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Acitretin for Hypertrophic Lichen Planus Like Reaction in a Burn Scar

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Acitretin for Hypertrophic Lichen Planus Like Reaction in a Burn Scar THE CUTTING EDGE SECTION EDITOR: GEORGE J. HRUZA, MD; ASSISTANT SECTION EDITORS: LYNN A. CORNELIUS, MD; JON STARR, MD Acitretin for Hypertrophic Lichen Planus–Like Reaction in a Burn Scar Steven Kossard, FACD; Phillip Artemi, FACD; Skin and Cancer Foundation Australia, Sydney The Cutting Edge: Challenges in Medical and Surgical Therapeutics REPORT OF A CASE men showed changes consistent with an early well- differentiated squamous cell carcinoma. A 60-year-old-man sustained a burn in childhood on the lower part of his right leg in a fire in a haystack. The area THERAPEUTIC CHALLENGE healed and remained as a stable scar for 50 years. Four months before presentation, he developed a series of hy- Squamous cell carcinoma may develop in the setting of pertrophic papules and plaques measuring up to 12 cm either a long-standing burn scar or hypertrophic lichen in diameter localized to the burn scar (Figure 1). The planus. Immunosuppressive agents, such as systemic cor- individual lesions were violaceous and hyperkeratotic. ticosteroids or cyclosporin, are used to treat lichen pla- There were no similar lesions at other skin sites or in- nus but inhibit cell-mediated immune responses that play volvement of his mucous membranes. The patient was a vital role in inhibiting the progression of skin cancers. taking warfarin sodium and digoxin, and 2 months after Clearly, the use of immunosuppressive drugs in our pa- the onset of his skin lesions, he began taking lisinopril tient, who had both a long-standing burn scar and le- for hypertension. sions resembling hypertrophic lichen planus, posed a po- Over the following 5 months, 4 skin biopsy speci- tential risk of enhancing tumor growth. We were mens were obtained from the most infiltrated areas. All concerned that the apparent absence of squamous cell 4 specimens showed an irregularly acanthotic epider- carcinoma in our patient’s initial biopsy specimens may mis with focal parakeratosis and prominent lichenoid in- have represented a sampling problem. flammation (Figure 2) concentrated at the tips of the rete ridges (Figure 3), with liquefaction degeneration SOLUTION of the basal layer. There were scattered eosinophils in the dermis. Three of the skin biopsy specimens, including 2 Acitretin is a synthetic retinoid that has been shown in a initial samples, showed no evident squamous cell carci- double-blind, placebo-controlled study to prevent skin noma, but a subsequent biopsy specimen showed a hy- cancers and reduce actinic keratoses in immunosup- pertrophic epidermis that was associated with large ir- pressed patients who have undergone renal transplan- regular clusters of keratinocytes that projected into the tation.1 It has also been successfully used to treat lichen dermis (Figure 4). These keratinocytes showed prema- planus in a double-blind, placebo-controlled study of 65 ture keratinization and focal nuclear atypia and were con- patients.2 Acitretin therapy (20 mg/d) was therefore ini- sistent with an early well-differentiated squamous cell car- tiated in our patient, and within 2 months there was cinoma. marked clearing of his skin lesions. Owing to a rise in his serum triglyceride levels, the acitretin dosage was re- DIAGNOSTIC CHALLENGE duced to 10 mg/d for 1 month, and the decrease in dos- age led to an increase in the thickness of 2 of the skin The clinical presentation and the initial skin biopsy find- lesions. Biopsy specimens were obtained from both ar- ings were consistent with hypertrophic lichen planus. Our eas and showed lichenoid inflammation with epidermal main concern was whether the multifocal epidermal hy- hyperplasia. One of the biopsy specimens also showed perplasia associated with lichenoid inflammation was a an early well-differentiated squamous cell carcinoma harbinger of skin cancer, particularly as the reaction was (Figure 4), but this was largely in situ and associated with localized to a long-standing burn scar. The presence of lichenoid inflammation. As the squamous cell carci- parakeratosis and eosinophils in all the skin biopsy speci- noma was not clinically well defined and the skin le- mens is not a typical feature of lichen planus but can be sions had been undergoing progressive regression dur- seen in hypertrophic lesions. A subsequent biopsy speci- ing acitretin therapy, the acitretin dosage was again ARCH DERMATOL / VOL 136, MAY 2000 WWW.ARCHDERMATOL.COM 591 ©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 Figure 1. Right ankle demonstrating multiple hypertrophic lichenoid lesions Figure 2. Skin biopsy specimen showing irregularly acanthotic epidermis within a burn scar. with lichenoid inflammation and underlying dermal scar (hematoxylin-eosin, original magnification 325). increased to 20 mg/d. The triglyceride levels were re- cinoma6 and its most frequent precursor, actinic kera- duced by