[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.

Treatment of Progressive Hemifacial Atrophy by Cartilage Graft and Free Adipofascial Flap Combined with Three-Dimensional Planning.

BACKGROUND: Progressive hemifacial atrophy (PHA) is a rare disease characterized by progressive atrophy of skin, soft tissue, muscles, and underlying bone structures. For severe PHA patients with obvious bone deformities, skeletal framework reconstruction is needed in addition to soft-tissue augmentation. The authors propose a new combinatorial surgical method using rib cartilage graft and free adipofascial flap for restoring facial symmetry. To improve the surgical accuracy, preoperative three-dimensional planning and printing was used. METHODS: Twelve patients with severe facial atrophy were included in the authors' study. Three-dimensional facial image analyses were performed preoperatively to quantify the facial asymmetry. Rib cartilages were harvested and sculptured to the appropriate shape created by three-dimensional planning and fixed to the atrophic bone. The circumflex scapular artery-based adipofascial flap was transplanted to repair soft-tissue deficiency. A residual small monitor flap was left with the adipofascial flap. A revision surgery was performed to perfect the repair if the contour was suboptimal 6 months postoperatively. RESULTS: The adipofascial flaps survived in all 12 patients. All patients achieved good healing without complications. At 1 more year after surgery, the rib cartilage was still in position and rarely absorbed. The morphologic and volumetric difference between the affected side and the unaffected side was improved significantly postoperatively. All patients were satisfied with the results, and no more additional operations were required. CONCLUSION: The combinatorial surgery of rib cartilage graft and free adipofascial flap in the setting of three-dimensional planning and printing can be a good choice in restoring facial symmetry in severe cases of PHA. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Application of free serratus anterior muscle-fascial composite tissue flap and facial lipofilling in repairing progressive hemifacial atrophy.

INTRODUCTION: Progressive hemifacial atrophy (PHA) is a nonnegligible disease, and its treatment currently lacks consensus. We aim to conduct an analysis of PHA patients to summarize the postoperative effect. Moreover, we introduced the free serratus anterior muscle-fascial composite tissue flap as a safe and novelty surgical procedure for moderate-severe PHA. METHODS: This clinical study included four patients who received a free serratus anterior muscle-fascial composite tissue flap and 19 patients who received Coleman fat transplantation. Preoperative (preoperative photograph and imageological examination) and postoperative (postoperative photograph, complications, therapeutic effect, and satisfaction) assessments were performed for all PHA patients. Body Image Concern Inventory (BICI), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS) were performed preoperatively and postoperatively. RESULTS: All the cases were cured with a good appearance with two kinds of operations. Free serratus anterior muscle-fascial composite tissue flap could correct face defects in one surgery and achieve good long time and short-time postoperative satisfaction in moderate-severe PHA. Fat transplantation could also enhance appearance in numerous operations for mild-moderate PHA. The volume of free-fat grafts decreased obviously after implantation in many cases. So, many patients (42.11%) accepted a series of operations to achieve satisfied postoperative effect. BICI, SAS, SDS score decreased a year later in all patients. CONCLUSION: Free serratus anterior muscle-fascial composite tissue flap transplantation is an effective and safe treatment for moderate to severe PHA.

A case of progressive crossed hemiatrophy mistaken as panniculitis.

Progressive crossed hemiatrophy is an extremely rare clinical type of facial hemiatrophy that presents primarily as unilateral facial atrophy and contralateral trunk or limb involvement. The undistinguishable clinical manifestation and pathological changes complicate diagnosis, especially at the onset of the disease when presenting with less clinical evidence. Here, we report a case of a 9-year-old boy started with left scalp induration, following with subcutaneous tissues atrophy on the right trunk. He was mistaken as panniculitis based on the pathologic findings and treated with topical tacrolimus without any improvement. Immune-related tests were implemented to exclude connective tissues. Imaging examinations such as magnetic resonance was conducted to evaluate the range and degree of the involvement of the skin, soft tissue, and cranial changes. Although no effective treatment to hold back the progress has been reported so far, surgeries might work to restore the appearance to some extent or improve central nerves symptoms if they exist.

Genetic variations in patient with Parry-Romberg syndrome.

