New Understanding of Skin Hardening Syndromes Found PDF Print E-mail
Thursday, 19 May 2011 09:52
New details about the underlying mechanisms of skin hardening syndromes, morphea, have been discovered by researchers from Boston University School of Medicine (BUSM). Morphea, also known as localized scleroderma, is a disorder characterized by excessive collagen deposition leading to thickening of the dermis, subcutaneous tissues, or both.

Thomas Ruenger, MD, PhD, a professor and vice-chair of dermatology at BUSM, and colleagues connected pharmacological properties of the Novartis Pharma AG drug called balicatib to the skin disorder for the first time after investigating adverse reactions suffered by patients participating in a clinical trial for the treatment of osteoporosis. The team’s findings appear online in the Journal of the American Academy of Dermatology.

Morphea is rare. The estimated incidence is approximately 25 cases per million population per year. Drug-induced morphea is even rarer as noted by Oliver Kraigher, MD and colleagues in their 2009 Archives of Dermatology article, “To our knowledge, only 10 cases of drug-associated morphea have been reported, induced by vitamin K1 (phytonadione), vitamin B12 (cyanocobalamin), penicillamine, bromocriptine, pentazocine, 5-hydroxytryptophan/carbidopa combination, and balicatib. In half of these cases, partial or complete response was achieved after the drug treatment was stopped.”

Balicatib was developed recently as an osteoporosis drug that can inhibit CathepsinK (catK), an enzyme involved with bone degradation. A phase II study of balicatib in women with postmenopausal osteoporosis showed dose-dependent reduction in levels of bone resorptive markers and an increase in bone mineral density, but a small number of patients developed morphealike skin changes.

Most of the patients in the balicatib trial who experienced the morphea skin changes did so in the neck, chest and abdomen regions.

Balicatib is lysosomotropic and can accumulate in lysosomes with a high enough concentration to cause off-target inhibition of other types of cathepsins, some of which are expressed by skin fibroblasts.

After examining the cases and relating them to recent reports of cathepsin K expression in the skin and the role of cathepsin K in degrading collagen and elastin, the investigators determined that the changes were a direct effect of the drug.

This case study proves that catK affects the skin as well as bones, and marks the first time that skin hardening can be convincingly linked to the pharmacologic properties of a drug.

"This observation emphasizes the importance of intracellular collagen degradation in the skin, a pathway so far vastly underappreciated," said Thomas Ruenger, MD, PhD, a professor and vice-chair of dermatology at BUSM. "This observation also sheds new light on our understanding of the mechanisms involved in morphea, or skin hardening. Failed collagen degradation has so far not been thought to cause morphea."

The researchers believe these findings have far-reaching implications for osteoporosis patients and those suffering from skin hardening syndromes.

Source: Bates, R. (2011), "New Understanding of Skin Hardening Syndromes Found"; source article can be viewed here.
 
More articles :

» Scientists Identify New Genetic Region Associated with Scleroderma

New research supported, in part, by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) has identified a new genetic link to systemic sclerosis (also known as systemic scleroderma) and confirmed three previously...

» Systemic Sclerosis Sine Scleroderma

HADI POORMOGHIM, MARY LUCAS, NOREEN FERTIG, and THOMAS A. MEDSGER, JR.ARTHRITIS & RHEUMATISM Vol. 43, No. 2, February 2000, pp 444–451 © 2000, American College of RheumatologyObjectiveTo describe the demographic, clinical, and laboratory...

» Insights on Autoimmune Diseases and their Impact on Women

In a recent press release by the , Dr. Vivian Pinn discussed the latest research on autoimmune diseases in two podcasts with Dr. Robert Carter. Your body's immune system protects you from disease and infection. But if you have an autoimmune disease,...

» Endothelin Drugs Benefit Those With Pulmonary Hypertension

Breaking news from has reported that recent research to block the effects of endothelin, a powerful substance that constricts blood vessels and stimulates cell growth, has led to successful treatment of and provides hope for treating other chronic...

» Thank You

The Scleroderma Care Foundation launched its one month ago on September 1st, and we did so with several aims in mind. Firstly we sought to provide patients, their families, and friends with relevant and timely information on Scleroderma, tips for...

» New Study Will Explore Impact of Exercise on Pulmonary Hypertension

For sufferers of Pulmonary Arterial Hypertension (PAH), maintaining healthy heart function isn't as simple as going for a jog every morning. Patients need to do all they can to slow damage to their heart, and exercise can improve potentially improve...