Linear hyperpigmentation with extensive epidermalapoptosis: A variant of linear lichen planus pigmentosus?

Atsushi Akagi, MD, Yoshihiro Ohnishi, MD, Shingo Tajima, MD, and Akira Ishibashi, MDTokorozawa, Japan

We report 3 female patients who rapidly developed pigmented patches in a linear arrangement. Histologically there was minimumepidermal basal cell damage and bandlike lymphocyte infiltration in the dermis, but focal massive apoptotic materials positivelystained with antikeratin antibody were prominently seen in the papillary and subpapillary dermis. We considered these cases as avariant of linear lichen planus pigmentosus with unique histologic change of severe epidermal apoptosis. These histologic features mayrepresent a severe apoptotic change in the end stage of lichenoid tissue reaction. (J Am Acad Dermatol 2004;50:S78-80.)

L ichen planus pigmentosus is a rare variant of lichen pla-nus and appears as hyperpigmented, dark brown, occa-sionally pruritic macules, papules, or both with a non-

characteristic distribution that predominates in exposed areasand flexor folds.1,2 Linear and zosteriform lichen planus, ofwhich lesions follow Blaschko’s line, have been reported andconsidered as a subtype of lichen planus.3-5 Linear lichen planuspigmentosus, the combined type of lichen planus pigmentosusand linear lichen planus, is quite rare and, to our knowledge,only a few cases have been reported.6-8

Lichen planus is a persistent lymphocyte-mediated immuno-logic disorder in which basal keratinocytes appear to be thetargets of T lymphocytes. T lymphocytes are thought to mediatedeath of basal keratinocytes resulting in the formation of colloidor Civatte’s bodies in the lower epidermis and papillary dermis.Such histologic changes are referred to as lichenoid tissue reac-tion.9-11

Here we report 3 cases of linear lichen planus pigmentosus.They showed unique histologic features with severe apoptoticchange of epidermis but without apparent vacuolar degenera-tion of basal cells or lymphocyte infiltration in the papillarydermis.

CASE REPORTSCase No. 1 was that of a 32-year-old woman, presenting a

2-mouth history of brownish macules without subjective symp-toms, which appeared first on the right buttock then graduallyextended to the right leg. On examination, the ashy brownmacules in a zosteriform or linear distribution were observedfrom the right lumbar region to the flexor aspect of the leg (Fig1, a). She had experienced a gastric ulcer and underwent gas-

This supplement is made possible through an unrestrictededucational grant from Stiefel Laboratories to the AmericanAcademy of Dermatology.

From the Department of Dermatology, National Defense Medical CollegeFunding sources: None.Conflicts of interest: None identified.Reprint requests: Atushi Akagi, MD, Department of Dermatology, National

Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513,Japan. E-mail: grd1401@gr.ndmc.ac.jp.

0190-9622/$30.00© 2004 by the American Academy of Dermatology, Inc.doi:10.1016/j.jaad.2003.11.067

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trectomy at age 30 years and surgical resection of ovarian cyst atage 31 years. She had been taking an antihistamine drug forbronchial allergic rhinitis for 5 years. Routine laboratory dataincluding peripheral blood cells and liver function were normal.

Case No. 2 was that of a 22-year-old healthy female medicalstudent. She presented asymptomatic gray macules on her rightshoulder and upper aspect of her arm with a 1-month history.New lesions appeared on the forearm, then on the lumbarregion. On examination the ashy brown pigmented maculeswere found from the right scapular region to the upper aspect ofher arm in a linear distribution and a group of those pigmentedmacules formed speckled lesions on the right buttock. In someareas, pinhead-sized brown papules were seen in the pigmentedfleck (Fig 1, b). She had taken no particular medicine during thepast 6 months. Routine laboratory data including peripheralblood cells and liver function were within normal limits.

Case No. 3 was that of a 30-year-old woman on whom rightshoulder pigmented patches appeared 1 year earlier. Physicalexamination denoted small dark brown or grayish brown mac-ules in a linear or zosteriform distribution from her right shoulderto the upper aspect of her arm and forearm. The patient hadtaken no medications during the previous 2 years expect antibi-otics and anti-inflammatory drugs (unknown ingredients) forcommon cold for 1 week. Laboratory examination was normalexcept anemia (hemoglobin 9.7 mg mL�1 and hematocrit 31.5%;normal ranges 11.4-14.7 mg mL�1 and 34.2-44.1%, respectively).

