Lichen planus and chronic graft-versus-host reaction. In situ identification of immunocompetent cell phenotypes

The purpose of the present study was lo examine the phenotype of the cutaneous immunocompetent cells in lichen planus and chronic graft versus host (GVH) reaction infiltrates, by the use of monoclonal antibodies directed against T cell populations and Langerhans cells.
Our results in lichen planus suggest an immunological reaction similar to the delayed hypersensitivity reaction, including all the immunocompetent cell sub-populations, with a first stage of antigenic information by Langerhans cells (OKT6 +, BL6 +, HLA-DR+) and helper cells, and a second stage mediated by suppressor/cytotoxic cells.
The results from the study of GVH reaction also suggest an effect mediated by suppressor/cytotoxic cells (OKT3+, OKT4−, OK.T8+, HLA-DR+).
Our results favour the existence of a lymphocytotoxic process in lichen planus and chronic GVH reaction.     

Expression of CD36 (OKM5) antigen on epidermal cells in normal and diseased skin

The expression of the CD36 (OKM5) antigen was studied with the PAP technique on sections of skin from healthy subjects and of normal and diseased skin from patients with various skin diseases. In specimens from healthy subjects the antigen was found on vascular and perivascular structures and in some cases it was seen on cells of the acrosyringium. A net-like pattern of CD36 was observed in the upper part of the stratum spinosum in skin lesions of patients with psoriasis, lichen planus, pityriasis rosea, morbilliform drug reactions, necrobiosis lipoidica, lichen amyloidosus, Darier's disease and ichthyosis vulgaris. Expression of CD36 was also seen in the nonlesional skin just below the granular layer in 3 of 5 patients with factitial urticaria with immediate dermographism, but not in delayed dermographism or chronic urticaria. In ichthyosis vulgaris CD36 was also expressed in dendritic cells of the basal layer and in a patient with a graft versus host reaction it was recognized both on scattered keratinocytes and on dendritic cells in the epidermis. The role of the expression of the CD36 antigen in the skin is unknown. The activated cells might possibly serve as antigen-presenting cells and/or have a modulatory influence on an inflammatory reaction.     

GRAFT VERSUS HOST REACTION

A 27-year-old man with acute lymphocytic leukemia (ALL) received a bone marrow transplant (BMT). On day 27, he developed erythematous maculopapular lesions all over his body. This rash improved within a month. Histological findings were obtained comparing those of the graft versus host reaction (GVHR). Five months later, he developed macular lesions on his body, clinically suggestive of lichen planus. Histologically, it was also compatible with lichen planus. He exhibited the grade I changes of acute GVHR described in Lerner's classification, and lichen planus-like eruptions as the chronic form.     

Ia-like antigens in lichen planus

The occurrence of Ia-like antigens in the skin of patients with lichen planus was studied by an indirect immunofluorescence (IIF) technique with use of immunosorbent-purified anti-Ia antibodies. Normal skin from the patients and skin from healthy persons showed dermal histiocytes and epidermal suprabasal dendritic cells expressing these antigens. In lichen planus lesions Ia-like antigens were found on virtually all mononuclear cells in the dermal infiltrate and showed an intercellular pattern in the epidermis. The finding of cells expressing Ia-like antigens in the dermal infiltrate, most probably activated T lymphocytes, renders likely a cell-mediated type of reaction in the pathogenesis of lichen planus.     

Lichen planus remission is associated with a decrease of human herpes virus type 7 protein expression in plasmacytoid dendritic cells

The cause of lichen planus is still unknown. Previously we showed human herpes virus 7 (HHV-7) DNA and proteins in lesional lichen planus skin, and significantly less in non-lesional lichen planus, psoriasis or healthy skin. Remarkably, lesional lichen planus skin was infiltrated with plasmacytoid dendritic cells. If HHV-7 is associated with lichen planus, then HHV-7 replication would reduce upon lichen planus remission. HHV-7 DNA detection was performed by nested PCR and HHV-7 protein by immunohistochemistry on lesional skin biopsies from lichen planus patients before treatment and after remission. Biopsies were obtained from lichen planus lesions before treatment (n = 18 patients) and after remission (n = 13). Before treatment 61% biopsies contained HHV-7 DNA versus 8% after remission (P = 0.01). HHV-7-protein positive cell numbers diminished significantly after remission in both dermis and epidermis. Expression of HHV-7 was mainly detected in BDCA-2 positive plasmacytoid dendritic cells rather than CD-3 positive lymphocytes. HHV-7 replicates in plasmacytoid dendritic cells in lesional lichen planus skin and diminishes after remission. This study further supports our hypothesis that HHV-7 is associated with lichen planus pathogenesis.     

