Treatment with ledipasvir-sofosbuvir for hepatitis C resulting in improvement of lichen planus.

Introduction

Lichen planus (LP) is a chronic inflammatory disease affecting the skin and mucosa of squamous cell origin and has a significantly higher prevalence in patients infected with the hepatitis C virus (HCV). Although ribavirin-based treatments frequently show exacerbations of these lesions, currently there is little information on the response of HCV-associated LP to newer direct antiviral agents (DAA), such as ledipasvir-sofosbuvir (Harvoni; Gilead Sciences, Foster City, CA).

Case report

A 55-year-old man with a 10-year history of HCV and cutaneous LP with prurigo nodularis on the bilateral hands, forearms, and torso was treated at the Hampton VA Medical Center. The patient endorsed that these lesions were extremely pruritic. He had no history of oral, scalp, or nail involvement. Skin biopsy sections were taken, and histology found interface dermatitis with saw tooth ridging and dyskeratotic keratinocytes (Fig 1). Review of medications was negative for causes of lichenoid drug eruption. Liver function tests and serum creatinine levels were within normal limits, and the clinical picture was consistent with classic findings of LP.

Fig 1

Lichen planus. Histopathology hematoxylin-eosin stain of biopsied lesion shows mixed infiltrate at the dermoepidermal junction and obliteration of the rete ridges, consistent with LP.

Oral hydroxyzine and topical triamcinolone 0.1% to the affected areas provided minimal relief of symptoms. The patient subsequently initiated treatment with ledipasvir-sofosbuvir, which resulted in marked improvement of cutaneous lesions. One month after the initiation of therapy, the patient had a marked decrease in pruritus, with partial regression of his lesions compared with photographs taken 7 months prior (Fig 2). At this point the patient also had decreases in serum HCV viral load from more than 1 million units to less than 15 units. The patient continued to have sustained remission during 3 months of treatment and throughout the third month after treatment. However, on follow-up 4 months after the end of therapy, our patient had an acute exacerbation of his lichenoid lesions with the return of intense pruritus. The patient had recently started colchicine therapy, which was the only new medication the patient received. Albeit temporary, to our knowledge, this is the first reported case of LP improving after the use of ledipasvir-sofosbuvir and may pave the way for potential future therapies for the cutaneous manifestation.

Fig 2

Lichen planus. Photographs taken 6 months before initiation of therapy (left) and 1 month after initiation of ledipasvir-sofosbuvir (right) show marked visible improvement of cutaneous lesions.

Discussion

Multiple systemic reviews have shown a statistically significant correlation between HCV and LP.1, 2 A 2010 meta-analysis by Lodi et al compared 33 studies involving LP and HCV and found that patients with LP have almost a 5-fold higher odds ratio of being HCV seropositive. Similarly, patients with HCV were found to have an almost 5-fold higher chance of having LP. Compared with 70 studies involving 678 patients, the overall prevalence of HCV in LP patients was found to be 22.3%. Therefore, many investigators recommend viral testing of patients with LP because of the increased odds of concomitant infection.

The previously accepted regimen of ribavirin and interferon produced mixed effects on LP, with some studies reporting improvement of lesions and others reporting exacerbations as well as the formation of de novo lesions.2, 3 The exact role of HCV in the disease process remains unclear, and studies have provided mixed results on the presence of HCV DNA in LP lesions. Current hypothesis on the pathogenesis of LP is via either CD8+ T cell or autoimmune antibody–stimulated apoptosis of keratinocytes.2, 3 Lesions have been found to produce high levels of interferon, which is believed to be a major inflammatory mediator in these lesions. This finding may partially explain the exacerbations of LP from classical interferon-based treatment regimens.

Ledipasvir-sofosbuvir is a once-daily oral DAA that received US Food and Drug Administration approval for the treatment of HCV in 2014 and has been largely successful in producing sustained virologic response. Ledipasvir functions by inhibiting the HCV nonstructural protein 5A, which is believed to play a role in a number of viral processes such as genome replication and assembly of infectious particles. Sofosbuvir is a nucleotide analog that inhibits the replicative functions of HCV RNA polymerase. At this time, minimal data exist detailing ledipasvir-sofosbuvir's effects on HCV-associated LP. There is only one case in the literature in which a patient with longstanding HCV and oral LP had an exacerbation of lesions and the onset of de novo widespread cutaneous lesions immediately after treatment and eradication of HCV with ledipasvir-sofosbuvir. In our case, there was a marked improvement in our patient's condition sustained for several months, followed by an acute exacerbation. Whether this was due to the etiology of his primary LP or a new lichenoid reaction is uncertain. He had recently initiated novel therapy with colchicine, and several reports implicate colchicine in lichenoid drug reactions.6, 7

The heterogenic response to interferon-based regimens as well as that of ledipasvir-sofosbuvir may provide evidence that not all LPs are mediated by the same mechanisms. Novel DAA treatment regimens may provide new hope for the resolution of HCV-associated LP. More data have yet to be collected regarding the effects of these agents on the course of LP, which may further aid in elucidating its true etiology and mechanism.