Faculty Bibliography

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 favorable 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 1-2g/day and may be titrated up to 10g/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.

Calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome is a form of a rare, clinical subtype of systemic sclerosis, known as limited systemic sclerosis. Limited systemic sclerosis, including CREST syndrome, manifests as fibrotic skin changes restricted to the hands and face, with vascular, musculoskeletal, and visceral involvement. We present a case of a 75-year-old woman with a longstanding history of CREST syndrome complicated by a digital ulceration and persistent pain associated with recalcitrant Raynaud phenomenon. After failing a number of first-line pharmacologic therapies such as diltiazem, sildenafil, and topical nitropaste, the patient was started on a trial of botulinum toxin for the left second digit, with 10 unit injections into both webspaces for a total of 20 units. Following injection, the patient reported no further baseline pain in the affected finger and an over fifty-percent improvement in discomfort with manipulation of the digit at a follow-up time of one week. The ulceration started healing within the following three weeks. This result was maintained at a follow-up time of six weeks.

BACKGROUND:Multiple placebo controlled trials have assessed locally applied topical nitrate preparations in treating Raynaud's phenomenon (RP). OBJECTIVES/OBJECTIVE:The objective of this meta-analysis was to assess the effects of local topical nitrates in primary and secondary RP with respect to a combined endpoint integrating parameters of digital blood flow and clinical severity. METHODS:A systematic review was performed using MEDLINE, Embase and the Cochrane library. Only trials comparing locally applied topical nitrates to placebo comparators were included. Studies were appraised for bias by two independent reviewers. RESULTS:Seven placebo controlled trials including 346 patients were used in meta-analysis. Four trials used nitroglycerin ointments, two used MQX-503 and one used compounded nitrite. Meta-analysis results support a moderate to large treatment effect in Raynaud's phenomenon, standardized mean difference (SMD)=0.70, (0.35 to 1.05, p<0.0001). Subgroup analyses showed a large treatment effect in secondary RP, SMD=0.95 (0.25 to 1.65, p=0.008) and moderate effect in primary RP, SMD=0.45 (0.05 to 0.85, p=0.03). LIMITATIONS/CONCLUSIONS:Limitations include the inclusion of multiple topical nitrate preparations and integration of different outcomes assessments. CONCLUSION/CONCLUSIONS:Local topical nitrates have significant efficacy in the treatment of both primary and secondary Raynaud's phenomenon.

Anetoderma is a rare benign elastolytic disorder that is characterized by focal loss of elastin fibers on histopathology and is often recalcitrant to treatment. We present a case of a patient with a 20-year history of pruritic and painful hyperpigmented atrophic papules clustered on the neck, axillae, inframammary folds, and right medial thigh. Although the histopathologyof her axillary lesions was consistent with anetoderma, her clinical presentation is unusual given the extent of involvement, reported pain and pruritus, and sharp demarcation of the distribution. The diagnosticuncertainty of this case led to added difficulty in management of a disease that is already notoriously difficult to treat and may significantly impact patient's quality of life.

Lichen myxedematosus is condition characterized by localized areas of dermal deposition of mucin, presenting with firm papules localized to few areas of the body. The condition needs to be excluded from scleromyxedema, which, in addition to the firm papular eruption, has areas of induration and is usually associated with a monoclonal gammopathyand systemic symptoms. We present a 62-year-old woman with a several-year history of asymptomatic, firm papules over the face and arms with no evidence of thyroid disease or a monoclonal gammopathy,which is consistent with a diagnosis of localized lichen myxedematosus, the discrete papular variant. The patient is being treated with a topical calcineurininhibitor.