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: 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*

OBJECTIVE: To study the preventive and therapeutic effects of safflower water extract on systemic scleroderma (SSc) in mice and its mechanism. METHODS: Sixty BALB/C mice were randomly divided into the control group, model group, prednisone group and safflower low, middle, high dose groups, 10 mice in each group.The control group was injected with normal saline, and the other five groups were subcutaneously injected with bleomycin hydrochloride with 100 μl at the concentration of 200 μg /ml on the back, once a day for 28 days to establish the SSc models.At the same time, the control group and model group were treated with normal saline (10 ml/kg), the prednisone group was treated with prednisone 4.5 mg/kg (10 ml/kg), and the low, middle, and high dose safflower groups were treated with safflower at the doses of 1.5, 3, 6 g/kg (10 ml/kg), and all groups were treated for 28 days.After 28 days, all mice were decapitated. The blood samples and back skin of the BLM injection part were collected.After that, all the tissue slices were taken to measure the dermal thickness, and the content of hydroxyproline (HYP) in the skin tissues was detected by hydrolysis method.The contents of tissue growth factor (CTGF) and transforming growth factor-β (TGF-β ) in the skin tissues and the levels of interleukin-6 (IL-6) and interleukin-17 (IL-17) in serum were determined by ELISA. RESULTS: Compared with the control group, the dermal thickness of the model group was increased(P＜0.05), the contents of CTGF, TGF-β and HYP in the skin tissues and the levels of IL-6 and IL-17 in the serum of the model group were increased(P＜0.05); compared with the model group, the dermal thickness in the prednisone group and safflower groups was decreased (P＜0.05), the levels of CTGF, TGF-β and HYP in the skin tissues and the serum levels of IL-6 and IL-17 in the prednisone group and safflower groups were decreased (P＜0.05). CONCLUSION Safflower water extract can improve skin condition (or dermal thickness) in SSc mice, and its mechanism may be related to reducing immune inflammatory response.
Animals ; Bleomycin ; Carthamus tinctorius ; chemistry ; Connective Tissue Growth Factor ; metabolism ; Disease Models, Animal ; Hydroxyproline ; analysis ; Interleukin-17 ; metabolism ; Interleukin-6 ; metabolism ; Mice ; Mice, Inbred BALB C ; Plant Extracts ; pharmacology ; Random Allocation ; Scleroderma, Systemic ; drug therapy ; Skin ; pathology ; Transforming Growth Factor beta1 ; metabolism

CD146 Antigen ; immunology ; Fibroblasts ; immunology ; pathology ; Humans ; Scleroderma, Systemic ; drug therapy ; immunology ; pathology

Systemic sclerosis is a connective tissue disease characterized by alterations in microvascular structure and function. In these patients, numerous studies have demonstrated a relationship between capillary morphology and peripheral blood perfusion. Nailfold videocapillaroscopy reveals the peripheral microvascular morphology and thus allows classification and scoring of capillary abnormalities with respect to different microangiopathy patterns (early, active, and late). Laser Doppler flowmetry and laser speckle contrast analysis can be used to estimate cutaneous blood flow through microvessels and to assess and quantify blood perfusion at peripheral sites. These two methods are also used to identify changes in digital blood perfusion after the infusion of vasodilators.
Blood Flow Velocity ; Humans ; *Laser-Doppler Flowmetry ; *Microcirculation ; Microscopic Angioscopy/*methods ; Microvessels/*pathology/*physiopathology ; Nails ; Predictive Value of Tests ; Regional Blood Flow ; Scleroderma, Systemic/*diagnosis/pathology/physiopathology ; Skin/*blood supply ; Vasodilator Agents/diagnostic use ; *Video Recording

Lysophosphatidic acid (LPA) is a signaling lipid that binds to six known lysophosphatidic acid receptors (LPARs), named LPA1-LPA6. These receptors initiate signaling cascades relevant to development, maintenance, and healing processes throughout the body. The diversity and specificity of LPA signaling, especially in relation to cancer and autoimmune disorders, makes LPA receptor modulation an attractive target for drug development. Several LPAR-specific analogues and small molecules have been synthesized and are efficacious in attenuating pathology in disease models. To date, at least three compounds have passed phase I and phase II clinical trials for idiopathic pulmonary fibrosis and systemic sclerosis. This review focuses on the promising therapeutic directions emerging in LPA signaling toward ameliorating several diseases, including cancer, fibrosis, arthritis, hydrocephalus, and traumatic injury.
Arthritis ; Autoimmune Diseases ; Fibrosis ; Hydrocephalus ; Idiopathic Pulmonary Fibrosis ; Pathology ; Pharmacology ; Receptors, Lysophosphatidic Acid ; Scleroderma, Systemic ; Sensitivity and Specificity

Uncontrolled fibrosis of skin and internal organs is the main characteristic of scleroderma, and collagen is a major extracellular matrix protein that deposits in the fibrotic organs. As the chaperone of collagen, heat shock protein 47 (HSP47) is closely related with the development of fibrosis. To explore the potential function of HSP47 in the pathogenesis of scleroderma, the clinical, in vivo and in vitro studies were performed. In clinical, the increased mRNA level of HSP47 was observed in the skin fibroblasts and PBMC from scleroderma patients, and the enhanced protein level of HSP47 was also detected in the skin biopsy and plasma of the above patients. Unexpectedly, the enhanced levels of HSP47 were positively correlated with the presence of anti-centromere antibody in scleroderma patients. Moreover, a high expression of HSP47 was found in the skin lesion of BLM-induced scleroderma mouse model. Further in vitro studies demonstrated that HSP47 knockdown could block the intracellular and extracellular collagen over-productions induced by exogenous TGF-β. Therefore, the results in this study provide direct evidence that HSP47 is involved in the pathogenesis of scleroderma. The high expression of HSP47 can be detected in the circulatory system of scleroderma patients, indicating that HSP47 may become a pathological marker to assess the progression of scleroderma, and also explain the systemic fibrosis of scleroderma. Meanwhile, collagen over-expression is blocked by HSP47 knockdown, suggesting the possibility that HSP47 can be a potential therapeutic target for scleroderma.
Adolescent ; Adult ; Animals ; Biopsy ; Blotting, Western ; Cells, Cultured ; Collagen ; metabolism ; Female ; Fibroblasts ; drug effects ; metabolism ; Fibrosis ; HSP47 Heat-Shock Proteins ; blood ; genetics ; metabolism ; Humans ; Leukocytes, Mononuclear ; metabolism ; Male ; Mice ; Mice, Inbred C3H ; Middle Aged ; NIH 3T3 Cells ; Protein Binding ; RNA Interference ; Reverse Transcriptase Polymerase Chain Reaction ; Scleroderma, Systemic ; blood ; genetics ; metabolism ; Skin ; metabolism ; pathology ; Transforming Growth Factor beta ; pharmacology ; Young Adult

Female ; Humans ; Middle Aged ; Sarcoidosis ; diagnosis ; pathology ; Scleroderma, Systemic ; diagnosis ; pathology

Systemic sclerosis (SSc) is a chronic systemic disease that affects the skin, lungs, heart, gastrointestinal tract, kidneys, and musculoskeletal system. Although up to 90% of patients with scleroderma have been estimated to have gastrointestinal involvement, liver disease has been reported only rarely. A 51-year-old woman was hospitalized due to esophageal variceal bleeding. Her serum was positive for anti-nuclear antibody and anti-centromere antibody. Sclerodactyly was noted on both hands, and she had recently developed Raynaud's syndrome. Punch biopsy of the hand showed hyperkeratosis, regular acanthosis, and increased basal pigmentation in the epidermis, and thick pale collagenous bundles in the dermis. Liver biopsy showed chronic active hepatitis with bridging fibrosis. Consequently, she was diagnosed with liver cirrhosis due to autoimmune hepatitis (AIH) combined with SSc. AIH had subsided after administration of prednisolone at 40 mg per day. She received 5-10 mg/day of prednisolone as an outpatient, and her condition has remained stable. Patients with either AIH or SSc should be monitored for further development of concurrent autoimmune diseases. The early diagnosis of AIH combined with SSc will be helpful in achieving optimal management.
Anti-Inflammatory Agents/therapeutic use ; Antibodies, Antinuclear/blood ; Esophageal and Gastric Varices ; Female ; Gastrointestinal Hemorrhage ; Hepatitis, Autoimmune/complications/*diagnosis/drug therapy ; Humans ; Liver Cirrhosis/*diagnosis/etiology/pathology ; Middle Aged ; Prednisolone/therapeutic use ; Raynaud Disease/diagnosis ; Scleroderma, Systemic/complications/*diagnosis ; Skin/pathology

Actins ; metabolism ; Adult ; Amyloidosis ; pathology ; Diagnosis, Differential ; Female ; Humans ; Intestinal Pseudo-Obstruction ; metabolism ; pathology ; Lupus Erythematosus, Systemic ; pathology ; Muscular Atrophy ; pathology ; Scleroderma, Systemic ; pathology ; Young Adult