Rheumatology 2001; 40: 709-711
© 2001 British Society for Rheumatology
Letters to the Editor |
Acute acalculous cholecystitis and cardiac tamponade in a patient with drug-induced lupus
Departments of Internal Medicine C,
1 Immunology and Allergy,
2 Cardiology and
3 Diagnostic Radiology, Rambam Medical Centre and The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
SIR, The syndrome of drug-induced lupus (DIL) exhibits considerable variability in terms of clinical severity, course and response to medical treatment. It is usually characterized by a benign course of arthralgia, myalgia, pleurisy, rashes and fever in association with antinuclear antibodies (ANA) in the serum [1]. Although they are not common, gallbladder diseases in patients with idiopathic lupus have been reported in the literature [2]. DIL pericarditis with massive pericardial effusion is also rare [3], and cardiac tamponade has been described in case reports [4]. The patient described here exemplifies the importance of maintaining heightened awareness of these uncommon disorders. Fortunately, normalization generally occurs after withdrawal of the offending agent(s). To our knowledge, this is the first reported case in which acute acalculous cholecystitis combined with cardiac tamponade is associated with DIL.
Our case concerns a 61-yr-old woman who was admitted to the hospital with fever, chest pain and progressive dyspnoea. Her history was significant for a 15-yr history of diabetes mellitus type 2 and chronic renal failure due to diabetic nephropathy. Six months earlier she had had pulmonary oedema due to acute myocardial ischaemia. Echocardiography revealed anteroseptal akinesia and moderately reduced left ventricular function. Treatment with carvedilol, felodipine, doxazocin and disothiazide had been initiated. Two months before admission she complained of progressive dyspnoea and chest pain at rest. Microcytic anaemia (haemoglobin 7.6 g/dl) was present (due to chronic renal failure); she received packed red blood cells in the emergency room, with partial alleviation of her symptoms, and she was discharged home. Echocardiography was not performed on that occasion. In spite of these symptoms she was not instructed to discontinue any of her previously prescribed medications. Three days prior to admission she had fever and chills associated with rest chest pain and dyspnoea.
Vital signs on admission were as follows: blood pressure 150/90, pulse 100/min, temperature 38.2°C, respiratory rate 30/min. Physical examination revealed congested neck veins, left subscapular dullness, friction rub over the left lower sternal border, decreased respiratory sounds, muffled cardiac sounds, ascites and right upper quadrant tenderness. Chest X-ray showed cardiomegaly and left pleural effusion. Electrocardiography showed low-voltage and inverted T waves on the lateral wall. Laboratory investigation showed microcytic anaemia (haemoglobin 8.9 g/dl), creatinine 3.5 mg/dl, blood urea nitrogen 67 mg/dl, erythrocyte sedimentation rate 90 mm/h and a prolonged partial thromboplastin time of 46 s (normally less than 36 s). Abdominal ultrasound demonstrated thickening of the gallbladder wall, pericholecystic oedema and the absence of gallstones, findings that were consistent with acute acalculous cholecystitis. Percutaneous cholecystostomy was performed, bile was cultured and intravenous ceftriaxone and metronidazole were given. At this point, dyspnoea and chest pain intensified and pulsus paradoxus was recorded (20 mmHg). Echocardiography revealed a large pericardial effusion with right atrial collapse (Fig. 1
). Pericardiocentesis yielded 1l of serosanguinose exudate containing 53% polymorphonuclear and 47% mononuclear cells, a high lactate dehydrogenase (LDH) concentration (605 IU/l) and a normal glucose level. Gram staining, culture of bile, fluid cytology and Ziehl–Neelsen staining were all negative.
