protein, 0.01 mg/dL (<0.3 mg/dL); complement component 3, 63 mg/dL (86-160 mg/dL); complement component 4, 10 mg/dL (17-45 mg/dL); CH50, 23.9 U/mL (25.048.0 U/mL); antinuclear antibody, 1:160 (homogeneous and speckled pattern); anti-single-stranded DNA antibody, 94 U/mL (<10 U/mL). Antibodies to double-stranded DNA, topoisomerase-1, centromere and SS-A were negative. The histological findings of a skin biopsy from the sclerotic erythema of the patient’s left arm were consistent with morphea (figure 1B); accordingly, we diagnosed the patient with generalized morphea. Initially, the patient was treated with topical application of tacrolimus. Two weeks after the onset of treatment, the sclerotic lesions of the left arm improved. However, since the amount of topical tacrolimus, if applied to 35% of the BSA, would exceed the permitted limit in Japan (<10 g/d), tacrolimus was administered orally (1 mg/d) and the dosage gradually increased to 3 mg/d with monthly monitoring of trough levels (<20 ng/mL). Six months after the beginning of treatment, the erythema and the whitish, itchy, atrophic plaques had improved and the sclerotic skin areas were much softer. Oral tacrolimus (3 mg/d) has been continued for 1.5 years, leading to a gradual improvement of the cutaneous condition (figure 1C). Morphea is an autoimmune inflammatory sclerosing disorder that primarily affects the dermis and sometimes extends into the subcutaneous fat and the fascia, producing thickening and hardening of the skin. Differentiating between morphea and lichen sclerosus et atrophicus (LSA) presents a clinical and (immune)histopathological challenge due to their similarity. In addition, LSA can develop either secondarily to morphea or simultaneously with it [1, 2]. In our patient, the typical histological findings of LSA (hydropic degeneration of the basal cell layer and homogenization of the collagen in the upper dermis) were not observed. Therefore, we concluded that generalized morphea was more likely than generalized LSA in our patient. There are two hypotheses on the association of low complement levels with autoimmune diseases, including morphea. One is that the activated complement system may contribute to tissue damage in patients with autoimmunity. The other is that genetic deficiencies or mutations of the complement-encoding genes may increase the risk of autoimmunity [3]. The low complement levels in our patient could be associated with the pathogenesis of generalized morphea, as previously reported [4]. Phototherapy, methotrexate/systemic corticosteroids and calcipotriene have the most evidence for efficacy in morphea [5]. Cyclosporine, a calcineurin inhibitor, acts as a potent immunosuppressant and was reportedly effective for the treatment of linear morphea [6]. Tacrolimus ointment, another calcineurin inhibitor, can serve as an alternative topical treatment for morphea and sclerotic chronic graft versus host disease [5, 7, 8]. Oral tacrolimus may also be an effective treatment option for generalized morphea. Accumulation of additional cases and evidence will facilitate the analysis of the effect of oral tacrolimus on this intractable disease.  Disclosure. Financial support: none. Conflict of interest: none.

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Department of Dermatology, Japan Community Healthcare Organization Osaka Hospital 2 Department of Dermatology, Tokyo Medical and Dental University, Graduate School of Medicine, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8519, Japan 3 Department of Respiratory Medicine, Allergy, and Rheumatic Diseases, Osaka University Graduate School of Medicine

Ayaki HIROHATA1 Takaaki HANAFUSA1,2 Ken IGAWA2 Tomoko INOUE-NISHIMOTO1 Eriko MABUCHIKIYOHARA1 Masayuki NISHIDE3 Hiroo YOKOZEKI2 Ryuta IKEGAMI1

