Codeine-induced generalized dermatitis and tolerance to other opioids.

Codeine (methyl morphine) is a widely used opioid that is administered alone or in combination with other drugs, such as antihistamines, decongestants, and mild analgesics. There are few reports of generalized dermatitis induced by oral codeine and cross-reactivity with morphine [1-4]. A 43-year-old man experienced 3 episodes of generalized pruriginous rash after taking analgesic and antitussive preparations containing codeine. The rash developed several hours after taking Algidol (paracetamol 650 mg and codeine 10 mg), Bisolvon compositum (bromhexine, diphenhydramine, ephedrine, and codeine), and Fludeten (paracetamol and codeine 30 mg). The rash improved and disappeared by desquamation 2 to 3 weeks after beginning treatment with oral corticosteroids and antihistamines. The patient subsequently tolerated Frenadol (paracetamol 650 mg, dextromethorphan, and chlorpheniramine) with no adverse effects. He also received fentanyl as an anesthetic with no further complications. Patch tests were performed with opioids: codeine and morphine (0.1%-1% aq), tramadol (0.1%-1% aq and pet), meperidine (0.5%-5% pet), and naloxone (0.4 mg/mL aq). These were read after day (D) 2 and D4, and reactions were scored as recommended by the International Contact Dermatitis Research Group. Skin prick testing was performed with dilutions of commercial solutions of meperidine (5 mg/mL), tramadol (1 mg/mL), and undiluted naloxone (0.4 mg/mL), and intradermal testing was performed with meperidine (0.0005 mg/mL), tramadol (0.1 mg/mL), and naloxone (0.004 mg/mL). An immediate reading was obtained after 20 minutes and late readings at D1, D2, and D4. Patch testing with codeine and morphine gave positive results at all concentrations, and negative results to the other drugs tested. The immediate and late readings for the prick and intradermal tests were negative. We describe a case of generalized dermatitis caused by codeine as a component of combination preparations. Positive patch test results and cross-reactivity with codeine and morphine have rarely been reported after systemic use of opium alkaloids [1-4]. On the basis of similarities in the chemical structures of phenanthrene derivatives, such as codeine and morphine, the safest approach is avoidance of all chemically related compounds in patients sensitized to any one of them (Figure). Dextromethorphan is the methylated dextrorotatory analog of levorphanol, which is a phenanthrene derivative. It is especially interesting to note that our patient was able to tolerate dextromethorphan (d-3-methoxymorphinan) following the reaction to codeine. The use of H1 antihistamines could have attenuated the effects of nonspecifi c histamine release, but the association of chlorpheniramine with dextromethorphan