10.5826/dpc.1401a23
Introduction: Morphea localized scleroderma (LS) is a rare skin disease with unknown pathogenesis, which causes sclerosis of the dermis and subcutaneous tissue.
Objectives: It was aimed to compare the characteristics of patients with pediatric and adult-onset morphea.
Methods: A retrospective analysis was performed on the records of 183 adult morphea patients. The demographics, clinical and laboratory characteristics, and treatment options of the patients were recorded. Adult patients with morphea over the age of 18 were divided into two groups according to the age of onset and compared.
Results: Twenty-two percent (N = 41) of the patients had pediatric-onset morphea (POLS) and 77.6% (n=142) had adult-onset morphea (AOLS). While POLS had a higher head-neck involvement, AOLS had a higher breast involvement (P &lt; 0.001 and P = 0.043). Patients with linear morphea were younger, and more frequently had at least one laboratory anomaly (P = 0.016 versus 0.024). Anti-dsDNA positivity and low hemoglobin (Hb) were observed more frequently in patients with breast involvement. Patients with inguinal involvement, on the other hand, had lower Hb and a higher rate of diabetes, and those patients were older (P = 0.042, 0.040, and 0.012, respectively).
Conclusions: Clinical characteristics and accompanying laboratory anomalies of the patients with morphea depend on the age of onset, involvement areas and the types of morphea, having such data readily available should guide the holistic approach for, and the monitoring process of, the disease.
text/xml
2160-9381
3506
en
Yıldız Hayran
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
morphea
A Comparison of Clinical, Demographic and Treatment Characteristics of Pediatric-Onset and Adult-Onset Patients Diagnosed With Localized Scleroderma
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2024-01-31
2023-05-05
2024-01-31
2024-02-21
e2024023
Dermatol Pract Concept
Introduction: Morphea localized scleroderma (LS) is a rare skin disease with unknown pathogenesis, which causes sclerosis of the dermis and subcutaneous tissue.
Objectives: It was aimed to compare the characteristics of patients with pediatric and adult-onset morphea.
Methods: A retrospective analysis was performed on the records of 183 adult morphea patients. The demographics, clinical and laboratory characteristics, and treatment options of the patients were recorded. Adult patients with morphea over the age of 18 were divided into two groups according to the age of onset and compared.
Results: Twenty-two percent (N = 41) of the patients had pediatric-onset morphea (POLS) and 77.6% (n=142) had adult-onset morphea (AOLS). While POLS had a higher head-neck involvement, AOLS had a higher breast involvement (P &lt; 0.001 and P = 0.043). Patients with linear morphea were younger, and more frequently had at least one laboratory anomaly (P = 0.016 versus 0.024). Anti-dsDNA positivity and low hemoglobin (Hb) were observed more frequently in patients with breast involvement. Patients with inguinal involvement, on the other hand, had lower Hb and a higher rate of diabetes, and those patients were older (P = 0.042, 0.040, and 0.012, respectively).
Conclusions: Clinical characteristics and accompanying laboratory anomalies of the patients with morphea depend on the age of onset, involvement areas and the types of morphea, having such data readily available should guide the holistic approach for, and the monitoring process of, the disease.
Yıldız Hayran
2024/01/31
10.5826/dpc.1401a23
e2024023
Ankara City Hospital, Dermatology, Ankara, Turkey
2160-9381
morphea
en
e2024023
center in Korea. Int J Rheum Dis. 2013;16(4):437-41. PMID: 23992265;DOI:10.1111/1756-185X.12080.
A Comparison of Clinical, Demographic and Treatment Characteristics of Pediatric-Onset and Adult-Onset Patients Diagnosed With Localized Scleroderma
https://dpcj.org/index.php/dpc/article/download/3506/2446
     A Comparison of Clinical, Demographic
 and Treatment Characteristics of Pediatric-Onset
and Adult-Onset Patients Diagnosed With Localized
                  Scleroderma
                                     Ayşe Akbaş1, Fadime Kılınç1, Yıldız Hayran1


