Upper gastrointestinal findings and detection of Helicobacter pylori in patients with oral lichen planus

Background. Lichen planus (LP) is a mucocutaneous disease of unknown aetiology, which may involve the gastrointestinal (GI) mucosa. The association of Helicobacter pylori with LP has been a subject of debate. Aim. To investigate upper GI findings and the presence of H. pylori in GI mucosa and oral LP (OLP). Methods. Oral biopsies from 20 patients with erosive OLP and 20 with non‐erosive OLP were investigated for the presence of H. pylori by histopathological examination and PCR. Upper GI endoscopy and GI mucosal biopsies were examined for LP lesions and/or H. pylori. Results. The endoscopic findings of both groups were oesophagitis, antral gastritis and duodenitis. No LP or LP‐like changes were found in the upper GI mucosa. H. pylori was found by histopathological examination in the gastric mucosa of 18 patients (45%), with equal distribution in both the control and study groups. Positive PCR results were obtained from biopsy specimens of oral lesions in all patients with erosive OLP and presence of H. pylori in the stomach (9 patients), but in none of the patients with non‐erosive OLP (P = 0.001). Conclusion. We did not find any difference in symptoms, endoscopic findings and histopathological results between patients with erosive and non‐erosive OLP. However, the concomitant presence of erosive OLP, of H. pylori nucleic acid in erosive OLP and the H. pylori organisms in gastric mucosa implies a possible pathogenic connection between this bacterium and erosive OLP.     

Clinical controversy on the effect of topical ciclosporin: what is the target site?

In recent years attempts have been made to treat T-cell-mediated skin diseases with topical therapeutics. Based on clinical data on the local treatment of recalcitrant erosive lichen planus (LP) with ciclosporin (CS) we discuss in vitro and in vivo studies on percutaneous absorption of CS, drug localization and drug metabolism in the skin as well as clinical data. Clinically relevant immunosuppressive activity depends not only on drug distribution in the target organ skin. The inhibition of T cell response is also dependent upon T cell subsets involved and the activation stage of the T cell. There are different proportions in T cell subpopulations during different evolutional stages of LP. Thus responsiveness to therapy with this drug may depend on the disease activity. Furthermore lymphocyte migration throughout various organs in the body including skin depend on a variety of molecular and cellular interactions. Whether local CS is sufficient to inhibit these interactions or to inactivate already activated T cells remains unclear. Assuming that the T lymphocyte is the target site for CS, local therapy reaches only a small fraction of the T cell population. This may be insufficient, and a systemic inhibition of helper/inducer T lymphocyte function is needed for successful therapy. With CS and with other drugs it seems that percutaneous absorption is not the only key to variable clinical responses to topical therapy.     

Photoinactivation of T-cell function with psoralen and UVA radiation suppresses the induction of experimental murine graft-versus-host disease across major histocompatibility barriers

Bone marrow transplantation is employed in the treatment of a number of hematologic and malignant diseases. A major complication is the induction of graft-versus-host disease. Whereas removal of T lymphocytes from the donor marrow effectively reduces the incidence of graft-versus-host disease, the incidence of graft failure often increases when T cells are depleted from the transplanted marrow. In the current study, photoinactivation of the donor cells with 8-methoxypsoralen coupled with exposure to long-wavelength ultraviolet radiation (PUVA therapy) was used to inactivate the response of the donor T cells against the host. PUVA therapy suppressed the ability of spleen cells to respond to alloantigen in the in vitro mixed lymphocyte reaction. The induction of acute graft-versus-host disease across complete major histocompatibility barriers in lethally X-irradiated mice was significantly suppressed after bone marrow transplantation with photoinactivated bone marrow cells. Long-term survivors demonstrated allogeneic reconstitution and partial restoration of T-cell function. Because PUVA therapy had no inhibitory effect on hematopoiesis, these data suggest that using phototherapy to inactivate the alloreactivity of T cells may provide an alternative to purging T cells from the donor marrow, thus suppressing both the incidence of graft-versus-host disease and the incidence of graft failure.     

Lichen planus on the palms and soles

Case reports Five cases of palm and sole lichen planus (LP) taken from our series of 263 cases observed from 1985 to date are reported. Comments The clinical features of LP on the palms and soles are hyperkeratotic papules, erythematous patches, erosive lesions and also acrosyringeal LP. It has been hypothesized that betablocker drugs excreted by the ecerine if glands could influence the physiology of the excretory duct producing the acrosyringeal modification of LP. The authors evidence the association, in two patients, between erosive palm and sole LP and HCV-positive hepatopathy and also the association between LP erosive features and liver involvement.     

