Part I: Epidemiology, Pathophysiology, and Clinical Considerations of Primary and Secondary Raynaud's Phenomenon.

Raynaud's Phenomenon is a relatively common disease with both primary and secondary forms. It is well understood as a vasospastic condition affecting the acral and digital arteries resulting in characteristic, well-demarcated color changes typically in the hands and feet in response to cold or stress. Secondary RP has been described in association with a variety of rheumatologic and non-rheumatologic diseases, environmental exposures, and/or medications. While both primary and secondary RP may impact quality of life, SRP may lead to permanent and potentially devastating tissue destruction when undiagnosed and untreated. It is therefore crucial for dermatologists to distinguish between primary and secondary disease forms early in clinical evaluation, investigate potential underlaying causes, and risk stratify SRP patients for the development of associated ACTD. The epidemiology, pathogenesis, and clinical presentation and diagnosis of both forms of Raynaud's Phenomenon are described in detail in this review article.

Part II: The Treatment of Primary and Secondary Raynaud's Phenomenon.

Raynaud's Phenomenon presents with either primary or secondary disease, of which both have the potential to negatively impact patient quality of life. First-line management of RP should include lifestyle modifications in all patients. Some patients with primary RP and most with secondary RP require pharmacologic therapies which may include CCBs, topical nitrates, PDE-5 inhibitors, or endothelin antagonists. Additional approaches to treatment for those with signs of critical ischemia or those who fail pharmacologic therapy include botulinum toxin injection and digital sympathectomy. Herein, we describe in detail the treatment options for patients with RP, as well as provide treatment algorithms for each RP subtype.

The clinical effects of l-arginine and asymmetric dimethylarginine: implications for treatment in secondary Raynaud's phenomenon.

Secondary Raynaud's phenomenon (RP) is often the sentinel clinical finding in systemic sclerosis and may precede systemic disease by several years. Altered nitric oxide metabolism plays a critical role in both fibrosis and severe secondary RP phenotypes in these patients. Increased flux through inducible nitric oxide synthase (iNOS) drives cutaneous fibrosis. Failure of flux through endothelial nitric oxide synthase (eNOS) contributes to increased vasoconstriction and decreased vasorelaxation. The underproduction of nitric oxide by eNOS is in part due to increased levels of asymmetric dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase. The inhibitory effects of increased ADMA levels may be counteracted increasing serum l-arginine, which is often an effective treatment strategy in these patients. As such, l-arginine-based therapies should be considered in managing secondary RP, particularly given their favourable safety and tolerability profile. While there is no established dosing regimen, studies of oral l-arginine in secondary RP suggest that divided dosing may begin at 1-2 g/day and may be titrated up to 10 g/day. Conversely, primary RP is not associated with increased ADMA production which likely accounts for the failure of l-arginine trials to show benefit in primary RP.

Eczematous reaction to IVIG for the treatment of dermatomyositis.

The use of high-dose intravenous immunoglobulin (IVIG) is an accepted therapy for patients with refractory dermatomyositis. Cases of eczematous reactions to IVIG have been reported in the literature, but to our knowledge, none in patients being treated for dermatomyositis. We report on the cases of two female patients with refractory dermatomyositis who developed pruritic, scaly pink plaques after receiving high-dose IVIG. This diffuse eczematous skin reaction to high-dose IVIG is a rare adverse event that most often occurs days after administration of therapy. Practitioners should be aware of this entity because the eczematous eruption may be extensive and can commonly worsen with subsequent re-exposure to IVIG.