El liquen plano, actualizacion !!!   

Data-Medicos 
Dermagic/Express No. 4-(115) 
30 Junio 2.002 / 30 June 2.002 

EDITORIAL ESPAÑOL
=================
Hola amigos de la red. DERMAGIC de nuevo con ustedes. En esta nueva revision sobre el LIQUEN PLANO, enfermedad descrita hace mas de 100 años y que hoy dia su tratamiento sigue siendo todo un reto para los dermatologos de la nueva era. 

Erasmus Wilson fue el primero en utilizar el termino Lichen Planus een el año 1869. La primera variante de la enfermedad fue descrita por Kaposi en 1892 denominandola Lichen Ruber Pemphigoides y Wickham describio las esgtrias blancas en la parte superior de las lesiones. Darier describio posteriormente las caracteristicas histopatologicas de la enfermedad. 

Despues de unos cuantos años el avance de la ciencia a logrado descifrar numerosos eventos en el LIQUEN PLANO, ellos son: 

TIPOS CLINICOS DE LIQUEN PLANO: 
------------------------------------------------------- 
1.) Actinico. 
2.) Anular. 
3.) Buloso. 
4.) Clasico. 
5.) Eritematoso. 
6.) Exfoliativo. 
7.) Familiar 
8.) En gota. 
9.) Hipertrofico. 
10.) "invisible" 
11.) Lineal. 
12.) Muco-membranoso (genital,esofago) 
13.) Uñas.
14.) Oral. 
15.) Penfigoide. 
16.) Perforante. 
17.) Pigmentoso. 
18.) Planopilar. 
19.) Ulcerativo 
20.) Zosteriforme 

El oral tiene 6 tipos: Reticulado, atrofico, papular, en placa, erosivo y buloso. 

ENFERMEDADES ASOCIADAS: 
-----------------------------------------------
Se han descrito numerosas enfermedades asociadas con LIQUEN PLANO entre ellas: 

A.) MALIGNAS: 
---------------------- 
1.) Cancer de estomago. 
2.) Limfoma. 
3.) Neuroblastoma. 
4.) Adenoma de la pituitaria. 
5.) Fibrohistiocitoma. 
6.) Paraproteinemia monoclonal por IGA Kappa. 
7.) Craneofaringioma 
8.) Malignidad pararenal. 
9.) Sarcoma. 

B.) ENFERMEDADES GASTROINTESTINALES Y ENDOCRINAS. 
----------------------------------------------------------------------------------------------
1.) Cirrosis biliar primaria. 
2.) Hepatitis cronica activa. 
3.) Colitis Ulcerativa. 
4.) Diabetes mellitus. 
5.) Anormalidad en el funcionamiento del higado (enzimas)

C.) ENFERMEDADES AUTOINMUNES: 
----------------------------------------------------------
1.) Alopecia Areata. 
2.) Dermatomiositis. 
3.) Dermatitis Herpetiforme. 
4.) Tiroiditis de Hashimoto. 
5.) Queratoconjuntivitis seca y xerostomia. 
6.) Morfea. 
7.) Miastenia Gravis. 
8.) Penfigo foliaceo. 
9.) Penfigo Vulgar. 
10.) Anemia perniciosa. 
11.) Esclerosis sistemica. 
12.) Timoma. 
13.) Vitiligo. 

Tambien el LIQUEN PLANO a sido asociado al uso de numerosas drogas y sustancias: 

DROGAS ASOCIADAS CON LIQUEN PLANO : 
------------------------------------------------------------------- 
Numerosas drogas han estado involucradas en la aparicion de LIQUEN PLANO, denominadas LIQUEN PLANO-LIKE reacciones, entre ellas: 

A.) ANTIHIPERTENSIVOS: Captopril, clorotiazida, Enalapril, Hidroclorotiazida, Labetolol, Metildopa, practolol, propranolol, spironolactona. 

B.) ANTIBIOTICOS: Demaclociclina, Etambutol, Griseofulvina, Ketoconazole, Levamisol, Acido para-amino-salicilico, estreptomicina, teraciclina. 

C: AINES: (ANTIINFLAMATORIOS NO ESTEROIDEOS: 
Naproxen, Indometacina, Feclofenac, Diflunisal, Flurbiprofen, Benoxaprofen, Acido acetil salicilico. 

D: ANTIMALARICOS: 
Cloroquina, Quinacrina, Quinidina, Quinina. 

E.) PSICOTROPICOS: 
Carbamazepina, Levomepromazina, Metopromazina, 

F.) AGENTES REVELADORES DE FILMS: 
4-Amino-N-dietil-analina sulfato (TTS), CD2, CD3, P-isopropilamino-difenilamina (IPPD) 

G.) SULFONILUREAS: 
Clorpropamida, Tolazamida, Tolbutamida. 

I.) MISCELANEOS: 
Alopurinol, anfenazole, arsenico, cinarizina, oro, meticran, Musk ambrette, penicilamina, probenecid, pirimetamina, mercaptopropionilglicina, piritioxina, Medios de radiocontraste, trihexifenidil, interferon-alpha-N1 

... y probablemente existan otras mas que no estan en esta lista. 

Geneticamente se ha establecido una asociacion de los antigenos HLA y EL LIQUEN PLANO, tembien el STRESS emocional es un factor desencadenante, el consumo de TABACO tambien se ha relacionado al mismo y las infecciones. 

ALTERNATIVAS TERAPEUTICAS: 
--------------------------------------------------- 
Se ha utilizado varias propuestas para el tratamiento del LIQUEN PLANO, entre ellas destacan: 

1.) RETINOIDES: Isotretinoina, Etretinato, Acitretin, 
2.) GRISEOFULVINA. 
3.) CICLOSPORINA A. 
4.) ANTIBIOTICOS: Penicilina, Isoniacida, Aureomicina, Trimetoprin-Sulfametoxazol, tetraciclina 
5.) ANTIPARASITARIOS: Metronidazol, Levamisol. 
6.) DAPSONA. 
7.) ANTIMALARICOS. Fenitoina 
8.) RADIOTERAPIA. 
9.) ANTIMETABOLITOS: Ciclofosfamida, metotrexato. 
10.) CORTICOSTEROIDES. 
11.) MEDICACION PSIQUIATRICA: Sulpiride. 
12.) AZATIOPRINA. 
13.) PUVA: psoralenos mas radiacion UVA 
14.) CIRUGIA.
15.) VIEJAS TERAPIAS INCLUYEN: Mercurio sistemico, Acido nicotinico, Bismuto, vitaminas, calcio intravenoso, y arsenicales. 

HACIENDO UN RASTREO POR LA RED ENCONTRE ESTAS NUEVAS ALTERNATIVAS DE 
TRATAMIENTO: 
------------------------------------------

1.) DERIVADOS DE PLAQUETAS E INMUNOSUPRESION. 
2.) glycyrrhizin (LICORICE), HIERBA DE ORIGEN CHINO. 
3.) TACROLIMUS Y PIMECROLIMUS TOPICO 
4.) HEPARINA (ENOXAPARIN) 
5.) INTERFERON ALFA- 2b 
6.) FOTOQUIMIOTERAPIA EXTRACORPOREA. 
7.) MICOFENOLATO DE MOFETIL 


Quiza una de las cosas mas importantes de esta revision es LA GRAN ASOCIACION QUE SE DESCRIBE actualmente ENTRE EL LIQUEN PLANO Y LA HEPATITIS CRONICA y la VACUNACION contra LA MISMA HEPATITIS B. 

En base a todos estos hallazgos PODRIAMOS CLASIFICAR EL EL LIQUEN PLANO DENTRO DE 6 VARIANTES, e cuanto a su ORIGEN. 

1.) ASOCIADO A ENFERMEDAD HEPATICA. 
2.) ASOCIADO A OTRAS ENFERMEDADES NO HEPATICAS. 
3.) INDUCIDO POR DROGAS Y CONTAMINANTES. 
4.) IDIOPATICO. 
5.) MARCADOR CUTANEO DE MALIGINIDAD. 
6.) GENETICO (HLA ANTIGENOS) 

Probablemente Erasmus Wilson NUNCA PENSO la gran relacion que se ha descubierto entre el LIQUEN PLANO Y ENFERMEDAD HEPATICA o ANORMALIDADES en el FUNCIONAMIENTO HEPATICO, repito, el HECHO MAS IMPORTANTE DE ESTA REVISION, pues las nuevas terapias parecen ser NO MUY CONVINCENTES. 

.. En las referencias los hechos.

Saludos a Todos.

Dr Jose Lapenta R. 

EDITORIAL ENGLISH
=================
Hello friends of the net. DERMAGIC again with you. In this new revision on the LICHEN PLANUS, illness described ago but of 100 years and that nowadays their treatment continues being an entire challenge for the dermatoligist of the new era. 

Erasmus Wilson was the first one in using the I term LICHEN PLANUS (LP) in the year 1869. The first variant of the illness was described by Kaposi in 1892 denominating it Lichen Ruber Pemphigoides and Wickham it described the white striae in the superior part of the lesions. Darier described the histopathologic characteristic of the illness later on. 

After some years the advance of the science had been able to decipher numerous events in the  LICHEN PLANUS, they are: 

CLINICAL TYPES OF LICHEN PLANUS: 
------------------------------------------------------- 
1.) Actinic. 
2.) Annulare 
3.) Bullous. 
4.) Classic. 
5.) Erythematosus. 
6.) Exfoliative. 
7.) familial 
8.) Guttate. 
9.) Hypertrophic. 
10.) "invisible" 
11.) Lineal. 
12.) Muco-membranous (genital, esophagus) 
13.) Nail. 
14.) Oral. 
15.) Penphigoides. 
16.) Perforanting. 
17.) Pigmentosus. 
18.) Planopilaris. 
19.) Ulcerative. 
20.) Zosteriform. 

The oral one has 6 types: Reticulated, atrophic, papular, plaquelike, erosive and bullous. 

ASSOCIATE DISEASES: 
------------------------------------ 
Numerous illnesses associated with LICHEN PLANUS have been described, among them: 

A.) MALIGNANCIES: 
-------------------------------
1.) Stomach Cancer. 
2.) Lymphoma. 
3.) Neuroblastoma. 
4.) Adenoma of the pituitary. 
5.) Fibrohistiocytoma. 
6.) IGA Kappa monoclonal paraproteinemia. 
7.) Craniopharyngioma 
8.) Pararrenal malignancy. 
9.) Sarcoma. 

B.) GASTROINTESTINAL AND ENDOCRINE DISEASES: 
-----------------------------------------------------------------------------------

1.) Primary biliar cirrhosis (PBC). 
2.) Chronic active hepatitis (CAH). 
3.) Ulcerative colitis. 
4.) Diabetes mellitus. 
5.) Abnormalities in the liver function (enzymes).

C.) AUTOIMMUNE DISEASES: 
----------------------------------------------

1.) Alopecia Areata. 
2.) Dermatomyositis. 
3.) Dermatitis Herpetiformis. 
4.) Hashimoto's Thyroiditis. 
5.) Keratoconjunctivitis sicca and xerostomia. 
6.) Morphea. 
7.) Myasthenia Gravis. 
8.) Penphigus foliaceus. 
9.) Penphigus Vulgaris. 
10.) Pernicious anemia. 
11.) systemic sclerosis. 
12.) Thymoma. 
13.) Vitiligo. 

Also the LICHEN PLANUS had been associated to the use of numerous drugs and substances: 

DRUG ASSOCIATED WITH LICHEN PLANUS: 
------------------------------------------------------------------- 
Numerous drugs have been involved in the appearance of LICHEN PLANUS, called LP-like reactions, among them: 

A.) ANTIHYPERTENSIVE: Captopril, chlorothiazide, Enalapril, Hydroclorothiazide, Labetolol, Methyldopa, practolol, propranolol, pironolactone. 

B.) ANTIBIOTICS: Demeclocycline, Ethambutol, Griseofulvin, Ketoconazole, Levamisole, Para-amino-salicylic acid, streptomycin, teracycline. 

C.) NON STEROIDAL ANTIINFLAMMATORY DRUGS: 
Naproxen, Indomethacin, Feclofenac, Diflunisal, Flurbiprofen, Benoxaprofen, acetylsalicylic acid. 

D: ANTIMALARIALS: 
Chloroquine, Quinacrine, Quinidine, Quinine. 

E.) PSYCHOTROPIC /NEUROLOGIC: 
Carbamazepine, Levomepromazine, Metopromazine, Olanzapine. 

F.) FILMS DEVELOPING AGENTS: 
4-Amino-N-diethyl-analine sulfate (TTS), CD2, CD3, p-Isopropylamino-diphenylamine (IPPD). 

G.) SULFONYLUREAS: 
Chlorpropamide, Tolazamide, Tolbutamide. 

I.) MISCELLANEOUS: 
Allopurinol, anphenazole, arsenic, cinnarizine, gold, methycran, Musk ambrette, penicillamine, probenecid, phyrimethamine, mercaptopropionylglycine, pyrithioxin, radiocontrast media, trihexyphenidyl, interferon-alpha-N1. 

... and probably exist other but that are not in this list. 

Genetically an association of the HLA antigens and THE LICHEN PLANUS it has been observed, also the emotional STRESS is a causing factor, the consumption of TOBACCO has also been related to the same one, and the infections. 

