CHRISTIEAMMIRATIMDMICHAEL P.HEFFERNANMDERIK J.STRATMANMD
A 19-year-old man presented with a 5-year history of a widespread cutaneous eruption. His previous treatment consisted of topical corticosteroids and keratolytics, topical vitamin D derivatives, UV-A phototherapy, oral methotrexate, and oral cyclosporine, without significant improvement. Physical examination revealed bilateral, symmetrical, intensely erythematous lichenoid hyperkeratotic papules forming a linear striated pattern on the antecubital and flexural surfaces of the forearms (Figure 1), popliteal areas, lateral aspect of the trunk, back, periumbilical region, and dorsum of the hands and feet. Erythematous and desquamative papules affected the central facial area, with a seborrheic dermatitislike appearance. Bilateral conjunctival hyperemia was present (Figure 2).
Keratosis lichenoides chronica with tiny keratotic papules that tend to be arranged in a striaelike pattern in the antecubital fold.
Bilateral conjunctival involvement. Note the seborrheic dermatitislike papules on the face.
Results of the following laboratory investigations were normal or negative: complete blood cell count; hepatic profile; glycemia; serum creatinine and urea levels; lipid profile; and serologic tests for hepatitis B and C, human immunodeficiency virus, syphilis, and antinuclear antibodies. Histopathologic examination showed marked hyperkeratosis with focal parakeratosis and epidermal hyperplasia. Multiple necrotic keratinocytes were evident at the basal membrane level, and incontinentia pigmenti was noted in the upper dermis. A moderate bandlike, lymphocytic infiltration was present in the superficial dermis, with some intermingled plasma cells and dilatation of capillary vessels.
In view of these clinical and histologic findings, the diagnosis of keratosis lichenoides chronica (KLC) was made, and oral acitretin therapy was initiated at an initial dosage of 25 mg/d. The dosage was increased to a maximum of 35 mg/d. The therapy was discontinued after 3 months because there was no improvement. The next treatment, acitretin (25 mg/d) with oral psoralen–UV-A (4 times per week) for 3 months, resulted in partial improvement, but the patient's skin phototype made phototherapy a suboptimal treatment. When the patient again returned to us for care, subcutaneous etanercept therapy (50 mg twice a week) was initiated. The therapy was discontinued after 12 weeks because of a lack of efficacy. The patient's disease significantly affected his quality of life owing to pruritus and the appearance of the lesions.
Keratosis lichenoides chronica is a rare chronic dermatosis that typically presents in adolescents or young adults as a widespread symmetrical lichenoid eruption, formed by hyperkeratotic papules that adopt a reticulate, striated, or linear pattern. The treatment of KLC is challenging because the disease is resistant to many different therapies, including topical and systemic corticosteroids, methotrexate, cyclosporine, antibiotics, antimalarial agents, and sulfones. In some cases, partial responses have been achieved with the use of psoralen–UV-A and oral retinoids and, more recently, narrowband UV-B and oral retinoids.1
We read with interest the article by Cheng and Mann,2 who treated a patient with efalizumab for oral erosive lichen planus that also presented with cutaneous lesions. Heffernan et al3 reported 4 cases of oral erosive lichen planus, and Böhm and Luger4 reported 1 case of generalized refractory lichen planus, which they treated with efalizumab. In all of those cases, there was significant improvement of the patients' lesions and clinical symptoms. Considering KLC a clinical chronic variant of lichen planus, we tried efalizumab therapy in our patient. We started treatment with subcutaneous efalizumab at an initial dose of 0.7 mg/kg, followed by 1 mg/kg/wk. After 16 weeks, the keratotic lesions were totally replaced by hyperpigmented macules, and the conjunctival hyperemia had disappeared (Figure 3 and Figure 4). The results of laboratory tests were normal. At the present time, the patient has received the treatment for 9 months, with no adverse effects, and he has no itching.
Marked improvement of the lesions after 16 weeks of treatment with efalizumab. Only residual hyperpigmentation was observed.
