A 50-year-old man comes to the office due to a rash, joint pain, malaise, and fatigue for the past several weeks. Medical history is significant for intravenous drug use with 5 years of abstinence since participating in a methadone treatment program. The patient takes no medications. He does not use alcohol and is a lifetime nonsmoker. Temperature is 37.7 C (99.9 F), blood pressure is 165/90 mm Hg, pulse is 80/min, and respirations are 14/min. Examination shows palpable purpura involving the lower extremities as well as hepatomegaly. Achilles reflexes are absent. Urinalysis reveals hematuria, red blood cell casts, and proteinuria. Laboratory results are as follows: Which of the following is the most likely diagnosis?

Question

A 50-year-old man comes to the office due to a rash, joint pain, malaise, and fatigue for the past several weeks.  Medical history is significant for intravenous drug use with 5 years of abstinence since participating in a methadone treatment program.  The patient takes no medications.  He does not use alcohol and is a lifetime nonsmoker.  Temperature is 37.7 C (99.9 F), blood pressure is 165/90 mm Hg, pulse is 80/min, and respirations are 14/min.  Examination shows palpable purpura involving the lower extremities as well as hepatomegaly.  Achilles reflexes are absent.  Urinalysis reveals hematuria, red blood cell casts, and proteinuria.  Laboratory results are as follows:  Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

Explanation: 11ec25c8_d4d8_af81_bc81_c369044f9d24_MD0003_00 This patient has palpable purpura, glomerulonephritis (eg, hematuria, red cell casts, azotemia), peripheral neuropathy (eg, hyporeflexia), arthralgias, and constitutional symptoms (eg, fever, malaise). Such a multisystem involvement is suggestive of small-vessel vasculitis (SVV), which can target the arterioles, capillaries, and venules of virtually any organ (eg, skin, kidney, nerve). Identification of the underlying cause of SVV requires a broad diagnostic strategy: palpable purpura Recognize vasculitic pattern Obtain serologies (eg, antineutrophil cytoplasmic antibodies [ANCA], complement) ± Biopsy affected organ Evaluate secondary causes (eg, viral studies, autoimmune testing, medication review) This patient's hepatitis C virus (HCV) antibodies and hepatomegaly suggest secondary SVV due to mixed cryoglobulinemia syndrome (MCS; cryoglobulinemic vasculitis). Chronic HCV infection is the most common cause of MCS. The exact pathogenesis is unclear, but HCV infection may be associated with B-cell activation that leads to selective production of cryoglobulins (immunoglobulins that precipitate at <37 C). In MCS, the cryoglobulins are a mixture of polyclonal IgGs and IgMs with rheumatoid factor (RF) activity (bind to Fc portion of IgG); cryoglobulin-containing immune complexes activate complement, causing hypocomplementemia, and deposit in small vessels, causing SVV. (Choice A) Like most SVV, IgA vasculitis can cause palpable purpura, glomerulonephritis, and arthralgias. However, it commonly has associated gastrointestinal symptoms and is relatively rare in adults. IgA nephropathy denotes renal-limited IgA vasculitis. (Choice B) Microscopic polyangiitis (MPA) is one of 3 small-vessel vasculitides mediated by ANCA rather than immune complexes; therefore, complements are normal. Although MPA commonly causes glomerulonephritis, palpable purpura, and neuropathy, ANCA is typically positive and pulmonary involvement is common. (Choice D) Rheumatoid arthritis usually produces RFs but only rarely causes SVV. Rheumatoid vasculitis can cause palpable purpura. However, skin findings classically involve leg ulcers, vasculitis typically occurs in patients with long-standing rheumatoid arthritis, and small joint synovitis/deformity would be expected. Glomerulonephritis is atypical, and HCV is not associated. (Choice E) Systemic lupus erythematosus (SLE) can closely mimic SVV (eg, glomerulonephritis, neuropathy, arthralgia) and, in rare cases, cause SVV due to MCS. Hypocomplementemia is common with active disease, and RF is not unusual (even in the absence of MCS). However, SLE usually affects young women and is unlikely in this patient without the typical symptoms (eg, malar rash, oral ulcers). Educational objective: Mixed cryoglobulinemia syndrome is a small-vessel vasculitis that commonly presents with palpable purpura, glomerulonephritis, peripheral neuropathy, and arthralgias. Chronic hepatitis C infection is the most common cause, and characteristic laboratory abnormalities include hepatitis C antibodies, rheumatoid factor, and hypocomplementemia.

A 50-Year-Old Man Comes to the Office Due to a Rash