Department of Rheumatology and
1 Dermatology, Wrexham Maelor Hospital, Croesnewydd Road, Wrexham LL13 7TD, UK.
Correspondence to:
A. Sinha, Department of Rheumatology, Wrexham Maelor Hospital, Croesnewydd Road, Wrexham LL13 7TD, UK.
SIR, The co-existence of systemic lupus erythematosus (SLE) and porphyria cutanea tarda (PCT) is rare, and poses diagnostic and therapeutic challenges. We report a case in which the development of PCT coincided with a flare of long-standing SLE.
A 42-yr-old woman was first diagnosed as having SLE in 1983 at the age of 27, when she presented 10 months after the delivery of her first child, with pain and swelling across the metacarpophalangeal and proximal interphalangeal joints of both hands. She responded to treatment with NSAIDs. In 1985, her second pregnancy ended in intrauterine death, during the third trimester, and at this point she was positive for lupus anticoagulant but negative for antiphospholipid antibody. Subsequently, she did well except for one episode of blistering skin lesions with scarring on her hands and face, and two episodes of pericarditis.
In September 1998, she presented with a 3 month history of increased skin pigmentation, general malaise, increased skin fragility and blisters on her face (Fig. 1) and hands (Fig. 2
), associated with significant scarring. A week later, she was admitted to the hospital with left-sided pleuritic chest pain. On examination, she was pyrexial (38.2°C) and had a left-sided pleural rub on auscultation. Skin examination revealed generalized hyperpigmentation, tense blisters with no associated inflammatory change on the dorsal aspects of fingers and milia and scarring over pressure areas. There was no associated hypertrichosis.
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Her other investigations showed her to have a haemoglobin of 9.6 g/dl, white cell count of 4.2x109 /l with lymphopenia of 0.7x109 /l and platelet count of 214x109 /l. The plasma viscosity was 2.22 and C-reactive protein was 88.8. Urea, electrolytes and liver function tests were normal. Total protein was raised at 86 g/l with albumin at 34 g/l and globulin at 52 g/l. IgG was 36.60 g/l [normal range (NR) 5.3016.50], IgA was 4.79 g/l (NR 0.804.00) and IgM was 1.07 g/l (NR 0.502.00). Complement levels showed C3c to be 0.85 g/l (NR 0.551.20) and C4 was <0.06 g/l (NR 0.20.5). Chest radiograph was normal, and ventilation and perfusion lung scan confirmed low probability for pulmonary embolism. Antiphospholipid antibodies were positive, but a test for lupus anticoagulant could not be performed as the patient was on anticoagulation. Serum ferritin was normal at 170.9 µg/l (NR 15300).
On light microscopy, the skin biopsy showed a subepidermal blister with no associated inflammatory infiltrate. Direct immunofluorescence revealed the presence of IgA, IgM and C3 in linear fashion at the dermo-epidermal junction. Periodic acidSchiff (PAS) staining revealed PAS-positive, diastase-resistant, hyaline material around papillary dermal capillaries. The porphyrin screen showed the total urinary porphyrin to be 11860 nmol/l (NR 20320). Total faecal porphyrin was 1967 nmol/g dry weight (NR 10200) and the erythrocyte total porphyrin was not increased. Plasma fluorescence emission spectroscopy showed a prominent porphyrin peak at 618 nm, confirming the diagnosis of PCT.
Because of her pleurisy, she was treated with prednisolone started at a dose of 40 mg/day, to which she responded well, and all the markers of lupus activity gradually settled down, but the blisters were still occurring. After confirmation of the diagnosis of PCT, she was started on treatment with hydroxychloroquine at a low dose of 100 mg twice weekly. Subsequently, azathioprine was added at a dose of 100 mg/day. The blistering skin lesions improved gradually and now her skin has largely cleared and even the pigmentation has improved. Advice on sun avoidance was given and a broad-spectrum sunblock applied to all exposed sites twice daily.
The co-existence of SLE and PCT is rare and was first reported by Wolfram in 1952 [1]. In 1962, Cripps and Curtis [2] first described three cases of chloroquine-induced porphyria. Subsequently, other cases of antimalarial drug-induced porphyria have been reported [3, 4]. More recently, in 1998, Gibson and McEvoy [5] presented a series of 15 patients who had co-existent PCT and various forms of lupus erythematosus.
PCT is a skin disease that results from decreased activity of uroporphyrinogen decarboxylase (UROD). About 80% of patients have the sporadic form in which UROD deficiency is restricted to the liver, and the rest have familial type in which mutations in the UROD gene are inherited in an autosomal dominant pattern with low clinical penetrance [6]. PCT is known to be precipitated by alcohol [7], oral contraceptives [8], polychlorinated hydrocarbons [9] and disturbances of iron metabolism [10]. Infections with HIV and hepatitis C virus have also been known to precipitate PCT [11]. In our patient, we could not find any precipitating factor.
Sweeney et al. [3], in 1965, noted that antimalarial drug-induced exacerbations of porphyria were followed by prolonged remission. Trials using antimalarials as treatment for PCT followed [12]. Severe toxicity resulted from using chloroquine in a dosage of 0.51.0 g/day [13], but twice-weekly dosing of 250500 mg was found to be much better tolerated and more effective [14]. Phlebotomy is the other mode of therapy for PCT. The need to avoid standard or high-dose antimalarial therapy emphasizes the need to recognize the co-existence of PCT and SLE. Sun avoidance, including the use of a total sunblock, should also be recommended [15].
Skin biopsy with electron microscopy and immunofluorescence studies helps with the diagnosis, and porphyria screen confirms the presence of PCT.
The co-existence of SLE and PCT presents a diagnostic and therapeutic challenge, and standard dose chloroquine used in SLE can precipitate PCT.
References