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Vasculitis

Contributor: Peter Valen, MD, FACP

+ CASE 1

A 50 year old female presents with a six-month history of " painful red spots" on her lower legs. They occur in crops over a period of time and resolve with residual hyperpigmentation. She has no systemic complaints to include fever, weight loss. She reports no circulatory, pulmonary, gastrointestinal, or other symptoms. Her past medical history is unremarkable and she is on no medications. There is no family history of bleeding disorders.

Physical examination is unremarkable except for palpable purpura on both lower extremities.  Initial laboratory tests include a normal complete blood count, ESR and urinalysis. A biopsy of a skin lesion reveals leukocytoclastic vasculitis (LCV).

What is the differential diagnosis?

  1. LCV resulting in palpable purpura is secondary to another underlying condition in more than 70% of cases. These include:
    1. Infections
      • Viral: consider hepatitis B and C, HIV, EBV
      • Acute bacterial: consider meningococcemia, GC, gram negative bacteremia
      • Chronic infections: consider SBE, fungal infections
    2. Drugs (hypersensitivity vasculitis)
    3. Para-proteins (cryoglobulins, macroglobulinemia)
    4. Systemic vasculitis: consider ANCA-associated vasculitis (Wegener's, Microscopic Polyangiitis (MPA), Churg-Strauss), Polyarteritis Nodosa (PAN)
    5. Rheumatic diseases: consider Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), Polymyositis/Dermatomyositis (PM/DM), Sjogren's syndrome (SS)
    6. Miscellaneous: consider malignancy, inflammatory bowel disease (IBD)
  2. The following tests can be done to look for systemic causes of LCV:
    • CBC, ESR, UA, anti-nuclear antibody (ANA), rheumatoid factor (RF), anti-neutrophil cytoplasmic antibody (ANCA), cryoglobulins, serum protein electrophoresis (SPEP), Hepatitis B and C serology, C3 and C4 complement levels, and echocardiography. All tests were negative or normal.
  3. This patient had LCV of unknown cause with no evidence of systemic vasculitis, underlying connective tissue disease or other systemic illness. Treatment often consists of low dose prednisone with a gradual taper. Other medications including colchicine, anti-histamines, and dapsone may be helpful in resistant cases.

+ CASE 2

A 43 year old man presents with a 2-3 week history of fever, cough, and migratory arthralgias. This was preceded by persistent nasal stuffiness and a mildly productive cough that on one occasion included bright red blood. He reports a 5-10 year history of recurrent sinus and ear infections that seem unresponsive to antibiotics and decongestants. Additionally, he reports recent malaise and fatigue with mild dyspnea on exertion. For the past 4-5 days, he has had a painful, red left eye.  He is a non-smoker with no recent travel or exposures and he denies cocaine or other drug use.

Physical examination reveals an ill-appearing male with a blood pressure of 140/90 and a pulse of 102, temperature is 101°F. There is no skin rash or adenopathy. He is tender over the maxillary sinuses and the left eye is injected and slightly swollen. Chest exam reveals decreased breath sounds with rales in the upper lung fields.

A chest X-ray reveals multiple large pulmonary nodules in both upper lobes with cavitation in several areas. Laboratory studies include a mild anemia and WBC of 12,200 cu/mm with a slight left shift and no significant eosinophilia. A urinalysis reveals 2+ protein and 20-30 RBCs. Serum creatinine is 1.5 mg/dL. Sinus films show opacification of the left maxillary sinus.

What is the likely diagnosis and what additional tests do you want to obtain to help confirm your diagnosis?
This patient presents with multi-organ system disease with prominent findings in the upper and lower respiratory tract and kidney. Systemic vasculitis as well as infection, malignancy, and vasculitis mimics should be considered.  The following tests should be considered in the evaluation a patient with this presentation:

