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Figure 1. Frequency of genital lichen sclerosus (LS) according to type of morphea.

Figure 1. Frequency of genital lichen sclerosus (LS) according to type of morphea.

Figure 2. A 66-year-old patient with multiple plaques of morphea (A) and biopsy-proven genital lichen sclerosus (B).

Figure 2. A 66-year-old patient with multiple plaques of morphea (A) and biopsy-proven genital lichen sclerosus (B).

Table 1. Classification of Morpheaa
Table 1. Classification of Morpheaa
Table 2. Clinical Characteristics of Patients With Morphea
Table 2. Clinical Characteristics of Patients With Morphea
1.
Powell JJ, Wojnarowska F. Lichen sclerosus.  Lancet. 1999;353(9166):1777-1783PubMedArticle
2.
Peterson LS, Nelson AM, Su WP, Mason T, O ’Fallon WM, Gabriel SE. The epidemiology of morphea (localized scleroderma) in Olmsted County 1960-1993.  J Rheumatol. 1997;24(1):73-80PubMed
3.
Aberer E, Stanek G, Ertl M, Neumann R. Evidence for spirochetal origin of circumscribed scleroderma (morphea).  Acta Derm Venereol. 1987;67(3):225-231PubMed
4.
Eisendle K, Grabner T, Zelger B. Focus floating microscopy: “gold standard ” for cutaneous borreliosis?  Am J Clin Pathol. 2007;127(2):213-222PubMedArticle
5.
Eisendle K, Grabner T, Zelger B. Morphoea: a manifestation of infection with Borrelia species?  Br J Dermatol. 2007;157(6):1189-1198PubMedArticle
6.
Buechner SA, Winkelmann RK, Lautenschlager S, Gilli L, Rufli T. Localized scleroderma associated with Borrelia burgdorferi infection: clinical, histologic, and immunohistochemical observations.  J Am Acad Dermatol. 1993;29(2, pt 1):190-196PubMedArticle
7.
Schempp C, Bocklage H, Lange R, K ölmel HW, Orfanos CE, Gollnick H. Further evidence for Borrelia burgdorferi infection in morphea and lichen sclerosus et atrophicus confirmed by DNA amplification.  J Invest Dermatol. 1993;100(5):717-720PubMedArticle
8.
Lecerf V, Bagot M, Revuz J, Touraine R, Dournon E. Borrelia burgdorferi and localized scleroderma.  Arch Dermatol. 1989;125(2):297PubMedArticle
9.
Meis JF, Koopman R, van Bergen B, Pool G, Melchers W. No evidence for a relation between Borrelia burgdorferi infection and old lesions of localized scleroderma (morphea).  Arch Dermatol. 1993;129(3):386-387PubMedArticle
10.
Dillon WI, Saed GM, Fivenson DP. Borrelia burgdorferi DNA is undetectable by polymerase chain reaction in skin lesions of morphea, scleroderma, or lichen sclerosus et atrophicus of patients from North America.  J Am Acad Dermatol. 1995;33(4):617-620PubMedArticle
11.
Wienecke R, Schl üpen EM, Z öchling N, Neubert U, Meurer M, Volkenandt M. No evidence for Borrelia burgdorferi -specific DNA in lesions of localized scleroderma.  J Invest Dermatol. 1995;104(1):23-26PubMedArticle
12.
Weide B, Schittek B, Klyscz T,  et al.  Morphoea is neither associated with features of Borrelia burgdorferi infection, nor is this agent detectable in lesional skin by polymerase chain reaction.  Br J Dermatol. 2000;143(4):780-785PubMedArticle
