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Objective of the Review: To demonstrate new approaches in management of generalized scleroderma (GSD), that gained relevance after publication of drug therapy recommendations in 2017. Key Points. GSD is a progressive immunoinflammatory rheumatic disease, that can cause severe damage of vitals; therefore, it is characterized with poor prognosis. Unfortunately, currently there are no approved drugs to modify the course of GSD. Biological disease-modifying agents are still rarely used in GSD, since none of them have approved indications. The recommendations of the European League Against Rheumatism on GSD drug therapy were last updated about 5 years ago. Scientists have been searching for efficient therapies and undertook clinical trials of various medicinal products. The review presents literature data evidencing expanded range of methods to correct immunoregulatory pathologies; discusses results of latest clinical trials, which can provide the basis for inclusion of such drugs into recommendations on GSD management. Conclusion. New randomised controlled trials and multicentre programs point to some progress in GSD curation and better prognosis. Keywords: generalized scleroderma, autologous haematopoietic stem cell transplantation, Rituximab, Tocilizumab, Abatacept, Nintedanib.

Dear Editor, Localized scleroderma (LSc; morphea) is a rare fibrosing disease of the skin and underlying tissues, which is different from systemic sclerosis (SSc). 1 LSc is classified based on clinical presentations: circumscribed, linear, generalized, pansclerotic, and mixed morphea. 1 Generalized morphea (GM) , which is characterized by widespread skin lesions with multiple indurated plaques or hyperpigmentation, is a relatively rare subtype occurring in 7-9% of patients with LSc. 1 Previous studies have shown that SSc can be complicated by GM, separately from GM-like SSc. Here, we present a rare case of coexistence of LSc and SSc in which LSc skin lesions appeared before SSc became apparent [...].

Nodular or keloidal morphea, also known as nodular scleroderma, is a rare form of localized sclerosis (SSc) or morphea. In this paper, we reported a case of this rare entity with a review of the literature.

Generalised morphea (GM) is a subtype of localised scleroderma that usually manifests with bilateral involvement. Unilateral generalised morphea (UGM) is a rare variant of GM. This is a case report of a Taiwanese girl with UGM over the left side of her body. She presented with hyperpigmentation, tightness, and skin atrophy over the left extremities and trunk. Mild range of motion (ROM) limitation over the left knee was also noted. At the clinic, the patient was given oral prednisolone, oral methotrexate (MTX), and oral D-penicillamine. topical emollient and topical glucocorticoids were also given. The dose of oral prednisolone was tapered gradually. All symptoms were improved under the treatment and regular rehabilitation program. To date, there is very little evidence to form the basis for treatment recommendations. This case report provides a treatment option for UGM in the paediatric group without the use of intravenous methylprednisolone pulse therapy.

We report the case of a 45-year-old female with generalized morphea (GM), who exhibited positivity for the anti-centromere antibody (Ab). She frequently developed multiple sclerotic skin lesions, whose histological findings were compatible with morphea. She demonstrated favorable responses to topical and oral steroids. Cases of GM associated with systemic sclerosis (SSc)-specific Abs (anti-Scl-70 Ab, anti-centromere Ab, and anti-RNA polymerase III Ab) have rarely been reported. The previously reported GM cases involving anti-SSc-specific Abs exhibited some skin manifestations of SSc, such as nailfold capillary changes. However, our case did not show any signs of SSc or limited cutaneous SSc. More cases are needed to clarify whether GM with SSc-specific Abs leads to SSc.

The patient in this report was diagnosed simultaneously with primary biliary cirrhosis (PBC), spondyloarthritis, and generalized morphea and was started on infliximab therapy. In addition to an improvement in clinical symptoms with this therapy, an improvement was also observed in laboratory parameters such as cholestatic enzymes, C-reactive protein, and erythrocyte sedimentation rate. Infliximab was well tolerated in this 56-year-old patient. However, further studies must be performed in order to clarify the therapeutic role of TNF-α blockers in, PBC and generalized morphea.

Objective: To study the clinical characteristics and prognosis of morphea in Thai adult patients. Methods: The medical records of 81 morphea adult patients who visited Siriraj Hospital, Thailand, between 2006 and 2015, were retrospectively reviewed. The demographics, clinical features, treatments and outcomes were analyzed. Clinical improvement was categorized as excellent (>80%), partial (1%–80%), and no response. Results: Circumscribed morphea was the most common subtype (34, 42%) of the 81 patients, followed by linear morphea (21, 26%), generalized morphea (14, 17%), en coup de sabre (11, 14%) and Parry–Romberg syndrome (1, 1%). Systemic treatment and ultraviolet A (UVA)1 phototherapy had satisfactory outcomes in 83% and 79% of cases, respectively, providing a partial to excellent response. For overall remission, one year after the treatment, 30% of patients achieved a partial to excellent response. After 2 years, this proportion rose to 50%. The median time to clinical response was 24 months. Conclusion: Morphea is a difficult-to-treat dermatosis, with the majority of the patients having a partial clinical response and a high recurrent rate. Combination of treatment might be a worthy option.

