0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Observation |

Pulsed High-Dose Corticosteroids Combined With Low-Dose Methotrexate Treatment in Patients With Refractory Generalized Extragenital Lichen Sclerosus FREE

Alexander Kreuter, MD; Christian Tigges, MD; Renata Gaifullina, MD; Julia Kirschke, MD; Peter Altmeyer, MD; Thilo Gambichler, MD
[+] Author Affiliations

Author Affiliations: Connective Tissue Disease Research Unit, Department of Dermatology and Allergology, Ruhr-University Bochum, Bochum, Germany.


Arch Dermatol. 2009;145(11):1303-1308. doi:10.1001/archdermatol.2009.235.
Text Size: A A A
Published online

ABSTRACT

Background  Lichen sclerosus (LS) is a rare, chronic inflammatory skin disease that predominantly affects the anogenital area. A few patients exhibit widespread extragenital disease that may lead to blister formation and superficial erosions. We evaluated the efficacy of pulsed high-dose corticosteroids combined with low-dose methotrexate treatment in patients with refractory generalized LS that had failed to respond to standard topical corticosteroid therapy.

Observation  Seven patients were included in this retrospective study, all of whom were treated with pulsed high-dose corticosteroids combined with low-dose methotrexate for at least 6 months. The outcome measure was an individual, nonvalidated clinical score. Overall, a significant decrease in the clinical score was observed, from a median score of 8 (range, 5 to 24) before treatment to 2 (range, 1 to 4) after treatment. Adverse effects observed during therapy were moderate and disappeared after the end of treatment. During the follow-up period of at least 3 months (mean, 4.7 [range, 3-8] months), none of the patients experienced a relapse of extragenital LS.

Conclusions  Patients with severe extragenital LS benefit from pulsed high-dose corticosteroids combined with low-dose methotrexate therapy. This combination therapy should be considered in generalized disease, especially disease that is refractory to conventional treatment.

Figures in this Article

Lichen sclerosus (LS) is a rare, chronic inflammatory skin disease that predominantly affects the anogenital area. Increasing evidence indicates that LS has an autoimmunological background. Circulating basement membrane antibodies and antibodies against the extracellular matrix protein 1 have been found in patients with LS, and an association of LS with other autoimmune diseases is frequent.13 Approximately 15% of patients with LS have extragenital disease, typically located on the inner thigh, neck, shoulder, arm, breast, and intertriginous areas.4 Clinically, extragenital LS presents as numerous white, scarlike lesions that are confettilike, scattered, aggregated, or coalescent into livid to ivory plaques. In more advanced stages, lesions can become atrophic or hypertrophic/sclerotic with a varying extent of induration and might be complicated by the occurrence of hemorrhagic bullae (Figure 1 and Figure 2).

Place holder to copy figure label and caption
Figure 1

Extragenital lichen sclerosus (LS) with blister formation in patient 6. A, Widespread skin lesions with characteristic white, porcelainlike polygonal macules and plaques are present on the trunk and left axilla of a patient with severe extragenital LS. The clinical subscore of this body area before treatment was 2 (1 point for <33% of body area involvement and 1 point for mild sclerosis/induration in the upper part of the lesions and mild atrophy with blister formation in the lower lesions), and the total score was 12 (see Table 2). B, A close-up view of the same patient's back shows extragenital LS with marked atrophy and concomitant occurrence of bullae.

Graphic Jump Location

Place holder to copy figure label and caption
Figure 2

Widespread extragenital lichen sclerosus (LS) in patient 4. A large indurated ivory plaque with some smaller satellite lesions is seen on the patient's abdomen. The clinical subscore of this body area before treatment was 2 (1 point for <33% of body area involvement and 1 point for mild induration/sclerosis), and the patient's total pretreatment score was 6 (see Table 2).

Graphic Jump Location

In contrast to genital LS, which is commonly associated with itching, burning, dysuria, dyspareunia, genital bleeding, and pain, extragenital LS causes only minor, if any, clinical symptoms. First-line treatment for genital LS consists of potent topical corticosteroids.5,6 Few data are available on the treatment of extragenital LS, and controlled studies have not yet been performed for this type of LS. Smaller extragenital lesions can be treated effectively with topical corticosteroids or with UV phototherapy (eg, UV-A1 or narrowband UV-B).710

A few patients with extragenital LS exhibit severe disease that may affect several anatomic regions of the body and lead to blister formation, superficial erosions, and complicating secondary bacterial or fungal infections (Figure 3). Skin disease in these patients often fails to respond to conventional treatment.