13.
De Vito JR, Merogi AJ, Vo T,  et al.  Role of Borrelia burgdorferi in the pathogenesis of morphea/scleroderma and lichen sclerosus et atrophicus: a PCR study of thirty-five cases.  J Cutan Pathol. 1996;23(4):350-358PubMedArticle
14.
Sherman V, McPherson T, Baldo M, Salim A, Gao XH, Wojnarowska F. The high rate of familial lichen sclerosus suggests a genetic contribution: an observational cohort study.  J Eur Acad Dermatol Venereol. 2010;24(9):1031-1034PubMed
15.
Gao XH, Barnardo MC, Winsey S,  et al.  The association between HLA DR, DQ antigens, and vulval lichen sclerosus in the UK: HLA DRB112 and its associated DRB112/DQB10301/04/09/010 haplotype confers susceptibility to vulval lichen sclerosus, and HLA DRB10301/04 and its associated DRB10301/04/DQB10201/02/03 haplotype protects from vulval lichen sclerosus.  J Invest Dermatol. 2005;125(5):895-899PubMedArticle
16.
Leitenberger JJ, Cayce RL, Haley RW, Adams-Huet B, Bergstresser PR, Jacobe HT. Distinct autoimmune syndromes in morphea: a review of 245 adult and pediatric cases.  Arch Dermatol. 2009;145(5):545-550PubMedArticle
17.
Majeed M, Al-Mayouf SM, Al-Sabban E, Bahabri S. Coexistent linear scleroderma and juvenile systemic lupus erythematosus.  Pediatr Dermatol. 2000;17(6):456-459PubMedArticle
18.
Bonifati C, Impara G, Morrone A, Pietrangeli A, Carducci M. Simultaneous occurrence of linear scleroderma and homolateral segmental vitiligo.  J Eur Acad Dermatol Venereol. 2006;20(1):63-65PubMedArticle
19.
Meyrick Thomas RH, Ridley CM, McGibbon DH, Black MM. Lichen sclerosus et atrophicus and autoimmunity —a study of 350 women.  Br J Dermatol. 1988;118(1):41-46PubMedArticle
20.
Aslanian FM, Marques MT, Matos HJ,  et al.  HLA markers in familial lichen sclerosus.  J Dtsch Dermatol Ges. 2006;4(10):842-847PubMedArticle
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Barete S, Lipsker D, Franc ès C. Morph ées. In: Allanore Y, Cabane J, Mouthon L, eds. Scl érodermies [in French]. 2nd ed. Paris, France: Med-Line; 2011:209-226
22.
Peterson LS, Nelson AM, Su WP. Classification of morphea (localized scleroderma).  Mayo Clin Proc. 1995;70(11):1068-1076PubMedArticle
23.
Sehgal VN, Srivastava G, Aggarwal AK, Behl PN, Choudhary M, Bajaj P. Localized scleroderma/morphea.  Int J Dermatol. 2002;41(8):467-475PubMedArticle
24.
Puzenat E, Humbert Ph, Aubin F. Scl érodermies localis ées: les morph ées. In: Saurat JH, Lachapelle JM, Lipsker D, Thomas L, eds. Dermatologie et Infections Sexuellement Transmissibles [in French]. 5th ed. Paris, France: Masson; 2009:364-374
25.
Freedberg IM, Eisen AZ, Wolff K,  et al.  Scleroderma. In: Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz S, eds. Fitzpatrick's Dermatology in General Medicine. Vol 1. 3rd ed. New York, NY: McGraw-Hill; 1999:1842-1850
26.
Champion RH, Burton JL, Burns DA, Breathnach SM. Perniosis: localized morphea. In: Rook A, Wilkinson DS, Ebling FJG, eds. Rook-Wilkinson-Ebling Textbook of Dermatology. Vol 3. 6th ed. Oxford, England: Blackwell Science Ltd; 1998:2502-2512
