Resident Corner

Concise Review of and Lichenoid Dermatoses

Amanda Pickert, MD

ichenoid dermatoses are named after lichen, a surface CD95L (FasL) on the CTLs to keratinocyte composite organism consisting of a fungus and CD95 (Fas) to activate apoptosis; (2) CTL and natu- Lphotosynthetic partner engaged in a symbiotic ral killer cell secretion of granzyme B, which enters relationship. In Latin, the word leichen means tree keratinocytes via cell membrane pores from perforin, moss and the word planus means flat. Lichenoid der- leading to apoptosis; and (3) lymphocyte secretion of matoses are a heterogeneous group of diseases with tumor necrosis factor a–inducing matrix metallopro- varying clinical presentations. Immune-mediated teinase 9, which can disrupt the basement membrane basal cell keratinocyte damage is a key finding on zone and promote keratinocyte apoptosis through histology. Herein, I will giveCUTIS a basic overview of deprivation of basement membrane zone–derived cell lichenoid dermatoses with a focus on classic lichen survival signals. Although lichenoid dermatoses have planus (LP) and its variants. Residents should be repeatedly been proposed as contributory, there has familiar with this disease and its variants and should been no conclusive evidence linking LP and LP variants be able to recognize these sometimes overlooked der- to , human herpesvirus 2, human immunode- matoses that can pose a diagnostic challenge. I will ficiency virus, chronic bladder infections, hepatitis C not be discussing oral (erosive) LP, lichen planopila- virus, Helicobacter pylori, or human papillomavirus.4 ris, andDo LP, as these are broadNot topics. However, Copy screening for hepatitis C virus infection is recommended, as case-control studies have shown an Pathophysiology of Lichen Planus association of hepatitis C virus and LP.5 The pathophysiology of LP and LP variants is unclear. However, LP is classified as a cell-mediated immune Lichen Planus reaction perpetuated by activated CD81 cytotoxic The prototypic lichenoid dermatosis of LP often is T lymphocytes (CTLs) and natural killer cells.1 described by the 4 p’s: purple, polygonal, pruritic pap- Although the antigen has yet to be identified, basal ules. are grouped and tend to coalesce. Thin, keratinocyte presentation of an unspecified agent transparent, adherent scales known as Wickham (eg, autoreactive peptide, altered protein, drug reac- striae give lesions a reticulated appearance. The visu- tion, contact allergen, hapten, and viral or infectious alization of Wickham striae can be enhanced with oil agents) on a class I major histocompatibility complex or water and use of a contact dermatoscope, which is molecule is believed to activate a CTL-inciting dis- a helpful clinical pearl. Wickham striae are thought ease.2 The subsequent immune cascade causes effector to correlate with the focal thickening of the stratum CTLs and natural killer cells to accumulate at the granulosum epidermidis, which is appreciated on his- dermoepidermal junction and keratinocyte apoptosis tology.6 Spots usually start as erythematous macules (Civatte bodies).3 The immune system can cause that evolve to the characteristic purplish papules over keratinocyte apoptosis via several mechanisms: several weeks’ duration. Initial lesions are symmetric; (1) the caspase cascade, which requires the binding of more commonly present on the lower extremities than the upper extremities; and favor the flexural From Mayo Clinic Arizona, Scottsdale. areas of the wrists, arms, and legs. In approximately The author reports no conflict of interest. one-third of cases, generalization can occur within a

WWW.CUTIS.COM VOLUME 90, SEPTEMBER 2012 E1 Copyright Cutis 2012. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. Resident Corner