Place holder to copy figure label and caption
Figure 3

Severe erosive extragenital lichen sclerosus in patient 1. A central superficial erosion is present on the patient's lower abdomen. Moreover, widespread atrophy is present. The clinical subscore of this body area before treatment was 6 (3 points for >67% body area involvement and 3 points for severe atrophy with superficial erosions), and the patient's total pretreatment score was 24 (see Table 2).

Graphic Jump Location

In the July 2005 issue of the Archives,11 our group reported on the efficacy of pulsed intravenous high-dose corticosteroids combined with orally administered low-dose methotrexate treatment (PCMT) in severe localized scleroderma. Lichen sclerosus and localized scleroderma share clinical similarities, and intraindividual coexistence of both conditions has been reported.12 We therefore speculated that PCMT might also be beneficial in patients with extragenital LS. The present report is a retrospective evaluation of PCMT in patients with generalized LS that failed to respond to conventional treatment.

METHODS

PATIENTS

Patients with extragenital LS were recruited from the outpatient clinic for connective tissue diseases at the Department of Dermatology and Allergology, Ruhr-University Bochum. Patients had to meet all of the following criteria to be eligible for the initiation of PCMT: biopsy-proved and clinically confirmed extragenital LS, the presence of generalized disease affecting more than 2 anatomic regions of the body, clinical signs of active disease manifested by growing lesions, the appearance of new lesions, clinical signs of inflammation within the past 3 months, and failure to respond to conventional treatment with a potent topical corticosteroid. The baseline examination consisted of a screening for other autoimmune diseases, as previously reported.3 The initial serologic examination included a complete blood cell count; measurement of antinuclear antibody, extractable nuclear antibody (including anti-Ro and anti-La antibodies), rheumatoid factor, circulating immune complex, and immunoglobulin (IgA, IgM, and IgG) levels; screening for Borrelia burgdorferi infection; and routine blood chemistry. We excluded patients younger than 18 years, those with concomitant severe chronic or malignant disease or with a contraindication for PCMT, and women with childbearing potential without acceptable means of contraception. A protocol on sclerotic skin diseases including LS was approved by the ethics review board of the Ruhr-University Bochum. Informed consent was obtained from every patient included.

TREATMENT

Pulsed intravenous high-dose corticosteroids combined with orally administered low-dose methotrexate therapy was administered according to a previously published treatment algorithm from our group.11 In brief, patients received an oral dose of methotrexate, 15 mg/wk. In addition, high-dose intravenous methylprednisolone sodium succinate, given as a 1000-mg single dose for 3 consecutive days monthly, was administered. Adjustments of the methotrexate dosage were allowed according to a previously published protocol.13 Treatment was administered to all patients for a duration of at least 6 months. Clinical examinations were performed every 4 weeks. At these visits, a complete blood cell count; serum chemical analysis, including measurement of glucose and electrolyte levels; and urinalysis were performed. Additional topical therapy was restricted to the use of emollients and hydrocolloid dressings (if erosions were present).

CLINICAL EVALUATION

For the clinical assessment of skin involvement before and after PCMT, an individual, nonvalidated clinical score was established on the basis of a modified skin score for localized scleroderma and a previously reported individual clinical score for extragenital LS.10,13 In brief, the body is divided into the 7 anatomic regions in which extragenital LS preferentially manifests: arms, shoulders, chest (including the submammary region), abdomen, back, inguinal area, and legs. Clinical severity of LS is assessed on a 4-point scale (a score of 0 indicates normal skin; 1, mild sclerosis/induration, atrophy, and/or depigmentation; 2, moderate sclerosis/induration, atrophy, and/or depigmentation with or without blister formation; and 3, severe sclerosis/induration, atrophy, and/or depigmentation with or without superficial erosions). Involvement of each body area is further assessed on a 4-point scale (a score of 0 indicates no involvement; 1, <33%; 2, 33%-67%; and 3, >67%). The sum of the numerical units for clinical severity and skin involvement of the affected anatomic areas represents the total clinical score.