27.
Yu BD, Eisen AZ. Morphea. In: Freedberg IM, Eisen AZ, Wolff K, Austen FK, Goldsmith LA, Katz S, eds. In: Fitzpatrick's Dermatology in General Medicine. Vol II. 6th ed. New York, NY: McGraw-Hill; 2010:1709-1718
28.
Derrick EK, Ridley CM, Kobza-Black A, McKee PH, Neill SM. A clinical study of 23 cases of female anogenital carcinoma.  Br J Dermatol. 2000;143(6):1217-1223PubMedArticle
29.
Sergeant A, Vernall N, Mackintosh LJ, McHenry P, Leman JA. Squamous cell carcinoma arising in extragenital lichen sclerosus.  Clin Exp Dermatol. 2009;34(7):e278-e279PubMedArticleArticle
30.
Wang SH, Chi CC, Wong YW, Salim A, Manek S, Wojnarowska F. Genital verrucous carcinoma is associated with lichen sclerosus: a retrospective study and review of the literature.  J Eur Acad Dermatol Venereol. 2010;24(7):815-819PubMedArticle
31.
Cooper SM, Gao XH, Powell JJ, Wojnarowska F. Does treatment of vulvar lichen sclerosus influence its prognosis?  Arch Dermatol. 2004;140(6):702-706PubMedArticle
32.
Pugliese JM, Morey AF, Peterson AC. Lichen sclerosus: review of the literature and current recommendations for management.  J Urol. 2007;178(6):2268-2276PubMedArticle
33.
van de Nieuwenhof HP, van der Avoort IA, de Hullu JA. Review of squamous premalignant vulvar lesions.  Crit Rev Oncol Hematol. 2008;68(2):131-156PubMedArticle
34.
Tremaine R, Adam JE, Orizaga M. Morphea coexisting with lichen sclerosus et atrophicus.  Int J Dermatol. 1990;29(7):486-489PubMedArticle
35.
Farrell AM, Marren PM, Wojnarowska F. Genital lichen sclerosus associated with morphoea or systemic sclerosis: clinical and HLA characteristics.  Br J Dermatol. 2000;143(3):598-603PubMedArticle
36.
Wu KH, Dai YS, Tsai MJ,  et al.  Lichen sclerosus et atrophicus, bullous morphea, and systemic lupus erythematosus: a case report.  J Microbiol Immunol Infect. 2000;33(1):53-56PubMed
37.
Kim DH, Lee KR, Kim TY, Yoon MS. Coexistence of lichen sclerosus with morphoea showing bilateral symmetry.  Clin Exp Dermatol. 2009;34(7):e416-e418ArticlePubMedArticle
38.
Connelly MG, Winkelmann RK. Coexistence of lichen sclerosus, morphea, and lichen planus: report of four cases and review of the literature.  J Am Acad Dermatol. 1985;12(5, pt 1):844-851PubMedArticle
39.
Sawamura D, Yaguchi T, Hashimoto I, Nomura K, Konta R, Umeki K. Coexistence of generalized morphea with histological changes in lichen sclerosus et atrophicus and lichen planus.  J Dermatol. 1998;25(6):409-411PubMed
40.
Mensing H, Schmidt KU. Diffuse fasciitis with eosinophilia associated with morphea and lichen sclerosus et atrophicus.  Acta Derm Venereol. 1985;65(1):80-83PubMed
41.
Lampert A, Fortier-Beaulieu M, Thomine E, Young P, Lauret P. Association sur un membre d ’un lichen scl éreux et d ’une scl érodermie monom élique [association of lichen sclerosus and monomelic scleroderma] [in French].  Ann Dermatol Venereol. 1995;122(3):102-104PubMed
Study
Jan 2012