1 Ankara City Hospital, Dermatology, Ankara, Turkey



Key words: adult, child, epidemiology, localized scleroderma, morphea
Citation: Akbaş A, Kılınç F, Hayran Y. A Comparison of Clinical, Demographic and Treatment Characteristics of Pediatric-Onset
and Adult-Onset Patients Diagnosed with Localized Scleroderma. Dermatol Pract Concept. 2024;14(1):e2024023. DOI: https://doi.
org/10.5826/dpc.1401a23
Accepted: July 15, 2023; Published: January 2024
Copyright: ©2024 Akbaş et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use,
distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing Interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding Author: Fadime Kılınç, MD, Associate professor, Ankara City Hospital, Dermatology, Ankara, Turkey. Tel:+905056842806
E-mail:fykilinc@yahoo.com




  ABSTRACT             Introduction: Morphea localized scleroderma (LS) is a rare skin disease with unknown pathogenesis,
                       which causes sclerosis of the dermis and subcutaneous tissue.
                       Objectives: It was aimed to compare the characteristics of patients with pediatric and adult-onset
                       morphea.
                       Methods: A retrospective analysis was performed on the records of 183 adult morphea patients.
                       The demographics, clinical and laboratory characteristics, and treatment options of the patients were
                       recorded. Adult patients with morphea over the age of 18 were divided into two groups according to
                       the age of onset and compared.
                       Results: Twenty-two percent (N = 41) of the patients had pediatric-onset morphea (POLS) and 77.6%
                       (n=142) had adult-onset morphea (AOLS). While POLS had a higher head-neck involvement, AOLS
                       had a higher breast involvement (P < 0.001 and P = 0.043). Patients with linear morphea were younger,
                       and more frequently had at least one laboratory anomaly (P = 0.016 versus 0.024). Anti-dsDNA pos-
                       itivity and low hemoglobin (Hb) were observed more frequently in patients with breast involvement.
                       Patients with inguinal involvement, on the other hand, had lower Hb and a higher rate of diabetes, and
                       those patients were older (P = 0.042, 0.040, and 0.012, respectively).
                       Conclusions: Clinical characteristics and accompanying laboratory anomalies of the patients with
                       morphea depend on the age of onset, involvement areas and the types of morphea, having such data
                       readily available should guide the holistic approach for, and the monitoring process of, the disease.


