S2k guideline: Diagnosis and therapy of localized scleroderma.

The updated S2k guideline deals with the diagnosis and therapy of localized scleroderma (LoS). LoS represents a spectrum of sclerotic skin diseases in which, depending on the subtype and localisation, structures such as adipose tissue, muscles, joints, and bones may also be affected. Involvement of internal organs or progression to systemic sclerosis does not occur. LoS can be classified into four main forms: limited, generalized, linear, and mixed forms, with some additional subtypes. For cases of limited skin involvement, the guideline primarily recommends therapy with topical corticosteroids. UV therapy can also be recommended. In subtypes with severe skin or musculoskeletal involvement, systemic therapy with methotrexate is recommended. During the active phase of the disease, systemic glucocorticosteroids can be used additionally. In cases of methotrexate and steroid refractory courses, contraindications, or intolerance, mycophenolate mofetil, mycophenolic acid, or abatacept can be considered as second-line systemic therapies. In the case of linear LoS, autologous adipose-derived stem cell transplantation can also be performed for correcting soft tissue defects.

[Localized scleroderma]. / Lokalisierte Sklerodermie.

Localized scleroderma (LS), also called circumscribed scleroderma or morphea, comprises a heterogeneous group of diseases that can be classified into four subtypes: limited, linear, generalized, and mixed LS. All manifestations are primarily due to chronic progressive fibrosis of the skin or structures close to the skin. Involvement of internal organs or the transition to systemic sclerosis is excluded by definition. A distinction is made between forms that primarily affect the skin (up to the dermis) or that severely involve subcutaneous fat tissue, muscle fascia or muscles. A detailed examination is required for clinical diagnosis. In order to improve comparability of findings, photo documentation and the use of clinical scores should be carried out. For superficial subtypes the use of topical glucocorticosteroids, calcineurin inhibitors or phototherapy is initially recommended, whereas for severe forms with deep involvement or overall therapy refractoriness, the diagnosis should first be expanded and systemic therapy initiated at an early stage. Especially, in cross joint or extremity-dominant forms of linear LS or in cases with head and neck involvement, such as en coup de sabre, Parry-Romberg syndrome and other subtypes with a prominent musculoskeletal affection, an MRI examination should be arranged. Depending on location, an ophthalmological, neurological, orthodontic, rheumatological or orthopedic consultation may be necessary. For systemic therapy, methotrexate alone or in combination with systemic glucocorticosteroids as pulse therapy is recommended as first-line treatment.

[Juvenile localized scleroderma]. / Zirkumskripte Sklerodermie im Kindesalter.

Juvenile scleroderma, often referred to as juvenile localized scleroderma or "morphea", is a rare inflammatory disease of the skin and skin-related structures, accompanied by local sclerosis and tissue fibrosis. Depending on the clinical manifestation, four different subtypes can be defined: limited, generalized, linear, and mixed. To prevent possible sequelae of the disease, the diagnosis should be made as early as possible and therapy should be initiated at specialized centers in multiprofessional pediatric and dermatologic collaboration. In this review, we present the main clinical, laboratory, and therapeutic characteristics of juvenile localized scleroderma and summarize recommendations.

[Radiation-induced morphea-an overview]. / Postradiogene Morphea ­ eine Übersicht.

BACKGROUND: Radiation-induced morphea is a fibro-inflammatory remodelling process of the subcutaneous connective tissue caused by ionising radiation, most commonly in the context of breast cancer treatment. The underlying pathomechanisms and putative risk factors are unknown. Therefore, misdiagnosis and inappropriate treatment pose a significant problem in the care of those patients. OBJECTIVES: The aim of the study was to provide an overview as well as guidance for the diagnosis and treatment of radiation-induced morphea based on current case reports and review articles. RESULTS AND CONCLUSIONS: Radiation-induced morphea is a rare condition that represents an interdisciplinary challenge for (gynaecological) oncology, radiotherapy and dermatology. Frequent misdiagnoses include infection (erysipelas), cancer recurrence or radiation dermatitis. Early histological diagnosis and the initiation of anti-inflammatory therapy using topical glucocorticoids or calcineurin inhibitors in combination with phototherapy and/or methotrexate are the most relevant success factors for an adequate clinical response.