A 56-year-old Korean female patient developed generalized morphea over three months. We focused on imbalance of the neuroendocrine-immune axis, mainly using Jiawei-Renshengyangrong-tang and Jiawei-Siqi-tang. Moxibustion on LU9 was conducted for skin symptoms. The patient’s modified localized scleroderma skin severity index score decreased from 22 to 6 over 22 weeks of treatment and to 4 during a 3-month follow-up. Her verbal rating scale score for general symptoms decreased from 17 to 1 during the 22-week treatment.

Morphea is a rare fibrosing disorder affecting the skin and underlying tissue. Also called localized scleroderma, morphea is characterized by lesions, which are initially erythematous or dusky violaceous patches eventually turning into hypopigmented sclerotic plaques with a typical lilac-coloured border. Generalized morphea is a rare subtype of morphea characterized by more than four lesions occurring in two or more body sites. Although it has not been fully elucidated yet, it is increasingly perceived that autoimmunity plays the central role in the pathogenesis of both morphea and vitiligo.

Eftychia Platsidaki,Vassiliki Tzanetakou,Anargyros Kouris,Panagiotis G Stavropoulos Department of Dermatology and Venereology, Andreas Syggros Hospital, University of Athens, Athens, Greece Introduction: Morphea is an inflammatory skin disorder characterized by excessive collagen deposition. Although treatment algorithms for morphea subtypes have been suggested, no consistent recommendations are available. This study attempts to evaluate the clinical efficacy of methotrexate (MTX) as monotherapy in refractory generalized morphea. Methods: It is a retrospective study, including 20 patients who had already been treated with various topical and systemic therapies with minimal clinical improvement. Patients received orally MTX at a of dosage 15 mg once weekly. Duration of the use, dosage of MTX, and adverse events were recorded. Clinical assessment of skin lesions was performed and documented. Results: The mean disease duration was 27 months before the initiation of MTX treatment. After 12 months of therapy, very good response was achieved in 6 patients (30%), good response in 10 patients (50%), and fair response in 2 patients (10%), while 2 patients (10%) had failed treatment. Patients were followed up for a mean time interval of 21 months. No serious adverse event was recorded. Conclusion: MTX has been already proved to be an effective and well-tolerated treatment in pediatric patients with morphea. The majority of the group of adult patients showed very good and good improvement when treated with MTX. Although this is an uncontrolled study, MTX monotherapy was considered a safe and effective treatment for the management of this specific clinical subset of morphea in adults. Keywords: methotrexate, adults, generalized morphea

Objective.Pansclerotic morphea is a poorly described form of morphea with little information on prevalence, demographics, and clinical features. Classification criteria for this subtype varies and the distinction from other forms of morphea, such as extensive generalized morphea and pansclerotic morphea, is not always clear. The purpose of our study was to clarify classification criteria for pansclerotic morphea by identifying its prevalence in the morphea in adults and children (MAC) cohort and describing its demographic and clinical features as compared with generalized morphea.Methods.Patients who met predefined criteria for generalized and pansclerotic morphea were identified using a modified Laxer and Zulian classification system. Baseline demographic and clinical features of the patients were compiled and then analyzed for traits characteristic of pansclerotic morphea versus those of generalized morphea. One hundred and thirteen patients met the criteria for inclusion: pansclerotic (n = 13) and generalized morphea type (n = 100).Results.Patients with pansclerotic morphea were more frequently male (46.2% vs 6%; p < 0.0001); had a shorter time to diagnosis (mean difference of 10.4 mos; 95% CI: 0.8–19.9 mos; p = 0.0332); higher rates of functional impairment (61.5% vs 16%; p = 0.0046); higher rates of deep involvement (61.5% vs 17%; p = 0.004); and higher average Rodnan Skin Score (mean difference of 10.8 points; 95% CI: 5–16.6; p = 0.0017), Localized Scleroderma Skin Damage Index (mean difference 28.3; 95% CI: 9–47.6; p = 0.009), and Physician Global Assessment of Disease Damage scores (mean difference 25.1; 95% CI: 0.3–50; p = 0.048).Conclusion.Our results suggest demographic and clinical features are sufficient to define the pansclerotic subtype as they represent a distinct clinical phenotype with a more rapidly progressive and severe course commonly accompanied by disability. Presence of features of the pansclerotic phenotype should alert practitioners to the possibility of significant morbidity and the need for early aggressive treatment.