Original Article | Dermatol Pract Concept. 2024;14(1):e2024023                                                                      1
Introduction                                                       of morphea after the age of 18 were considered as POLS.
                                                                   Demographics such as the age of onset of the disease, its
Morphea localized scleroderma (LS) is an uncommon in-              duration, patient gender, the clinical type, dermatological
flammatory skin disease which causes sclerosis on the der-         examination results such as the anatomical region involved,
mis and subcutaneous tissue. The pathogenesis of morphea           extracutaneous signs, accompanying systemic findings and
is unknown. Numerous factors can contribute to its etiol-          symptoms, triggering factors, laboratory findings, additional
ogy, including trauma, environmental factors like radiation,       comorbid disease, history of autoimmune disease, and the
drugs and chemicals, infections, vascular dysregulation, and       administered treatment option were recorded. The first ex-
autoimmunity [1-3]. These stimuli are thought to cause the         amination data was used in the analysis.
release of adhesion molecules and microvascular injuries.              Disease subtyping was done according to the Laxer
Vascular cell adhesion molecule-1, intercellular adhesion          classification [8]. Anatomical localization was classified as
molecule-1 and E-selectin can induce T-cells and cause the         involving the head, neck, extremities, body and/or multiple
release of transforming growth factor-beta (TGFβ) and pro-         areas of involvement. The presence of sclerosis (skin fibrosis)
fibrotic cytokines such as interleukin (IL) 4 and IL-6. As a       and pigmentation on the skin were examined.
result, excessive collagen production and decreased matrix
metalloproteinases contribute to the development of the            Statistical Analysis
disease [2]. It is more common in women. The incidence of          SPSS/IBM for Windows 21.0 was used to analyze the data.
morphea ranges from 0.4 to 2.7 per 100,000 people and it           The sample was defined using descriptive statistics such as
is similar in children and adults. [2-5]. In children with mor-    percentage, mean, median, standard deviation, and inter-
phea it is mostly seen between ages of 2 and 14 and in adults      quartile range (IQR). The chi-square significance test or
with morphea it is mostly seen in middle ages [6]. It can          Fisher Exact test was used to examine categorical data, and
lead to functional and cosmetic issues. In the inflammatory        the Student t test or Mann-Whitney U test was used to exam-
phase, erythematous purple-colored patches and plaques are         ine numerical variables. A 95% significance level (or α=0.05
observed, which gradually transform into white, sclerotic le-      error margin) was used to identify differences in the analyses.
sions that are surrounded by violet halos. As lesions heal,
post-inflammatory hyperpigmentation occurs [1,7].
    Laxer et al. classified morphea into the following five
                                                                   Results
types: plaque, generalized, linear, pansclerotic, and mixed [8].   One hundred eighty-three adult patients were included in the
    There are few studies compare pediatric-onset morphea          study. The female/male ratio was 5.1:1.
(POLS) and adult-onset morphea (AOLS) with variable re-                The demographic data of the patients are shown in
sults [9,10].                                                      Table 1. The most common type of morphea was the plaque
                                                                   type (Figures 1-3). Morphea types were similar in POLS
Objectives                                                         and AOLS. Body and extremities were the most frequently
                                                                   affected body sites. Head and neck involvement was more
The aim of this study was to investigate the clinical and de-      frequent in patients with POLS whereas, breast involvement
mographic characteristics of both POLS and AOLS patients           was more frequent in AOLS patients. Although arthralgia
who were followed up with the diagnosis of morphea in our          was more frequent among AOLS patients. Laboratory find-
clinic, evaluate the results, examine the clinical pattern and     ings, systemic diseases and laboratory findings were similar
laboratory findings, and compare the treatment options with        among AOLS and POLS patients. Although, anti-dsDNA
each other in the light of the literature data.                    positivity and systemic steroid treatment frequencies were
                                                                   higher in AOLS patients the results did not reach statistically
Methods                                                            significant levels.

Retrospective data analysis was performed on the records           The Evaluation of Demographical, Clinical,
of patients who were clinically and histopathologically diag-      Laboratory Findings, and Treatment Based on the
nosed with morphea between 2016 and 2022. The inclusion            Type of Morphea
criterion for the study was that the patients be at least 18       Sclerosis (tissue fibrosis) was significantly more common in
years old at the time of diagnosis. Children under the age of      patients with generalized morphea (30.6%, P = 0.001). In
18 were excluded in the study. Morphea patients who were           generalized morphea, topical treatments were significantly
18 years of age or older were divided into two categories:         less common, whereas methotrexate (MTX) and systemic
AOLS and POLS. Those with onset of morphea before the              steroid treatments were used significantly more (P values
age of 18 were considered as AOLS, and those with onset            <0.001, <0.001, and 0.028, respectively). Patients with