Ocular and eyelid involvement in collagen vascular diseases. Part II. Dermatomyositis, scleroderma, and sarcoidosis.

Collagen vascular disease is a heterogeneous group of autoimmune diseases that affect multiple organ systems. Sjögren syndrome, dermatomyositis, scleroderma, systemic lupus erythematosus, and sarcoidosis are collagen vascular diseases that often present with characteristic cutaneous manifestations. Although less known, various ocular manifestations that affect both external and internal structures of the eye can also be seen in these conditions. Multidisciplinary management between dermatologists and ophthalmologists is essential in the early diagnosis and management of collagen vascular diseases affecting both the skin and eye. In part II of our series, we discuss the ocular manifestations, diagnosis, and therapeutic options of dermatomyositis, scleroderma, and sarcoidosis.

Morphea as an isotopic response to pigmented purpuric dermatosis and lichen striatus.

Morphea is an uncommon inflammatory and fibrosing disorder that has a polymorphous clinical presentation. We report two cases of morphea developing as an isotopic response after a preceding benign skin disease, accompanied by a review of the literature. This case series highlights the importance of return to care recommendations for benign skin conditions such lichen striatus and pigmented purpuric dermatoses due to the rare possibility of subsequent morphea development.

Systematic Review of Health-Related Quality of Life Impact in Juvenile Localized Scleroderma.

OBJECTIVE: The prevalence and types of psychosocial complications of juvenile localized scleroderma (JLS), also known as morphea, an inflammatory and sclerosing disease involving the skin, fascia, muscle, and bone, are poorly understood. METHODS: We performed a systematic review of literature published between 2000 and 2020 in PubMed, EMBASE, the Cochrane Skin Group Specialized Register, the Cochrane Central Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature using the search terms "scleroderma, localized," "Morphea," "anxiety," "depression," "resilience," "social stigma," "quality of life," "mood," or "stress" and limited the search to pediatric patients and English language. Patient demographics, characteristics of JLS, and comorbidities were extracted. The outcomes included measures of health-related quality of life (HRQoL), psychosocial functioning, evaluation of self-perception, and the treatment burden of the study population. The protocol was registered with PROSPERO (CRD42021257124). Thematic synthesis generated descriptive analysis. RESULTS: Thirteen studies fulfilled the inclusion criteria: three retrospective cohort studies, two prospective cohort studies, and eight cross-sectional studies. A total of 690 pediatric patients with JLS were included (n = 484 with linear scleroderma). Six studies used the Children's Dermatology Life Quality Index, reporting little to no effect on HRQoL. One study used the Health-Related Quality of Life in Children and Adolescents Questionnaire and did not find differences between children with JLS or atopic dermatitis and healthy controls. One study used a self-perception questionnaire that showed normal self-worth of patients with JLS. Two studies used focus groups, both reporting elevated levels of stress, decreased self-worth, "feeling different," and bullying/teasing in patients with JLS. These emotions were associated with skin symptoms (pain, itch, and tightness), physical limitations, and treatment burden. CONCLUSION: Overall, quantitative studies did not report a statistically significant impairment in HRQoL in JLS. However, qualitative studies (focus groups) reported significant psychosocial impacts related to JLS. There is a need to develop a JLS-specific tool for the HRQoL evaluation of this population.

Successful treatment with baricitinib of linear morphea following the lines of Blaschko mimicking lichen striatus.

Linear morphea, also known as linear scleroderma, is a localized form of scleroderma characterized by the presence of lesions that follow a linear distribution pattern. Apart from the typical inflammation and fibrosis of the skin, the linear subtype of morphea often affects underlying structures such as muscles and bones, which can lead to functional limitations. Lichen striatus, a linear inflammatory skin condition, primarily affects children aged 5 to 15 years. Interestingly, both diseases can exhibit lesions that follow the lines of Blaschko. Here we report a case with linear morphea following the lines of Blaschko mimicking lichen striatus in a 4-year-old child. This unique case represents the first documented instance of linear morphea exhibiting a precise Blaschko pattern and being successfully treated with baricitinib. The patient received oral baricitinib at a daily dosage of 2 mg for a duration of 1 year, resulting in remarkable improvement. The majority of the lesions softened, and there was no significant disease progression or occurrence of adverse events throughout the treatment period. Recognizing linear morphea at an early stage is of utmost importance in ensuring effective treatment and preventing disfiguring sequelae. Patients suspected of lichen striatus should also be closely followed and linear morphea should be excluded during the follow-up. The recent breakthrough in the application and the safety of baricitinib in scleroderma is also reviewed.