THERAPEUTIC ALTERNATIVES: 
----------------------------
It has been used several proposals for the treatment of the LICHEN PLANUS, among them they highlight: 

1.) RETINOIDS: Isotretinoin, Etretinat, Acitretin, Temarotene. 
2.) GRISEOFULVIN. 
3.) CYCLOSPORINE A. 
4.) ANTIBIOTICS: Penicillin, Isoniazid, Aureomycin, Trimethoprim-Sulfamethoxazole, tetracycline. 
5.) ANTIPARASITE DRUGS: Metronidazole, Levamisole. 
6.) DAPSONE. 
7.) ANTIMALARIALS: Phenytoin. 
8.) RADIOTHERAPY. 
9.) ANTIMETABOLITES: Cyclophosphamide, metotrexate. 
10.) CORTICOSTEROIDS. 
11.) PSYCHIATRIC MEDICATION: Sulpiride. 
12.) AZATHIOPRINE. 
13.) PUVA: psoralens plus UVA radiation. 
14.) SURGERY.
15.) OLD THERAPIES INCLUDE: Systemic Mercury, nicotinic acid, Bismuth, vitamins, intravenous calcium, and arsenicals. 

MAKING A SURVEY FOR THE NET I FOUND THESE NEW ALTERNATIVES OF 
TREATMENT: 
-------------------------------------------------------------
1.) RECOMBINANT PLETELET-DERIVED GROWHT FACTOR AND INMUNOSUPRESION. 
2.) glycyrrhizin (LICORICE), GRASS OF CHINESE ORIGIN. 
3.) TACROLIMUS AND PIMECROLIMUS TOPIC. 
4.) HEPARIN. (ENOXAPARIN) 
5.) INTERFERON ALFA - 2b 
6.) EXTRACORPOREAL PHOTOCHEMOTHERAPY. 
7.) MOFETIL MYCOPHENOLATE 

Maybe one of the things but important of this revision it is THE GREAT ASSOCIATION THAT is DESCRIBED at the moment BETWEEN THE LICHEN PLANUS AND THE CHRONIC HEPATITIS and the VACCINATION against THE SAME HEPATITIS B. 

Based on all these discoveries we could CLASSIFY THE LICHEN PLANUS on their origin IN SIX (6) VARIANTS. 

1.) ASSOCIATED TO HEPATIC DISEASES. 
2.) ASSOCIATED TO OTHER NON HEPATIC DISEASES. 
3.) INDUCED BY DRUGS AND POLLUTANTS. 
4.) IDIOPATIC. 
5.) CUTANEOUS MARKER OF MALIGNANCY. 
6.) GENETIC (HLA ANTIGENS) 

Easmus Wilson probably NEVER THOUGHT the great relationship that has been discovered between the LICHEN PLANUS AND HEPATIC ILLNESS. or ABNORMALITIES in the HEPATIC FUNCTION, I repeat, the MOST IMPORTANT FACT OF THIS REVISION, because the new therapies seem to NOT be VERY CONVINCING. 

in the references the facts ... 

Greetings to all

Dr. Jose Lapenta R.
===============================================================
REFERENCIAS BIBLIOGRAFICAS / BIBLIOGRAPHICAL REFERENCES
===============================================================
1.) Lichen planus involving the esophagus.
2.) 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.
3.) [Lichen planus and hepatitis C virus. Apropos of 5 new cases] TO: Lichen plan et virus de l'hepatite C. A propos de 5 nouveaux cas.
4.) Lichen planus occurring after hepatitis B vaccination: a new case.
5.) A case of oral lichen planus with chronic hepatitis C successfully treated by glycyrrhizin (LICORICE)
6.) Nail lichen planus in children: clinical features, response to treatment, and long-term follow-up.
7.) Azathioprine for the treatment of severe erosive oral and generalized lichen planus.
8.) Ulcerative lichen planus: a case responding to recombinant platelet-derived growth factor BB and immunosuppression.
9.) [Study on regulatory effect of composite taixian tablet on immune function of red blood cell in patients with oral lichen planus]
10.) Topical tacrolimus and pimecrolimus: future directions.
11.) Tacrolimus clinical studies for atopic dermatitis and other conditions.
12.) Low-dose low-molecular-weight heparin (enoxaparin) is beneficial inlichen planus: a preliminary report 
13.) Low-dose low-molecular-weight heparin in lichen planus 
14.) Management of recalcitrant ulcerative oral lichen planus with topical tacrolimus.
15.) Topical tacrolimus in the treatment of symptomatic oral lichen planus: a series of 13 patients.
16.) Mast cell degranulation and the role of T cell RANTES in oral lichen planus.
17.) Levamisole and/or Chinese medicinal herbs can modulate the serum level of squamous cell carcinoma associated antigen in patients with erosive oral lichen planus.
18.) Dramatic response to levamisole and low-dose prednisolone in 23 patients with oral lichen planus: a 6-year prospective follow-up study.
19.) Successful treatment of generalized lichen planus with recombinant interferon alfa-2b.
20.) [Prevalence of oral lichen planus and oral leukoplakia in 112 patients with oral squamous cell carcinoma]
21.) Dental metal allergy in patients with oral, cutaneous, and genital lichenoid reactions.
22.) [Cellular immune alterations in fifty-two patients with oral lichen planus.]
23.) Isolated lichen planus of the toe nails treated with oral prednisolone.
24.) Lichen planus-like eruption following autologous bone marrow transplantation for chronic myeloid leukaemia.
25.) Immune mechanisms in oral lichen planus.
26.) Cyclosporin A in the treatment of lichen planus.
27.) Oral metronidazole treatment of lichen planus.
28.)Idiopathic lichen planus: treatment with metronidazole.
29.) Intestinal amebiasis, lichen planus, and treatment with metronidazole.
30.) Urinary tract infection as a cause of lichen planus: metronidazole therapy.
31.) [Metronidazole treatment of the erosive ulcerative form of lichen ruber planus of the oral mucosa]
32.) Clinical and pathological characteristics of oral lichen planus in hepatitis C-positive and -negative patients.
33.) High prevalence of anticardiolipin antibodies in patients with HCV-associated oral lichen planus.
34.) The clinical features, malignant potential, and systemic associations of oral lichen planus: a study of 723 patients.
35.) Management of oral lichen planus.
36.) Lichen planus occurring after hepatitis B vaccination: a new case.
37.) TT virus detection in oral lichen planus lesions.
38.) Lichenoid eruption following hepatitis B vaccination: first North American case report.
39.) Increased frequency of HLA-DR6 allele in Italian patients with hepatitis C virus-associated oral lichen planus.
40.) Extrahepatic manifestations of chronic viral hepatitis.
41.) Prevalence of hepatitis C virus in patients with lichen planus of the oral cavity and chronic liver disease.
42.) Histopathological and immunohistochemical study of oral lichen planus-associated HCV infection.
43.) Previous tuberculosis, hepatitis C virus and lichen planus. A report of 10 cases, a causal or casual link?
44.) [Skin diseases and hepatitis virus C infection]
45.) [Extrahepatic manifestations of hepatitis C virus infection]
46.) Detection of hepatitis C virus RNA in oral lichen planus and oral cancer tissues.
46.) Oral lichenoid lesions after hepatitis B vaccination.
47.) [The extrahepatic manifestations in hepatitis C virus (HCV) infection]
48.) Association of HLA-te22 antigen with anti-nuclear antibodies in Chinese patients with erosive oral lichen planus.
49.) Treatment of autoimmune and extra-hepatic manifestations of HCV infection.
50.) Lichen planus, erythema nodosum, and erythema multiforme in a patient with chronic hepatitis C.
51.) [Clinical considerations and statistical analysis on 100 patients with oral lichen planus]
52.) Lichen planus in children: a possible complication of hepatitis B vaccines.
53.) Lichen planus actinicus treated with acitretin and topical corticosteroids.
54.) Alendronate-induced lichen planus.
55.) Hepatitis C virus and lichen planus in Nigerians: any relationship?
56.) Helicobacter pylori Infection in Skin Diseases: A Critical Appraisal.
57.) Presence of lichen planus during a course of interferon alpha-2a therapy for a viral chronic C hepatitis.
58.) Lichen planus-like eruption following autologous bone marrow transplantation for chronic myeloid leukaemia.
59.) [Clinical evaluation in oral lichen planus with chronic hepatitis C: the role of interferon treatment]
60.) Oral lichen planus induced by interferon-alpha-N1 in a patient with hepatitis C.
61.) Treatment of lichen planus. An evidence-based medicine analysis of efficacy.
62.) Successful Treatment of Resistant Hypertrophic and Bullous Lichen Planus With Mycophenolate Mofetil 
63.) Liver abnormalities in patient with lichen planus.
64.) Lichen planus.
===============================================================
===============================================================
1.) Lichen planus involving the esophagus.
===============================================================
Dig Dis Sci 2001 Oct;46(10):2292-7 

Ukleja A, DeVault KR, Stark ME, Achem SR.

Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA.

Lichen planus is a common mucocutaneus disorder that rarely involves the esophagus. We report two challenging cases presenting with recurrent dysphagia originally suspected due to gastroesophageal reflux. Subsequent evaluation revealed peculiar endoscopic findings of desquamative esophagitis leading to the diagnosis of lichen planus of the esophagus. This disorder should be considered in middle age or elderly women presenting with unexplained dysphagia or odynophagia. In this paper we review the available literature on the subject and summarize every case reported to date.

===============================================================
2.) 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.
===============================================================
Clin Exp Dermatol 2001 Sep;26(6):540-4

Erkek E, Bozdogan O, Olut AI.

Kirikkale University Faculty of Medicine, Kirikkale, Turkey. [email protected]

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.

===============================================================
3.) [Lichen planus and hepatitis C virus. Apropos of 5 new cases]
TO: Lichen plan et virus de l'hepatite C. A propos de 5 nouveaux cas.
================================================================
AU: Hyrailles-V; Peyron-N; Blanc-P; Mark-Y; Meunier-L; Meynadier-J;
Larrey-D; Michel-H
AD: Service d'Hepato-Gastroenterologie, Hopital Saint-Eloi, Montpellier.
SO: Gastroenterol-Clin-Biol. 1995 Oct; 19(10): 833-6
ISSN: 0399-8320
PY: 1995
LA: FRENCH; NON-ENGLISH
CP: FRANCE
AB: Lichen planus is an immunologically mediated skin or mucous disease,
which has recently been described in some patients with hepatitis C
virus-related liver disease. We report 5 new cases of the association of
hepatitis C with lichen planus, to be added to the 15 cases published in
the literature. The sex ratio (female/male) was of 1.2. Lichen planus
occurred more frequently in chronic active hepatitis (2/3 of cases) than in
cirrhosis (1/3 of cases). Lichen planus manifestations were only mucous
(30%), only cutaneous (40%) or both (30%). Mucous lesions were mainly
observed in patients with cirrhosis (3/4 of cases). The onset of skin and
hepatic manifestations was variable, with liver disease as the most
frequent revealing symptom (60%). The influence of interferon remains
unclear. However, it seemed to trigger more than to relieve lichen planus.


===============================================================
4.) Lichen planus occurring after hepatitis B vaccination: a new case.
===============================================================
J Am Acad Dermatol 2001 Oct;45(4):614-5
Al-Khenaizan S.

Division of Dermatology, Department of Medicine, King Fahad National Guard Hospital, Riyadh, Saudi Arabia.

Lichen planus is a pruritic inflammatory dermatosis of unknown origin. An increased prevalence of a wide range of liver disease in lichen planus has been observed by many authors. Most recently, many reports appeared of the occurrence of lichen planus after administration of different types of hepatitis B vaccines. We report one case and briefly review this intriguing observation.

===============================================================5.) A case of oral lichen planus with chronic hepatitis C successfully treated by glycyrrhizin (LICORICE)
===============================================================

AU: Nagao-Y; Sata-M; Tanikawa-K; Kameyama-T
SO: Kansenshogaku-Zasshi. 1995 Aug; 69(8): 940-4
ISSN: 0387-5911
LA: ENGLISH
AN: 96083310
===============================================================

===============================================================
6.) Nail lichen planus in children: clinical features, response to treatment, and long-term follow-up.
===============================================================
Arch Dermatol 2001 Aug;137(8):1027-32 

Tosti A, Piraccini BM, Cambiaghi S, Jorizzo M.

Department of Dermatology, University of Bologna, Via Massarenti 1, 40138 Bologna, Italy. [email protected]

OBJECTIVE: To report clinical features, response to treatment, and long-term follow-up of nail lichen planus in children. DESIGN: Retrospective study involving 15 children with nail lichen planus. SETTING: Outpatient consultation for nail disorders at the Department of Dermatology of the University of Bologna, Bologna, Italy. PATIENTS OR OTHER PARTICIPANTS: We diagnosed nail lichen planus in 15 children younger than 12 years, including 10 children with typical nail matrix lesions, 2 children with 20-nail dystrophy (trachyonychia), and 3 children with idiopathic atrophy of the nails. Only 2 of the 15 children had oral lichen planus; none had cutaneous lesions. A nail biopsy confirmed the diagnosis in all cases. INTERVENTION: Intramuscular triamcinolone acetonide, 0.5 to 1 mg/kg per month, was prescribed to children with typical nail lichen planus and prolonged from 3 to 6 months until the proximal half of the nail was normal. No treatment was prescribed to patients with 20-nail dystrophy or idiopathic atrophy of the nails. RESULTS: Treatment with systemic corticosteroids was effective in curing typical nail lichen planus. Two children experienced a recurrence of the disease during the follow-up. Recurrences were always responsive to therapy. The 2 children with 20-nail dystrophy improved without any therapy. Nail lesions caused by idiopathic atrophy of the nails remained unchanged during the follow-up period. CONCLUSIONS: Nail lichen planus in children is not rare but probably underestimated. It often presents with atypical clinical features such as 20-nail dystrophy or idiopathic atrophy of the nails.