High Frequency of Genital Lichen Sclerosus in a Prospective Series of 76 Patients With MorpheaToward a Better Understanding of the Spectrum of Morphea

Author Affiliations

Author Affiliations: Facult é de M édecine, Clinique Dermatologique (Drs Lutz and Lipsker), Study Group of Systemic Diseases in Dermatology (EMSED: Étude des Maladies Syst émiques en Dermatologie) (Drs Franc ès, Bessis, Cosnes, and Lipsker), and D épartement de Sant é Publique, Secteur Biostatistiques et M éthodologies (Drs Godet and Sauleau), Universit é de Strasbourg, Centre Hospitalier Universitaire de Strasbourg, Strasbourg; Service de Dermatologie, H ôpital Tenon, Universit é Pierre et Marie Curie-Paris 6, Paris (Dr Franc ès); Universit é Montpellier I, Service de Dermatologie, Centre Hospitalier Universitaire de Montpellier, Montpellier (Dr Bessis); and Service de Dermatologie, H ôpital Henri Mondor, Cr éteil (Dr Cosnes), France; and Departments of Dermatology, Allergology and Venereology, Institute of Clinical Medicine, University of Helsinki, Skin and Allergy Hospital, Helsinki University Central Hospital, Finland (Dr Kluger).

Arch Dermatol. 2012;148(1):24-28. doi:10.1001/archdermatol.2011.305
Abstract

Objective To compare the frequency of genital lichen sclerosus (LS) in patients with morphea with that of control patients.

Design A prospective multicenter study.

Setting Four French academic dermatology departments: Strasbourg, Montpellier, Tenon Hospital Paris, and Henri Mondor Hospital Cr éteil.

Patients Patients were recruited from November 1, 2008, through June 30, 2010. Seventy-six patients with morphea and 101 age- and sex-matched controls, who underwent complete clinical examination, were enrolled.

Interventions A complete clinical examination and, if deemed necessary, a cutaneous biopsy.

Main Outcome Measure The frequency of genital LS.

Results There were 58 women and 18 men (a 3:1 ratio) with a median age of 59 years. Mean (range) age at diagnosis was 54 (13-87) years. Forty-nine patients had plaque morphea, 9 had generalized morphea, and 18 had linear morphea. Three patients (3%) in the control group and 29 patients (38%) with morphea had LS (odds ratio,  19.8; 95% CI, 5.7-106.9; P   <  .001). Twenty-two patients with plaque morphea (45%) and only 1 patient with linear morphea (6%) had associated genital LS.

Conclusions Genital LS is significantly more frequent in patients with morphea than in unaffected individuals. Forty-five percent of patients with plaque morphea have associated LS. Complete clinical examination, including careful inspection of genital mucosa, should therefore be mandatory in patients with morphea because genital LS bears a risk of evolution into squamous cell carcinoma and thus needs treatment with topical corticosteroids.

Morphea and lichen sclerosus (LS) are 2 entities that are characterized clinically by plaques of indurated, sclerotic, and dyschromic skin and pathologically by an inflammatory dermal infiltrate and dermal fibrosis. Their cause is largely unknown, although both genetic factors, such as predisposing HLA alleles, and environmental factors, such as infection with Borrelia burgdorferi, have been involved in some cases.115 Autoimmune diseases and/or stigmata are more frequent in patients with morphea or LS than in unaffected persons.1,1620

Different clinicopathologic variants of morphea, summarized in Table 1, have been described.21 Morphea involves the skin, but the extremities, the face, and the aerolar area are usually spared, while LS usually involves the genital mucosa. Skin involvement can occur in LS but is rare.

Although there are some similarities between morphea and LS, their exact relationship remains debated. Some authors22 consider that LS is a superficial variant of morphea occurring mostly in the genital area, whereas others2325 consider that they are 2 unrelated entities. In some cases involving the skin, referred to as “white spot disease, ” the differential diagnoses between morphea and LS can be impossible. However, lesions occurring on genital mucosa are usually considered synonymous with LS. Yet, to our knowledge, no study has evaluated the frequency of LS in patients with typical morphea. Furthermore, in clinical practice, genital examination is not systematically performed in patients with morphea. Neither is it recommended in most dermatology textbooks.24,26,27 However, it is important to diagnose genital LS if present, because this entity bears a significant risk of squamous cell carcinoma.2830 This risk can probably be reduced by early and sustained treatment with topical corticosteroids.3133 Thus, the aim of this study was to evaluate the frequency of genital LS in patients with morphea.

METHODS

This is a prospective multicenter study. Patients were recruited from November 1, 2008, through June 30, 2010, in the departments of dermatology from 4 French university hospitals: Strasbourg, Montpellier, Tenon Hospital Paris, and Henri Mondor Hospital Cr éteil. Patients were included if the diagnosis of morphea was confirmed clinically by an experienced dermatologist or after a skin biopsy. Data were collected on a standardized questionnaire and included age and sex. The various forms of morphea were specified according to the classification used in this study (Table 1): plaque, linear, and/or generalized. The number of plaques, their size, their location, their clinical description, and the functional consequences were reported. When patients had both plaque morphea and linear lesions, they were classified as having linear morphea. The genital area was examined in every patient by an experienced dermatologist to search for signs of LS. The diagnosis of LS was accepted in the case of typical clinical and/or histopathologic findings. Patients with systemic sclerosis as defined by the criteria of the American College of Rheumatology were not included in this study.