  1. CBC with differential, UA, C3 and C4 complement levels, ESR, CRP
  2. Hepatitis Serologies and HIV
  3. PPD skin testing and sputum for AFB and fungal cultures
  4. Urine drug screen if drug use is suspected
  5. Serum antibody testing for ANA, RF, anti-GBM (Goodpasture's disease), ANCA (with antigen-specific  anti-PR3 and anti-MPO if ANCA is positive)
  6. Biopsy of tissue to look for granulomatous inflammation with necrotizing vasculitis; the highest yield is found with lung biopsy (open or video-assisted thoracoscopic surgery)
  • A PPD skin test was negative; sputum for AFB and fungal cultures were obtained; AFB smears and sputum cytology were negative. Serum antibody tests for ANA, RF, and HIV were negative. Anti-GBM antibodies were negative. ANCA was positive at a titer of 1:1280 with cytoplasmic staining (c-ANCA) and anti-proteinase 3 (PR3) antibodies by ELISA were also positive. Serum C3 and C4 complement levels were normal. Bronchoscopy revealed no obstructing lesions or bloody secretions. An open lung biopsy was performed and tissue sections revealed granulomatous inflammation, necrotizing vasculitis, and multi-nucleated giant cells.
  • This patient's presentation suggests a pulmonary-renal syndrome, the most common causes of which include Goodpasture's (anti-GBM disease), post-infectious, lupus and other auto-immune diseases, and ANCA-associated vasculitis. Several additional clinical features in this case suggest Granulomatosis with Polyangiitis - Wegener's (GPA) as a likely diagnosis. This condition should be suspected in patients with chronic epistaxis, septal perforation, nasal bridge collapse, chronic sinus and/or ear infections, hearing loss, hoarseness, necrotizing scleritis of the eye, proptosis, hemoptysis' and glomerulonephritis. Several conditions may mimic GPA including cocaine-induced midline destructive lesion (CIMDL), sino-nasal sarcoid, relapsing polychondritis, fungal infections (esp. mucormycosis), and NK/T cell lymphomas. Although c-ANCA and anti-PR3 positivity are highly suggestive, tissue biopsy is recommended in most cases to confirm the diagnosis and rule out malignancy and infections.
  • In this case, a diagnosis of Granulomatosis with Polyangiitis-Wegener's was made based on clinical presentation, laboratory tests, and biopsy results. He was treated with high-dose corticosteroids and oral cyclophosphamide with trimethoprim-sulfa for pneumocystis prophylaxis.  Plasmapheresis may be indicated in certain patients with alveolar hemorrhage, rapidly progressive renal failure, or concomitant anti-GBM antibodies.  Rituximab has recently been approved to treat this condition and may be an alternative to cyclophosphamide.  The treatment plan was to continue cyclophosphamide and taper steroids for 3-6 months until clinical remission then switch to methotrexate or azathioprine for maintenance therapy.

Patient Care

  1. Identify common complaints suggestive of vasculitis, including fever, weight loss, fatigue, skin rash, hemoptysis, mononeuritis multiplex, circulatory problems, etc.
  2. Recognize the urgency of confirming a diagnosis and initiating appropriate therapy in patients with organ-threatening disease.
  3. Implement and interpret appropriate clinical laboratory and radiologic testing to suggest, confirm or exclude a diagnosis of vasculitis.
  4. Recognize the risks and benefits of individual treatments/medications for vasculitis.
  5. Describe the management strategies for vasculitis and match the most appropriate strategy to the clinical situation.

Medical Knowledge

  1. Understand the basic pathophysiology and pathogenic mechanisms of vasculitis

  2. Distinguish the nomenclature and unique pathophysiologic and histologic features of the individual vasculitis syndromes including:
    1. Large vessel vasculitis
    2. Medium vessel vasculitis
  3. Describe the general classification schemes (1, 2) for vasculitis
  4. Describe a diagnostic approach for a patient with a suspected vasculitis
  5. Recognize multi-organ system involvement of the individual vasculitis syndromes and discriminate clinical patterns that identify them
  6. Understand the treatment options for systemic vasculitis, including the risks and benefits of commonly used drugs for the treatment of vasculitis
  7. Recognize common vasculitis mimics:

Practice-Based Learning and Improvement

  1. Identify personal learning goals in the diagnosis and treatment of vasculitis
  2. Engage in ongoing self-assessment and continuous self-evaluation of learning needs
  3. Utilize information technology to search for and critically evaluate medical information relevant to the care of patients with vasculitis

Interpersonal and Communication Skills

  1. Engage the patient and ask probing questions to maximize the value of the clinical history which is an essential part of the evaluation of vasculitis
  2. Recognize the patient's fears in dealing with a potentially life-threatening condition and establish a trusting relationship with the patient and family
  3. Allow the patient and their family to express concerns and openly ask questions about their condition and treatment options
  4. Summarize the information to be provided to a specialist to whom you might refer a patient with suspected vasculitis

Professionalism

  1. Provide compassionate and respectful care
  2. Take on the role of patient advocate when their medical condition leads to conflicts and issues at home or workplace
  3. Ensure that medical decision-making is always done with the best interests of the patient at the forefront

Systems Based Practice

  1. Recognize the importance of a multi-disciplinary approach to the diagnosis and treatment of vasculitis
  2. Identify any system problems that interfere with the timely and efficient care of patients with vasculitis
  3. Incorporate considerations of cost-effectiveness in the diagnosis and treatment of vasculitis

Keywords: Vasculitis, Large vessel vasculitis, Medium vessel vasculitis, Small vessel vasculitis, ANCA-associated vasculitis, Giant cell arteritis, Takayasu's Arteritis, Polyarteritis nodosa, Kawasaki's disease, Primary CNS vasculitis, Churg Strauss syndrome, Granulomatosis with polyangiitis (Wegener's), Microscopic polyangiitis, Henoch-Schonlein purpura, Cryoglobulinemic vasculitis, Hypersensitivity vasculitis

References