2                                                                      Original Article | Dermatol Pract Concept. 2024;14(1):e2024023
     Table 1. General clinical, demographic characteristics of all patients and comparison of pediatric
                                    and adult-onset morphea patients.
                                                                 Total patient Adult-onset Pediatric-onset
                                                                   N =183       N = 142        N = 41
    Characteristics                                                (100%)       (77.6%)       (22.4%)                   P
    Gender
      Female                                                      153 (83.6)     120 (84.5)        33 (80.5)           0.54
      Male                                                         30 (16.4)      22 (15.5)        8 (19.5)
    Age -*years (18-82)a                                         41.1 (16.9)    45.5 (34-59)      21 (15.5-28)       <0.001
                         b
    Age of onset years                                           36 (19.5-55)   43 (29.5-57)      13.5 (12-17)       <0.001
    Duration of the disease yearsb                                 2 (1-6)         1 (1-2)        8 (5.3-12.8)       <0.001
    Morphea type
     Plaque                                                       124 (67.8)       98 (69)         26 (63.4)           0.25
     Linear                                                        20 (10.9)       12 (8.5)         8 (19.5)
     Generalized                                                    33 (18)        27 (19)          6 (18.2)
     Mixed                                                          6 (3.3)         5 (3.5)          1 (2.4)
    Involved sites
      Head/neck                                                    19 (10.4)        7 (4.9)        12 (29.3)         <0.001
      Body                                                        115 (62.8)      94 (66.2)        21 (51.2)          0.080
      Extremity                                                   101 (55.2)      79 (55.6)        22 (53.7)           0.82
      Inguinal areas                                               23 (12.6)      20 (14.1)         3 (7.3)           0.25
      Breast                                                        13 (7.1)       13 (9.2)            0              0.043
    Triggering factors (exp;vaccination, laser application,
    surgery, trauma, autoimmunity and psychological stress)
      Yes                                                          12 (6.6)        9 (6.3)          3 (7.3)            0.82
      No                                                          171 (93.4)     133 (93.7)        38 (92.7)
    Sclerosis presence
      Yes                                                          62 (33.9)      49 (34.5)        13 (31.7)           0.74
      No                                                          121 (66.1)      93 (65.5)        28 (68.3)
    Pigmentation presence
      Yes                                                          55 (30.1)      29 (30.3)        12 (29.3)           0.90
      No                                                          128 (69.9)      99 (69.7)        29 (70.7)
    Arthralgia presence
      Yes                                                          19 (10.4)      18 (12.7)         1 (2.4)           0.058
      No                                                          164 (89.6)     124 (87.3)        40 (97.6)

a
main (standard deviation, sd), bmedian (interquartile range).



generalized morphea had significantly higher platelet levels      additional skin diseases were more prevalent (P = 0.049).
(P = 0.010), neutrophil/lymphocyte ratios (NLR) (P = 0.029)       Patients with plaque-type morphea received significantly
and age of onset (P = 0.042).                                     less MTX therapy and significantly more topical treatments
      Patients with linear morphea had a significantly lower      (P values 0.004 and <0.001, respectively).
mean age and age of onset (P = 0.025 and P = 0.005). Pa-
tients with linear morphea had a significantly longer dura-       The Evaluation of Demographic, Clinical,
tion of disease (P = 0.016). At least one laboratory finding      and Laboratory Findings Based on Involved Sites
was abnormal in 21% of the patients with linear morphea           Pediatric onset was more frequent in patients with head
(P = 0.024). In non-linear morphea, this rate was 8.1%.           and neck involvement (Figures 3 and 4). The mean age
      Eighty percent of patients with plaque-type morphea         and age of onset of the disease in patients with head and
were female while 91.5% of the patients with non-plaque           neck involvement were significantly lower (P = 0.003 and
morphea were female. Number of males was significantly            P < 0.001).
higher in plaque-type morphea (P = 0.046). Sclerosis was              Patients with body involvement used MTX and systemic
found in 28.2% of patients with plaque-type morphea and in        steroids at a higher rate (P = 0.024). Their mean age and dis-
45.8% of patients with non-plaque morphea. In plaque-type         ease age of onset were significantly higher (both P = 0.005)
morphea, sclerosis was less prevalent (P = 0.019), and            and platelet levels were significantly higher (P = 0.017).



Original Article | Dermatol Pract Concept. 2024;14(1):e2024023                                                                 3
Figure 1. ​​​​​​​Plaque type morphea.




                                                              ​​​​​​​Figure 3. Plaque type morphea on the face.




                                                              ​​​​​​​Figure 4. Atrophic morphea.


                                                              breast involvement. Patients with breast involvement had a
                                                              significantly lower Hb (P = 0.017).
                                                                  All of the patients with inguinal involvement were fe-
                                                              male. The patients were significantly older (P = 0.012), and
                                                              their Hb levels were lower than the patients without inguinal
​​​​​​​Figure 2. En coup de sabre.                            involvement (P = 0.042). Sclerosis was more common in pa-
                                                              tients with inguinal involvement (P = 0.014). The incidence
    All patients with breast involvement were adult-onset.    of diabetes in patients with inguinal involvement was higher
Anti-dsDNA positivity was seen in 37.5% of the patients       (P = 0.040)
with breast involvement and in 9.2% of the patients without       Table 1 shows the clinical characteristics of the patients
breast involvement. Anti-dsDNA positivity was significantly   including triggering agents and presence of arthralgia. Table 2
higher in the patients with breast involvement (P = 0.014).   illustrates the laboratory findings and the Table 3 shows the
Hemoglobin (Hb) levels were 12.4 (SD 1.4) in patients with    accompanying comorbidities. The treatments given to pedi-
breast involvement and 13.6 (SD 1.4) in patients without      atric morphea and adult morphea were shown Table 4.



