Musculoskeletal Imaging Original Research

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1 Musculoskeletal Imaging Original Research Schanz et al. MRI of Treatment Response in Patients With Deep Morphea Musculoskeletal Imaging Original Research Stefan Schanz 1 Jörg Henes 2 Anja Ulmer 1 Ina Kötter 2 Gerhard Fierlbeck 1 Claus Detlef Claussen 1 Marius Horger 3 Schanz S, Henes J, Ulmer A, et al. Keywords: fasciitis, localized scleroderma, localized scleroderma severity index, morphea, MRI, myositis, skin induration DOI: /AJR Received June 1, 2012; accepted after revision July 20, Department of Dermatology, Eberhard-Karls-University Tuebingen, Tuebingen, Germany. 2 Department of Internal Medicine, Eberhard-Karls- University Tuebingen, Tuebingen, Germany. 3 Department of Radiology, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Strasse 3, Tuebingen 72076, Germany. Address correspondence to M. Horger. WEB This is a Web exclusive article. AJR 2013; 200:W376 W X/13/2004 W376 American Roentgen Ray Society Response Evaluation of Musculoskeletal Involvement in Patients With Deep Morphea Treated With Methotrexate and Prednisolone: A Combined MRI and Clinical Approach OBJECTIVE. The purpose of this article is to explore the role of MRI in monitoring musculoskeletal involvement in patients with morphea who are undergoing treatment with methotrexate and prednisolone. SUBJECTS AND METHODS. Twenty-two consecutive patients (six men and 16 women; median age, 52 years) with systemic scleroderma and deep morphea prospectively underwent whole-body MRI twice, before treatment (time 1) and during follow-up after 6 12 months (time 2). Images were evaluated for abnormal signal intensity or thickening of subcutaneous fatty tissue septa, muscular fasciae, intramuscular perifascial septa, muscle signal intensity, and articular or tendon sheath synovial abnormalities on STIR and gadolinium-enhanced scans. For clinical assessment, the localized scleroderma (morphea) severity index and a 0 6 pain score were applied. RESULTS. From a clinical point of view, none of our patients had progression of the disease, 12 patients were responders (defined as an improvement of localized scleroderma severity index and pain score 50%), and 10 patients had stable disease. Among responders, the number of patients with subcutaneous septal thickening (time 1, n = 9; time 2, n = 2), fascial enhancement (time 1, n = 8; time 2, n = 3), and articular synovitis (time 1, n = 5; time 2, n = 1) decreased more than in the stable disease group (subcutaneous septal thickening: time 1, n = 9; time 2, n = 8; fascial enhancement: time 1, n = 5; time 2, n = 5; articular synovitis: time 1, n = 8; time 2, n = 6). Subcutaneous thickening, fascial thickening, and fascial enhancement were scored significantly lower at follow-up MRI in responders. CONCLUSION. MRI findings were sensitive to changes in musculoskeletal manifestations in patients with deep morphea undergoing systemic treatment with methotrexate and prednisolone. Thus, MRI can be recommended as an additional tool for response monitoring. M orphea, also called localized scleroderma, is an inflammatory disease that may lead to skin thickening and hardening due to fibrosis. It has to be distinguished from systemic scleroderma, which is characterized by Raynaud phenomenon, digital sclerosis, and potential involvement of internal organs [1]. In contrast, morphea was long thought to involve the skin only, but the disease may also affect underlying structures [2]. If this occurs, morphea may be associated with heavy pain, flexion contractures, and considerable impairment [3 5]. In recent years, the first data documenting a high prevalence of musculoskeletal involvement in patients with morphea have been published [6 9]. These surveys were based on clinical data and did not systematically include imaging procedures. Thus, little is still known about the characteristics of musculoskeletal manifesta- tions. In particular, to our knowledge, there are no systematic data about the course and outcome of musculoskeletal manifestations. Thus, the clinical relevance is not clear yet. Numerous treatments have been discussed for these debilitating forms of morphea, including corticosteroids [10], sulfasalazine [11], plasmapheresis [12], or d-penicillamine [13]. In recent years, bath phototherapy and ultraviolet A1 phototherapy have been established for the treatment of morphea and have been shown to be effective in uncontrolled clinical trials [14, 15]. However, in cases with deep infiltration, particularly fascial involvement, these treatments have limitations [16]. Also, in cases of synovitis, the efficacy of topical phototherapy is questionable. Hence, for deep morphea (a subtype of morphea involving subcutaneous tissue), therapy with methotrexate in combination with prednisolone has W376 AJR:200, April 2013