=============================================================== 
7.) Azathioprine for the treatment of severe erosive oral and generalized lichen planus.
=============================================================== 
Acta Derm Venereol 2001 Oct-Nov;81(5):378-9 

Verma KK, Mittal R, Manchanda Y.

Publication Types: 
Letter 

=============================================================== 

=============================================================== 
8.) Ulcerative lichen planus: a case responding to recombinant platelet-derived growth factor BB and immunosuppression.
=============================================================== 
Acta Derm Venereol 2001 Oct-Nov;81(5):364-5 

Wollina U, Konrad H, Graefe T.

Publication Types: 
Letter 

=============================================================== 

=============================================================== 
9.) [Study on regulatory effect of composite taixian tablet on immune function of red blood cell in patients with oral lichen planus]
=============================================================== 
Zhongguo Zhong Xi Yi Jie He Za Zhi 2000 Apr;20(4):261-3 

[Article in Chinese]

Wu Y, Zeng G, Li B.

Department of Stomatology, First Affiliated Hospital of Shanxi Medical University, Taiyuan (030001).

OBJECTIVE: To explore the regulatory effect of Composite Taixian tablet (CTXT) on red blood cell (RBC) immune function in patients with oral lichen planus (OLP) for the sake of providing the basis of clinical medication. METHODS: Sixty patients with OLP were assigned randomly into three groups and were treated by CTXT, Tripterygium hypoglaucum tablet and polyactin-A tablet respectively. And the changes of RBC-C3b receptor and immune circulating rosette complex on the surface of erythrocytes (RBC-ICR) were measured by saccharomycetic assay. RESULTS: Effect of CTXT was superior to that of Tripterygium hypoglaucum and polyactin-A tablets. CONCLUSION: CTXT is a relatively effective remedy with less side effect, it is worthy to be studied further.

=============================================================== 

=============================================================== 
10.) Topical tacrolimus and pimecrolimus: future directions.
=============================================================== 
Semin Cutan Med Surg 2001 Dec;20(4):268-74 

Ling MR.

Emory University School of Medicine, Atlanta, GA, USA.

Topical tacrolimus ointment and pimecrolimus cream represent the first members of a new class of medications. Topical immunomodulators have been developed for the treatment of atopic dermatitis. Their superb safety profiles and excellent efficacy as anti-inflammatory agents make them attractive candidates to treat a host of other skin disorders. This article reviews published experiences that use them for psoriasis, seborrheic dermatitis, lichen planus, pyoderma gangrenosum and other diseases. Possible modifications to these compounds and novel untested applications are discussed.

=============================================================== 
11.) Tacrolimus clinical studies for atopic dermatitis and other conditions.
=============================================================== 
Semin Cutan Med Surg 2001 Dec;20(4):250-9 

Bergman J, Rico MJ.

Division of Pediatric and Adolescent Dermatology, Children's Hospital, San Diego, CA, USA.

The first topical immunomodulator approved for human use, tacrolimus ointment (Protopic, Fujisawa, Healthcare, Inc, Deerfield, IL), has been shown to be effective and safe in the treatment of children (aged 2 years and older) and adults with atopic dermatitis (AD). Clinical trials conducted worldwide have involved 12,000 patients, with safety and efficacy data available for up to 3 years of treatment. In addition to its beneficial effects in the management of AD, topical tacrolimus has also been reported to be of benefit in other immunologically mediated skin diseases including: hand dermatitis, contact dermatitis, eyelid dermatitis, erosive lichen planus, steroid-induced rosacea, pyoderma gangrenosum, and graft-versus-host disease. This article reviews the clinical experience of topical tacrolimus in the treatment of AD and other skin conditions.

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12.) Low-dose low-molecular-weight heparin (enoxaparin) is beneficial inlichen planus: a preliminary report 
===============================================================
Emmilia Hodak, MD,a Gil Yosipovitch, MD,a Michael David, MD,a Arieh Ingber,
MD,b
Liran Chorev, MD,b Ofer Lider, PhD,c Leora Cahalon, PhD,c and Irun R.
Cohen, MDc 
Petah Tikva, Tel Aviv, Jerusalem, and Rehovot, Israel 

Background: Low-dose heparin devoid of anticoagulant activity inhibits
T-lymphocyte heparanase activity, which is crucial in T-cell migration to
target tissues. 

Objective: The purpose of this study was to assess the efficacy of low-dose
enoxaparin (Clexane), a low-molecular-weight heparin, as monotherapy in
lichen planus. 

Methods: Included in the study were 10 patients with widespread
histopathologically
proven lichen planus (LP) associated with intense pruritus of several
months' duration. Patients were given 3 mg enoxaparin, subcutaneously once
weekly; three patients received four injections, and seven patients
received six injections. 

Results: In nine patients the itch disappeared within 2 weeks. Within 4 to
10 weeks
in eight of these patients, there was complete regression of the eruption
with residual postinflammatory hyperpigmentation; in one patient, there was
marked improvement. In one patient, no effect was observed. Of the four
patients who also had oral LP, only one showed improvement. No side effects
were observed in any of the patients. 

Conclusion: These findings indicate that enoxaparin may be a simple,
effective treatment for cutaneous LP. (J Am Acad Dermatol 1998;38:564-8.) 

=============================================================== 
13.) Low-dose low-molecular-weight heparin in lichen planus 
=============================================================== 
J Am Acad Dermatol 2002 Jan;46(1):141-3 

Ranju Rai, MD
Inderjeet Kaur, MD, MNAMS
Bhushan Kumar, MD, MNAMS
Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh-160 012, India, Correspondence to Dr Kumar

To the Editor:

Lichen planus is a T-cell-mediated disorder. Low-dose heparin devoid of anticoagulant activity inhibits the activity of T-lymphocyte heparanase, which is the enzyme crucial in T-cell migration to target tissues.1,2 This enzyme degrades the heparin-sulfate moiety of the proteoglycan of the extracellular matrix. 

We read with great interest the article by Hodak et al3 (J Am Acad Dermatol 1998;38:564-8) on the use of low-dose, low-molecular-weight heparin (enoxaparin) in lichen planus. On the basis of the findings of this preliminary report, we administered enoxaparin (Aventis Pharmaceuticals Inc, Bridgewater, NJ) as monotherapy to 10 previously untreated patients with histologically proven lichen planus (with or without associated oral lesions) attending our Dermatology Outpatient Department. Exclusion criteria included any known hemostatic defect, uncontrolled hypertension, renal or hepatic insufficiency, known history of peptic ulcer, diabetic retinopathy, hemorrhagic stroke, or hypersensitivity to either enoxaparin, heparin, or its derivatives. Patients were not concomitantly receiving any nonsteroidal anti-inflammatory drugs or systemic glucocorticoids. There was no history of intake of any medication known to induce lichen planus-like reactions. A baseline hemogram and coagulation profile were done in all patients. Renal function tests, hepatic function tests, and diabetic status of the patient were also evaluated. 

Enoxaparin was administered to all the patients in a dose of 3 mg subcutaneously once a week for a period of 6 weeks. Response was judged weekly on the basis of (1) reduction in itching, (2) reduction in infiltration, (3) decrease in the size of lesions, (4) time required for complete clinical remission, (5) histopathologic changes, (6) response of oral lesions, and (7) side effects. Of these, itching, infiltration, and size of the lesions were graded as follows and recorded on each weekly visit: itching: mild, +; moderate, ++; severe, +++; infiltration: mild, +; moderate, ++; severe, +++; size of lesions: 0, 0.5 cm; 1, 0.5-1 cm; 2, 1.5-2.5 cm; 3, >2.5 cm. 

Details of the results are shown in Table I. 



=============================================================== 
Table I. Clinical profile and response to treatment 
=============================================================== 
Patient No. Age (y)/Sex Duration of disease Distribution of lesions Koebnerization Nail involvement Mucosal involvement Response (after 6th dose) 
1 32/F 7 mo Arm, forearm – – – Minimal decrease in infiltration (clinical) 
2 56/M 2 mo Arm, forearm, hands, wrist + – – Disappearance of itching 
3 60/F 2 mo Hands – – – No change 
4 23/F 4 y LPH (generalized) + – – Minimal decrease in itching, skin necrosis 
5 33/F 3 mo Generalized + – – Increased itching, LN-like lesions at the end of 3rd wk 
6 60/F 6 mo Generalized – – Lacy pattern (R) buccal mucosa No change 
No change 
7 40/M 8 mo Generalized – – – No change 
8 26/M 3 y Forearms, legs – – – No change 
9 48/F 8 mo Generalized – – Lacy pattern (L) buccal mucosa No change 
10 32/F 7 mo Generalized + – – 

+, Presence; –, absence; L, left; LN, lichen nitidus; LPH, lichen planus hypertrophicus; R, right. 

=============================================================== 
Clinical response was noted in patients 1 and 2 only. In patient 1, there was minimal decrease in infiltration of the lesions after the sixth injection. In patient 2, the itching completely disappeared at the end of the study. In patients 4 and 5 side effects necessitated discontinuation of treatment after the fourth injection. Complete remission was not seen in any patient. Oral lesions were noted in patients 6 and 9. These too did not show any clinical change at the end of the study. 
Posttherapy biopsy specimens were obtained in patients 1 and 2 who showed clinical response. There was no histopathologic change at the end of treatment in terms of epidermal thinning, basal cell degeneration, or decrease in the degree of lymphocytic infiltrate. 

Authors in the previous study3 did not note any significant side effects with enoxaparin. However, we noticed skin necrosis after the fourth injection in the lesions of patient 4 with lichen planus hypertrophicus. We were forced to stop further injections in her. Skin necrosis is a rare complication of heparin administration and is usually localized to injection sites. If skin necrosis is seen at sites far from the injection site, it is said to be a warning sign of potentially lethal complications.4 In patient 5, multiple lichen nitidus-like lesions developed over both upper and lower extremities with increased itching after the fourth injection. Further treatment was also stopped in this patient. The remaining patients completed 6 weekly injections without any clinical response or side effects. 

It has been suggested that the immunomodulatory molecules in heparin are probably sulfated disaccharides that act by inhibiting the production of the key proinflammatory cytokine tumor necrosis factor .5,6 Only certain batches of heparin that contain these active disaccharide molecules will thus be effective in lichen planus. Our batch of enoxaparin was not tested for immunomodulatory activity and this could be the reason for its failure in our patients with lichen planus. Procuring a batch of enoxaparin with tested immunomodulatory activity may not be feasible to all, which hampers its use in regular practice. 

Our experience differs from that of Hodak et al3 who have suggested that enoxaparin may be a simple and effective treatment for cutaneous lichen planus. None of our patients showed complete clinical remission at the end of the study. We did not extend our study to more than 6 weeks because it would then have been difficult to evaluate the actual efficacy of therapy. 


=============================================================== 
14.) Management of recalcitrant ulcerative oral lichen planus with topical tacrolimus.
=============================================================== 
J Am Acad Dermatol 2002 Jan;46(1):35-41 

Kaliakatsou F, Hodgson TA, Lewsey JD, Hegarty AM, Murphy AG, Porter SR.

Unit of Oral Medicine, Eastman Dental Institute for Oral Health Care Sciences, University College London, United Kingdom

OBJECTIVE: Our purpose was to investigate the efficacy and safety of 0.1% topical tacrolimus in erosive or ulcerative oral lichen planus. METHODS: This was an open-label, noncomparative study conducted in an outpatient oral medicine unit in London, United Kingdom. The study covered an 8-week period with a 22-week follow-up after cessation of therapy. Nineteen patients, aged 28 to 87 years with biopsy-proven oral lichen planus refractory to, or dependent on, systemic immunosuppressive agents, were enrolled. Seventeen patients (89%) completed the study. Application of 0.1% tacrolimus was administered to all symptomatic oral mucosal lesions. Clinical review took place 1, 3, 5, 7, and 8 weeks after commencing therapy. Alleviation of symptoms was evaluated by using a visual analogue scale as well as the McGill Pain and Oral Health Impact profile questionnaires. The extent of the oral mucosal erosion or ulceration was directly measured by the same clinician at all visits. Safety assessments included monitoring of adverse events, complete blood cell count, renal and hepatic clinical chemistry, and tacrolimus blood concentrations. RESULTS: Tacrolimus caused a statistically significant improvement in symptoms within 1 week of commencement of therapy. A mean decrease of 73.3% occurred in the area of ulceration over the 8-week study period. Local irritation (in 6 subjects, 35%) was the most commonly reported adverse effect. Laboratory values showed no significant changes with time. Therapeutic levels of tacrolimus were demonstrated in 8 subjects but were unrelated to the extent of oral mucosal involvement. Thirteen of 17 patients suffered a relapse of oral lichen planus within 2 to 15 weeks of cessation of tacrolimus therapy. CONCLUSION: Topical tacrolimus is effective therapy for erosive or ulcerative oral lichen planus.

