Chelating agents
These agents may improve the fibrotic aspects of systemic sclerosis.
Penicillamine (Cuprimine, Depen)
Penicillamine inhibits the formation of mature collagen crosslinks, rendering un-crosslinked molecules more susceptible to proteolytic degradation. The inhibition of collagen crosslink formation very likely causes a marked decrease in tissue stiffness, an important profibrotic mechanism.
Related Questions:
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Tightening of the skin in the face, with a characteristic beaklike facies and paucity of wrinkles.
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Sclerodactyly with digital ulceration, loss of skin creases, joint contractures, and sparse hair.
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Anterior chest demonstrating salt-and-pepper hypopigmentation and diffuse hyperpigmentation in a white woman.
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A radiograph of the distal digits demonstrating calcinosis and distal phalanx reabsorption (acral osteolysis).
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Fingernail capillary bed demonstrating capillary dropout with large dilated vessels.
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Lung biopsy demonstrating severe interstitial fibrosis and medial fibrosis and smooth muscle hyperplasia of a pulmonary arteriole compatible with pulmonary hypertension.
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Lung biopsy demonstrating expansion of the interstitium of the lung by fibrous tissue along with chronic inflammatory cells.
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Barium swallow demonstrating reflux into the distal esophagus, as well as an accordion appearance in the duodenum.
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Skin biopsy showing extensive fibrosis. The biopsy has a square morphology, which reflects the rigidity of the tissue biopsy specimen due to striking pan-dermal sclerosis. In addition, the fibrosing reaction extends into the panniculus. The number of adnexal structures is reduced, another characteristic feature of scleroderma. A significant inflammatory cell infiltrate is not observed. This is in contradistinction to morphea, in which a prominent inflammatory cell infiltrate is present.
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Skin biopsy showing severe fibrosis. The fibrosis reflects a widening of collagen bundles in concert with an increase in the number of collagen fibers. Note the superimposed deposition of the newly synthesized delicate collagen bundles interposed between the preexisting collagen bundles, the latter appearing wide and manifesting a hyalinized morphology.
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Overall scheme illustrating a current understanding of SSc pathogenesis. Hypothetical sequence of events involved in tissue fibrosis and fibroproliferative vasculopathy in SSc. An unknown causative agent induces activation of immune and inflammatory cells in genetically predisposed hosts resulting in chronic inflammation. Activated inflammatory and immune cells secrete cytokines, chemokines, and growth factors which cause fibroblast activation, differentiation of endothelial and epithelial cells into myofibroblasts, and recruitment of fibrocytes from the bone marrow and the peripheral blood circulation. The activated myofibroblasts produce exaggerated amounts of ECM resulting in tissue fibrosis.
Tables
Sergio A Jimenez, MD, MACR, FACP, FRCP(UK Hon) Professor and Director, The Scleroderma Center; Co-Director, Jefferson Institute of Molecular Medicine; Director, Division of Connective Tissue Diseases, Jefferson Medical College of Thomas Jefferson University
Sergio A Jimenez, MD, MACR, FACP, FRCP(UK Hon) is a member of the following medical societies: Royal College of Physicians, American Society for Biochemistry and Molecular Biology, American College of Physicians, American College of Rheumatology, Society for Investigative Dermatology
Disclosure: Nothing to disclose.
Fabian A Mendoza, MD, FACR Assistant Professor of Medicine, Division of Rheumatology, Jefferson Medical College and Jefferson Institute of Molecular Medicine; Associate Director of The Scleroderma Center, Director of Scleroderma Program, Thomas Jefferson University
Fabian A Mendoza, MD, FACR is a member of the following medical societies: American College of Rheumatology
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Elliot Goldberg, MD Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Lewis Katz School of Medicine at Temple University
Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology
Disclosure: Nothing to disclose.
Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital
Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa
Disclosure: Nothing to disclose.
John Varga, MD Professor, Department of Internal Medicine, Division of Rheumatology, Northwestern University
John Varga, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, Central Society for Clinical and Translational Research, Society for Investigative Dermatology
Disclosure: Nothing to disclose.
Patrick M Cronin, DO, FACR Clinical Associate Professor of Medicine, Department of Medicine, Division of Rheumatology, University of Pennsylvania Health System, Pennsylvania Hospital
Patrick M Cronin, DO, FACR is a member of the following medical societies: American College of Rheumatology, American Osteopathic Association, and Pennsylvania Medical Society
Disclosure: Nothing to disclose.
Andrew S Koenig, DO Consulting Staff, Division of Rheumatology, Rancoccas Hospital
Andrew S Koenig, DO is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American College of Rheumatology, and American Osteopathic Association
Disclosure: Nothing to disclose.
Marie Spevak O'Brien, DO Assistant Clinical Professor of Medicine, Arthritis and Rheumatology, Lehigh Valley Physician Group
Marie Spevak O'Brien, DO is a member of the following medical societies: American College of Physicians, American College of Rheumatology, American Medical Association, American Osteopathic Association, International Society for Clinical Densitometry, and Pennsylvania Medical Society
Disclosure: Nothing to disclose.
Acknowledgments
The assistance of Kenneth Brown in the preparation of this manuscript is gratefully acknowledged.
Sergio A Jimenez, MD, was recipient of NIH/NIAMS grant #RO-1 AR19616.