4                                                                  Original Article | Dermatol Pract Concept. 2024;14(1):e2024023
  Table 2. Laboratory findings of all patients with morphea and comparison of pediatric and adult-
                                       onset morphea patients.
                                         Total patient             Adult-onset                 Pediatric-onset
 Characteristic                             N (%)                    N (%)                         N (%)                 P
 Borelia
   Positive                                   5 (6)                   3 (4.8)                      2 (9.5)             0.42
   Negative                                  79 (94)                 60 (95.2)                    19 (90.5)
 ANA
  Positive                                 51 (38.6)                 41 (38.3)                     10 (40)             0.88
  Negative                                 81 (61.4)                 66 (61.7)                     15 (60)
 Anti-dsDNA
   Positive                                 13 (11.1)                13 (13.7)                      0 (0)             0.066
   Negative                                104 (88.9)                82 (86.3)                    22 (100)
 Hba                                       13.5 (1.4)                13.5 (1.4)                   13.5 (1.7)           0.71
 Leukocytea                                 6.7 (1.8)                6.8 (1.8)                    6.1 (1.4)            0.14
            a
 Platelet                                 276.7 (67.8)             275.1 (66.6)                 288.9 (77.6)           0.78
       b
 NLR                                      1.9 (1.5-2.6)            1.9 (1.5-2.6)                1.9 (1.3-2.2)          0.33
                b
 Eosinophil                            0.14 (0.08-0.25)           0.14 (0.09-0.25)             0.15 (0.07-0.29)        0.95
 Eosinophil (%)b                          2.1 (1.2-3.4)            2.1 (1.2-3.4)                 2.6 (1-3.2)           0.77
                    b
 Sedimentation                             10 (6-19)                 10 (6-19)                    9 (5.3-17)           0.52
       b
 CRP                                    0.06 (0.01-7.5)           0.07 (0.01-10)               0.03 (0.005-2)          0.17
 Vit D deficiency                        38 (20.76%)                30 (21.12)                    14 (19.5)            0.19
 Iron deficiency                         47 (25.68%)                33 (23.23)                    14 (34.1)            0.11
 Vit B12 deficiency                        18 (9.8%)                 12 (8.45)                     6 (14.6)            0.46

NLR = neutrophil lymphocyte ratio.
a
 main (standard deviation, sd), bmedian (interquartile range).



Conclusions                                                        of the patients, especially in the group with linear morphea.
                                                                   Since the platelet and ESR levels are significantly lower in
In our study, the characteristics of pediatric and adult-onset     this type compared to the generalized type, there may be a
morphea patients were compared, and some of them showed            lower risk of systemic involvement and a lower tendency
similarities with the literature, while some findings showed       to thrombosis. The fact that the extremity involvement is
differences [8-19].                                                around 50% in both types of onset suggests that the disease
    According to the previous studies, disease onset was be-       has a progressive course.
tween the ages of 2 and 14 for children and 43.3 to 44.8 for           In various studies, the incidence of plaque type in chil-
adults [8,11,13,15,17,18,20]. We found that the average age        dren ranges from 15.3% to 69.2% [6,14-17]. In the present
at which the disease manifested itself was 36-43 for AOLS,         study, the plaque type was found to be high in both groups.
and 13.5 for POLS.                                                 This rate was similar to the rates in our previous research
    The incidence of linear morphea in children range from         with children cases [17]. A significant data here was that
15.3% to 81% [2,4,5,11,17,18,21]. In this study, linear mor-       the plaque type was higher in men, but sclerosis was less
phea was found to be 19.5% for POLS and 8.5% for AOLS              common than other types. Morphea appears to have a
Supporting the fact that the linear type starts more frequently    milder course in men. This finding also supports the view
in the childhood [6,11,14]. Those patients with the pediat-        that autoimmune diseases are more frequent and more se-
ric onset naturally had a longer duration of illness. Some         vere in women.
researchers state that the disease is more active (20%-59%)            Mixed type, in which more than one type of morphea
in patients with POLS [2,5,11]. The linear type was also re-       coexists, was found at a rate of 7.6%-23% in various studies
ported to be more sclerotic than in adult-onset patients, and      in children [2,13,15-17]. Saracino et al reported mixed type
in the present study, we found that there was more sclerosis       morphea in 27.1% of the adults with morphea, in 28% of
in both linear and generalized types. Sarocino et al found         POLS and 25.9% of AOLS [18]. In our study, we found that
laboratory anomalies as 40.4% in linear type [18]. In this         mixed type morphea was 3.3% lower in total, 3.5% lower in
study, at least one laboratory anomaly was present in 21%          AOLS and 2.4% lower in POLS.