Acitretin in erosive penile lichen planus

Lichen planus (LP) is an incompletely understood T‐cell mediated auto‐immune dermatosis. When LP involves the genitalia it may present as painful, pruritic erosions that can be exquisitely tender, causing distress and genitourinary and sexual dysfunction. Management of erosive genital LP is often suboptimal. Despite higher order evidence demonstrating the efficacy of oral acitretin in the management of cutaneous and oral LP, it still features below other immunosuppressive and immunomodulatory therapies in many clinicians’ therapeutic ladder. We present a case of severe erosive penile LP, successfully treated with oral acitretin after topical and oral corticosteroids failed to induce remission.     

Lichen planus and hepatitis C virus infection

BACKGROUND: The association of lichen planus (LP) with liver diseases is well established. The reported prevalence rates of hepatitis C virus (HCV) antibodies in patients with LP tend to appear quite variable. OBJECTIVE: The aim of this study was to assess the prevalence of HCV antibodies in a group of patients with LP and evaluate the clinical characteristics of the subgroup with LP associated with HCV. METHODS: We studied 101 patients, 57 (56.4%) women and 44 (43.5%) men with a mean age of 48 years, consecutively diagnosed with cutaneous and/or mucosal LP between January 1992 and December 2000. We used 99 age- and sex-matched controls. RESULTS: Anti-HCV antibodies were detected in nine cases (8.9%) of the LP group but only two (2.02%) of the controls. The odds ratio between the subjects with HCV positivity and those with negative HCV virus was 4.74, with a confidence interval at 95%, between 0.999 and 22.545. A statistically significant association was only demonstrated between erosive LP and infection by HCV. CONCLUSIONS: The possibility of liver disease caused by HCV should be ruled out in patients with LP, especially in the erosive form.     

Management of erosive lichen planus with topical tacrolimus and recurrence secondary to metoprolol

Metoprolol, a widely prescribed beta-adrenergic receptor blocker, has occasionally been associated with a diversity of cutaneous reactions. We present a 79-year-old male patient with erosive lichen planus (LP) on the feet and hands who was successfully treated with topical tacrolimus. Six months after the lesions had been cured the patient received the beta-receptor blocker metoprolol for the treatment of hypertonus. Within only 2 weeks of metoprolol intake the erosive lesions on the palms and feet recurred. After discontinuation of the drug and repetitive topical treatment with tacrolimus a complete remission of the lesions could be achieved. The recurrence of erosive LP probably secondary to metoprolol and the therapeutic success of topical tacrolimus in the treatment of LP are discussed.     

Basic and interleukin-2-augmented natural killer cell activity in lichen planus

Natural killer cell (NK) activity of peripheral blood lymphocytes against K 562 cells was investigated in lichen planus (LP). 38 LP patients with cutaneous or oral mucosal involvement and 20 healthy controls participated in the study. A statistically significant decrease in the NK response in LP patients with extensive erosive oral mucosal involvement (p less than 0.02) and in generalized acute eruptive LP (p less than 0.01) was noted compared to those with nonerosive LP of the oral mucosa or healthy controls. Interleukin 2 failed to restore completely the reduced NK activities in our patients with LP.     

Antinuclear antibodies in patients with lichen planus

Abstract Lichen planus (LP) is a mucocutaneous syndrome of yet uncertain pathogenesis, and it has usually been considered to be a dermatosis without antinuclear antibodies (ANA) nor other specific auto-antibodies. Over 10 years ago a series of indirect immunofluorescence researches with patients' lesional skin and serum disclosed the presence of lichen planus specific antigens (LPSA). After this, a number of substrates have been submitted for evaluation. In this study we have carried out indirect immunofluorescent test in relation with different substrates, with the aim of verifying whether the negative results previously obtained were due to poor sensitivity of the substrates employed. Subsequently we have compared the results obtained in the erosive forms of LP with those obtained in the non-erosive forms. We have concluded that rat oesophagus is a better substrate for the detection of ANA in patients with LP, as it has proved to have a positivity rate of 40.42%. Monkey oesophagus has provided a rate of 27.6%, and HEP-2 cells and rat liver have proved to be unsuitable. In addition, we have observed that the frequency of ANA is higher in the erosive forms of LP (P= 0.0389). In this article we demonstrate that the presence of ANA in patients with LP depends on the substrate employed, the most suitable substrate being rat oesophagus. Also, we demonstrate that ANA is more frequently observed in patients with erosive LP.     