Morphea or localized scleroderma is a distinctive inflammatory disease that leads to sclerosis of the skin and subcutaneous tissues. It comprises a number of subtypes differentiated according to their clinical presentation and the structure of the skin and underlying tissues involved in the fibrotic process. However, classification is difficult because the boundaries between the different types of morphea are blurred and different entities frequently overlap. The main subtypes are plaque morphea, linear scleroderma, generalized morphea, and pansclerotic morphea. With certain exceptions, the disorder does not have serious systemic repercussions, but it can cause considerable morbidity. In the case of lesions affecting the head, neurological and ocular complications may occur. There is no really effective and universal treatment so it is important to make a correct assessment of the extent and severity of the disease before deciding on a treatment approach.

Generalized morphea is a rare idiopathic form of scleroderma that literally means “hard skin.” Morphea is usually considered an isolated event that is not associated with malignancy. However, case reports of lung, hematologic, and breast cancer occurring simultaneously with large plaque morphea have caused dermatologists to question whether a work-up for malignancy is appropriate. We highlight a case of generalized morphea that preceded invasive ductal carcinoma of the breast and provide a discussion about the possible paraneoplastic origin of generalized morphea and systemic sclerosis (SSc).

35歳, 女性。2002年, Raynaud症状と手指から前胸部まで連続する皮膚硬化が出現した。近医で抗セントロメア抗体陽性のdiffuse cutaneous systemic sclerosis(SSc)と診断され, ステロイド, D-ペニシラミン, サラゾスルファピリジン, シクロスポリン内服や内服PUVA等の治療を受けるも軽快せず, 2005年8月当科紹介となった。全身に著明な皮膚硬化を認め, 逆流性食道炎を合併していた。プレドニゾロン(prednisolone ; PSL) 30mg/日内服開始し, 次第に皮膚硬化は改善した。PSL 7mg/日まで減量していたが, 2007年9月全身そう痒が出現し, 12月には手背, 背部, 下肢に紅色斑状硬化性局面を認めるようになった。病理組織所見も含め, generalized morphea様皮疹を伴ったSScと診断した。PSL 20mg/日内服に反応せず, タクロリムス軟膏外用, シクロスポリン内服併用で皮膚硬化・そう痒ともに軽快した。SScにはmorphea様皮疹を伴うことがあり, 限局性強皮症に準じた治療が行われる。自験例からステロイド抵抗性の限局性強皮症, 特にSScに合併したものに対して, タクロリムス軟膏外用やシクロスポリン内服併用は効果が期待できる治療法の一つと考えた。

We present further evidence that generalized morphea (GM) and primary biliary cirrhosis (PBC) may be associated. As far as we know, only six cases with this association have been previously reported in the published work, all of which were observed in women. We describe the case of a 62-year-old man diagnosed with M2-antibody-positive PBC who developed multiple generalized indurated plaques on the trunk and extremities 3 years later. Clinical history, laboratory data and histopathological examination were consistent with the diagnosis of GM. The coexistence in a male of these two entities that predominantly affect females reinforces the hypothesis that a pathogenic link exists between GM and PBC. Consequently, PBC should be looked for in all patients with GM.

A 27-year-old Japanese woman presented with erythema on the trunk and extremities and a 10-day history of low-grade fever (approximately 37.5 °C) in February 2014. At the age of seven, the patient had been diagnosed with morphea based on the histopathological findings of a skin biopsy taken from an erythematous lesion of the right leg. The erythema gradually spread from the limbs to the trunk and whitish atrophic plaques also appeared. 15 years previously, she had been diagnosed with an autoimmune [...]

Localized scleroderma is a connective tissue disorder generally involving de entire dermis and usually limited to the subcutaneous tissue; however, it may progress to large indurated plaques, growth retardation, muscle atrophy, and even to flexion deformities or poorly healing ulcers. Unilateral generalized morphea is an extremely rare variant of localized scleroderma which has seldom been reported in the literature. We report the case of a girl who developed unilateral generalized morphea on the right side of the body.