few months of the initial outbreak.6 Spots usually heal regions. Patients also may have classic LP at other with . The duration of LP is vari- anatomic locations. Hyperpigmented macules and able but oral (erosive), hypertrophic, and nail vari- patches usually are present on clinical presentation. ants of LP tend to be more recalcitrant. Ulcerative Histopathology can show evidence of epidermal atro- lesions usually present on the mucous membranes, phy and pigment incontinence. glans penis, and vulva. Oral (erosive) LP, anogenital LP, and vulvovaginal LP are special forms of LP. Atro- Hypertrophic LP phic LP is common on the lower extremities and may Hypertrophic LP most commonly presents on the represent a resolving phase of LP. extremities (eg, shins). The disease is extremely pruritic and is associated with chronic venous insuf- Familial LP ficiency. Hypertrophic LP often is confused both There are fewer than 200 cases of familial LP reported clinically and histologically with squamous cell carci- in the literature.7-9 Oftentimes this disease is more noma. The clinical course of hypertrophic LP is more severe and protracted and presents with erosive, lin- chronic than other LP variants. ear, or ulcerative patterns, usually affecting several family members. Familial LP has been associated Vesiculobullous LP with HLA-B7, HLA-A3, HLA-B18, and HLA-Cw8, Vesiculobullous LP is a rare variant of LP. It pres- though there have been mixed results.7-9 The exis- ents with vesicles or bullae within lesions caused by tence of familial LP has purported to support the intense inflammation, and it is the clinical equivalent hypothesis that genetic factors are of etiologic impor- of Max-Joseph spaces, which is a subepidermal cleft tance in LP. formed by acantholysis or hydropic degeneration of basal keratinocytes on histology.6 Vesiculobullous LP should not arise from healthy-appearing skin and Lichen nitidus has a predilection for children and must be differentiated from LP pemphigoides, an usually presents in the upper extremities, chest, LP-pemphigoid overlap syndrome. abdomen, and male genitalia.6 Lichen nitidus has its own unique picturesque histology,CUTIS often described as Lichen Planus Pigmentosus ball-and-claw pattern. Generalized lichen nitidus is Lichen planus pigmentosus most commonly occurs rare and has been reported in association with genetic in individuals with Fitzpatrick skin types III and syndromes, such as Down syndrome.10 IV. Usual presentation includes brown to gray mac- ules in sun-exposed areas of the face and neck with subsequent generalization and potential involve- Lichen striatus is described as a benign self-limited ment of intertriginous areas. Both histologically and dermatosis,Do primarily affecting Not adolescent children. clinically, Copy LP pigmentosus often appears similar to Classically, it arises suddenly as crops of pink-tan dyschromicum perstans (ashy dermatosis); papules often on the extremities and along the lines however, the former may be differentiated by its pre- of Blaschko.6 Digital involvement may be associated dilection for sun-exposed skin, intertriginous areas, with a nail dystrophy. A deep perivascular and periec- and older age of onset (40–50 years).6 crine infiltrate with granulomatous inflammation on histology is not uncommon. Actinic LP Actinic LP also is referred to as LP subtropicus, LP Annular LP tropicus, summertime actinic , Annular LP is a rarely reported variant of LP seen in LP actinicus, LP atrophicus annularis, and lichenoid approximately 10% of cases.6 There often is an arcu- melanodermatitis. This variant of LP is more com- ate grouping of papules or rings with central clearing mon in the Middle East and most commonly occurs and hyperpigmentation. This dermatosis more com- in young adults in the spring and summer months. monly presents in darker skin types and on the penis It presents as hyperpigmented to red-brown papules and/or scrotum. I have seen several pediatric patients with an annular configuration and develops on sun- with generalized dramatic disease. Postinflammatory exposed surfaces including the face, dorsal hands, and hyperpigmentation can be notable and is difficult arms.6 The clinical differential diagnosis may be simi- to treat. lar to . I have never seen a case of actinic LP.

Inverse LP Lichenoid Drug Eruptions Inverse LP is a clinical variant of LP with lesions There can be a long latency between drug initiation appearing in the axillae, groin, and inframammary and involving the onset of a lichenoid