Original Article | Dermatol Pract Concept. 2024;14(1):e2024023                                                                5
Table 3. Comparison of presence of additional disease of adolescent- and adult-onset morphea patients.
                                                 Adult-onset                   Pediatric onset                     Total
 Comorbid diseases                             N = 142 patients                N = 41 patients                    N = 183
 Skin diseases N (%)                                                                                              13 (7.1)
 Vitiligo                                          3 (2.11)                             -                         3 (1.63)
 Psoriasis                                         3 (2.11)                             -                         3 (1.63)
 A.Areata                                           2 (1.4)                             -                         2 (1.09)
 LSA                                               3 (2.11)                             -                         3 (1.63)
 BCC                                                1 (0.7)                             -                          1 (0.5)
 Verruka vulgaris                                   1 (0.7)                             -                          1 (0.5)
 Rheumatological diseases, N (%)                                                                                  7 (3.18)
 Ankylosing spondylitis                             1 (0.7)                             -                         2 (1.09)
 Rheumatoid arthritis                              3 (2.11)                             -                         2 (1.09)
 Scleroderma                                        1 (0.7)                             -                         1 (0.5)
 Sacroileitis                                       1 (0.7)                             -                         1 (0.5)
 Spondyloarthropathy                                1 (0.7)                             -                          1 (0)
 Thyroid disease N (%)                            15 (10.56)                         1 (2.4)                    16 (8.74)
 Diabetes mellitus N (%)                           11 (7.74)                        3 (7.31)                    14 (7.65)
 Hypertension, N (%)                              15 (10.56)                         2 (4.9)                      17 (7.1)
 Asthma N (%)                                      3 (2.11)                          2 (4.9)                      5 (1.73)
 Fibromyalgia, N (%)                                2 (1.4)                             -                         2 (1.09)
 Ulcerative colitis, N (%)                          1 (0.7)                             -                          1 (0.5)
 Autoimmune hepatitis, N (%)                        1 (07)                              -                          1 (0.5)
 Familial Mediterranean Fever, N (%)                2 (1.4)                             -                         2 (1.09)
 Ferritin deficiency anemia N (%)                 33 (23.23)                        14 (34.1)                  47 (25.68)
 Vitamin B12 deficiency anemia N (%)               12 (8.45)                        6 (14.6)                      18 (9.8)
 Vitamin D deficiency N (%)                       30 (21.12)                        8 (19.5)                   38 (20.76)
 Depression N (%)                                   2 (1.4)                          1 (2.4)                      3 (1.63)
 Other diseases migraine, vertigo, renal           3 (1.4%)                             -                         3 (1.5%)
 failure N (%)
 Total N (%) 101 (55.19%)                       137 (96.47%)                     36 (87.80%)                   173 (95%)



