Dermatology Online Journal

Erythrodermic lichen planus
Amy E Rose MD, Utpal Patel MD PhD, Julie Chu MD, Rishi Patel MD, Shane Meehan MD, Jo-Ann M Latkowski MD
Dermatology Online Journal 17 (10): 26

Department of Dermatology, New York University, New York, New York

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Abstract

Lichen planus (LP) is a relatively common papulosquamous disorder that is characterized by pruritic, polygonal papules in a characteristic distribution. We present a case of a 71-year-old man with erythroderma, who was ultimately diagnosed with severe, generalized LP. Treatment of severe LP is challenging, and there are few, robust, clinical trials in the literature to guide the selection of appropriate treatment. We discuss the treatment options for generalized LP and the evidence in support of these agents.

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History

A 71-year-old man presented to the Cutaneous Lymphoma Clinic of Bellevue Hospital Center for evaluation of a diffuse, pruritic eruption that affected the face, trunk, and extremities. He reported having had similar focal lesions for approximately 30 years that had flared over the past three years. Previous treatment with intralesional and topical glucocorticoids was unsuccessful, and the eruption continued to progress. He reported shaking chills but denied fevers, night sweats, or other constitutional symptoms. Past medical history included hypertension for which he was taking an angiotensin receptor blocker that was only available in his home country of Ecuador. He denied medication allergies, and his family history was non-contributory.

Physical examination

Figure 1	Figure 2

The patient was afebrile with shaking chills, erythroderma, and a leonine facies. There was palpable, non tender axillary and inguinal lymphadenopathy without hepatosplenomegaly. There were no lesions of the oral mucosa. On the face, trunk, buttocks, and extremities there were erythematous, hyperpigmented papules that coalesced into plaques with thick scale. On the face and chest there were areas with discrete, polygonal, hyperpigmented papules. The left lower extremity was edematous, erythematous, and tender to palpation with intact, tense bullae, ruptured bullae, and shallow ulcers with overlying serous crust on the anterior tibial surface.

Laboratory data

The white-cell count was 15.4 x 10⁹/L. Comprehensive metabolic and lipid panels were normal. Lactic dehydrogenase was elevated at 442 units/L. Hepatitis C antibody was negative. A wound culture from the left lower extremity grew methicillin-sensitive Staphylococcus aureus.

Histopathology

Figure 3

There is a perivascular and band-like, inflammatory infiltrate that is comprised predominantly of lymphocytes with scattered eosinophils. Some lymphocytes extend to the overlying epidermis where there is vacuolar alteration at the dermoepidermal junction, irregular epidermal hyperplasia with saw-tooth rete ridges, and necrotic keratinocytes.

Discussion

Lichen planus (LP) is a relatively common, chronic, papulosquamous disorder that is characterized by polygonal, pruritic papules and erosive lesions of the oral mucosa. Although the etiology of LP has yet to be fully elucidated, it is thought to be related to autoimmunity and is associated with HLA types-A3, -A5, -B8, -Bw35, and -DR1 [1]. The link between LP and hepatitis C virus remains controversial and is thought to be most relevant for mucosal forms of LP [2]. Lichen planus is variable in its clinical presentation and natural history, with several well-characterized subtypes, such as eruptive, hypertrophic, atrophic, bullous, actinic, and oral.

It is unusual for patients with LP to present with erythroderma, which emphasizes the importance of considering a broad differential diagnosis for erythrodermic skin disease. There are few reports in the literature of such a severe presentation of LP as was observed in the patient described in our report. We speculate that the clinical presentation was the result of the progression of uncontrolled disease over several years or possibly a more acute exacerbation triggered by medication. Numerous medications have been implicated in the development of lichenoid eruptions that can appear identical to classic LP, with the most common classes including antihypertensives, antimalarials, diuretics, gold salts, penicillamine, and quinidine [3, 4]. Differentiating between idiopathic LP and a lichenoid drug eruption can be difficult as there are no well-established clinical or histopathologic criteria that strictly define the two entities. Lichenoid drug eruptions have a mean age of onset of 66 years as compared to 50 years in idiopathic LP. Drug eruptions have a more generalized distribution and a more eczematous or psoriasiform morphology than does idiopathic LP, which has a predilection for the classic sites of involvement, such as the wrists and genitalia, and the classic morphology of polygonal, flat-topped, violaceous papules. Lichenoid drug reactions more often have a photodistribution and spare the mucous membranes [4]. Other factors that may induce LP include hepatitis B vaccination [5], influenza vaccination [6], bacteria, viruses, and contact allergy to metal in cases of oral LP [7]. One report described a patient with a generalized eruptive LP after treatment with acupuncture, which suggested an immune response to cutaneous injury [1]. Severe, generalized LP has been reported in patients undergoing radiation therapy [8].

