Background/Purpose: Illicit cocaine use is associated with the development of serum anti-neutrophil cytoplasmic autoantibodies (ANCA) and a variety of clinical manifestations. However, the mechanisms linking cocaine use and autoimmunity remain obscure. A causal link between cocaine use and ANCA is suggested by known immunostimulatory properties of cocaine, and its frequent contamination with levamisole, an immunomodulatory chemical. Here, we describe the immunologic and clinical characteristics of a series of cocaine users found to have extremely high-titer serum ANCA. The purpose of this report is to generate testable hypotheses regarding possible links between cocaine use and autoimmunity.

Methods: Chart review of 12 consecutive patients referred for rheumatologic evaluation at 2 tertiary referral centers from 2008 and 2013 for active cocaine use and high-titer serum ANCA. Clinical and immunologic parameters with complete or near-complete data sets were chosen.

Results: Results are summarized in the table below. The majority of subjects were female users of crack cocaine. Half presented with hematologic abnormalities, but only a minority (2) presented with purpura, a frequently reported manifestation. Interestingly, 2 patients presented with diffuse alveolar hemorrhage (DAH) not readily explained by vasculitis or cryoglobulinemia. 3 patients presented glomerular disease. One presented with supraglottic inflammation, and another with ischemic bowel. Arthralgia/arthritis was common.

All patients had high-titer P-ANCA reactivity with variable MPO and PR reactivity, suggesting reactivity against unmeasured neutrophil antigens (Ags). High-titer ANA was not observed in any patient, although some displayed reactivity against select ANA-associated Ags. Most patients showed serum IgM (but not IgG) cardiolipin and/or b2-glycoprotein reactivity, along with frequent lupus inhibitor positivity, again consistent with previous reports. Hypocomplementemia was frequent among those patients with active HCV infection. Finally, there were no clear correlations between route/nature of cocaine exposure and either clinical or immunologic features.

Conclusion: We observed a wide variety of clinical manifestations in cocaine users with high-titer serum ANCA reactivity. Immunologically, patients were more homogeneous, showing near-exclusive P-ANCA reactivity, frequent IgM (but not IgG) cardiolipin/b2-glycoprotein reactivity and a complete absence of significant titer ANA – suggesting loss of immune tolerance to a limited set of self-Ags. That MPO reactivity was variably present further suggests P-ANCA reactivity was directed against other perinuclear neutrophil cytoplasmic Ags. The nature of these Ags in cocaine-users, as well as the effects of cocaine and levamisole on neutrophils, are the subjects of ongoing investigation.

Age at presentation

42

49

52

49

28

46

54

35

53

39

43

46

Sex

F

F

F

F

F

F

F

F

M

F

F

F

Clinical manifestations

Skin

P

–

–

–

–

P

–

–

–

U

U

U

Hematologic

Pan

Pan

Pan

N

N

–

–

–

–

–

–

N

Kidney

–

–

–

GN+

Amyloid

–

GN-

–

–

–

–

–

Lung

–

DAH

–

DAH

–

–

–

–

–

–

–

–

Other

–

–

–

–

Arth

GI isch.

–

Glottitis

Arth

Arth

Arth

Arth

Immunologic parameters

ANCA IF (titer)

1:4,096

1:4,096

>1:65,536

>1:65,536

1:4,096

1:4,096

1:16,384

1:16,384

1:4,096

1:8,192

1:16,384

1:1,024

ANCA IF (pattern)

P,C

P

P

P

P

P

P,C,N

P

P

P

P

P

anti-PR3

+

+

+

–

–

+

+

–

–

–

–

–

anti-MPO

–

–

+

+

–

+

+

–

+

+

+

+

ANA IF (titer)

–

–

–

–

1:80

1:80

–

–

–

–

–

–

ANA-assoc. autoAbs

NT

–

–

SSA, RibP

Ch

dsDNA, Ch

SSA, Ch

dsDNA, Ch

dsDNA, Ch

–

–

NT

Anti-cardiolipin

IgM

IgM

–

IgM

IgM

NT

IgM

IgM

NT

IgM

IgM

NT

Anti-b2 glycoprotein

NT

IgM

IgM

IgM

–

NT

–

IgM

NT

IgM

–

NT

Lupus inhibitor

–

+++

+/-

–

+++

NT

NT

+/-

NT

+

–

++

Rheumatoid factor

–

–

–

–

–

NT

–

–

–

–

–

–

Hypocomplementemia

–

–

+

+

+

+

+

+

–

–

–

–

Cryoglobulinemia

–

+/-

+

–

–

–

+

–

NT

+

–

–

Active viral infection

–

–

HCV

HCV

HCV

HCV

HCV

–

HCV

–

–

–

Nature of cocaine exposure

C

C

P

P

IV

IV, C

IV, C

C

C

P

C

C

Abbreviations. NT, not tested, -, negative/normal, Skin (P, purpura; U, ulcers), Hematologic (Pan, pancytopenia; N, neutropenia), Kidney (GN+, glomerulonephritis – immune complex; GN-, glomerulonephritis – pauci-immmune), Lung (DAH, diffuse alveolar hemorrhage), Other (Arth, arthralgia/arthritis), ANCA IF pattern (P, perinuclear; C, cytoplasmic; N, nuclear), ANA-associated Abs (RibP, ribosomal P; Ch, chromatin), Nature of cocaine exposure (C, crack/smoked/inhaled; P, powder/inhaled; IV, intravenous)

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-and-immunologic-correlates-in-cocaine-users-with-serum-anti-neutrophil-cytoplasmic-antibodies/