           Table 4. Comparison of treatments given to pediatric morphea and adult morphea.
 Treatments used                               Total patients         Adult-onset               Pediatric-onset              P
 Topical treatments, N (%)                        120(65.6)             89 (62.7)                  31 (75.6)             0.13
 Methotrexate, N (%)                              50(27.3)              39 (27.5)                  11 (26.8)             0.94
 Colchicine, N (%)                                31(16.9)              21 (14.8)                  10 (24.4)             0.15
 Systemic steroid, N (%)                           12(6.6)               12 (8.5)                     0                  0.054
 Phototherapy, N (%)                                9(4.9)                7 (4.9)                   2 (4.9)              0.99
 Hydroxychloroquine, N (%)                          7(3,8)                5 (3.5)                   2 (4.9)              0.69
 Others N (%)                                  10 (1.09-0.54)             7 (4.9)                   3 (7.3)
 Zinc, Salazopyrin, Vitamin D
 Mycophenolate mofetil,
 Azathioprine, Isotretinoin,
 Untreated N (%)                                 22 (15.38)                                        6 (4.22)              0.84


    Although the affected areas were similar in both groups        There are multiple localizations in generalized mor-
of patients, special region involvement such as the inguinal    phea. The previous studies found it as 7%-47% [2,4,6,17].
region was more common in AOLS. Breast involvement was          In our study, the rate of generalized morphea was 18% in
observed only in AOLS. This particular group of patients        total, 19% in AOLS, and 18.2% in POLS. High platelet
were older and female.                                          levels in this group of patients may indicate a proclivity for



6                                                                   Original Article | Dermatol Pract Concept. 2024;14(1):e2024023
thrombosis. More research should be conducted on this sub-        morphea [13]. These authors found that patients with lin-
ject. The ratios of neutrophils / lymphocytes (NLR), which        ear morphea had a high number of ocular and neurological
are indicators of acute inflammation in this type, were also      findings [25,27]. However, unlike other studies conducted in
found to be significantly higher. This may indicate that there    Turkey, no neurological or ocular involvement was observed
is a tendency of inflammation in generalized morphea, and         in the cases with ECDS in our study [8]. This could also be
that it may be even more progressive. Therefore, these mark-      due to the fact that the study was retrospective and the re-
ers can be used for treatment follow-up and progression [22].     cords were missing.
    In various studies, factors that can trigger the forma-          Various laboratory changes in the serum of morphea pa-
tion of the disease in morphea were identified as 7.3-16.6%       tients have also been observed in studies [15,28-31]. Rheu-
[3,18,23]. Saracino et al determined the presence of trig-        matoid factor (RF), C-reactive protein (CRP), and ESR is
gering factors as 16.5% in all morphea patients, 20.9% in         higher in patients with extracutaneous involvement [13].
AOLS and 14.7% in POLS [18]. We found these rates as              The authors reported high inflammatory parameters (ESR,
6.6% in general, 6.3% in AOLS and 7.3% in POLS. These             CRP, RF) rather than skin manifestations, especially in pa-
were consistent with the literature.                              tients with deep morphea and arthritis [13,14,32]. The RF
    Some studies confirm the association of infectious agents     rate in the patients with joint damage is up to 25%-40%
such as Borrelia with morphea, while others do not [3,24].        [13,28,33]
Only 5 (6%) of the cases in the present study were detected          Morphea is frequently associated with auto-antibody
to have the Borrelia antibody.                                    positivity [28,31,33-35]. The clinical and prognostic signif-
    In morphea patients, extracutaneous abnormalities have        icance of these autoantibodies is unknown [13]. In the gen-
also been reported in addition to skin abnormalities [14,25].     eralized type, it may be especially important in clinical and
These findings range from 10.9% to 46 % [18,20,25]. There         prognostic terms or for investigating the presence of comor-
have been reports of extracutaneous involvement being more        bid diseases [31].
prevalent in generalized and mixed type [13,17]. We found ex-        In the literature, ANA positivity was detected in
tracutaneous involvement (arthralgia) in 10.4% of the cases.      5.9%-68.7% of the cases [6,15,17,25,31]. The rate of ANA
The low rate might be due to the fact that the cases could not    positivity has been reported to be higher in patients with
be questioned because of the retrospective nature of the study.   generalized and mixed types, as well as those with extracu-
    Some authors have reported more frequent (43%-45%)            taneous involvement [6,10,11,15,31,34]. According to some
deformities in children with linear morphea [15,16]. Saracino     studies, there is no difference in the ANA ratio among the
et al detected functional impairment in 24.8% of adult, 28%       various subtypes of morphea, but the presence of extracuta-
of pediatric-onset and 20.7% of adult-onset patients [18]. In     neous findings may increase these rates [28,34].
our study, although linear morphea was found in 10.9% of             Some studies have also reported that ANA positivity var-
the cases, no functional impairment was detected except for       ies between patients with AOLS and POLS [6,10,11,19,31].
cosmetic problems.                                                In our study, the ANA positivity rate was found 38.3% for
    Morphea is an immune disorder and can often be ac-            AOLS and 40 % for POLS, which was similar in both groups.
companied by various systemic, autoimmune, and rheu-                 In addition to ANA, Scl-70, anti-dsDNA, anti-histone
matological diseases. Diseases such as thyroid diseases and       antibody positivity can be seen in patients. Some research-
diabetes play a predisposing role. The presence of accompa-       ers found anti-dsDNA positivity in 4%-8% of morphea
nying autoimmune systemic disease differs between 1%-4.9          patients with AOLS and POLS [25]. These rates were par-
% [6,17,18,20,25]. In some studies, the association of auto-      ticularly higher in those with the linear type and with joint
immune diseases is up to 17 % [6,14,20,21]. Saracino et al        involvement [28,29]. In our study, the anti-dsDNA antibody
found autoimmune disease comorbidity as 11.3% in general,         was found positive only for AOLS (13.7%, N = 13), but not
15.5% for AOLS and 8.0% for POLS [18]. In our study,              for POLS.
the rate of comorbid diseases was similar to other studies           Sato et al found that anti-histone antibodies were related
[19,26]. Eleven patients had comorbid autoimmune skin             to the number of morphea lesions and the skin localization
disease. These diseases were only in the adult-onset group.       of the lesions, and suggested that they may be serological in-
Comorbid diseases increase with age [11]. Furthermore, in         dicators in cases with generalized morphea [29]. We detected
our cases, iron deficiency was found in 25.7% of the women.       anti-histone antibodies in only one patient. The presence of
Low Hb levels may be a sign of an additional comorbid dis-        autoantibodies may indicate that morphea is a connective
ease. In the present study, the rate of vit B12 deficiency ane-   tissue disease with systemic involvement rather than a skin
mia was 9.8%, and the rate of vit D deficiency was 20.8%.         disease [31,35].
    The most comprehensive multi-centred study so far was            Due to the incomplete understanding of the cause of mor-
conducted by Zulian et al with 750 patients with juvenile         phea, there is no specific effective treatment. The purpose of