The control patients in our study consisted of patients seen in the dermatology department for a reason other than morphea and who had a complete skin and mucosal examination. Most were followed up as part of surveillance of cutaneous malignancies. Some had inflammatory diseases, such as psoriasis or lupus erythematosus.

Statistical analyses were performed in collaboration with the Secteur Biostatistiques et M éthodologies at the Universit é de Strasbourg. Before starting the study, we estimated that the number of patients to be included, assuming that the incidence of LS in the general population is 1 in 300 to 1 in 1000 and that the expected difference in prevalence would be 10%, would be 50 to 80 patients with a power of 95%.

The main objective was to compare the frequency of genital LS in patients with morphea with that of the control group. For this purpose, a comparison test was conducted between the frequency of genital LS in these 2 groups. The odds ratio was calculated by the Fisher exact test. We compared the age and sex between case patients and the control group by the χ2 method. Under French law, this type of study, which does not involve any invasive investigation but relies on a questionnaire performed during a regular consultation, does not need the approval of the institutional review board.

RESULTS
EPIDEMIOLOGY

We included 76 patients with morphea. This group consisted of 18 men (24%) and 58 women (76%). The mean (range) age was 54 (13-87) years. The mean (range) duration of morphea was estimated to be 7.9 years (6 months –36 years), but it was not specified in 46 cases. The diagnosis was made on typical clinical findings in 50 patients and was confirmed by a biopsy in 26.

One hundred one controls were included (68 women and 33 men). The mean (range) age was 57 (1-87) years. There was no significant statistical difference between the patients and the control group for age (P  =  .44) and sex (P  =  .30).

Forty-nine patients had plaque morphea, 18 had linear morphea, and 9 had generalized morphea. In only 1 patient, the clinicopathologic findings were typically those of extragenital LS. This patient had pathologically confirmed plaques of both morphea and extragenital LS. The clinical characteristics in these patients are summarized in Table 2.

FREQUENCY OF GENITAL LS

Quiz Ref IDThree patients (3%) in the control group and 29 patients (38%) with morphea had LS. Thus, compared with the frequency in the control group, genital LS is significantly more frequent in patients with morphea, with an odds ratio of 19.8 (95% CI, 5.7-106.9; P   <  .001).

The frequency of LS according to type of morphea is illustrated in Figure 1. Quiz Ref IDForty-five percent of patients with plaque morphea and only 6% of patients with linear morphea had genital LS (P   <  .001).

Twenty percent of patients had genital pruritus. Interestingly, none of the patients spontaneously complained about this symptom, which was always revealed through specific questioning.

INCIDENT CASES

Twenty-seven patients were incident cases of morphea who did not see a dermatologist before this study and in whom diagnosis of morphea was previously not established. Their mean (range) age was 50.8 (13-84) years, and the female to male ratio was 21:6. The mean (range) duration of morphea was estimated as 4.6 years (6 months –33 years). Of these 27 patients, 13 (48%) had genital LS. The mean (range) age of the 13 patients with genital LS was 64.9 (14-84) years. Ten of the 13 patients had plaque morphea (Figure 2) and 3 had generalized morphea.

COMMENT

This study shows that genital LS is significantly more frequent in patients with morphea than in controls and that LS is found with an unexpected high frequency of 38% in patients with morphea. The prevalence of LS in the population is difficult to evaluate, but it is estimated from 1 in 300 to 1 in 1000.

