D. penicillamine

D. Penicillamine is the product of acid hydrolysis of penicillin. It is used in the treatment of rheumatoid polyarthritis, Wilson’s disease, scleroderma, cystinuria, and heavy metal poisoning.
50 % of patients will have an adverse drug reaction during the first 6 months of therapy (600 mg/day) and about 1/4 to 1/3 will discontinue therapy.
Clinical manifestations
Cutaneous: maculopapular and pruriginous eruptions, urticaria (early), autoimmune bullous syndrome almost of pemphigus type and rare but severe cicatricial pemphigoides (late), contact allergy (eye drops).
Renal: glomerulonephritis with membrane proliferation.
Hematological: neutropenia, thrombocytopenia, aplastic anemia.
Autoimmune: myasthenia, polymyositis, dermatomyositis, lupus, Goodpasture’s syndrome.
Respiratory: obstructive bronchiolitis, pneumonitis, asthma.
Diagnostic methods
No in vivo or in vitro diagnostic methods are currently available, other than the lymphocyte stimulation test which may be positive in some cases of glomerulonephritis and polymyositis.
Patch-tests (penicillamine 0.15 M aq.): positive in contact allergy.
D. penicillamine-induced pemphigus generally has a lower prevalence of tissue-fixed or circulating antibodies than spontaneous pemphigus.
If severe glomerulonephritis occurs, do not attempt to re-administer unless no other therapeutic option is available.
If use is absolutely necessary, first perform the following desensitization to avoid risk of severe delayed reactions:
  • first week: 1/ 100th of the total dose
  • second week: 1/ 10th of the total dose
  • third week: 1/3 rd of the total dose
  • fourth week: total dose.

Should kidney dysfunction or other severe manifestations develop, discontinueD.penicillamine and give 40 to 80 mg of prednisone/ day.

In Wilson’s disease, alternative treatments are trientine and zinc; desensitization can be performed as follows:
  • day 1: prednisone 30 mg
  • day 3-4-5: D. penicillamine 125 mg
  • day 6-7-8: D.penicillamine 250 mg
  • day 9-10-11: D. penicillamine 375 mg
  • day 12-13-14: D.penicillamine 500 mg
  • day 15-16-17: D.penicillamine 750 mg
  • day 18 and subsequently: D.penicillamine 1 g.

If a patient allergic to penicillin requires treatment with D.penicillamine, start with 1/ 1000th of the total dose then 3 to 10 times more every 30 minutes (although no cross-reactivity has been clinically demonstrated between penicillin and D. penicillamine).


  1. Bialy-Golan S, Brenner S, "Penicillamine-induced bullous dermatoses", J. Am. Acad. Dermatol., 1996; 35:732-42
  2. Chan C.Y, Baker A.L, "Penicillamine hypersensitivity: successful desensitization of a patient with severe hepatic Wilson’s disease (see comments)", Am. J. Gastroenterol., 1994; 89 (3): 442-3
  3. de Moor A, Van Hecke E, Kestelyn P, "Contact allergy to penicillamine in eye drops", Contact Dermatitis, 1993; 29 (3): 155-6
  4. Matsumura T, Yuhara T, Yamane K, Kono I, Kabashima T, Kashiwagi H, "D. penicillamine-induced polymyositis occurring in patients with rheumatoid arthritis: a report of 2 cases and demonstration of positive lymphocyte stimulation test to D penicillamine", Henry Ford Hosp. Med. J, 1986; 34:
  5. Jaffe I.A, "Adverse effects profile of sulfhydryl compounds in man", Am. J. Med, 1986; 80: 471-6

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