Recent Advances in Treatment of Systemic Sclerosis and Morphea.

Systemic sclerosis (SSc) and morphea are autoimmune sclerosing diseases that cause significant morbidity, and in the case of SSc, mortality. The pathogenesis of both SSc and morphea share vascular dysfunction, auto-reactive T cells and Th2-associated cytokines, such as interleukin 4, and overproduction of transforming growth factor beta (TGFß). TGFß stimulates fibroblast collagen and extra-cellular matrix production. Although morphea and SSc have similar pathogenic pathways and histological findings, they are distinct diseases. Recent advances in treatment of morphea, skin sclerosis in SSc, and interstitial lung disease in SSc are focused on targeting known pathogenic pathways.

Generalized early inflammatory morphea mimicking interstitial T-cell lymphoma: A diagnostic pitfall.

Early generalized morphea can clinically mimic mycosis fungoides. The microscopic features of early inflammatory morphea may show variable degrees of infiltration and do not have the characteristic dermal collagen sclerosis. We report the case of a 63-year-old female patient who presented with a 2-month history of an asymptomatic skin rash. Physical examination revealed multiple erythematous to dusky patches on the trunk and thighs, resembling the patch stage of mycosis fungoides. Two skin biopsies were performed, both of which showed prominent interstitial lymphoid infiltration in the reticular dermis without dermal sclerosis. Small lymphocyte exocytosis and lining along the dermal-epidermal junction were observed focally in the epidermis. Small clusters of plasma cells and eosinophils were observed in perivascular areas. Although no predominant clonality was found for CD4 and CD8 stains, 50% loss of CD5 antigen and 90% loss of CD7 antigen expression were apparent in immunohistochemical studies. Subsequent blood tests showed a normal blood cell count and positive human T-lymphotropic virus Type 1 antibodies. The overall findings suggested interstitial mycosis fungoides or early adult T-cell lymphoma-leukemia. The patient refused aggressive treatment, and 3 months later, she presented with indurated plaques from the previous rash. A repeat biopsy revealed the typical features of morphea. This report discussed the pitfalls in the clinical and histopathological diagnosis of early generalized inflammatory morphea that both clinicians and pathologists should consider.

Connective tissue nevus misdiagnosed as juvenile localized scleroderma.

BACKGROUND: Connective tissue nevi (CTN) are congenital hamartomas caused by excessive proliferation of dermis components. In children, CTN can mimic juvenile localized scleroderma (JLS), an immune mediated skin disorder that requires aggressive immunosuppression. OBJECTIVES: Aim of our study was to describe a series of pediatric patients with CTN misdiagnosed as JLS and the discerning characteristics between the two conditions. METHODS: Retrospective analysis of children referred to our Center during the last two decades for JLS who received a final diagnosis of CTN. Clinical, laboratory, histopathological and instrumental data (MRI and thermography) were collected and compared with those with JLS. RESULTS: Seventeen patients with mean age at onset 4.6 years entered the study. All came to our Center with a certain diagnosis of JLS (n = 15) or suspected JLS (n = 2). The indurated skin lesions were flat and resembled either circumscribed morphea or pansclerotic morphea. In 14 patients (82.4%) they were mainly localized at the lower limbs and in three (17.6%) at the upper limbs. No patient had laboratory inflammatory changes or positive autoantibodies. Skin biopsies confirmed the diagnosis of CTN: non-familial collagenoma in eleven (64.7%), mixed CTN in four (23.5%) and familial CTN in two (11.8%). Mean age at final diagnosis was 9.5 years, with a mean diagnostic delay of 4.8 years (range 1-15 years). Sixteen patients underwent musculoskeletal MRI that was normal in all except two who showed muscle perifascial enhancement. Thermography was normal in all patients. At our first evaluation, eleven patients (64.7%) were on systemic treatment (methotrexate 11, corticosteroids 7, biologics 2), three (17.6%) on topical corticosteroids and three untreated. CONCLUSIONS: CTN can be misdiagnosed as JLS and therefore aggressively treated with prolonged and inappropriate immunosuppression. The absence of inflammatory appearance of the skin lesions, normal instrumental and laboratory findings and the accurate evaluation of skin biopsy are crucial to address the right diagnosis.

