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Briefly Noted

Transforming growth factor-β in Marfan syndrome, rituximab for hepatitis C–related vasculitis, and ichthyosis in newborns

IMPROVING THE OUTCOME FOR PATIENTS WITH MARFAN SYNDROME

Marfan syndrome (MFS) is an autosomal dominant genetic disorder caused by mutations in FBN1, which encodes fibrillin 1. Beyond the defects in connective tissues, the major cause of morbidity and mortality in patients with this condition is aortic root dilatation, and MFS pathogenesis has been demonstrated to involve disordered transforming growth factor-β (TGF-β) activation and signaling. Investigators studied the effect of beta-blockers and the angiotensin-receptor blocker losartan in a mouse model of MFS and in human patients^1,2. Losartan decreased the occurrence of aortic root dilatation in the mouse model, and in humans, TGF-β concentrations were significantly lower in losartan or beta-blocker recipients than in nonrecipients.

Bottom line: This study is important because it demonstrates that knowledge of a disease's pathogenesis allows physicians to identify therapies that might improve patient outcomes.

— Jeffrey P. Callen, MD

RITUXIMAB IS USEFUL ADJUNCTIVE THERAPY FOR HEPATITIS C VIRUS–RELATED VASCULITIS

Interferon and ribavirin are used to manage hepatitis C virus–related vasculitis, but about 40% of patients fail to have a sustained response. Because this vasculitis is caused by B-cell activation, researchers evaluated the efficacy of treatment with rituximab, an anti-CD20 monoclonal antibody. In this relatively small study³ of 32 patients, 20 received rituximab along with antiviral therapy and 12 received rituximab alone. Both groups responded, but clinical response was better in those receiving combined therapy (80% vs. 59% had complete response, and 15% vs. 9% had partial response). Relapses were associated with a lack of virologic control. No safety signals appeared in rituximab recipients.

Bottom line: Rituximab is a useful adjunctive therapy, but employed alone without virologic control, it might be insufficient to completely control the vasculitis.

— Jeffrey P. Callen, MD

ICHTHYOSIS IN THE NEWBORN

Diagnosing ichthyosis in the newborn is often challenging. The authors of a recent article⁴ describe a new form of autosomal recessive congenital ichthyosis caused by mutations in the fatty acid transport protein 4 (FATP4) gene. The gestation of these children is complicated by polyhydramnios and prematurity; the newborn is covered with thick caseous debris, not a collodion membrane, and respiratory complications are frequent. After a few months, ichthyosis is mild, and there is no internal disease. The bedside pearl is that in biopsy exams, oil red O staining shows numerous lipid droplets in the epidermis of patients but few in healthy control skin, whereas immunostaining with a FATP4 antibody is strongly expressed in normal skin but is absent in patient samples.

Bottom line: When patients present with a rare condition, to them it is their very familiar disease. This is an example of how the phenotype of congenital ichthyoses can change over time.

— Lowell A. Goldsmith, MD, MPH

Published in Journal Watch Dermatology October 30, 2009

Citation(s):

1. Matt P et al. Circulating transforming growth factor-β in Marfan syndrome. Circulation 2009 Aug 11; 120:526.

• Original article (Subscription may be required)
• Medline abstract (Free)

2. Braverman AC. Transforming growth factor-β: A biomarker in Marfan syndrome? Circulation 2009 Aug 11; 120:464.

• Original article (Subscription may be required)
• Medline abstract (Free)

3. Terrier B et al. Efficacy and tolerability of rituximab with or without PEGylated interferon alfa-2b plus ribavirin in severe hepatitis C virus–related vasculitis: A long-term followup study of thirty-two patients. Arthritis Rheum 2009 Aug; 60:2531.

• Medline abstract (Free)

4. Klar J et al. Mutations in the fatty acid transport protein 4 gene cause the ichthyosis prematurity syndrome. Am J Hum Genet 2009 Aug 14; 85:248.

• Medline abstract (Free)