Quiz Ref IDThus, the frequency of LS in the controls of this study is ten times higher than the frequency usually estimated to occur in the general population. This can be explained by a selection bias in our control group of patients mainly recruited in a dermatology department and examined by experienced dermatologists. However, it should also raise some doubt about the usually published data regarding prevalence rates of LS in the general population. It might be that the exact prevalence of LS in the general population is largely underestimated. Indeed, evaluation of prevalence is difficult because the manifestation may be asymptomatic, patients do not consult for discomfort because of the genital location of the lesions, and many physicians are not familiar with this entity and are thus unable to correctly diagnose it. Only a systematic genital examination by an experienced practitioner will provide valuable prevalence rates. In any case, this unusually high frequency of LS in the control group could have harmed this study by lowering our ability to demonstrate a difference in the frequency of genital LS between controls and patients with morphea. This was not the case because there is still a large and significant difference.

Genital LS was significantly more frequent in patients with plaque morphea than in patients with linear morphea. This observation further supports the fact that those 2 entities might result from different pathomechanisms. Only 1 patient with linear morphea had associated LS. There were, however, too few patients with linear morphea included in this study to draw any definitive conclusion about a possible association. Patients with plaque morphea are those with the highest risk of associated genital LS, with occurrences in about 45% of patients. Furthermore, when we restrict our analysis to patients with incident morphea, that is, those who were not diagnosed with morphea before entering this study, we find a comparatively high frequency of LS of 48%. This fact could suggest that LS usually precedes morphea. The association between morphea and LS has been reported previously, mainly in patients with plaque morphea,3440 but it was reported only once in a case of linear monomelic morphea in a young boy.40 In most cases, however, the LS was extragenital.35,3739,41 Only 1 study35 reported 7 cases of patients with morphea and genital LS. Quiz Ref IDThe fact that 38% of patients with morphea have associated genital LS strongly supports the fact that these 2 diseases share common pathogenetic pathways, and possibly a common genetic background, if they are not one and the same disease. Indeed, both entities are chronic inflammatory skin diseases characterized by dermal fibrosis. Lichen sclerosus could be the genital manifestation of morphea.

In conclusion, this study clearly shows that LS is significantly more frequent in patients with morphea. This finding should definitely affect our clinical practice. Indeed, it is not the standard of care to completely undress patients with morphea, and this practice is not recommended in the major dermatology textbooks.24,26,27Quiz Ref IDThe results of this study, however, show that it is mandatory to perform a complete examination, including the genital mucosa. That will allow us to diagnose a substantial number of cases of LS and eventually to prevent or at least to provide early diagnosis of the genital carcinomas that will arise on them.

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Article Information

Correspondence: Dan Lipsker, MD, PhD, Clinique Dermatologique, 1, Place des l ’H ôpital, BP 426, 67  091 Strasbourg CEDEX, France (dan.lipsker@chru-strasbourg.fr).

Accepted for Publication: August 10, 2011.

Published Online: October 17, 2011. doi:10.1001/archdermatol.2011.305

Author Contributions:Study concept and design: Lutz, Franc ès, Bessis, Cosnes, Kluger, Sauleau, and Lipsker. Acquisition of data: Lutz, Franc ès, Bessis, Cosnes, Kluger, and Lipsker. Analysis and interpretation of data: Lutz, Godet, Sauleau, and Lipsker. Drafting of the manuscript: Lutz, Sauleau, and Lipsker. Critical revision of the manuscript for important intellectual content: Lutz, Franc ès, Bessis, Cosnes, Kluger, Godet, Sauleau, and Lipsker. Statistical analysis: Godet and Sauleau. Study supervision: Franc ès, Bessis, Cosnes, and Lipsker.

Financial Disclosure: None reported.

Additional Information: Drs Lutz, Franc ès, Bessis, Cosnes, and Lipsker are members of the Study Group of Systemic Diseases in Dermatology, France.

This article was corrected for errors on February 10, 2012.

