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.

OBJECTIVE: It has been reported that the mRNA expression of serine protease 23 (PRSS23) was increased in skin fibroblasts from systemic sclerosis patients (SSc). The purpose of this study is to explore the pathogenetic effect and mechanism of PRSS23 in skin fibrosis of SSc. METHODS: The expression of PRSS23 in skin tissues from the SSc patients and healthy controls was detected by immunohisto-chemistry. Fibroblasts isolated from fresh skin tissue were used to detect the expression of PRSS23 by real-time quantitative PCR (RT-qPCR) and Western blot. Overexprssion of PRSS23 in BJ, the fibroblasts cell line of skin, was constructed by lentivirus. After stimulation with 400 μmol/L hydrogen peroxide for 12 h, Annexin V/7-AAD staining was used to detect apoptosis of fibroblasts; flow cytometry and Western blot were used to detect the expression of apoptosis-related protein cleaved Caspase-3. The expression of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in fibroblasts was detected by RT-qPCR and enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with the healthy controls, the expression of PRSS23 in skin tissues of the SSc patients was significantly increased [4.952 (3.806-5.439) vs. 0.806 (0.395-1.173), P < 0.001], and fibroblast was the main cell that expressed PRSS23. The mRNA [27.59 (25.02-30.00) vs. 1.00, P < 0.001] and protein [0.675 (0.587-0.837) vs. 0.451 (0.342-0.502), P=0.029] of PRSS23 in skin fibroblasts isolated from the SSc patients were significantly up-regulated. Compared with the control group, the anti-apoptotic ability of skin fibroblasts overexpressing PRSS23 was enhanced, and the proportion of apoptotic cells was significantly reduced after hydrogen peroxide induction [(5.043±1.097)% vs. (17.480±3.212)%, P=0.022], the expression of apoptosis-related protein cleaved Caspase-3 was also markedly reduced [(0.718±0.022) vs. (1.422±0.105), P=0.003]. In addition, the mRNA [(99.780±1.796) vs. (1.000±0.004), P < 0.001] and protein [(211.600±2.431) ng/L vs. (65.930±1.768) ng/L, P < 0.001] of IL-6 in the fibroblasts overexpressing PRSS23 were significantly up-regulated; the mRNA[(3.555±0.555) vs. (1.000±0.004), P < 0.001] and protein levels [(41.190±0.949) ng/L vs. (31.150±0.360) ng/L, P < 0.001] of TNF-α in the fibroblasts overexpressing PRSS23 were also significantly up-regulated. CONCLUSION The expression of PRSS23 is increased in skin fibroblasts of SSc patients. PRSS23 can inhibit cell apoptosis, promote the secretion of inflammatory factors such as IL-6 and TNF-α, and regulate the process that skin fibroblasts transform into pro-inflammatory type. So, PRSS23 is associated with the development of skin fibrosis.
Humans ; Scleroderma, Systemic/enzymology* ; Fibroblasts/pathology* ; Apoptosis ; Skin/metabolism* ; Fibrosis ; Interleukin-6/metabolism* ; Caspase 3/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Male ; Female ; Cells, Cultured ; RNA, Messenger/metabolism* ; Middle Aged ; Adult ; Serine Endopeptidases/genetics*

Morphea is a rare, chronic inflammatory condition that affects the skin and subcutaneous tissues with an unclear etiology. Genetic predisposition, autoimmune dysregulation, and environmental factors play a role in its pathogenesis. It affects both adults and children and presents as erythematous patches or plaques that develop sclerotic centers with a violaceous border. Early diagnosis and treatment are crucial to minimize damage and physical sequelae.

We present here a 30-year old female who presented with a solitary, violet-hue in color, indurated plaque on her left forearm after wearing a metal smartwatch for 4 months. She experienced on and off episodes of overheating from the watch but continued wearing it. There was no associated pruritus, tenderness, or loss of sensation. Anti-dsDNA showed a borderline positive result. Vitamin D levels were below the lower limit revealing a severe Vitamin D deficiency. Dermoscopy revealed fibrotic beams, branching vessels and an erythematous to pink background. Histopathologic analysis showed superficial and deep perivascular and periadnexal infiltrates of lymphocytes and plasma cells with compact collagen bundles and notable loss of periadnexal fat. The patient was started on topical halobetasol then shifted to tacrolimus 0.01% and started on targeted NB-UVB. Excellent response was seen after 9 sessions of phototherapy. There was a decrease in induration, size and no further progression.

Morphea is a rare inflammatory condition without a clear etiology and early diagnosis and treatment are important. This case highlights the relationship between gadget trauma and the development of Morphea.

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.

Introduction: Morpheq, also known as localized scleroderma, describes a distinctive inflammatory skin disorder that ultimately leads to sclerosis. It is differentiated from systemic scleroderma by the absence of vasculopathy and organ involvement. Initial erythema may precede the sclerotic stage by a few months causing initial diagnostic confusion. High index of suspicion and knowledge of disease evolution are essential. We report a case of morphea and its progression, the diagnostic approach and the importance of early treatment and long-term monitoring. Case Summary: A 3l-year-old Filipino female who presented with multiple erythematous plagues on the trunk and extremities and arthralgia was initially diagnosed with cutaneous drug reaction. Prompt treatment led to partial relief of symptoms. However, two months later, eruption of multiple ivory-white small patches and plaques were noted on the same affected areas prompting an impression of morphea. Serum markers revealed elevated antinuclear antibody levels and negative anti-Scl70/anti-centromere serum autoantibodies. Skin biopsy showed homogenized thick dermal collagen bundles confirming the diagnosis of morphea. Topical therapy with calcipotriol + betamethasone dipropionate ointment showed remarkable improvement with decrease in erythema and softening of the lesions while adjunct narrowband-UVB phototherapy also provided relief due to its ability to reduce collagen synthesis and cytokine production. Conclusion Morphea may be easily misdiagnosed during the early stages especially if sclerosis ensues late in the disease. Characteristic clinical appearance of erythematous plaques with violaceous borders may not always be present. Histologic examination and serum autoantibodies help exclude other disorders with the same clinical and histopathological spectrum. Treatment is individualized depending on the severity and depth of skin involvement, early treatment and monitoring should be initiated before complications arise.
Scleroderma, Localized ; Fibrosis

