Lichen Planus and Lichen Nitidus 24
24.1
Lichen Planus
Like psoriasis, lichen planus is a worldwide disease.
The prevalence is about 1% of the general population.
There are no race or sex differences and no genetic disposition. It appears most often between 30 and 60 years of age, but children and older persons may also be affected (Daoud and Pittelkow 1999a).
24.1.1
Clinical Appearance
The disease starts insidiously, progresses slowly and remains delimited. While older lesions resolve and wane, new lesions appear. If no treatment is given, le- sions usually recede and vanish after a couple of years.
Sometimes one or several lesions become chronic and hypertrophic. Rarely an acute and more or less gener- alized form may appear.
All parts of the skin, including the palms, soles, scalp, hair and nails, and genital and oral mucous membranes, may be involved; predilection sites are the ventral part of the wrists, ankles, and the buccal mucosa. Usually the lesions are severely, and some- times unbearably itching. However, occasionally itch is lacking. Oral lesions are most often located on the buccal mucosa, but also the gingiva, tongue and lips may be affected. Ulcerated, erosive, oral lichen is pain- ful and may be disabling.
The primary efflorescence is a flat, polygonal and reddish papule with a violaceous hue. Papules that may be of different sizes coalesce to plaques, the sur- face of which is crowned with a white and delicate net- work of lines. Sometimes annular lesions occur due to central clearing of the plaques. Papules can be trig- gered by mechanical injury, the Köbner phenomenon.
If scratching is the cause of the injury, the lesion may be linear. Due to different locations and development of the lesions they may become atrophic, vesicular, bullous, ulcerated (erosive) or hypertrophic. In lichen follicularis mainly hair follicles are affected. In the scalp, lichen follicularis may cause patchy hair loss or
scarring alopecia as the only sign of the disease (Meh- regan et al. 1992)
24.1.2
Histopathologic Appearance
A typical lesion shows a dense, band-like infiltrate of lymphocytes that is strictly confined to the subepider- mal area. The lymphocytes attack and destroy the basic part of the epidermis, giving rise to characteristic saw- tooth-like rete ridges and often to deposition of a large number of apoptotic bodies at the epidermal–dermal interface. However, the remaining part of the epider- mis is also affected. Here the cells are only slightly stained, are sometimes vacuolated, and many of them have no nucleus; this is in contrast to the usually better preserved cells of the granular cell layer, which may even be hypertrophic. Scattered apoptotic bodies are also seen in the epidermis, but no or only scattered lymphocytes. The horny layer is thickened and never parakeratotic (Fig. 24.1).
If the process advances further, the epidermis gradually disintegrates from the base towards the surface and a cleft appears between the flattened epidermis and dermis. This is atrophic lichen (Fig. 24.1c). Finally, a subepidermal vesicle or bulla, and even ulceration, may occur. The roof of vesicles and bullae consists of a thickened horny layer and scattered disintegrating granular cells, and the floor of lymphocytes and a variable number of apoptotic bodies (Fig. 24.1d).
Apoptotic bodies in the dermis are eosinophilic and slightly PAS-positive; those in the epidermis are PAS-negative. Apoptotic bodies in the dermis may be- come coated with IgM (Abell et al. 1975; Mehregan et al. 1992; Boyd 1996). This may explain why they are PAS-positive in the dermis but not in the epidermis.
The cell infiltrate in the dermis consists of lympho- cytes with an admixture of some mast cells and mac- rophages; there is also a variable amount of melanin pigment which has leaked from the injured epidermis.
There are no plasma cells or eosinophils.
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Fig. 24.1 Lichen planus. a The epidermis is pale, has few nuclei, sawtooth rete ridges, a thickened nonparakeratotic horny layer, and apoptotic bodies at the epidermal–dermal interface (arrow- heads).b There are also vacuolated keratinocytes and scattered intraepidermal apoptotic bodies (arrows). The granular cell layer is accentuated. c Atrophic lichen. There is a cleft between the flat epidermis and the band-like cell infiltrate. Note the apoptotic bodies along the cleft (arrowheads).d Vesicular lesion. The roof consists of a thickened horny layer and scattered disintegrating keratinocytes, the floor of a broad band of apoptotic bodies. The lumen contains red blood cells. e Buccal lesion. The pale epithe- lium has sawtooth-like rete ridges (arrows), a distinct granular layer, and a thickened horny layer. H&E
24.1 Lichen Planus
Fig. 24.2 Lichen hypertrophicus and lichen follicularis. a The hair follicle is hypertrophic, markedly widened and filled with nonparakeratotic keratin. The stratum granulosum is thick- ened and the cells are stuffed with large granules. In the area indicated (arrows) there are several apoptotic bodies. The dense lymphocytic cell infiltrate appears to gnaw at and is destroying
the basic part of the epithelium. b Close-up of the area indicated (arrows) in a shows four large apoptotic bodies just above the interface. c In addition to follicular hypertrophy the epidermis is also thickened and shows elongated sawtooth-like rete ridges.
