule which gradually increased to 2.5 cm  1.5 cm in size .
two years later similar lesions appeared on the forehead , both arms and upper back .
past and personal history was unremarkable . before treatment  single , grey - brown nodule with prominent follicular orifices over left cheek .
after treatment  residual lesion after three months of tacrolimus application general physical and systemic examination was normal .
cutaneous examination revealed multiple , well - defined , grey - brown , indurated , non - tender plaques , varying in size from 0.5 cm  0.5 cm to 1.5 cm  2.5 cm , present on the left cheek , left forehead , both arms and upper back .
multiple grey - brown plaques over upper back routine hematological and biochemical investigations were normal .
skin biopsy ( 4 mm ) from plaque revealed normal epidermis with clear sub epidermal 
grenz zone and pan dermal dense infiltrate comprising of neutrophils , lymphocytes , histiocytes and plasma cells .
small dermal vessels showed infiltration of neutrophils in the vessel wall along with peri - appendageal and peri - neural infiltrate in subcutaneous fat [ figure 3 ] .
( h and e , 100  ) skin biopsy with normal epidermis and dense , mixed inflammatoey infiltrate beneath a narrow grenz zone in the dermis .
infiltrate is composed of mononuclear cells with neutrophils and eosinophils she was started on intralesional triamcilone acetonide 10 mg / ml injection monthly with tab .
six sessions of cryotherapy were performed once monthly after which she developed erythema and itching over the plaques and discontinued treatment .
the lesions showed 40 - 50% improvement after 3 months of therapy [ figure 1 ] .
classically , red - brown or violaceous nodules or plaques with associated telangiectasia and follicular accentuation are seen on the face over sun - exposed sites .
differential diagnosis includes lupus pernio , lupus vulgaris , lymphoma , discoid lupus erythematosus and deep mycotic infection .
skin biopsy is characterized by a mixed inflammatory infiltrate with a predominance of neutrophils and eosinophils in the dermis , in conjunction with small vessel vasculitis .
there is a grenz zone that separates the infiltrate from the epidermis and pilosebaceous units .
the disease is notoriously resistant to therapies and often tends to relapse once the treatment is discontinued .
several medical and surgical modalities like topical and intralesional corticosteroids , cryotherapy , pulsed dye laser , puva , systemic corticosteroids , dapsone and antimalarials have been tried with variable success rates .
carbon dioxide laser has also been used in a case of recurrent gf . surgical excision has been performed with often unsatisfactory results .
ablative procedures may leave residual pigmentation and scarring , whereas long - term application of corticosteroids is associated with skin atrophy , telangiectasia and other possible adverse effects . in recent years successes with topical calcineurin inhibitors has been reported .
several authors have reported complete or near - complete resolution of lesions after application of topical tacrolimus 0.1% ointment.[48 ] treatment regimens , duration and time to resolution of lesions have varied in these case reports [ table 1 ] .
others have found time to resolution to be between 4 and 6 months . in our patient ,
treatment with tacrolimus 0.1% ointment twice daily for 3 months has resulted in improvement . reported cases of successful treatment of granuloma faciale ( gf ) with topical tacrolimus tacrolimus
inhibits t - cell proliferation , production and release of several pro - inflammatory cytokines like interleukin-2 ( il-2 ) , il-4 , tumor necrosis factor - alpha , and interferon - gamma ( ifn - gamma ) .
although the pathogenesis is still unknown , it has been suggested that gf may be an ifn - gamma mediated disease .
in addition , an increased production of il-5 , probably induced by the clonal expansion of a locally recruited t - cell population may enhance the attraction of eosinophils into the lesions of gf .
therefore , a possible mechanism of action of topical tacrolimus in this condition may be the inhibition of ifn - gamma and il-5 production and release , induced by the down - regulation of the t - cell activity , primarily involving the calcineurin binding and inactivation .
however , we did observe eosinophils in skin biopsy in our case , probably since the biopsy was taken after one year of oral dapsone .
our patient experienced a relevant improvement within 3 months of treatment with tacrolimus ointment after no response with intra lesional steroids , dapsone and cryo therapy . in conclusion
, the previous reports and our observation suggest that topical tacrolimus may be a well - tolerated , efficacious therapy for gf .
 granuloma faciale ( gf ) is a chronic condition characterized by red - brown plaques with follicular accentuation present usually on the face . 
 we present a case of 35-year - old female with 5 year history of plaques over cheek and extra facial sites consistent with gf and its response to topical tacrolimus . 
 this case supports previous reports of successful treatment of gf with topical tacrolimus . 
INTRODUCTION
CASE REPORT
DISCUSSION