References
1.
Powell JJ, Wojnarowska F. Lichen sclerosus.  Lancet. 1999;353(9166):1777-1783PubMedArticle
2.
Peterson LS, Nelson AM, Su WP, Mason T, O ’Fallon WM, Gabriel SE. The epidemiology of morphea (localized scleroderma) in Olmsted County 1960-1993.  J Rheumatol. 1997;24(1):73-80PubMed
3.
Aberer E, Stanek G, Ertl M, Neumann R. Evidence for spirochetal origin of circumscribed scleroderma (morphea).  Acta Derm Venereol. 1987;67(3):225-231PubMed
4.
Eisendle K, Grabner T, Zelger B. Focus floating microscopy: “gold standard ” for cutaneous borreliosis?  Am J Clin Pathol. 2007;127(2):213-222PubMedArticle
5.
Eisendle K, Grabner T, Zelger B. Morphoea: a manifestation of infection with Borrelia species?  Br J Dermatol. 2007;157(6):1189-1198PubMedArticle
6.
Buechner SA, Winkelmann RK, Lautenschlager S, Gilli L, Rufli T. Localized scleroderma associated with Borrelia burgdorferi infection: clinical, histologic, and immunohistochemical observations.  J Am Acad Dermatol. 1993;29(2, pt 1):190-196PubMedArticle
7.
Schempp C, Bocklage H, Lange R, K ölmel HW, Orfanos CE, Gollnick H. Further evidence for Borrelia burgdorferi infection in morphea and lichen sclerosus et atrophicus confirmed by DNA amplification.  J Invest Dermatol. 1993;100(5):717-720PubMedArticle
8.
Lecerf V, Bagot M, Revuz J, Touraine R, Dournon E. Borrelia burgdorferi and localized scleroderma.  Arch Dermatol. 1989;125(2):297PubMedArticle
9.
Meis JF, Koopman R, van Bergen B, Pool G, Melchers W. No evidence for a relation between Borrelia burgdorferi infection and old lesions of localized scleroderma (morphea).  Arch Dermatol. 1993;129(3):386-387PubMedArticle
10.
Dillon WI, Saed GM, Fivenson DP. Borrelia burgdorferi DNA is undetectable by polymerase chain reaction in skin lesions of morphea, scleroderma, or lichen sclerosus et atrophicus of patients from North America.  J Am Acad Dermatol. 1995;33(4):617-620PubMedArticle
11.
Wienecke R, Schl üpen EM, Z öchling N, Neubert U, Meurer M, Volkenandt M. No evidence for Borrelia burgdorferi -specific DNA in lesions of localized scleroderma.  J Invest Dermatol. 1995;104(1):23-26PubMedArticle
12.
Weide B, Schittek B, Klyscz T,  et al.  Morphoea is neither associated with features of Borrelia burgdorferi infection, nor is this agent detectable in lesional skin by polymerase chain reaction.  Br J Dermatol. 2000;143(4):780-785PubMedArticle
13.
De Vito JR, Merogi AJ, Vo T,  et al.  Role of Borrelia burgdorferi in the pathogenesis of morphea/scleroderma and lichen sclerosus et atrophicus: a PCR study of thirty-five cases.  J Cutan Pathol. 1996;23(4):350-358PubMedArticle
14.
Sherman V, McPherson T, Baldo M, Salim A, Gao XH, Wojnarowska F. The high rate of familial lichen sclerosus suggests a genetic contribution: an observational cohort study.  J Eur Acad Dermatol Venereol. 2010;24(9):1031-1034PubMed
15.
Gao XH, Barnardo MC, Winsey S,  et al.  The association between HLA DR, DQ antigens, and vulval lichen sclerosus in the UK: HLA DRB112 and its associated DRB112/DQB10301/04/09/010 haplotype confers susceptibility to vulval lichen sclerosus, and HLA DRB10301/04 and its associated DRB10301/04/DQB10201/02/03 haplotype protects from vulval lichen sclerosus.  J Invest Dermatol. 2005;125(5):895-899PubMedArticle
16.
Leitenberger JJ, Cayce RL, Haley RW, Adams-Huet B, Bergstresser PR, Jacobe HT. Distinct autoimmune syndromes in morphea: a review of 245 adult and pediatric cases.  Arch Dermatol. 2009;145(5):545-550PubMedArticle
17.
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