d The typical band-formed lymphocytic cell infiltrate is con- fined to the follicles. H&E
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In hypertrophic and follicular lichen, both epidermis and follicles or only follicles are hypertro- phic (Fig. 24.2). The follicles are enlarged and widened and filled with nonparakeratotic keratin and the gran- ular layer is accentuated. As in common lichen planus, there is a band-like lymphocytic cell infiltrate that ap- pears to gnaw at and destroying the basal part of the follicular epithelium. If only follicles are involved the inflammatory cell infiltrate is more or less confined to the follicular area.
Oral lesions, if not erosive, show the same histo- pathologic pattern as those of the skin (Fig. 24.1e).
Thus there are hyperkeratosis and a granular cell layer, not normally present in the buccal mucosa (compare Fig. 29.6a). Oral erosive (ulcerated) lichen planus is often a difficult histologic diagnosis because the ulcer- ation and dense inflammatory cell infiltrate disguise the typical changes of lichen. In nonulcerated lesions, to establish the typical pattern of lichen demonstrated in Fig. 24.1e is a requirement for the diagnosis.
24.1.3 Pathogenesis
The cause of lichen planus is not known; however, it is generally thought that the mechanism is an immuno- logic reaction. Recent investigations have shown that the cell infiltrate in active lichen planus lesions con- tains a high number of CD8+ (i.e., cytotoxic T cells) and that some CD8+cells secrete granzyme B granules (see Glossary) and induce apoptosis of the keratino- cytes (Akasu et al. 1993: Gadenne et al. 1994; Shimizu et al. 1997). Also the presence of Langerhans cells is increased. These findings indicate that lichen planus may be a type IV hypersensitivity reaction mediated by sensitized CD8+ cells.
24.1.4
Differential Diagnosis
• Drugs and chemicals can provoke lichenoid lesions both in the skin and the oral mucosa. The presence of eosinophils in the inflammatory cell infiltrate and/or parakeratosis indicates a drug reaction. Fig- ure 24.3 demonstrates a lichenoid lesion caused by handling the color-developing agent CD-2 (a de- rivate of p-phenylenediamine). In some areas the appearance is lichenoid, in others that of chronic dermatitis. The chemical may be introduced to the body by inhalation, ingestion or absorption through the skin (Lidén and Brehmer-Andersson 1988).
• Chronic graft-versus-host disease may be difficult to differentiate histologically from lichen planus. As always it is important to know the case history.
• Chronic lupus erythematosus may be similar to li- chen atrophicus. Both types of lesion show atrophy of the epidermis and scattered epidermal apoptotic bodies. However, a large number of apoptotic bod- ies at the epidermal–dermal interface indicates li- chen planus.
• Paraneoplastic pemphigus may be both clinically and histologically similar to lichen planus (Sect.
25.3).
• Lichenoid mycosis fungoides (synonyms, among others, are poikiloderma atrophicans vasculare, and parapsoriasis lichenoides) is a chronic condi- tion which after many years ends up as mycosis fungoides. Earlier stages show a more or less band- like lymphocytic cell infiltrate close to an atrophic epidermis. The cell infiltrate consists mainly of small and normal looking lymphocytes, a fair num- ber of which migrate into the dermis. In contrast to lichen planus there are also a variable number of somewhat larger and more compact cells (atypi- cal lymphocytes). These cells may be found both in the dermal cell infiltrate and in the epidermis, but are most easily seen in the epidermis. There are no apoptotic bodies.
• Lichen planus pemphigoides is an autoimmune sub- epidermal bullous disease. Bullae occur both on li- chenoid plaques and on otherwise unaffected skin.
Fig. 24.3 Lichenoid lesion. The epidermis is flattened and has two sawtooth-like rete ridges. Located close to the epidermis there is a large conglomeration of apoptotic bodies, diffusely infiltrated by lymphocytes. H&E (reproduced from Lidén and Brehmer-Andersson 1988, with permission)
24.1 Lichen Planus
It is provoked by autoantibodies directed against a glycoprotein in the hemidesmosomes (Fig. 25.1) and has nothing to do with lichen planus (Zillikens et al. 1999)
24.2
Lichen Nitidus
Lichen nitidus is much less common than lichen pla- nus. The two diseases have some similarities, both clinically and histologically, and have been observed concurrently in the same patient. It has therefore been seriously discussed as to whether they are variations of one disease or two different dermatoses. The latter view prevails (Daoud and Pittelkow 1999b).
