Monoclonal gammopathy of undetermined significance associated with blue finger syndrome

Abstract

An 86-year-old Caucasian woman with a medical history of monoclonal gammopathy of undetermined significance (MGUS) was admitted to the hospital with a chief complaint of sudden onset of bluish discolouration of the fifth left hand digit. On a physical examination, cyanosis of the fifth digit of the left hand was noticed with decreased capillary fill but no ulcers. The patient had no tenderness on palpation. Pulses were palpable over the radial arteries bilaterally. Patients with MGUS may be at increased risk of thromboembolic disease. A clear explanation for this association in these patients is not currently known. This case report highlights the association between MGUS and thromboembolic events, particularly blue finger syndrome.

Background

Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant lymphoplasmacytic proliferative disorder. MGUS is defined by the presence of a serum M-protein ≤ of 3 g/dl, with less than 10% plasma cells in the bone marrow, and the absence of lytic bone lesions, anaemia, hypercalcemia and renal insufficiency. MGUS occurs in approximately 3% of the general population over the age of 50 and is typically detected as an incidental finding when patients undergo a protein electrophoresis as part of an evaluation for a wide variety of clinical symptoms and disorders.^1–4 Patients with MGUS are at risk of progressing to a malignant plasma cell dyscrasia or lymphoproliferative disorder, including: multiple myeloma, Waldenstrom macroglobulinemia, amyloidosis and idiopathic Bence Jones proteinuria.^5–9 There are no data that treatment of asymptomatic disease affects mortality and therefore, no treatment is indicated. Patients with MGUS should be followed with serial history and physical examination looking for signs and symptoms of progressive disease.

Patients with MGUS may be at increased risk of thromboembolic disease.^10–16 Increasing evidence has emerged about the risk of venous thromboembolism (VTE) in patients with multiple myeloma who were treated with thalidomide and lenalidomide, in combination with dexamethasone and/or chemotherapy.^{17 18} However, patients with MGUS were found to be at increased risk of VTE in spite of the lack of chemotherapy, corticosteroids or immunosuppressant therapy.¹⁰ A clear aetiology for this increased risk of VTE is yet to be identified.

A number of studies have reported an increased incidence of VTE and arterial thrombosis in patients with MGUS. We report a case of a patient with MUGS who developed the ‘blue finger syndrome’. We will review the case, discuss the literature and review the scientific data via which mechanisms MGUS may increase thrombotic events.

Case presentation

The patient is an 86-year-old Caucasian woman who was admitted to the telemetry floor of the hospital with a chief complaint of bluish discolouration of the fifth left-hand digit. The patient noticed that her thumb suddenly became purple few days ago prior to admission. The patient denied any pain, numbness or coolness in her hand or fingers or a recent trauma to her hands. On the review of symptoms the patient denied chest pain, shortness of breath, palpitations and recent medical procedures. The photo of the patient's left hand is presented in figure 1.

Figure 1.

Bluish discolouration of the fifth digit.

Medical history is relevant for arterial hypertension, MGUS, aortic stenosis and hypothyroidism. The patient was using amlodipine, enalapril and levothyroxine.

Physical examination: cyanosis of the fifth digit of left hand and decreased capillary refill was noticed. There was no local tenderness, ulcers, sensory or motor deficit. Skin examination showed multiple senile purpura with no rash, ulcers or livedo reticularis. Pulses were palpable over the radial arteries bilaterally. Cardiovascular exam showed 2/6 systolic murmur in the aortic area. The rest of the physical examination was grossly normal.

Investigations

Complete blood count (CBC) and comprehensive metabolic profile were drawn, which did not show any abnormality. Urinalysis failed to detect white blood cells. International normalised ratio (INR) of the prothrombin time and activated partial thromboplastin time did not detect abnormalities.

No rhythm abnormalities were detected on telemonitor and on serial 12 lead electrocardiography. Bilateral US arterial Doppler of the upper extremity was done. It showed markedly diminished finger-brachial index for the fifth digit which was the symptomatic site. ECG showed normal sinus rhythm. Transesophageal echocardiogram was done which did not show any left atrial or ventricular thrombi. Left atrial spontaneous echo contrast was not noted. No atrial septal aneurysm, aortic atherosclerotic plaques, vegetations, mitral valve calcifications or intracardiac mass were found.

CT angiogram of the chest was done, which showed no aortic, left subclavian or brachial artery ulcer, aneurysm or atherosclerotic plaque.

The patient was offered to undergo cardiac catheterisation and a biopsy of the affected finger for establishing a histological diagnosis, on which she refused. Because of the acuity of presentation and no medical history of connective tissue disease it was deemed unlikely to be a precipitant factor. Although cardioembolic source could not be completely ruled out, it was presumed to be unlikely given the negative imaging studies.

Differential diagnosis

Several potential diagnoses were considered: thromboembolic disease, atheroembolism, arterial insufficiency and connective tissue diseases.

Treatment

The patient was started on warfarin and discharged after therapeutic INR was achieved.

Outcome and follow-up

On a follow-up visit after 5 months, the cyanosis of her finger has improved with no pain, sensory or motor deficit. She had no complaints. The patient was still on warfarin with therapeutic INR.

Discussion

Recent evidence indicates that patients with multiple myeloma receiving combination chemotherapy containing thalidomide are at a significantly high-risk VTE.^{17 18} However, information on the occurrence of VTD and other thromboembolic diseases in MGUS is limited.

MGUS has been proposed to be a risk factor for VTE and arterial thrombosis. This case report highlights the association between MGUS and thromboembolic disease, particularly blue finger syndrome.

Some studies have shown that MGUS patients are more likely to experience thromboembolic events, such as deep vein thrombosis (DVT). Kristinsson et al¹⁴ examined the records of 2374 MGUS patients who had been admitted at least once to a hospital. They found that risks for DVT, coronary artery disease and cerebrovascular events were increased. Patients were at the greatest risk for developing during the first year after diagnosis of MGUS. It is important to note that patients were still at higher risk for developing these outcomes at 10 years follow-up.

Two small hospital-based studies also found that MGUS patients are at increased risk for DVT.^{10 11} However, another large population-based study does not show a higher risk of thromboembolic events among MGUS patients.¹⁹

While these studies did not provide an explanation for the increase in thrombotic complications in patients with MGUS, many theories were suggested. Abnormalities in the stromal cell environment along with the effect of the monoclonal protein on fibrin formation may potentiate a thrombogenic state in MGUS. Interestingly, factor VIII and von Willebrand factor levels were found to be increased among MGUS cases.¹² Further studies are necessary to define the mechanisms involved.

Our patient presented with acute blue finger syndrome. Although the likelihood that this presentation is due to thromboembolic source is low with negative imaging studies, thromboembolic cannot completely be ruled out. This case highlights the fact that physicians should be aware of the high risk of thrombosis (venous and arterial) in MGUS compared to non-MGUS individuals.

Learning points.

• Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant lymphoplasmacytic proliferative disorder. Patients with MGUS should be monitored for progression and complications of the disease.

• Patients with MGUS have a high risk of thrombosis (venous and arterial) compared with non-MGUS individuals.

• A clear explanation for this association between MGUS and thromboembolic events is yet to be investigated.

• Blue finger syndrome can be a benign process with no long-term complications.