Resolution of conjunctival hyperemia during efalizumab treatment (week 16).
Keratosis lichenoides chronica is a controversial entity, and there is ongoing discussion about its independent nature. In an exhaustive review, Böer5 concluded that KLC can be diagnosed only when the following 2 clinical and histopathologic features are present: (1) a chronic widespread eruption that affects the face in a way similar to seborrheic dermatitis and (2) a papular eruption that evolves into a characteristic linear or reticulate pattern on the trunk and limbs. The center of the papules is an infundibulum or an acrosyringium. Histologically, lichenoid dermatitis with numerous necrotic keratinocytes and parakeratosis is present. There can be mucosal involvement, including conjunctival lesions, as in our patient, although it is not a characteristic finding.
Concurrence with systemic disorders has been reported, but no association has been established. The 2 diseases that are most similar to KLC, both clinically and histologically, are lichen planus and chronic cutaneous lupus erythematosus.5 Some authors consider KLC to be a peculiar variant of other well-known inflammatory diseases, particularly lichen planus.6- 10 Because KLC is refractory to conventional treatment, we considered the potential role of biologic treatment in our patient. We chose lichen planus as a reference, as it is a similar disease. We initially started treatment with etanercept, based on the cases in which it was used for diseases that share pathogenic features with lichen planus, such as graft-vs-host disease11 and aphthous stomatitis.12 Furthermore, it seems that tumor necrosis factor could play a pathogenic role in lichen planus.13,14 When etanercept therapy did not provide significant improvement in our patient, we considered treatment with efalizumab, which was successful in several patients with severe oral erosive lichen planus2- 4 and in patients with cutaneous lupus erythematosus.15
Efalizumab is a humanized monoclonal antibody that binds to CD11a, a subunit of leukocyte function–associated antigen 1, which is a ligand of intercellular adhesion molecule 1; therefore, efalizumab acts as a T-cell modulator. In lichen planus, an infiltration of the skin by cytotoxic CD8+ lymphocytes has been observed. The response of lichen planus may be due to efalizumab indirectly acting by decreasing activation and traffic of CD4+ lymphocytes to the dermis, blocking them from activating CD8+ lymphocytes. In support of the action of efalizumab, immunohistochemical studies have disclosed expression of intercellular adhesion molecules 1 and 3 in infiltrating cells of lesional skin of lichen planus.16 Discoid lupus erythematosus is also pathogenically mediated by T lymphocytes. It is possible that the mechanism of action of efalizumab in KLC involves its modulatory effect over T cells in a disease in which lichenoid infiltrates composed predominantly of lymphocytes are observed, thus supporting a role for infiltrating T cells in the pathogenesis of KLC. Future immunohistochemical studies are required to ascertain which subclass of lymphocytes is predominant in the infiltrate in KLC. Multicenter studies involving optimal treatment for this disorder, which would include efalizumab in the therapeutic armamentarium, are also needed.
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Correspondence: Carlos Muñoz-Santos, MD, Department of Dermatology, Hospital de Sabadell, Corporació Sanitaria Parc Taulí, Parc Tauli s/n, 08208 Sabadell, Barcelona, Spain (firstname.lastname@example.org).
Accepted for Publication: August 12, 2008.
Author Contributions: Drs Muñoz-Santos and Luelmo had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Muñoz-Santos, Yébenes, and Luelmo. Acquisition of data: Muñoz-Santos and Romaní. Analysis and interpretation of data:Muñoz-Santos and Luelmo. Drafting of the manuscript: Muñoz-Santos, Yébenes, and Luelmo. Critical revision of the manuscript for important intellectual content: Muñoz-Santos, Romaní, and Luelmo. Administrative, technical, or material support: Muñoz-Santos and Romaní. Study supervision: Yébenes and Luelmo.
Financial Disclosure: None reported.
Response of Keratosis Lichenoides Chronica to Efalizumab Therapy. Arch Dermatol. 2009;145(8):867-869. doi:10.1001/archdermatol.2009.179