Adalimumab-induced lupus erythematosus

ARTICLE

Auteur(s) : Firas Al-Niaimi

Department of Dermatology, Cumberland Infirmary, Newtown Road, Carlisle, CA2 7PH, UK

Drug-induced lupus is a syndrome with symptoms, signs and laboratory findings similar to idiopathic systemic lupus erythematosus (SLE). More than 80 drugs have been implicated, with sulfadiazine being the first reported in 1945 [1]. The condition is usually reversible with the withdrawal of the drug. We present here a case of adalimumab-induced lupus erythematosus in a patient treated for rheumatoid arthritis.

A 43-year-old woman who was suffering from severe rheumatoid arthritis was treated with the biological agent adalimumab. Full screening for biological agents showed no contra-indications to treatment and she was on adequate contraception. A week after receiving the second treatment she developed annular, erythematous patches with teleangiectasia on her face, shoulders and back. They all appeared on the predominantly sun-exposed areas. The patches had a slightly atrophic appearance, clinically resembling chronic cutaneous lupus, although a sub-acute variant was considered, due to the annular and sub-acute appearance of the patches. A skin biopsy showed basement membrane damage and positive immunofluoresence predominantly demonstrating an IgG band along the dermo-epidermal junction. In addition, she developed marked prolonged photosensitivity resulting in the persistence of cutaneous lesions, mouth ulcers, hair loss, myalgia and positive anti-Nuclear Antibody (ANA, titre 1/640). This ANA positivity was previously persistently negative. She was negative for double stranded DNA Antibody. Anti-Ro and anti-La antibodies were both negative. Full blood count and electrolytes were normal. Her urinalysis was negative for blood and protein. The diagnosis of drug-induced lupus erythematosus was made and although she would meet the ARA-criteria for systemic lupus (cutaneous lesions, photosensitivity, mouth ulcers and positive ANA), it was felt that this represented mainly a cutaneous lupus. Adalimumab was withdrawn and high factor sunscreens were applied and topical clobetasol propionate cream (Dermovate^®) used for the cutaneous lupus, to which she reacted strongly with a burning sensation and erythema and was unable to tolerate. A similar reaction occurred with topical betamethasone valerate (Betnovate^®). Contact dermatitis to these agents was suspected but the patient declined investigation with patch tests. Treatment with protopic ointment (Tacrolimus^®) was used with a gradual response, with reduction of the erythema and the disappearance of cutaneous lesions, albeit with scarring. Her photosensitivity, mouth ulcers and myalgia gradually improved over 8 weeks but she remained positive for ANA Ab. The resolution of the symptoms is thought to be related to the withdrawal of the drug.

The efficacy of anti-tumour necrosis factor (anti-TNF) agents has led to an increase in their use in dermatology and rheumatology. Infectious complications and immunogenicity are the main limitations, however more recently cases of lupus-like syndrome have been reported with infliximab and to a lesser extent with adalimumab [2, 3]. In the UK, adalimumab has a license in the treatment of psoriasis, psoriatic arthritis and rheumatoid arthritis. Various cutaneous manifestations have been reported with anti-TNF therapies: cutaneous vasculitis, palmoplantar pustulosis, psoriasis, superficial granuloma annulare, eczematous reactions, erythema-multiforme and cutaneous malignancies [4, 5]. Adalimumab induces apoptosis, which prompts the release of nuclear antigens. The engagement of rheumatoid factor-expressing B cells and Toll-like receptor-9 with these agents results in antibody formation [6].

In our patient, anti-nuclear antibodies became strongly positive a few weeks after treatment with adalimumab. Withdrawal of adalimumab may reduce the severity of the symptoms, however, positive autoimmunity may remain for a long period. Topical tacrolimus was successful in our patient and this may prove beneficial in similar cases, where topical steroids may be contra-indicated or ineffective.

Systemic lupus erythematosus/lupus-like syndrome is a rare but potentially serious complication of adalimumab and clinicians need to be aware of this as the use of biological therapies in dermatology is increasing.

Acknowledgements

Références

2 Spillane AP, Xia Y, Sniezek PJ. Drug-induced lupus erythematosus in a patient treated with adalimumab. J Am Acad Dermatol 2007; 56 (5 Suppl): S114-S116.

3 Sheth N, Greenblatt D, Patel S, Acland K. Adalimumab-induced cutaneous lupus. Clin Exp Dermatol 2007; 32: 593-4.

4 Flendrie M, Vissers WH, Creemers MC, et al. Dermatological conditions during TNF-alpha-blocking therapy in patients with rheumatoid arthritis: a prospective study. Arthritis Res Ther 2005; 7: R666-R676.

5 Devos SA, van den Bosche N, de Vos M, Naeyaert JM. Adverse skin reactions to anti-TNF-[alpha] monoclonal antibody therapy. Dermatology 2003; 206: 388-90.

6 Pisetsky DS. Tumour necrosis factor alpha blockers and the induction of anti-DNA autoantibodies. Arthritis Rheum 2000; 43: 2383-90.