1. Uitto J, Santa Cruz DJ, Bauer EA, Eisen AZ. Morphea and lichen sclerosus et atrophicus. Clinical and histopathologic studies in patients with combined features. J Am Acad Dermatol 1980; 3: 271-9. 2. Kakizaki A, Fujimura T, Furudate S, Kambayashi Y, Aiba S. Immunohistochemical Similarities between Lichen Sclerosus et Atrophicus and Morphea: A Case Study. Case Rep Dermatol 2015; 7: 39-45. 3. Ballanti E, Perricone C, Greco E, et al. Complement and autoimmunity. Immunol Res 2013; 56: 477-91. 4. Venneker GT, Van Meegen M, De Kok-Nazaruk M, et al. Incomplete functional deficiencies of the fourth (C4) and second (C2) components of complement in a patient with linear frontoparietal scleroderma and his family. Deficiencies determined by a gene not linked to human leukocyte antigen system. Exp Clin Immunogenet 1996; 13: 104-11. 5. Zwischenberger BA, Jacobe HT. A systematic review of morphea treatments and therapeutic algorithm. J Am Acad Dermatol 2011; 65: 925-41. 6. Perez Crespo M, Betlloch Mas I, Mataix Diaz J, Lucas Costa A, Ballester Nortes I. Rapid response to cyclosporine and maintenance with methotrexate in linear scleroderma in a young girl. Pediatr Dermatol 2009; 26: 118-20. 7. Cantisani C, Miraglia E, Richetta AG, Mattozzi C, Calvieri S. Generalized morphea successfully treated with tacrolimus 0.1% ointment. J Drugs Dermatol 2013; 12: 14-5. 8. Choi CJ, Nghiem P. Tacrolimus ointment in the treatment of chronic cutaneous graft-vs-host disease: a case series of 18 patients. Arch Dermatol 2001; 137: 1202-6. doi:10.1684/ejd.2015.2689

Satisfaction with treatment and healthrelated quality of life among patients with lichen planus: a web-based survey Although considered relevant, little is known about satisfaction with treatment and health-related quality of life (HRQoL) among lichen planus (LP) patients. There are only two studies that evaluated LP patients’ satisfaction with treatment and both used global, single item measures [1, 2]. Studies on the HRQoL of patients with oral LP showed that the impact of LP is comparable to other mouth diseases [3, 4] and that topical therapies improved HRQoL [5, 6].

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In 1) 2) of

the present cross-sectional study we aimed to assess LP patients’ satisfaction with their current treatment, the importance LP patients attach to specific domains satisfaction, 3) domains with potential for quality

improvement from patients’ perspective, and 4) LP patients’ HRQoL. All members of the Dutch LP Patient Association (N = 138) were invited to register online. Eligible patients were asked

Table 1. Background characteristics Total sample (N=58)

Sub sample (N=39)

6 (10.3) 52 (89.7) 61.5 (13.0) 7.0 (56.0)

0 39 (100) 62.0 (13.0) 7.0 (9.0)

32 (55.2) 15 (25.9) 8 (13.8) 2 (3.4) 1 (1.7)

23 (59.0) 8 (20.5) 7 (17.9) 1 (2.6) 0

44 (75.9) 14 (24.1)

30 (76.9) 9 (23.1)

Self-reported type of LP2 , N (%) Mouth/esophagus Skin Genitals Other

48 (82.8) 30 (51.7) 35 (60.3) 5 (8.6)

34 (87.2) 24 (61.5) 26 (66.7) 4 (10.3)

Patient reported global disease severity1 , median (IQR)

3.0 (1.0)

3.0 (1.0)

33 (56.9) 16 (27.6) 9 (15.5) 1 (1.7) 1 (1.7) 1 (1.7)

24 (61.5) 14 (35.9) 5 (12.8) 0 1 (2.6) 1 (2.6)

25 (43.1) 10 (17.2) 8 (13.8) 8 (13.8) 6 (10.3) 5 (8.6) 3 (5.2) 2 (3.4) 2 (3.4) 1 (1.7) 1 (1.7) 1 (1.7) 1 (1.7) 1 (1.7)

21 (53.8) 8 (20.5) 6 (15.4) 7 (17.9) 5 (12.8) 4 (10.3) 3 (7.7) 2 (5.1) 1 (2.6) 1 (2.6) 1 (2.6) 1 (2.6) 1 (2.6) 0

1 (1.7) 1 (1.7) 3 (5.2)

0 0 0

7 (12.1) 2.0 (5.5)

2 (5.1) 1.0 (6.0)

Sex, N (%) Male Female Age (years), median (IQR) Time since diagnosis (years), median (IQR) Diagnosis given by, N (%) Dermatologist Oral surgeon / dentist Gynaecologist Other General Pracitioner Diagnosis confirmed by biopsy Yes No

2

Current treatment by, N (%) Dermatologist Gynaecologist Oral surgeon / dentist General Practitioner Alternative healer Other

Current treatment, N (%)2 Topical Clobetasol propionate Emollients of indifferent topical treatment Betamethasone Tacrolimus Triamcinolone acetonide Fluticasone propionate Mometasone furoate Desoximetasone Vitamin D Betamethasone valerate Betamethasone dipropionate Clobetasone butyrate Hydrocortisone butyrate Mometason ointment Systemic Cyclosporin Acitretin Prednisone Other3 Duration of current treatment (years), median (IQR)

1 1 = not severe, 5 = very severe; 2 Percentages may not add up to 100% due to the possibility to give multiple answers; 3 pelvic floor therapy, treatment by oral hygienist.