=============================================================== 
15.) Topical tacrolimus in the treatment of symptomatic oral lichen planus: a series of 13 patients.
=============================================================== 
J Am Acad Dermatol 2002 Jan;46(1):27-34 

Rozycki TW, Rogers RS 3rd, Pittelkow MR, McEvoy MT, el-Azhary RA, Bruce AJ, Fiore JP, Davis MD.

Department of Dermatology, Mayo Clinic, Rochester, Minnesota, USA.

BACKGROUND: Oral lichen planus (OLP) is a relatively common, chronic inflammatory condition, which frequently presents with symptoms of pain and irritation. OLP is often difficult to manage. Therefore there is a need for more effective and safer therapies for symptomatic OLP. OBJECTIVE: Our purpose was to determine the effectiveness of topical tacrolimus as therapy for symptomatic OLP. METHODS: A retrospective review was performed of 13 patients with symptomatic OLP treated with topical tacrolimus between September 1999 and September 2000. RESULTS: Eleven of the 13 patients reported definite symptomatic response to treatment and 2 had no response. Eight patients had a partial response, whereas 3 patients had a complete response with respect to lesion clearance. Seven of the responding patients had no flares with continued treatment. The other 4 patients noted flares soon after stopping the treatment. Side effects were rare and minor. CONCLUSIONS: In this retrospective case series of 13 patients, topical tacrolimus was well tolerated and appeared to be an effective therapy to control symptoms and clear lesions of OLP.


=============================================================== 
16.) Mast cell degranulation and the role of T cell RANTES in oral lichen planus.
=============================================================== 
Oral Dis 2001 Jul;7(4):246-51 

Zhao ZZ, Sugerman PB, Zhou XJ, Walsh LJ, Savage NW.

School of Dentistry, The University of Queensland, Brisbane, Australia.

OBJECTIVES: The present study investigated mast cell degranulation in oral lichen planus (OLP) and the effect of OLP lesional T cell supernatants on mast cell degranulation. MATERIALS AND METHODS: Immunohistochemistry was used to identify mast cell degranulation in both OLP (n = 22) and normal control (n = 14) tissues. OLP lesional T cell lines (n = 5) and HMC-1 (a human leukemia mast cell line) were used to examine the effects of OLP T cell supernatants on mast cell degranulation in vitro. RESULTS: Approximately 60% of mast cells were degranulated in OLP. OLP lesional T cells expressed mRNA for RANTES, and TNF-alpha stimulation upregulated OLP lesional T cell RANTES secretion. OLP lesional T cell supernatants induced degranulation of HMC-1 with release of TNF-alpha and histamine. Human recombinant RANTES similarly induced mast cell degranulation. Anti-RANTES antibody blocked OLP lesional T cell supernatant-induced mast cell degranulation. CONCLUSIONS: This study is the first to show that OLP lesional T cells produce and secrete RANTES which triggers human mast cell degranulation. Degranulating mast cells release TNF-alpha which upregulates OLP lesional T cell RANTES secretion. Such a cyclical mechanism may underlie disease chronicity and future therapies may include blocking RANTES or TNF-alpha activity in OLP.

=============================================================== 
17.) Levamisole and/or Chinese medicinal herbs can modulate the serum level of squamous cell carcinoma associated antigen in patients with erosive oral lichen planus.
=============================================================== 
J Oral Pathol Med 2001 Oct;30(9):542-8
Sun A, Chiang CP.

School of Dentistry, College of Medicine, National Taiwan University, No. 1 Chang-Te Street, Taipei, Taiwan.

The serum levels of squamous cell carcinoma associated antigen (SCCA) were determined by a microparticle enzyme immunoassay in a group of patients with stage I oral squamous cell carcinoma (OSCC), major or minor type erosive oral lichen planus (EOLP), recurrent aphthous stomatitis (RAS), Behcet's disease (BD), oral leukoplakia (OL), or oral submucous fibrosis (OSF), and in normal control subjects. About 97% of the normal control subjects and the patients with minor type EOLP, RAS, BD, OL or OSF had a serum level of SCCA within the normal limit of 1.2 ng/ml. However, 6 of the 12 (50%) patients with stage I OSCC and 14 of the 31 (45.2%) patients with major type EOLP had a serum level of SCCA greater than 1.2 ng/ml. The mean serum level of SCCA in stage I OSCC patients (1.38+/-1.16 ng/ml) or in major type EOLP patients (1.32+/-1.23 ng/ml) was significantly higher than that in normal control subjects (P<0.001) and that in the patients with minor type EOLP (P<0.001), RAS (P<0.001), BD (P<0.05), OL (P<0.05), or OSF (P<0.05). Either major or minor type EOLP patients could obtain a significant mean reduction of the serum SCCA level of 0.34-0.63 ng/ml after treatment with levamisole and/or Chinese medicinal herbs for 1-30 months. Combination therapy with levamisole plus Chinese medicinal herbs could achieve a shorter duration of treatment to get complete remission than the single therapy with either levamisole only or Chinese medicinal herbs only. We conclude that levamisole and/or Chinese medicinal herbs can modulate the serum SCCA level in EOLP patients. SCCA may be a useful marker in evaluating therapeutic effects and in monitoring the disease status of EOLP. For EOLP patients, the combination therapy is superior to the single therapy of levamisole or of Chinese medicinal herbs.

===============================================================
18.) Dramatic response to levamisole and low-dose prednisolone in 23 patients with oral lichen planus: a 6-year prospective follow-up study.
===============================================================
AU: Lu-SY; Chen-WJ; Eng-HL
AD: Department of Dentistry, Ghang Gung Memorial Hospital, Kaohsiung,
Taiwan, Republic of China.
SO: Oral-Surg-Oral-Med-Oral-Pathol-Oral-Radiol-Endod. 1995 Dec; 80(6): 705-9
ISSN: 1079-2104
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: The purpose of this prospective study was to evaluate the short-term
and long-term clinical efficacy of levamisole used with low-dose
prednisolone in patients with refractory oral lichen planus. Twenty-three
patients with OLP who had been treated unsuccessfully with other modalities
were given 150 mg/day levamisole and 15 mg/day prednisolone for 3
consecutive days each week. Twelve patients showed dramatic remission of
signs and symptoms within 2 weeks, whereas 11 had partial remission. All 23
reported significant pain relief and showed no evidence of erosive oral
lichen planus after 4 to 6 weeks of treatment. All 23 also remained free
from symptoms for 6 to 9 months after the treatment ended. There were few
side effects from this treatment besides minor skin rash, headache, and
insomnia from the levamisole in three cases. We conclude that the addition
of levamisole to prednisolone may produce improved results in the
management of erosive oral lichen planus.

===============================================================
19.) Successful treatment of generalized lichen planus with recombinant interferon alfa-2b.
===============================================================
AU: Hildebrand-A; Kolde-G; Luger-TA; Schwarz-T
AD: Department of Dermatology, University of Munster, Germany.
SO: J-Am-Acad-Dermatol. 1995 Nov; 33(5 Pt 2): 880-3
ISSN: 0190-9622
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Three patients with generalized lichen planus were treated with
interferon alfa-2b. The therapy was tolerated well by all patients with
only minor side effects. A response was observed within 2 to 3 weeks.
Itching and erythema decreased first, followed by gradual flattening and
disappearance of papules and plaques after 8 to 10 weeks of treatment.
After 12 weeks, therapy was discontinued after stepwise dosage reduction.
In two patients, minor lesions recurred during dosage reduction. Both
flares were controlled by readministration of interferon.

===============================================================
20.) [Prevalence of oral lichen planus and oral leukoplakia in 112 patients with oral squamous cell carcinoma]
===============================================================
Acta Otorrinolaringol Esp 2001 Apr;52(3):239-43 

[Article in Spanish]

Haya Fernandez MC, Bagan Sebastian JV, Basterra Alegria J, Lloria de Miguel E.

Servicio de Estomatologia del HGU, Universidad de Valencia.

OBJECTIVE: To study the association existing between precancerous conditions, like oral lichen planus and oral leukoplakia into 112 patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: We applied a protocol to 112 patients with OSCC in the "Servicio de Estomatologia del Hospital General Universitario de Valencia". We made two groups: 1. patients with precancerous lesions and oral carcinoma, 2. patients with OSCC and no precancerous lesions. RESULTS: The average age was 61.4 years, 85 of them being men and 27 women. The tongue and floor of the mouth were the most common locations. 33.6% of the tumours presented stage TNM I, most of them being histologically well differentiated and the 55.8% were ulcerated. We found differences between two groups of the patients regarding alcohol and tobacco habits, location, size and clinical stage and histological differentiation of the malignant lesions.

===============================================================
21.) Dental metal allergy in patients with oral, cutaneous, and genital lichenoid reactions.
===============================================================
Am J Contact Dermat 2001 Sep;12(3):146-50 

Scalf LA, Fowler JF Jr, Morgan KW, Looney SW.

Division of Dermatology, University of Louisville School of Medicine, Louisville, KY, USA.

BACKGROUND: The subject of lichen planus (LP) and dental metal allergy long has been debated. An overwhelming majority of the existing literature focuses on mercury and gold salts in relation to oral lichen planus. OBJECTIVE: Our objective was to expand current knowledge regarding LP and lichenoid lesions (LL) and dental metal allergy by investigating more metals and investigating cutaneous and genital disease in addition to oral disease. METHODS: Fifty-one patients with known LP or LL were patch tested to a series of dental metals. Patients chose to replace their dental metals or make no revision. A telephone survey was conducted after 1 year to determine disease state. RESULTS: Thirty-eight of 51 patients (74.5%) had at least 1 positive reaction. Twenty-five of 51 patients (49.0%) showed sensitivity to at least 1 mercurial allergen. Prevalence data for patients patch tested by the North American Contact Dermatitis Group (NACDG) from 1996 to 1998 was available for chromate, cobalt, gold, nickel, and thimerosal. The prevalence of positive reactions was higher in our group than in the NACDG group for all 5 of these allergens, and statistical significance was achieved for chromate (P = .028), gold (P = .041), and thimerosal (P = .005). Of patients who had a positive patch test reaction to 1 or more metals, 100% (9 of 9) reported improvement after metal replacement, whereas 62.5% (15 of 24) reported improvement without metal replacement. CONCLUSION: Sensitization to dental metals is more common among LP and LL patients than in routinely tested patients, and might be an etiologic or triggering factor in the disease. 

===============================================================
22.) [Cellular immune alterations in fifty-two patients with oral lichen planus.]
===============================================================
Med Oral 2001 Aug-Oct;6(4):246-62 

[Article in English, Spanish]

Gandara Rey J, Garcia Garcia A, Blanco Carrion A, Gandara Vila P, Rodriguez Nunez I.

Departamento de Medicina Oral y Maxilofacial, Facultad de Medicina y Odontologia, Universidad de Santiago de Compostela, Santiago de Compostela, Espana. [email protected]

OBJECTIVES: Abnormal immune mechanisms appear to play an important role in the pathogenesis of lichen planus (LP). DESIGN: A prospective clinical study was made to investigate the differences in T cell subpopulations in 52 patients with oral lichen planus (OLP) and 54 healthy controls. RESULTS: Statistically significant differences were observed among the OLP patients versus the controls: the percentages of CD3+, CD8+, DR+, CD57+ and CD8CD45RA+ cells were depressed, while elevations were recorded in the subpopulations expressing CD4+, and in the ratios CD4/CD8+ and CD8CD45RO+/CD8CD45RA+. CONCLUSIONS: These results suggest the existence of differences in the lymphocyte subpopulations between healthy subjects and patients with OLP. These findings do not coincide with the previously published observations, however; the observed cellular immune alterations thus appear to relate more to lymphocyte reaction capacity than to the actual number of cells in each population subgroup.

===============================================================
23.) Isolated lichen planus of the toe nails treated with oral prednisolone.
===============================================================
Clin Exp Dermatol 2001 Jul;26(5):412-4 

Evans AV, Roest MA, Fletcher CL, Lister R, Hay RJ.

Department of Dermatology, Guy's Hospital, London, UK. [email protected]

We report a case of lichen planus affecting the toe nails without involvement of the skin or finger nails. To our knowledge this is the first time this has been reported. We also discuss the clinical features, histology and treatment of nail lichen planus.

===============================================================
24.) Lichen planus-like eruption following autologous bone marrow transplantation for chronic myeloid leukaemia.
===============================================================
Australas J Dermatol 2001 Aug;42(3):188-91 

Pagliaro JA, White S, Strutton G, Guerin D.

Department of Dermatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.

A 47-year-old female treated with an autologous bone marrow transplant and cytotoxic chemotherapy developed a lichen planus-like eruption 12 months later. It involved the skin and oral mucosa, with the histological features of a lichenoid graft-versus-host reaction, including satellite cell necrosis. This eruption developed de novo. The eruption resolved with topical betamethasone valerate 0.1% cream despite the ongoing use of the immunomodulatory agent interferon-alpha2b. Such a reaction in an autologous setting has only been described once previously.

===============================================================
25.) Immune mechanisms in oral lichen planus.
===============================================================
Acta Odontol Scand 2001 Jun;59(3):174-7 

Thornhill MH.