STATISTICAL ANALYSIS

Data analysis was performed using a commercially available statistical software package (MedCalc; MedCalc Software, Mariakerke, Belgium). The distribution of data was graphically assessed. Nonnormally distributed data were expressed as medians, including the range. Pretherapeutic and postherapeutic comparisons were performed using the Wilcoxon test for paired samples. The Spearman coefficient of rank correlation was evaluated for the clinical score and the duration of disease. P < .05 was considered significant.

RESULTS

PATIENT CHARACTERISTICS

A total of 7 patients (6 women and 1 man; mean age, 67.6 [range, 50-80] years) fulfilling the criteria of severe extragenital LS were included in this retrospective analysis. Patients' relevant clinical characteristics are depicted in Table 1. Five of the 7 patients had concomitant genital LS, and 3 of them had other autoimmune diseases. None of them had clinical or histopathologic signs of morphea overlap. All of them had previously been treated with topical corticosteroids without substantive clinical benefit. Moreover, 6 of them had received insufficient pretreatment with different kinds of phototherapy. The mean duration of disease was 90.3 (range, 18-156) months.

Table Graphic Jump LocationTable 1 Characteristics of Patients With Extragenital LS Treated With PCMT
TREATMENT RESPONSE

All of the 7 patients completed PCMT. Six patients were treated for a total of 6 months, and 1 (patient 1) was treated for 10 months because of a delayed response to PCMT. Dose reductions were not performed in any of the cases. The cumulative dose of methotrexate was 360 mg (except for patient 1, who received a cumulative methotrexate dose of 600 mg).

Overall, a significant decrease of the clinical score was observed from a median of 8 (range, 5 to 24) before treatment to 2 (range, 1 to 4) after PCMT (P = .02; Table 2). Representative clinical pictures of response to PCMT are provided in Figure 4. In most patients, the first signs of improvement were seen after the third month of treatment. We observed a significant inverse correlation between the baseline score and the duration of disease (r = −0.81; P = .047). However, there was no correlation between the duration of disease and the relative score reduction (r = −0.54; P = .18). Patients 6 and 7 experienced a notable reduction of lesional itching after the second and third months of PCMT, respectively. Adverse effects observed during PCMT (nausea in 3 patients, headache in 3, and a 2-fold increase of liver enzyme levels in 1) were moderate and disappeared after the end of treatment.

Place holder to copy figure label and caption
Figure 4

Pulsed intravenous high-dose corticosteroids combined with orally administered low-dose methotrexate treatment (PCMT) in generalized and refractory extragenital lichen sclerosus (LS) (patient 1). A, Clinical aspects of widespread disease. B, Marked improvement of former skin lesions 6 months after the end of treatment. These clinical pictures are representative of the whole outcome of the study and demonstrate that the combination of PCMT is effective in patients with extensive extragenital LS.

Graphic Jump Location
Table Graphic Jump LocationTable 2 Clinical Score Before and After PCMT and at the End of the Follow-up Perioda

The follow-up period was at least 3 months (mean, 4.7 [range, 3-8] months). Patients 2 and 5 showed further improvement of skin lesions during follow-up (both had a reduction of the clinical score from 2 at the end of treatment to 1 at the end of follow-up). The other 5 patients had unchanged residual lesions (Table 2). Remarkably, none of the patients experienced a relapse of extragenital LS during the follow-up period.

COMMENT

This retrospective study demonstrated that PCMT is a safe and effective treatment option for patients with severe extragenital LS. Because this was a noncontrolled study design, bias owing to spontaneous remission cannot fully be excluded. However, all of our patients had active progressive disease that had been recalcitrant to several prior treatments. Thus, it appears very unlikely that the improvement of extragenital LS observed in this study was coincidental.

So far, most studies, including controlled clinical trials on the use of calcineurin inhibitors, have been performed in LS affecting the anogenital region.14,15 In contrast, only a few case reports exist on the management of extragenital disease. Genital LS frequently leads to distinct morbidity, whereas extragenital LS usually is asymptomatic and therefore often represents only a cosmetic problem for the patient. Nevertheless, a few patients have severe extragenital LS that requires intensive treatment.