2 MRI of Treatment Response in Patients With Deep Morphea been recommended [17] and already has been studied in some retrospective case series and uncontrolled trials in adults [18 20] and children [10, 21, 22]. A randomized controlled trial revealed the effectiveness of methotrexate in juvenile patients with morphea [23]. In most trials, low-dose methotrexate is used [19 23], either as a single agent [23] or combined with prednisolone [19, 21, 22]. A very recent trial used a high-dose methotrexate regimen in children with morphea [24]. The treatment outcome was mainly determined by semiquantitative clinical expert scores [20, 22 24]; some studies have also used infrared thermography [22, 23] or the measurement of skin thickening by high-resolution ultrasound [19]. However, detailed information about the outcome of musculoskeletal manifestations are lacking in these observations. Recently, MRI has been shown to be a useful diagnostic tool for displaying musculoskeletal involvement in patients with morphea [25]. The aim of this study was to document with MRI changes in patients with morphea with musculoskeletal involvement who were treated with methotrexate and prednisolone. Subjects and Methods In accordance with the regulations of the hospital review board, we included 22 consecutive patients with systemic scleroderma and deep morphea who presented from November 2005 to June 2010 at the department of dermatology in this prospective study. The diagnosis of deep morphea was based on clinical symptoms and histology, according to the Mayo Clinic [26] and the Padua classification criteria [2]. Overlap with other rheumatic diseases was excluded by clinical examination and laboratory tests according to international applicable regulations. All patients had deep morphea. According to the suggestions of the German Dermatologic Society [17], all patients had an indication for treatment with systemic methotrexate and prednisolone because they had a generalized or deep form of morphea or they had involvement of the fasciae, muscles, or bones. We included six male and 16 female consecutive patients with a median age of 52 years and a mean disease duration before therapy of 18 months who fulfilled these criteria (Table 1). The treatment protocol was as follows: Patients received 15 mg of methotrexate per week subcutaneously and 5 mg of folic acid the day after methotrexate administration. Prednisolone treatment was started with 1 mg of prednisolone per kilogram of body weight for 2 4 weeks and was then slowly tapered, considering disease activity and individual aspects and comorbidities. Clinical Examination Protocol Two dermatologists with more than 10 years of clinical practice in the diagnosis and treatment of dermatologic autoimmune diseases independently assessed the clinical status of the patients. This assessment consisted of three parts. First, patients were rated according to the localized scleroderma (morphea) severity index, which has been published and validated specifically for patients with morphea [27]. This score reflects the clinical status based on four parameters: surface area involved by the disease, erythema at the margin of the lesions, skin thickness (which was adopted from the modified Rodnan skin score), and new lesion or extension within the past 3 months [28]. Second, we used a 0 6 score for rating periarticular and soft-tissue pain. Third, patients were clinically classified according to the generally accepted Padua classification criteria of morphea [2] and were subdivided into subtypes, as follows: for the first subtype, circumscribed morphea is characterized by oval or round areas, often with altered pigmentation and a lilac ring. This subtype is subdivided into a superficial form that involves only the skin and a deep variant that also affects subcutaneous structures. For this study, only the deep variant was considered. The second subtype is linear morphea with linear induration involving the dermis and subcutaneous structures and possible extension to the fascia, muscles, tendons, or even bones. This subtype may affect the trunk, limbs, or the head ( en coup de sabre scleroderma ). The third subtype is generalized morphea, which is characterized by four or more plaques larger than 3 cm, which tend to become confluent and affect two or more anatomic sites. The fourth subtype, pansclerotic morphea, circumferentially involves limbs affecting subcutaneous tissues, muscles, and bones. The fifth subtype is mixed morphea, where different subtypes are present. MRI Examination Protocol MRI examinations were conducted on a 1.5-T closed-bore whole-body MRI scanner (Avanto, Siemens Healthcare) equipped with parallel-imaging technology of up to 32 independent receiver channels (Total Imaging Matrix technique, Siemens Healthcare). Signal was recorded with the matrix coil. The patients were positioned supine and head-first in the magnet bore, with multiple sets of phased-array surface coils installed simultaneously to cover the head, neck, chest and arms, abdomen, pelvis, thighs, and calves down