Novel multispectral imaging to predict disease progression in pediatric morphea.

BACKGROUND: Morphea, or localized scleroderma, is an inflammatory, fibrosing skin disorder that can be progressive and debilitating. Infrared thermography frequently has false positive results. The aim of this study was to assess the ability of multispectral imaging to predict disease progression in children with morphea. METHODS: Children with morphea were recruited between 2016 and 2022. Multispectral images of affected and matched contralateral unaffected sites were obtained using the Antera™ 3D camera. Clinical assessment was performed using the Localized Scleroderma Assessment Tool (LoSCAT). Children were followed up every 3 months for imaging and clinical review. The main outcome measurement was correlation of hemoglobin gradient between affected and matched contralateral unaffected tissue and progression. RESULTS: Of 17 children, the average age was 12 years (range 6-18 years); most were female (76.5%) and white (94.1%). Nearly two-thirds (64.7%) had linear morphea, 35.2% had plaque morphea; 58.8% had been treated with systemic agents. The average LoSCAT score was 20.6 (range 5-73). The average hemoglobin gradient between affected and matched contralateral unaffected skin was four times higher in those who had progression (average differential 0.3, range 0.1-0.4) compared to those who did not (average differential 0.08, range 0.02-0.15). Using a cut off of a 0.18 hemoglobin gradient between affected and unaffected skin, the sensitivity of multispectral imaging for detecting progression in pediatric morphea is 90% with specificity of 100%. CONCLUSIONS: Multispectral imaging is a novel assessment tool with promising accuracy in predicting progression as an adjunct to clinical assessment in pediatric morphea. Further research should examine its performance against thermography.

Nephrotic syndrome due to focal segmental glomerulosclerosis complicating scleroderma: a case report.

BACKGROUND: Systemic scleroderma (SSc) is an insidious autoimmune connective tissue disorder with multiorgan involvement. Renal involvement is one of the important causes of morbidity and mortality in scleroderma; however, nephrotic syndrome is reported rarely in association with SSc. We present a patient with SSc who developed focal segmental glomerulosclerosis (FSGS) as a complication of scleroderma. CASE PRESENTATION: A 59 year old Caucasian female patient, with a known history of diffuse systemic sclerosis from 8 years, presented to our clinic with symptoms of anasarca and weight gain. Her physical examination was unremarkable except for periorbital and extremity edema. Her biochemistry assessment revealed decreased serum albumin levels and elevated serum creatinine levels. A renal biopsy was performed, which showed histopathological patterns of FSGS type of nephrotic syndrome. After administration of high doses of steroid and rituximab in the course of her treatment for 6 months, her symptoms and proteinuria were improved without the occurrence of scleroderma renal crises. CONCLUSION: SSc is a complex multisystemic autoimmune disorder. SRC is the most prominent renal involvement in SSc, but other renal pathologies may also occur. Each patient should be precisely investigated since managing these renal conditions can differ significantly. Nephrotic syndrome is a rare complication of SSc, which could be managed with prompt diagnosis and steroid administration.

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.

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.

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.

Adult-Onset Linear Morphea (en coupe de sabre) of the Face Successfully Treated with Photoactivated Low-Temperature Platelet-Rich Plasma: A Valid Therapeutic Option.

Localized scleroderma (also known as morphea) is a chronic autoimmune disorder characterized by depressed, fibrotic, and dyschromic cutaneous lesions. It has a significant impact on the patient's daily life due to the unaesthetic evolution of the cutaneous lesions. Morphea is clinically divided into linear, circumscribed (plaque), generalized, pansclerotic, and mixed forms. Linear morphea en coupe de sabre (LM) usually arises in childhood. However, in about 32% of cases, it may arise in adulthood, showing a more aggressive course with also an increased risk of systemic involvement. Methotrexate is the first-line treatment for LM, although systemic steroids, topical agents (corticosteroids and calcineurin inhibitors), hyaluronic acid injections, and hydroxychloroquine or mycophenolate mofetil are valid therapeutic options. In any case, these treatments are not always effective and sometimes can be associated with important side effects and/or not tolerated by the patients. In this spectrum, platelet-rich plasma (PRP) injection can be considered a valid and safe alternative since PRP injections in the skin induce the release of anti-inflammatory cytokines and growth factors, thus reducing inflammation and increasing collagen remodeling. Herein, we describe a successful treatment of an adult-onset LM en coupe de sabre with photoactivated low-temperature PRP (Meta Cell Technology Plasma) sessions, showing an important local improvement of the lesion and patient satisfaction.

Remission rates and risk factors for relapse in pediatric morphea: a multicenter retrospective study of Pediatric Rheumatology Academy (PeRA)-Research Group (RG).

AIM: Morphea, also known as localized scleroderma, is an immune-mediated disease and the most common form of scleroderma in children. It is a localized sclerosing disease of the skin, but can also involve such adjacent tissues as the fascia, muscle, bone, and underlying tissues. This multicenter study aimed to evaluate Turkish pediatric morphea patients, regarding demographics, treatments, and response to treatment. MATERIALS AND METHODS: The study was performed by the Pediatric Rheumatology Academy and included pediatric morphea patients from 6 Turkish pediatric rheumatology centers who were followed up for ≥6 months. Demographic, clinical, and laboratory findings and treatment modalities were analyzed. The patients were divided into 3 groups according to treatment response, as follows: group 1: topical treatment response, group 2: methotrexate response, and group 3: methotrexate resistance. Clinical findings were compared between the 3 groups. RESULTS: The study included 76 patients, of which 53 (69.7%) were female. Mean age at diagnosis of morphea was 9.7 ± 4.3 years and mean duration of follow-up was 3.2 ± 2.9 years. Linear morphea was the most common form, accounting for 43.4% (n = 33) of the patients. Extracutaneous features were noted in 17 patients (22.4%) and anti-nuclear antibody positivity was noted in 32 (42.1%). In all, 14.4% of the patients received topical treatment only, whereas 86.6% received both topical and systemic treatment. The methotrexate response rate was 76.9% in the patients that received systemic immunosuppressive therapy. The overall relapse rate while under treatment was 19.7%. CONCLUSION: In this study, most of the pediatric morphea patients responded well to methotrexate. Bilateral lesions were more common in the methotrexate-resistant group. Multiple involvement, and bilateral lesions, were more common in relapsed patients than in non-relapsed patients. Key points • Most of the pediatric morphea patients respond well to MTX. • Multiple involvement, and bilateral involvement, were more common in relapsed patients than in non-relapsed patients. • Presence of extracutaneous findings in patients increased relapse rate 5.7 times.