A 33-year-old male with typical carpal tunnel syndrome also showed sclerotic skin, sausage-like fingers, and finger/wrist contracture. He had a two-year history of using organic solvents (acetone and ethanol) in IC manufacturing. Skin biopsy showed thick bundles of collagen, replacement of surrounding fatty tissue by collagen, and slight mononuclear cell infiltration. The final diagnosis was therefore generalized morphealike scleroderma. The administration of corticosteroids (30mg/day) resulted in the subsidence of symptoms. Related literature was referenced.

Generalized morphea is a subtype of localized scleroderma, which lacks systemic manifestations and displays widespread, multiple, well-circumscribed, indurated plaques. We represent a 46-year-old woman with generalized morphea. More than 3 years ago she developed multiple, nonpruritic plaques symmetrically on the trunk and extremities. The patient’s clinical history, laboratory analysis and histopathologic examination were consistent with generalized morphea, a rare subtype of localized scleroderma.

Localized scleroderma is a chronic sclerodermic disease that involves the skin and subcutaneous tissues without internal organ manifestations. Generalized morphea (GM) is a form of localized scleroderma, which is characterized by widespread skin involvement with multiple sclerotic plaques and hyperpigmentation [1]. Patients with GM classically present with localized sclerotic skin lesions without any associated symptoms including pain.Primary biliary cirrhosis (PBC) is a chronic cholestatic liver [...]

PUVA therapy was carried out on four patients with scleroderma; three of them had cutaneous manifestations of progressive systemic sclerosis and one other exhibited generalized morphea. PUVA therapy was given with daily doses of 0.25 J/cm2 or 0.4 J/cm2 for 3–8 weeks, resulting in total doses between 3.5 J/cm2 and 9.6 J/cm2. All four patients responded well to this treatment; improvements of hand closure, skin sclerosis index, and flexion of fingers or knee joints were obtained. Thus, PUVA appeared to be beneficial for treating scleroderma.

Background: The skin score, a subjective assessment of skin elasticity, is widely used in patients with systemic sclerosis. Although this scoring method is regarded as a validated and accepted tool, the interobserver and intraobserver reproducibility is relatively poor. Objective: Our purpose was to investigate whether the recently developed SEM 474 cutometer, which exerts a controlled vacuum force to the skin, can measure skin elasticity more objectively than the skin score. Methods: Skin elasticity was measured in 74 different body areas in patients with systemic sclerosis and compared with the skin score obtained from the same areas. Results: The cutometer produced quantitative and reproducible data. A large-diameter (8 mm) measuring probe was superior to a small probe. The interobserver intraclass correlation coefficient (ICC) was 0.92; the intraobserver ICC was 0.94. A linear correlation was found with the clinical skin score; the Spearman rank correlation test was 0.69. Conclusion: The correlation with the skin score was reasonable, despite the observation that regional differences in skin elasticity were detected by the cutometer but not by the human observer, who automatically compensates for these factors and integrates them into the skin score. The high interobserver and intraobserver ICC makes the cutometer more suitable for quantifying changes in skin thickness than the subjective skin score.

Background: Recently we demonstrated the presence of antihistone antibodies (AHA) in localized scleroderma. Objective: Our purpose was to determine clinical characteristics associated with AHA in patients with localized scleroderma. Methods: We examined 57 serum samples by an enzyme-linked immunosorbent assay in the following three subgroups: 15 patients with generalized morphea, 27 with linear scleroderma, and 15 with morphea, We classified the patients as having generalized morphea when they had four or more lesions on at least two areas of the body, irrespective of whether the lesions were of morphea or linear type. Results: AHA were detected in 42% of patients with localized scleroderma (24 of 57), and in 87% of patients with generalized morphea (13 of 15). The presence of AHA strongly correlated with the number of morphea lesions, the total number of lesions, and the number of involved areas of the body. However, AHA did not correlate with the presence or number of linear lesions. The presence of AHA showed a 87% sensitivity (13 of 15 patients) and a 74% specificity (31 of 42 patients) for generalized morphea. Conclusion: Our data suggest that AHA are a serologic marker for generalized morphea and that the validity of our new classification for generalized morphea is supported by the high frequency of AHA detection.

Morphea, also called localized scleroderma, is a fibrosing disorder that resembles scleroderma (systemic sclerosis) microscopically, but typically has a quite different clinical presentation, course and possible pathophysiology. The individual with morphea has single or multiple circumscribed indurated cutaneous plaques that can have variable appearances, depending on the subtype (see classification below and Table 12.1). The main variants are circumscribed or plaque-type morphea (Fig. 12.1a), generalized morphea (Fig. 12.1b), linear morphea (Figs. 12.1c–f and 12.2a–d), and deep morphea or morphea profunda. Unlike scleroderma, systemic disease and involvement of internal organs are uncommon in morphea.