Oral Disease Research Centre, Bart's and the London, Queen Mary School of Medicine and Dentistry, UK. [email protected]

Although we still don't know the cause, there has been much research into the immune and pathological mechanisms that underlie oral lichen planus (OLP) and it is now possible to piece together a much clearer picture of the disease process. There is consensus that in OLP there is chronic, cell-mediated, immune damage to basal keratinocytes in the oral mucosa that are recognized as being antigenically foreign or altered. In most cases, however, the identity of the target antigen remains unknown. It is likely that cytokines released by the affected keratinocytes, and the associated inflammatory infiltrate, play a key role in the selective recruitment of the T-cell-dominated infiltrate that characterizes OLP, through their ability to induce adhesion molecule expression as well as further cytokine and chemokine release. In susceptible individuals, chronic presentation of antigen by basal keratinocytes may perpetuate the condition and direct cell-mediated immune damage on the keratinocytes.

===============================================================
26.) Cyclosporin A in the treatment of lichen planus.
===============================================================
Arch Dermatol 1989 Oct;125(10):1436 

Higgins EM, Munro CS, Friedmann PS, Marks JM.

Publication Types: 
Letter 

PMID: 2802654 [PubMed - indexed for MEDLINE] 
===============================================================

===============================================================
27.) Oral metronidazole treatment of lichen planus.
===============================================================
J Am Acad Dermatol 2000 Aug;43(2 Pt 1):260-2 

Buyuk AY, Kavala M.

Division of Dermatology, SSK Goztepe Educational Hospital, IStanbul, Turkey.

BACKGROUND: Oral metronidazole has been reported to be effective in some patients with idiopathic lichen planus (LP) who did not have concomitant protozoal infections of the intestinal or genital tracts. OBJECTIVE: Our purpose was to evaluate the efficacy of this drug in the treatment of generalized LP. METHODS: Nineteen patients with LP who were free from intestinal and genital protozoal infections were treated with oral metronidazole, 500 mg twice daily, for 20 to 60 days and were followed up for a period of 5 to 36 months. RESULTS: Fifteen patients (78.9%) improved with metronidazole treatment. Complete response was observed in 13 patients (7 women and 6 men). Two patients responded partially. Worsening of the lesions was observed in 1 of the 4 nonresponding patients. CONCLUSION: Metronidazole may be an alternative therapy for the treatment of generalized LP. Its immunomodulatory activity seems to be a possible mechanism of action besides its antimicrobial activity.

Publication Types: 
Clinical Trial 

===============================================================
28.)Idiopathic lichen planus: treatment with metronidazole.
===============================================================
J Am Acad Dermatol 1995 Aug;33(2 Pt 1):301-2 

Wahba-Yahav AV.

PMID: 7622660 [PubMed - indexed for MEDLINE] 
===============================================================


===============================================================
29.) Intestinal amebiasis, lichen planus, and treatment with metronidazole.
===============================================================
J Am Acad Dermatol 1989 Jun;20(6):1128-9 

Wahba-Yahav AV.

PMID: 2754064 [PubMed - indexed for MEDLINE] 

===============================================================
30.) Urinary tract infection as a cause of lichen planus: metronidazole therapy.
===============================================================
J Am Acad Dermatol 1984 May;10(5 Pt 2):905-7 Related Articles, Books, LinkOut 

Shelley WB, Shelley ED.

A 51-year-old woman with generalized lichen planus for 23 years experienced total involution of her lesions during metronidazole therapy. Discontinuance of the treatment on two occasions led to partial recurrence of the skin lesions, which again promptly cleared on reinstitution of metronidazole. It is believed that this patient's lichen planus was an immune reaction to circulating bacterial antigen. The presumed source was a chronic urinary bladder infection. Continued remission of the lichen planus and the cystitis was subsequently achieved for over a year by daily prophylactic nitrofurantoin therapy. Identification and eradication of chronic foci of infection are suggested for the management of generalized chronic lichen planus.

===============================================================
31.) [Metronidazole treatment of the erosive ulcerative form of lichen ruber planus of the oral mucosa]
===============================================================
Stomatologiia (Mosk) 1981 Nov-Dec;60(6):61-2 

[Article in Russian]

Antonova TN, Kutin SA.

PMID: 6947570 [PubMed - indexed for MEDLINE] 
===============================================================
===============================================================
32.) Clinical and pathological characteristics of oral lichen planus in hepatitis C-positive and -negative patients.
===============================================================
Clin Otolaryngol 2002 Feb;27(1):22-6 

Romero MA, Seoane J, Varela-Centelles P, Diz-Dios P, Otero XL.

Department of Stomatology, School of Medicine and Dentistry, University of Santiago de Compostela, Canton Grande 5, E-15003 A Coruna, Spain. [email protected]

The reported prevalence rate of anti-hepatitis C virus (HCV) antibodies in patients with oral lichen planus shows wide geographical variation and ranges from 0 to 65%. Certain characteristic clinical features have been attributed to oral lichen planus associated to HCV infection. The purpose of this investigation has been to assess hypothetical clinical differences, as well as differences in the intensity of the subepithelial inflammatory infiltrate between oral lichen planus-HCV +ve patients and oral lichen planus-HCV -ve patients. A total of sixty-two patients entered the study. Their mean age was 63.5 +/- 14.49 years, and 48.4% of them were men and 51.6% women. Patients were classified according to their serum HCV positivity. Age, sex, clinical presentation (reticular or atrophic-erosive), extension of the lesions, location of the lesions, number of locations affected, intensity of the inflammatory infiltrate and Candida albicans colonization were recorded for each patient. Reticular lichen planus was the most frequent clinical presentation in both HCV +ve (57.1%) and HCV -ve patients (63.6%). C. albicans colonization ranged from 42.8% in HCV +ve and 41.7% in HCV -ve patients. HCV + ve patients showed certain oral locations more frequently affected than HCV -ve ones: lip mucosa, 28.6% versus 7.3%; tongue, 57.1% versus 29.1%; and gingiva, 71.4% versus 23.6%. The number of affected intraoral locations was higher in HCV +ve patients (71.4%) than among HCV -ve ones (20.4%; chi2 = 8.34; P < 0.011). No statistically significant differences could be established in terms of density of subepithelial inflammatory infiltrate between the groups. Our results reinforce the need for liver examination in all patients with oral lichen planus, particularly those showing lesions on the gingiva with multiple intraoral locations affected, as no pathological differences could be identified between HCV + ve and HCV -ve patients.

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33.) High prevalence of anticardiolipin antibodies in patients with HCV-associated oral lichen planus.
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Int J Mol Med 2002 Mar;9(3):293-7 
Nagao Y, Tsubone K, Kimura R, Hanada S, Kumashiro R, Ueno T, Sata M.

Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume 830-0011, Japan. [email protected]

Hepatitis C virus (HCV) has been linked to extrahepatic manifestations such as oral lichen planus (OLP). In addition, anticardiolipin antibodies (aCL) and cryoglobulin have been demonstrated in chronic hepatitis C. The aim of this study was to investigate these prevalences in patients with HCV-associated OLP. The prospective study investigated the role of these factors in 133 subjects: 28 with OLP-HCV(+) (group 1), 22 with OLP-HCV(-) (group 2), 33 without OLP-HCV(+) (group 3), and 50 healthy volunteers matched for age and sex served as control group (group 4). Levels of immunoglobulin G (IgG) and IgM aCL antibodies, and cryoglobulin in serum were evaluated by enzyme-linked immunosorbent assay. The prevalence of aCL in groups 1, 2, 3, and 4 were 32.1, 18, 36.3, and 8%, respectively. The positive rate of aCL was significantly higher in groups 1 and 3 than that in the control group (group 1; p=0.02 vs. the control group, group 3; p<0.01 vs. the control group). There were no significant differences in cryoglobulin among the groups. The findings of the present study showed a high prevalence of IgG and IgM aCL in the serum of patients with HCV infectious diseases. A positive factor for aCL was determined by age, sex, the presence of OLP, and HCV infection.

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34.) The clinical features, malignant potential, and systemic associations of oral lichen planus: a study of 723 patients.
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J Am Acad Dermatol 2002 Feb;46(2):207-14 

Eisen D.

Dermatology Research Associates, Cincinnati, OH 45230, USA. [email protected]

BACKGROUND: Although oral lichen planus (OLP) is a relatively common disorder, reports comprising large numbers of patients with the disease are lacking in the dermatology literature. OBJECTIVE AND METHODS: The purpose of this investigation was to describe the clinical characteristics of 723 patients with biopsy-proven OLP who were followed up from 6 months to 8 years (mean, 4.5 years). RESULTS: Of the 723 patients, 75% were women and 25% men. The erosive form of the disease was the predominant type in 40% of patients at initial presentation, and symptoms were present in the majority of patients with all forms of the disease. Isolated gingival lichen planus was observed in 8.6% of patients. Precipitating factors that resulted in an exacerbation of the disease were frequently noted and included stress, foods, dental procedures, systemic illness, and poor oral hygiene. In 195 patients prospectively screened, no liver abnormalities or antibodies to hepatitis B or C were detected. Oral squamous cell carcinoma developed in 6 patients (0.8%) at sites previously diagnosed by clinical examination as erosive or erythematous lichen planus. CONCLUSIONS: Patients with OLP usually display lesions with distinctive clinical morphology and characteristic distribution but may also present with a confusing array of forms and patterns mimicking other diseases. Because patients with OLP may be at an increased risk for the development of squamous cell carcinoma, periodic follow-up is mandatory to detect malignant transformation. Routine screening of American patients with OLP for hepatitis C and other liver abnormalities does not appear to be warranted as in Italian and Japanese patients with OLP.

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35.) Management of oral lichen planus.
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Am J Clin Dermatol 2000 Sep-Oct;1(5):287-306 

Scully C, Eisen D, Carrozzo M.

International Centres for Excellence in Dentistry, Eastman Dental Institute for Oral Healthcare Sciences, University College London, University of London, London, England. [email protected]

Lichen planus is a relatively common disorder of the stratified squamous epithelia. Most dental and medical practitioners see patients with lichen planus, but not all are recognized as having the disease. Patients with lichen planus may have concomitant involvement of the disease in multiple sites. Oral lichen planus lesions usually have a distinctive clinical morphology and characteristic distribution, but oral lichen planus may also present a confusing array of patterns and forms, and other disorders may clinically mimic oral lichen planus. The etiopathogenesis of lichen planus appears to be complex, with interactions between genetic, environmental, and lifestyle factors. Much has now been clarified about the etiopathogenic mechanisms involved and interesting new associations, such as with liver disease, have emerged. The management of lichen planus is still not totally satisfactory in all cases and there is as yet no definitive treatment that results in long term remission, but there have been advances in the control of the condition. Amongst the many treatments available, high potency topical corticosteroids remain the most reliably effective, though topical cyclosporine, topical tacrolimus, or systemic corticosteroids may be indicated in patients whose condition is unresponsive to topical corticosteroids.

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36.) Lichen planus occurring after hepatitis B vaccination: a new case.
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J Am Acad Dermatol 2001 Oct;45(4):614-5 

Al-Khenaizan S.

Division of Dermatology, Department of Medicine, King Fahad National Guard Hospital, Riyadh, Saudi Arabia.

Lichen planus is a pruritic inflammatory dermatosis of unknown origin. An increased prevalence of a wide range of liver disease in lichen planus has been observed by many authors. Most recently, many reports appeared of the occurrence of lichen planus after administration of different types of hepatitis B vaccines. We report one case and briefly review this intriguing observation.

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37.) TT virus detection in oral lichen planus lesions.
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J Med Virol 2001 Jun;64(2):183-9 

Rodriguez-Inigo E, Arrieta JJ, Casqueiro M, Bartolome J, Lopez-Alcorocho JM, Ortiz-Movilla N, Manzarbeitia F, Pardo M, Carreno V.

Fundacion para el Estudio de las Hepatitis Virales, C/Guzman el Bueno, 72, 28015 Madrid, Spain.

Epidemiological studies have demonstrated a correlation between oral lichen planus and different liver diseases. The new virus termed TT virus (TTV) is highly prevalent in patients with chronic hepatitis of different etiology and it may be speculated that TT virus may be involved in the pathogenesis of oral lichen planus. This study examined the presence of TT virus DNA in serum by PCR and in oral mucosa biopsies by in situ hybridization from 20 patients with oral lichen planus (13 with chronic hepatitis and seven without liver disease). Serum and oral mucosa biopsies from six patients all with chronic hepatitis with leukoplakia were also studied as controls. TT virus DNA was positive in the serum of 17/20 (85%) of the patients with oral lichen planus and in all the controls. TT virus DNA hybridization signals were detected in mucosa biopsies from all the patients with TT virus DNA in serum but in none of the three cases without this marker. The percentage of positive cells ranged from 1.6-80%. No differences were found in the percentage of positive cells between TT virus positive patients with and without oral lichen planus and there was no relationship between the number of positive cells and the intensity of the inflammatory infiltrate. In conclusion, TT virus infects oral epithelial cells but the results do not support a role for TT virus in causing oral lichen planus. 

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38.) Lichenoid eruption following hepatitis B vaccination: first North American case report.
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Pediatr Dermatol 2001 Mar-Apr;18(2):123-6 

Usman A, Kimyai-Asadi A, Stiller MJ, Alam M.

Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.

