Karolina Niklas

Rheumatic diseases induced by drugs and environmental factors: the state-of-the-art – part one

The majority of rheumatic diseases belong to the group of autoimmune diseases and are associated with autoantibody production. Their etiology is not fully understood. Certain medications and environmental factors may have an influence on the occurrence of rheumatic diseases. Establishing a cause-effect relationship between a certain factor and disease induction is not always simple. It is important to administer the drug continuously or monitor exposure to a given factor in the period preceding the onset of symptoms. The lack of previously diagnosed autoimmune disease, or finally the lack of symptoms within a few weeks/months after discontinuation of the drug/cessation of exposure, is also important. The most frequently mentioned rheumatic diseases caused by drugs and environmental factors include systemic lupus erythematosus, scleroderma, systemic vasculitis, polymyositis, dermatomyositis, and Sjögrens syndrome. The objective of this study is to summarize current knowledge on rheumatic diseases induced by drugs and environmental factors.

Polymyositis induced by atorvastatin

We present the case of a 61-year-old female who developed polymyositis after atorvastatin treatment. She was admitted to hospital in July 2014 with fever, weight loss, myalgia, and limb weakness. Additionally in anamnesis, the following are seen: diabetes type 2, hypertension, and hypercholesterolaemia (treated with atorvastatin 20 mg daily for 6 months). In physical examination muscle weakness was observed (upper limbs 4° and lower limbs 3° in Lovett scale). Laboratory tests revealed increased levels of creatine kinase (CK) — 3977 U/L, alanine aminotransferase (ALT) — 176 U/L and aspartate aminotransferase (AST) — 128 U/l. In electromyography myogenic-dominant damage was described. Atorvastatin was withdrawn. Methylprednisolone pulse therapy was started (3 × 500 mg). Then the patient, with a diagnosis of myopathy, was sent (in August 2014) to the Department of Rheumatology for continuation of treatment. The muscle weakness was still observed (upper limbs 4° and lower limbs 3° in Lovett scale) and laboratory results were as follows: CK 1299.7 U/L, ALT 133.2 U/L, AST 50.5 U/L, aldolase 15.6 U/L, lactate dehydrogenase (LDH) — 742 U/L. Antinuclear antibodies were negative. The presence of anti-SS-A antibodies was observed (Fig. 1). The myositis profile was negative (Fig. 2). In spite of such results the clinical diagnosis of atorvastatin-induced polymyositis was made. Treatment with methylprednisolone pulse (3 × 500 mg) was continued with subsequent oral prednisone therapy (25 mg daily). In control after 1 month a slight improvement of lower limbs muscle strength was observed (4° in Lovett scale, upper limbs remain constant). Laboratory tests revealed the following: CK 873.5 U/L, ALT 77.6 U/L, AST 39 U/L, LDH 704 U/L, aldolase 9.7 U/L. We continued treatment with methylprednisolone pulse (3 × 500 mg). Subsequently the oral prednisone dose was reduced to 20 mg daily. The latest observation was made in November 2014. The upper limbs muscle strength was normal and lower limbs remained constant (4° in Lovett scale). Laboratory results were as follows: CK 259.3 U/L, ALT 40.5 U/L, AST 23 U/L, LDH 401 U/L. The treatment with methylprednisolone pulse was continued, but the dose was reduced (3 × 250 mg). Oral prednisone dose was also decreased to 17.5 mg. Because of permanent hypercholesterolaemia ezetimibe was prescribed. Now patient is under our observation with planned control. Our case describes patients who develop polymyositis after atorvastatin therapy. Because of the non-autoimmune origin of the disease the patient did not reveal a characteristic immunological pattern. Withdrawing the drug did not improve the symptoms. Immunosuppressive therapy with corticosteroids was necessary. Statins may be a cause of the whole spectrum of muscle damage, but full-blown polymyositis or dermatomyositis are rather rare. It is crucial to establish any association with a drug as soon as possible because a key role in the treatment is played by the elimination of any agent causing the disease.

Intra-atrial course of the right coronary artery: an uncommon anomaly diagnosed by coronary computed tomography angiography.

