Overlap syndrome is a rare condition involving the coexistence of at least two distinct autoimmune diseases, such as systemic lupus erythematosus and systemic sclerosis. This condition has limited studies on epidemiology probably because it is often under-recognized. We present a 22-year-old Filipino female with a 10-month history of hyperpigmented patches on the malar surface and extremities, with associated photosensitivity, fatigue, pallor, arthralgia, and oral ulcers, and positive antinuclear antibody titer. She was treated with oral Prednisone in tapering doses, leading to clinical improvement. Eight months later, there was a recurrence of hyperpigmented patches on the face and extremities with skin tightening and diffuse hair loss, development of shiny skin with facial fold loss, a beak-like nasal appearance, and episodes of dyspnea and malaise. Consistent with scleroderma, the patient was started on mycophenolate mofetil (MMF) 500 mg daily, with close monitoring for disease progression and systemic involvement. Overlap syndrome remains under-recognized due to its variable presentation and rarity. Treatment is individualized based on the specific connective tissue diseases involved and the patient’s symptoms. Multidisciplinary care is crucial for timely management and to adjust treatment as needed, given the potential for life-threatening complications involving cutaneous and internal organs.

Diffuse cutaneous Systemic Sclerosis (dsSSc) is an uncommon subtype of Scleroderma or Systemic Sclerosis (SSc), a multisystemic autoimmune disease. Philippine reports remain limited, hence there is a need to review this condition to accurately diagnose and manage Filipino patients. We present the case of a 52-year old Filipino female with a one-year history of pruritus and generalized skin thickening presenting as multiple, well-defined, hyperpigmented patches and plaques. She also presented with systemic symptoms like fever, dysphagia, and finger tenderness, swelling, numbness, and color changes upon exposure to extreme temperatures known as Raynaud’s Phenomenon. Clinical findings, alongside dermoscopic, histopathologic, nail capillaroscopy, and diagnostic data, confirmed dsSSc diagnosis with complications like Barrett’s Esophagus and Interstitial Lung Disease. Treatment options include corticosteroids, emollients, immunosuppressants, biologics, and phototherapy. Multidisciplinary teams are essential to address systemic complications.

Systemic sclerosis is a disease characterized by skin and internal organ fibrosis, lacking specific therapeutic drugs and having a poor prognosis. Early diagnosis and intervention of the disease is of significant value in improving patient prognosis. This article provides a systematic review of the early diagnosis and treatment of systemic sclerosis, including early symptom recognition, laboratory testing, and drug intervention. It will provide a reference for the prevention of this disease.
Humans ; Scleroderma, Systemic/prevention & control*

Systemic sclerosis is a disease characterized by skin and internal organ fibrosis, lacking specific therapeutic drugs and having a poor prognosis. Early diagnosis and intervention of the disease is of significant value in improving patient prognosis. This article provides a systematic review of the early diagnosis and treatment of systemic sclerosis, including early symptom recognition, laboratory testing, and drug intervention. It will provide a reference for the prevention of this disease.
Humans ; Scleroderma, Systemic/prevention & control*