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Table 2. Satisfaction of female LP patients with current topical treatment (N = 39) Treatment satisfaction1

Importance2

Dissatisfied3

Median (IQR)

Median (IQR)

N (%)

Global satisfaction Effectiveness Safety Convenience

3 (1) 3 (2) 3 (1) 4 (1)

NA 2.7 (1.4) 1.7 (1.0) 1.0 (1.0)

NA 11 (28.2%) 9 (23.1%) 5 (12.8%)

NA 0.76 0.39 0.13

Doctor-patient relation5 Information provision Organization

4 (0) 3 (2) 4 (1)

2.0 (0.9) 1.3 (1.0) 1.0 (1.8)

6 (15.4%) 12 (30.8%) 5 (12.8%)

0.31 0.40 0.13

5

Quality improvement score4

NA: Not available (not measured); 1 1 = “not satisfied at all“ to 5 = “very satisfied; 2 Patients divided 10 points over the six domains. They were instructed to assign more points to a domain that they found more important; 3 number and proportion of patients with a treatment satisfaction score of 1 or 2; 4 quality improvement score = median importance score x proportion dissatisfied. Scores near zero indicate an already favourable situation for a specific treatment domain, whereas higher scores indicate more potential for quality improvement; 5 N=38.

to complete a web-based survey. Patient inclusion criteria were: diagnosis of LP, 18 years or older, currently under treatment for LP, and access to the internet. Data were collected in March 2012. The central Ethics Committee of the Academic Medical Centre of Amsterdam exempted this study for ethical approval. For observational research, this is common policy in the Netherlands. We measured satisfaction with treatment with a studyspecific, multi-domain questionnaire, adapted from previous research in patients with psoriasis [7]. An Overall satisfaction score was calculated by summing all items (range 7-35, Cronbach’s alpha 0.84). HRQoL was measured with the Skindex-29, a wellestablished dermatology-specific, questionnaire [8]. We calculated domain scores for Symptoms, Emotions, and Functioning and categorized scores into mildly, moderately or severely impaired HRQoL [9]. All statistical analyses were performed in SPSS 19.0. 105 patients (76.1%) registered for participation, of which 42 (40.0%) did not meet inclusion criteria or did not give informed consent. Five patients did not complete the questionnaire, thus a total of 58 patients (table 1) resulted for analyses. As male patients (n = 6) and patients with a systemic treatment (n = 4) were under-represented, further analyses had to focus on a subsample of female patients who currently had a topical treatment and no other medical treatment (N = 39). Satisfaction scores are presented in table 2. Median Overall satisfaction score was 24.5 (IQR = 6.5; N = 38). HRQoL impairment (table 3) for the sample was moderate for Symptoms, mild for Emotions, mild for Functioning and moderate for the Overall score. At each HRQoL domain,

approximately one third of patients reported severe impairment (33.3-35.9%). Our results indicate that female LP patients were only moderately satisfied with their topical treatment. Patients were mostly satisfied with doctor-patient relation, convenience of treatment and the way the care was organized in their treatment center. They rated treatment effectiveness as most important, which is consistent with previous research in psoriasis [7]. Furthermore, our findings indicate that the effectiveness of topical treatment and information provision have potential for quality improvement. Our results with respect to HRQoL impairment are in line with previous research [3, 4]. Our study has several limitations. First, generalization of results is uncertain as we only included members of a LP Patient Association, as we had to restrict our analyses to women, and as our sample was on average older than LP patients seen in routine clinical practice. Second, we used a study-specific questionnaire, which was not formally validated but showed good reliability in our sample. Third, clinical characteristics were self-reported and not confirmed by a health care provider. For clinical practice, our results show that the routine assessment of LP patients’ satisfaction with treatment and HRQoL is important to provide a more detailed picture of patients’ needs, opinions and impact of LP on patients’ daily life, in addition to clinical outcome measures. Also, it may be beneficial to actively involve patients in the management of their disease. Actively involving patients in their care may lead to increased patient satisfaction, more treatment adherence, improved recovery and better health outcomes [10]. 