Lichen planus is often found in association with a variety of underlying conditions. In particular, liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, hepatitis C, and hepatitis B have been implicated in cutaneous lichen planus. Of interest, there is mounting evidence that lichen planus-like eruptions can occur following administration of the hepatitis B vaccine, which has recently become a routine immunization in many parts of the world. We present what we believe to be the first North American case of lichenoid drug eruption associated with the hepatitis B vaccine and provide a brief review of other reported cases of lichenoid eruption seen following hepatitis B vaccination.

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39.) Increased frequency of HLA-DR6 allele in Italian patients with hepatitis C virus-associated oral lichen planus.
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Br J Dermatol 2001 Apr;144(4):803-8 

Carrozzo M, Francia Di Celle P, Gandolfo S, Carbone M, Conrotto D, Fasano ME, Roggero S, Rendine S, Ghisetti V.

Department of Oral Medicine, School of Medicine and Dentistry, University of Turin, C.so Dogliotti 14, I-10126 Turin, Italy. [email protected]

BACKGROUND: Recent controlled studies have confirmed that hepatitis C virus (HCV) is the main correlate of liver disease in patients with lichen planus (LP), mainly in southern Europe and Japan. However, a low prevalence of HCV infection has been found in LP patients in England and northern France, and significant differences in serum HCV RNA levels or HCV genotypes have not been found between LP patients and controls. Thus host rather than viral factors may be prevalent in the pathogenesis of HCV-related LP. The HLA-DR allele may influence both the outcome of HCV infection and the appearance of symptoms outside the liver. OBJECTIVES: To assess whether major histocompatibility complex class II alleles play a part in the development of HCV-related LP. METHODS: Intermediate-resolution DRB typing by hybridization with oligonucleotide probes was performed in 44 consecutive Italian oral LP (OLP) patients with HCV infection (anti-HCV and HCV RNA positive), in an age, sex and clinically comparable disease control group of 60 Italian OLP patients without HCV infection (anti-HCV and HCV RNA negative), and in 145 healthy unrelated Italian bone marrow donors without evidence of liver disease or history of LP and with negative tests for HCV. RESULTS: Patients with exclusive OLP and HCV infection possessed the HLA-DR6 allele more frequently than patients with exclusive OLP but without HCV infection (52% vs. 18%, respectively; Pc (Pcorrected) = 0.028, relative risk = 4.93). We did not find any relationship between mucocutaneous LP, HCV infection and HLA-DR alleles. CONCLUSIONS: HCV-related OLP therefore appears to be a distinctive subset particularly associated with the HLA class II allele HLA-DR6. This could partially explain the peculiar geographical heterogeneity of the association between HCV and LP.

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40.) Extrahepatic manifestations of chronic viral hepatitis.
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Curr Gastroenterol Rep 2001 Feb;3(1):71-8 

Pyrsopoulos NT, Reddy K.

Division of Hepatology, Center for Liver Diseases, University of Miami School of Medicine, 1500 NW 12th Avenue, Suite 1100, Miami, FL 33136, USA. [email protected]

Hepatitis B (HBV) and C (HCV) viruses are well-recognized causes for chronic hepatitis, cirrhosis, and even for hepatocellular carcinoma. Apart from liver disease, these viral infections are known to be associated with a spectrum of extrahepatic manifestations. The prevalence of clinically significant extrahepatic manifestations is relatively low, but it can be associated with significant morbidity and even mortality. An awareness and recognition of these manifestations is of paramount importance in facilitating early diagnosis and in offering treatment. However, treatments are not necessarily effective, and patients may continue with disabling extrahepatic manifestations. Hepatitis B virus has been well recognized as causing a variety of manifestations that include skin rash, arthritis, arthralgia, glomerulonephritis, polyarteritis nodosa, and papular acrodermatitis. More recently, infection with hepatitis C virus has elicited considerable interest for its role in a spectrum of extrahepatic manifestations. Among the best-reported are cryoglobulinemia, glomerulonephritis, high titer of autoantibodies, idiopathic thrombocytopenic purpura, lichen planus, Mooren's corneal ulcer, Sjogren's syndrome, porphyria cutanea tarda, and necrotizing cutaneous vasculitis. The precise pathogenesis of these extrahepatic complications has not been determined, although the majority represent the clinical expression of autoimmune phenomena.

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41.) Prevalence of hepatitis C virus in patients with lichen planus of the oral cavity and chronic liver disease.
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Eur J Oral Sci 2000 Oct;108(5):378-82 

del Olmo JA, Pascual I, Bagan JV, Serra MA, Escudero A, Rodriguez F, Rodrigo JM.

Service of Hepatology, Hospital Clinico Universitario, Valencia, Spain. [email protected]

Lichen planus (LP) may represent a mucosal reaction to a variety of factors including hepatitis C virus (HCV) infection. We compared the prevalence of HCV infection in patients with LP of the oral mucosa and chronic liver disease (LP-CLD) with those suffering exclusively from LP or from chronic liver disease (CLD). A total of 267 outpatients participated in a prospective study. There were 41 patients in the LP-CLD group, 128 in the LP group, and 98 in the CLD group. The diagnosis of LP was based on typical macroscopic and histopathologic features and the diagnosis of liver disease on liver histology. Serum samples were screened for anti-HCV antibodies. In 89 patients, serum HCV RNA was also measured. The overall prevalence of anti-HCV antibodies was 29.2% (78/267 patients). Serum HCV RNA levels were positive in 96.2% of anti-HCV-positive patients and in none of anti-HCV-negative subjects. Anti-HCV-positivity was more frequent in the groups of LP-CLD (78%) and CLD (42.8%) than in the LP group (3.1%). It is concluded that HCV infection plays an etiopathogenetic role in CLD associated with oral LP, whereas according to the present findings, the majority of patients suffering exclusively from oral LP are not infected by the HCV.

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42.) Histopathological and immunohistochemical study of oral lichen planus-associated HCV infection.
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Eur J Intern Med 2000 Oct;11(5):277-282 

Nagao Y, Sata M, Kage M, Kameyama T, Ueno T.

Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Asahi-machi, Kurume, 830-0011, Fukuoka, Japan

Background: In recent years, it has been suggested that oral lichen planus (OLP), a chronic inflammatory keratotic lesion, is related to hepatitis C virus (HCV) infection. Therefore, we evaluated whether the presence or absence of HCV infection caused any histopathological differences in OLP tissues. Methods; The subjects consisted of 31 patients with HCV-related liver disease complicated by OLP (32 OLP lesions) and ten OLP patients without complications due to either HCV infection or liver disease (control). A histopathological evaluation was performed in these patients. In addition, immunostaining was done on nine OLP tissues infected with HCV and on six OLP tissues without HCV infection in order to evaluate lymphocyte subsets (T cells or B cells) infiltrating into topical regions with OLP. Furthermore, the severity of hepatic fibrosis and inflammation was evaluated in liver tissues obtained by liver biopsy from six patients with HCV-related liver disease to evaluate whether there were any relationships between the severity of hepatic fibrosis or inflammation and OLP tissues. Results: There were no significant differences in the histopathological characteristics specific to OLP or in the ratios of T and B cells among infiltrating lymphocytes regardless of the presence or absence of HCV infection. Moreover, there were no certain relationships between the severity of hepatic fibrosis or inflammation and the severity of lymphocytic infiltration in OLP. Conclusions: HCV infection does not appear to influence the histopathological and immunohistochemical features of OLP.

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43.) Previous tuberculosis, hepatitis C virus and lichen planus. A report of 10 cases, a causal or casual link?
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Panminerva Med 2000 Mar;42(1):77-81 

Pellicano R, Palmas F, Leone N, Vanni E, Carrozzo M, Gandolfo S, Puiatti P, Marietti G, Rizzetto M, Ponzetto A.

Department of Gastroenterology, Molinette Hospital, Turin, Italy. [email protected]

We report 10 cases of lichen planus (LP) and chronic liver disease linked to HCV. The mean age was 63.4 +/- 5.1 years (range 51-73), five were female; six patients had an established cirrhosis of the liver, as shown by either a liver biopsy or the ultrasonographic and biohumoral evidence. The remaining four patients had chronic hepatitis. Histological examination confirmed the presence of LP: the localization of the dermatosis was restricted to the skin in four patients, to the mucous membranes in five (4 atrophic erosive and one erosive) while the remaining had mucous-cutaneous localization. A type II cryoglobulinemia was demonstrated in two and a type III in one of the patients, while no one had otherwise circulating autoantibodies (anti-nuclear, anti-smooth muscle, anti-liver kidney microsomal type 1 and anti-mitochondrial antigens) such as other etiological factors of liver disease. In six of the patients the history was positive for previous Mycobacterium tuberculosis infection. In clinical practice the patients with chronic liver disease and HCV infection can also suffer from severe extrahepatic manifestations, including lichen planus.

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44.) [Skin diseases and hepatitis virus C infection]
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Med Pregl 2000 Mar-Apr;53(3-4):141-5 

[Article in Serbo-Croatian (Roman)]

Poljacki M, Gajinov Z, Ivkov M, Matic M, Golusin Z.

Medicinski fakultet, Novi Sad Klinika za kozno-venericne bolesti, Klinicki centar, Novi Sad.

INTRODUCTION: Using a creative molecularbiologic technique in 1989 Choo and co-workers isolated a new virus of hepatitis C, an agent responsible for numerous cases of parenterally transmissible viral hepatitis. Hepatitis C virus is a RNA virus with unique genomic organisation. Six genotypes of hepatitis C virus have been identified, which differ in geographical distribution, tendency towards chronicity and sensitivity to antiviral therapy. Transmission occurs due to apparent and inapparent parenteral procedures (after transfusion, transplantation, transplacentally, during lactation, sexually or after accidental injury of medical staff). Mode of transmission through intact skin or mucosa has not been proved yet. Due to development of laboratory methods for detection of anti-hepatitis C virus antibodies and obligation for routine testing of blood donors for hepatitis C in majority of countries in the world, risk of post-transfusion hepatitis C is minimised to less than 1%. In 70% of patients the infection runs a chronic course, affecting numerous extrahepatic organ systems, including skin. VASCULITIS ASSOCIATED WITH MIXED ESSENTIAL CRYOGLOBULINEMIA: Mixed essential cryoglobulinemia is a disorder with deposition of circulating immune complexes in small and medium blood vessels. Clinical characteristics comprise palpable purpura on lower extremities, arthralgias and weakness. It might occur during autoimmune disorders, liver diseases and viral infections, among which hepatitis C infection has a central part. Mixed cryoglobulins can be detected in 35-54% of patients with hepatitis C and symptomatic vasculitis associated cryoglobulinemia, decreased C4 component of complement, positive rheumatoid factor and elevation of hepatic enzymes occurs in 10-21% of patients. Findings of anti-hepatic C virus antibodies and/or viral RNA in 96% of patients with mixed cryoglobulinemia can be considered as a definitive proof of etiopathogenetic association between hepatitis C infection and mixed cryoglobulinemia. Interferon alpha therapy is a first-choice therapy, although transient responses are frequent. PORPHYRIA CUTANEA TARDA: Hepatitis C infection has recently been recognised as an important precipitating factor of clinical porphyria cutanea tarda sympotomatology. Apart from high level of seropositivity among porphyria cutanea tarda patients (62-100%), association between these two entities hasn't been clearly revealed yet. The question whether hepatitis C infection is enough to be the only precipitating factor, or other hepatotoxic cofactors are necessary, still exits. Interferon therapy has been a meter of several studies, but no definite recommendations had been given about its administration in these cases. LICHEN PLANUS: About possible association between lichen planus and chronic liver diseases, and hepatitis C infection as well, suggest 35% prevalence of hepatic disorders in patients with lichen planus, and 9.8-23% of hepatitis C virus seropositivity. The clinical picture of lichen planus in hepatitis C virus infection is characterised by generalised skin lesions, with erosive involvement of oral mucous membrane, and by chronic course. Therapeutical efficiency of interferon is unpredictable, with possible improvement, cure or deterioration of lichen planus. OTHER DERMATOLOGICAL DISORDERS: Other dermatological disorders (erythema nodosum, erythema multiforme, urticaria) may be direct consequences of hepatitis C infection, of other extrahepaic non-dermatological manifestations, or fortuitous reports. CONCLUSION: Considering big pathogenetic potentials of hepatitis C virus with possible skin involvement, and proved association between cutaneous necrotising vasculitis with mixed essential cryoglobulinemia, porphyria cutanea tarda, lichen planus and chronic hepatitis C infection, all patients with these disorders should be tested for hepatitis C and all cases of hepatitis C should be searched for signs and symptoms of these skin diseases.

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45.) [Extrahepatic manifestations of hepatitis C virus infection]
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Rev Prat 2000 May 15;50(10):1089-93 Related Articles, Books 

[Article in French]

Loustaud-Ratti V, Lunel F.

Service de medecine interne A CHRU Hopital universitaire Dupuytren, Limoges.