In recent years, combining methotrexate with corticosteroids has become an increasingly reported treatment strategy for localized scleroderma.16 Uziel et al17 were the first to report on the beneficial effects of PCMT in a case series of 10 children with localized scleroderma. These results were later confirmed by Weibel et al18 in a larger retrospective study of PCMT that included 34 patients with juvenile localized scleroderma. Our group's previous experiences with PCMT in 15 adult patients with severe localized scleroderma11 encouraged us to investigate PCMT in a well-selected patient population with extragenital LS.

The exact mechanism of action of PCMT in sclerotic skin diseases is still unknown. It seems that PCMT combines the early anti-inflammatory effects of corticosteroids with the prolonged antifibrotic effects of methotrexate.11 Methotrexate inhibits several cytokines that play a central role in sclerotic skin diseases, such as interleukins 2, 4, and 6.19 Interleukin 6 has been shown to be upregulated in LS and localized scleroderma and seems to parallel with the extent of disease and response to treatment.20,21

Although orally administered low-dose methotrexate causes adverse effects in the gastrointestinal tract (eg, nausea or vomiting), liver (elevations in liver enzyme levels), and central nervous system (eg, dizziness or headache) in about one-third of patients, clinically relevant complications, fortunately, are rare. In clinical trials of methotrexate therapy for rheumatoid arthritis, life-threatening pancytopenia and methotrexate-induced lung disease have been observed in 1.4% and in 2.1% to 6.8% of patients, respectively.22 Although the typical long-term adverse effects of corticosteroids usually do not occur with high-dose treatment, physicians should be aware of rare severe adverse events such as aseptic bone necrosis, anaphylaxis, or even sudden death in patients with renal insufficiency and/or imbalances in electrolyte levels.23,24 Therefore, patients should be carefully monitored while receiving PCMT, especially those with a history of cardiac and/or renal disease.

The results reported herein should be viewed in light of the limitations of the study. We performed an unblinded, uncontrolled retrospective analysis of a relatively small number of patients with a short follow-up period. Moreover, we evaluated treatment outcome by using an individual, nonvalidated clinical score, and secondary outcome measures such as ultrasonographic or histopathologic evaluation are missing. Finally, a severely affected patient population as described in the present study is rare in general practice and thus might predominantly be seen in an academic specialty clinic with a focus on sclerotic skin diseases.

Further studies on extragenital LS, gathered under more rigorous, prospective conditions with the aid of a standardized instrument to measure treatment response, would be ideal. However, such conditions are difficult to create given the rarity of this particular disease.

In conclusion, our experience suggests that patients with severe extragenital LS benefit from PCMT. This combination therapy should be considered in generalized disease, especially disease that is refractory to conventional treatment.

ARTICLE INFORMATION

Correspondence: Alexander Kreuter, MD, Department of Dermatology and Allergology, Ruhr-University Bochum, Gudrunstrasse 56, D-44791 Bochum, Germany (a.kreuter@derma.de).

Accepted for Publication: March 20, 2009.

Author Contributions: Dr Kreuter had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Kreuter. Acquisition of data: Kreuter, Tigges, Gaifullina, and Kirschke. Analysis and interpretation of data: Kreuter, Altmeyer, and Gambichler. Drafting of the manuscript: Kreuter and Gambichler. Critical revision of the manuscript for important intellectual content: Tigges, Gaifullina, Kirschke, Altmeyer, and Gambichler. Statistical analysis: Gambichler. Administrative, technical, and material support: Kreuter, Tigges, Gaifullina, and Kirschke. Study supervision: Kreuter and Altmeyer.

Financial Disclosure: None reported.