Presenting characteristics and progression of pediatric-onset morphea: Interim analysis of a prospective registry.

Morphea is a rare fibrosing disorder with a highly variable disease course, which can complicate management. Here, we present a prospective cohort study describing the current treatments used in the management of pediatric-onset morphea and assessing responses to systemic and topical therapies. Most patients demonstrated inactive disease by 1 year, regardless of treatment, though recurrences were common in our cohort overall (39%). Our results support the need for continuous monitoring of all children with morphea following the completion of treatment, including topical treatment, due to high rates of disease relapse.

Bilateral en coup de sabre morphea in a male child: A rare presentation.

En coup de sabre is a rare subtype of morphea. Only a few bilateral cases have been reported to date. We report a case of a 12-year-old male child with two linear brownish depressed asymptomatic lesions over the forehead with hair loss on the scalp. After thorough clinical, ultrasonography and brain imaging, a diagnosis of bilateral en coup de sabre morphea was made and the patient was treated with oral steroids and weekly methotrexate.

Morphea after initiation of dupilumab in two pediatric atopic dermatitis patients.

Morphea is a rare multifactorial autoimmune disorder characterized by a complex and dynamic interplay between Th1 and Th2 signaling. Active clinical trials are currently investigating the safety and efficacy of dupilumab for the treatment of primary morphea. Here, we present two cases of morphea that developed in pediatric atopic dermatitis patients treated with dupilumab. These findings may support a causal relationship between IL-4 receptor blockade and the development of the early inflammatory phase of morphea.

Study about evaluation of efficacy of methotrexate in localized scleroderma using ultrasonography.

BACKGROUND: The treatment and curative effect evaluation of localized scleroderma (LS) still perplexes many clinical workers. PURPOSE: To investigate the efficiacy of methotrexate in the treatment of LS by the evaluation of ultrasonography. METHODS: A prospective study enrolled 10 patients treated with MTX for at least 6 months was conducted. Treatment outcome was evaluated by a clinical score and 15-MHz ultrasonography. Safety assessment included the monitoring of adverse drug reactions and clinical laboratory examinations. RESULTS: Eight of the 10 patients achieved clinical remission only with MTX. One patient was relieved after MTX combined with corticosteroids, while another one does not improve after the treatment of mycophenolate mofetil and corticosteroids. The effective rate of MTX is 80%. Nine patients were significantly improved with a decrease of the Localized Scleroderma Cutaneous Assessment Tool (the mean score of the LoSCAT cutaneous activity dropped from 5.2 to 1.0, p < 0.001, the mean score of the LS cutaneous damage dropped from 4.3 to 2.3, p = 0.002). The average difference of thickness between skin lesions and normal skin evaluated by ultrasonography decreased from 0.13 cm to 0.04 cm (p = 0.009) in eight patients. No serious adverse reactions occurred. CONCLUSION: Methotrexate is a safe and effective treatment for patients with LS. Ultrasonography can be considered as an efficient assessment tool for evaluation LS.

Clinical and Molecular Findings After Autologous Stem Cell Transplantation or Cyclophosphamide for Scleroderma: Handling Missing Longitudinal Data.

OBJECTIVE: Among individuals with systemic sclerosis (SSc) randomized to cyclophosphamide (CYC) (n = 34) or hematopoietic stem cell transplantation (HSCT) (n = 33), we examined longitudinal trends of clinical, pulmonary function, and quality of life measures while accounting for the influence of early failures on treatment comparisons. METHODS: Assuming that data were missing at random, mixed-effects regression models were used to estimate longitudinal trends for clinical measures when comparing treatment groups. Results were compared to observed means and to longitudinal trends estimated from shared parameter models, assuming that data were missing not at random. Longitudinal trends for SSc intrinsic molecular subsets defined by baseline gene expression signatures (normal-like, inflammatory, and fibroproliferative signatures) were also studied. RESULTS: Available observed means for pulmonary function tests appeared to improve over time in both arms. However, after accounting for participant loss, forced vital capacity in HSCT recipients increased by 0.77 percentage points/year but worsened by -3.70/year for CYC (P = 0.004). Similar results were found for diffusing capacity for carbon monoxide and quality of life indicators. Results for both analytic models were consistent. HSCT recipients in the inflammatory (n = 20) and fibroproliferative (n = 20) subsets had superior long-term trends compared to CYC for pulmonary and quality of life measures. HSCT was also superior for modified Rodnan skin thickness scores in the fibroproliferative subset. For the normal-like subset (n = 22), superiority of HSCT was less apparent. CONCLUSION: Longitudinal trends estimated from 2 statistical models affirm the efficacy of HSCT over CYC in severe SSc. Failure to account for early loss of participants may distort estimated clinical trends over the long term.