A distinctive eruption in patients receiving oxprenolol

We describe an eruption with distinctive clinical and histological features which occurred in four patients during oxprenolol treatment and cleared following withdrawal of the drug. Certain similarities to the eruption occurring during treatment with the beta blocking drug practalol were noted. The histological appearances are compared with the changes seen in lichen planus, lupus erythematosus and the graft versus host reaction.     

The effects of experimental skin damage in patients with lichen planus

Experimental scratching induced phloxinophilic eosinophilic bodies in unaffected skin of ten patients with active lichen planus. This reaction was inhibited by concomitant local injection of methylprednisolone acetate and could not be induced in patients with inactive lichen planus, in patients with other dermatoses, nor in healthy subjects. The findings are consistent with a viral aetiology for lichen planus.     

Behandlung des therapieresistenten erosiven,oralen Lichen ruber mit extrakorporaler Photopherese (ECP)

Background: Erosive, oral lichen planus is typically therapy‐resistant. Histologically and immunopathologically there are many similarities between lichen planus and lichenoid graft versus host disease (GvHD). Extracorporeal photopheresis (ECP) therapy has been shown effective in GvHD in several publications; only one study addresses its use in chronic erosive lichen planus. Patients and Methods: Four patients with erosive oral lichen planus were treated. Therapy was performed on two consecutive days (therapy cycle) every two weeks. Following clinical improvement, the therapy intervals were prolonged. Results: In all four patients clinical symptoms and mucosal lesions improved after seven to nine therapy cycles. A temporary worsening occurred in two patients following dental procedures. One of those patients still requires regular ECP therapy. Two patients discontinued therapy following nearly complete remission for other reasons. One patient stopped therapy after 19 cycles of ECP therapy and has remained in complete remission for 9 months. No side effects were seen during treatment. Conclusions: Extracorporeal photopheresis is an effective therapeutic option for the treatment of erosive oral lichen planus, especially due to the lack of side effects in contrast to other established therapies. Adjunctive topical treatment is also required.     

Superficial mucoceles and lichenoid graft versus host disease: report of three cases

Superficial mucoceles are subepithelial extravasations of sialomucin that occur at the epithelial-connective tissue interface and are directly related to minor salivary glands. They have been described in association with oral lichen planus and, exceptionally, with chronic graft versus host disease. Three patients who underwent an allogeneic bone marrow transplantation for a chronic myelogenous leukaemia presented multiple superficial mucoceles and an oral lichenoid graft versus host disease.     

The specificity and cellular origin of phenylethanolamine N-methyltransferase (PNMT)-like immunoreactivity in psoriatic skin

Phenylethanolamine N-methyltransferase (PNMT)-like immunoreactivity has been found in psoriatic skin and in this study, PNMT-like immunoreactivity was investigated in the involved and uninvolved skin of six patients with lichen planus and four patients with lichen simplex. No PNMT immunoreactivity was observed in these diseases. Studies were carried out using cultured fibroblasts from two patients with psoriasis from uninvolved and involved areas of skin and from two controls using antibodies to PNMT, as well as antibodies to the chemical messengers somatostatin, substance P, parathyroid hormone and peptide histidine isoleucine amide. No immunoreactivity to these substances was found, and fibroblasts are unlikely to be the cellular origin of the PNMT-like immunoreactivity as seen in psoriatic skin.     

Lichen planus and malignancy. An epidemiologic study of 2071 patients and a review of the literature

The literature contains 36 reports of squamous cell cancer associated with lichen planus, and several reports on increased frequency of oral cancer in patients with oral lichen planus. To examine the risk of malignant transformation, 2071 patients with lichen planus were followed up for an average of 9.9 years. Only eight squamous cell carcinomas were observed in this population after the first visit for lichen planus, producing a morbidity ratio of 1.0 (95% confidence interval, 0.9 to 1.2). Significant increase for oral cancer was observed in male subjects, with a morbidity ratio of 5.9 (95% confidence interval, 2.5 to 11.4). This study indicates that patients with cutaneous lichen planus do not carry an increased risk of malignant transformation of the skin lesions or internally; however, there is increased risk of oral cancer.     