Therapeutic options for severe LP include glucocorticoids, phototherapy, oral retinoids, and immune modulators, such as cyclosporine or sulfasalazine. There are few, large, randomized studies that evaluate the efficacy of treatment of LP. With rates of spontaneous remission as high as 68 percent within one year, studies that are not placebo-controlled must be interpreted cautiously [9, 10]. The largest placebo-controlled trial evaluated the efficacy of 30 mg of acitretin administered daily for eight weeks in 65 patients with cutaneous LP. Improvement was achieved in 64 percent of the treatment group compared to only 13 percent of the placebo group, with 83 percent of the placebo group noting improvement after changing to the treatment arm [11]. Phototherapy is another commonly utilized treatment for severe, generalized LP, with most of the literature focusing on the use of psoralen and ultraviolet A (PUVA) photochemotherapy. The body of evidence in support of oral and bath PUVA is considered to be relatively weak [10] and two reports have demonstrated induction of LP with PUVA photochemotherapy [12, 13]. One retrospective study of 50 patients with generalized LP, who were treated with broad-band and narrow-band ultraviolet B (NB-UVB) phototherapy, showed complete responses in 70 percent of broad-band treated patients and in 85 percent of NB-UVB treated patients [14]. A study comparing PUVA photochemotherapy to NB-UVB phototherapy showed that PUVA photochemotherapy resulted in a better initial response, but, after a mean follow-up period of 20.5 months, there was no difference between the two groups with regard to recurrence or sustained overall clinical response [15].

Oral metronidazole has emerged as an alternative therapy based on case reports of improvement of cutaneous and oral lesions in LP patients being treated for intestinal giardiasis. An open-label, non-placebo-controlled study of 49 LP patients treated with metronidazole 250 mg every eight hours for three months reported an overall treatment response rate (including complete and partial responses) of 73.47 percent [16]. A prospective, open-label study of itraconazole 200 mg twice daily for one week of each month for three months in 16 patients with severe LP reported complete cessation of new lesions in 77.7 percent, complete relief of pruritus in 55.55 percent, and complete flattening of lesions in 33.33 percent [17]. The mechanism of action is believed to be due to the immunomodulatory effects of itraconazole. One placebo-controlled study reported efficacy of griseofulvin for the treatment of cutaneous LP [18]. The conclusions that could be drawn from the study, however, are limited by lack of detail regarding the study methods and criteria for determining responses [10].

Immune modulators also play a role in the management of severe generalized LP. A randomized, placebo-controlled trial of 52 patients with generalized LP treated with 2.5 gm of sulfasalazine daily for six weeks reported lesion improvement in 82.6 percent of treated patients compared to 9.6 percent in the placebo group [19]. Adverse effects were reported in 31 percent of the treated group, the most common of which were gastrointestinal disturbance and headache [19]. A small study of five patients with refractory LP treated with 100 mg per day of thalidomide reported a mean time to complete remission of three months [20]. One retrospective study of ten patients reported improvement in the extent of lesions and pruritus in all patients within one month of starting methotrexate at 15 to 20 mg per week [21]. Other agents that have been reported to be efficacious in small case series and anecdotal reports include dapsone, hydroxychloroquine, cyclosporine, and adalimumab [22]. There are limited studies to support a specific approach to treating severe cutaneous LP. There are no Class A studies as defined by the Sackett [23] criteria of evidence-based medicine and only one Class B study demonstrating the efficacy of acitretin.

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