Original Article | Dermatol Pract Concept. 2024;14(1):e2024023                                                                7
the treatment is to stop the disease from progressing at an       anomalies. That why patients with adult and pediatric on-
early stage in order to avoid functional and cosmetic com-        set morphea require different management and treatment
plications. Treatment options were assessed according to the      strategies. Additionally, clinicians should be aware of the
subtype of the disease, the extent of involvement, the level of   extracutaneous disease and anomalies that may accompany
activation and the presence of complications [27,36].             morphea and patients should be examined accordingly.
    While some studies report that topical treatment was ad-            The retrospective nature, inability to create a morphea
ministered at a rate of 45.9 %, in this study, topical agents     severity scale, and the lack of standardization in the treat-
were preferred as the first line in 65.6% (N = 120) of both       ment administered for different types of morphea are the
groups [18].                                                      limitations of our study. Multi-centered, more comprehen-
    In our study, patients with limited plaque-type lesions       sive and prospective studies are required to obtain more ac-
were treated with topical corticosteroids, calcipotriol, cal-     curate data.
cipotriol + steroid combination, tacrolimus and pimecroli-
mus. This rate was found to be 65.6% (N = 120) in general,
62% in AOLS, and 75.6% in POLS.
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Original Article | Dermatol Pract Concept. 2024;14(1):e2024023                                                                                    9