Mucosal vulval lichen planus: outcome, clinical and laboratory features

BACKGROUND: Mucosal lichen planus of the vulva is a rare but increasingly recognized condition. It has potentially severe complications such as fusion of the labia and vagina; the risk of developing squamous cell carcinoma (SCC) may be increased. An association between hepatitis B and C infection and skin or oral lichen planus appears to exist in certain geographical areas. OBJECTIVE: To investigate the course of mucosal vulval lichen planus, its response to treatment and associated laboratory features. SUBJECTS AND METHODS: Forty-four women with mucosal vulval lichen planus were studied between 1997 and 2000 and laboratory data were collected. RESULTS: Thirty of 44 patients had additional oral lesions, only nine had cutaneous findings compatible with lichen planus. We did not find an association with antibodies to hepatitis B or C virus in this British study population. All women were treated with potent to very potent topical corticosteroids; however, in the majority of patients symptoms persisted. In seven (16%) patients vulval lichen planus was in remission after a disease duration between 2 and 18 years (mean 10.6 years). One patient developed a vulval SCC. CONCLUSIONS: Screening for hepatitis B and C in women with mucosal vulval lichen planus in the UK seems unnecessary. We recommend long-term follow-up, and that all non-healing ulcerative and papular lesions should be biopsied.     

Hepatitis C virus infection prevalence in lichen planus: examination of lesional and normal skin of hepatitis C virus-infected patients with lichen planus for the presence of hepatitis C virus RNA

Hepatitis C virus (HCV) is the main cause of parenterally transmitted non-A, non-B viral hepatitis. In recent years, a significant association between lichen planus and chronic HCV infection has been reported. Anti-HCV antibody status was evaluated by ELISA in 54 patients with lichen planus and 54 patients with minor dermatological disorders. PCR was used to examine HCV RNA from serum and lesional and nonlesional cutaneous biopsy samples of HCV-infected patients. Seven patients with lichen planus (12.9%) and two patients in the control group (3.7%) were anti-HCV antibody positive. Five out of seven patients with anti-HCV antibodies had demonstrable HCV RNA in lesional skin biopsies. The viral RNA was absent in three out of four patients with lichen planus whose serum samples were positive for HCV RNA and agreed to biopsy of nonlesional skin. The prevalence of HCV infection is not increased in Turkish patients with lichen planus. However our findings suggest that the virus may play a potential pathogenic role by replicating in cutaneous tissue and triggering lichen planus in genetically susceptible HCV-infected patients.     

Quantitative analysis of contact sites between mast cells and sensory nerves in cutaneous psoriasis and lichen planus based on a histochemical double staining technique

Summary The aim of the present study was to test further our previous hypothesis that the inflammatory reaction in psoriasis is neurogenic. For this purpose, contact sites between mast cells and sensory nerves were morphometrically analysed in the basement membrane zone, papillary dermis and three dermal zones of lesional/non-lesional psoriatic and lichen planus skin as well as in healthy control skin. The analyses were made on sections stained with a histochemical double stain developed for this study. With the double stain, active mast cell tryptase was stained blue enzyme histochemically, and the sensory nerves black using specific monoclonal anti-neurofilament antibodies with immunogold. In psoriatic lesions, both mast cells and mast cell — nerve contacts were markedly more frequent in the basement membrane zone and in the papillary dermis when compared with the corresponding areas in the other groups. Mast cell numbers were increased in both lesional and symptom-free skin in lichen planus, but no increase was found in the mast cell — nerve contacts. Increased contacts between mast cells and sensory nerves indicate that the elements exist for neurogenic inflammation in psoriatic lesions. These increased contacts are not due to the extensive inflammatory reaction only, because they were not observed in lichen planus lesions.     