to the ankles. For all patients, MRI scans were performed using high-performance gradients (maximum amplitude, 45 mt/m; minimum rise time, 200 μs; maximum slew rate, 200 T/m/s) with integrated parallel acquisition techniques in three spatial directions. The imaging protocol consisted of gradient-echo localizers on each table position followed by coronal whole-body STIR images for assessment of pathologic signal changes occurring in the musculoskeletal system. According to the clinical classification (generalized plus pansclerotic vs linear plus circumscribed morphea), we performed whole-body coronal STIR MRI screening in the former group (n = 12) and regional (e.g., lower limb) MRI coronal STIR screening in the latter group (n = 10). Coronal STIR images were acquired (TR/TE, 6700/87; inversion time, 140 ms; one excitation; echo-train length, 19; matrix, ; slice thickness, 5 mm with 20% gaps). Subsequently, unenhanced axial T1-weighted turbo spin-echo (TR/TE, /12; echo-train length, 3; matrix, ; slice thickness, 5 mm with 20% gap; pixel spacing, mm) or gradient-recalled echo sequences (TR/TE, 121/4.76) for the torso and abdomen, STIR (TR/TE, 4010/103; inversion time, 160 ms; number of excitations, 2; echo-train length, 17; slice thickness, 5 mm with 7-mm gaps for rapid coverage of the extremities; matrix, ; pixel spacing, 1 mm), and T1-weighted fat-suppressed spin-echo gadolinium-enhanced sequences (TR/TE, 686/12; number of excitations, 1; slice thickness, 6 7 mm; matrix, ; 7-mm gaps; pixel spacing, mm) were performed after IV application of a bolus injection of gadopentetate dimeglumine (Magnevist, Bayer-Schering) or gadobutrol (Gadovist, BayerHealthcare) (0.1 mmol/kg of body weight for both) at the anatomic site exhibiting the highest degree of pathologic musculoskeletal changes. We TABLE 1: Patient Demographics and Distribution of Clinical Subtypes of Morphea Sex (No. of Patients) Mean Disease Clinical Subtype Median Age (y) Male Female Duration Before First MRI (mo) Circumscribed deep morphea (n = 3) Linear morphea (n = 7) Generalized morphea (n = 11) Pansclerotic morphea (n = 1) Total (n = 22) AJR:200, April 2013 W377

3 Schanz et al. TABLE 2: Response to Methotrexate Treatment Localized Scleroderma Severity Index Score a Pain Score a,b MRI Sum Score a,c No. of Patients No. of With Stable Clinical Subtype Time 1 Time 2 Time 1 Time 2 Time 1 Time 2 Responders d Disease e Circumscribed deep morphea (n = 3) Linear morphea (n = 7) f f 5 2 Generalized morphea (n = 11) g g f 5 6 Pansclerotic morphea (n = 1) Total (n = 22) g g g a Data are mean scores. Pain is scored from 0 to 6. c Sum of MRI assessment scores (0 2) per patient. d Response is defined as a reduction of both localized scleroderma (morphea) severity index and pain score 50%. e Stable disease is defined as a reduction of localized scleroderma (morphea) severity index or pain score < 50%. f p < 0.05 for time 1 versus time 2 (related samples Wilcoxon signed rank test). g p < for time 1 versus time 2 (related samples Wilcoxon signed rank test). used a rectangular FOV of 100% or 80%, according to the examined anatomic region, and between two and four signals were acquired per sequence. These scans were acquired at least at one table position over the main involved site including at least one large joint next to it both at first and second MRI examinations. The total examination time was about 30 minutes for one MRI study. MRI Evaluation Two radiologists with more than 10 years of expertise in musculoskeletal diagnosis analyzed all image sets separately, and decisions were made in consensus. Studies were presented in random order, blinded to patient data, date, and time. The individual cross-sectional images were evaluated for evidence of pathologic changes (thickening or increased signal intensity on STIR and gadolinium-enhanced images) in the subcutaneous fatty tissue septa, muscle fasciae, perifascial intramuscular septa, and muscles, as well as in the articular or tendon sheath synovium and entheses. Subcutaneous septal thickening was defined as a fine or coarse latticelike septa appearance in the subcutaneous fat tissue, exhibiting hyperintense signal intensity on STIR and hypointense signal intensity on T1-weighted scans. We graded this finding as follows: inconspicuous (score, 0) if it could not be delineated, moderate (score, 1) if it was up to 1 mm, or marked (score, 2) if it was larger than 1 mm. The degree of enhancement on T1-weighted fat-suppressed gadolinium-enhanced images was registered and classified as inconspicuous (score, 0) if it was less than that of the adjacent muscle, mild (score, 1) if it was isointense to musculature, or marked (score, 2) if it was greater than the adjacent muscular signal. Fascial thickening was graded as inconspicuous (score, 0) if it could not be delineated, moderate (score, 1) if it was up to 2 mm, or marked (score, 2) if it was larger than 2 mm. The degree of enhancement was scored analogously