OBJECTIVE: To detect the expression of plasma exosomal microRNA (miRNA) in systemic sclerosis (SSc), and to investigate its clinical significance. METHODS: A total of 20 patients who were initially diagnosed with SSc and did not receive medication in Department of Rheumatology and Immunology of Meizhou People' s Hospital from January 2020 to January 2022 were recruited, as well as 15 healthy individuals whose gender and age matched with those of the SSc patients. Plasma exosomes were isolated using ultracentrifugation method. The expression levels of exosomal miR-34-5p, miR-92-3p and miR-142-3p were detected by quantative real-time polymerase chain reaction (qRT-PCR). Correlations between the expression levels of exosomal miRNAs and clinical characteristic were analyzed by Spearman's rank correlation coefficient test. RESULTS: The mean age of 20 patients with SSc was (52.6±12.6) years, including 7 males and 13 females. Among the 20 SSc patients, 13 cases were diagnosed as limited cutaneous systemic sclerosis (lcSSc) and 7 cases were diagnosed as diffuse cutaneous systemic sclerosis (dcSSc) according to the extent of skin involvement. According to the findings of high resolution chest CT, 7 of 20 SSc patients were diagnosed with interstitial lung disease (ILD) and 13 SSc patients were diagnosed with non-ILD. The expression levels of exosomal miR-34-5p, miR-92-3p and miR-142-3p were significantly elevated in the SSc patients compared with those in the healthy controls group (P=0.003, P=0.000 1, and P=0.016, respectively). Compared with the SSc patients without ILD, the expression levels of miR-34-5p and miR-142-3p were significantly lower in the SSc patients with ILD (P=0.037 and P=0.015, respectively). The expression levels of exosomal miR-34-5p and miR-142-3p showed negative correlation with ILD (r=-0.48, P=0.031 and r=-0.55, P=0.011, respectively), and arthritis (r=-0.46, P=0.040 and r=-0.48, P=0.032, respectively). The expression levels of exosomal miR-142-3p showed a negative correlation with erythrocyte sedimentation rate (ESR) (r=-0.55, P=0.012). CONCLUSION Plasma exosomal miR-34-5p, miR-92-3p and miR-142-3p were dysregulated in SSc. The dyregulation of exosomal miR-34-5p and miR-142-3p showed correlation with SSc associated ILD (SSc-ILD).
Male ; Female ; Humans ; Young Adult ; Adult ; Clinical Relevance ; MicroRNAs/genetics* ; Scleroderma, Systemic/genetics* ; Lung Diseases, Interstitial

Antibodies, Antinuclear ; Autoantibodies ; China ; Cohort Studies ; Humans ; Scleroderma, Systemic

OBJECTIVE: To explore the significance of lymphocytes in systemic sclerosis (SSc), by detecting the levels of T lymphocytes, B lymphocytes and natural killer (NK) cells, and analyzing the correlation between the lymphocytes and clinical laboratory indexes. METHODS: The numbers and proportion of T, CD4⁺T, CD8⁺T, B, and NK cells were detected by flow cytometry in peripheral blood of 32 SSc patients who had taken immunosuppressive drugs and 30 healthy controls (HC). The comparison of the lymphocyte subsets in SSc with them in the HC groups, and the correlation between the lymphocytes and other clinical and laboratory indicators were analyzed by the relevant statistical analysis. RESULTS: Compared with the HC group, the numbers of T, CD4⁺T, CD8⁺T, and NK cells in peripheral blood of SSc group, who had taken immunosuppressive drugs, were significantly decreased (P < 0.05). More-over, the proportion of NK cells in peripheral blood of the SSc group was also significantly lower than that in the HC group (P=0.004). In addition, all the lymphocyte subsets were decreased in peripheral blood of more than 65% of the SSc patients who had taken immunosuppressive drugs. Compared with CD4⁺T normal group, the positivity of Raynaud's phenomenon, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) was significantly increased in CD4⁺T reduction group, respectively (P＝0.024, P < 0.001, P=0.018). ESR was higher in CD8⁺T reduction group than CD8⁺T normal group (P＝0.022). The prevalence of fingertip ulcer was significantly increased in B cell decrease group (P=0.019). Compared with NK cell normal group, the prevalence of fingertip ulcer was significantly increased in NK cell lower group (P=0.033), IgM was remarkablely decreased yet (P=0.049). The correlation analysis showed that ESR was negatively correlated with the counts of T lymphocytes (r＝－0.455, P＝0.009), CD4⁺T lymphocytes (r＝－0.416, P＝0.018), CD8⁺T lymphocytes (r＝－0.430, P=0.014), B cells (r＝－0.366, P＝0.039). CONCLUSION The number of CD4⁺T, CD8⁺T, B, and NK cells significantly decreased in peripheral blood of SSc patients who had used immunosuppressive drugs, some lymphocyte subsets might be related with Raynaud's phenomenon and fingertip ulcer, and reflected the disease activity by negatively correlated with ESR and CRP; the numbers of lymphocyte subsets in peripheral blood should be detected regularly in SSc patients who had taken immunosuppressive drugs.
B-Lymphocytes ; Flow Cytometry ; Humans ; Killer Cells, Natural ; Lymphocyte Subsets ; Scleroderma, Systemic ; T-Lymphocyte Subsets ; T-Lymphocytes