REFERENCES

Howard  ADean  DCooper  SKirtshig  GWojnarowska  F Circulating basement membrane zone antibodies are found in lichen sclerosus of the vulva. Australas J Dermatol 2004;45 (1) 12- 15
PubMed Link to Article
Oyama  NChan  INeill  SM  et al.  Autoantibodies to extracellular matrix protein 1 in lichen sclerosus. Lancet 2003;362 (9378) 118- 123
PubMed Link to Article
Cooper  SMAli  IBaldo  MWojnarowska  F The association of lichen sclerosus and erosive lichen planus of the vulva with autoimmune disease: a case-control study. Arch Dermatol 2008;144 (11) 1432- 1435
PubMed
Powell  JJWojnarowska  F Lichen sclerosus. Lancet 1999;353 (9166) 1777- 1783
PubMed Link to Article
Renaud-Vilmer  CCavelier-Balloy  BPorcher  RDubertret  L Vulvar lichen sclerosus: effect of long-term topical application of a potent steroid on the course of the disease. Arch Dermatol 2004;140 (6) 709- 712
PubMed Link to Article
Neill  SMRidley  CM Management of anogenital lichen sclerosus. Clin Exp Dermatol 2001;26 (8) 637- 643
PubMed Link to Article
Colbert  RLChiang  MPCarlin  CSFleming  M Progressive extragenital lichen sclerosus successfully treated with narrowband UV-B phototherapy. Arch Dermatol 2007;143 (1) 19- 20
PubMed Link to Article
Kreuter  AGambichler  T Narrowband UV-B phototherapy for extragenital lichen sclerosus. Arch Dermatol 2007;143 (9) 1213
PubMed Link to Article
Kreuter  AGambichler  T UV-A1 phototherapy for sclerotic skin diseases: implications for optimizing patient selection and management. Arch Dermatol 2008;144 (7) 912- 916
PubMed Link to Article
Kreuter  AGambichler  TAvermaete  A  et al.  Low-dose ultraviolet A1 phototherapy for extragenital lichen sclerosus: results of a preliminary study. J Am Acad Dermatol 2002;46 (2) 251- 255
PubMed Link to Article
Kreuter  AGambichler  TBreuckmann  F  et al.  Pulsed high-dose corticosteroids combined with low-dose methotrexate in severe localized scleroderma [published correction appears in Arch Dermatol. 2005;141(9):1091]. Arch Dermatol 2005;141 (7) 847- 852
PubMed Link to Article
Uitto  JSanta Cruz  DJBauer  EAEisen  AZ Morphea and lichen sclerosus et atrophicus: clinical and histopathologic studies in patients with combined features. J Am Acad Dermatol 1980;3 (3) 271- 279
PubMed Link to Article
Seyger  MMvan den Hoogen  FHde Boo  Tde Jong  EM Low-dose methotrexate in the treatment of widespread morphea. J Am Acad Dermatol 1998;39 (2, pt 1) 220- 225
PubMed Link to Article
Hengge  URKrause  WHofmann  H  et al.  Multicentre, phase II trial on the safety and efficacy of topical tacrolimus ointment for the treatment of lichen sclerosus. Br J Dermatol 2006;155 (5) 1021- 1028
PubMed Link to Article
Oskay  TSezer  HKGenç  CKutluay  L Pimecrolimus 1% cream in the treatment of vulvar lichen sclerosus in postmenopausal women. Int J Dermatol 2007;46 (5) 527- 532
PubMed Link to Article
Zulian  F New developments in localized scleroderma. Curr Opin Rheumatol 2008;20 (5) 601- 607
PubMed Link to Article
Uziel  YFeldman  BMKrafchik  BRYeung  RSLaxer  RM Methotrexate and corticosteroid therapy for pediatric localized scleroderma. J Pediatr 2000;136 (1) 91- 95
PubMed Link to Article
Weibel  LSampaio  MCVisentin  MTHowell  KJWoo  PHarper  JI Evaluation of methotrexate and corticosteroids for the treatment of localized scleroderma (morphoea) in children. Br J Dermatol 2006;155 (5) 1013- 1020
PubMed Link to Article
Ihn  HSato  SFujimoto  MKikuchi  KTakehara  K Demonstration of interleukin-2, interleukin-4 and interleukin-6 in sera from patients with localized scleroderma. Arch Dermatol Res 1995;287 (2) 193- 197
PubMed Link to Article
Romero  LIPincus  SH In situ localization of interleukin-6 in normal skin and atrophic cutaneous disease. Int Arch Allergy Immunol 1992;99 (1) 44- 49
PubMed Link to Article
Kreuter  AHyun  JSkrygan  M  et al.  Ultraviolet A1–induced downregulation of human β-defensins and interleukin-6 and interleukin-8 correlates with clinical improvement in localized scleroderma. Br J Dermatol 2006;155 (3) 600- 607
PubMed Link to Article
Rau  RHerborn  G Benefit and risk of methotrexate treatment in rheumatoid arthritis. Clin Exp Rheumatol 2004;22 (5) (suppl 35)S83- S94
PubMed
Thompson  JFChalmers  DHWood  RFKirkham  SRMorris  PJ Sudden death following high-dose intravenous methylprednisolone. Transplantation 1983;36 (5) 594- 596
PubMed Link to Article
Haajanen  JSaarinen  OLaasonen  LKuhlbäck  BEdgren  JSlätis  P Steroid treatment and aseptic necrosis of the femoral head in renal transplant recipients. Transplant Proc 1984;16 (5) 1316- 1319
PubMed