to that of subcutaneous septal thickening. Increased signal intensity seen within the muscle fibers immediately adjacent to the fascia on fluid-sensitive sequences as well as on gadolinium-enhanced T1-weighted fat-suppressed images reflects involvement of perifascial intramuscular septa and was likewise scored. Abnormal signal intensity in the musculature on STIR and gadolinium-enhanced images representing edema and hyperemia due to either inflammation or an admixture of incipient collagenization was classified as focal or diffuse and was scored analogously. Hyperintense signal on both STIR and fat-saturated gadolinium-enhanced images in a thickened articular and tendon sheath synovium were similarly scored, whereas for enthesitis, only the presence or absence of enthesitis was registered. Statistical Analysis For statistical evaluation, SPSS software (version 19, SPSS) was used. The Wilcoxon signed rank test was applied to examine differences between time points. Results Our 22 patients (six men and 16 women; median age, 52 years; mean duration of disease, 18 months) belonged to the clinical subgroups of circumscribed deep morphea (n = 3), linear morphea (n = 7), generalized morphea (n = 11), and pansclerotic morphea (n = 1). The patient with pansclerotic morphea had a long duration of disease (120 months). For the other clinical subgroups, the mean duration of disease before the first MRI was months (Table 1). Clinical Response Evaluation Patients who experienced improvement in both localized scleroderma severity index and pain score 50% or greater between the two evaluation time points were defined as responders. According to this criterion, 12 patients were responders, whereas 10 patients had stable disease (Table 2). For both the mean localized scleroderma severity index and pain score, a highly significant improvement was found in the total group. The most remarkable improvement of mean localized scleroderma severity index score was found in the subgroup of patients with generalized morphea, followed by patients with linear scleroderma. MRI Response Evaluation We identified three patients without MRI findings at either the first or second time point, despite clinical involvement (localized scleroderma severity index score, 9 11; pain score, 0 2). The number of abnormal MRI findings at the two time points is displayed in Table 3. Striking differences were found between responders and patients with stable disease. The number of patients with subcutaneous septal thickening decreased much more in the responder group. Also, the number of patients with fascial enhancement markedly regressed in responders, whereas it stayed unchanged in patients with stable disease (Figs. 1 3). For articular synovitis, we found also a remarkable difference in the magnitude of response. This symptom resolved at follow-up MRI in four of the five responding patients, whereas it resolved in only two of eight patients with stable disease. Table 4 records the mean scores of the respective musculoskeletal manifestations detected by MRI. In responders, we found a significant decrease with respect to the extent and degree of MRI findings. In responding patients subcutaneous thickening, fascial thickening and fascial enhancement were scored W378 AJR:200, April 2013

4 MRI of Treatment Response in Patients With Deep Morphea TABLE 3: Follow-Up of Initially Abnormal MRI Findings Responder a (n = 12) Stable Disease b (n = 10) Total (n = 22) Abnormal Findings Time 1 Time 2 Time 1 Time 2 Time 1 Time 2 Subcutaneous septal thickening Fascial thickening Fascial enhancement Perifascial enhancement Myopathy or myositis Articular synovitis Tenosynovitis Enthesitis Bone marrow involvement Note Data are number of patients. a Defined as a reduction of both localized scleroderma (morphea) severity index and pain score 50%. b Defined as a reduction of localized scleroderma (morphea) severity index or pain score < 50%. significantly lower at follow-up MRI, whereas in patients with stable disease, no significant change was found between the two time points. A C Discussion To our knowledge, the current study is the first to provide a systematic MRI-based response monitoring data in patients with morphea. The data clearly show that MRI is able to document both musculoskeletal involvement at initial presentation, as well as its changes occurring during therapy. In our series, the improvement of fascial involvement and articular synovitis in particular could be recorded via MRI. A valuable follow-up instrument should be able to differentiate between therapy responders, patients with stable disease, and those who are unresponsive to treatment. In our series, the clearance of abnormal findings under treatment appeared to be related to the treatment success. This was particularly true for subcutaneous septal thickening, fascial enhancement, and articular synovitis. The magnitude of response B Fig year-old woman with generalized morphea who presented