Patients' perception of the cause of their melanoma differs from that of epidemiologists

SIR, Interferon alfa (IFN-a) therapy is highly effective in patients with chronic myelogenous leukaemia and other malignant diseases. Most side-effects, such as chills, malaise, myalgia and fatigue, are transient and tend to disappear with ongoing therapy, while others, such as anorexia, neurological and mood disorders, are dose-related and need dose adjustment or withdrawal of IFN-a. Induction of immunemediated disease, including thyroid disease, rheumatoid arthritis, systemic lupus erythematosus, vasculitis, thrombocytopenia, autoimmune haemolytic anaemia, and insulin-dependent diabetes mellitus, has also been described. Moreover, other immunological entities, such as myasthenia gravis, vitiligo, lichen planus, Henoch–Schönlein purpura and Sjögren syndrome, have been reported after IFN-a therapy for chronic viral hepatitis or multiple sclerosis (MS). Here, we report on the first case of systemic sclerosis (SSc) developing after therapy with IFN-a for chronic myelogenous leukaemia. In October 1998, a 52-year-old-woman without a personal or a familiar history of autoimmune disease, was diagnosed as having chronic myelogenous leukaemia, with a karyotype 46,XX,t(9;22), bcr ⁄ abl positive in all the metaphases. She was given hydroxyurea 20 mg kg day for 2 months and then IFN-a 2a to a maximum daily dose of 10 · 10 U. In June 1999, cytogenic evaluation showed a normalization of the karyotype in up to 33% of metaphases. Meanwhile, treatment was reduced to 6 · 10 U day for the appraisal of arthralgias, ataxia and depression. In June 2000 a further evaluation revealed the loss of efficacy of therapy (Ph chromosome positive in all the analysable metaphases). In the same period, the patient experienced fever, dyspnoea and oedema of the extremities. Laboratory findings were normal, except for an increased erythrocyte sedimentation rate (ESR, 50 mm in the first hour). Chest X-ray and computed tomography (CT) of the lung demonstrated the presence of pulmonary vascular congestion. Cardiac function, evaluated by electrocardiogram and Doppler echocardiography, was normal. The possible diagnosis of congestive heart failure was discarded and the patient’s symptoms were ascribed to a leak capillary syndrome secondary to interferon therapy; interferon therapy was interrupted. Peripheral oedema and respiratory symptoms improved on treatment with diuretics. Nevertheless, 3 months later, in November 2000 she experienced dyspnoea, oedema of both the upper and lower limbs and progressive skin thickening of the hands and wrists. A further echocardiographic evaluation revealed a normal ejection fraction (70%) and minimal tricuspid regurgitation with increased pulmonary artery pressure (34 mmHg). CT of the chest showed a picture of diffuse parenchymal and interstitial fibrosis with multiple areas of ground-glass attenuation. Pulmonary function tests demonstrated the presence of reduced volumes with an impaired diffusion capacity for carbon monoxide (DLCO, 46% predicted). Oesophagogastroduodenoscopy showed a total absence of peristalsis. Laboratory examination indicated: elevated ESR (80 mm in the first hour), impaired renal function (creatinine, 1Æ8 mg dL) with mild proteinuria (72 mg 24 h) and positive antisclero-70 antibodies. Her complete major histocompatibility phenotype was HLA-DRB1*11; 07, DQA*05;0201, DQB*03;02, A28, A24, B35, B13, Bw4, Bw6, Cw4. Capillaroscopy findings were consistent with scleroderma, showing multiple microhaemorrhages, dilation, distortion and rarefaction of capillaries. No skin biopsy was performed. A diagnosis of localized SSc was put forward, according to LeRoy et al. The patient was given loop diuretics, cyclophosphamide 100 mg day, prostanoids (iloprost, 2 ng kg min for 8 h for five consecutive days and then thrice monthly), steroids (methylprednisolone 750 mg intravenously for 3 days and then prednisone 25 mg day). In the following months the patient’s clinical condition improved, scleroedema decreased, the skin thickening partially receded and the signs of alveolitis were no longer detectable at a further CT evaluation of the lung (October 2001). Therapy has been gradually tapered and the patient is now receiving cyclophosphamide 50 mg day, prednisone 12Æ5 mg day, iloprost 2 ng kg min for 8 h every 3 weeks and hydroxyurea 10 mg kg on every alternate day. The patient’s main clinical and laboratory findings, before and after 10 months of therapy, are summarized in Table 1. Several authors showed that IFN-a therapy for malignancies, chronic viral hepatitis or MS may trigger the formation of autoantibodies directed toward various substrates, such as thyroid, platelets, erythrocytes, pancreas, parietal cells and nuclei. Their occurrence is sometimes, but not necessarily, coupled with the onset or the exacerbation of autoimmune diseases. In most cases endocrine disorders are described, but rheumatic and collagen–vascular diseases have been observed as well. Nevertheless, to date, no reports of SSc after interferon therapy have been made. However, Wandl et al. noticed that patients who develop antinuclear antibodies may experience Raynaud’s phenomenon, one of the diagnostic findings in SSc. Moreover, Black et al. pointed out that IFN-a therapy in the treatment of scleroderma may be deleterious, exacerbating life-threatening symptoms and precipitating the lung deterioration. As far as our patient is concerned, the laboratory findings, typical vascular alterations and ⁄ or clinical signs of autoimmunity are ascribable to interferon therapy. The patient had neither a personal nor a familiar history of autoimmunity, and a clear temporal relation between IFN-a administration and the occurrence of initial symptoms can be seen. Besides, she did receive IFN-a continuously for approximately 2 years. Fattovich et al. indeed noticed that de novo immuneBritish Journal of Dermatology 2002; 147: 385–410.

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