Lichen striatus associated with etanercept treatment of rheumatoid arthritis
Authors: Viviana Lora, Jean Kanitakis, Alessandra Latini, Carlo Cota
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: Lichenoid eruptions are an emerging adverse event of anti-TNFα therapy. They share the common histopathologic features of a lichenoid reaction, but present with 3 different clinical patterns: (1) lichen planus-like (LPLE), (2) nonspecific maculopapular, and (3) psoriasis-like.1Asarch A. Gottlieb A.B. Lee J. Masterpol K.S. Scheinman P.L. Stadeker M.J. et al.Lichen planus-like eruptions: an emerging side effect of tumor necrosis factor-α antagonists.J Am Acad Dermatol. 2009; 61: 104-111Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar Lichenoid eruptions with a segmental arrangement have rarely been observed in the setting of anti-TNFα therapy.2Utsu M. Hida T. Takahashi H. Yamashita T. Etanercept-induced lichen planus-like eruption following the lines of Blaschko.Eur J Dermatol. 2012; 22: 544-545PubMed Google Scholar, 3Monteagudo B. Cabanillas M. Suarez-Amor O. Ramirez-Santos A. Alvarez J.C. de Las Heras C. Adult blaschkitis in a patient treated with adalimumab.Actas Dermosifilogr. 2010; 101: 891-892Crossref PubMed Scopus (15) Google ScholarWe encountered a 70-year-old woman in whom a linear dermatosis developed 8 months after starting therapy with etanercept (50 mg/week) for severe rheumatoid arthritis. The patient had no history of infection while on therapy and no clinical evidence of an infection before the onset of the eruption existed. Her medical history was notable for hypertension, thyroiditis, dyslipidemia, and diabetes mellitus, for which she was treated with fosinopril/hydrochlorothiazide, nebivolol, levothyroxine, atorvastatin, and metformin. No changes in the dosing of these drugs were introduced during the 12 months preceding initiation of etanercept. Eight months after starting etanercept treatment, an erythematous, scaly, papular eruption with a linear arrangement along Blaschko lines developed over the right side of her body (Fig 1, A). Microscopic examination of a biopsy specimen obtained from the leg showed epidermal orthohyperkeratosis, acanthosis, and a lichenoid lymphocytic interface dermatitis associated with a deep lymphocytic infiltrate surrounding eccrine sweat glands (Fig 1, B and C), that are features suggestive of lichen striatus (LS). Etanercept was discontinued and a local steroid treatment was prescribed. A 7-month follow up showed regression of skin lesions with secondary hyperpigmentation.LS is an uncommon self-limiting lichenoid dermatosis following Blaschko lines of the skin. Its etiopathogenesis remains unknown. It has been speculated that the disease could be due to loss of immune tolerance induced by an acquired stimulus, resulting in a cytotoxic reaction toward mutated, post-zygotic skin cells distributed along Blaschko lines.4Muller C.S.L. Schmaltz R. Vogt T. Pfohler C. Lichen striatus and blaschkitis: reappraisal of the concept of blaschkolinear dermatoses.Br J Dermatol. 2011; 164: 257-262Crossref PubMed Scopus (51) Google Scholar LS is rare in adults and controversies exist regarding the differential diagnosis for adult blaschkitis.4Muller C.S.L. Schmaltz R. Vogt T. Pfohler C. Lichen striatus and blaschkitis: reappraisal of the concept of blaschkolinear dermatoses.Br J Dermatol. 2011; 164: 257-262Crossref PubMed Scopus (51) Google Scholar The patient described here meets the diagnostic criteria for LS (scaly papular lesions with a segmental pattern, typical histologic features, recovery with postinflammatory hyperpigmentation).4Muller C.S.L. Schmaltz R. Vogt T. Pfohler C. Lichen striatus and blaschkitis: reappraisal of the concept of blaschkolinear dermatoses.Br J Dermatol. 2011; 164: 257-262Crossref PubMed Scopus (51) Google ScholarAnti-TNFα therapy can exceptionally induce segmental lichenoid reactions. To our knowledge, only 1 case of etanercept-induced LPLE following Blaschko lines and 1 case of adult blaschkitis due to adalimumab have been reported thus far. In these cases, as well as in the other cases of lichenoid eruptions secondary to biologic therapy, an up-regulation of interferon-alfa synthesis following TNFα inhibition has been suggested.1Asarch A. Gottlieb A.B. Lee J. Masterpol K.S. Scheinman P.L. Stadeker M.J. et al.Lichen planus-like eruptions: an emerging side effect of tumor necrosis factor-α antagonists.J Am Acad Dermatol. 2009; 61: 104-111Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar, 2Utsu M. Hida T. Takahashi H. Yamashita T. Etanercept-induced lichen planus-like eruption following the lines of Blaschko.Eur J Dermatol. 2012; 22: 544-545PubMed Google Scholar In our case, a role for a transient (subclinical) infectious episode cannot be completely excluded, even though there was no evidence for an associated one. In fact, patients with rheumatoid arthritis, as the one presented here, are at higher risk for infection when treated with biologic agents, such as TNFα inhibitors.5Lecluse L.L. Dowlatshshi E.A. Limpens J.M. de Rie M.A. Bos J.D. Spuls P.I. Etanercept. An overview of dermatologic adverse events.Arch Dermatol. 