diet control. Six weeks later, the areas were no tosis. longer indurated. A biopsy specimen obtained from the Lichen planus, particularly of the oral cavity,7,8 and site of the skin cancer 3 months later showed nonre- hypertrophic lichen planus9 may be complicated by squa- sidual tumor. Because of the continued risk of skin can- mous cell carcinoma. However, the development of skin cers developing in the patient’s burn scar, the acitretin cancers usually occurs in long-standing chronic disease therapy was continued at a dosage of 20 mg/d as a che- and contrasts with the short history of the hypertrophic moprophylactic measure. This regimen has resulted in lichenoid lesions seen in our patient. The limitation of clearing of the patient’s skin lesions and in residual mottled the lichenoid reaction to the burn scar, as well as the pres- pigmentation over the burn scar (Figure 5). It has been ence of parakeratosis and eosinophils in the skin biopsy 1 year since the acitretin therapy was initiated, and no specimens obtained from our patient, raised our suspi- further skin cancers have emerged. cion that we were dealing with an unusual host re- sponse directed to preneoplastic changes in a long- COMMENT standing burn scar. A subsequent biopsy specimen showed changes consistent with an early squamous cell carci- The risk of skin cancer developing in long-term burn scars noma. However, the bulk of the lichenoid inflammation is well recognized.3 Cell-mediated immunity is an im- in the skin biopsy specimens was associated with an epi- portant factor in controlling the emergence of skin can- dermis that lacked evidence of atypia and was consis- cers, and its role is illustrated in the marked increase in tent with hypertrophic lichen planus. skin cancers in organ transplant patients who are receiv- Acitretin has been used in the chemoprophylaxis of ing long-term immunosuppression.4,5 In specimens sub- skin cancers and is not recommended as a therapy for mitted for histological diagnosis, lichenoid tissue reac- established squamous cell carcinomas. In our patient, the tions and lymphocytic inflammation reflecting host decision to postpone surgery was based on the well- immunological response may be seen in the setting of a differentiated and largely in situ nature of the tumor and broad range of skin cancers, including squamous cell car- the associated lichenoid inflammation, as well as on the ARCH DERMATOL / VOL 136, MAY 2000 WWW.ARCHDERMATOL.COM 592 ©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 Figure 3. Detail of lichenoid reaction concentrated at tips of rete ridges. Figure 5. Marked clearing of hypertrophic lesions after acitretin treatment. Epidermis is well differentiated (hematoxylin-eosin, original magnification 3100). It is important to distinguish lichenoid reactions oc- curring in the setting of epithelial dysplasia from lichen planus. Particular caution needs to be taken when re- porting on skin samples that have been obtained from localized or solitary hypertrophic lichenoid lesions in pa- tients who lack evidence of lichen planus at other sites. Multiple samples may be required to confirm the pres- ence of a squamous cell carcinoma, as the transition to frank carcinoma may be focal. In certain settings, such as long-standing burn scars, the presence of a lichenoid tissue reaction may represent a host response to early neo- plastic changes. Hypertrophic lichen planus developing within a long-standing burn scar is rare, and we were not able to find a previous report of this event. The mode of action of acitretin in chemoprophy- laxis of skin cancer may be related to its ability to pro- Figure 4. Irregular clusters of keratinocytes in dermis demonstrating focal 10 nuclear atypia and disorganized architecture (hematoxylin-eosin, original mote differentiation of keratinocytes. A recent study in- magnification 31000). dicates that there is aberrant expression of fetal cytokeratin in lichen planus,11 which may be one of the reasons that progressive regression of his skin lesions during higher- acitretin has been successful in the treatment of lichen dosage acitretin therapy. The regression of the skin can- planus. The use of agents that are capable of promoting cer was probably a reflection of the marked host re- the differentiation of keratinocytes, such as acitretin, may sponse occurring in the burn scar that resembled provide an effective treatment strategy when the alter- hypertrophic lichen planus, and the role of acitretin may native option is the use of immunosuppressive agents in have been a secondary one. Close monitoring of the course the setting of increased risk of tumor enhancement. In of the skin cancer was required in this setting in case sur- our patient, the use of acitretin as monotherapy not only gery was needed. cleared the hypertrophic lichen planus–like reaction, but ARCH DERMATOL / VOL 136, MAY 2000 WWW.ARCHDERMATOL.COM 593 ©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 it also acted as a chemoprophylactic agent for skin can- 8.
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