HCV virus is associated with various immunological disorders. Some of them like mixed cryoglobulinemia, are proved by molecular biology and virology. Others are presumed auto-immune: auto-antibodies production (antinuclear, anti-smooth muscle, anti-liver-kidney microsomal antibodies...) has generally no pathological significance; however, true auto-immune diseases such as auto-immune hepatitis type 1 or 2, Sjogren's syndrome, lichen planus and auto-immune thyroiditis can be associated with HCV related liver disease. Finally, the association of some extra-hepatic manifestations like porphyria cutanea tarda with hepatitis C virus are only based on epidemiological data. Alpha interferon, the reference treatment of chronic hepatitis C, can be efficient on manifestations such as cryoglobulinemia which are directly linked to the virus. However, because of its immunological effect, the same treatment can severely worsen auto-immunological diseases associated with hepatitis C virus (autoimmune hepatitis, thyroiditis...). In practice, it's of great importance to identify and classify these extra-hepatic manifestations to optimize the treatment of chronic hepatitis C.

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46.) Detection of hepatitis C virus RNA in oral lichen planus and oral cancer tissues.
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J Oral Pathol Med 2000 Jul;29(6):259-66 

Nagao Y, Sata M, Noguchi S, Seno'o T, Kinoshita M, Kameyama T, Ueno T.

Research Center for Innovative Cancer Therapy, University School of Medicine, Kurume, Fukuoka, Japan.

Hepatitis C virus (HCV) infection not only causes chronic liver diseases but shows extrahepatic manifestations as oral lichen planus (OLP) and oral cancer. To elucidate the direct relationships among these diseases and HCV infection, we investigated the detection of positive- and negative-strand HCV-RNA from serum, OLP (n=19), and oral cancer (n=17) tissues. We used a sensitive reverse transcription to polymerase chain reaction (RT-PCR) method, and analyzed sequences from the HCV El/E2 region of the genome from serum and tissue. Positive and negative HCV-RNA strands were observed in 13 (92.9%) and 3 (21.4%) OLP tissues, respectively. In oral cancer tissues, positive HCV-RNA strands were detected in all tissues from anti-HCV positive patients. Negative HCV-RNA strands were observed in 5 of 7 (71.4%) patient's tissues. Furthermore, it was confirmed that the sequence from one of each OLP and oral cancer patient differed between serum and tissue HCV-RNA. These results may indicate that HCV persists and replicates in these lesions, suggesting a pathological role for HCV, although the mechanisms are unclear.

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46.) Oral lichenoid lesions after hepatitis B vaccination.
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Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000 Jun;89(6):717-9 


Pemberton MN, Sloan P, Thakker NS.

Department of Dental Medicine and Surgery, University Dental Hospital of Manchester, Manchester, England.

The association of mucocutaneous lichen planus and chronic liver disease is widely recognized. The hepatitis B and C viruses have been implicated as being important in this association, although their exact role remains unclear. Recently, lichenoid lesions of the skin after a hepatitis B vaccination have also been reported. In this case, a woman of Southeast Asian origin had lichenoid lesions affecting the oral mucous membranes develop after she was vaccinated against hepatitis B. The lesions appeared 3 weeks after the administration of the third dose of the vaccine and persisted for about 1 year. As the use of the hepatitis B vaccine becomes more widespread, more such cases can be expected to be encountered.

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47.) [The extrahepatic manifestations in hepatitis C virus (HCV) infection]
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Vutr Boles 1999;31(2-3):11-5 

[Article in Bulgarian]

Kolarski V, Petrova D, Todorov A, Slavchev B.

The hepatitis C virus (HCV) infection could affect not only the liver, but also other tissues, organs and systems. The number of the reported in the literature extrahepatic lesions by HCV incessantly increases. A reliable association between the infections by HCV and the mixed cryoglobulinaemias, membrano-proliferative glomerulonephritis and porphyria cutanea tarda is confirmed. The participation of HCV in the pathogenesis of some diseases of the thyroid gland, the lymphocytic sialadenitis, lichen planus, diabetes mellitus, thrombocytopenia, antiphospholipid syndrome, etc., is assumed. The extrahepatic lesions by HCV are probably connected with the participation of the immune system, but they may be as well due to the replicating virus in the affected tissues, organs and systems. The pathogenetic mechanisms of the extrahepatic and autoimmune manifestations of the infection with HCV are not elucidated, which poses difficult therapeutic problems regarding the choice of interferon and/or corticosteroid hormones.

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48.) Association of HLA-te22 antigen with anti-nuclear antibodies in Chinese patients with erosive oral lichen planus.
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Proc Natl Sci Counc Repub China B 2000 Apr;24(2):63-9 

Sun A, Wu YC, Wang JT, Liu BY, Chiang CP.

School of Dentistry, College of Medicine, National Taiwan University, Taipei, ROC.

The purpose of this study was to determine the frequencies of the presence of serum anti-nuclear antibodies (ANA) and smooth muscle antibodies (SMA) in 76 patients with oral lichen planus (OLP), in 77 patients with other oral mucosal diseases, and in 41 healthy control subjects. HLA phenotypes in some of the patients with OLP and recurrent aphthous ulcers (RAU) were determined to show whether there was an association of HLA antigens with the presence of autoantibodies. Indirect immunofluorescence techniques with mouse liver or stomach as the substrate were used to detect the serum ANA or SMA, respectively. The B lymphocytes isolated from peripheral blood were used for HLA typing by means of a standard microcytotoxicity assay. We found that the positive rate of serum ANA in patients with OLP (29%, p < 0.01), especially in patients with erosive OLP (34%, p < 0.001), was significantly higher than that in the normal control subjects (5%). The frequency of serum SMA in patients with OLP (20%, p < 0.01), in patients with RAU (17%, p < 0.01), or in patients with oral squamous cell carcinomas (41%, p < 0.001) was also significantly higher than that in normal control individuals (0%). In the erosive OLP group, the HLA-Te22 antigen occurred more frequently in patients with positive ANA (75%, p < 0.05) than in those with negative ANA (25%). We conclude that there is an association of HLA-Te22 antigen with ANA in Chinese patients with erosive OLP.

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49.) Treatment of autoimmune and extra-hepatic manifestations of HCV infection.
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Ann Med Interne (Paris) 2000 Feb;151(1):58-64 

Lunel F, Cacoub P.

Laboratoire de Bacterio-Virologie, CHU Angers.

Hepatitis C virus (HCV) infects mononuclear cells and may, like other viruses, cause immunological disorders. Immunological abnormalities observed in HCV infections are usually nonspecific (e.g. cryoglobulinemia, immune complex deposits, autoantibodies). There is a clear association between cryoglobulinemia and hepatitis C and cryoglobulinemia related symptoms are usually improved by treatment with interferon alpha, although patients usually relapse after treatment end. The relationships between hepatitis C and other immunological abnormalities are unclear. The association between chronic hepatitis C and anti-smooth muscle or anti-nuclear antibodies does not appear to be significantly different from that in other hepatic disorders, particularly hepatitis B. Conversely, patients with hepatitis C have significantly more often anti-liver kidney microsomal (LKM1) antibodies than patients with other causes of liver diseases. When clinical, histological and biological findings are indicative of HCV infection with chronic hepatitis, interferon alpha or combination therapy with ribavirin are treatments options. Conversely, when clinical context and results of laboratory tests are in favor of an autoimmune disorder or of overlap-syndromes (i.e. both autoimmune and viral hepatitis), interferon should not be given in first intention, since revelation or exacerbation of autoimmune hepatitis have been reported under interferon. An important prevalence of anti-HCV antibodies has also been reported in patients with sialadenitis, lichen planus and thyroiditis. It has been clearly demonstrated that interferon may induce or worsen such immunological diseases, but there are very few studies showing improvement of these manifestations under interferon. In conclusion, interferon may be appropriate in patients with HCV infection and extrahepatic manifestations linked to immune complex deposition, whereas, in other cases, careful assessment of patients with autoimmune processes is necessary before choosing any treatment strategy.

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50.) Lichen planus, erythema nodosum, and erythema multiforme in a patient with chronic hepatitis C.
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Cutis 2001 Jun;67(6):454-6 

Calista D, Landi G.

Department of Dermatology, M. Bufalini Hospital, Viale Ghirotti 286, 47023 Cesena, Italy. [email protected]

After identification of the hepatitis C virus (HCV) in 1989, evidence was established supporting its role in the pathogenesis of a number of cutaneous diseases. This evidence ranges from mere epidemiologic associations, such as lichen planus, to molecular biological investigations that have identified the virus in the pathologic tissues of cutaneous vasculitis, vasculitis with mixed cryoglobulinemia, and porphyria cutanea tarda. We describe a 52-year-old man who was diagnosed with chronic hepatitis C, preceding the appearance of lichen planus, erythema nodosum, and erythema multiforme that coincided with the reactivation of viral replication.

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51.) [Clinical considerations and statistical analysis on 100 patients with oral lichen planus]
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Minerva Stomatol 2000 Sep;49(9):393-8 

[Article in Italian]

Rossi L, Colasanto S.

Divisione Chirurgia Maxillo-Facciale, Ospedale G. Eastman, Azienda Sanitaria Locale RM/A, Roma.

BACKGROUND: Oral Lichen planus (OLP) is an inflammatory disease, characterized by the presence of polygonal papules which can confluence and affect any part of the oral mucosa, and occurring in many different forms. The clinical picture of the popular form may be characterized exclusively by asymptomatic whitish striae, while the erosive form is extremely painful and disabling. The aim of this research was to evaluate the behavior of the reticular and erosive form of OLP taking into consideration the following three pathologies: hepatitis B, C and diabetes. METHODS: The data of 100 patients affected by OLP (43 males and 57 females) where analyzed, the patients have been observed at the G. Eastman hospital in Rome, Italy in the period between November 1995 and May 1998. Group I presented papular lesions, while group II presented atrophic-erosive lesions with or without the presence of papular lesions. RESULTS: A comparative analysis between the two groups, performed with chi 2 corrected by the Yates formula and if necessary followed by the Fisher test, demonstrated a higher average age and a larger extension of the oral lesions for group II (p < 0.05). The presence of viral hepatitis B was 6% overall, its prevalence in group II, 5% (p > 0.05); the presence of viral hepatitis C was 13% overall, its prevalence in group II 11%; the presence of diabetes was 10% overall, its prevalence in group II 7%. The buccal mucosa was the most frequently affected area in both groups. CONCLUSIONS: The results obtained confirm the possibility of an association between hepatitis and OLP, but a statistically significant relationship between hepatitis and OLP erosive type, has not been observed.

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52.) Lichen planus in children: a possible complication of hepatitis B vaccines.
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Pediatr Dermatol 2002 May-Jun;19(3):204-9 

Limas C, Limas CJ.

Department of Dermatopathology, "Andreas Sygros" Hospital, Athens, Greece.

Lichen planus (LP) has been reported as a complication of hepatitis B vaccination in both adults and children. According to published observations, an autoimmune reaction may be triggered by the viral S epitope. In children, LP is uncommon and, because of its atypical clinical presentation, definitive diagnosis may require biopsy. We investigated the possible association of recombinant hepatitis B virus (HBV) vaccines with childhood LP or LP-like eruptions seen in our hospital over the last 3 years. Only biopsy-confirmed cases in which the clinical history could be thoroughly scrutinized were included. We report five patients less than 16 years of age in whom such an association could be supported by relevant data. Thirteen similar pediatric and 15 adult cases have been reported from various countries in the last 5 years. The data indicate that LP is a complication that rarely occurs in children receiving the HBV vaccine. It appears without known predisposing factors and has variable clinical presentations while the histologic findings are consistent and, with minor variations, typical of LP.

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53.) Lichen planus actinicus treated with acitretin and topical corticosteroids.
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J Eur Acad Dermatol Venereol 2002 Mar;16(2):174-5 

Jansen T, Gambichler T, von Kobyletzki L, Altmeyer P.

Publication Types: 
Letter 
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54.) Alendronate-induced lichen planus.
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Isr Med Assoc J 2002 May;4(5):389-90 

Lazarov A, Moss K, Plosk N, Cordoba M, Baitelman L.

Dermatology Consulting Clinic, Meir Hospital, Kfar Saba, Israel. [email protected]

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55.) Hepatitis C virus and lichen planus in Nigerians: any relationship?
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Int J Dermatol 2002 Apr;41(4):217-9 

Daramola OO, George AO, Ogunbiyi AO.

Dermatology Division, Department of Medicine, University College Hospital, Ibadan, Nigeria. [email protected]

BACKGROUND: The association of lichen planus with Hepatitis C virus (HCV) has been widely reported in the literature. No such association, however, has been reported amongst black Africans in whom HCV is thought to be endemic. Lichen planus is a frequently encountered dermatosis in this racial group as well. The aim of this study was to determine the prevalence of anti-HCV amongst Nigerians with lichen planus. METHODS: Fifty-seven Nigerians with lichen planus (LP group) and 24 patients with other dermatoses not reportedly associated with HCV (control group A) and 24 apparently normal subjects (control group B) were screened for the presence of anti-HCV by second generation ELISA. RESULTS: Nine (15.8%) of the 57 LP group, 6 (25%) of the 24 control group A and none out of the 24 control group B were seropositive for anti-HCV. CONCLUSION: The prevalence of anti-HCV amongst Nigerian with lichen planus is lower than amongst patients with other dermatoses not associated with HCV but higher than amongst apparently normal control. It would appear that the prevalence of HCV is high in Nigeria and not necessarily in lichen planus as a specific entity.

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56.) Helicobacter pylori Infection in Skin Diseases: A Critical Appraisal.
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Am J Clin Dermatol 2002;3(4):273-82 

Wedi B, Kapp A.

Department of Dermatology and Allergology, Hannover Medical University, Hannover, Germany.

