Other mechanisms that have been proposed include: upregulation of matrix metalloproteinases that disrupt the epithelial basement membrane zone and allow entry of immune cells into the epidermis, the release of proinflammatory mediators and proteases by mast cells, and perturbations in the innate immune response that may involve toll-like receptors. Oral LP may also be caused by genetic factor which influence the immune function. A separate study performed in China found an association between a polymorphism in the TNF-alpha gene and risk for oral LP in a subset of patients. An Italian study found a significant increase in a genetic polymorphism of the first intron of the interferon (IFN)-gamma promoter in patients with oral LP compared with controls. Diagnosis Skin Patient history and clinical presentation need to be taken to diagnose lichen planus. Patients with suspected cutaneous lichen planus need to be evaluated clinically through patient interviews and physical examinations. Patients should be questioned about their medication history, any history of pruritus or genital pain and history of dysphagia or odynophagia. Examination of entire cutaneous surface including the scalp, oral cavity and external genitalia need to be included. Wickham's striae often can be seen during microscopic examination of cutaneous lesions of lichen planus. To confirm the diagnosis of cutaneous lichen planus, a skin biopsy can be done. A punch biopsy of sufficient depth to the mid dermis is usually significant. Immunofluorescence studies are not always needed. Direct immunofluorescence (DIF) can be useful in patients with bullous lesions to differentiate the condition from an autoimmune vesiculobullous disease. Mouth A diagnosis of oral lichen planus (LP) is confirmed through review of the patient history, physical examination, and histologic findings. The clinical evaluation should include a patient history that assesses the following: History of LP involving other body sites or other skin disorders that may present with similar findings (e.g., autoimmune blistering diseases) Presence of associated symptoms (e.g., pain, burning) Medication the patients are taking within the few weeks to months after drug initiation e.g. antihypertensives, antidepressants, diuretics, antidiabetics, NSAIDs, etc. to evaluate for the possibility of an oral lichenoid drug eruption History of dental restorations, use of dental appliances, or oral exposure to substances that may cause oral lichenoid contact eruptions (e.g. dental composites, cobalt chromium based dentures etc.) A full examination that includes the evaluation of the mucosal and cutaneous surfaces, including the vulva, vagina, penis, scalp, and nails should be performed.