Chymopapain is a proteolytic enzyme with a molecular weight of 27 000 D. It is extracted from a fraction of non-crystallized latex from a tropical tree: Carica papaya. Since 1965 it has been used to treat herniated discs (chemonucleolysis).
Because they have the same antigenic determinants, papain and chymopapain exhibit cross-reactivity (chymopapain is the major active component of papain). Chymopapain is more soluble and has greater proteolytic activity than papain.
Incidence: 0.44 to 2% of chemonucleolysis procedures.
Incidence of severe anaphylactic reactions: 0.18% to 0.45% at the first injection; 9 to 17% after a second injection.
8 deaths reported before 1974, 7 deaths from 1982 to 1991.
Modes of sensitization to papain
Food: Papaya in any form, pineapple (bromelain), various mixed foods (appetizer mixes, yogurt), beverages containing exotic fruits, beer, Coca-Cola, meat tenderizer containing papain.
Drugs containing papain: digestive aids, ENT solutions, anti-inflammatory drugs, contact lens cleaning solutions, detergents, ointments containing papain.
Occupational: inhalation of airborne papain and bromelain.
Risk factors
Atopy (O.R 13.8).
Exposure to papain (O.R 7.3).
Clinical manifestations
Immediate (within 30 minutes after injection of the test dose or total dose): discomfort, pruritus, urticaria, angioedema, fatal anaphylactic shock.
Delayed (up to 2 weeks after chemonucleolysis): urticaria, angioedema, serum sickness.
Diagnostic methods
Cutaneous testing.
Skin prick-tests: chymopapain 1 mg/ml to 10 mg/ml (one case of anaphylaxis during cutaneous testing).
Specific IgE (ImmunoCAP/Pharmacia CAP System).
IgE-mediated hypersensitivity is responsible for most reactions. This is suggested by previous history, immediately positive skin tests, and detection of IgE antibodies.
Activation of the alternate complement route by the enzyme or activation of the normal complement route by chymopapain specific IgG immune complexes.
Non-specific histamine release.
Autoimmune responses against proteoglycans derived from mucopolysaccharide protein complexes which are produced in great quantity during the 24 hours after injection into the disc.
In high risk patients (atopy and/or exposure to papain) before first chemonucleolysis, and in all patients before second chemonucleolysis: predictive skin prick-tests.
Excellent negative predictive value.
If the skin test is negative: chemonucleolysis; if the skin test is positive: surgery.
Surgery is indicated in patients with a history of allergic reaction during previous chemonucleolysis.
The choice of anesthesia remains controversial. In America, local anesthesia is advocated, while in France general anesthesia is usually performed.


  1. Moneret-Vautrin D.A, Feldmann L, Kanny G, Baumann A, Roland J, Pere P, "Incidence and risk factors for latent sensitization to chymopapain: predictive skin-prick tests in 700 candidates for chemonucleolysis", Clin.Exp.Allergy., 1994; 24 (5): 471-6
  2. Nordby E.J, Wright P.H, Schofield S.R, "Safety of chemonucleolysis. Adverse effects reported in the United States, 1982-1991"., Clin. Orthop., 1993; 293: 122-34
  3. Grammer L.C, Schafer M, Bernstein D, Bernstein I.L, Cogen F, Dolovich J, Schatz M, Zeiger R, Shaughnessy J.J., Gutt L, Roberts M, Patterson R, "Prevention of chymopapain anaphylaxis by screening chemonucleolysis candidates with cutaneous chymopapain testing"., Clin. Orthop. 1988; 234: 12-15.

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.