2011; 147: 79-94Crossref PubMed Scopus (14) Google Scholar This infection could cause the expression of aberrant membrane antigens in susceptible mutated keratinocytes, thereby triggering the disease. Finally, a direct toxic effect of the drug on the abnormal cells distributed along Blaschko lines can be also hypothesized.In conclusion, we report what we believe is the first case of adult LS associated with etanercept therapy. This observation further expands the clinical spectrum of lichenoid reactions due to TNFα inhibitors. To the Editor: Lichenoid eruptions are an emerging adverse event of anti-TNFα therapy. They share the common histopathologic features of a lichenoid reaction, but present with 3 different clinical patterns: (1) lichen planus-like (LPLE), (2) nonspecific maculopapular, and (3) psoriasis-like.1Asarch A. Gottlieb A.B. Lee J. Masterpol K.S. Scheinman P.L. Stadeker M.J. et al.Lichen planus-like eruptions: an emerging side effect of tumor necrosis factor-α antagonists.J Am Acad Dermatol. 2009; 61: 104-111Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar Lichenoid eruptions with a segmental arrangement have rarely been observed in the setting of anti-TNFα therapy.2Utsu M. Hida T. Takahashi H. Yamashita T. Etanercept-induced lichen planus-like eruption following the lines of Blaschko.Eur J Dermatol. 2012; 22: 544-545PubMed Google Scholar, 3Monteagudo B. Cabanillas M. Suarez-Amor O. Ramirez-Santos A. Alvarez J.C. de Las Heras C. Adult blaschkitis in a patient treated with adalimumab.Actas Dermosifilogr. 2010; 101: 891-892Crossref PubMed Scopus (15) Google Scholar We encountered a 70-year-old woman in whom a linear dermatosis developed 8 months after starting therapy with etanercept (50 mg/week) for severe rheumatoid arthritis. The patient had no history of infection while on therapy and no clinical evidence of an infection before the onset of the eruption existed. Her medical history was notable for hypertension, thyroiditis, dyslipidemia, and diabetes mellitus, for which she was treated with fosinopril/hydrochlorothiazide, nebivolol, levothyroxine, atorvastatin, and metformin. No changes in the dosing of these drugs were introduced during the 12 months preceding initiation of etanercept. Eight months after starting etanercept treatment, an erythematous, scaly, papular eruption with a linear arrangement along Blaschko lines developed over the right side of her body (Fig 1, A). Microscopic examination of a biopsy specimen obtained from the leg showed epidermal orthohyperkeratosis, acanthosis, and a lichenoid lymphocytic interface dermatitis associated with a deep lymphocytic infiltrate surrounding eccrine sweat glands (Fig 1, B and C), that are features suggestive of lichen striatus (LS). Etanercept was discontinued and a local steroid treatment was prescribed. A 7-month follow up showed regression of skin lesions with secondary hyperpigmentation. LS is an uncommon self-limiting lichenoid dermatosis following Blaschko lines of the skin. Its etiopathogenesis remains unknown. It has been speculated that the disease could be due to loss of immune tolerance induced by an acquired stimulus, resulting in a cytotoxic reaction toward mutated, post-zygotic skin cells distributed along Blaschko lines.4Muller C.S.L. Schmaltz R. Vogt T. Pfohler C. Lichen striatus and blaschkitis: reappraisal of the concept of blaschkolinear dermatoses.Br J Dermatol. 2011; 164: 257-262Crossref PubMed Scopus (51) Google Scholar LS is rare in adults and controversies exist regarding the differential diagnosis for adult blaschkitis.4Muller C.S.L. Schmaltz R. Vogt T. Pfohler C. Lichen striatus and blaschkitis: reappraisal of the concept of blaschkolinear dermatoses.Br J Dermatol. 2011; 164: 257-262Crossref PubMed Scopus (51) Google Scholar The patient described here meets the diagnostic criteria for LS (scaly papular lesions with a segmental pattern, typical histologic features, recovery with postinflammatory hyperpigmentation).4Muller C.S.L. Schmaltz R. Vogt T. Pfohler C. Lichen striatus and blaschkitis: reappraisal of the concept of blaschkolinear dermatoses.Br J Dermatol. 2011; 164: 257-262Crossref PubMed Scopus (51) Google Scholar Anti-TNFα therapy can exceptionally induce segmental lichenoid reactions. To our knowledge, only 1 case of etanercept-induced LPLE following Blaschko lines and 1 case of adult blaschkitis due to adalimumab have been reported thus far. In these cases, as well as in the other cases of lichenoid eruptions secondary to biologic therapy, an up-regulation of interferon-alfa synthesis following TNFα inhibition has been suggested.1Asarch A. Gottlieb A.B. Lee J. Masterpol K.S. Scheinman P.L. Stadeker M.J. et al.Lichen planus-like eruptions: an emerging side effect of tumor necrosis factor-α antagonists.J Am Acad Dermatol. 2009; 61: 104-111Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar, 2Utsu M. Hida T. Takahashi H. Yamashita T. Etanercept-induced lichen planus-like eruption following the lines of Blaschko.Eur J Dermatol. 2012; 22: 544-545PubMed Google Scholar In our case, a role for a transient (subclinical) infectious episode cannot be completely excluded, even though there was no evidence for an associated one. In fact, patients with rheumatoid arthritis, as the one presented here, are at higher risk for infection when treated with biologic agents, such as TNFα inhibitors.5Lecluse L.L. Dowlatshshi E.A. Limpens J.M. de Rie M.A. Bos J.D. Spuls P.I. Etanercept. An overview of dermatologic adverse events.Arch Dermatol. 2011; 147: 79-94Crossref PubMed Scopus (14) Google Scholar This infection could cause the expression of aberrant membrane antigens in susceptible mutated keratinocytes, thereby triggering the disease. Finally, a direct toxic effect of the drug on the abnormal cells distributed along Blaschko lines can be also hypothesized. In conclusion, we report what we believe is the first case of adult LS associated with etanercept therapy. This observation further expands the clinical spectrum of lichenoid reactions due to TNFα inhibitors.