The lesions most commonly produce an extensive and symmetric outbreak on the trunk and limbs, such as the palmar surfaces and gluteal folds, but they can appear anywhere on the body including the oral mucosa. Whenever one area of the body is affected, a full skin exam should be done to properly assess the extent of disease. The idiopathic disease has a more prominent presentation on the flexor surfaces of the wrists, ankles, lumbar region, and mucosal surfaces than the drug-induced form.

An extended latent period is noted from the time of drug initiation to the presence of a lichen planus-like skin eruption. The eruptions can occur from 1 month to 2 years after drug initiation, in contrast to most other skin drug eruptions whose latent period is usually confined to between one and two weeks. Certain lichen planus-like skin eruptions may disappear or reoccur intermittently if the offending drug is not discontinued. At the discontinuation of the inciting drug, resolution most commonly occurs within months to years. However, not all lichen planus-like skin eruptions will resolve.

Most cases of lichen planus-like drug eruptions occur between 30 and 60 years of age, similar to the idiopathic disease. Pediatric cases of a lichen planus-like drug eruption have been reported, though, and therefore age should not rule out the cause of the skin eruption.

A 4-mm punch biopsy should represent an adequate biopsy of the skin or oral mucosa. Histopathological examination will show a characteristic “saw tooth” pattern of epidermal hyperplasia and hyperparakeratosis with a thickened granular cell layer. The basal cell layer of the epidermis will show vacuolar alteration and the dermal-epidermal junction will demonstrate an intense T-cell infiltration. The presence of eosinophils and lymphocytes extending into the deep dermis involving the follicles and perivascular regions favor a lichen planus-like drug eruption as opposed to an idiopathic outbreak.

Idiopathic lichen planus has most closely been linked to a T-cell mediated autoimmune process. The triggering agent remains unknown. The basal keratinocyte degeneration is attributed to cytotoxic CD8+ T lymphocytes, while CD4+ helper T lymphocytes lead to destruction in the lamina propria. As the disease progresses, CD8+ lymphocytes are found to increase in number at the sites of the lesions. It is postulated that the underlying mechanism may be due to an imbalance between the CD4+ helper T lymphocytes and T suppressor lymphocyte activity. Kertatinocytes are the main target of the dysregulated T lymphocytes because of their expression of foreign or altered self-antigens on their surfaces.

A significant association between lichen planus and hepatitis C and hepatitis B has been reported. Patients with lichen planus have higher rates of hepatitis C and B infection than the general population, and conversely patients with hepatitis C and B are more likely to develop lichen planus than the general population. The relation between lichen planus and hepatitis seropositivity is even stronger in patients co-infected with HIV. Due to this correlation, many providers will screen all patients presenting with lichen planus for hepatitis C and hepatitis B.

Although the exact mechanism for the disease has not been established, the relatively benign and many times self-resolving nature of lichen planus should be reassuring to the patient. However, protracted courses of the disease have been reported and can be linked to drug-induced eruptions. Lichen planus-like drug eruptions are postulated to be induced by medications altering the balance of cytokines in the immune system or by antigen mimicry. These drug categories include NSAIDS, antihypertensives, antimicrobials, antiparasitics, and antiarthritics. It is important to differentiate the drug-induced disease from the idiopathic disease because recovery of the drug-induced eruption can depend on the identification and withdrawal of the inciting drug.

Skin involvement in adverse drug reactions is common, and the prevalence increases with the addition of new drugs and new drug classes. The diagnosis of drug-induced skin eruptions can often be intuitive, however, lichen planus-like drug eruptions can be especially difficult to diagnose. Lichen planus-like drug eruptions have a protracted latent period. The latent period has been documented as 4–6 weeks in certain drug categories and as long as 3 years in others. The drug-induced lesions can have a prolonged course, with no improvement after application of topical steroid solutions. Idiopathic lichen planus improves after topical steroid use, so resistance to this treatment should lead to the suspicion of a drug-induced pathogenesis as opposed to the idiopathic disease. While a protracted course not improved by topical steroids is a differentiating factor, it is not reliable in all cases. Lichen planus-like drug eruptions can regress even with continuation of the inciting drug, and can even develop an intermittent course characterized by resolution and reoccurrence of the lesions. Idiopathic lichen planus also commonly develops an intermittent course with periods of resolution and reoccurrence. Due to the similarity in presentations, a mistaken diagnosis of idiopathic lichen planus may be made.

Idiopathic lichen planus and lichen planus-like drug eruptions can be clinically indistinguishable. Histological examination can be a distinguishing factor that is important to help guide treatment selection. The presence of an increased number of necrotic keratinocytes, plasma cells, and eosinophils on histological examination has shown to have a statistical significance in favor of identifying lichen planus-like drug eruptions.