Parry-Romberg syndrome is a rare craniofacial disorder which is characterized by progressive facial atrophy. The etiology and pathogenesis of the disease are not known. Herein, we report the genetic variants in patient with this disease. A 25-year-old woman was diagnosed with Parry-Romberg syndrome according to her clinical manifestation, which presented with typical progressive unilateral facial soft tissue atrophy. Using peripheral blood samples, Whole exome sequencing (WES) was conducted on this patient and her parents. Variant loci of the genes were validated by Sanger sequencing in her twin sister who had no Parry-Romberg syndrome. Subsequently, we searched the GeneCards®: the Human Gene Database for variant genes, annotated them and analyzed their functions. The results of WES showed that 2 genes (MTOR, DHX37) were mutated, and the variant loci were MTOR: NM_004958.4: exon31: c.4487A>T: p.Q1496L and DHX37: NM_032656.4: exon17: c.2180C>T: p.T727M, respectively. However, the variant loci were also detected in her twin sister by Sanger sequencing. The Human Gene Database for variant genes shows that the two genes may be associated with craniomaxillofacial developmental abnormalities. Although MTOR and DHX37 genes were tested and found to have mutations in patient with Parry-Romberg syndrome, these variants may not directly determine the clinical phenotype. When studying clinical etiology, other factors, such as the environment, should also be taken into account.

Dental Anomalies in Parry-Romberg Syndrome: A 40-Year Retrospective Review.

OBJECTIVE: This study investigates crown and root anomalies in patients with Parry-Romberg Syndrome. DESIGN: This is a retrospective review of patients with Parry-Romberg Syndrome who were evaluated at a tertiary care center from 1980-2020. SETTING: Patients seen in the dental unit from 1980-2020. PATIENTS, PARTICIPANTS: Seventeen patients with documented Parry-Romberg Syndrome were referred for dental evaluation. MAIN OUTCOME MEASURES: All dental anomalies were documented. Root anomalies were assessed using panoramic radiographs and cone beam CT (CBCT) scans to evaluate buccal-lingual, mesio-distal, and axial measurements of hypoplastic teeth, which were compared to those of contralateral teeth. RESULTS: Findings included agenesis (29%, n = 5), hypoplastic teeth (29%, n = 5), delayed canine eruption (24%, n = 4), and mulberry molars (12%, n = 2). Of the five patients with tooth hypoplasia, four had CBCT records and the fifth had panoramic radiographs available for assessment. Axial length was always shorter in hypoplastic teeth relative to contralateral teeth, with differences ranging from 1.2-9.2 mm. Differences in crown size of hypoplastic versus contralateral teeth were unpredictable but always present. CONCLUSIONS: Patients with Parry-Romberg Syndrome can have hypoplastic roots with atypical crown morphology. A patient's specific dental anomaly will influence planning and treatment.

Clinical and therapeutic course in head variants of linear morphea in adults: a retrospective review.

Parry Romberg Syndrome (PRS) and en coup de sabre (ECDS) are head variants of linear morphea with functional and structural implications. This study describes the clinical course, autoimmune co-morbidities, complications, and treatment of adults with PRS/ECDS at a tertiary referral center. We retrospectively reviewed the records of all 34 adult patients with PRS/ECDS identified through billing code search and seen by dermatologists at our institution between 2015 and 2021. Eight patients (23.5%) had ECDS, 8 (23.5%) had PRS, and 18 (52.9%) had overlap. Twenty-six patients (76.5%) reported ocular, oral, and/or neurologic symptoms, and 8 (23.5%) had concomitant autoimmune/inflammatory conditions. Sixteen patients (47.1%) had a skin biopsy, and 25 (73.5%) had imaging. Forty-six MRIs were obtained, of which 6 (13.0%) reported intracranial findings and 25 (54.3%) reported disease-related connective tissue damage. Twenty-four patients (70.6%) underwent systemic treatment during their disease course per available clinical records. Seventeen patients (70.8%) had improved or stable disease upon treatment completion, with an average duration of 22.2 months. Ten patients (41.7%) reported recurrence of disease following the treatment course. To address changes to facial contour, 6 patients (17.6%) opted for procedural treatments. One patient (16.7%) experienced morphea reactivation following a filler injection performed off-immunosuppression. Compared to findings in children, our study suggests adults with PRS/ECDS are more likely to have oral and ocular complications but experience less severe neurologic symptoms. While systemic treatments appear beneficial in most adult patients with PRS/ECDS, disease may recur following discontinuation.

[Ocular involvement in Parry-Romberg syndrome]. / Porazhenie organa zreniya pri sindrome Parri­Romberga.