Figures

Place holder to copy figure label and caption
Figure 1

Extragenital lichen sclerosus (LS) with blister formation in patient 6. A, Widespread skin lesions with characteristic white, porcelainlike polygonal macules and plaques are present on the trunk and left axilla of a patient with severe extragenital LS. The clinical subscore of this body area before treatment was 2 (1 point for <33% of body area involvement and 1 point for mild sclerosis/induration in the upper part of the lesions and mild atrophy with blister formation in the lower lesions), and the total score was 12 (see Table 2). B, A close-up view of the same patient's back shows extragenital LS with marked atrophy and concomitant occurrence of bullae.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2

Widespread extragenital lichen sclerosus (LS) in patient 4. A large indurated ivory plaque with some smaller satellite lesions is seen on the patient's abdomen. The clinical subscore of this body area before treatment was 2 (1 point for <33% of body area involvement and 1 point for mild induration/sclerosis), and the patient's total pretreatment score was 6 (see Table 2).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3

Severe erosive extragenital lichen sclerosus in patient 1. A central superficial erosion is present on the patient's lower abdomen. Moreover, widespread atrophy is present. The clinical subscore of this body area before treatment was 6 (3 points for >67% body area involvement and 3 points for severe atrophy with superficial erosions), and the patient's total pretreatment score was 24 (see Table 2).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4

Pulsed intravenous high-dose corticosteroids combined with orally administered low-dose methotrexate treatment (PCMT) in generalized and refractory extragenital lichen sclerosus (LS) (patient 1). A, Clinical aspects of widespread disease. B, Marked improvement of former skin lesions 6 months after the end of treatment. These clinical pictures are representative of the whole outcome of the study and demonstrate that the combination of PCMT is effective in patients with extensive extragenital LS.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1 Characteristics of Patients With Extragenital LS Treated With PCMT
Table Graphic Jump LocationTable 2 Clinical Score Before and After PCMT and at the End of the Follow-up Perioda

