A 39-year-old, previously healthy man presented to rheumatology clinic with 6 days of a progressively severe rash on his lower legs and pain in his knees and ankles. He denied recent upper respiratory or other infection. He took no medications. He was afebrile, and vital signs were normal. Physical examination revealed a rash on the feet and lower legs characterized by palpable purpura with several large areas of confluence (Figure 77-1). His knees were tender, and the ankles were tender and swollen; the remainder of the joint examination was unremarkable. The cardiopulmonary, abdominal, and neurologic examinations were normal. Laboratory values were remarkable for creatinine of 1.4 and a spot urine protein or creatinine ratio of 1.9. Chemistries, including liver functions, and a complete blood count (CBC) were normal. Antineutrophil cytoplasmic antibody (ANCA) studies were negative. A renal biopsy was performed and confirmed a diagnosis of Henoch-Schönlein purpura (HSP) (Figures 77-2 and 77-3).

The ANCA-negative small vessel vasculitis (SVV) have in common the pathogenic mechanism of immune-complex (IC) formation and deposition in and around small blood vessels, often with fixation of complement followed by varying degrees of inflammation. They also have in common almost universal cutaneous involvement that most frequently manifests clinically as palpable purpura and histologically as leukocytoclastic vasculitis. The clinical syndromes are distinguished by the nature of the immune complexes, epidemiology, and pattern of organ involvement (Table 77-1).

Henoch-Schönlein Purpura

• 
  

  Characterized by deposition of immunoglobulin A (IgA)-containing IC and complement components within the walls of affected vessels. IC deposition may also occur within the renal mesangium.

  
  
• 
  

  Mainly affects the skin, joints, gastrointestinal tract, and, more rarely, kidneys.

  
  
• 
  

  Frequently mild and self-limited in children, although may be complicated by severe renal disease and intussusception.

  
  
• 
  

  Prognosis in adults is more guarded because of a higher incidence of progression to end-stage renal disease.

  
  
• 
  

  The following classification criteria were proposed by the American College of Rheumatology (ACR) in 1990¹:

  
  
  
  
  • 
    

    Palpable purpura

    
    
  • 
    

    Age 20 years or less at disease onset

    
    
  • 
    

    Bowel angina

    
    
  • 
    

    Granulocytes in arteriole or venule walls on biopsy

If two or more criteria are present, the sensitivity and specificity for HSP are 87% and 88%, respectively.

Cryoglobulinemic Vasculitis

• 
  

  Cryoglobulins are ICs that precipitate from serum when exposed to cold (Figure 77-4).

  
  
• 
  

  Three types are recognized:

  
  
  
  
  • 
    

    Type I—isolated monoclonal IgG or IgM isotype, most often associated with Waldenström macroglobulinemia or multiple myeloma.

    
    
  • 
    

    Type II—comprised of polyclonal IgG plus monoclonal IgM with rheumatoid factor (RF) activity. Represents 80% of all cryoglobulins. About 90% of cases are associated with the hepatitis C virus (HCV).

    
    
  • 
    

    Type III—comprised of IgG and IgM that are both polyclonal, associated with many chronic inflammatory conditions, especially connective tissue diseases.

Type I cryoglobulinemia may cause a hyperviscosity syndrome leading to neurologic sequelae and cutaneous ischemia (Figure 77-5). Types II and III cryoglobulinemia are more likely to present with classic features of SVV: purpura, arthralgias, and glomerulonephritis. Peripheral neuropathy is common in type II; the finding of mononeuritis multiplex is highly suggestive of an SVV.

Hypersensitivity Vasculitis

• 
  

  A heterogeneous group of disorders characterized by antibody response to a foreign antigen with subsequent IC formation and deposition in small blood vessels.

  
  
• 
  

  Isolated skin involvement is very common, but fever, arthralgias, and lymphadenopathy are not infrequent. Visceral organ involvement has been described but when present should prompt workup for other causes.

  
  
• 
  

  Multiple inciting factors have been implicated (Table 77-2); however, a precipitating agent cannot always be identified. Antibiotics are among the most frequently implicated medications.

  
  
• 
  

  The following classification criteria were proposed by the ACR in 1990²:

  
  
  
  
  • 
    

    Age greater than 16 years

    
    
  • 
    

    Use of a possible offending medication in temporal relation to the symptoms

    
    
  • 
    

    Palpable purpura

    
    
  • 
    

    Maculopapular rash

    
    
  • 
    

    Biopsy of skin lesion showing neutrophils around an arteriole or venule