Intra-atrial course of the right coronary artery (RCA) is a very rare anomaly. The frequency of anomalous course of RCA through the right atrium in the population is approximately 0.1%. Intracavitary course of RCA was first described by McAlpine in 1975 [McAlpine WA ed. Heart and coronary arteries. An anatomical atlas for clinical diagnosis, radiological investigation, and surgical treatment. Springer-Verlag, New York 1975]. The growing clinical use of cardiac computed tomography (CT) is enabling accurate assessment of the morphology and location of anomalous vessel course. We present the case of a 78-year-old female who was referred to cardiac CT to rule out ischaemic heart disease. The patient came to the cardiology outpatient clinic with non-specific chest pain, low tolerance of physical effort, dry cough, and raised blood pressure (BP) to 200/100 mm Hg. In anamnesis: hypertension for 6 years, and an acute coronary syndrome 2 years ago without hospitalisation but with pharmacological treatment. In physical examination: regular heart rate (HR) of 68/min with normal heart sounds and normal breath sounds over the lungs, BP 140/80 mm Hg. In resting electrocardiogram: regular HR of 68/min and left branch bundle block. In echocardiography: global hypokinesis with ejection fraction of about 45%. On account of her age and the non-specific cardiac trouble, a cardiac CT was recommended. The origin and proximal segment of the RCA was normal with an epicardial course in the right atrioventricular groove. RCA passed through the anterior right atrial wall (Fig. 1). The mid-segment of RCA had 2 cm of intra-atrial course. The distal segment of RCA exited from the right atrium. This divided into a posterolateral ventricular branch and a posterior descending artery which runs to the heart apex in the posterior interventricular groove. Previously published case reports of intra-atrial RCA evaluated by CT angiography have shown variable lengths of 1.5 to 5.5 cm, which run inside the cavity of the right atrium (Fig. 2). The left main coronary artery, including the left anterior descending and the left circumflex, had normal origin and epicardial course. The above arteries were unobstructed, with numerous soft and mixed plaques causing less than 50% stenosis. The patient was given a dose of 90 mL iodinated contrast medium 400 mg/mL, followed by saline solution. HR during examination was 54–56/min. Multi-detector CT (MDCT) provides a high-quality, noninvasive technique which can help diagnose and visualise the origin and course of anomalous coronary arteries by a 3D display of anatomy. Recognition of such anomalies may help prevent unsafe consequences during interventional procedures or bypass surgery. Anomalous intracavitary RCA may be damaged during procedures including inferior vena cava cannulation, right heart catheterisation, coronary sinus cannulation, pacemaker implantation, invasive electrophysiology testing, ablation of atrial dysarrhythmias arising in the right atrium, transseptal puncture for left atrial access and coronary artery bypass surgery. Therefore, identifying this anomalous course provides significant information to the interventional cardiologist or cardiothoracic surgeon. The detection of these abnormalities is improving with the growing use of cardiac CT. MDCT angiography enabled better and noninvasive visualisation of the anomalous course of coronary artery and associated findings. CT is the diagnostic method for detecting coronary anomalies associated with a low risk of complications. The course of an anomalous coronary artery can be identified with very high accuracy.

Altered course of non-affected left coronary artery as a reason for symptoms of coronary artery disease

Anomalies of coronary arteries are rare (about 0.3–1.3% of patients undergoing a coronary angiography procedure), and left coronary artery (LCA) going from the right sinus of Valsalva (RSV) is described in 0.09–0.15% of cases. We present the case of a 61-year-old female who complained of typical angina symptoms for two years. A cardiac stress test was performed with positive result. The patient was admitted to hospital for coronary catheterisation. Electrocardiogram (ECG) revealed: sinus rhythm 66/min, with T-wave inversion in leads III and aVF and ST depression in leads V4–V6. Echocardiography showed: no segmental wall motion abnormalities and ejection fraction 65%. A coronary angiography was performed. Anomalous origin of LCA from the RSV was observed. Apart from that, the coronary arteries were not affected. Because coronary angiography reveals only two-dimensional views, coronary computed tomography angiography was performed to evaluate the detailed anatomy and course of the coronary arteries. A study was performed with ECG gating at 56–61 bpm using a retrospective acquisition technique. Anatomy and patency of coronary arteries was evaluated using dedicated coronary software. Coronary arteries and their braches were free of plaques, which might have caused significant stenoses and related symptoms. RSV was a source of short common trunk, which bifurcated into the right coronary artery (RCA) and LCA (Fig. 1). The RCA followed its typical anatomical course, and the LCA ran to the left, initially between the right ventricular outflow tract and ascending aorta, and subsequently within the basal anterior segment of the intraventricular septum (Fig. 2A, B). Intramuscular segment supplied the branch corresponding with the diagonal (D1) branch of left anterior descending artery (LAD) and a tiny branch that seemed to supply the intraventricular septum. Further segments of the LCA anatomically corresponding to the LAD ran in epicardial fat tissue giving an origin to the left circumflex artery and its obtuse marginal branches. The type of anomalous course of LCA described in our patient (inter-arterial) has the worst prognosis and is associated with sudden cardiac death (> 50%), especially connected with exercise. For that reason the case of our patient is also unusual. As a young woman she practiced athletics for several years. Her professional work was connected with great physical effort. And finally she gave birth to three children (forces of nature). None of these situations provoked any symptoms. At the time of writing, the state of the patient is stable, so she has been offered optimal medical treatment.