initially with symmetric sclerosis of arms, hands, calves, and feet (localized scleroderma severity index score, 14). A and B, At first MRI, axial (A) and coronal (B) STIR images show marked fascial thickening (arrows) and synovitis (not shown), which were responsible for heavy pain (score, 4). C, On second MRI performed 6 months later during ongoing methotrexate therapy, axial STIR images show complete resolution of musculoskeletal findings. Clinically, skin sclerosis had markedly improved (localized scleroderma severity index score, 6) and pain was less severe (pain score, 2). on MRI correlated better with the pain score than with the localized scleroderma severity index score. One of the most challenging problems in the treatment of patients with morphea is the assessment of treatment efficacy. For the follow-up of musculoskeletal manifestations in morphea in particular, no established imaging concept exists. Surveillance procedures used to objectively evaluate these changes, such as high-resolution ultrasound for the measurement of skin thickening, localized scleroderma AJR:200, April 2013 W379

5 Schanz et al. severity index score, and thermography, do not reveal sufficient information about musculoskeletal structures. Musculoskeletal involvement, however, has a considerable prevalence in morphea [6 9]. Large studies containing data on the prevalence of musculoskeletal manifestations in morphea are predominantly based on retrospective clinical data rather than on imaging. Zulian et al. [6, 7] recently found A Fig year-old woman with generalized morphea who presented with generalized sclerosis of extremities and trunk (localized scleroderma severity index score, 24) and heavy pain at her arms, legs, and thorax (pain score, 4). A, On first MRI performed before initiation of systemic therapy with methotrexate, fat-saturated contrast-enhanced T1-weighted image shows marked fatty tissue septa (thin arrows) and fascial thickening (thick arrow). Note also perifascial intramuscular septal thickening and increased enhancement in anterior muscle compartment. B, At follow-up, 9 months after onset of systemic methotrexate treatment, there is considerable improvement of musculoskeletal involvement. Clinically, after 9 months, her pain had markedly improved (score, 1), whereas improvement of her generalized skin sclerosis was less impressive (localized scleroderma severity index score, 19). A Fig year-old man with circumscribed deep morphea who complained of deep firm sclerotic plaque involving scapular region of right shoulder (localized scleroderma severity index score, 8), which caused marked pain (score, 4). A, At first MRI, contrast-enhanced axial T1-weighted image shows subcutaneous infiltration with increased enhancement (arrow). B, Seven months later, after systemic methotrexate therapy, entire resolution of clinical symptoms and associated musculoskeletal MRI abnormalities was seen on fat-saturated contrast-enhanced axial T1- weighted image. Clinically, sclerotic plaque had become less firm (localized scleroderma severity index score, 4) and pain had decreased (score, 2). arthralgia in 91 of 750 (12%) patients. Christen- Zaech et al. [8] found arthralgia in 23 of 136 (17%) patients and muscular cramps in four of 136 (3%) patients. In a review of 123 adult and 122 pediatric patients with morphea, Leitenberger et al. [9] found a similar prevalence: 48 (19%) of the patients presented with arthralgia, 32 (13%) with myalgia, and 48 (19%) with a limited range of motion. B B Furthermore, musculoskeletal manifestations may be important arguments for systemic rather than topical therapy. The recent German Society of Dermatology guidelines for the management of patients with morphea recommend treatment with methotrexate and prednisolone if the patient has a deep, linear, or generalized form of morphea or if fasciae, muscles, or bones are involved [17]. Recent studies suggest the use of methotrexate combined with prednisolone for the treatment of severe morphea in juvenile [23, 24] and adult [20] patients. In our series, we found treatment success, which is in line with the previous studies. More than half of our patients could be classified as responders according to our clinical criteria, which were based on localized scleroderma severity index and pain score. Both scores reflect significant clinical improvement. The localized scleroderma severity index score mainly reflects involvement of the skin with regard to its severity (erythema, induration, development of new lesions, and enlargement of lesions) [24, 28]. Very recently, in a longitudinal study of methotrexate and prednisolone treatment of morphea in children [24], the score has been shown to be sensitive to changes. Similar to our data, the authors found a significant decrease in the patients localized scleroderma severity index scores under treatment, without an increase of this score in any patient. They found a median time of 1.77 months to reach