DETECTION OF T LYMPHOCYTES AND T LYMPHOCYTE SUBSETS IN LICHEN PLANUS: IN SITU AND IN PERIPHERAL BLOOD

Background. Abnormal immune mechanisms are thought to be important in the pathogenesis of lichen planus (LP). This is a study to clarify the changes that occur in T lymphocytes and T lymphocyte subsets, both in situ and in peripheral blood. Methods. A group of 100 patients with LP were included in this study. T lymphocytes and T lymphocyte subsets were detected in lesional skin by immunoperoxidase cell surface staining using monoclonal antibodies. Peripheral T lymphocytes and T lymphocyte subsets were also detected by indirect immunofluorescence using monoclonal antibodies. A group of 10 normal healthy subjects were used as controls. Results. The study of the lesional T lymphocytes and T lymphocyte subsets demonstrated that helper T cells was the predominant subset in LP lesions in most of the patients. This predominance was evident irrespective of the duration of the disease and was more evident in late than in early lesions. The percentage of both total T lymphocytes and helper T cells in peripheral blood was decreased significantly in patients compared with controls. A significant decrease in helper T cells and the helper/cytotoxic T cell ratio was detected in patients with a longer duration of the disease. Conclusion. Activation of helper T lymphocytes that were found to be the predominant subsets in LP lesions may be responsible for epidermotropic cellular infiltrates leading to damage and destruction of epidermal cells.     

Isolated lichen planus of the lip

Lichen planus (LP) is an inflammatory disease that may involve multiple skin sites as well as mucous membranes, hair follicles and nails. It rarely occurs on the lips and usually then in association with oral lesions. We report a 43-year-old man with a 7-month history of inflammation and erosive lesions of the lower lip. Histopathological and immunofluorescence studies showed features of LP. Local treatment with betamethasone dipropionate 0.5% ointment led to complete resolution within 1 month. Four months later, the patient developed typical cutaneous LP. Isolated LP of the lip is unusual, although this condition may be underestimated and therefore under-reported in the literature.     

Reaction to biological drugs: infliximab for the treatment of toxic epidermal necrolysis subsequently triggering erosive lichen planus

Toxic epidermal necrolysis (TEN) is a rare, life‐threatening skin reaction for which there is currently has no standardized treatment, despite its significant mortality. Biological agents such as tumour necrosis factor (TNF)‐α antagonists are emerging as a novel treatment for patients with TEN. We report a 32‐year‐old woman who developed TEN secondary to sulfasalazine, which was treated with infliximab. The infliximab treatment subsequently triggered erosive lichen planus (LP) involving the mouth and vulva. Clinicians should be aware that TNF‐α antagonists can cause LP as a paradoxical complication of treatment.     

Recent advances in phototherapy and photochemotherapy of skin disease

The therapeutic spectrum for ultraviolet radiation treatment of skin disease has continued to be broadened. Psoralen photochemotherapy is beneficial in chronic lichenoid graft-versus-host disease and disseminated granuloma annulare. This treatment is now being found more useful in atopic eczema and chronic photosensitivity with some modifications of the therapy. UV phototherapy has also been found useful in mild to moderate atopic eczema. The nature of these treatments is also changing with greater use of selective UV phototherapy and definition of the required schedule for maintenance treatment with UVB phototherapy. The mechanism of therapeutic benefit remains unknown although one possibility is selective phototoxicity for inflammatory cells in the dermis. Nonmelanoma skin cancer, premature aging of the skin and freckling are the main long-term adverse effects of these treatments.     

Graft-versus-host disease: part I. Pathogenesis and clinical manifestations of graft-versus-host disease

Approximately 25,000 allogeneic hematopoietic cell transplants are performed worldwide each year for a variety of malignant and non-malignant conditions. Graft-versus-host disease represents one of the most frequent complications and is a major source of long-term morbidity and mortality. Whereas acute graft-versus-host disease is induced by recognition of host tissues as foreign by immunocompetent donor cells, the pathogenesis of chronic graft-versus-host disease is not as well understood, and continues to be a major treatment challenge. Part I of this two-part series reviews the epidemiologic factors, classification, pathogenesis, and clinical manifestations of acute and chronic graft-versus-host disease. Part II discusses the topical, physical, and systemic treatment options available to patients with graft-versus-host disease.     

Murine graft-versus-host skin disease: a chronologic and quantitative analysis of two histologic patterns

Human graft-versus-host disease (GVHD) has several cutaneous manifestations, including a lichenoid and a sclerotic injury pattern. A versatile animal model of graft-versus-host skin disease (GVHSD) would facilitate study of the pathophysiology of these two cutaneous injury patterns. We have examined two murine chimeras histologically and have found two distinct patterns. Allogeneically transplanted B1/6 mice show a prolonged lichenoid-interface dermatitis that eventuates in clinical alopecia, whereas LP/J recipients of allogeneic cells do not show hair loss. Their histopathology consists of an early lichenoid phase that abates and is replaced by dermal sclerosis. Because of the versatility of the mouse as a laboratory animal, we feel that this model provides an excellent opportunity to define the immunopathologic mechanisms responsible for skin injury in GVHD. In addition, an understanding of the pathogenesis of the T cell-dependent, lichenoid, and sclerotic patterns of tissue injury in GVHSD might well provide insight into the pathogenesis of the GVHSD analogs, cutaneous lupus erythematosus and scleroderma.     