E2 CUTIS® WWW.CUTIS.COM Copyright Cutis 2012. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. Resident Corner

drug eruption. Halevy and Shai11 reported an average RANTES/CCL5 and IP-10/CXCL10 in their cytolytic latency period of up to 12 months. Additionally, the granules: a potential self-recruiting mechanism. Am J eruption may appear similar to LP; however, there Pathol. 2003;163:261-268. are key differences between the 2 variants. In classic 2. Sugerman PB, Savage NW, Walsh LJ, et al. The patho- LP, generalized or photodistributed sites are spared. genesis of oral lichen planus. Crit Rev Oral Biol Med. In lichenoid drug eruptions, Wickham striae are not 2002;13:350-365. present, there are larger monomorphic lesions with 3. Prpi´c Massari L, Kastelan M, Gruber F, et al. Perforin a psoriasiform appearance, and with expression in peripheral blood lymphocytes and skin- crusting is present. The presence of eosinophils, infiltrating cells in patients with lichen planus. Br J plasma cells, or parakeratosis on histology is sup- Dermatol. 2004;151:433-439. portive of a drug-induced eruption.11-14 Medications 4. Lodi G, Scully C, Carrozzo M, et al. Current controver- that can cause lichenoid drug eruptions include gold, sies in oral lichen planus: a report of an international penicillamine (latency period, 2–3 years), antimalar- consensus meeting: part 1. viral infections and etiopatho- ial agents, angiotensin-converting enzyme inhibitors genesis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. (latency period, 3–6 months), angiotensin II recep- 2005;100:40-51. tor blockers, nonsteroidal anti-inflammatory drugs, 5. Birkenfeld S, Dreiher J, Weitzman D, et al. A study benzothiadiazides, beta-blockers (latency period, on the association with hepatitis B and hepatitis C in 1 year), statins, tumor necrosis factor a inhibitors, 1557 patients with lichen planus. J Eur Acad Dermatol and more.6,11-14 When lichenoid drug eruptions are Venereol. 2011;25:436-440. suspected, the most important step is to discontinue 6. Shiohara T, Kano Y. Lichen planus and lichenoid der- the medication; however, resolution is slow and may matoses. In: Bolognia JL, Jorizzo JL, Schaffer JV, eds. take several months to up to 1 year. I have seen . 3rd ed. Philadelphia, PA: Elsevier Saunders; 2 unpublished cases of lichenoid drug eruptions due to 2012:183-202. the use of statins. In both cases, the eruption was gen- 7. Katzenelson V, Lotem M, Sandbank M. Familial lichen eralized and the statins had been initiated more than planus. Dermatologica. 1990;180:166-168. 5 months prior to presentation. It is a crafty entity, as 8. Mahood JM. Familial lichen planus. a report of nine cases there is a loss of temporality andCUTIS slow improvement. from four families with a brief review of the literature. Arch Dermatol. 1983;119:292-294. Conclusion 9. Sodaify M, Vollum DI. Familial lichen planus. a case When I first started in dermatology, I had no idea report. Br J Dermatol. 1978;98:579-581. there were so many variants of LP, and the informa- 10. Botelho LF, Magalhães JP, Ogawa MM, et al. Generalized tion provided here is not an exhaustive list. When lichen nitidus associated with Down’s syndrome: case faced with a patient with an unknown eruption, it is report. An Bras Dermatol. 2012;87:466-468. helpfulDo to determine if the eruptionNot is lichenoid. If 11. HalevyCopy S, Shai A. Lichenoid drug eruptions. J Am Acad so, you must identify the type of dermatosis. Having Dermatol. 1993;29(2, pt 1):249-255. knowledge of the many types and faces of lichenoid 12. Pua VS, Scolyer RA, Barnetson RS. Pravastatin-induced dermatoses enables recognition of atypical versus lichenoid drug eruption. Australas J Dermatol. 2006;47:57-59. usual presentations. If you do not know about a dis- 13. Ruiz Villaverde R, Blasco Melguizo J, Linares Solano J, ease, you will not diagnose it. et al. Lichen planus-like eruption due to enalapril. J Eur Acad Dermatol Venereol. 2003;17:612-614. REFERENCES 14. Asarch A, Gottlieb AB, Lee J, et al. Lichen planus-like 1. Iijima W, Ohtani H, Nakayama T, et al. Infiltrating CD8 eruptions: an emerging side effect of tumor necrosis T cells in oral lichen planus predominantly express CCR5 factor-a antagonists. J Am Acad Dermatol. 2009;61: and CXCR3 and carry respective chemokine ligands 104-111.

WWW.CUTIS.COM VOLUME 90, SEPTEMBER 2012 E3 Copyright Cutis 2012. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher.