Scleredema adultorum of Buschke is a rare disorder of the connective tissue that involves a non-pitting and progressive expansion of the skin due to the buildup of glycosaminoglycans and collagen in the dermis layer. This disorder is commonly seen in association with other diseases such as diabetes mellitus and paraproteinemia. Protheragen is actively involved in the preclinical development of novel therapies aimed at rare connective tissue disorders, including Scleredema adultorum of Buschke.
Introduction to Scleredema Adultorum of Buschke
Scleredema adultorum of Buschke is considered a rare and inflammatory skin disorder of which the incidence is largely unknown. The skin is uniformly thickened and the area around the mouth and neck becomes involved. The skin thickening can also extend to the rest of the body, including the upper arms and thighs. Unlike many other conditions that can lead to skin thickening, the patient does not have pitting. The condition is traditionally classified into three different forms which include: an infection type which occurs after an infection, a type that occurs with paraproteinemia, and a type that occurs with diabetes mellitus.
Fig.1 Histopathological image showing the normal epidermis with mild hyperkeratosis. (Patel
et al., 2023)
Pathogenesis of Scleredema Adultorum of Buschke
In scleredema, the pathogenesis is caused by a severe modification of the extracellular matrix in the dermis. The defect in scleredema is predominantly connected to the excessive production and retention of glycosaminoglycans (GAGs) like hyaluronic acid, as well as excessive collagen by dermal fibroblasts. This scleredema undergoes a change and is considered to be a reactive response to some other systemic condition. As an example, in the case of diabetes, chronic elevated blood glucose levels and inflammation could become a stimulus for fibroblasts through some mechanism linked to TGF-β, resulting in heightened production of GAGs and collagens. This phenomenon leads to the indurated thickened skin changes, but how exactly the systemic condition triggers dermal changes is still being studied.
Therapeutics Development for Scleredema Adultorum of Buschke
| Therapeutic Strategy |
Therapeutic Target |
Mechanism of Action |
Development Stage |
| IVIG |
FcγR / Complement C3 |
Complete remission in streptococcal-triggered SAB; neutralizes autoantibodies |
Phase II |
| Mycophenolate |
IMPDH inhibition |
Combined with IVIG achieves major skin softening; suppresses T/B-cell proliferation |
Phase II |
| Recombinant Factor XIII |
Fibrin crosslinking enzyme |
Enhances skin elasticity and joint function; promotes collagen breakdown |
Preclinical |
| Fresolimumab |
TGF-β1/2/3 |
Inhibits SMAD2/3 phosphorylation and collagen deposition in preclinical models |
Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen offers an integrated approach to scleredema therapeutic development, providing comprehensive preclinical solutions that set us apart in the industry. Our specialists use sophisticated platforms for expedited drug development, working in synergy with advanced therapeutic and advanced disease models.
Therapeutics Development Platforms for Scleredema Adultorum of Buschke
Disease Model Development for Scleredema Adultorum of Buschke
Protheragen develops scleredema pathology-relevant 2D cell models, 3D skin models, and animal models that accurately reflect the accumulation of glycosaminoglycans and collagen, along with the subsequent dermal induration. Our models are specifically designed to recapitulate disease triggers and pathways to advance dermatology-focused therapeutic discovery.
2D Cell Models & 3D Skin Models
- Type I/III collagen-overproducing dermal cell lines
- Mucin-rich 3D fibroblast-keratinocyte co-cultures
- Stratified scleredema skin equivalent
- Paraprotein-exposed dermal organoid
Animal Models Development
- Monoclonal gammopathy-associated mouse
- Collagen fibrillogenesis-defective rat
- Zebrafish has2 overexpression model
- Post-infectious swine model
DMPK Services and Drug Safety Evaluation
Protheragen offers comprehensive DMPK and drug safety evaluation services, specifically designed to accelerate the preclinical development of novel therapies for scleredema adultorum of Buschke. We are committed to generating robust data to support the efficacy and safety of your innovative drug candidates.
In Vitro ADME Services
- Metabolic Stability
- Reaction Phenotyping
- CYP450 Inhibition/Induction
- Blood/Plasma Partitioning
As a preclinical research service provider focused on rare dermatological and connective tissue disorders, Protheragen accelerates therapeutic development for systemic conditions like scleredema adultorum of Buschke. We provide target validation, scleredema-specific disease modeling, drug safety evaluation and DMPK services.
Contact us to explore how our end-to-end solutions can advance your research.
References
- Patel, D. R., et al. "Scleredema Adultorum of Buschke Associated with Diffuse Eosinophilia and Hepatitis B Virus Infection." Cureus 15.4 (2023): e38300.
- Pfeiffer, C., and C. Sunderkotter. "[Differential Diagnosis of Sclerosing Skin Diseases: Scleredema Adultorum of Buschke]." Dermatologie (Heidelb) 75.3 (2024): 232-36.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