More than 50% of the human population have long-term Helicobacter pylori infection, causing, in some cases, severe diseases such as peptic ulcers and stomach cancer. In the last few years several extra-gastrointestinal disorders have been associated with H. pylori infection. This review summarized the current medical literature, identified through hand searching and MEDLINE research, including our own studies, with regard to H. pylori and skin diseases. From the literature it can be seen that the role of H. pylori in skin diseases is still a controversial subject. Randomized controlled trials with adequate masking and sample sizes are still lacking. The best evidence comes from studies investigating chronic urticaria in which chronic urticaria disappeared in many patients with H. pylori infection after careful eradication of the H. pylori. Moreover, there are promising recent reports of beneficial H. pylori eradication in Behcet's disease, pruritus cutaneus, prurigo chronica, prurigo nodularis and in some patients with lichen planus, but not in rosacea or psoriasis. Before any conclusions with respect to other skin diseases such as atopic dermatitis, Schoenlein-Henoch Purpura, Sweet's syndrome, Sjogren syndrome or systemic sclerosis may be drawn, additional randomized, double-blinded and placebo-controlled studies including adequate diagnostic schedules, sufficient eradication treatment protocols, confirmation of eradication and adequate control groups are needed. The cutaneous pathology of H. pylori is far from being clear, but it is speculated that the systemic effects may involve increased mucosal permeability to alimentary antigens, immunomodulation, an autoimmune mechanism or the impairment of vascular integrity.

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57.) Presence of lichen planus during a course of interferon alpha-2a therapy for a viral chronic C hepatitis.
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Med Oral 2001 Nov-Dec;6(5):358-63 

Guijarro Guijarro B, Lopez Sanchez AF, Hernandez Vallejo G.

Departamento de Odontologia, Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Spain.

We present the case of a 66-year-old woman with a diagnosis of chronic active viral C hepatitis, for whom a course of interferon alpha-2A was prescribed at a dose of 4.5 MU per day for a 2 month period, followed by the same dose on alternate days for 4 months. After completion of a month of therapy, the patient presented with painful oral lesions that made normal oral food intake impossible. These lesions persisted, in spite of withdrawal of interferon therapy. Intraoral examination revealed erosive intraoral lesions in both yugal mucosae, the upper vestibular gum, the floor of the mouth, the ventral region of the tongue, and the lower lip. A diagnosis of erosive lichen planus induced by interferon therapy was established. The prescribed treatment was 0.1% triamcinolone acetonide in orabase applied 3 times a day for 4 weeks. Following the therapeutical course, the erosive lesions disappeared, and the symptoms stopped, although the reticular lesions remained visible.

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58.) Lichen planus-like eruption following autologous bone marrow transplantation for chronic myeloid leukaemia.
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Australas J Dermatol 2001 Aug;42(3):188-91 

Pagliaro JA, White S, Strutton G, Guerin D.

Department of Dermatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.

A 47-year-old female treated with an autologous bone marrow transplant and cytotoxic chemotherapy developed a lichen planus-like eruption 12 months later. It involved the skin and oral mucosa, with the histological features of a lichenoid graft-versus-host reaction, including satellite cell necrosis. This eruption developed de novo. The eruption resolved with topical betamethasone valerate 0.1% cream despite the ongoing use of the immunomodulatory agent interferon-alpha2b. Such a reaction in an autologous setting has only been described once previously.

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59.) [Clinical evaluation in oral lichen planus with chronic hepatitis C: the role of interferon treatment]
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Nippon Shokakibyo Gakkai Zasshi 2000 May;97(5):568-74 


[Article in Japanese]

Sugiyama T, Shimizu M, Ohnishi H, Noguchi N, Iwata K, Kojima Y, Watanabe Y, Kawase K, Fukutomi Y, Yamauchi O, Yasuda S, Yamada M, Kobayashi S, Kojima M.

Department of Gastroenterology, Gifu Prefectural Gifu Hospital.

Hepatitis C virus (HCV) infection induces a variety of extrahepatic manifestations such as oral lichen planus (OLP). To clarify the role of HCV in the development of OLP, we investigated the occurrence of OLP in patients with chronic hepatitis C treated with interferon (IFN). Of 275 patients with chronic hepatitis C, 6 developed OLP during the IFN treatment. However, OLP developed in none of 230 patients with chronic hepatitis C who did not undergo the IFN therapy. The IFN treatment in chronic hepatitis C patients developed OLP significantly, as compared with the non-treated group (p < 0.05). 4 of 6 patients who developed OLP during the IFN treatment had a complete response with normalization of ALT levels and undetectable HCV RNA after the treatment. There were no significant correlations between the effect of the IFN treatment and outcome of OLP. Furthermore, 3 of the 6 patients developed OLP, when serum HCV RNA became negative. These results suggest that direct viral factors may not be important in the pathogenesis of OLP in patients with chronic hepatitis C. Immunological changes caused by IFN may play a role in the development of OLP associated with HCV infection.

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60.) Oral lichen planus induced by interferon-alpha-N1 in a patient with hepatitis C.
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Int J Dermatol 2000 Mar;39(3):239-40 

Varela P, Areias J, Mota F, Canelhas A, Sanches M.

Publication Types: 
Letter 

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61.) Treatment of lichen planus. An evidence-based medicine analysis of efficacy.
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Arch Dermatol 1998 Dec;134(12):1521-30 

Comment in: 
Arch Dermatol. 1999 Nov;135(11):1420-1. 

Cribier B, Frances C, Chosidow O.

Dermatology Clinic, Hopitaux Universitaires de Strasbourg, France.

OBJECTIVE: To critically appraise the body of literature concerning treatment of lichen planus (LP). DESIGN: Review of MEDLINE and BIOSIS databases to identify articles published with at least an English abstract before March 1998 that examined treatment of LP. MAIN OUTCOME MEASURES: Forming a primary database on which most recommendations are based. We thus selected 83 clinical trials or small series of patients in the medical literature that referenced clinical data on patients treated for LP. RESULTS: There are no large randomized trials with definitive results in the medical literature examining the efficacy of the various drugs or physical treatments of LP. There are only 3 level B trials (small randomized trials with uncertain results because of moderate to high alpha or beta error) that address efficacy of treatment in LP, i.e., 1 with acitretin in cutaneous LP and 2 with topical corticosteroids in mucosal LP. The remainder of the published trials are observational and are not always prospective. Many of the recommendations of the experts are based on their personal experience. CONCLUSIONS: Although LP may be associated with substantial morbidity and altered quality of life, especially the erosive mucosal LP, definitive clinical trials have not been performed. Acitretin is the first-line therapy in cutaneous LP. The efficacy of systemic corticosteroids and psoralen plus UV-A therapy has not been established with a high level of proof. Topical corticosteroids are the first-line therapy in mucosal erosive LP. Other treatments, such as topical cyclosporine or extracorporeal photochemotherapy, remain to be evaluated. European-US cooperation is warranted to perform large randomized controlled trials in cutaneous and mucosal LP.

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62.) Successful Treatment of Resistant Hypertrophic and Bullous Lichen Planus With Mycophenolate Mofetil 
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Vol. 135 No. 11, November 1999 correspondence



Hossein C. Nousari, MD
Division of Dermatoimmunology
Ross Research Bldg
Room 771
720 Rutland Ave
Baltimore, MD 21205
(e-mail: [email protected])

Supriya Goyal, BA, BS
Grant J. Anhalt, MD
Baltimore


Mycophenolate mofetil is an immunosuppressive drug that has recently been used to treat autoimmune and inflammatory skin diseases.1, 2 We herein report the first case of lichen planus (LP) successfully treated with mycophenolate.




Report of a Case.



A 55-year-old white woman with a 10-year history of LP of the lower extremities presented for a therapeutic alternative. Prior treatments included several courses of tapered oral and topical steroids, including a 9-week course of flurandrenolide tape applied nightly, psoralen–UV-A, hydroxychloroquine sulfate (400 mg/d for 10 months), azathioprine (150 mg/d for 8 months), and methotrexate (15 mg/wk for 7 months), none of which led to sustained improvement. On physical examination, she had multiple hypertrophic scaly papules and plaques on the pretibial areas bilaterally, some of which were ulcerated. On the medial aspects of the feet, she had violaceous bullous plaques. No mucosal lesions were present. Histological examination of the hypertrophic and bullous lesions demonstrated changes characteristic of LP.

She was treated with mycophenolate mofetil, 1500 mg twice daily, and a tapering course of prednisone, starting at 40 mg/d. After 6 weeks, the previously existent hypertrophic lesions had decreased in thickness and substantially resolved. There was also significant improvement in all of the previous areas of ulceration. No new plaques were present. Mycophenolate mofetil treatment was continued at 1500 mg twice daily, and prednisone treatment was continued at 10 mg/d for 2 weeks, followed by 5 mg/d. By 15 weeks, the lesions were markedly improved, but the patient still complained of significant pruritus. Mycophenolate mofetil treatment was continued at 1500 mg twice daily, and prednisone treatment was discontinued. At week 20, the patient continued to be treated with mycophenolate mofetil, 1500 mg twice daily, and had not experienced any adverse effects; the results of routine laboratory tests were within normal limits, and her lesions underwent complete remission.




Comment.



Lichen planus is an inflammatory mucocutaneous disease primarily mediated by T-lymphocytes. Current treatments include psoralen–UV-A and systemic and topical steroid, systemic retinoid, antimalarial, and immunosuppressive agents, all of which have been reported to be effective in anecdotal reports.3 Several clinical variants of LP exist, including hypertrophic and ulcerative subtypes, which are generally more refractory to treatment.

Mycophenolate mofetil has recently been added to the therapeutic armamentarium for autoimmune and inflammatory skin diseases. Mycophenolate mofetil is the ester prodrug of mycophenolic acid, a product isolated from the Penicillium species. Mycophenolic acid interferes with de novo purine synthesis by inhibiting type II inosine monophosphate dehydrogenase, an enzyme expressed in both stimulated T- and B-lymphocytes. Mycophenolate mofetil, which was synthesized to increase the bioavailability of mycophenolic acid, is well absorbed orally but is rapidly conjugated to glucuronide and eliminated in the urine. Mycophenolate treatment is usually well tolerated; however, a potential increased risk of infection and lymphoproliferative malignant neoplasms has been suspected. In transplant patients receiving mycophenolate treatment, the incidence of skin cancer appears to be related to the degree of immunosuppression rather than to a particular immunosuppressant.

Based on the potential for developing painful refractory lesions and the very infrequent but still theoretically possible risk of developing squamous cell carcinoma in ulcerative and hypertrophic LP, aggressive therapy for these variants of LP is frequently recommended.4, 5 Although the potency of mycophenolate is equal to or lower than that of azathioprine, mycophenolate treatment at moderate dosages was more effective for our patient than azathioprine treatment. This may have been caused by the fact that in addition to its cytostatic effect on lymphocytes, mycophenolate, unlike azathioprine, also has anti-inflammatory properties. Mycophenolate exerts its anti-inflammatory effect by inhibiting leukocyte recruitment and adhesion to endothelial cells. While it is not known if mycophenolate treatment alters the risk of developing squamous cell carcinoma in patients with hypertrophic and ulcerative LP, its efficacy in rapidly resolving our patient's lesions suggests that it may decrease this risk. The treatment of our patient demonstrates a novel therapeutic option for patients with refractory LP with ulcerative and bullous lesions; mycophenolate treatment may be preferable to azathioprine treatment because it has a safer adverse effect profile. However, larger studies must be performed to establish the risk-benefit ratio of various therapeutic dosages of mycophenolate for these patients.



1. Nousari HC, Lynch WA, Petri M, Anhalt GJ. The effectiveness of mycophenolate mofetil in refractory pyoderma gangrenosum. Arch Dermatol. 1998;134:1509-1511. MEDLINE 

2. Nousari HC, Sragovich A, Kimyai-Asadi A, Orlinsky D, Anhalt GJ. Mycophenolate mofetil in autoimmune and inflammatory skin disorders. J Am Acad Dermatol. 1999;40:265-268. MEDLINE 

3. Cribier B, Frances C, Chosidow O. Treatment of lichen planus: an evidence-based medicine analysis of efficacy. Arch Dermatol. 1998;134:1521-1530. MEDLINE 

4. Castano E, Lopez-Rios F, Alvarez-Fernandez JG, Rodriguez-Peralto J, Iglesias L. Verrucous carcinoma in association with hypertrophic lichen planus. Clin Exp Dermatol. 1997;22:23-25. MEDLINE 

5. Mayron R, Grimwood RE, Siegle RJ, Camisa C. Verrucous carcinoma arising in ulcerative lichen planus of the soles. J Dermatol Surg Oncol. 1988;14:547-551. MEDLINE 

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63.) Liver abnormalities in patien with lichen planus
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Wiwath Korkojj, MD., Tsu-Yi Chuang, M.D, et al 

A retrospective case-control study

J Am Acad Dermatol 11:609-615,1984.
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64.) Lichen Planus
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Alan S. Boyd MD, and Kenneth H. Nelder, MD

CONTINUING MEDICAL EDUCATION

J Am Acad Dermatol 1991;25:593-619
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DATA-MEDICOS/DERMAGIC-EXPRESS No 4-(115) 30/07/2.002 DR. JOSE LAPENTA R. 
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