inactive disease. The authors described extracutaneous manifestations of 25% of their patients at baseline, most of whom were experiencing contractures. In one patient, MRI had been performed and revealed arthritis with synovitis. However, these musculoskeletal manifestations were not assessed systematically. Instead, the authors stated that information about extracutaneous involvement may be included in a one-question physician global assessment score (100-mm visual analog scale) [24]. Kroft et al. [20] showed the effectiveness of methotrexate in treating morphea in a cohort study based on a semiquantitative 6-point assessment score without reflecting the musculoskeletal system. In the first placebo-controlled randomized trial on methotrexate treatment of morphea in children, clinical assessment was based on a computerized scoring system [23]. Using a transparent film, the borders of target lesions were first drawn and then scanned and calculated [29]. With this method, the authors found an improvement of target skin lesions in the methotrexate group, whereas in the placebo group, it worsened. Via infrared thermography, W380 AJR:200, April 2013

6 MRI of Treatment Response in Patients With Deep Morphea TABLE 4: Follow-Up of MRI Findings in Relation to Clinical Resolution Responder (n = 12) a Stable Disease (n = 10) b Finding Time 1 Time 2 Time 1 Time 2 Subcutaneous septal thickening c Fascial thickening c Fascial enhancement c Perifascial enhancement Myopathy or myositis Articular synovitis Tenosynovitis Enthesitis Bone marrow involvement MRI sum score d e Note Data are mean scores. a Defined as a reduction of both localized scleroderma (morphea) severity index and pain score 50%. b Defined as a reduction of localized scleroderma (morphea) severity index or pain score < 50%. c p < 0.05 for time 1 versus time 2 (related samples Wilcoxon signed rank test). d Sum of MRI assessment scores (0 2) per patient. e p < for time 1 versus time 2 (related samples Wilcoxon signed rank test). they found a mean temperature decrease in the skin target lesion of 44% in the methotrexate group versus 12% in the placebo group [23]. Obviously, these assessment systems could not include manifestations in the musculoskeletal system. It has been shown that, in patients with morphea, MRI is a useful tool for detection of musculoskeletal manifestations [25]. They were found in a considerable number of patients, including patients in whom musculoskeletal manifestations were not suspected clinically. Our results show that MRI is an additional surveillance tool for patients with morphea that may provide helpful and important information about musculoskeletal manifestations and appears to be sensitive toward changes related to therapy. With the use of MRI, it was possible to objectively evaluate clinical response by imaging, in addition to the more subjective clinical evaluation scores. It provided complementary information about the depth of the involvement of underlying morphologic structures, contrary to the clinical examination, which generally reveals information about the superficial involvement in this disorder. The use of MRI makes it possible to objectively evaluate changes of fascial, muscular, and joint tissues. Thus, MRI may confirm findings from the physical examination. However, sometimes discrepancies between the superficial and deep involvement of the disease are found that elude either clinical or MRI examination. In three of our patients with moderate clinical involvement, MRI did not reveal deep musculoskeletal alterations. On the other hand, we identified three patients with moderate clinical improvement (localized scleroderma severity index < 50%) in whom the musculoskeletal manifestations did not improve at all during therapy. The presence or absence of these alterations may have consequences for individual decisions about treatment, because involvement of the musculoskeletal system is an important argument for systemic treatment of the disease. Finally, correct application of the clinical scores is highly dependent on the expertise of the physician, whereas MRI findings are generally easier to interpret. However, we did not focus our attention on this issue in the current article. Our study has some limitations. First, the number of patients in this series is too small for a definite determination of the diagnostic value of MRI in the follow-up of patients with morphea. Larger studies will have to provide further evidence to support our observations. Second, because this is one of the first MRI-based studies of patients with morphea, we cannot determine the clinical significance of the existence and clearance of the musculoskeletal manifestations we detected. Long-term follow-up will be needed to gather more information about this topic. In conclusion, MRI is a promising tool for the assessment of musculoskeletal involvement in patients with deep morphea. 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