Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.

Hydroxychloroquine-Induced Hyperpigmentation in Patients with Systemic Lupus Erythematosus. A Series of 23 Cases.

Jallouli,  Moez, Frances,  C., Piette,  Jean-Charles, Huong,  Du Le Thi, Miyara,  M., Saadoun,  D., Mathian,  A.


To describe the clinical features and outcome of hydroxychloroquine-induced pigmentation in patients with systemic lupus erythematosus (SLE).


This was a retrospective, monocentric (SLE clinic, Pitié-Salpêtrière, Paris) study of SLE patients with pigmented lesions considered to be related to hydroxychloroquine (HCQ). All patients fulfilled the 1997 ACR revised criteria for SLE. The medical files of patients were analysed and all patients were interviewed. Pictures of skin lesions were systematically reviewed by a dermatologist. In five patients, the concentration of iron was measured on samples of skin biopsy performed both in healthy skin and pigmented lesions.


We found 23 patients who developed HCQ-induced pigmentation. All were women. Mean age at pigmentation development was 33.8 ± 13.1 years. Skin pigmentation appeared after a median duration of HCQ therapy of 64 months (range: 3 months-22 years). At the time of cutaneous pigmentation development, the median cumulative dose of HCQ was 657 grams (range: 36–3,168). During follow-up, 21 patients had measurements of blood HCQ concentration [HCQ]. The median number of measurements in a patient was 3 ( range: 1–11). The mean [HCQ] was 1,189 ± 436 ng/ml. This value was not significantly different from that in a group of 143 unselected SLE patients who had been receiving HCQ 400 mg daily for at least 6 months [1].

Hyperpigmentation was localized on the anterior side of the legs (n=23), on the arms (n=5), and on oral mucosa (n=1). Twenty one patients (91.3%) reported that appearance of pigmented lesions was preceded by the occurrence of ecchymotic areas, which gave way to a localized blue-gray or black pigmentation that persisted.

Twenty two patients (95.6%) had at least one condition predisposing them to easy bruising: at the onset of pigmented lesions, 1 patient had persistent thrombocytopenia, 14 patients were treated with platelet antiagregants and 8 with oral anticoagulants. Four patients recalled a previous severe trauma to their legs (accident in 3 cases and combat sport in 1 case).

Six patients also presented HCQ retinopathy, that occurred before (n=4) or after (n=2) skin pigmentation. One patient developed an atrioventricular block of first degree which was reversible after discontinuation of HCQ.

HCQ was discontinued definitively because of skin pigmentation in 2 patients who reported a gradual incomplete fading of hyperpigmentation. Among patients who continued HCQ (n=21), an improvement of pigmented lesions was reported in 6, despite the maintenance of a similar daily dose of HCQ. Pigmentation was found stable in the other 15 patients.

The median concentration of iron in the skin samples taken from five patients was higher in pigmented lesions (4115 nmol/g) compared to normal skin (413 nmol/g).


we report a large single-center series of SLE patients with HCQ-induced skin pigmentation. These lesions were often secondary to ecchymosis. They were not clearly related to duration, cumulative dose or blood concentration of HCQ.

[1]Costedoat-Chalumeau, N. Low blood concentration of hydroxychloroquine is a marker for and predictor of disease exacerbations in patients with systemic lupus erythematosus. Arthritis Rheum. 2006.

To cite this abstract, please use the following information:
Jallouli, Moez, Frances, C., Piette, Jean-Charles, Huong, Du Le Thi, Miyara, M., Saadoun, D., et al; Hydroxychloroquine-Induced Hyperpigmentation in Patients with Systemic Lupus Erythematosus. A Series of 23 Cases. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1409

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