24.2.1
Clinical Appearance
The primary efflorescence is a pinpoint- to pinhead- sized, dome-shaped, flesh-colored, shiny papule. Pap- ules may be closely set, but do not coalesce. Eruptions can be generalized, but are usually confined to one or several areas. Predilection sites are the forearms, penis, abdomen, chest and buttocks. Also the oral mucosa may be affected. Usually eruptions do not itch. The disease is self-limiting.
24.2.2
Histopathologic Appearance
The lesion consists of a small, well-circumscribed gran- uloma located in a dermal papilla between elongated rete ridges. The epidermis between the elongated rete ridges is flattened and hyperkeratotic, but usually not parakeratotic. Sometimes there is a cleft between the flattened epidermis and the granuloma. The granu- loma is composed of histiocytes, a few multinucleated giant cells of Langhans type, and lymphocytes. Apop- totic bodies are not observed.
24.2.3 Pathogenesis
Both the etiology and pathogenesis of lichen nitidus are unknown. An immunophenotypic investigation made on three patients with lichen nitidus showed that the cell infiltrate contained a high number of Langer- hans cells, and that the lymphocytes mainly consisted of CD4+ cells (Wright et al. 1990). These findings were then thought to be characteristic also of lichen planus.
However, as already mentioned above, recent investi-
gations have shown that most lymphocytes in active lichen planus lesions are CD8+ cells. Furthermore, in lichen nitidus apoptotic bodies are lacking and the cell infiltrate is granulomatous, but mainly lymphocytic in lichen planus. Presumably both diseases are due to a type IV hypersensitivity reaction, but the pathways are different. Thus in lichen nitidus the lesions are ini- tiated by sensitized CD4+ cells and in lichen planus by sensitized cytotoxic CD8+ cells.
24.2.4 Example
Case 1. Lichen Nitidus
A 29-year-old man had observed non-itching pap- ules on the upper extremities and the penile shaft for 6 months. A biopsy specimen taken from the arm showed a typical granuloma described above (Fig. 24.4).
References
Abell E, Presbury DGC, Marks R, Ramnarain D (1975) The diagnostic significance of immunoglobulin and fibrin de- position in lichen planus. Br J Dermatol 93:17–24
Akasu R, From L, Kahn HJ (1993) Lymphocyte and macro- phage subsets in active and inactive lesions of lichen planus.
Am J Dermatopathol 15:217–223
Boyd AS (1996) Update on the diagnosis of lichenoid der- matitis. Adv Dermatol 11:287–316
1.
2.
3.
Fig. 24.4 Lichen nitidus. The small and strictly confined le- sion is hugged by slightly elongated rete ridges and covered by a flat epidermis with a thickened, nonparakeratotic horny layer.
Centrally there is a cleft between the epidermis and the dermal infiltrate, which consists of lymphocytes, histiocytes, and multi- nucleated giant cells. H&E
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Daoud MS, Pittelkow MR (1999a) Lichen planus. In: Freed- berg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SI, Fitzpatrick TB (eds) Fitzpatrick’s dermatology in general medicine. McGraw-Hill, New York, pp 561–577
Daoud MS, Pittelkow MR (1999b) Lichen nitidus. In: Freed- berg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SI, Fitzpatrick TB (eds) Fitzpatrick’s dermatology in general medicine. McGraw-Hill, New York, pp 577–581
Gadenne A-S, Strucke R, Dunn D, Wagner M, Bleicher P, Bigby M (1994) T-cell lines derived from lesional skin of lichen planus patients contain a distinctive popula- tion of T-cell receptor γδ-bearing cells. J Invest Dermatol 103:347–351
Lidén C, Brehmer-Andersson E (1988) Occupational der- matoses from colour developing agents. Acta Derm Vene- reol 68:514–522
4.
5.
6.
7.
Mehregan DA, Van Hale HM, Muller SA (1992) Lichen pla- nopilaris: clinical and pathologic study of forty-five patients.
J Am Acad Dermatol 27:935–942
Shimizu M, Higaki Y, Higaki M, Kawashima M (1997) The role of granzyme B-expressing CD8-positive T cells in apoptosis of keratinocytes in lichen planus. Arch Dermatol Res 289:527–532
Wright AL, Mcvittie E, Hunter JAA (1990) An immu- nophenotypic study of lichen nitidus. Clin Exp Dermatol 15:273–276
Zillikens D, Caux F, Mascaro JM Jr, Wesselmann U, Schmidt E, Prost C, Callen JP, Bröcker E-B, Diaz LA, Giudice GJ (1999) Autoantibodies in lichen planus pemphigoides react with a novel epitope within the C-terminal NC16A domain of BP180. J Invest Dermatol 113:117–121
8.
9.
10.
11.
References