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The diagnosis of polyserositis in the presence of sterile blood and negative bile and pericardial fluid cultures led us to investigate further for a possible autoimmune or hypersensitivity disease. An elevated titre of ANA (306 U/ml, normal<80 U/ml) and a high titre of total antihistone antibodies (106U/ml, normally less than 25 U/ml) were found. ANA were determined by enzyme immunoassay for quantitation (EIA kits; Novamed, Jerusalem, Israel). Total antihistone antibodies were determined by enzyme-linked immunosorbent assay (ELISA) (Organtec Diagnostiqa, Frankfurt, Germany). Tests for anti-double-stranded DNA antibodies and anticardiolipin antibodies were negative.
All medications prescribed 6 months earlier were discontinued and prednisone 1 mg/kg was administered. The patient's condition improved dramatically. She was discharged on the 16th hospital day, symptom-free on 40 mg prednisone daily, which was gradually tapered. No recurrence was observed and DIL disease activity subsided completely. After 1 yr of follow-up, she is doing well with no pericardial effusion. Her ANA levels are still elevated (179 U/ml).
Over 70 drugs used in the treatment of diverse medical conditions have been found to cause a lupus-like illness or exacerbate pre-existing lupus [5]. Of these drugs, only procainamide and hydralazine have been examined carefully in prospective and retrospective studies.
There is no consensus on the diagnostic criteria for DIL, and many patients with DIL do not fulfil four out of the 11 American College of Rheumatology criteria for the diagnosis of systemic lupus erythematosus (SLE) [6]. In general, patients with DIL are older than those with idiopathic lupus, and the female predominance seen in idiopathic lupus is usually not seen in DIL. Thus, DIL should be suspected in every patient without a history of idiopathic lupus who tests positive for ANA, exhibits at least one clinical feature of lupus after an appropriate duration of drug treatment, and whose symptoms resolve after discontinuation of the offending drug [7].
Positive ANA is the most common serological abnormality in DIL. It should be noted that only a minority of patients who develop a positive ANA develop the clinical disease. Thus, seroconversion alone is not an indication to discontinue the offending drug. The specificity of ANA is more restricted in DIL than in idiopathic lupus and is directed primarily against histone proteins [8]. Antihistone antibodies are not exclusive to DIL but are also seen in about 20–30% of cases of SLE. While anti-DNA and anti-Sm antibodies are often found in patients with SLE, these antibodies are rarely produced in DIL [9].
The diagnosis of DIL was suspected in our patient by the clinical picture, positive ANA test and high titre of antihistone antibodies. Four new medications were prescribed 6 months before admission: carvedilol, felodipine, doxazosin and disothiazide. Each of them separately or in combination could cause DIL. Medline and Index Medicus were searched to obtain relevant published literature concerning DIL in association with the above-mentioned drugs; none of them has been reported to cause DIL.
Seven cases of acalculous cholecystitis in SLE have been reported in the literature. Six patients were treated surgically, and in one case corticosteroid therapy alone improved the symptoms of acute cholecystitis dramatically [2]. Gallbladder involvement in this case may be considered as a part of the DIL syndrome, as the patient had no history of biliary tract disease, bile culture was negative and there was no evidence of cholelithiasis. As no histological investigation was performed, it should be speculated that cholecystitis in this case could have been caused by either vasculitis or serositis.
Pericardial involvement occurs slightly more frequently with procainamide than with other drugs. Although such involvement is usually benign, there are reports of pericardial effusion and cardiac tamponade secondary to procainamide [4]. As in other reports of DIL [9, 10], in our case pericardiocentesis revealed a serosanguinous inflammatory exudate with predominant polymorphonuclear cells, a high LDH concentration and a normal glucose level.
While the offending drug could not be identified because of polypharmacy and the lack of prior reports of DIL with any of these medications, it seems possible that several drugs were acting additively.
In summary, the key to the diagnosis of DIL is recognition of the temporal relationship between the use of agents known to induce lupus and the onset of characteristic symptoms.
Notes
Correspondence to: H. Ben-Ami, Department of Internal Medicine C, Rambam Medical Centre, PO Box 9602, Haifa 31096, Israel. 
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