Peptic ulcer and Helicobacter pylori in patients with lichen planus

The aetiology of lichen planus is unknown, but it is often connected with infections. In recent years peptic ulcer disease has also been closely linked with an infectious agent, Helicobacter pylori. A case-control study was conducted in 78 patients with lichen planus to find out a previous history of peptic ulcer disease, using a questionnaire and a medical record review. Patients were also asked about family history in first- and second-degree relatives. Fifty-seven patients with other skin diseases were interviewed as controls. The prevalence of H. pylori infection in patients with lichen planus was compared to that of 39 patients with other skin diseases and to the overall prevalence rates of H. pylori infection in Finland. Our findings are consistent with an approximately three-fold increased risk of peptic ulcer in patients with chronic/repeating lichen planus, when compared to the control patients (p = 0.04) and also to the overall peptic ulcer prevalence rates in Finland. Forty-one percent of the patients with chronic/repeating lichen planus had a first- or second-degree family member with a peptic ulcer, while the corresponding rate in the control group was only 12% (p=0.003). The prevalence of H. pylori infection in patients with chronic/repeating lichen planus and transient lichen planus was not significantly different from that in patients with other skin diseases.     

Coexistence of lichen planus and bullous pemphigoid (an immunofluorescence study of a "lichen pemphigoides") (author's transl)]

A 35 year old black man presented with a generalized eruption of lichen planus; subsequently tense blisters appeared within the lichenoid lesions and on clinically normal skin. Histopathological characteristics of lichen planus were present in the papules, and those of bullous pemphigoid were seen in the bullae taken from non-lichenoid skin. Direct immunofluorescence studies revealed immunological characteristics of lichen planus in skin and mucosal lesions of L. P. Bound IgG and beta1 C/beta1 A with tubular patterns were detected at the dermo-epidermal junction in all the skin fragments (clinically normal skin, bullous lesions lichenoid skin and mucous lesions). Indirect immunofluorescence studies showed at several intervals that the patient had circulating antibasement membrane zone antibodies (IgG; titres 1/50). This is the third published case in which immunofluorescence studies have established the "pemphigoid" nature of some bullous lichen planus. These findings are in favour of an immune disorder in lichen planus.     

The lichen planus-like eruption after bone marrow transplantation

A lichen planus-like eruption was seen in four patients after bone marrow transplantation. The skin and mucous membrane appearance closely mimicked lichen planus. The histopathology was also very similar to lichen planus. The occurrence of a lichen planus-like eruption (LPLE) after an immune basal cell damage related to the graft-versus-host reaction raised the question of the immune nature of this eruption. The correlation found between biological signs of graft-versus-host reaction and the out-break or relapse of the lichen planus-like eruption supports the hypothesis that the skin changes could be a sign of a chronic immune response against recipient epidermis.     

Indirect immunofluorescence microscopy of lichen planus

Indirect immunofluorescence microscopy using serum and lesional skin revealed a lichen planus specific antigen (LPSA) in 80% of patients with lichen planus. This antigen is found only in the stratum granulosum and stratum spinosum. It was demonstrated in skin lesions in Caucasians and Negroes in South Africa and the U. S. A. but was not found in the skin of normal people or patients with other dermatoses. Indirect immunofluorescence should prove useful in distinguishing atypical forms of lichen planus from other dermatoses.     

The role of perforin-mediated apoptosis in lichen planus lesions

Lichen planus is recognized as a T-cell-mediated disease. Histologically, it is characterized by the formation of colloid bodies representing apoptotic keratinocytes. The apoptotic process mediated by CD8⁺ cytotoxic T lymphocytes (CTLs) and NK cells mainly involves two distinct pathways: the perforin/granzyme pathway and the Fas/FasL pathway. So far, little is known regarding the role of perforin-mediated apoptosis in lichen planus. In the present study, the expression and distribution of perforin, T and NK cell subsets in the epidermis and dermis of lesional and nonlesional lichen planus skin were studied. Skin biopsy specimens from lesional and nonlesional skin of ten patients with lichen planus and eight healthy persons were analysed by immunohistochemistry. Significant accumulation of T cells, particularly of CD4⁺ and CD8⁺ subsets, was found in both epidermis and dermis of lichen planus lesions compared with nonlesional and healthy skin. There were no significant differences in the incidence of NK cells (CD16⁺ and CD56⁺) between lesional, nonlesional and healthy skin. Perforin expression was significantly upregulated in the epidermis of lichen planus lesions. In conclusion, accumulation of perforin⁺ cells in the epidermis of lichen planus lesions suggest a potential role of perforin in the apoptosis of basal keratinocytes.