A 52-year-old man comes to the physician with a week of pain and discoloration of his fingers. He has had profound fatigue and diffuse arthralgias for the past 6 months. He denies weight loss, fever, chills, hematuria, cough, hemoptysis, or shortness of breath. He has a history of asthma, intravenous drug abuse, depression, and peptic ulcer disease. He smoked 2 packs per day for 20 years but quit 10 years ago. He drinks occasionally but has not used intravenous recreational drugs for more than 10 years. He works as an auto mechanic.
On examination, the right hand appears as shown below. The remainder of the physical examination is unremarkable.

Laboratory results are as follows:

Chest x-ray shows no infiltrates or cardiomegaly.
Which of the following is the most likely diagnosis?

Question

A 52-year-old man comes to the physician with a week of pain and discoloration of his fingers.  He has had profound fatigue and diffuse arthralgias for the past 6 months.  He denies weight loss, fever, chills, hematuria, cough, hemoptysis, or shortness of breath.  He has a history of asthma, intravenous drug abuse, depression, and peptic ulcer disease.  He smoked 2 packs per day for 20 years but quit 10 years ago.  He drinks occasionally but has not used intravenous recreational drugs for more than 10 years.  He works as an auto mechanic.
On examination, the right hand appears as shown below.  The remainder of the physical examination is unremarkable.

Laboratory results are as follows:

Chest x-ray shows no infiltrates or cardiomegaly.
Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

This patient's presentation is consistent with likely essential mixed (type 2) cryoglobulinemia, a lymphoproliferative disorder with immune complex deposition in small- to medium-sized blood vessels. Patients may have palpable purpura, arthralgias, membranoproliferative glomerulonephritis, low serum complement, cutaneous vasculitis, and neuropathy. The purpura usually occurs in patches on the lower legs. The vasculitis may manifest as skin ulceration and necrosis (as in this patient). Diagnosis is suspected clinically and confirmed with positive serum cryoglobulins. Because up to 90% of mixed cryoglobulinemia patients are positive for hepatitis C, all cryoglobulinemia patients should be tested. Hepatitis C causes non-specific stimulation of lymphocytes resulting in excess production of immunoglobulins, which can lead to false-positive serologies (eg, anti-nuclear antibody [ANA] and high-titer rheumatoid factor [RF]). Treatment of hepatitis C may decrease cryoglobulin levels and improve skin symptoms. This patient's history of intravenous drug use, low complement levels, and high RF suggest possible hepatitis C with cryoglobulinemia. (Choice A) Buerger's disease (thromboangiitis obliterans) usually presents in active smokers age <45 with digital necrosis. This patient is not an active smoker, and Buerger's disease would not explain his positive ANA or RF. (Choice B) Cholesterol embolization syndrome is a complication of atherosclerosis and follows invasive procedures (eg, angiography) involving the aorta and major arteries. Patients may have livedo reticularis, cyanosis, and gangrene. This patient's lack of invasive procedures makes this unlikely. (Choice C) Churg-Strauss syndrome usually presents with a prodromal phase (asthma, allergic rhinitis, or atopic dermatitis), followed by an eosinophilic phase (eg, peripheral eosinophilia, lung eosinophilia with infiltrates), and a vasculitic phase (polyangiitis) up to 10 years later. This patient's normal eosinophil count and absence of lung infiltrates makes this less likely. (Choice E) Primary Raynaud's phenomenon can occur in 5%-10% of the general population and is not associated with any underlying disease. Primary Raynaud's phenomenon usually presents with mild attacks in colder weather and without significant tissue damage. Educational objective: Essential mixed cryoglobulinemia is usually associated with hepatitis C and may present with palpable purpura, arthralgias, membranoproliferative glomerulonephritis, low serum complement, cutaneous vasculitis, and neuropathy. The vasculitis may cause skin necrosis and gangrene in some patients. Treatment of hepatitis C may reduce cryoglobulins and improve skin symptoms. __________ References: Management of hepatitis C virus-related mixed cryoglobulinemia. (http://www.ncbi.nlm.nih.gov/pubmed/20399313) Hepatitis C-associated rheumatic disorders. (http://www.ncbi.nlm.nih.gov/pubmed/19481000) Rheumatic manifestations of hepatitis C infection. (http://www.ncbi.nlm.nih.gov/pubmed/12744811)

A 52-Year-Old Man Comes to the Physician with a Week