OBJECTIVE: To investigate the expression and physiological significance of the ferroptosis marker 4-hydroxynonenal (4-HNE) in myofibroblasts induced by transforming growth factor-β1 (TGF-β1), providing theoretical evidence for its potential role in the diagnosis and treatment of fibrosis in systemic sclerosis (SSc). METHODS: Mouse embryonic fibroblasts (NIH3t3) were cultured and divided into two groups after 12 h of starvation: the control group (cultured in 1% serum-containing medium) and the TGF-β1 group (cultured in 10 μg/L TGF-β1 with 1% serum-containing medium). Cell morphology changes in both groups were observed under a microscope. To confirm successful establishment of the SSc cell model, fibrosis markers were analyzed using reverse transcription quantitative real-time PCR (RT-qPCR) and Western blot. Next, flow cytometry was employed to assess the intracellular levels of reactive oxygen species (ROS) in both groups. Finally, Western blot and immunofluorescence staining were used to measure the expression of 4-HNE in the TGF-β1-treated cells. RESULTS: Microscopic observations revealed that TGF-β1 treatment caused the NIH3t3 cells to transition from a typical spindle shape to a flat, polygonal shape with multiple protrusions, indicating fibroblast activation. The RT-qPCR and Western blot analyses showed that the expression of the fibrosis marker Vimentin was significantly upregulated in the TGF-β1 group compared with the control group (P < 0.01), confirming that TGF-β1 effectively promoted fibrosis-related gene and protein expression. Flow cytometry results indicated that TGF-β1 significantly elevated intracellular ROS levels, suggesting the induction of oxidative stress. Furthermore, both Western blot and immuno-fluorescence staining demonstrated a significant increase in 4-HNE expression in the TGF-β1-treated cells (immunofluorescence intensity P < 0.05). CONCLUSION TGF-β1 promotes fibroblast activation and fibrosis while inducing ROS production, leading to a marked increase in 4-HNE expression. Given the role of 4-HNE as a marker of lipid peroxidation and its elevated levels in the SSc cell model, this study suggests that 4-HNE could serve as a potential biomarker for fibrosis in SSc. The findings highlight the importance of investigating the mechanisms of 4-HNE in fibrosis and suggest that targeting this pathway could offer new therapeutic opportunities for treating SSc.
Animals ; Mice ; Scleroderma, Systemic/pathology* ; Aldehydes/pharmacology* ; Transforming Growth Factor beta1/metabolism* ; NIH 3T3 Cells ; Ferroptosis ; Reactive Oxygen Species/metabolism* ; Fibrosis ; Fibroblasts/metabolism* ; Biomarkers/metabolism* ; Myofibroblasts/metabolism*

OBJECTIVE: To comprehensively understand the COVID-19 vaccination and infection status among patients with systemic sclerosis (SSc). METHODS: We conducted a retrospective analysis of patients diagnosed with SSc who were hospitalized in the Rheumatology and Immunology Department of Peking University People' s Hospital from January 2016 to March 2023. We collected detailed clinical cha-racteristics, vaccination status, and infection details through a systematic review of medical records and telephone follow-ups with the SSc patients. RESULTS: Out of 236 identified patients, 99 SSc patients participated in the follow-up. This cohort included 41 patients with limited SSc, 28 with diffuse SSc, and 30 with SSc overlap syndromes. Treatments varied, with glucocorticoids administered to 57.58% of patients, immunosuppressants to 56.57%, biologic agents to 7.07%, and small molecule targeted therapies to 6.06%. Notably, 49 patients had received the COVID-19 vaccine. Between November 2022 and March 2023, a total of 81 patients contracted COVID-19. The infection rate among those who received three doses or more (19/29, 65.5%) was significantly lower compared with unvaccinated patients (45/50, 90.0%, P=0.007). Fourteen of these patients required hospitalization due to COVID-19. Furthermore, 26 patients reported exacerbation of SSc symptoms post-infection, which included severe manifestations, such as Raynaud phenomenon, skin lesions, fingertip ulcers, pulmonary hypertension, and interstitial lung disease. Compared with healthy cohabitants, the SSc patients exhibited more severe symptoms following COVID-19, including fever (36.71%) and fatigue (35.44%). Multivariate regression analysis identified subcutaneous calcinosis (OR=7.713, 95%CI: 1.142-45.051) and positivity for anti-centromere antibodies (OR=9.210, 95%CI: 1.211-70.028) as independent risk factors for hospitalization due to COVID-19. CONCLUSION Vaccination is both effective and safe in preventing COVID-19 among SSc patients. Additionally, it underscores that these patients experience exacerbation of their underlying disease and more severe COVID-19 symptoms compared with individuals without underlying conditions. Thus, proactive prevention, continuous monitoring, and early treatment of COVID-19 are of significant importance for the health and well-being of SSc patients. Timely interventions can help mitigate the impact of infections and improve overall patient outcomes.
Humans ; COVID-19/epidemiology* ; Scleroderma, Systemic/complications* ; COVID-19 Vaccines/administration & dosage* ; Retrospective Studies ; Male ; Female ; Middle Aged ; SARS-CoV-2 ; Vaccination ; Immunosuppressive Agents/therapeutic use* ; Cohort Studies

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