Rheumatology 2002; 41: 473-474
© 2002 British Society for Rheumatology
Letters to the Editor |
Stevens–Johnson syndrome in association with hydroxychloroquine treatment for rheumatoid arthritis
Department of Rheumatology, St Mary's NHS Trust, St Mary's Hospital, Praed Street, London W2 1NY, UK
SIR, Hydroxychloroquine is widely used in the treatment of rheumatoid arthritis and systemic lupus erythematosus, with very few reported side-effects. We report the case of a 65-yr-old woman who developed Stevens–Johnson syndrome 2 weeks after commencing treatment with hydroxychloroquine. Our patient had a 9-yr history of rheumatoid arthritis with multiple episodes of relapse and remission. She also had a medical history of hypertension (treated with bendrofluazide). Over the course of her disease, she had been treated with prednisolone at doses ranging from 5 to 20 mg, but was intolerant of gold (diarrhoea), sulphasalazine (nausea and vomiting), penicillamine (proteinuria) and methotrexate (mouth ulcers, nausea and constipation). In March 2001, she had a flare in her arthritis, with pain, morning stiffness and active synovitis of her wrists, knees and ankles, and an acute inflammatory response (erythrocyte sedimentation rate 62 mm/h, C-reactive protein 140 g/l). She was therefore started on hydroxychloroquine at a dose of 200 mg twice daily. Within 2 weeks, whilst she was on holiday in Tenerife, she developed a pruritic rash over her abdomen, which she described as ‘targets’. She stopped the hydroxychloroquine but within 24 h the rash had become exfoliating, and she developed oral ulceration and hypotension. This required a 3-day hospital admission and treatment with intravenous followed by high-dose oral (60 mg) and topical steroids, which resulted in gradual improvement. On her return to the UK (6 weeks after starting hydroxychloroquine), she was seen in clinic with a persisting exfoliating rash and eczematous patches. This was treated with emollients and topical steroids. Viral serology on her return to the UK showed negative HSV IgG and Mycoplasma IgM titres. Since the acute phase of her disease, the steroids have been reduced to 20 mg daily but the rash, although improving, persists.
Stevens–Johnson syndrome is a severe form of erythema multiforme characterized by a systemic illness with lesions in mucus membranes [1]. The disease has been related to some drugs, such as the sulphonamides, penicillin, salicylates, anti-retroviral drugs and anticonvulsants, and there is an association with Herpes simplex and Mycoplasma pneumoniae infections [2].
There are no specific treatments of proven efficacy for this syndrome, and controlled clinical trials in the use of corticosteroids are required [3].
There are a few isolated cases of Stevens–Johnson syndrome associated with hydroxychloroquine reported by the pharmaceutical company Sanofi-Synthelabo (Guildford, UK), but none has been definitively linked to hydroxychloroquine. In addition, according to the Medicines Control Agency, there have been four reports of erythema multiforme since 1964 related to hydroxychloroquine use (Medicines Control Agency, personal communication, 2001). There is a single case report in the literature describing a case of erythema annulare centrifugum related to the use of hydroxychloroquine sulphate [4]. In addition, there is a report of acute generalized exanthematous pustulosis which began 12 days after the commencement of hydroxychloroquine treatment and resulted in skin desquamation [5]. Furthermore, it is recognized that hydroxychloroquine can exacerbate psoriatic skin lesions [6], an effect thought to be related to inhibition of epidermal transglutaminase activity [7].
Other serious adverse effects of hydroxychloroquine reported include fulminant hepatic failure [8], ototoxicity [9] and neuromyotoxicity [10].
We have reported a serious and life-threatening side-effect which was temporally related to the commencement of treatment with hydroxychloroquine, a drug which has been used in this department until now with the expectation of very few side-effects.
Notes
Correspondence to: M. J. Leckie. 
References
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[Abstract/Free Full Text] - Johansen PB, Gran JT. Ototoxicity due to hydroxychloroquine: report of two cases. Clin Exp Rheumatol1998;16:472–4.[Web of Science][Medline]
- Stein M, Bell MJ, Ang LC. Hydroxychloroquine and neuromyotoxicity. J Rheumatol2000;27:2927–31.[Web of Science][Medline]
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