References

Howard  ADean  DCooper  SKirtshig  GWojnarowska  F Circulating basement membrane zone antibodies are found in lichen sclerosus of the vulva. Australas J Dermatol 2004;45 (1) 12- 15
PubMed Link to Article
Oyama  NChan  INeill  SM  et al.  Autoantibodies to extracellular matrix protein 1 in lichen sclerosus. Lancet 2003;362 (9378) 118- 123
PubMed Link to Article
Cooper  SMAli  IBaldo  MWojnarowska  F The association of lichen sclerosus and erosive lichen planus of the vulva with autoimmune disease: a case-control study. Arch Dermatol 2008;144 (11) 1432- 1435
PubMed
Powell  JJWojnarowska  F Lichen sclerosus. Lancet 1999;353 (9166) 1777- 1783
PubMed Link to Article
Renaud-Vilmer  CCavelier-Balloy  BPorcher  RDubertret  L Vulvar lichen sclerosus: effect of long-term topical application of a potent steroid on the course of the disease. Arch Dermatol 2004;140 (6) 709- 712
PubMed Link to Article
Neill  SMRidley  CM Management of anogenital lichen sclerosus. Clin Exp Dermatol 2001;26 (8) 637- 643
PubMed Link to Article
Colbert  RLChiang  MPCarlin  CSFleming  M Progressive extragenital lichen sclerosus successfully treated with narrowband UV-B phototherapy. Arch Dermatol 2007;143 (1) 19- 20
PubMed Link to Article
Kreuter  AGambichler  T Narrowband UV-B phototherapy for extragenital lichen sclerosus. Arch Dermatol 2007;143 (9) 1213
PubMed Link to Article
Kreuter  AGambichler  T UV-A1 phototherapy for sclerotic skin diseases: implications for optimizing patient selection and management. Arch Dermatol 2008;144 (7) 912- 916
PubMed Link to Article
Kreuter  AGambichler  TAvermaete  A  et al.  Low-dose ultraviolet A1 phototherapy for extragenital lichen sclerosus: results of a preliminary study. J Am Acad Dermatol 2002;46 (2) 251- 255
PubMed Link to Article
Kreuter  AGambichler  TBreuckmann  F  et al.  Pulsed high-dose corticosteroids combined with low-dose methotrexate in severe localized scleroderma [published correction appears in Arch Dermatol. 2005;141(9):1091]. Arch Dermatol 2005;141 (7) 847- 852
PubMed Link to Article
Uitto  JSanta Cruz  DJBauer  EAEisen  AZ Morphea and lichen sclerosus et atrophicus: clinical and histopathologic studies in patients with combined features. J Am Acad Dermatol 1980;3 (3) 271- 279
PubMed Link to Article
Seyger  MMvan den Hoogen  FHde Boo  Tde Jong  EM Low-dose methotrexate in the treatment of widespread morphea. J Am Acad Dermatol 1998;39 (2, pt 1) 220- 225
PubMed Link to Article
Hengge  URKrause  WHofmann  H  et al.  Multicentre, phase II trial on the safety and efficacy of topical tacrolimus ointment for the treatment of lichen sclerosus. Br J Dermatol 2006;155 (5) 1021- 1028
PubMed Link to Article
Oskay  TSezer  HKGenç  CKutluay  L Pimecrolimus 1% cream in the treatment of vulvar lichen sclerosus in postmenopausal women. Int J Dermatol 2007;46 (5) 527- 532
PubMed Link to Article
Zulian  F New developments in localized scleroderma. Curr Opin Rheumatol 2008;20 (5) 601- 607
PubMed Link to Article
Uziel  YFeldman  BMKrafchik  BRYeung  RSLaxer  RM Methotrexate and corticosteroid therapy for pediatric localized scleroderma. J Pediatr 2000;136 (1) 91- 95
PubMed Link to Article
Weibel  LSampaio  MCVisentin  MTHowell  KJWoo  PHarper  JI Evaluation of methotrexate and corticosteroids for the treatment of localized scleroderma (morphoea) in children. Br J Dermatol 2006;155 (5) 1013- 1020
PubMed Link to Article
Ihn  HSato  SFujimoto  MKikuchi  KTakehara  K Demonstration of interleukin-2, interleukin-4 and interleukin-6 in sera from patients with localized scleroderma. Arch Dermatol Res 1995;287 (2) 193- 197
PubMed Link to Article
Romero  LIPincus  SH In situ localization of interleukin-6 in normal skin and atrophic cutaneous disease. Int Arch Allergy Immunol 1992;99 (1) 44- 49
PubMed Link to Article
Kreuter  AHyun  JSkrygan  M  et al.  Ultraviolet A1–induced downregulation of human β-defensins and interleukin-6 and interleukin-8 correlates with clinical improvement in localized scleroderma. Br J Dermatol 2006;155 (3) 600- 607
PubMed Link to Article
Rau  RHerborn  G Benefit and risk of methotrexate treatment in rheumatoid arthritis. Clin Exp Rheumatol 2004;22 (5) (suppl 35)S83- S94
PubMed
Thompson  JFChalmers  DHWood  RFKirkham  SRMorris  PJ Sudden death following high-dose intravenous methylprednisolone. Transplantation 1983;36 (5) 594- 596
PubMed Link to Article
Haajanen  JSaarinen  OLaasonen  LKuhlbäck  BEdgren  JSlätis  P Steroid treatment and aseptic necrosis of the femoral head in renal transplant recipients. Transplant Proc 1984;16 (5) 1316- 1319
PubMed

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
JAMAevidence.com