Table 3. HRQoL of female LP patients with topical treatment (N = 39), as measured with Skindex-29 95% CI

M (SD) Symptoms Emotions Functioning Overall

Mild impairment

Moderate impairment

Severe impairment

Lower bound

Upper bound

N (%)

N (%)

N (%)

42.1 28.3 20.1 29.1

53.3 37.3 33.4 38.7

4 (10.3%) 9 (23.1%) 3 (7.7%) 10 (25.6%)

8 (20.5%) 7 (17.9%) 3 (7.7%) 8 (20.5%)

14 (35.9%) 13 (33.3%) 13 (33.3%) 10 (25.6%)

47.7 (17.4) 32.8 (13.9) 26.8 (20.5) 33.9 (14.7)

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Disclosure. Financial support: Fund of the Dutch Ministry of Health, Welfare and Sport (“Fonds PGO”); the Dutch Lichen Planus Patient Association (“Lichen Planus Vereniging Nederland”); the Dutch Skin Foundation (“Stichting Nationaal Huidfonds”). Conflict of interest: MA de Rie received honoraria for participating in advisory boards from AbbVie, Amgen, Artax, Biogen Idec, Centocor, Eli Lilly, GSK, Janssen-Cilag, LEO Pharma, MSD, Novartis Pharma, Pfizer, Roche, Sandoz, Waldmann and Xenon Pharma. The Department of Dermatology received an unrestricted grant in the past from Schering Plough, and an educational research grant from Pfizer. J de Korte is joint copyright owner of the Dutch version of the Skindex-29. 1

Department of Dermatology, Dutch Skin Foundation, Utrecht, the Netherlands 3 Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands 4 Department of Dermatology, 5 Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands 2

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Oda D VAN CRANENBURGH1,2 Sandra B W NIJLAND2 John DE KORTE1,2 Robert LINDEBOOM3 Menno A DE RIE1,4 Jacqueline A TER STEGE2 Cecilia A C PRINSEN1,5

1. Jensen JT, Bird M, Leclair CM. Patient satisfaction after the treatment of vulvovaginal erosive lichen planus with topical clobetasol and tacrolimus: a survey study. Am J Obstet Gynecol 2004; 190: 1759-63, discussion 63-5. 2. Hegarty AM, Hodgson TA, Lewsey JD, et al. Fluticasone propionate spray and betamethasone sodium phosphate mouthrinse: A randomized crossover study for the treatment of symptomatic oral lichen planus. J Am Acad Dermatol 2002; 47: 271-9. 3. Lopez-Jornet P, Camacho-Alonso F. Quality of life in patients with oral lichen planus. J Eval Clin Pract 2010; 16: 111-3. 4. Rajan B, Ahmed J, Shenoy N, et al. Assessment of quality of life in patients with chronic oral mucosal diseases: a questionnaire-based study. Perm J 2014; 18: e123-7. 5. Gorouhi F, Solhpour A, Beitollahi JM, et al. Randomized trial of pimecrolimus cream versus triamcinolone acetonide paste in the treatment of oral lichen planus. J Am Acad Dermatol 2007; 57: 806-13. 6. Salazar-Sanchez N, Lopez-Jornet P, Camacho-Alonso F, et al. Efficacy of topical Aloe vera in patients with oral lichen planus: a randomized double-blind study. J Oral Pathol Med 2010; 39: 735-40. 7. Cranenburgh OD van, Korte J de, Sprangers MAG, et al. Satisfaction with treatment among patients with psoriasis: a web-based survey study. Br J Dermatol 2013; 169: 398-405. 8. Chren M-M, Lasek RJ, Flocke SA, et al. Improved Discriminative and Evaluative Capability of a refined version of Skindex, a Quality-of-Life Instrument for Patients with Skin Diseases. Arch Dermatol 1997; 133: 1433-40. 9. Prinsen CAC, Lindeboom R, Korte Jd R. Interpretation of Skindex-29 Scores: Cutoffs for Mild. Moderate, and Severe Impairment of HealthRelated Quality of Life. J Invest Dermatol 2011; 131: 1945-7. 10. Groene O. Patient centredness and quality improvement efforts in hospitals: rationale, measurement, implementation. Int J Qual Health Care 2011; 23: 531-7. doi:10.1684/ejd.2015.2703

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