Parry-Romberg syndrome (PRS) is a rare degenerative disease of unknown etiology, characterized by slow progressive hemifacial atrophy of the soft tissues (subcutaneous fat, muscles), cartilage and bones. Beside hemifacial atrophy, various ophthalmic and periocular manifestations of PRS has been described. Progressive enophthalmos and eyelid changes are only some of many other symptoms, as the disease can affect all layers of the eyeball. This article reviews literature on ophthalmic manifestations of PRS and reports our own case and treatment approach for a patient with this pathology.

Progressive hemifacial atrophy in a Chinese patient: A case report.

BACKGROUND: Progressive hemifacial atrophy (PHA) is a rare and progressive condition of unknown etiology that is characterized by chronic progressive atrophy of the skin, subcutaneous tissue, muscle, and bone on 1 side of the face. However, its precise pathogenesis remains poorly understood. CASE PRESENTATION: Here, we report a case of PHA, which manifested as left-sided facial atrophy. Whole-exome sequencing of peripheral blood samples from the patient and his parents, together with bioinformatics analyses, led to the identification of mutations in ARHGAP4 and CFAP47. CONCLUSION: This report is the first to describe ARHGAP4 and CFAP47 mutations in a patient with PHA. These mutations may be related to the occurrence of hemifacial atrophy, although further studies are needed to clarify the role of ARHGAP4 and CFAP47 in the context of PHA pathogenesis.

Association of intracranial abnormalities with the development of epilepsy and drug-resistant epilepsy in patients with Parry-Romberg syndrome.

BACKGROUND: Epilepsy represents an essential component of Parry Romberg syndrome (PRS). This study aimed to identify clinical factors that influence the development of epilepsy and drug-resistant epilepsy (DRE) in PRS. METHODS: We retrospectively reviewed the medical records of eighty patients with PRS. Data including the age of onset for PRS, history of seizures, use and timing of immunotherapy, antiseizure medication use, and EEG and brain imaging findings were reviewed. For comparison with the patients with epilepsy (PRSe+) group, we selected 18 age and sex-matched controls from the patient without epilepsy (PRSe-) cohort using propensity score matching. RESULTS: Eighteen (22.5%) had epilepsy: 12 were female, and the median age was 14.5 years (range = 6-48 years). Eleven patients developed DRE. The median latency between the onset of cutaneous manifestations and diagnosis and timing and use of immunotherapy was similar between the PRSe + and PRSe- groups. Intracranial abnormalities were commonly seen in the PRSe + group (16 vs. 2, p < 0.01). White matter disease and ipsilateral atrophy were common among the PRSe + group. Timing and use of immunotherapy, epileptiform discharges, and brain imaging abnormalities did not differ between those with DRE and without. CONCLUSIONS: The presence and degree of severity of ipsilateral brain abnormalities are risk factors for the development of epilepsy in PRS but not factors in predicting drug resistance. The timing of immunotherapy did not influence the development of PRSe + or DRE. Prospective studies are needed to identify biomarkers for epilepsy and assess the role of immunotherapy on seizure outcomes in PRSe + .

Soft-Tissue Reconstruction in Progressive Hemifacial Atrophy: Current Evidence and Future Directions.

BACKGROUND: Progressive hemifacial atrophy is a rare disorder characterized by gradual unilateral soft-tissue atrophy in the face, which may also include clinically significant degeneration of underlying muscle and bone. In recent years, there has been a growing body of evidence regarding different soft-tissue reconstructive strategies in progressive hemifacial atrophy and the impact of intervention timing on disease progression. This article provides a comprehensive synthesis of the latest evidence to guide optimal management. METHODS: A comprehensive multidatabase search was performed through April of 2020 using relevant search terms to identify clinical studies. Outcomes, complications, and disease- and patient-related indications pertaining to different soft-tissue reconstructive strategies in progressive hemifacial atrophy were collected and critically appraised. RESULTS: Thirty-five articles reporting on a total of 824 progressive hemifacial atrophy patients were evaluated; 503 patients (61 percent) were managed by microvascular free flaps, 302 patients (37 percent) were managed by autologous fat grafts, and 19 patients (2 percent) were managed by pedicled flaps. A detailed synthesis of outcomes is presented in this article, as is a comparative evaluation of different microvascular free flap options. CONCLUSIONS: Soft-tissue reconstruction in progressive hemifacial atrophy remains an evolving field. Operative decision-making is often multifaceted, and guided by specific volumetric, aesthetic, and functional deficiencies. Serial fat grafting is the primary modality used for patients with mild soft-tissue atrophy, whereas microvascular free flaps widely remain the treatment of choice for reconstruction of large-volume defects. There exists a growing role of graft supplementation to improve fat graft survival, whereas recent evidence demonstrates that early intervention may help curb disease progression.

