Atorvastatin-induced Lichenoid Drug Eruption: A Case Report and Review of Statin-associated Cutaneous Adverse Events

Statin medications [3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors] are generally used to treat hypercholesterolemia. Lichenoid drug eruptions are a potential cutaneous side effect of medications including antibiotics, antimalarials, and statins. This drug eruption can mimic features of idiopathic lichen planus in clinical presentation and pathology. We describe the case of a 73-year-old man who developed a lichenoid drug eruption secondary to atorvastatin. His clinical features, in addition to histological findings, helped to establish the diagnosis. The cutaneous eruption resolved one month after the cessation of atorvastatin and with corticosteroid therapy. Statins have been associated with adverse events including bullous dermatosis, eosinophilic fasciitis, lichenoid drug eruption, and phototoxicity. Lichenoid drug eruption associated with statin therapy requires discontinuation of the statin medication; an alternative class of medication for the treatment of hypercholesterolemia is usually necessary.

We report the case of a man with atorvastatin-induced lichenoid drug eruption. In addition, we describe the clinical and histopathologic characteristics of idiopathic lichen planus and lichenoid drug eruptions as well as cutaneous adverse reactions observed with statin medications.

Case Presentation
A 73-year-old man presented with a pruritic rash of two months' duration on his arms, chest, and neck. His past medical history was significant for asthma, erectile dysfunction, gastroesophageal reflux disease, and hypercholesterolemia. His current medications included atorvastatin, omeprazole, ranitidine, sildenafil, and Singulair (Merck & Co, Kenilworth, NJ). He had previously been seen by another physician who had topically treated him for eczema with betamethasone dipropionate 0.05% cream and crisaborole 2% ointment twice daily. His dermatitis had persisted despite therapy and he subsequently obtained a second opinion.
Cutaneous examination revealed erythematous to purple scaly plaques on the bilateral forearms, chest, upper back, and neck ( Figure 1). A shave biopsy of skin eruptions on both the left and right forearm was performed ( Figure 2).   Microscopic examination revealed orthokeratosis, acanthosis, and spongiosis. A dense, bandlike inflammatory infiltrate composed predominantly of lymphocytes was present in the upper dermis and along the dermoepidermal junction. In addition, apoptotic cells, eosinophils, and histiocytes were observed.

FIGURE 1: Cutaneous presentation of atorvastatin-induced lichenoid drug eruption
Pathologic findings pointed to lichenoid dermatitis with eosinophils. Correlation of the clinical history, lesion morphology, and pathologic findings established a diagnosis of a lichenoid drug eruption. We suspected that the causative agent was atorvastatin, which the patient had begun taking two months prior to the onset of his eruption.
Management included discontinuing the atorvastatin and treatment with prednisone, initially 40 mg daily with a gradual tapering of the dosage over 20 days. Additionally, a topical betamethasone dipropionate 0.05% cream to be applied twice daily for three weeks was also prescribed. His symptoms and skin eruption completely resolved and had not recurred at a onemonth follow-up.

Discussion
Adverse cutaneous events are a consequence of various medications including antibiotics, anticonvulsants, and statins. Earlier studies have observed that the majority of lichenoid drug eruptions were caused by either antimalarial agents or oral gold therapy [19].
The duration and onset of lichenoid drug eruptions are often dependent on the causative agent and dosage. Lichenoid drug eruptions occur most often in individuals between the age of 57 to 66 years and can have an average latent period of one year between the beginning of the medication treatment and the onset of an eruption [19]. This medication-induced eruption should be considered when an individual receiving statin treatment develops new lesions akin to lichen planus.
The clinical presentation and pathology of lichenoid drug eruptions can mimic those of lichen planus ( Table 1) [15][16][19][20]. Both conditions present as erythematous to purple papules and plaques; however, lichenoid drug eruptions may be scaly, more pruritic, and resolve with greater residual hyperpigmentation [15,19]. In addition, Wickham's striae (a lacy, white network of streak often located bilaterally on the buccal mucosa) and involvement of other mucosal areas are observed less frequently in drug-induced lesions [15,19]. Compared to the flexor surface distribution on extremities seen with idiopathic lichen planus, lichenoid drug eruptions may present in a photodistributed or symmetric pattern [15].

Lichenoid drug eruption Reference
Morphology Erythematous, planar, and polygonal papules are commonly described Similar to lichen planus but can be scaly and more pruritic; alopecia, desquamation, eczematous papules, and greater residual hyperpigmentation may also occur [15,19] Pathology A band-like lymphocyte infiltrate along the dermoepidermal junction is present along with apoptotic keratinocytes (Civatte bodies) Similar to lichen planus but can also present with an infiltrate containing eosinophils. Focal parakeratosis, more prominent perivascular inflammation, and irregular granular layers may be present [19,20] Onset Variable

TABLE 1: Comparison between lichen planus and lichenoid drug eruption
Microscopically, both lichenoid drug eruptions and idiopathic lichen planus exhibit a band-like lymphocytic infiltrate along the dermal-epidermal junction and apoptotic keratinocytes. Both conditions also show acanthosis, hypergranulosis, and hyperkeratosis [20]. However, an infiltrate with eosinophils in the dermis can help delineate lichenoid drug eruption from lichen planus [20].
Lichenoid drug eruptions are associated with medications. In contrast, lichen planus can be associated with systemic conditions such as diabetes mellitus and hepatitis B or hepatitis C viral infections. Lichenoid drug eruptions are also less likely to spontaneously resolve and may require discontinuation of the causative agent in addition to topical and/or oral corticosteroid therapy.
Our patient with the atorvastatin-induced lichenoid eruption was being treated at 40 mg/day. Another patient developed a lichenoid drug eruption with pravastatin; however, this patient's dosage was not stated [14]. Another patient developed a lichenoid drug eruption on fluvastatin 20 mg daily; when she switched to lovastatin 20 mg daily, she redeveloped this drug-induced eruption [13].
Management of statin-induced lichenoid drug eruptions includes discontinuation of the causative statin agent and treatment with topical and/or oral corticosteroids. Six of the seven patients' skin lesions, including ours, resolved with cessation of the statin medication and additional therapy: an oral corticosteroid, a topical corticosteroid, or both [13,[15][16][17][18]. In some instances, the eruption persisted for several months after discontinuing the instigating agent. Indeed, with or without additional treatment, the statin-induced drug eruptions resolved within three weeks to nine months after the causative drug was stopped [13][14][15][16][17][18].

Conclusions
Lichenoid drug eruptions share several features with lichen planus. However, unique characteristics of these drug-induced eruptions (including delayed onset, absence of Wickham's striae, and presence of eosinophils microscopically) can help distinguish lichenoid drug eruptions from idiopathic lichen planus. Statins are generally used in the management of hypercholesterolemia; however, several adverse cutaneous events have been observed in patients treated with statins. Lichenoid drug eruptions are an uncommon adverse cutaneous event associated with statin medications. The new onset of lichenoid dermatitis in an individual receiving statin therapy should raise the concern that this skin eruption may be associated with the medication.

Additional Information Disclosures
Human subjects: Consent was obtained by all participants in this study.

Conflicts of interest:
In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.