Fatal case of toxic erythema after chlorpropamide (Diabinese).

Abstract

Chlorpropamide is widely used for the control of late onset nonketotic diabetes mellitus, and is classed as an arylsulphonylurea. Among its many side-effects are blood dyscrasias, which include thrombocytopenia (Fitzpatrick, 1963), leucopenia, low-grade anaemia, eosinophilia (Rothfeld et al., 1960), aplastic anaemia (Erslev, 1964), and agranulocytosis (Stein, 1964). Transient gastrointestinal disturbances, intolerance of alcohol, hypoglycaemia (sometimes prolonged), impairment of liver function (Rothfeld et al., 1960), foetal damage (Campbell, 1963), and neuropathy have been reported.Purely dermatological toxicity often shows itself as an erythematous rash of varying severity which disappears on withdrawal of the drug. Photosensitivity (Hitselberger and Fosnaugh, 1962), erythema nodosum, erythema multiforme (Stewart et al., 1959), and the Stevens-Johnson syndrome (Yaffee, 1960) have occurred, but hitherto no fatal reaction has been reported in the literature. These skin manifestations are paralleled closely by those due to the sulphonamides, and the fatal effects of some long-acting preparations have recently been reviewed in these columns (B.M.7., 1964). CASE REPORTA lady of 71 consulted her doctor about a scaly rash on her knees and excessive thirst. Psoriasis and diabetes mellitus were diagnosed and Diabinese (chlorpropamide) prescribed, 250 mg. twice daily being given for three days, then increased to 500 mg. twice daily for two days, and-lowered to 250 mg. twice daily as glycosuria was controlled. A few days later she developed an extensive purplish skin eruption, while mouth lesions rendered swallowing painful.The drug was withdrawn on the third day of this reaction and antihistamine given.She was admitted to hospital on the tenth day of the rash, and examination showed perhaps 85% of the skin involved by purpuric lesions, some of which could be recognized as target-like. Marked crusting was present on her face and lips, there was severe conjunctivitis and chemosis, and the oral mucosae were denuded. Large intact bullae were present on the feet and ankles. Her blood-pressure was 150/70 mm. Hg, and no abnormality was found in the heart, lungs, or abdomen. Though a diagnosis of severe drug eruption was made at this time, her general condition gave no cause for alarm. Plasma electrolytes, alkali reserve, and urea were normal, while the blood sugar was 296 mg./100 ml. A radiograph of the chest showed slight cardiac enlargement, a clean sample of urine revealed 20 leucocytes per high-power field, and culture yielded a moderate growth of Staph. pyogenes. Her white cell count was 5,000, and E.S.R. was 27 mm./hour.However, after a further 48 hours her condition deteriorated, the eruption had become more extensive, and a staphylococcus was isolated from the mouth and conjunctivae which was sensitive to a wide range of antibiotics, though untypable by phages. Her blood sugar rose to 520 mg./100 ml. and urine became strongly positive for ketones. Treatment with soluble insulin controlled this moderate ketosis, but sh...

Photodermatitis Induced by Chlorpropamide

“…Recently it has also been used with some success in the treatment of pitressin-sensitive diabetes insipidus [2,3,6,7,13], Skin rashes occur in 2-3% of patients receiving chlorpropamide. Most cases are of the exanthematic erythematous type [15], but rashes with the morphology of urticaria [I, 4], erythema exudativum multiforme [16,17], purpura [10] and lichen planus mucosae oris [5] have been reported. Hitsel-Feukrman/F rumkin berger and F o sn a u g h [11] have reported a case of photosensitivity with cross-reaction to tolbutamide.…”

Lichenoid eruption due to chlorpropamide.

“…The rapid clearing of the eruption is also quite unlike the slow resolution of the mucosal lesions of lichen planus. It is of interest that the eruption probably occurred only when the daily dose-of chlorpropamide was raised to 250 mg. Maculopapular eruptions, urticaria, exfoliative dermatitis, erythema multiforme, erythema nodosum, Stevens-Johnson syndrome, photosensitivity, purpura, and proctitis (Rothfeld et al, 1960;Tullett, 1966) have been described as rare skin and epithelial complications of chlorpropamide therapy, but lichenoid eruptions due to this drug do not appear to have been previously reported. Lichenoid eruptions may also occur after treatment with gold, organic arsenic, bismuth, mepacrine, chloroquine, hydrochloroquine, and amiphenazole (Sneddon, 1965;Dinsdale and Walker, 1966), and represent yet another condition in which diagnosis and treatment are greatly helped by knowing what drugs the patient has been taking.…”