The management of oral lichen planus

Oral lichen planus is a relatively common inflammatory disease affecting between 0.5% and 2.2% of the population in epidemiological studies. In contrast with cutaneous lichen planus (LP), in which the clinical course is often mild and resolves within 2 years, mucosal LP tends to follow a more chronic course often punctuated by acute exacerbations. Furthermore, although distinct clinical subtypes such as reticular, atrophic, hypertrophic and erosive forms are well recognized, more than one clinical phenotype may be seen at a time. The rare association with oral neoplasia should always be considered and high-risk patients must be kept under close observation. Thus the management of this disorder will vary widely both between patients, and for individual patients, with fluctuations in disease activity. Here we discuss the therapeutic options available and review the evidence for their use.     

Sclerodermatous chronic graft-versus-host disease. Analysis of seven cases.

BACKGROUND: Sclerodermatous chronic graft-versus-host disease is a disabling complication after allogeneic bone marrow transplantation from HLA-identical sibling donors. Only a few series of patients have been reported and the dermatologic features have never been extensively described. OBJECTIVE: The purpose of the study was to describe clinical and biologic features of chronic sclerodermatous graft-versus-host disease and to compare them with scleroderma. METHODS: We reviewed 196 patients grafted between April 1973 and July 1987 with survival times sufficient to be at risk of chronic graft-versus-host disease. Seven had the sclerodermatous form. RESULTS: Most patients had disseminated sclerosis of the trunk and the proximal portions of the limbs. In two cases, atrophy of the skin was predominant, corresponding with a severe clinical evolution. Periorbital pigmentation was observed as an initial manifestation in three cases. Visceral manifestations resembled those observed in scleroderma but histologic and immunologic studies demonstrated clear differences. Response to therapy was variable. CONCLUSION: Chronic sclerodermatous graft-versus-host disease may realize two different patterns. Major atrophy is associated with a more severe progression.     

Linear porokeratosis associated with disseminated superficial actinic porokeratosis: a new example of type II segmental involvement

The coexistence of linear porokeratosis (LP) and disseminated superficial actinic porokeratosis (DSAP) in a 3-year-old girl with a family history of DSAP is presented. Happle proposed loss of heterozygosity (LOH) to explain the origin of this unusual phenomenon. Homozygosity would explain why lesions in LP are far more pronounced than those of the associated heterozygous DSAP lesions. LOH would also explain the early age of presentation of the linear lesions, the family history of DSAP, and why LP cases are particularly prone to malignant transformation. This case is also important for molecular studies because of the presence of heterozygous and homozygous mutated cells in the same patient and the familial occurrence of the heterozygous form of the disease.     

Comparative immunological and histopathological study in fifty cases of mucosal/nonmucosal lichen planus

Lichen planus is a common disorder and 40-50% of LP patients also reveal mucosal lesions. It is well known that mucosal LP lesions take very long to heal in comparison to cutaneous lesions. Rarely erosive mucosal LP can turn malignant. Both CMI and humoral immunity may play role in aetiopathogenesis of LP. Present study was conducted to study and compare CMI, Humoral Immunity, histopathology in mucosal and nonmucosal LP.     

Lichen planus and hepatitis C virus: prevalence and clinical presentation of patients with lichen planus and hepatitis C virus infection

Summary Although cases of lichen planus (LP) associated with hepatitis C virus (HCV) infection have been described, the association between the two diseases has not been established because the geographic origin of patients could be an important factor in HCV prevalence in patients with LP. The serum samples of 78 consecutive patients with cutaneous and/or mucous LP and 82 control patients were analysed for the presence of antibodies to HCV by enzyme-immunoassay and for the presence of antigens of HCV by two-stage polymerase chain reaction (PCR). The clinical features of patients with LP associated with HCV infection were compared with patients with LP without HCV infection. Sixteen of the 78 (20%) patients had anti-HCV antibodies. In 13 of these 16 cases (81%), HCV-RNA was detected by PCR in serum samples. In the 82 control patients, anti-HCV antibodies was observed in two (2·4%) patients. We have found a statistically significant association (P < 0·05) between erosive LP and HCV infection. We conclude that the high prevalence of HCV-RNA in patients with LP provides some evidence for the role of HCV in the pathogenesis of LP. Our results suggest an association between erosive LP and HCV infection.