Disappearance of systemic lupus erythematous after radical treatment of concomitant pheochromocytoma.

Abstract

Three case reports on the association between systemic lupus erythematous (SLE) and pheochromocytoma have been published.1-3 In the first two cases, the pheochromocytoma appeared several years after the diagnosis of SLE,1, 2 while in the last case the two diseases were diagnosed at the same time.3 We report an additional case of a young woman with simultaneous diagnosis of SLE and pheochromocytoma. A 39-year-old female patient, with a history of hypertension treated with amlodipine 10 mg/day, was hospitalized for an episode of pleuro-pericarditis in 2009. Autoimmunity tests were negative. In 2010, the patient was re-hospitalized for a second episode of pleuro-pericarditis. At that time, an abdominal computed tomography scan showed a right adrenal nodule, not further investigated. In the following years, until January 2013, two further episodes of pleuro-pericarditis requiring hospital admissions occurred. At the last hospitalization, a positive antinuclear antibody (ANA) titer of 1 : 160 appeared. The patient was thereafter diagnosed with undifferentiated connective disease, and therapy with hydroxychloroquine was proposed, but the patient refused. In July 2013, she experienced an acute and widespread rash of urticaria that was successfully treated with antihistamines and steroids, interrupted after 2 weeks. In November 2013, she came for the first time to our observation for joint pain in the fingers, wrists, feet, ankles and knees, with functional limitation. Biochemistry confirmed the positivity of ANA (1:160), elevated erythrocyte sedimentation rate (40 mm/h) and C-reactive protein, while rheumatoid factor, anti-double stranded-DNA, extractable nuclear antigen profile, anti-citrulline and anti-cardiolipin antibodies were negative. Blood cell count, immunoglobulins, complement levels, urinalysis, kidney and liver tests were normal. In view of the clinical history (serositis, acute cutaneous lupus, arthritis and ANA positivity), a diagnosis of SLE was made, according to Systemic Lupus International Classification Criteria.4 Among the various investigations, based on the previous diagnosis of a right adrenal mass and a history of unstable hypertension, urinary values of catecholamines and their metabolites were assessed, and the results showed an increase of adrenaline at 26 μg/24 h (normal: 4–20) and metanephrine at 620 mg/24 h (normal 50–340). A subsequent abdominal magnetic resonance imaging confirmed the presence of the right adrenal nodule of 2.8 cm in diameter that showed intense hyperfixation at MIBG (meta-iodobenzyl guanidine I 123) scintigraphy, that was indicative for the diagnosis of pheochromocytoma. Therefore, the patient underwent surgical resection of the right adrenal gland in May 2014. Histological examination confirmed the diagnosis of pheochromocytoma. Normalization of blood pressure, remission of pain at the joints, and the disappearance of ANA occurred the following month, and no clinical or biochemical signs related to SLE were present 6 months after surgery. Our case has some peculiarities. As in the previously described case,3 the diagnoses of SLE and pheochromocytoma were contemporary, but in our patient remission of the clinical and laboratory symptoms was complete, while in the other case was only partial, when considering the permanence of antibody positivity. Second, in our case there was no specific treatment of SLE, either before or after adrenalectomy, in contrast to the previous observation in which the patient was under a chronic steroid therapy. Then, in our case, the resolution of the clinical and laboratory features was clearly related to the pheochromocytoma removal. The association between SLE and pheochromocytoma is unlikely to be casual, and some pathogenetic correlations may exist. An increase in sympathetic activity in rheumatoid arthritis and SLE has been highlighted,5 and it has been hypothesized that elevated levels of norepinephrine, through genetic and environmental factors, can lead to the development of some diseases, including SLE.6 The increase in norepinephrine results in reduced activity of lymphocyte Th1 and Th2 subsets of hyperactivity, with an increase of humoral immunity.7 Thus, when SLE is suspected, it is always advisable to assess the function of the sympathetic nervous system, especially in patients with high blood pressure. On the other hand, the pathogenesis of SLE is complex8 and it may be induced by some drugs, including antihypertensive therapy, such as hydralazine and, less frequently, beta-blockers or angiotensin-converting enzyme inhibitors.9 However, our patient was taking amlodipine, which has been associated with a subacute cutaneous lupus,10 but not with SLE. No funding was received.