BACKGROUND AND OBJECTIVE: Melkersson Rosenthal syndrome (MRS) is a rare disorder 
of unknown etiology and comprises the triad: orofacial edema, recurrent facial 
paralysis and lingua plicata. In the current literature confusing heterogeneity 
exists, mixing together the historically grown terms cheilitis granulomatosa or 
granulomatous cheilitis, Melkersson Rosenthal syndrome and the umbrella term 
Orofacial Granulomatosis (OFG).
METHODS: We provide a systematic review comprising all three disease entities of 
orofacial granulomatosis using the computerized database "Pubmed Medline" 
entering the keywords "orofacial granulomatosis" (141 references), 
"Melkersson-Rosenthal syndrome" (207 references), "granulomatous cheilitis" or 
"cheilitis granulomatosa" (102 references) back to 1956. Full-text journals and 
case studies were included, and data synthesis was performed individually.
RESULTS: Etiology remains unclear for all three disease entities. Etiological 
relatedness to chronic inflammatory bowel disease is under discussion and 
effectiveness was found for different treatments, e.g. local triamcinolone 
injections, antibiotics, surgical interventions, TNF alpha blockers or exclusive 
enteral nutrition. No randomized controlled trial concerning the therapy of 
orofacial granulomatosis was found. As a consequence, the therapeutic conclusion 
is drawn mainly from small case series, thus limiting the evidence of 
therapeutic interventions.
CONCLUSION: OFG with the sub-entities MRS and cheilitis granulomatosa is an 
etiological obscure disease process with various possible therapeutic 
interventions potentially alleviating the disease course but to broaden 
treatment knowledge further study in randomized controlled trials is needed.