Histology and immunohistochemistryHistopathologic findings of the biopsied specimens from 3

patients were essentially similar. There were densely aggregatedeosinophilic bodies beneath the epidermis. No apparent vacuo-lar degeneration in the basal layer was recognized. Bandlike cellinfiltration was not observed, although a slight cell infiltration oflymphocytes, spindle cells, and melanophages was found in thepapillary dermis (not shown). The eosinophilic bodies werepositive with periodic acid�Schiff (PAS) staining, and weresurrounded by PAS-positive remnant basement membrane (Fig2, a). They looked like denatured epidermal rete ridge damagedby apoptotic change (Fig 2). The amyloid staining with Congored, Dylon dyes, and thioflavin T fluorescence were negative(not shown). Paraffin-embedded sections were incubated for24 hours with antikeratin antibody (clone AE1, monoclonal,Boehringer Mannheim Biochemicals, Indianapolis, Ind) at1:50 dilution, antiamyloid AA protein antibody (monoclonal

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antibody, Dako, Glostrup, Denmark) at 1:50 dilution, or an-ti-�- or �-light chain (monoclonal, Zymed Laboratories, SouthSan Francisco, Calif) at 1:10 dilution, then reacted with anti-mouse immunoglobulin at 1:500 dilution for 1 hour. Antigen-antibody complex was visualized by avidin-biotin complex.Immunohistochemical studies indicated that the eosinophilicbodies were immunoreactive with keratin (Fig 3), whereas

Fig 1. a, Case 1. Clinical appearances. Brown pigmentation following Blpapules on right shoulder.

Fig 2. Immunohistochemistry of lesional skin. Eosinophilic bodieswere immunoreactive with antikeratin antibody in cases 1 (a) and 2 (b).Basal layer of epidermis is also positive. (a and b, Antikeratin antibody(clone AE1, monoclonal); a and b, original magnification �100.)

antibodies for amyloid AA protein and �- or �-light chain werenegative (not shown).

DISCUSSIONOn the basis of clinical and histopathologic findings, we

diagnosed our cases as linear lichen planus pigmentosus. His-tology of these cases is atypical for lichen planus and is unique

Fig 3. Immunohistochemistry of lesional skin. Eosinophilic bodieswere immunoreactive with antikeratin antibody in cases 1 (a) and 2 (b).Basal layer of epidermis is also positive. (a and b, Original magnification�100.)

o’s lines is noted from right buttock to right leg. b, Case 2. Pinhead-sized

aschk

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for the (1) occurrence of massive eosinophilic materials in thepapillary dermis, (2) lack of mononuclear cell infiltration orbandlike cell infiltration in the dermis, and (3) lack of apparentvacuolar degeneration of epidermal basal cells. The eosinophilicbodies in the papillary dermis were found to be negative forvarious amyloid stainings and positive for antikeratin antibody,indicating that they are originated from apoptotic change ofepidermal keratinocytes. However, unlike a typical Civatte bodyresulting from epidermal basal cell damage, they appeared largerand more massive, and sometimes looked like whole epidermalrete ridges having undergone an apoptotic change (Fig 2). Thisis supported by PAS stain, which showed PAS-positive remnantbasement membrane around massive apoptotic bodies (Fig 2,a). The severe apoptotic change of keratinocytes in our casesmay be considered to represent an end stage of lichenoid tissuereaction lacking an initial inflammatory stage.

Apoptosis is considered to be mediated by cytotoxic T lym-phocytes in which target cells show rapid nuclear damage andDNA fragmentation. Cytotoxic T lymphocyte–mediated attack onepidermal cells could be a primary event in lichenoid tissuereaction seen in lichen planus. The intensity of keratinocyteapoptosis in these cases was more pronounced than in ordinarylichen planus. It is uncertain what factor or factors may deter-mine the intensity and extension of apoptosis. A case of lichenplanopilaris, pseudopelade, with a massive apoptosis of theepidermal sheath of the hair follicles has been reported.12 Inpseudopelade, clinical examination of the skin often fails toreveal inflammatory signs. Our cases similarly showed linearpigmentation without an apparent inflammatory sign at theironset. It will be postulated that a different apoptotic pathwaymay operate in the cases of pseudopelade and ours, resulting inthe unusual and pronounced apoptotic reaction.

The linear lesions in our cases seem to follow the lines ofBlaschko. A number of skin diseases such as congenital, nevoid,and acquired skin diseases may follow Blaschko’s lines. Blasch-ko’s lines are thought to reflect T-lymphocyte migration andclonal expansion during embryogenesis of the skin. The genetic

mosaicism in an acquired Blaschko-linear inflammatory derma-tosis could be responsible for cutaneous antigenic mosaicismthat may induce mosaic T-cell response by the triggers of viralinfection or drug.13,14 Severe apoptotic change in our cases maybe responsible for the response of mosaic T cells present alongBlaschko’s lines.

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