Nodular (keloidal) scleroderma.

Keloidal or nodular scleroderma (NS) is a variant of localized scleroderma (LS) frequently seen in patients with limited or diffuse systemic sclerosis (SSc). It presents as raised, firm plaques or nodules with extensive dermal fibrosis and hyalinized collagen bundles. We present a patient with SSc who presented with this rare entity.

BULGARIAN PATIENT WITH ATROPHODERMA OF PASINI AND PIERINI- DESCRIPTION OF A CASE AND SHORT UPDATE.

Atrophoderma of Pasini and Pierini is a rare, considered benign, skin disease characterized by single or multiple asymptomatic atrophic plaques. Lesions can occur everywhere on the body with the trunk being the most often reported affected site. It appears in the second or third decade of life and affects mostly the female population, with male to female ratio of 1:6, commonly of white European descent. Different risk factors were described in the literature - genetic predisposition, infections with Epstein-Barr virus, varicella zoster and Borrelia burgdorferi, vaccinations, local trauma and more. Since the pandemic with COVID-19, skin manifestations after the viral infection with COVID-19 were reported. After a thorough search of the existing medical literature, we believe, we present the first case of a rapid progression of Atrophoderma of Pasini and Pierini after COVID-19 infection. Due to its similarity to morphea in some aspects, the condition is often misdiagnosed, and the proper treatment is often delayed. Sometimes the dilemma "Is it atrophoderma Pasini-Pierini or is it in fact morphea?" stays, but the exact histopathological verification and the "diagnostic clues" which can be used during the examination stage, are usually enough to diagnose the condition. We present a 63-year-old female with a rapid progression of atrophoderma of Pasini and Pierini after a COVID-19 infection. The lesion that she presented with was single, asymptomatic, with central hypopigmentation and slight atrophy, with a smooth, shiny surface and ivory color, and peripheral hyperpigmentation, measured 18x5cm, without the presence of perilesional erythema. The patient was initially diagnosed clinically with localized scleroderma (morphea) and treated with hydroxychloroquine 200 mg once daily for a 5-year period without improvement. Years later two biopsies from different lesional sites were taken, resulting in absence of sclerosis and dermal atrophy, but - reduction in the thickness of the dermis with fragmentation and hyalinization of collagen fibers forming a parallel orientation, dilated vascular vessels of small caliber and reduced number of skin appendages, confirming the diagnosis of atrophoderma Pasini-Pierini. The patient's therapy was switched to methotrexate with good therapeutic response. Often, the two conditions - morphea and atrophoderma of Pasini and Pierini can be mistaken due to its clinical similarity and sometimes coexistence. Therefore, we will shortly review the existing literature with key points on the similarities and differences.

Systemic therapy in juvenile localized scleroderma.

INTRODUCTION: Juvenile localized scleroderma (JLS) is a rare sclerosing disorder of childhood which can result in permanent morbidity and functional disability, if not effectively treated. Treatment should be started in the inflammatory phase before the development of any complication and/or damage. AREAS COVERED: In this review, we will discuss how to assess disease activity and damage in JLS, and propose an escalation plan for systemic treatment, according to a treat-to-target concept. We will discuss the definition of inactive disease and how and when to discontinue medications. EXPERT OPINION: Before starting treatment, it is extremely important to assess baseline disease activity for treatment response to be adequately checked. Moreover, the activity of the extra cutaneous involvement is an important part of the assessment. Patients should be treated in the 'therapeutic window,' before significant fibrosis results. Most patients should receive systemic treatments; in these patients, Methotrexate should be used as the first-line disease-modifying anti-rheumatic drug (DMARD). However, methotrexate intolerance or non-response is an issue, and these patients should be proposed a treatment escalation according to results of latest studies. Future research can develop better prognostic markers to help to guide our decision.