Advanced Raynaud’s disease: A vascular medicine-initiated team-based approach and nationwide cohort analysis

Raynaud’s phenomenon (RP) reflects episodic digital vasospasms primarily related to cold exposure. Primary Raynaud’s is a relatively common ailment without a clear cause, affecting close to 5% of the general population, but is generally self-limited and does not result in tissue loss. ¹ However, secondary Raynaud’s is often associated with a more severe clinical sequelae driven by an underlying process, most commonly a connective tissue disorder, and can result in digital ulceration or gangrene in the most advanced forms. ² Conservative measures and oral vasodilators are the mainstay of therapy for RP; however, there are little data, guidance, or understanding of practices for more severe cases of RP.^3,4

To further evaluate practice patterns for patients with severe RP, we analyzed all hospitalized patients with a diagnosis of RP in the Nationwide Readmission Database (NRD) from 2016 to 2020 to evaluate associations and outcomes in a nationwide cohort (see online supplemental material). Additionally, with institutional review board approval, we reviewed an internal registry of hospitalized patients evaluated by our multidisciplinary team, which was formed in 2020. Consults are placed to the vascular medicine consult service and additional members of the team, including rheumatology, hand surgery, and pulmonary hypertension, are involved on the specific patient’s needs. Patients were included in this analysis if vasospasm was clinically believed to be a significant component of their digital ischemia.

In a review of the NRD, 4056 patients were admitted with a diagnosis of RP. Baseline characteristics and outcomes are noted in Table 1. The majority had an underlying connective tissue disease (69.8%) and a high prevalence of cardiovascular risk factors including tobacco use (41.3%), hypertension (36.1%), and diabetes mellitus (20.9%). Angiograms were rarely performed, particularly of the upper extremities. Sympathectomy was performed in only 1% of patients. Hand/finger amputation occurred in 8.7% and foot/toe amputation in 9.7%. After performing multivariable logistic regression, factors associated with amputation included diabetes, peripheral artery disease, tobacco use, anemia, hypertension, and CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia syndrome) (online supplemental Table 1).

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Table 1.

Demographics and disease characteristics of patients admitted with Raynaud’s phenomenon in the Nationwide Readmissions Database from 2016 to 2020 (N = 4056).

Characteristic	n (%)
Age, years, mean ± SD	57.1 ± 16.64
Female sex	3049 (75.2)
Comorbidities
Systemic sclerosis (including CREST)	1159 (28.6)
CREST syndrome	326 (8.0)
SLE	765 (18.9)
RA	445 (11.0)
Sjogren	181 (4.5)
MCTD	244 (6.0)
Cryoglobulinemia	38 (0.9)
Acute embolism / thrombosis of UE	58 (1.4)
Peripheral vascular disease	1189 (29.3)
Myocardial infarction	131 (3.2)
CVA (ischemic)	72 (1.8)
Tobacco use	1674 (41.3)
Alcohol use	149 (3.7)
Illicit drug use	289 (7.1)
Arterial hypertension	1466 (36.1)
Diabetes mellitus
Uncomplicated	158 (3.9)
Complicated	674 (16.6)
Chronic lung disease	933 (23.3)
Renal failure	840 (20.7)
Liver disease	232 (5.7)
Coagulopathy	384 (9.5)
Anemia	1288 (31.8)
Solid tumor without metastasis	119 (2.9)
Metastatic cancer	75 (1.8)
Hypothyroidism	702 (17.3)
Fluid or electrolyte disorders	1446 (35.7)
Unintentional weight loss	706 (17.4)
HIV / AIDS	12 (0.3)
Neurological disorders	345 (8.5)
Paralysis	99 (2.4)
Depression	671 (16.5)
Outcomes
Upper-extremity angiogram	125 (3.1)
Lower-extremity angiogram	244 (6.0)
Chemical sympathectomy	22 (0.5)
Surgical sympathectomy	22 (0.5)
Finger amputation	320 (7.9)
Hand amputation	32 (0.8)
Toe amputation	274 (6.8)
Foot amputation	157 (3.9)

AIDS, acquired immunodeficiency syndrome; CREST, calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia; CVA, cerebrovascular accident; HIV, human immunodeficiency virus; MCTD, mixed connective tissue disease; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; UE, upper extremity.

In a review of our institutional registry, vascular medicine was consulted on 23 inpatients with RP or suspected RP from January 2020 through June 2023. Patients had an average age of 54 ± 13.8 years and 15 (65%) of the patients were women. Comorbidities included 16 (70%) with a prior diagnosis of a connective tissue disease, 10 (43%) with hypertension, five (22%) with type 2 diabetes mellitus, five (22%) with hyperlipidemia, and only one patient with peripheral artery disease. An invasive angiogram was performed in seven (30%). Advanced therapeutic interventions included eight (35%) patients who received intravenous vasodilators, four (17%) who underwent chemical sympathectomy, and three patients who underwent amputation.

In a nationwide cohort, hospitalization for RP is frequently associated with an underlying connective tissue disease and high rate of smoking. Nearly 20% of patients underwent amputation, but rarely had an angiogram performed during the same hospitalization. There is no billing code for intravenous vasodilator administration, so this could not be evaluated in the NRD, but was utilized in one-third of our patients. The role of sympathectomy is poorly defined in such patients, but is a consideration in those with advanced disease despite maximally tolerated medical therapy. Chemical sympathectomy confers overall low risk for complications. In small studies it has demonstrated improvement in perfusion, ⁵ but in randomized trials has not demonstrated benefit in patients with systemic sclerosis. ⁶ Sympathectomy was rarely performed nationally, though our group was more aggressive and performed this for patients with refractory ischemia. Additionally, angiograms were performed in a small minority of patients nationally. We more frequently perform angiography as a means to exonerate alternative contributors to digital ischemia, evaluate vasodilator response with administration of intra-arterial nitroglycerin, and better define digital artery anatomy.

The most notable limitation of our study is the inability to verify diagnoses and outcomes utilizing an administrative claims-based dataset like the NRD. It is possible that patients underwent amputation due to concomitant PAD, leading to an overestimate of the amputation rate. Most RP is managed as an outpatient, and as such, we also captured a unique population with severe manifestations. Additionally, our institutional experience was limited to patients in whom the vascular medicine service was consulted and to our unique team-based approach.

Given the relative infrequent nature of severe RP presentations and significant risk of amputation, with a dearth of evidence to guide optimal management, a multidisciplinary team with involvement of vascular medicine specialists at tertiary centers may be the most appropriate care model for such patients. As has been recommended for other vascular diseases like pulmonary embolism and acute aortic syndromes, ⁷ a multidisciplinary team approach allows exchange of ideas and increased experience with a unique set of specialists in an attempt to decrease the amputation rate and optimize short- and long-term outcomes. Further studies are warranted to evaluate optimal care for advanced RP and the role of a multidisciplinary team approach for improved clinical outcomes and the cost implications for such an approach Like many other vascular disease states, RP lacks a clear optimal approach to management. Vascular medicine specialists are well-positioned to lead multidisciplinary efforts to optimize care for complex RP.