Brain Abnormalities and Epilepsy in Patients with Parry-Romberg Syndrome.

BACKGROUND AND PURPOSE: Parry-Romberg syndrome is a rare disorder characterized by progressive hemifacial atrophy. Concomitant brain abnormalities have been reported, frequently resulting in epilepsy, but the frequency and spectrum of brain involvement are not well-established. This study aimed to characterize brain abnormalities in Parry-Romberg syndrome and their association with epilepsy. MATERIALS AND METHODS: This is a single-center, retrospective review of patients with a clinical diagnosis of Parry-Romberg syndrome and brain MR imaging. The degree of unilateral hemispheric atrophy, white matter disease, microhemorrhage, and leptomeningeal enhancement was graded as none, mild, moderate, or severe. Other abnormalities were qualitatively reported. Findings were considered potentially Parry-Romberg syndrome-related when occurring asymmetrically on the side affected by Parry-Romberg syndrome. RESULTS: Of 80 patients, 48 (60%) had brain abnormalities identified on MR imaging, with 26 (32%) having abnormalities localized to the side of the hemifacial atrophy. Sixteen (20%) had epilepsy. MR imaging brain abnormalities were more common in the epilepsy group (100% versus 48%, P < .001) and were more frequently present ipsilateral to the hemifacial atrophy in patients with epilepsy (81% versus 20%, P < .001). Asymmetric white matter disease was the predominant finding in patients with (88%) and without (23%) epilepsy. White matter disease and hemispheric atrophy had a higher frequency and severity in patients with epilepsy (P < .001). Microhemorrhage was also more frequent in the epilepsy group (P = .015). CONCLUSIONS: Ipsilateral MR imaging brain abnormalities are common in patients with Parry-Romberg syndrome, with a higher frequency and greater severity in those with epilepsy. The most common findings in both groups are white matter disease and hemispheric atrophy, both presenting with greater severity in patients with epilepsy.

Biological characteristics of adipose-derived stem cells from patients with progressive hemifacial atrophy: An in vivo study.

OBJECTIVE: In this study, we investigate the biological characteristics of ADSCs from patients with progressive hemifacial atrophy (PHA) in vivo and try to explore the theoretical support for cell-assisted lipotransfer in treating patients with PHA. METHODS: ADSCs and exosomes were respectively extracted from patients with PHA and healthy ones. PHA-ADSC was detected the differentiation ability, phenotype, and anoxic resistance. NTA particle size, electron microscopy (TEM), and WB for CD63 and TSG10 were used to detect the exosomes. ADSCs of PHA (PHA-ADSCs) and healthy ones (NORM-ADSCs) mixed with their granular fat, exosomes mixed with PHA-granular fat, and PBS mixed with PHA-granular fat as the control group. The four groups of different grafts were, respectively, transplanted into nude mice, and the fat grafts were dissected and weighed at 2, 4, 8 and 12 w. Weight and volume retention were calculated for each of the four groups. Then, the four groups of fat grafts were tested for hematoxylin-eosin (HE) and immunohistochemical stainings, CD31 for blood vessel formation, CD68 for macrophage infiltration, and perilipin for fat formation, RT-PCR analysis of the APRC5, ATG5, ATG7, ATG12, BAX, PPARG, CDKN1A, and CDKN2A genes. RESULTS: ADSCs in the PHA group had typical phenotypes and multidirectional abilities. The PHA-ADSCs -assisted lipotransfer group, exhibited a weaker droplet formation and lower volume retention rate than the NORM-ADSCs-assisted lipotransfer group but much better than the non-cell-assisted lipotransfer group. Exosome-assisted lipotransfer group showed benefits, too. CONCLUSIONS: The PHA-ADSCs-assisted lipotransfer and the exosome-assisted lipotransfer improved the fat survival rate after fat filling in patients with hemifacial atrophy. Cell-assisted and exosome-assisted lipotransfer is an effective method to treat hemifacial atrophy.