Idiopathic pulmonary fibrosis (IPF) is a condition that has been described as alveolar collapse and thickening, which correlate with dysregulated surfactant production and injury to type 2 alveolar cells. As resolution of chest computed tomography has improved, especially with the development of high-resolution computed tomography (HRCT), the diagnostic measures adopted for pulmonary fibrosis has gradually shifted from biopsy to HRCT. This shift towards HRCT has aided in diagnostic evaluation and detection of the therapeutic and adverse effects of drugs for pulmonary fibrosis. Further, after the endpoint was changed to forced vital capacity, significant improvements are being observed in clinical trial outcomes. Currently active clinical trials are replacing lung biopsy with HRCT. In 2014, pirfenidone and nintedanib gained approval for tandem use in patients with IPF. These drugs were found to not only reduce the progression of pulmonary fibrosis, but also the acute exacerbation and mortality associated with the condition. These drugs showed consistent benefits regardless of the severity of patients' symptoms. Additionally, both nintedanib and pirfenidone were found to be effective in patients with advanced pulmonary fibrosis that was not classified as IPF. Nintedanib has been shown to reduce forced vital capacity in interstitial lung diseases associated with systemic sclerosis. In the next three to five years, many changes in treatment are expected, not only for IPF, but also for the entire spectrum of pulmonary fibrotic diseases. Pirfenidone and nintedanib are now considered standard treatments for IPF and few other fibrotic lung diseases. Clinicians treating patients with pulmonary fibrosis should keep themselves updated with the results of clinical trials that are currently underway.
Biopsy ; Humans ; Idiopathic Pulmonary Fibrosis ; Lung ; Lung Diseases ; Lung Diseases, Interstitial ; Mortality ; Pulmonary Fibrosis ; Scleroderma, Systemic ; Thorax ; Vital Capacity

OBJECTIVE: To investigate the expression of tumor-transforming gene-1 (PTTG1) in systemic sclerosis (SSc) and its role in fibrosis. METHODS: Skin biopsy samples were collected from 21 patients with SSc and 22 patients with healthy skin for detecting the mRNA and protein expressions of PTTG1 using real-time PCR (RT-PCR) and immunohistochemistry, respectively. In cultured primary human dermal fibroblasts, PTTG1 expression was knocked down via RNA interference (siRNA), and the mRNA expression levels of PTTG1 and the fibrosis-related genes RESULTS: Compared with those in normal skin samples, the mRNA and protein expressions of PTTG1 increased significantly in the skin tissue of patients with SSc ( CONCLUSIONS PTTG1 is highly expressed in skin tissues of patients with SSc, and PTTG1 knockdown can reduce the activity of the dermal fibroblasts, suggesting a close correlation of PTTG1 with fibrosis in SSc.
Cells, Cultured ; Fibroblasts ; Fibrosis ; Humans ; Scleroderma, Systemic/pathology* ; Securin ; Skin/pathology*

INTRODUCTION: Fibroblast growth factor-23 (FGF23) is a circulating regulator of phosphate and vitamin D metabolism and has been implicated as a putative pathogenic factor in cardiovascular disease. The objectives of this study were: to compare serum FGF23 levels between systemic sclerosis (SSc) patients and healthy controls and to investigate possible associations between FGF23 and serum lipid profile in SSc patients. METHODS: This cross-sectional study was performed in San Cecilio Hospital, Granada (Spain) from November 2017 to May 2019. We enrolled 62 consecutive female patients affected by SSc and 62 healthy women who served as controls. Cardiovascular risk factors and related biochemical parameters were collected. Serum FGF23 was analyzed using enzyme- linked immunosorbent assay (ELISA). Linear regression was used to examine the cross-sectional associations of serum FGF23 concentrations with high density lipoprotein-cholesterol (HDL-c). RESULTS: There was no significant differences in FGF23 levels between the patients and controls (78.2 ± 60.5 vs. 80.3 ± 56.3 pg/mL, p= 0.662), but we found a statistically significant inverse relationship between FGF23 and HDL-c measurements (r= -0.27; p= 0.03) in women with SSc. In addition, in the linear regression model, higher FGF23 concentrations were associated with lower HDL-c [β = -1.45 95% CI (-2.81, -0.08); p < 0.05]. CONCLUSIONS: We report an association between circulating FGF23 and HDL-c in SSc female patients, representing a novel pathway linking high FGF23 to an increased cardiovascular risk.
Lipoproteins, HDL ; fibroblast growth factor 23 ; Scleroderma, Systemic ; Fibroblast Growth Factors