Patient with advanced coronary artery disease and psoriasis

A 67-year-old patient was admitted to the hospital due to the retrosternal pain appearing during moderately physical activity. An interview revealed the following: symptomatic angina pectoris, hypertension, diabetes type 2, and psoriasis with psoriatic arthritis for several years (Fig. 1). Laboratory results showed the following: elevated C-reactive protein, total cholesterol, and glycated haemoglobin. Electrocardiogram revealed the following: regular sinus rhythm, 68/min. Echocardiography: enlargement of the left ventricle with hypokinesis of the basal segment of the inferior wall and the septum, and ejection fraction 60%. Coronary angiography revealed the following: left main artery: minor changes; left anterior descending artery (LAD): aneurysmal extended, distally closed (Fig. 2), diagonal branch: closed; left circumflex artery: aneurysmal extended; 90% narrowing in first marginal branch (Fig. 3); right coronary artery: dominant, wide, 90% distally narrowing (Fig. 4); and posterior descending artery: closed. After the heart team consultation, the changes in coronary arteries were treated conservatively. Doppler ultrasound showed unobstructed both carotid arteries and intima–media thickness of 0.6 mm. An inflammatory process and hyperlipidaemia play roles in the development of atherosclerosis. Psoriasis is a chronic inflammatory disease that belongs to the dermatosis group. Its aetiology includes: genetic factors, vascular changes, and immunological phenomena, as well as environmental factors. The pathophysiology is associated with the inflammatory pathway response of cytokines released by Th1 and Th17 lymphocytes. Patients with psoriasis have increased risk of coronary artery disease (CAD); in this group the probability of myocardial infarction is significantly increased. Moreover, in coronary angiography up to 84% of patients had atherosclerotic lesions vs. 75% observed in the control group. Atherosclerotic lesions in LAD were observed more frequently compared with the general population, and their intensity correlated with the duration of the psoriasis. The inflammatory process is the connecting element between these two diseases. In the pathogenesis of psoriasis one of the main roles is played by the immune processes with the cascade of cytokines released by Th1 and Th17 lymphocytes (TNF-a, IFN-g, IL-17, IL-12, IL-2, and IL-23). The activation of Th1 and its mediators (INF-g, TNF-a, IL-1, IL-12, and IL-18) play a role in the pathogenesis of atherosclerosis. IL-12 and IFN-g are the elements connecting these diseases. European Society of Cardiology guidelines list psoriasis as an independent risk factor for CAD. A key role is attributed to the immune process, especially T-helper response. Patients with concomitant psoriasis and CAD represent an uncommon and complicated group of patients who require significant cardiovascular prevention. It is also worth noting that such patients are good candidates for omega-3 fatty acids supplementation, which is known for both cardiovascular prevention and improvement of psoriasis symptoms. Figure 1. Psoriasis in the joints and nails of both hands

Hypertension in selected rheumatic diseases

Nadciśnienie tętnicze to poważny problem zdrowotny zarówno w Polsce, jak i na całym świecie. Około 10% stanowi nadciśnienie wtórne, do którego zalicza się nadciśnienie spowodowane przez choroby reumatyczne. W jego patogenezie decydującą rolę odgrywa uszkodzenie nerek lub naczyń krwionośnych prowadzące do wzrostu wolemii, wydzielania substancji wazoaktywnych czy zwiększenia oporu naczyń (ryc. 1), dlatego nadciśnienie tętnicze bardzo często towarzyszy toczniowi rumieniowatemu układowemu, zapaleniu naczyń lub twardzinie układowej. Dotyczy ono również znacznej liczby chorych na dnę moczanową. Należy także pamiętać, że część leków powszechnie stosowanych w reumatologii może wpływać na wzrost ciśnienia tętniczego czy interferować z lekami hipotensyjnymi. Z uwagi na poważne powikłania, które mogą wystąpić na skutek nadciśnienia, należy dążyć do jego wczesnego wykrycia i skutecznej terapii (tab. I). S u m m a r y